Molecular Medicine (MM)
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Research Annual Report 2010 Molecular Medicine (MM) Solid tumors between bench and bed Pharmacogenetics Improving Clinical andaccuracy experimental and therapeutic neuroendocrinology ratio in radiation oncology Hyperthermia: Regulation of calcium a treatment and bone for cancer metabolism Photodynamic Regulation of the therapy bioactivity of thyroid hormone Neuro-oncology Signalling in reproduction and pain and ageing Pathophysiological Localisation, detection aspects and radionuclide and treatment therapy of gastro-intestinal of various diseases diseases Surgical The musculoskeletal trauma and the system development and tissue-engineering of tumour recurrence in orthopaedics and otorhinolaryngology Innovative tumor Regulation of follicle model development, development/tumor oocyte andvasculature/tumor endometrial embryo targeting/locoregional quality control Clinical and experimental Pathophysiology of pediatric aspects endocrine, of urological metabolic tumors and renal diseases Gynaecological Malignant transformation oncology; basics, of hematopoietic epidemiology stem andcells: clinical pathophysiology aspects and development of therapy Developmental biology; Hematopoiesis: regulation pathophysiology of the proliferation of the and newborn differentiation of hematopoietic progenitor cells Experimental Molecular determinants therapeutical of therapy approaches response in inflammatory and outcome dermatoses in childhood and cancer cutaneous oncology Translational Lymphoid differentiation genomics and and proteomics immunodeficiencies of cancer Translational Immune regulation pharmacology and autoimmunity Neoplastic classification Diagnosis, lesions and chronic and treatment inflammatation evaluation of the of leukemias gastrointestinal and malignant tract lymphomas 11771, B&T Ontwerp en advies (http://www.b-en-t.nl) Research Annual Report 2010 Molecular Medicine (MM) Solid tumors between bench and bed Improving accuracy and therapeutic ratio in radiation oncology Hyperthermia: a treatment for cancer Photodynamic therapy Neuro-oncology and pain Pathophysiological aspects and treatment of gastro-intestinal diseases Surgical trauma and the development of tumour recurrence Innovative tumor model development/tumor vasculature/tumor targeting/locoregional control Clinical and experimental aspects of urological tumors Gynaecological oncology; basics, epidemiology and clinical aspects Developmental biology; pathophysiology of the newborn Experimental therapeutical approaches in inflammatory dermatoses and cutaneous oncology Translational genomics and proteomics of cancer Translational pharmacology Neoplastic lesions and chronic inflammatation of the gastrointestinal tract 11771, B&T Ontwerp en advies (http://www.b-en-t.nl) Research Annual Report 2010 Molecular Medicine (MM) Liverspecific immunopathology; mechanism and therapeutic modulation Human virus infections: immunity, therapy and epidemiology Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention Clinical research in infectious diseases in adults Renal insufficiency and organ transplantation Cell biological and pathophysiological investigations on pulmonary diseases Neuromuscular and Neuroinflammatory Disorders Organ transplantation Genitourinary tract disorders in children Disorders of the gastrointestinal tract in childhood Clinical, epidemiological and basic research of infectious diseases and immunological diseases in children 11771, B&T Ontwerp en advies (http://www.b-en-t.nl) < back to index EMC MM-01-25-01 – Pharmacogenetics Programme in brief design The focus of this program is on molecular markers that can predict the effectiveness or the risk of adverse reactions of therapeutic interventions. In particular, the contribution of genetic factors in the drug metabolism is investigated. Translational research is performed to define and evaluate the clinical significance of genetic polymorphisms in drug metabolizing enzymes (o.a. CYP450s, UGTs, TPMT and NAT genes), drug transporters (OATPS, OATS, ABC-Transporters) and drug targets (a.o. Folate-Dependant Emzymes). Drug classes include immuno-suppressives, anti-depressants, anti-cancer drugs, anaesthetics, anti-arrhytmics, anti-viral drugs, anti-coagulation drugs, proton pump inhibitors, opioids and anti-rheumatoïd drugs. In addition, genetic and metabolic factors are investigated that determine the level of plasma homocysteine and its deleterious effect on methylation reactions. Key figures Department clinical chemistry internal medicine medical oncology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 3,53 0 0 0 3,53 0,3 0 0 0 0,3 1 0 0 0 1 4,83 0 0 0 4,83 0 0 0 0 23 3 1 27 Artikel/Letter to the editor Bangma, C.H., Schaik, R.H.N. van, Blijenberg, B.G., Roobol, M.J., Lilja, H. & Stenman, UH (2010). On the use of prostatespecific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer. European Journal of Cancer, 46(17), 3109-3119. Becker, M.L., Visser, L.E., Schaik, R.H.N. van, Hofman, A., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy. Pharmacoepidemiology and Drug Safety, 19(1), 75-81. Becker, M.L., Visser, L.E., Schaik, R.H.N. van, Hofman, A., Uitterlinden, A.G. & Stricker, B.H.C. (2010). Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics Genomics, 20(1), 38-44. Blonk, M.I., Velde, N. van der, Bemt, P.M.L.A. van den, Schaik, R.H.N. van & Cammen, T.J.M. van der (2010). CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people. Pharmacy World & Science, 32(1), 26-29. Boer, D.P., Rijke, Y.B. de, Hop, W.C.J., Cransberg, K. & Dorresteijn, E.M. (2010). Reference values for serum creatinine in children younger than 1 year of age. Pediatric Nephrology, 25, 2107-2113. Bol, J.M. van der, Jong, F.A. de, Schaik, R.H.N. van, Sparreboom, A., Fessem, M.A.C. van, Geijn, F.E. van de, Daele, P.L.A. van, Verweij, J., Sleijfer, S. & Mathijssen, R.H.J. (2010). Effects of Mannose-Binding Lectin Polymorphisms on IrinotecanInduced Febrile Neutropenia. Oncologist, 15(10), 1063-1072. Crop, M.J., Rijke, Y.B. de, Verhagen, P.C.M.S., Cransberg, K. & Zietse, R. (2010). Diagnostic Value of Urinary Dysmorphic Erythrocytes in Clinical Practice. Nephron Clinical Practice, 115(3), C203-C212. Deenik, W., Holt, B. van der, Janssen, J.J.W.M., Chu, IWT, Valk, P.J.M., Ossenkoppele, G.J., Heiden, I.P. van der, Sonneveld, P., Schaik, R.H.N. van & Cornelissen, J.J. (2010). Polymorphisms in the multidrug resistance gene MDR1 (ABCB1) predict for molecular resistance in patients with newly diagnosed chronic myeloid leukemia receiving high-dose imatinib. Blood, 116(26), 6144-6145. Gensburger, O, Schaik, R.H.N. van, Picard, N., Meur, Y. Le, Rousseau, A, Woillard, JB, Gelder, T. van & Marquet, P (2010). Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil. Pharmacogenetics Genomics, 20(9), 537-543. Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), 4227-4234. Jansen, F.H., Schaik, R.H.N. van, Kurstjens, J, Horninger, W, Klocker, H, Bektic, J, Wildhagen, M.F., Roobol, M.J., Bangma, C.H. & Bartsch, G. (2010). Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection. European Urology, 57(6), 921-927. Jonge, R. de, Brouwer, R., Graaf, M.T. de, Luitwieler, RL, Fleming, C, Frankrijker-Merkestijn, M. de, Sillevis Smitt, P.A.E., Boonstra, J.G. & Lindemans, J. (2010). Evaluation of the new body fluid mode on the Sysmex XE-5000 for counting leukocytes and erythrocytes in cerebrospinal fluid and other body fluids. Clinical Chemistry and Laboratory Medicine, 48(5), 665-675. Lammers, L.A., Mathijssen, R.H.J., Gelder, T. van, Bijl, M.J., Graan, A.M. de, Seynaeve, C., Fessem, M. van, Berns, E.M.J.J., Vulto, A.G. & Schaik, R.H.N. van (2010). The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. British Journal of Cancer, 103(6), 765-771. 70 < back to index Luin, M van, Ende, M.E. van der, Richter, C., Visser, M., Faraj, D, Ven, A. van de, Gelinck, L.B.S., Kroon, F., Wit, FW, Schaik, R.H.N. van, Kuks, PFM & Burger, D.M. (2010). Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. Aids, 24(8), 1223-1226. Meesters, R.J.W., Cornelissen, R., Klaveren, R.J. van, Jonge, R. de, Boer, E., Lindemans, J. & Luider, T.M. (2010). A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients. Analytical and Bioanalytical Chemistry, 398(7-8), 2943-2948. Payne, DA, Mamotte, CDS, Gancberg, D, Pazzagli, M, Schaik, R.H.N. van, Schimmel, H & Rousseau, F. (2010). Nucleic acid reference materials (NARMs): definitions and issues. Clinical Chemistry and Laboratory Medicine, 48(11), 1531-1535. Pekelharing, J.M., Hauss, O, Jonge, R. de, Lokhoff, J, Sodikromo, J, Spaans, M, Brouwer, R., Lathouder, S. de & Hinzmann, R (2010). Haematology reference intervals for established and novel parameters in healthy adults. Diagnostic Perspectives, 1, 111. Rakhmanina, N.Y., Anker, J.N. van den, Soldin, SJ, Schaik, R.H.N. van, Mordwinkin, N & Neely, MN (2010). Can Therapeutic Drug Monitoring Improve Pharmacotherapy of HIV Infection in Adolescents? Therapeutic Drug Monitoring, 32(3), 273-281. Re, M. Del, Paolo, A. Di, Schaik, R.H.N. van, Bocci, G, Simi, P, Falcone, A & Danesi, R. (2010). Dihydropyrimidine dehydrohenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine. EPMA Journal, 1, 495-502. Rotte, M.C.F.J. de, Luime, J.J., Bulatovic, M, Hazes, J.M.W., Wulffraat, N.M. & Jonge, R. de (2010). Do snapshot statistics fool us in MTX pharmacogenetic studies in arthritis research? Rheumatology, 49(6), 1200-1201. Ruiter, R. de, Bijl, M.J., Schaik, R.H.N. van, Berns, P.M.J.J., Hofman, A., Coebergh, J.W.W., Noord, C. van, Visser, L.E. & Stricker, B.H.C. (2010). CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen. Pharmacogenomics, 11(10), 1367-1375. Russcher, H., Herwaarden, AE van, Boesten, L.S.M., Kemna, MS, Curvers, J, Heijboer, AC, Engbers-Buijtenhuis, P & Deckers, MML (2010). Klinische chemie voor iedereen: het Wikipedia-project. Nederlands Tijdschrift voor Klinische Chemie, 35, 70-75. Sandberg, Y., Rood, P.P.M., Russcher, H., Zwaans, J.J.M., Weigel, J.D. & Daele, P.L.A. van (2010). Falsely elevated lactate in severe ethylene glycol intoxication. Netherlands Journal of Medicine, 68(7-8), 320-323. Schenk, P.W., Vliet, M. van, Mathot, R.A.A., Gelder, T. van, Vulto, A.G., Fessem, M.A.C. van, Rij, SVV, Lindemans, J., Bruijn, J.A. & Schaik, R.H.N. van (2010). The CYP2C19(star)17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients. Pharmacogenomics Journal, 10(3), 219-225. Schiettecatte, J, Russcher, H., Anckaert, E, Mees, M., Leeser, B, Tirelli, AS, Fiedler, GM, Luthe, H, Denk, B & Smitz, J (2010). Multicenter evaluation of the first automated Elecsys sFlt-1 and PlGF assays in normal pregnancies and preeclampsia. Clinical Biochemistry, 43(9), 768-770. Siemes, C., Visser, L.E., Jong, F.H. de, Coebergh, J.W.W., Uitterlinden, A.G., Hofman, A., Stricker, B.H.C. & Schaik, R.H.N. van (2010). Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer-The Rotterdam Study. Steroids, 75(12), 1024-1032. Part of book - abstract Gysel, D. van, Schaik, R.H.N. van & Oranje, A.P. (2010). Mastocytosis. In J Harper, AP Oranje & N Prose (Eds.), Textbook of pediatric dermatology (pp. 75). New York: Blackwell Publishing. 71 < back to index EMC MM-01-39-01 - Clinical and experimental neuroendocrinology Programme in brief design A. Studies on the regulation of hormone secretion by the normal pituitary gland as well as by human pituitary tumours in vivo and in vitro. B. An integrative approach to the endocrinology of ageing. Hormonal factors related to the ageing process are investigated in population studies. Intervention studies with hormones (growth hormone, dehydroepiandrosterone) are carried out. C. An integrative approach to factors determining glucocorticoid sensitivity in man. Molecular studies of mutations in the glucocorticoid receptor and in the translational regulation of glucocorticoid action are carried out in cells obtained from patients with glucocorticoid resistance and from patients with transient changes in glucocorticoid sensitivity. D. Studies on the expression of growth factor and peptide receptors in cancer and in immune cells. E. The regulation of the growth and activity of immune and of tumour cells in vitro by manipulation of the expression of peptide receptors is studied in relation with the potential endocrine manipulation of immune diseases and cancer growth in vivo. F. An integrative approach of clinical and surgical endocrinology is used in studies aimed at improving patient care. Key figures Department internal medicine surgery Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,9 1,4 0,82 3,67 7,79 0,1 0 0 0 0,1 2 1,4 0,82 3,67 7,89 1 0 0 1 33 3 0 37 Thesis Brugts, M.P. (2010, januari 06). IGF-I bioactivity in aging, health and disease. EUR (252 pag.). Prom./coprom.: Prof.Dr. S.W.J. Lamberts & Dr. J.A.M.J.L. Janssen. Artikel/Letter to the editor Alwani, R.A., Herder, W.W. de, Aken, M.O. van, Berge, J.H. van den, Delwel, E.J., Dallenga, A.H.G., Jong, F.H. de, Lamberts, S.W.J, Lelij, A.J. van der & Feelders, R.A. (2010). Biochemical Predictors of Outcome of Pituitary Surgery for Cushing's Disease. Neuroendocrinology, 91(2), 169-178. Brugts, M.P., Tjiong, H.L., Rietveld, T., Wattimena, J.L.D., Berg, J.W.O. van den, Fieren, M.W.J.A. & Janssen, J.A.M.J.L. (2010). Bioactive rather than total IGF-I is involved in acute responses to nutritional interventions in CAPD patients. Nephrology Dialysis Transplantation, 25(3), 940-946. Brugts, M.P., Duijn, C.M. van, Hofland, L.J., Witteman, J.C.M., Lamberts, S.W.J & Janssen, J.A.M.J.L. (2010). IGF-I Bioactivity in an Elderly Population Relation to Insulin Sensitivity, Insulin Levels, and the Metabolic Syndrome. Diabetes, 59(2), 505-508. Bruynzeel, J.A., Feelders, R.A., Groenland, T.H.N., Meiracker, A.H. van den, Eijck, C.H.J. van, Lange, J.F., Herder, W.W. de & Kazemier, G. (2010). Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 95(2), 678-685. Chai, W., Hofland, J., Jansen, P.M., Garrelds, I.M., Vries, R.D. de, Bogaerdt, A.J. van den, Feelders, R.A., Jong, F.H. de & Danser, A.H.J. (2010). Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors? Journal of Hypertension, 28(5), 1044-1053. Daly, AF, Tichomirowa, MA, Petrossians, P., Heliovaara, E, Jaffrain-Rea, ML, Barlier, A, Naves, LA, Ebeling, T, Karhu, A, Raappana, A, Cazabat, L, Menis, E De, Montanana, CF, Raverot, G, Weil, RJ, Sane, T, Maiter, D, Neggers, S.J.C.M.M., Yaneva, M, Tabarin, A, Verrua, E, Eloranta, E, Murat, A, Vierimaa, O, Salmela, PI, Emy, P, Toledo, RA, Sabate, MI, Villa, C, Popelier, M, Salvatori, R, Jennings, J, Longas, AF, Aizpun, JIL, Georgitsi, M., Paschke, R, Ronchi, C, Valimaki, M, Saloranta, C, Herder, W.W. de, Cozzi, R, Guitelman, M, Magri, F, Lagonigro, MS, Halaby, G, Corman, V, Hagelstein, MT, Vanbellinghen, JF, Barra, GB, Gimenez-Roqueplo, AP, Cameron, FJ, Borson-Chazot, F, Holdaway, I, Toledo, S.P.A., Stalla, GK, Spada, A, Zacharieva, S, Bertherat, J, Brue, T, Bours, V, Chanson, P., Aaltonen, LA & Beckers, A. (2010). Clinical Characteristics and Therapeutic Responses in Patients with Germ-Line AIP Mutations and Pituitary Adenomas: An International Collaborative Study. Journal of Clinical Endocrinology and Metabolism, 95(11), E373-E383. Delhanty, P.J.D., Sun, YX, Visser, J.A., Kerkwijk, A.J. van, Huisman, M., Ijcken, W.F.J. van, Swagemakers, S.M.A., Smith, RG, Themmen, A.P.N. & Lelij, A.J. van der (2010). Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice. PLoS One, 5(7). Delhanty, P.J.D., Kerkwijk, A.J. van, Huisman, M., Zande, B. van de, Verhoef-Post, M., Gauna, C., Hofland, L.J., Themmen, A.P.N. & Lelij, A.J. van der (2010). Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. American Journal of Physiology, Endocrinology and Metabolism, 299(3), E497-E505. Essen, M. van, Krenning, E.P., Kam, B.L.R., Herder, W.W. de, Feelders, R.A. & Kwekkeboom, D.J. (2010). Salvage Therapy with Lu-177-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors. Journal of Nuclear Medicine, 51(3), 383-390. Feelders, R.A., Hofland, L.J. & Herder, W.W. de (2010). Medical Treatment of Cushing's Syndrome: Adrenal-Blocking Drugs and Ketaconazole. Neuroendocrinology, 92, 111-115. 72 < back to index Feelders, R.A., Bruin, C. de, Pereira, AM, Romijn, J.A., Netea-Maier, RT, Hermus, A.R., Zelissen, PM, Heerebeek, R.E.A. van, Jong, F.H. de, Lelij, A.J. van der, Herder, W.W. de, Hofland, L.J. & Lamberts, S.W.J (2010). Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease. New England Journal of Medicine, 362(19), 1846-1848. Giustina, A, Chanson, P., Bronstein, MD, Klibanski, A., Lamberts, S.W.J, Casanueva, F.F., Trainer, P, Ghigo, E., Ho, K & Melmed, S. (2010). A Consensus on Criteria for Cure of Acromegaly. Journal of Clinical Endocrinology and Metabolism, 95(7), 3141-3148. Granata, R, Volante, M., Settanni, F, Gauna, C., Ghe, C, Annunziata, M, Deidda, B, Gesmundo, I, Abribat, T., Lelij, A.J. van der, Muccioli, G., Ghigo, E. & Papotti, M. (2010). Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of Molecular Endocrinology, 45(1), 9-17. Groot, JWB de, Links, T.P., Themmen, A.P.N., Looijenga, L.H.J., Krijger, R.R. de, Koetsveld, P.M. van, Hofland, J., Berg, G. van den, Hofland, L.J. & Feelders, R.A. (2010). Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome. European Journal of Endocrinology, 163(2), 293-299. Hoek, J. van der, Lamberts, S.W.J & Hofland, L.J. (2010). The somatostatin receptor subtype 5 in neuroendocrine tumours. Expert Opinion on Investigational Drugs, 19(3), 385-399. Hofland, L.J., Feelders, R.A., Herder, W.W. de & Lamberts, S.W.J (2010). Pituitary tumours: The sst/D-2 receptors as molecular targets. Molecular and Cellular Endocrinology, 326(1-2), 89-98. Hofland, L.J., Lamberts, S.W.J & Feelders, R.A. (2010). Role of Somatostatin Receptors in Normal and Tumoral Pituitary Corticotropic Cells. Neuroendocrinology, 92, 11-16. Kaltsas, G., Androulakis, II, Herder, W.W. de & Grossman, A.B. (2010). Paraneoplastic syndromes secondary to neuroendocrine tumours. Endocrine-Related Cancer, 17(3), R173-R193. Kianmanesh, R., Ruszniewski, P., Rindi, G., Kwekkeboom, D.J., Pape, U.F., Kulke, M, Garcia, IS, Scoazec, JY, Nilsson, O., Fazio, N, Lesurtel, M, Chen, YJ, Eriksson, B., Cioppi, F & O'Toole, D (2010). ENETS Consensus Guidelines for the Management of Peritoneal Carcinomatosis from Neuroendocrine Tumors. Neuroendocrinology, 91(4), 333-340. Kulke, MH, Anthony, LB, Bushnell, DL, Herder, W.W. de, Goldsmith, S.J., Klimstra, D.S., Marx, SJ, Pasieka, JL, Pommier, RF, Yao, J.C. & Jensen, R.T. (2010). NANETS Treatment Guidelines Well-Differentiated Neuroendocrine Tumors of the Stomach and Pancreas. Pancreas, 39(6), 735-752. Kumsta, R., Entringer, S, Koper, J.W., Rossum, E.F.C. van, Hellhammer, D.H. & Wust, S (2010). Working memory performance is associated with common glucocorticoid receptor gene polymorphisms. Neuropsychobiology, 49-56. Kwekkeboom, D.J., Herder, W.W. de, Eijck, C.H.J. van, Kam, B.L.R., Essen, M. van, Teunissen, J.J.M. & Krenning, E.P. (2010). Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors. Seminars in Nuclear Medicine, 40(2), 78-88. Kwekkeboom, D.J., Kam, B.L.R., Essen, M. van, Teunissen, J.J.M., Eijck, C.H.J. van, Valkema, R., Jong, M. de, Herder, W.W. de & Krenning, E.P. (2010). Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancer, 17(1), R53-R73. Lelij, A.J. van der (2010). Multiple Sources of Information for the Hypothalamus. Frontiers of Hormone Research, 38, 190-195. Manenschijn, L., Akker, E.L.T. van den, Ester, W.A., Leunissen, R.W.J., Willemsen, R.H., Rossum, E.F.C. van, Koper, F.J.W., Lamberts, S.W.J & Hokken-Koelega, A.C.S. (2010). Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age. European Journal of Endocrinology, 163, 911-918. Martino, M.C. de, Koetsveld, P.M. van, Pivonello, R. & Hofland, L.J. (2010). Role of the mTOR Pathway in Normal and Tumoral Adrenal Cells. Neuroendocrinology, 92, 28-34. Martino, M.C. de, Hofland, L.J. & Lamberts, S.W.J (2010). Somatostatin and somatostatin receptors: from basic concepts to clinical applications. Progress in Brain Research, 182, 252-280. Oosten, M.J.M. van, Dolhain, R.J.E.M., Koper, F.J.W., Rossum, E.F.C. van, Emonts, M., Han, KH, Wouters, J.M.G.W., Hazes, J.M.W., Lamberts, S.W.J & Feelders, R.A. (2010). Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Research & Therapy, 12(4). Pavel, M, Grossman, A., Arnold, R., Perren, A, Kaltsas, G., Steinmuller, T., Herder, W.W. de, Nikou, G., Plockinger, U, Lopes, JM, Sasano, H, Buscombe, J, Lind, P, O'Toole, D & Oberg, K (2010). ENETS Consensus Guidelines for the Management of Brain, Cardiac and Ovarian Metastases from Neuroendocrine Tumors. Neuroendocrinology, 91(4), 326-332. Pereira, AM, Delgado, V, Romijn, J.A., Smit, J.W.A., Bax, J.J. & Feelders, R.A. (2010). Cardiac dysfunction is reversed upon successful treatment of Cushing's syndrome. European Journal of Endocrinology, 162(2), 331-340. Varewijck, A.J., Goudzwaard, J.A., Brugts, M.P., Lamberts, S.W.J, Hofland, L.J. & Janssen, J.A.M.J.L. (2010). Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir. Growth Hormone and IGF Research, 20(6), 427-431. Waas, M. van, Neggers, S.J.C.M.M., Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Components of the metabolic syndrome in 500 adult long-term survivors of childhood cancer. Annals of Oncology, 21, 1121-1126. 73 < back to index Webb, S.M., Mo, DJ, Lamberts, S.W.J, Melmed, S., Cavagnini, F., Giraldi, FP, Strasburger, C.J., Zimmermann, AG & Woodmansee, WW (2010). Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing's Disease or Non-Functioning Pituitary Adenoma. Journal of Clinical Endocrinology and Metabolism, 95(2), 630-638. Woodmansee, WW, Hartman, M.L., Lamberts, S.W.J, Zagar, AJ & Clemmons, D.R. (2010). Occurrence of impaired fasting glucose in GH-deficient adults receiving GH replacement compared with untreated subjects. Clinical Endocrinology, 72, 59-69. Part of book - abstract Herder, W.W. de & Feelders, R.A. (2010). Imaging for the Differential Diagnosis of Cushing¿s Syndrome: MRI, CT and Isotopic Scanning. In M Bronstein (Ed.), Cushings Syndrome ¿ Pathophysiology, Diagnosis and Treatment. Contemporary Endocrinology (pp. 91-103). New York: Humana Press. Rossum, E.F.C. van & Lamberts, S.W.J (2010). Glucocorticoid Resistance. In M Bronstein (Ed.), Cushing's Syndrome, Pathophysiology, Diagnosis and Treatment (pp. 235-248). New York: Humana Press. 74 < back to index EMC MM-01-39-02 - Regulation of calcium and bone metabolism Programme in brief design Research focus is skeletal and calcium homeostasis and development and progression of related disorders with particular emphasis on ageing. Increasing life span is accompanied by an increase in age-related diseases such as osteoporosis. Osteoporosis is an important common disease with a large impact on quality of life as well as health care budget. Development of pharmaceutical and life style interventions as prevention or as treatment is important and requires an optimal knowledge in aetiology and mechanisms of development of osteoporosis. Current therapies for osteoporosis are directed to inhibit bone loss and thereby its progression. There is, however, a major need for anabolic therapies which stimulate bone formation because bone loss has already occurred when the consequences of osteoporosis have become overt. Directly coupled to this is improvement in early diagnostics. The overall aim of this research line is to develop better diagnostics and therapies for skeletal disorders and disturbances in calcium homeostasis by a combination of molecular, cellular, animal, epidemiological and eventually clinical studies. Four integrated lines of research can be identified. 1) Characterisation of molecular mechanisms of bone cell differentiation and of bone formation and degradation using human bone cell models by bioinformatic and systems biological analyses of gene, protein and enzyme activity profiles. 2) Identification of risk determinants for osteoporosis and osteoarthritis on basis of genetic epidemiological and serum proteomic studies within a.o. the Rotterdam Study. 3) Calcium homeostasis and skeletal metabolism in relation to ageing by analyses of experimental animal models, e.g. premature ageing mice, as well as human population research. 4) Development of medium/high throughput screenings procedures to quickly screen therapeutic targets and to evaluate novel therapeutic compounds Key figures Department internal medicine Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 12,31 3,74 0 2,64 18,69 12,31 3,74 0 2,64 18,69 3 0 0 3 69 0 0 72 Thesis Botter, S.M. (2010, december 21). Dynamic subchondral bone changes in murine models of osteoarthritis. EUR (172 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans, Prof.dr. J.P.T.M. van Leeuwen & Dr. G.J.V.M. van Osch. Diderich, K.E.M. (2010, januari 06). Bone aging in DNA Repair deficient trichothiodystrophy mice. EUR (252 pag.). Prom./coprom.: Prof. Dr. J.H.J. Hoeijmakers, Prof. Dr. G.T.J. van der Horst & Prof.dr. J.P.T.M. van Leeuwen. Jansen, J.H.W. (2010, mei 12). Mechanotransduction in bone, Dependency on Human Osteoblast Differation. EUR (133 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans & Prof.dr. J.P.T.M. van Leeuwen. Artikel/Letter to the editor Allen, HL, Estrada, K, Lettre, G., Berndt, SI, Weedon, MN, Rivadeneira Ramirez, F., Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, JH, Yang, J., Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L., Smith, AV, Magi, R, Pastinen, T, Liang, L., Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, Y.S., Johansson, A, Zillikens, M.C., Feitosa, MF, Esko, T, Johnson, T, Ketkar, S., Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J.J., Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J.F., Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, ML, Altmaier, EL, Amin, N., Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C., Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Konig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Muller, M., Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, JX, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L., Grandi, A De, Dominiczak, A, Duan, J, Elliott, P., Elosua, R, Eriksson, JG, Freimer, N.B., Geus, E.J.C. de, Glorioso, N, Haiqing, S, Hartikainen, AL, Havulinna, AS, Hicks, AA, Hui, JN, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, JJ, Lokki, ML, Marusic, A, Maschio, A. del, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, J.H., Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, M.J., Ripatti, S, Meurs, J.B.J. van, Aben, KK, Ardlie, KG, Beckmann, J.S., Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, Heijer, M. den, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A., Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, L.J., Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B.A., Palmer, LJ, Raitakari, O, Ridker, P.M., Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H., Shuldiner, AR, Siscovick, D.S., Stumvoll, M., Tonjes, A, Tuomilehto, J, Ommen, G.J. van, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M., Arnold, AM, Atwood, LD, Boerwinkle, E., Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P., Hattersley, A.T., Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S., Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A., Mohlke, KL, Boomsma, D.I., Caulfield, MJ, Cupples, L.A., Erdmann, J., Fox, CS, Gudnason, V, Gyllensten, U, Harris, T.B., Hayes, RB, Jarvelin, MR, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, P.P., Quertermous, T, Rudan, I, Samani, NJ, Spector, T.D., Volzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, HE, Thorsteinsdottir, U, Peltonen, L., Uitterlinden, A.G., Visscher, P.M., Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, T.M. & Hirschhorn, JN (2010). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature, 467(7317), 832-838. 75 < back to index Alves, R., Eijken, M, Swagemakers, S.M.A., Chiba, H., Titulaer, M.K., Burgers, P.C., Luider, T.M. & Leeuwen, J.P.T.M. van (2010). Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation. Journal of Proteome Research, 9(9), 4688-4700. Anttila, V, Stefansson, H, Kallela, M, Todt, U, Terwindt, G.M., Calafato, MS, Nyholt, DR, Dimas, AS, Freilinger, T, MullerMyhsok, B, Artto, V, Inouye, M, Alakurtti, K, Kaunisto, MA, Hamalainen, E, Vries, B de, Stam, AH, Weller, CM, Heinze, A, Heinze-Kuhn, K, Goebel, I, Borck, G, Gobel, H, Steinberg, S, Wolf, C, Bjornsson, A, Gudmundsson, G, Kirchmann, M, Hauge, A, Werge, T, Schoenen, J., Eriksson, JG, Hagen, K, Stovner, L, Wichmann, E, Meitinger, T, Alexander, M, Moebus, S, Schreiber, S., Aulchenko, Y.S., Breteler, M.M.B., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Tikka-Kleemola, P, Vepsalainen, ., Lucae, S, Tozzi, F, Muglia, P, Barrett, J, Kaprio, J, Farkkila, M, Peltonen, L., Stefansson, K, Zwart, JA, Ferrari, M.D., Olesen, J, Daly, M., Wessman, M, Maagdenberg, A.M.J.M., Dichgans, M, Kubisch, C, Dermitzakis, ET, Frants, R.R. & Palotie, A (2010). Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics, 42(10), 869-873. Baas, DC, Ho, L., Ennis, S, Merriam, JE, Tanck, M.W.T., Uitterlinden, A.G., Jong, P.T.V.M. de, Cree, AJ, Griffiths, HL, Rivadeneira, F., Hofman, A., Duijn, C.M. van, Smith, R.T., Barile, GR, Gorgels, TGMF, Vingerling, J.R., Klaver, C.C.W., Lotery, AJ, Allikmets, R. & Bergen, A.A.B. (2010). The Complement Component 5 Gene and Age-Related Macular Degeneration. Ophthalmology, 117(3), 500-511. Baas, DC, Despriet, D.D., Gorgels, T.G.M.F., Bergeron-Sawitzke, J, Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Merriam, JE, Smith, R.T., Barile, GR, Brink, J.B., Vingerling, J.R., Klaver, C.C.W., Allikmets, R., Dean, M & Bergen, A.A.B. (2010). The ERCC6 Gene and Age-Related Macular Degeneration. PLoS One, 5(11). 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Debette, S, Bis, JC, Fornage, M, Schmidt, H., Ikram, M.A., Sigurdsson, S, Heiss, G, Struchalin, M, Smith, AV, Lugt, A. van der, DeCarli, C., Lumley, T, Knopman, DS, Enzinger, C, Eiriksdottir, G, Koudstaal, P.J., DeStefano, AL, Psaty, B.M., Dufouil, C., Catellier, DJ, Fazekas, F., Aspelund, T, Aulchenko, Y.S., Beiser, A, Rotter, JI, Tzourio, C., Shibata, DK, Tscherner, M, Harris, T.B., Rivadeneira, F., Atwood, LD, Rice, K, Gottesman, RF, Buchem, M.A. van, Uitterlinden, A.G., Kelly-Hayes, M, Cushman, M., Zhu, YC, Boerwinkle, E., Gudnason, V, Hofman, A., Romero, JR, Lopez, O, Duijn, C.M. van, Au, R., Heckbert, SR, Wolf, PA, Mosley, TH, Seshadri, S, Breteler, M.M.B., Schmidt, R., Launer, L.J. & Longstreth, W.T. (2010). Genome-Wide Association Studies of MRI-Defined Brain Infarcts Meta-Analysis From the CHARGE Consortium. Stroke, 41(2), 210-217. Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R., Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Magi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P., Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P., Grallert, H, Dehghan, A., Hottenga, J.J., Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M., Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L., Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y., Balkau, B, Barter, P., Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E., Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Bottcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, YDI, Chines, P, Clarke, R., Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, Geus, E.J.C. de, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, XJ, Hartikainen, AL, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C. den, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A., Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Bacquer, O Le, Lecoeur, C, Li, Y., Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, B.D., Morken, MA, Mukherjee, S., Naitza, S, Narisu, N, Neville, MJ, Oostra, B.A., Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, 76 < back to index Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, B.M., Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira Ramirez, F., Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, E.J.G., Silveira, A, Simpson, L, Singleton, A., Smith, NL, Sovio, U, Swift, A., Syddall, H, Syvanen, AC, Tanaka, T, Thorand, B, Tichet, J, Tonjes, A, Tuomi, T, Uitterlinden, A.G., Dijk, KW van, Hoek, M. van, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, J.C.M., Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, GJ, Zhao, JH, Zillikens, M.C., Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, A.T., Silander, K, Salomaa, V, Smith, G.D., Bornstein, S.R., Schwarz, P, Spranger, J., Karpe, F, Shuldiner, AR, Cooper, C., Dedoussis, GV, Serrano-Rios, M, Morris, A.D., Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M., Hansen, T., Pedersen, O, Pramstaller, P.P., Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M., Campbell, H, Wilson, JF, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, D.S., Penninx, BWJH, Boomsma, D.I., Deloukas, P, Spector, T.D., Frayling, T.M., Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Duijn, C.M. van, Aulchenko, Y.S., Cao, A., Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, MR, Waterworth, D.M., Vollenweider, P, Peltonen, L., Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC & Barroso, I (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature Genetics, 42(2), 105-U32. Durme, Y.M.T.A. van, Eijgelsheim, M., Joos, G.F., Hofman, A., Uitterlinden, A.G., Brusselle, GG & Stricker, B.H.C. (2010). Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study. European Respiratory Journal, 36(1), 89-95. 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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 42(7), 579-U155. Vujkovic, M., Steegers, E.A.P., Meurs, J. van, Yazdapanahm, M., Rooij, IA van, Uitterlinden, A.G. & Steegers-Theunissen, R.P.M. (2010). The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring. European Journal of Clinical Nutrition, 64(3), 266-273. Winkel, M.L. te, Beek, R.D. van, Muinck Keizer-Schrama, S.M.P.F., Uitterlinden, A.G., Hop, W.C.J., Pieters, R. & HeuvelEibrink, M.M. van den (2010). Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia. Haematologica, 95(5), 752-758. Wockel, V.J., Alves, RDAM, Swagemakers, S.M.A., Eijken, M, Chiba, H., Eerden, B.C.J. van der & Leeuwen, J.P.T.M. van (2010). 1 alpha,25-(OH)(2)D-3 Acts in the Early Phase of Osteoblast Differentiation to Enhance Mineralization Via Accelerated Production of Mature Matrix Vesicles. Journal of Cellular Physiology, 225(2), 593-600. 82 < back to index Yang, QO, Kottgen, A, Dehghan, A., Smith, AV, Glazer, NL, Chen, MH, Chasman, DI, Aspelund, T, Eiriksdottir, G, Harris, T.B., Launer, L, Nalls, M, Hernandez, D., Arking, DE, Boerwinkle, E., Grove, ML, Li, M., Kao, WHL, Chonchol, M, Haritunians, T, Li, G., Lumley, T, Psaty, B.M., Shlipak, M, Hwang, SJ, Larson, MG, O'Donnell, CJ, Upadhyay, A, Duijn, C.M. van, Hofman, A., Rivadeneira, F., Stricker, B.H.C., Uitterlinden, A.G., Pare, G, Parker, AN, Ridker, P.M., Siscovick, D.S., Gudnason, V, Witteman, J.C.M., Fox, CS & Coresh, J (2010). Multiple Genetic Loci Influence Serum Urate Levels and Their Relationship With Gout and Cardiovascular Disease Risk Factors. Circulation-cardiovascular genetics, 3(6), 523-530. Zillikens, M.C., Uitterlinden, A.G., Leeuwen, J.P.T.M. van, Berends, A.L., Henneman, P., Dijk, KW van, Oostra, B.A., Duijn, C.M. van, Pols, H.A.P. & Rivadeneira Ramirez, F. (2010). The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density. Calcified Tissue International, 86(2), 116-125. 83 < back to index EMC MM-01-39-03 - Regulation of the bioactivity of thyroid hormone Programme in brief design Thyroid hormone (TH) is essential for the development of virtually all tissues. The prohormone T4 is converted by outer ring deiodination to the active hormone T3 and by inner ring deiodination to the inactive metabolite rT3. The three deiodinases (D1-3) involved are expressed in different tissues, where they play different roles in systemic and local control of T3 levels. The deiodinases are located in cell membranes with their active site exposed to the cytoplasm, while the T3 receptors (TRs) reside in the nucleus. Uptake of thyroid hormone a cross the plasma membrane is thus required for thyroid hormone action and metabolism, and is mediated by specific transporters. Recently, our group identified an important T3 transporter (MCT8) which was shown to be mutated in patients with severe psychomotor retardation and grossly elevated serum T3 levels. This project concerns the characterization of the deiodinases and transporters in human tissues as well as their importance in the regulation of the bioactivity of thyroid hormone in development and disease. In addition, the specific role of the alpha-type TR (TR¿) in the tissue-specific action of thyroid hormone, particularly in the brain, is investigated. It has been shown that there is substantial variation in thyroid hormone levels between different individuals, and that minor changes in thyroid status can result in a higher risk of diseases such as cardiovascular disease and osteoporosis. This project also involves the identification of new genes involved in determining an individual¿s thyroid hormone set-point, and studies consequences of genetic variants in those genes on different thyroid hormone related clinical endpoints. Key figures Department internal medicine nuclear medicine Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,58 3,73 0 0,33 4,64 0,2 0 0 0 0,2 0,78 3,73 0 0,33 4,84 1 0 0 1 14 1 0 16 Thesis Visser, W.E. (2010, juni 30). Thyroid hormone and development; the importance of transporters and deiodinases. EUR. Prom./coprom.: Prof. Dr. Ir. T.J. Visser. Artikel/Letter to the editor Abdulrahman, RM, Verloop, H, Hoftijzer, H, Verburg, E, Hovens, GC, Corssmit, EP, Reiners, C, Gelderblom, H., Pereira, AM, Kapiteijn, E., Romijn, J.A., Visser, T.J. & Smit, J.W. (2010). Sorafenib-Induced Hypothyroidism Is Associated with Increased Type 3 Deiodination. Journal of Clinical Endocrinology and Metabolism, 95(8), 3758-3762. Benhadi, N., Fliers, E., Visser, T.J., Reitsma, J.B. & Wiersinga, W.M. (2010). Pilot study on the assessment of the setpoint of the hypothalamus-pituitary-thyroid axis in healthy volunteers. European Journal of Endocrinology, 162(2), 323-329. Bolk, N., Visser, T.J., Nijman, J.M., Jongste, IJ, Tijssen, J.G.P. & Berghout, A. (2010). Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial. Archives of Internal Medicine, 170(22), 1996-2003. Deure, W.M. van der, Peeters, R.P. & Visser, T.J. (2010). Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters. Journal of Molecular Endocrinology, 44(1), 1-11. Friesema, E.C.H., Visser, W.E. & Visser, T.J. (2010). Genetics and phenomics of thyroid hormone transport by MCT8. Molecular and Cellular Endocrinology, 322(1-2), 107-113. Heemstra, KA, Hoftijzer, H, Deure, W.M. van der, Peeters, R.P., Hamdy, NA, Pereira, A, Corssmit, EP, Romijn, J.A., Visser, T.J. & Smit, J.W. (2010). The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Increased Bone Turnover and Decreased Femoral Neck Bone Mineral Density. Journal of Bone and Mineral Research, 25(6), 1385-1391. Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), 4227-4234. Ianculescu, AG, Friesema, E.C.H., Visser, T.J., Giacomini, KM & Scanlan, TS (2010). Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. Molecular BioSystems, 6(8), 1403-1410. Moreno, JC & Visser, T.J. (2010). Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations. Molecular and Cellular Endocrinology, 322(1-2), 91-98. Paschke, R & Visser, T.J. (2010). Clinical application and consequences of molecular genetics of thyroid diseases. Molecular and Cellular Endocrinology, 322(1-2), 1-1. Trajkovic-Arsic, M, Visser, T.J., Darras, V.M., Friesema, E.C.H., Schlott, B, Mittag, J., Bauer, K. & Heuer, H. (2010). Consequences of Monocarboxylate Transporter 8 Deficiency for Renal Transport and Metabolism of Thyroid Hormones in Mice. Endocrinology, 151(2), 802-809. Trajkovic-Arsic, M, Muller, J, Darras, V.M., Groba, C, Lee, S., Weih, D, Bauer, K., Visser, T.J. & Heuer, H. (2010). Impact of Monocarboxylate Transporter-8 Deficiency on the Hypothalamus-Pituitary-Thyroid Axis in Mice. Endocrinology, 151(10), 50535062. 84 < back to index Visser, W.E., Wong, W.S., Mullem, A.A.A. van, Friesema, E.C.H., Geyer, J & Visser, T.J. (2010). Study of the transport of thyroid hormone by transporters of the SLC10 family. Molecular and Cellular Endocrinology, 315(1-2), 138-145. Visser, W.E., Swagemakers, S.M.A., Ozgur, Z., Schot, R., Verheijen, F.W., Ijcken, W.F.J. van, Spek, P.J. van der & Visser, T.J. (2010). Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome. Human Molecular Genetics, 19(21), 4189-4200. Part of book - abstract Deure, W.M. van der, Medici, M., Peeters, R.P. & Visser, T.J. (2010). Genetic influences on thyroid function tests. In G.A. Brent (Ed.), Thyroid Function Testing (pp. 21-43). New York: Springer Verlag. 85 < back to index EMC MM-01-39-04 - Signalling in reproduction and ageing Programme in brief design Hormones, such as growth hormone secretagogues and members of the TGF¿/activin family of growth and differentiation factors play a central role in development and functioning of the organism throughout life. This program focuses on the effect of variations in signal transduction of hormones (including ghrelin and unacylated ghrelin) and TGF¿ family members (including anti-Müllerian hormone, BMPs, inhibins and activins) during foetal and postnatal development and subsequent functioning and ageing of the organism. Furthermore, effects of mutations or single nucleotide polymorphisms in enzymes involved in biosynthesis or catabolism of steroid hormones are investigated. Variations in signaling through these pathways affect the early make-up of physiological response systems that can have effects during adult life and in the ageing process. Variations in signal transduction of ligand-receptor interaction, gene expression, proliferation and apoptosis are studied; not only at the molecular and cellular level, but also at the level of the whole body in animal models of ageing, in patients and in populations of ageing men and women. Specific areas are: 1. The role of TGF¿ family members in female ageing, oestrogen effects and age at menopause 2. The influence of gene variants in female and male physiology 3. Development of animal models for the study of the role of hormones and TGF¿ family members in the pathophysiology of metabolism and ageing. 4. Causes and effects of changes in steroid biosynthetic pathways. 5. Evaluation of the (metabolic) role of natural and synthetic growth hormone secretatogues in peripheral tissues in vitro and in vivo. Key figures Department internal medicine Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 2,96 0 0 1,88 4,84 2,96 0 0 1,88 4,84 0 0 0 0 20 0 2 22 Artikel/Letter to the editor Alwani, R.A., Herder, W.W. de, Aken, M.O. van, Berge, J.H. van den, Delwel, E.J., Dallenga, A.H.G., Jong, F.H. de, Lamberts, S.W.J, Lelij, A.J. van der & Feelders, R.A. (2010). Biochemical Predictors of Outcome of Pituitary Surgery for Cushing's Disease. Neuroendocrinology, 91(2), 169-178. Burgers, J.A., Lie Fong, S., Louwers, Y.V., Valkenburg, O., Jong, F.H. de, Fauser, B.C.J.M. & Laven, J.S.E. (2010). Oligoovulatory and Anovulatory Cycles in Women with Polycystic Ovary Syndrome (PCOS): What's the Difference? Journal of Clinical Endocrinology and Metabolism, 95(12), E485-E489. Chai, W., Hofland, J., Jansen, P.M., Garrelds, I.M., Vries, R.D. de, Bogaerdt, A.J. van den, Feelders, R.A., Jong, F.H. de & Danser, A.H.J. (2010). Steroidogenesis vs. steroid uptake in the heart: do corticosteroids mediate effects via cardiac mineralocorticoid receptors? Journal of Hypertension, 28(5), 1044-1053. Delhanty, P.J.D., Sun, YX, Visser, J.A., Kerkwijk, A.J. van, Huisman, M., Ijcken, W.F.J. van, Swagemakers, S.M.A., Smith, RG, Themmen, A.P.N. & Lelij, A.J. van der (2010). Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice. PLoS One, 5(7). Delhanty, P.J.D., Kerkwijk, A.J. van, Huisman, M., Zande, B. van de, Verhoef-Post, M., Gauna, C., Hofland, L.J., Themmen, A.P.N. & Lelij, A.J. van der (2010). Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. American Journal of Physiology, Endocrinology and Metabolism, 299(3), E497-E505. Elks, CE, Perry, JRB, Sulem, P, Chasman, DI, Franceschini, N, He, CY, Lunetta, KL, Visser, J.A., Byrne, EM, Cousminer, DL, Gudbjartsson, DF, Esko, T, Feenstra, B., Hottenga, J.J., Koller, DL, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, McArdle, PF, Smith, AV, Stolk, L., Wingerden, S.H. van, Zhao, JH, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, PKE, Smith, EN, Ulivi, S, Warrington, NM, Zgaga, L, Alavere, H, Amin, N., Aspelund, T, Bandinelli, S, Barroso, I, Berenson, GS, Bergmann, S, Blackburn, H, Boerwinkle, E., Buring, JE, Busonero, F, Campbell, H, Chanock, SJ, Chen, W., Cornelis, MC, Couper, D, Coviello, AD, d'Adamo, P, Faire, U de, Geus, E.J.C. de, Deloukas, P, Doring, A, Smith, G.D., Easton, D.F., Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, A.R., Foroud, T., Garcia, M, Gasparini, P, Geller, F, Gieger, C, Gudnason, V, Hall, P., Hankinson, SE, Ferreli, L, Heath, AC, Hernandez, DG, Hofman, A., Hu, FB, Illig, T, Jarvelin, MR, Johnson, AD, karasik, D., Khaw, KT, Kiel, DP, Kilpelainen, TO, Kolcic, I, Kraft, P, Launer, L.J., Laven, J.S.E., Li, SX, Liu, JJ, Levy, D., Martin, NG, McArdle, WL, Melbye, M, Mooser, V, Murray, JC, Murray, SS, Nalls, MA, Navarro, P, Nelis, M, Ness, AR, Northstone, K, Oostra, B.A., Peacock, M., Palmer, LJ, Palotie, A, Pare, G, Parker, AN, Pedersen, NL, Peltonen, L., Pennell, CE, Pharoah, P., Polasek, O, Plump, AS, Pouta, A, Porcu, E, Rafnar, T, Rice, JP, Ring, SM, Rivadeneira Ramirez, F., Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, NJ, Scuteri, A, Segre, AV, Shuldiner, AR, Soranzo, N, Sovio, U, Srinivasan, SR, Strachan, DP, Tammesoo, ML, Tikkanen, E, Toniolo, D., Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, Dam, RM van, Meurs, J.B.J. van, Vollenweider, P, Waeber, G, Wareham, NJ, Waterworth, D.M., Weedon, MN, Wichmann, HE, Willemsen, G, Wilson, JF, Wright, AF, Young, L, Zhai, GJ, Zhuang, WV, Bierut, LJ, Boomsma, D.I., Boyd, HA, Crisponi, L, Demerath, EW, Duijn, C.M. van, Econs, M.J., Harris, T.B., Hunter, DJ, Loos, RJF, Metspalu, A, Montgomery, GW, Ridker, P.M., Spector, T.D., Streeten, EA, Stefansson, K, Thorsteinsdottir, U, Uitterlinden, A.G., Widen, E, Murabito, JM, Ong, KK & Murray, A (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-U73. 86 < back to index Feelders, R.A., Bruin, C. de, Pereira, AM, Romijn, J.A., Netea-Maier, RT, Hermus, A.R., Zelissen, PM, Heerebeek, R.E.A. van, Jong, F.H. de, Lelij, A.J. van der, Herder, W.W. de, Hofland, L.J. & Lamberts, S.W.J (2010). Pasireotide Alone or with Cabergoline and Ketoconazole in Cushing's Disease. New England Journal of Medicine, 362(19), 1846-1848. Ginhoven, T.M. van, Huisman, T.M., Berg, J.W. van den, Ijzermans, J.N.M., Delhanty, P.J.D. & Bruin, R.W.F. de (2010). Preoperative fasting induced protection against renal ischemia/reperfusion injury is independent of ghrelin in mice. Nutrition Research, 30(12), 865-869. Granata, R, Volante, M., Settanni, F, Gauna, C., Ghe, C, Annunziata, M, Deidda, B, Gesmundo, I, Abribat, T., Lelij, A.J. van der, Muccioli, G., Ghigo, E. & Papotti, M. (2010). Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats. Journal of Molecular Endocrinology, 45(1), 9-17. Groot, JWB de, Links, T.P., Themmen, A.P.N., Looijenga, L.H.J., Krijger, R.R. de, Koetsveld, P.M. van, Hofland, J., Berg, G. van den, Hofland, L.J. & Feelders, R.A. (2010). Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing's syndrome. European Journal of Endocrinology, 163(2), 293-299. Hempel, R.J., Tulen, J.H.M., Beveren, N.J.M. van, Roder, C.H., Jong, F.H. de & Hengeveld, M.W. (2010). Diurnal cortisol patterns of young male patients with schizophrenia. Psychiatry and Clinical Neurosciences, 64(5), 548-554. Hendriks, A.E.J., Boellaard, W.P.A., Casteren, N.J. van, Romijn, J.C., Jong, F.H. de, Boot, A.M. & Drop, S.L.S. (2010). Fatherhood in tall men treated with high-dose sex steroids during adolescence. Journal of Clinical Endocrinology and Metabolism, 95(12), 5233-5240. Hofland, J., Weerden, W.M. van, Dits, N.F.J., Steenbergen, J., Leenders, G.J.L.H. van, Jenster, G.W., Schroder, F.H. & Jong, F.H. de (2010). Evidence of Limited Contributions for Intratumoral Steroidogenesis in Prostate Cancer. Cancer Research, 70(3), 1256-1264. Hofland, J., Weerden, W.M. van, Jenster, G.W., Schroder, F.H. & Jong, F.H. de (2010). Intraprostatic Steroidogenic Enzymes Response. Cancer Research, 70(20), 8249-8250. Houten, E.L.A.F. van, Themmen, A.P.N. & Visser, J.A. (2010). Anti-Mullerian hormone (AMH): Regulator and marker of ovarian function. Annales d' Endocrinologie, 71(3), 191-197. Huang, KY, Groot, S.A. de, Woelders, H, Horst, G.T.J. van der, Themmen, A.P.N., Colenbrander, B & Vlissingen, JMF van (2010). Functionality of cryopreserved juvenile ovaries from mutant mice in different genetic background strains after allotransplantation. Cryobiology, 60(2), 129-137. Kerkhof, G.F., Leunissen, R.W.J., Jong, F.H. de, Visser, J.A., Laven, J.S.E. & Hokken-Koelega, A.C.S. (2010). Influence of preterm birth and small birth size on serum anti-Mullerian hormone levels in young adult women. European Journal of Endocrinology, 163, 937-944. Kok, R.C., Timmerman, M.A., Wolffenbuttel, K.P., Drop, S.L.S. & Jong, F.H. de (2010). Isolated 17,20-Lyase deficiency due to the cytochrome b5 mutation W27X. Journal of Clinical Endocrinology and Metabolism, 95(3), 994-999. Noord, C. van, Dorr, M, Sturkenboom, M.C.J.M., Straus, S.M.J.M., Reffelmann, T, Felix, SB, Hofman, A., Kors, J.A., Haring, R, Jong, F.H. de, Nauck, M., Uitterlinden, A.G., Wallaschofski, H., Witteman, J.C.M., Volzke, H & Stricker, B.H.C. (2010). The association of serum testosterone levels and ventricular repolarization. European Journal of Epidemiology, 25(1), 21-28. Siemes, C., Visser, L.E., Jong, F.H. de, Coebergh, J.W.W., Uitterlinden, A.G., Hofman, A., Stricker, B.H.C. & Schaik, R.H.N. van (2010). Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer-The Rotterdam Study. Steroids, 75(12), 1024-1032. Part of book - abstract Jong, F.H. de & Ronde, W. de (2010). Problemen rond de hypofyse-gonaden as. In MA Bex, RA Feelders, JM Kaufman, AJ van der Lely, FRE Nobels & APN Themmen (Eds.), 36e Erasmus Endocrinologie Cursus (pp. 55-57). Rotterdam: Erasmus MC. Themmen, A.P.N. & Leeuwen, J.P.T.M. van (2010). Oestrogeen signaling: 14 jaar na de ontdekking van de oestrogeen receptor-beta. In MA Bex, RA Feelders, JM Kaufman, AJ van der Lely, FRE Nobels & APN Themmen (Eds.), 36e Erasmus Endocrinologie Cursus. Rotterdam: Erasmus MC. 87 < back to index EMC MM-01-40-01 - Localisation, detection and radionuclide therapy of various diseases Programme in brief design The focus of the research is on intermediary metabolism and inherited disorders of intermediary metabolism. The group continues to participate on projects on inflammation and cencer with an accent on inherited predisposition. The flcilities of the group include mass spectrometry and stable isotope methods to study lipid, protein and carbohydrate metabolism, clinical chemistry and enzymology and molecular genetics. In the past years the klowledge derived from ongoing research on hereditary disorders of iron, heme and porphyrin metabolism has been used to start new lines of research focused on Pompe's disease and MPS-1, linked to enzyme ereplacement therapy (ERT) and pheno/genotype relation with respect to effectiveness of ERT as well as exploration of other new therapeutic modalities. In many cases the affected enzymes function in complex pathways and are genetically coded by genes on different chromosomes. Analysis will focus on the presence of abnormal concentration of intermediate(s) from relevant pathways in these diseases. The result of abnormal presence indicate which enzyme(s) in the pathway are involved as well as indicate the extent of impairment of the mutated enzymes. The same approach will be used in other more prevalent disorders of carbohydrate metabolism like type two diabetes. The major focus in this complex disease will be impairment of the beta-cell function in multi-case affected families. All genes involved in induction, processing and secretion of insulin will be tested under capacity related conditions (OGTT) We will search for gene alterations if intermediates or precursors formed under these conditions indicate that the capacity for a specific part of the pathway is lower than normal. Another line of clinical research addresses the determinants and improvement of the quality of care for patients with diabetes mellitus. Key figures Department nuclear medicine Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,4 0 2 0,75 4,15 1,4 0 2 0,75 4,15 1 0 0 1 23 2 1 27 Thesis Melis, M.L. (2010, december 16). Radiopeptides for targeted tumour therapy and the kidney. EUR (257 pag.). Prom./coprom.: Dr.Ir. M. de Jong & Prof. Dr. E.P. Krenning. Artikel/Letter to the editor Boot, A.M., Ridder, M.A.J. de, Sluis, I.M. van der, Slobbe, I.M. van, Krenning, E.P. & Muinck Keizer-Schrama, S.M.P.F. (2010). Peak bone mineral density, lean body mass and fractures. Bone, 46(2), 336-341. Essen, M. van, Krenning, E.P., Kam, B.L.R., Herder, W.W. de, Feelders, R.A. & Kwekkeboom, D.J. (2010). Salvage Therapy with Lu-177-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors. Journal of Nuclear Medicine, 51(3), 383-390. Hanin, FX, Pauwels, S., Bol, A, Breeman, W.A.P., Jong, M. de & Jamar, F. (2010). Tumor uptake of Ga-68-DOTA-Tyr(3)octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model. Nuclear Medicine and Biology, 37(2), 157-165. Jong, M. de & Maina, T (2010). Of Mice and Humans: Are They the Same?-Implications in Cancer Translational Research. Journal of Nuclear Medicine, 51(4), 501-504. Kate, G.L. ten, Sijbrands, E.J.G., Valkema, R., Cate, F.J. ten, Feinstein, SB, Steen, A.F.W. van der, Daemen, M.J.A.P. & Schinkel, A.F.L. (2010). Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques? Journal of Nuclear Cardiology, 17(5), 897-912. Kianmanesh, R., Ruszniewski, P., Rindi, G., Kwekkeboom, D.J., Pape, U.F., Kulke, M, Garcia, IS, Scoazec, JY, Nilsson, O., Fazio, N, Lesurtel, M, Chen, YJ, Eriksson, B., Cioppi, F & O'Toole, D (2010). ENETS Consensus Guidelines for the Management of Peritoneal Carcinomatosis from Neuroendocrine Tumors. Neuroendocrinology, 91(4), 333-340. Konijnenberg, M.W. & Olch, A (2010). Pediatric dosimetry for intrapleural lung injections of P-32 chromic phosphate. Physics in Medicine and Biology, 55(19), 5735-5751. Kos-Kudla, B, O'Toole, D, Falconi, M, Gross, D, Kloppel, G., Sundin, A, Ramage, J, Oberg, K, Wiedenmann, B., Komminoth, P., Custem, E Van, Mallath, M, Papotti, M. & Caplin, M. (2010). ENETS Consensus Guidelines for the Management of Bone and Lung Metastases from Neuroendocrine Tumors. Neuroendocrinology, 91(4), 341-350. Kwekkeboom, D.J., Herder, W.W. de, Eijck, C.H.J. van, Kam, B.L.R., Essen, M. van, Teunissen, J.J.M. & Krenning, E.P. (2010). Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors. Seminars in Nuclear Medicine, 40(2), 78-88. Kwekkeboom, D.J., Kam, B.L.R., Essen, M. van, Teunissen, J.J.M., Eijck, C.H.J. van, Valkema, R., Jong, M. de, Herder, W.W. de & Krenning, E.P. (2010). Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancer, 17(1), R53-R73. Melis, M.L., Vegt, E, Konijnenberg, M.W., Visser, M., Bijster, M., Vermeij, M., Krenning, E.P., Boerman, O.C. & Jong, M. de (2010). Nephrotoxicity in Mice After Repeated Imaging Using In-111-Labeled Peptides. Journal of Nuclear Medicine, 51(6), 973977. 88 < back to index Mitchell, J.R., Verweij, M., Brand, K., Ven, M. van der, Goemaere, N.N.T., Engel, S. van den, Chu, T, Forrer, F., Muller, C., Jong, M. de, Ijcken, W.F.J. van, Ijzermans, J.N.M., Hoeijmakers, J.H.J. & Bruin, R.W.F. de (2010). Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell, 9(1), 40-53. Oberg, K, Hellman, P, Kwekkeboom, D.J. & Jelic, S (2010). Neuroendocrine bronchial and thymic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21, v220-v222. Oberg, KE, Reubi, J.C., Kwekkeboom, D.J. & Krenning, E.P. (2010). Role of Somatostatins in Gastroenteropancreatic Neuroendocrine Tumor Development and Therapy. Gastroenterology, 139(3), 742-U79. Pavel, M, Grossman, A., Arnold, R., Perren, A, Kaltsas, G., Steinmuller, T., Herder, W.W. de, Nikou, G., Plockinger, U, Lopes, JM, Sasano, H, Buscombe, J, Lind, P, O'Toole, D & Oberg, K (2010). ENETS Consensus Guidelines for the Management of Brain, Cardiac and Ovarian Metastases from Neuroendocrine Tumors. Neuroendocrinology, 91(4), 326-332. Phan, AT, Oberg, K, Choi, J, Harrison, LH, Hassan, MM, Strosberg, JR, Krenning, E.P., Kocha, W., Woltering, E.A. & Maples, WJ (2010). NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors Well-Differentiated Neuroendocrine Tumors of the Thorax (Includes Lung and Thymus). Pancreas, 39(6), 784-798. Pool, S.E., Krenning, E.P., Koning, G.A., Eijck, C.H.J. van, Teunissen, J.J.M., Kam, B.L.R., Valkema, R., Kwekkeboom, D.J. & Jong, M. de (2010). Preclinical and Clinical Studies of Peptide Receptor Radionuclide Therapy. Seminars in Nuclear Medicine, 40(3), 209-218. Rolleman, E.J., Melis, M.L., Valkema, R., Boerman, O.C., Krenning, E.P. & Jong, M. de (2010). Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. European Journal of Nuclear Medicine and Molecular Imaging, 37(5), 1018-1031. Roosenburg, S, Laverman, P., Joosten, L, Eek, A, Oyen, W.J.G., Jong, M. de, Rutjes, FPJT, Delft, FL van & Boerman, O.C. (2010). Stabilized In-111-Labeled sCCK8 Analogues for Targeting CCK2-Receptor Positive Tumors: Synthesis and Evaluation. Bioconjugate Chemistry, 21(4), 663-670. Schinkel, A.F.L., Valkema, R., Geleijnse, M.L., Sijbrands, E.J.G. & Poldermans, D. (2010). Single-photon emission computed tomograph for assessment of myocardial viability. EuroIntervention, 6, 115-122. Schroeder, R.P.J., Muller, C.M., Reneman, S., Melis, M.L., Breeman, W.A.P., Blois, E. de, Bangma, C.H., Krenning, E.P., Weerden, W.M. van & Jong, M. de (2010). A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues. European Journal of Nuclear Medicine and Molecular Imaging, 37(7), 1386-1396. Schroeder, R.P.J., Visser, M., Weerden, W.M. van, Ridder, C.M.A. de, Reneman, S., Melis, M.L., Breeman, W.A.P., Krenning, E.P. & Jong, M. de (2010). Androgen-regulated gastrin-releasing peptide receptor expression in androgen-dependent human prostate tumor xenografts. International Journal of Cancer, 126(12), 2826-2834. Vegt, E, Eek, A, Oyen, W.J.G., Jong, M. de, Gotthardt, M & Boerman, O.C. (2010). Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides. European Journal of Nuclear Medicine and Molecular Imaging, 37(2), 226-234. Vegt, E, Jong, M. de, Wetzels, J.F.M., Masereeuw, R, Melis, M.L., Oyen, W.J.G., Gotthardt, M & Boerman, O.C. (2010). Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention. Journal of Nuclear Medicine, 51(7), 1049-1058. Octrooi Jong, M. de, Krenning, E.P. & Rolleman, E.J. (24-12-2009). Combination of amino acid solution and a gelatine derivative for inhibiting renal up-take. no. Part of book - abstract Essen, M. van, Kwekkeboom, D.J., Herder, W.W. de, Bodei, L., Kam, B.L.R., Jong, M. de, Valkema, R. & Krenning, E.P. (2010). Peptide receptor radionuclide therapy in patients with somatostatin receptor-positive neuroendocrine tumors. In Monoclonal antibody and peptide-targeted radiotherapy of cancer (pp. 121). Hoboken NJ: John Wiley & Sons. 89 < back to index EMC MM-01-51-01 - The musculoskeletal system and tissue-engineering in orthopaedics and otorhinolaryngology Programme in brief design The main purpose of this program is to study the basic principles of growth, healing, ageing and degeneration of bone, cartilage and tendon tissue. Critical stages in growth are dictated by molecular and mechanical stimuli. In adult stages and particularly during healing the same stimuli are still active, albeit their influence is usually less strong then during development. Surgery on bone and cartilage for reconstructions in the head and neck region, in joints due to osteoarthritis or osteoporosis and after fractures or injuries is partly based on the self-healing regenerative capacity of these tissues. The research in this programme involves a fundamental approach, using cell and molecular biology techniques, computer models and imaging techniques and aims to find the essential physical and molecular stimuli to (re)generate cartilage, bone and tendon. Cell differentiation stages and appropriate matrix development from precursor (adult stem) cells is examined and its critical stimuli are influenced. In particular the effects of mechanical forces is studied in cell cultures and computational biology models. The general aim in the cartilage research is to develop an optimal cartilage repair method, either from a biomaterial, a cultured autograft, bone marrow derived stem cells or a combination. Bioengineering methods are used to stimulate bone and cartilage cells and effects are studied by molecular techniques. Bone tissue from various clinical and animal experimental sources is evaluated using micro-CT scanning and computer models to study bone strength and turnover. Clinical studies focus on improved evaluation of reconstruction techniques (e.g. x-ray stereophotogrammetry) and the incorporation of more subtle interventions (e.g. growth factors, cell therapy, computer aided surgery). Further work concerns clinical outcome studies with respect to implant surgery, sport injuries, knee trauma and pediatric orthopaedics. Key figures Department orthopaedics Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 2,3 3,22 2,8 4,83 13,15 2,3 3,22 2,8 4,83 13,15 4 0 0 4 24 8 0 36 Thesis Botter, S.M. (2010, december 21). Dynamic subchondral bone changes in murine models of osteoarthritis. EUR (172 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans, Prof.dr. J.P.T.M. van Leeuwen & Dr. G.J.V.M. van Osch. Jansen, J.H.W. (2010, mei 12). Mechanotransduction in bone, Dependency on Human Osteoblast Differation. EUR (133 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans & Prof.dr. J.P.T.M. van Leeuwen. Uitterlinden, E.J. (2010, februari 17). Glucosamine in Osteoarthritis, Effect on articular joint tissues. EUR (144 pag.). Prom./coprom.: Prof. Dr. J.A.N. Verhaar, Prof. Dr. Ir. H.H. Weinans & Dr. G.J.V.M. van Osch. Vos, R.J. de (2010, september 22). Imaging and treatment of Chronic Midportion Achilles Tendinopathy. EUR (196 pag.). Prom./coprom.: Prof. Dr. Ir. H.H. Weinans & Prof. Dr. J.A.N. Verhaar. Artikel/Letter to the editor Bosch, G, Schie, J.T.M. van, Groot, M.W. de, Cadby, J.A., Lest, CHA van de, Barneveld, A & Weeren, PR van (2010). Effects of Platelet-Rich Plasma on the Quality of Repair of Mechanically Induced Core Lesions in Equine Superficial Digital Flexor Tendons: A Placebo-Controlled Experimental Study. Journal of Orthopaedic Research, 28(2), 211-217. Brinks, A., Koes, B.W., Volkers, A.C.W., Verhaar, J.A.N. & Bierma-Zeinstra, S.M.A. (2010). Adverse effects of extra-articular corticosteroid injections: a systematic review. BMC Musculoskeletal Disorders, 11. Bunge, E.M., Bekker- Grob, E.W. de, Biezen, F.C. van, Essink-Bot, M.L. & Koning, H.J. de (2010). Patients' Preferences for Scoliosis Brace Treatment A Discrete Choice Experiment. Spine, 35(1), 57-63. Clockaerts, S.B.F., Bastiaansen-Jenniskens, Y.M., Runhaar, J., Osch, G.J.V.M. van, Offel, JF Van, Verhaar, J.A.N., Clerck, LS De & Somville, J. (2010). The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthritis and Cartilage, 18(7), 876-882. Colaris, J.W., Linden, M.W. van der, Selles, R.W., Coene, N, Allema, J.H. & Verhaar, J.A.N. (2010). Pronation and supination after forearm fractures in children: Reliability of visual estimation and conventional goniometry measurement. Injury-International Journal of the Care of the Injured, 41(6), 643-646. Das, R.H.J., Osch, G.J.V.M. van, Kreukniet, M, Oostra, J, Weinans, H.H. & Jahr, H. (2010). Effects of Individual Control of pH and Hypoxia in Chondrocyte Culture. Journal of Orthopaedic Research, 28(4), 537-545. Das, R.H.J., Jahr, H., Osch, G.J.V.M. van & Farrell, E.J. (2010). The Role of Hypoxia in Bone Marrow-Derived Mesenchymal Stem Cells: Considerations for Regenerative Medicine Approaches. Tissue Engeneering Part B-Reviews, 16(2), 159-168. Gawlitta, D, Farrell, E.J., Malda, J, Creemers, LB, Alblas, J. & Dhert, WJA (2010). Modulating Endochondral Ossification of Multipotent Stromal Cells for Bone Regeneration. Tissue Engeneering Part B-Reviews, 16(4), 385-395. Gorgels, TGMF, Waarsing, J.H., Wolf, A, Brink, J.B., Loves, WJP & Bergen, A.A.B. (2010). Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum. Journal of Molecular Medicine-Jmm, 88(5), 467-475. Hellingman, C.A., Koevoet, J.L.M., Kops, N., Farrell, E.J., Jahr, H., Liu, WJ, Baatenburg de Jong, R.J., Frenz, D.A. & Osch, G.J.V.M. van (2010). Fibroblast Growth Factor Receptors in In Vitro and In Vivo Chondrogenesis: Relating Tissue Engineering Using Adult Mesenchymal Stem Cells to Embryonic Development. Tissue Engineering Part A, 16(2), 545-556. 90 < back to index Intema, F, Hazewinkel, H.A.W., Gouwens, D, Bijlsma, J.W.J., Weinans, H.H., Lafeber, FPJG & Mastbergen, SC (2010). In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model. Osteoarthritis and Cartilage, 18(5), 691-698. Intema, F, Sniekers, Y.H., Weinans, H.H., Vianen, ME, Yocum, SA, Zuurmond, AMM, DeGroot, J., Lafeber, FP & Mastbergen, SC (2010). Similarities and Discrepancies in Subchondral Bone Structure in Two Differently Induced Canine Models of Osteoarthritis. Journal of Bone and Mineral Research, 25(7), 1650-1657. Jansen, J.H.W., Jagt, O.P. van der, Punt, B.J., Verhaar, J.A.N., Leeuwen, J.P.T.M. van, Weinans, H.H. & Jahr, H. (2010). Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study. BMC Musculoskeletal Disorders, 11. Jansen, J.H.W., Eijken, M, Jahr, H., Chiba, H., Verhaar, J.A.N., Leeuwen, J.P.T.M. van & Weinans, H.H. (2010). StretchInduced Inhibition of Wnt/beta-Catenin Signaling in Mineralizing Osteoblasts. Journal of Orthopaedic Research, 28(3), 390-396. Janssen, L.M., Osch, G.J.V.M. van, Li, JP, Kops, N., Groot, K de, Feenstra, L. & Hardillo, J.A.U. (2010). Laryngotracheal reconstruction with porous titanium in rabbits: are vascular carriers and mucosal grafts really necessary? Journal of Tissue Engineering and Regenerative Medicine, 4(5), 395-403. Jonge, S. de, Vos, R.J. de, Schie, J.T.M. van, Verhaar, J.A.N., Weir, A & Tol, JL (2010). One-year follow-up of a randomised controlled trial on added splinting to eccentric exercises in chronic midportion Achilles tendinopathy. British Journal of Sports Medicine, 44(9), 673-677. Malda, J, Hoope, W ten, Schuurman, W, Osch, G.J.V.M. van, Weeren, PR van & Dhert, WJA (2010). Localization of the Potential Zonal Marker Clusterin in Native Cartilage and in Tissue-Engineered Constructs. Tissue Engineering Part A, 16(3), 897-904. Meuffels, D.E., Schuit, S.J., Biezen, F.C. van, Reijman, M. & Verhaar, J.A.N. (2010). The posterior bone block procedure in posterior shoulder instability a long-term follow-up study. Journal of Bone and Joint Surgery-British Volume, 92B(5), 651-655. Raaij, T.M. van, Reijman, M., Brouwer, R.W., Bierma-Zeinstra, S.M.A. & Verhaar, J.A.N. (2010). Medial Knee Osteoarthritis Treated by Insoles or Braces: A Randomized Trial. Clinical Orthopaedics & Related Research, 468(7), 1926-1932. Schie, J.T.M. van, Vos, R.J. de, Jonge, S. de, Bakker, E.M., Heijboer, M.P., Verhaar, J.A.N., Tol, JL & Weinans, H.H. (2010). Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel noninvasive approach. British Journal of Sports Medicine, 44(16), 1153-1159. Sniekers, Y.H., Osch, G.J.V.M. van, Jahr, H., Weinans, H.H. & Leeuwen, J.P.T.M. van (2010). Estrogen Modulates IodoacetateInduced Gene Expression in Bovine Cartilage Explants. Journal of Orthopaedic Research, 28(5), 607-615. Sniekers, Y.H., Weinans, H.H., Osch, G.J.V.M. van & Leeuwen, J.P.T.M. van (2010). Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis. Arthritis Research & Therapy, 12(5). Verseijden, F., Sluijs, S.J. van, Pavljasevic, P., Hofer, S.O.P., Osch, G.J.V.M. van & Farrell, E.J. (2010). Adult Human Bone Marrow- and Adipose Tissue-Derived Stromal Cells Support the Formation of Prevascular-like Structures from Endothelial Cells In Vitro. Tissue Engineering Part A, 16(1), 101-114. Verseijden, F., Sluijs, S.J. van, Farrell, E.J., Neck, J.W. van, Hovius, S.E.R., Hofer, S.O.P. & Osch, G.J.V.M. van (2010). Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs Upon Implantation. Cell Transplantation, 19(8), 1007-1020. Vissers, M.M., Groot, I.B. de, Reijman, M., Bussmann, J.B.J., Stam, H.J. & Verhaar, J.A.N. (2010). Functional capacity and actual daily activity do not contribute to patient satisfaction after total knee arthroplasty. BMC Musculoskeletal Disorders, 11. Vos, R.J. de, Weir, A, Schie, J.T.M. van, Bierma-Zeinstra, S.M.A., Verhaar, J.A.N., Weinans, H.H. & Tol, JL (2010). PlateletRich Plasma Injection for Chronic Achilles Tendinopathy A Randomized Controlled Trial. Jama - Journal of the American Medical Association, 303(2), 144-149. Waarsing, J.H., Rozendaal, R.M., Verhaar, J.A.N., Bierma-Zeinstra, S.M.A. & Weinans, H.H. (2010). A statistical model of shape and density of the proximal femur in relation to radiological and clinical OA of the hip. Osteoarthritis and Cartilage, 18(6), 787-794. Wagemakers, H.P.A., Luijsterburg, P.A., Boks, S.S., Heintjes, E.M., Berger, M.Y., Verhaar, J.A.N., Koes, B.W. & BiermaZeinstra, S.M.A. (2010). Diagnostic Accuracy of History Taking and Physical Examination for Assessing Anterior Cruciate Ligament Lesions of the Knee in Primary Care. Archives of Physical Medicine and Rehabilitation, 91(9), 1452-1459. Wagemakers, H.P.A., Luijsterburg, P.A.J., Heintjes, E.M., Berger, M.Y., Verhaar, J.A.N., Koes, B.W. & Bierma-Zeinstra, S.M.A. (2010). Outcome of knee injuries in general practice: 1-year follow-up. British Journal of General Practice, 60(571), 106-112. Windt, A.E. van der, Jahr, H., Farrell, E.J., Verhaar, J.A.N., Weinans, H.H. & Osch, G.J.V.M. van (2010). Calcineurin Inhibitors Promote Chondrogenic Marker Expression of Dedifferentiated Human Adult Chondrocytes via Stimulation of Endogenous TGF beta 1 Production. Tissue Engineering Part A, 16(1), 1-10. Windt, A.E. van der, Haak, E., Das, R.H.J., Kops, N., Welting, TJM, Caron, MMJ, Til, N.P. van, Verhaar, J.A.N., Weinans, H.H. & Jahr, H. (2010). Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated Tcells 5 in vitro. Arthritis Research & Therapy, 12(3). 91 < back to index Yusuf, E, Nelissen, RG, Ioan-Facsinay, A, Stojanovic-Susulic, V, DeGroot, J., Osch, G.J.V.M. van, Middeldorp, S, Huizinga, T.W.J. & Kloppenburg, M (2010). Association between weight or body mass index and hand osteoarthritis: a systematic review. Annals of the Rheumatic Diseases, 69(4), 761-765. 92 < back to index EMC MM-01-52-07 - Regulation of follicle development, oocyte and endometrial embryo quality Programme in brief design General objectives: The ability of a primordial follicle to undergo folliculogenesis constitutes the very foundation of the expression of the menstrual cycle. During its growth important changes occur within the oöcyte, as well as in its granulose- and theca-cells. These changes include proliferation, differentiation and as well as growth and apoptosis. Hormones (steroid as well proteins) and growth factors control the early (gonadotropin-independent) and late (gonadotropin-dependent) follicle development. Regulation of follicle recruitment and dominant follicle selection as well as ovarian dysfunction is studied in the human model both in-vivo and in-vitro using morphometric, molecular and genetic techniques. Clinical studies involve a) Genetic (genotype - phenotype association) and environmental determinants of anovulatory infertility, especially polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). b) Development of new ovulation induction strategies and optimization of fertility treatment and outcome in patients with ovarian dysfunction. c) Prevention of long-term health implications of reproductive, metabolic and cardiovascular components of ovarian dysfunction especially PCOS and POF. d) Gamete and embryo quality using genetic (preimplantation genetic aneuploidy screening) and molecular techniques in subfertile patients as well as in patients with anovulatory dysfunction. Key figures Department gynaecology/obstetrics urology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 2,97 0 0 1,53 4,5 1,8 0 0 0 1,8 4,77 0 0 1,53 6,3 3 0 0 3 23 4 1 31 Thesis Casteren, N.J. van (2010, december 07). Aspects of early detection of testicular cancer and cancer related. EUR. Prom./coprom.: Prof. Dr. L.H.J. Looijenga, Prof. Dr. C.H. Bangma & G.R. Dohle. Niet, J.E. de (2010, december 14). New approaches in obesity treatment. EUR (125 pag.). Prom./coprom.: Prof.Dr. J. Passchier & Prof. Dr. J.S.E. Laven. Schoenmakers, S. (2010, oktober 15). Silencing of sex chromosomes from meiosis to early embryonic development. EUR. Prom./coprom.: Prof. Dr. J.S.E. Laven, Prof. Dr. J.A. Grootegoed & Dr. Ir. W.M. Baarends. Artikel/Letter to the editor Burgers, J.A., Lie Fong, S., Louwers, Y.V., Valkenburg, O., Jong, F.H. de, Fauser, B.C.J.M. & Laven, J.S.E. (2010). Oligoovulatory and Anovulatory Cycles in Women with Polycystic Ovary Syndrome (PCOS): What's the Difference? Journal of Clinical Endocrinology and Metabolism, 95(12), E485-E489. Casteren, N.J. van, Boellaard, W.P.A., Romijn, J.C. & Dohle, G.R. (2010). Gonadal dysfunction in male cancer patients before cytotoxic treatment. International Journal of Andrology, 33(1), 73-79. Dohle, G.R. (2010). Male infertility in cancer patients: Review of the literature. International Journal of Urology, 17(4), 327-331. Dubbelman, Y., Wildhagen, M.F., Schroder, F.H., Bangma, C.H. & Dohle, G. (2010). Orgasmic Dysfunction After Open Radical Prostatectomy: Clinical Correlates and Prognostic Factors. Journal of Sexual Medicine, 7(3), 1216-1223. Elks, CE, Perry, JRB, Sulem, P, Chasman, DI, Franceschini, N, He, CY, Lunetta, KL, Visser, J.A., Byrne, EM, Cousminer, DL, Gudbjartsson, DF, Esko, T, Feenstra, B., Hottenga, J.J., Koller, DL, Kutalik, Z, Lin, P, Mangino, M, Marongiu, M, McArdle, PF, Smith, AV, Stolk, L., Wingerden, S.H. van, Zhao, JH, Albrecht, E, Corre, T, Ingelsson, E, Hayward, C, Magnusson, PKE, Smith, EN, Ulivi, S, Warrington, NM, Zgaga, L, Alavere, H, Amin, N., Aspelund, T, Bandinelli, S, Barroso, I, Berenson, GS, Bergmann, S, Blackburn, H, Boerwinkle, E., Buring, JE, Busonero, F, Campbell, H, Chanock, SJ, Chen, W., Cornelis, MC, Couper, D, Coviello, AD, d'Adamo, P, Faire, U de, Geus, E.J.C. de, Deloukas, P, Doring, A, Smith, G.D., Easton, D.F., Eiriksdottir, G, Emilsson, V, Eriksson, J, Ferrucci, L, Folsom, A.R., Foroud, T., Garcia, M, Gasparini, P, Geller, F, Gieger, C, Gudnason, V, Hall, P., Hankinson, SE, Ferreli, L, Heath, AC, Hernandez, DG, Hofman, A., Hu, FB, Illig, T, Jarvelin, MR, Johnson, AD, karasik, D., Khaw, KT, Kiel, DP, Kilpelainen, TO, Kolcic, I, Kraft, P, Launer, L.J., Laven, J.S.E., Li, SX, Liu, JJ, Levy, D., Martin, NG, McArdle, WL, Melbye, M, Mooser, V, Murray, JC, Murray, SS, Nalls, MA, Navarro, P, Nelis, M, Ness, AR, Northstone, K, Oostra, B.A., Peacock, M., Palmer, LJ, Palotie, A, Pare, G, Parker, AN, Pedersen, NL, Peltonen, L., Pennell, CE, Pharoah, P., Polasek, O, Plump, AS, Pouta, A, Porcu, E, Rafnar, T, Rice, JP, Ring, SM, Rivadeneira Ramirez, F., Rudan, I, Sala, C, Salomaa, V, Sanna, S, Schlessinger, D, Schork, NJ, Scuteri, A, Segre, AV, Shuldiner, AR, Soranzo, N, Sovio, U, Srinivasan, SR, Strachan, DP, Tammesoo, ML, Tikkanen, E, Toniolo, D., Tsui, K, Tryggvadottir, L, Tyrer, J, Uda, M, Dam, RM van, Meurs, J.B.J. van, Vollenweider, P, Waeber, G, Wareham, NJ, Waterworth, D.M., Weedon, MN, Wichmann, HE, Willemsen, G, Wilson, JF, Wright, AF, Young, L, Zhai, GJ, Zhuang, WV, Bierut, LJ, Boomsma, D.I., Boyd, HA, Crisponi, L, Demerath, EW, Duijn, C.M. van, Econs, M.J., Harris, T.B., Hunter, DJ, Loos, RJF, Metspalu, A, Montgomery, GW, Ridker, P.M., Spector, T.D., Streeten, EA, Stefansson, K, Thorsteinsdottir, U, Uitterlinden, A.G., Widen, E, Murabito, JM, Ong, KK & Murray, A (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-U73. Elzinga-Tinke, J.E., Sirre, ME, Looijenga, L.H.J., Casteren, N.J. van, Wildhagen, M.F. & Dohle, G.R. (2010). The predictive value of testicular ultrasound abnormalities for carcinoma in situ of the testis in men at risk for testicular cancer. International Journal of Andrology, 33(4), 597-603. Empel, IWH van, Aarts, JWM, Cohlen, B.J., Huppelschoten, DA, Laven, J.S.E., Nelen, WLDM & Kremer, J.A.M. (2010). Measuring patient-centredness, the neglected outcome in fertility care: a random multicentre validation study. Human Reproduction, 25(10), 2516-2526. 93 < back to index Hendriks, A.E.J., Boellaard, W.P.A., Casteren, N.J. van, Romijn, J.C., Jong, F.H. de, Boot, A.M. & Drop, S.L.S. (2010). Fatherhood in tall men treated with high-dose sex steroids during adolescence. Journal of Clinical Endocrinology and Metabolism, 95(12), 5233-5240. Heuvel-Eibrink, M.M. van den, Dohle, G.R., Muinck Keizer-Schrama, S.M.P.F., Laven, J.S.E. & Neggers, S.J.C.M.M. (2010). Late effecten van kankerbehandeling bij kinderen. Deel 3: endocriene effecten. Oncollectie, 2, 2-7. Inagaki, A., Schoenmakers, S. & Baarends, W.M. (2010). DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis. Epigenetics, 5(4), 255-266. Janse, F, Knauff, E.A.H., Niermeijer, M.F., Eijkemans, M.J., Laven, J.S.E., Lambalk, C.B., Fauser, B.C.J.M. & Goverde, A.J. (2010). Similar phenotype characteristics comparing familial and sporadic premature ovarian failure. Menopause. The Journal of the North American Menopause Society, 17(4), 758-765. Kerkhof, G.F., Leunissen, R.W.J., Jong, F.H. de, Visser, J.A., Laven, J.S.E. & Hokken-Koelega, A.C.S. (2010). Influence of preterm birth and small birth size on serum anti-Mullerian hormone levels in young adult women. European Journal of Endocrinology, 163, 937-944. Lie Fong, S., Heuvel-Eibrink, M.M. van den, Eijkemans, M.J.C., Schipper, I., Hukkelhoven, C.W.P.M. & Laven, J.S.E. (2010). Pregnancy outcome in female childhood cancer survivors. Human Reproduction, 25(5), 1206-1212. Niet, J.E. de, Koning, C.M. de, Pastoor, H., Duivenvoorden, H.J., Valkenburg, O., Ramakers, M.J., Passchier, J., Klerk, C. de & Laven, J.S.E. (2010). Psychological well-being and sexarche in women with polycystic ovary syndrome. Human Reproduction, 25(6), 1497-1503. Santos, MA, Teklenburg, G, Macklon, N.S., Opstal, D. van, Schuring-Blom, GH, Krijtenburg, P.J., Vreeden-Elbertse, J de, Fauser, BC & Baart, E.B. (2010). The fate of the mosaic embryo: chromosomal constitution and development of Day 4, 5 and 8 human embryos. Human Reproduction, 25(8), 1916-1926. Schoenmakers, S., Wassenaar, E., Laven, J.S.E., Grootegoed, J.A. & Baarends, W.M. (2010). Meiotic silencing and fragmentation of the male germline restricted chromosome in zebra finch. Chromosoma, 119(3), 311-324. Schouten, B.W.V., Bohnen, A.M., Groeneveld, F.P.M.J., Dohle, G.R., Thomas, S. & Bosch, J.L.H.R. (2010). Erectile Dysfunction in the Community: Trends over Time in Incidence, Prevalence, GP Consultation and Medication Use-the Krimpen Study: Trends in ED. Journal of Sexual Medicine, 7(7), 2547-2553. Shang, P., Baarends, W.M., Hoogerbrugge, J., Ooms, M.P., Cappellen, W.A. van, Jong, A.A.W. de, Dohle, G.R., Eenennaam, H. van, Gossen, JA & Grootegoed, J.A. (2010). Functional transformation of the chromatoid body in mouse spermatids requires testis-specific serine/threonine kinases. Journal of Cell Science, 123(3), 331-339. Smit, M., Dohle, G.R. & Romijn, J.C. (2010). Acridine orange binding to RNA interferes DNA fragmentation index calculation in sperm chromatin structure assay Reply. Fertility & Sterility, 94(1), E38-E38. Smit, M., Romijn, J.C., Wildhagen, M.F., Veldhoven, JLM, Weber, R.F.A. & Dohle, G.R. (2010). Decreased sperm DNA fragmentation after surgical variocelectomy is associated with increased pregnancy rate. Journal of Urology, 183(1), 270-274. Smit, M., Wissenburg, O.G., Romijn, J.C. & Dohle, G.R. (2010). Increased Sperm DNA Fragmentation in Patients With Vasectomy Reversal Has No Prognostic Value for Pregnancy Rate. Journal of Urology, 183(2), 662-665. Smit, M., Romijn, J.C., Wildhagen, M.F., Weber, R.F.A. & Dohle, G.R. (2010). Sperm chromatin structure is associated with the quality of spermatogenesis in infertile patients. Fertility & Sterility, 94(5), 1748-1752. Smit, M., Casteren, N.J. van, Wildhagen, M.F., Romijn, J.C. & Dohle, G.R. (2010). Sperm DNA integrity in cancer patients before and after cytotoxic treatment. Human Reproduction, 25(8), 1877-1883. Vujkovic, M., Vries, J.H. de, Lindemans, J., Macklon, N.S., Spek, P.J. van der, Steegers, E.A.P. & Steegers-Theunissen, R.P.M. (2010). The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertility & Sterility, 94(6), 2096-2101. Part of book - abstract Santbrink, E.J.P. van & Fauser, B.C.J.M. (2010). Ovulation induction in anovulatory patients. In A BotrosRisk (Ed.), Ovarian Stimulation. Cambridge: Cambridge University Press. Twigt, J.M., Laven, J.S.E. & Steegers-Theunissen, R.P.M. (2010). Folate in human reproductive performance. In H Obeid (Ed.), Vitamins in the prevention of human diseases. Berlin: De Gruyter STM Medicine. Voorst, S.F. van & Johnson, NP (2010). Management of Hydrosalpinges. In How to improve your ART Succes Rates. Cambridge: Cambridge University Press. Boekredactie Dohle, G.R., Jungwirth, A., Colpi, G., Giwercman, A., Diemer, T. & Hargreave, TB (Eds.). (2010). European association of urology guidelines on male infertility. --: --. 94 < back to index EMC MM-01-54-01 - Pathophysiology of pediatric endocrine, metabolic and renal diseases Programme in brief design Human growth and development including sexual differentiation and puberty and individual organ systems such as the kidney and bone are regulated by the concerted action of a large number of endocrine, paracrine and autocrine factors. This programme aims at: a. Studying normal growth and development and the role of growth hormone and growth factors in congenital and acquired growth disorders by means of epidemiological investigations and clinical trials as well as laboratory studies using various in vitro techniques. b. Long term goals are to unravel in molecular detail the factors involved in the etiology of type 1 diabetes. We want to develop techniques to predict and prevent this disease, eventually applicable in the general population. Immunological, genetic and betacell factors are studied. These aims and goals should allow to develop concomitant strategies to cure or improve the current treatment of those who have already developed the disease. The search for the pathogenesis of type 1 diabetes mellitus the optimal treatment and ultimately its prevention is highly relevant for longterm morbidity, prognosis and socioeconomic consequences at adulthood. c. Studying normal and abnormal renal development as well as therapeutic options by means of multicenter clinical trials. d. Studying intermediary metabolism of patients with inborn errors of aminoacids, organic acids, lipids and defects of cellular organelles, some of them by newborn screening. Development of therapeutic options by dietary intervention or enzyme replacement therapy in nationwide and international collaboration. Special attention is focused on congenital defects of glycosylation, a recently detected group of inborn errors. Key figures Department pediatrics pediatrics-hematology pediatrics-other Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,86 0 0 2 3,86 0 0,72 0 0 0,72 2 3 4,78 2,89 12,67 3,86 3,72 4,78 4,89 17,25 3 0 0 3 52 2 7 64 Thesis Beek, R.D. van (2010, maart 17). Endocrine effects of the treatment for acute lymphoblastic leukemia and Hodgkin's lymphoma in childhood. EUR (191 pag.) (Ridderkerk: Ridderprint B.V.). Prom./coprom.: Prof. Dr. R. Pieters, Dr. M.M. van den HeuvelEibrink & S.M.P.F. Muinck Keizer-Schrama. Damen, G.M. (2010, april 14). Pediatric Inflammatory Bowel Disease. EUR (134 pag.) (Breda: NPN drukkers B.V.). Prom./coprom.: Prof.dr. A.J. van der Heijden, E.E.S. Nieuwenhuis, Dr. J.C. Escher & Dr. J.N. Samsom. Lierop, P.P.E. van (2010, september 15). The role of the innate immune system in inflammatory bowel disease. EUR (172 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. A.J. van der Heijden, E.E.S. Nieuwenhuis, Dr. J.N. Samsom & Dr. J.C. Escher. Artikel/Letter to the editor Aldenhoven, M., Koning, T.J. de, Verheijen, F.W., Prinsen, BHCMT, Wijburg, F.A., Ploeg, A.T. van der, Sain-v.d. Velden, M.G.M. & Boelens, J.J. (2010). Dried blood spot analysis: an easy and reliable tool to monitor the biochemical effect of hematopoietic stem cell transplantation in Hurler Syndrome patients. Biology of Blood and Marrow Transplantation, 16, 701-704. Bannink, E.M.N., Djurhuus, C.B., Christensen, T., Jons, K. & Hokken-Koelega, A.C.S. (2010). Adult height and health-related quality of life after growth hormone therapy in small for gestational age subjects. Journal of Medical Economics, 221-227. Berg, L.E.M. van den, Zandbergen, A.A.M., Capelle, C.I. van, Vries, J.M. de, Hop, W.C.J., Hout, J.M.P. van den, Reuser, A.J.J., Zillikens, M.C. & Ploeg, A.T. van der (2010). Low bone mass in Pompe disease. Muscular strength as a predictor of bone mineral density. Bone, 47, 649-7. Boer, D.P., Rijke, Y.B. de, Hop, W.C.J., Cransberg, K. & Dorresteijn, E.M. (2010). Reference values for serum creatinine in children younger than 1 year of age. Pediatric Nephrology, 25, 2107-2113. Boot, A.M., Ridder, M.A.J. de, Sluis, I.M. van der, Slobbe, I.M. van, Krenning, E.P. & Muinck Keizer-Schrama, S.M.P.F. (2010). Peak bone mineral density, lean body mass and fractures. Bone, 46(2), 336-341. Breukhoven, P.E., Leunissen, R.W.J., Kort, S.W.K. de, Willemsen, R.H. & Hokken-Koelega, A.C.S. (2010). Preterm birth does not affect bone mineral density in young adults. European Journal of Endocrinology, 164, 133-138. Burton, B.K., Guffon, N., Roberts, J., Ploeg, A.T. van der & Jones, S.A. (2010). Home treatment with intravenous enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II - data from the Hunter Outcome Survey. Molecular Genetics and Metabolism, 101, 123-129. Capelle, C.I. van, Beek, N.A.M.E. van der, Hagemans, M.L.C., Arts, W.F.M., Hop, W.C.J., Lee, P., Jaeken, J., Frohn-Mulder, I.M.E., Merkus, P.J.F.M., Corzo, D, Puga, A.C., Reuser, A.J.J. & Ploeg, A.T. van der (2010). Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. Neuromuscular Disorders, 20, 775-782. Capelle, C.I. van, Goedegebure, A., Homans, N.C., Hoeve, L.J., Reuser, A.J.J. & Ploeg, A.T. van der (2010). Hearing loss in Pompe disease revisited: results from a study of 24 children. Journal of Inherited Metabolic Disease, 33(5), 597-602. 95 < back to index Crop, M.J., Rijke, Y.B. de, Verhagen, P.C.M.S., Cransberg, K. & Zietse, R. (2010). Diagnostic Value of Urinary Dysmorphic Erythrocytes in Clinical Practice. Nephron Clinical Practice, 115(3), C203-C212. Feith, E.A., Holthe, JE Kist-van & Heijden, A.J. van der (2010). Nephrocalcinosis in preterm neonates. Pediatric Nephrology, 25, 221-230. Geelhoed, J.J.M., Taal, H.R., Steegers, E.A., Arends, L.R., Lequin, M., Moll, H.A., Hofman, A., Heijden, A.J. van der & Jaddoe, V.W.V.K. (2010). Kidney growth curves in healthy children from the third trimester of pregnancy until the age of two years. The Generation R Study. Pediatric Nephrology, 25(2), 289-298. Gelder, C.M. van, Hagemans, M.L.C., Hout, J.M.P. van den, Smeitink, J.A.M.., Coo, I.F.M. de & Ploeg, A.T. van der (2010). Tijdige diagnostiek en behandeling van de ziekte van Pompe kan irreversibele orgaanschade voorkomen. Tijdschrift voor Kindergeneeskunde, 78(2), 81-88. Gool, S.A. van, Kamp, G.A., Odink, RJ, Muinck Keizer-Schrama, S.M.P.F., Delemarre van de Waal, HA, oostdijk, W. & Wit, J.M. (2010). High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height. European Journal of Endocrinology, 162, 653-660. Graaff, L.C.G. de, Argente, J., Meurs, J.B.J. van, Uitterlinden, A.G. & Hokken-Koelega, A.C.S. (2010). Genetic polymorphisms in the locus control region and promoter of GH1 are related to serum IGF-I levels and height in patients with isolated growth hormone deficiency and healthy controls. Hormone Research, 73, 25-34. Graaff, L.C.G. de, Argente, J., Veenma, D.C.M., Drent, M., Uitterlinden, A.G. & Hokken-Koelega, A.C.S. (2010). PROP1, HESX1, POU1F1. LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Hormone Research, 73, 363-371. Grijpink-van den Biggelaar, K., Drop, S.L.S. & Schuwirth, L. (2010). Development of an e-learning portal for pediatric endocrinology: educational considerations. Hormone Research, 73, 223-230. Hagemans, M.L.C., Stigter, R.L., Capelle, C.I. van, Beek, N.A.M.E. van der, Winkel, L.P.F., Vliet, L. van, Hop, W.C.J., Reuser, A.J.J., Beishuizen, A. & Ploeg, A.T. van der (2010). PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease. Journal of Inherited Metabolic Disease, 33, 133-139. Hagemans, M.L.C., Brands, M.M.M.G., Capelle, C.I. van, Mulder, M.F., Helbing, W.A., Arts, W.F.M. & Ploeg, A.T. van der (2010). Mucopolysacharidose type II en type IV: de ziekten van Hunter en van Maroteaus-Lamy. Tijdschrift voor Kindergeneeskunde, 78(2), 62-69. Hendriks, A.E.J., Boellaard, W.P.A., Casteren, N.J. van, Romijn, J.C., Jong, F.H. de, Boot, A.M. & Drop, S.L.S. (2010). Fatherhood in tall men treated with high-dose sex steroids during adolescence. Journal of Clinical Endocrinology and Metabolism, 95(12), 5233-5240. Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), 4227-4234. Heuvel-Eibrink, M.M. van den, Dohle, G.R., Muinck Keizer-Schrama, S.M.P.F., Laven, J.S.E. & Neggers, S.J.C.M.M. (2010). Late effecten van kankerbehandeling bij kinderen. Deel 3: endocriene effecten. Oncollectie, 2, 2-7. Hunter, K.B., Lucke, T., Spranger, J., Smithson, S., Alpay, H., Andre, J.L., Asakura, Y., Bogdanovic, R., Bonneau, D, Cairns, R., Cransberg, K., Frund, S., Fryssira, H., Goodman, D., Helmke, K., Hinkelmann, B., Lama, G, Lamfers, P., Loirat, C., Majore, S., Mayfield, C., Pontz, B.F., Rusu, C., Saraiva, J.M., Schmidt, B., Shoemaker, L., Sigaudy, S, Stajic, N., Taha, D. & Boerkoel, C.F. (2010). Schimke immuunoosseous dysplasia: defining skeletal features. European Journal of Pediatrics, 169, 801-811. Jaddoe, V.W.V.K., Duijn, C.M. van, Heijden, A.J. van der, Mackenbach, J.P., Moll, H.A., Steegers, E.A.P., Tiemeier, H.W., Uitterlinden, A.G., Verhulst, F.C. & Hofman, A. (2010). The Generation R Study: design and cohort update 2010. European Journal of Epidemiology, 25(11), 823-841. Kaay, D.C.M. van der, Bakker, B., Hulst, F van der, Mul, D., Mulder, J, Schroor, E, Elswijk, D van, Rowaan, I, Willeboer, M, Ridder, M.A.J. de & Hokken-Koelega, A.C.S. (2010). Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels. European Journal of Endocrinology, 162(5), 887-895. Keijzer-Veen, M.G., Devos, A.S., Meradji, M., Dekker, F.W., Nauta, J. & Heijden, A.J. van der (2010). Reduced renal length and volume 20 years after very preterm birth. Pediatric Nephrology, 25, 499-507. Keijzer-Veen, M.G., Dulger, A, Dekker, F.W., Nauta, J. & Heijden, A.J. van der (2010). Very preterm birth is a risk factor for increased systolic blood pressure at a young adult age. Pediatric Nephrology, 25, 509-516. Kerkhof, G.F., Leunissen, R.W.J., Jong, F.H. de, Visser, J.A., Laven, J.S.E. & Hokken-Koelega, A.C.S. (2010). Influence of preterm birth and small birth size on serum anti-Mullerian hormone levels in young adult women. European Journal of Endocrinology, 163, 937-944. Kok, R.C., Timmerman, M.A., Wolffenbuttel, K.P., Drop, S.L.S. & Jong, F.H. de (2010). Isolated 17,20-Lyase deficiency due to the cytochrome b5 mutation W27X. Journal of Clinical Endocrinology and Metabolism, 95(3), 994-999. 96 < back to index Kort, S.W.K. de, Mook-Kanamori, D.O., Jaddoe, V.W.V.K. & Hokken-Koelega, A.C.S. (2010). Interactions between TCF7L2 genotype and growth hormone-induced changes in glucose homeostatis in small for gestational age children. Clinical Endocrinology, 72, 47-52. Kort, S.W.K. de, Doorn, J. van, Sande, A.G.M. van de, Leunissen, R.W.J. & Hokken-Koelega, A.C.S. (2010). Serum insulin-like growth factor-Binding protein-2 levels and metabolic and cardiovascular risk factors in young adults and children born small for gestational age. Journal of Clinical Endocrinology and Metabolism, 95(2), 864-871. Kort, S.W.K. de & Hokken-Koelega, A.C.S. (2010). The PPAR-y Pro12Ala polymorphisms associated with weight gain during GH-treatment in short children born small for gestationa age. European Journal of Endocrinology, 162, 49-52. Lem, A.J., Kort, S.W.K. de, Ridder, M.A.J. de & Hokken-Koelega, A.C.S. (2010). Should short children born small for gestational age with a distance to target height <1 standard deviation score be excluded form growth hormone treatment? Clinical Endocrinology, 73, 355-360. Leunissen, R.W.J., Gao, Y., Cianflone, K., Stijnen, T. & Hokken-Koelega, A.C.S. (2010). Growth patterns during childhood and the relationship with acylation-stimularing protein. Clinical Endocrinology, 72, 775-780. Levy-Marchal, C., Arslanian, S., Cutfield, WS, Sinaiko, A., Druet, C., Marcovecchio, L. & Chiarelli, F. (2010). Insulin Resistance in Children: Consensus, perspective and future directions. Journal of Clinical Endocrinology and Metabolism, 95(12), 51895198. Lind van Wijngaarden, R.F.A. de, Cianflone, K., Gao, Y., Leunissen, R.W.J. & Hokken-Koelega, A.C.S. (2010). Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi Syndrome and effects of growth hormone treatment. Journal of Clinical Endocrinology and Metabolism, 95(4), 1758-1766. Looijenga, L.H.J., Hersmus, R., Leeuw, H.C.G.M. de, Stoop, H., Cools, MBC, Oosterhuis, J.W., Drop, S.L.S. & Wolffenbuttel, K.P. (2010). Gonadal tumours and DSD. Best Practice & Research Clinical Endocrinology & Metabolism, 24, 391-310. Maas, A.J.B.M., Mook-Kanamori, D.O., Ay, L., Steegers, E.A.P., Duijn, C.M. van, Hofman, A., Hokken-Koelega, A.C.S. & Jaddoe, V.W.V.K. (2010). Insulin VNTR and IGF-1 promotor region polymorphisms are not associated with body composition in early childhood: The Generation R Study. Hormone Research, 73, 120-127. Manenschijn, L., Akker, E.L.T. van den, Ester, W.A., Leunissen, R.W.J., Willemsen, R.H., Rossum, E.F.C. van, Koper, F.J.W., Lamberts, S.W.J & Hokken-Koelega, A.C.S. (2010). Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age. European Journal of Endocrinology, 163, 911-918. Mehls, O., Lindberg, A., Nissel, R., Haffner, D., Hokken-Koelega, A.C.S. & Ranke, M. (2010). Predicting the response to growth hormone treatment in short children with chronic kidney disease. Journal of Clinical Endocrinology and Metabolism, 95(2), 686692. Menke, L.A., Sas, T.C.J., Muinck Keizer-Schrama, S.M.P.F., Zandwijken, G.R.J., Ridder, M.A.J. de, Odink, RJ, Jansen, M., Delamarre- van de Waal, H.A., Stokvis-Brantsma, W.H., Waelkens, J., Westerlaken, C., Reeser, H.M., Trotsenburg, A.S.P. van, Gevers, E., Buuren, S. van, Dejonckere, P.H.O., Hokken-Koelega, A.C.S., Otten, B.J. & Wit, J.M. (2010). Efficacy and safety of Oxandrolone in growth hormone-treated girls with Turner Syndrome. Journal of Clinical Endocrinology and Metabolism, 95(3), 1151-1160. Menke, L.A., Sas, T.C.J., Zandwijken, G.R.J., Ridder, M.A.J. de, Stijnen, Th., Muinck Keizer-Schrama, S.M.P.F., Otten, B.J. & Wit, J.M. (2010). The effect of oxandrolone on body proportions and body composition in growth hormone-treated girls with Turner syndrome. Clinical Endocrinology, 73, 212-219. Menke, L.A., Sas, T.C.J., Visser, M., Kreukels, B.P.C., Stijnen, Th., Zandwijken, G.R.J., Muinck Keizer-Schrama, S.M.P.F., Otten, B.J., Wit, J.M. & Cohen-Kettenis, P.T. (2010). The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome. Hormones & Behavior, 57, 297-305. Mul, D., Grote, F.K., Goudriaan, J.R., Muinck Keizer-Schrama, S.M.P.F., Wit, J.M. & oostdijk, W. (2010). Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis. Hormone Research, 74, 351-357. Otten, M.H., Cransberg, K., Rossum, M.A.J. van, Groothoff, J.W., Kist - van Holthe tot Echten, J.E., Cate, R. ten & SuijlekomSmit, L.W.A. van (2010). Disease activity patterns in juvenile systemic lupus erythematosus and its relation to early aggressive treatment. Lupus, 19, 1550-1556. Pleskacova, J., Hersmus, R., Oosterhuis, J.W., Setyawati, B.A., Faradz, SMH, Cools, M.B.C., Wolffenbuttel, K.P., Lebl, J., Drop, S.L.S. & Looijenga, L.H.J. (2010). Tumor risk in disorders of sex development. Sexual Development, 4, 259-269. Ploeg, A.T. van der, Clemens, P.R., Corzo, D, Escolar, D.M., Florence, J., Groeneveld, G.J., Herson, S., Kishnani, PS, Laforet, P, Lake, S., Lange, D.J., Leshner, R.T., Morgan, C., Nozaki, K., Park, D.J., Pestronk, A., Rosenbloom, B., Skrinar, A., Capelle, C.I. van, Beek, N.A. van der, Wasserstein, M. & Zivkovic, S.A. (2010). A randomized study of alglucosidase alfa in late-onset Pompe's disease. New England Journal of Medicine, 362, 1396-1406. Ploeg, A.T. van der (2010). Where do we stand in enzyme replacement therapy in Pompe's disease? Neuromuscular Disorders, 20, 773-774. Ploeg, A.T. van der & Wijburg, F.A. (2010). Lysosomale stapelingsziekten: van diagnose naar behandeling. Tijdschrift voor Kindergeneeskunde, 78(2), 46-49. 97 < back to index Prytula, A.A., Iijima, K., Kamei, K., Geary, D., Gottlich, E., Majeed, A., Taylor, M., Marks, S., Tuchman, SA, Camilla, R., Ognjanovic, M., Filler, G., Smith, G. & Tullus, K. (2010). Rituximab in fefractory nephrotic syndrome. Pediatric Nephrology, 25, 461-468. Rossem, L. van, Silva, L.M., Hokken-Koelega, A., Arends, L.R., Moll, H.A., Jaddoe, V.W.V.K., Hofman, A., Mackenbach, J.P. & Raat, H. (2010). Socioeconomic status is not inversely associated with overweight in preschool children. Journal of Pediatrics, 157(6), 929-935. Sas, T.C.J., Ridder, M.A.J. de, Wit, J.M., Rotteveel, J, oostdijk, W., Reeser, H.M., Otten, B.J. & Muinck Keizer-Schrama, S.M.P.F. (2010). Adult height in children with growth hormone deficiency: a randomized, controlled, growth hormone doseresponse trial. HORMONE RESEARCH IN PAEDIATRICS, 74, 172-181. Teunissen, Q., Spronsen, F.J. van, Visser, G., Brands, M.M.M.G., Ploeg, A.T. van der & Wijburg, F.A. (2010). Mucopolysacharidose type I: de ziekten van Hurler en Scheie. Tijdschrift voor Kindergeneeskunde, 78(2), 57-62. Til, N.P. van, Stok, M., Aerts, F.S.F., Waard, M.C. de, Farahbakhshian, E., Visser, T.P., Kroos, M.A., Jacobs, E.H., Willart, M.A., Wegen, C.G. van der, Scholte, B.J., Lambrecht, B.N.M., Duncker, D.J.G.M., Ploeg, A.T. van der, Reuser, A.J.J., Verstegen, M.M.A. & Wagemaker, G. (2010). Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood, 115(26), 5329-5337. Touw, C.M.L., Aldenhoven, M., Hasselt, P.M. van, Wijburg, F.A., Teunissen, Q., Ploeg, A.T. van der, Mulder, M.F., Boelens, J.J. & Koning, T.J. de (2010). Presenterende symptomen bij het syndroom van Hurler. Tijdschrift voor Kindergeneeskunde, 78(4), 149-154. Veenma, D.C.M., Eussen, H.J.F.M.M., Govaerts, L.C.P., Kort, S.W.K. de, Odink, RJ, Wouters, C.H., Hokken-Koelega, A.C.S. & Klein, A. de (2010). Phenotype-genotype correlation in a familial IGF1R microdeletion care. Journal of Medical Genetics, 47, 492-498. Vliet, M. van, Heyden, J.C. van der, Diamant, M., Rosenstiel, I.A. von, Schindhelm, R.K., Aanstoot, H.J. & Veeze, H.J. (2010). Overweight is highly prevalent in children with type 1 diabetes and associates with cardiometabolic risk. Journal of Pediatrics, 156(6), 923-929. Vries, J.M. de, Hagemans, M.L.C., Bussmann, J.B.J., Ploeg, A.T. van der & Doorn, P.A. van (2010). Fatigue in neuromuscular disorders: focus on Guillain-Barr, syndrome and Pompe disease. Cellular and Molecular Life Sciences, 67(5), 701-713. Vries, J.M. de, Beek, N.A.M.E. van der, Kroos, M.A., Ozkan, L., Doorn, P.A. van, Richards, S.M., Sung, C.C.C., Brugma, J.C., Zandbergen, A.A.M., Ploeg, A.T. van der & Reuser, A.J.J. (2010). High antibody titer in an adult with Pompe disease affects treatment with alglucosidase alfa. Molecular Genetics and Metabolism, 101, 338-345. Winkel, M.L. te, Beek, R.D. van, Muinck Keizer-Schrama, S.M.P.F., Uitterlinden, A.G., Hop, W.C.J., Pieters, R. & HeuvelEibrink, M.M. van den (2010). Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia. Haematologica, 95(5), 752-758. Boekredactie Heijden, A.J. van der (Ed.). (2010). Het pediatrisch formularium. Houten: Bohn Stafleu van Loghum. 98 < back to index EMC MM-02-41-03 - Malignant transformation of hematopoietic stem cells: pathophysiology and development of therapy Programme in brief design In this project we investigate abnormalities in the cellular responsiveness to hematopoietic growth factors, the expression, structure and function of hematopoie¬tic growth factor receptors as well as alterations of signal transduction and transcripti¬on that may contribute to the develop¬ment of hematological malignancies. The abnormalities may influence the survival, cell cycle regulation, commitment or maturation of hematopoietic progenitor cells. The investiga¬ti¬ons on the genetic abnormalities of hemato-oncologic diseases extend towards the development of a specific diagnosis and the detection of minimal residual disease, as well as new therapeutic interventions of hematological malignancies. With respect to the development of new treatment strategies aimed at eradicating malignant hematopoietic progenitor cells, we address questions related to their sensitivity to chemotherapy, the response to novel drugs that target specific genes and the clinical development of stem cell transplantation. The modalities are explored in relevant animal models as well as in clinical studies. Key figures Department hematology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,95 5,41 8,18 6,75 22,29 1,95 5,41 8,18 6,75 22,29 2 0 0 2 37 0 1 40 Thesis Deenik, W. (2010, januari 15). Prevention of resistance in chronic myeloid leukemia: the role of combination therapy. EUR (171 pag.). Prom./coprom.: Prof. Dr. J.J. Cornelissen. Lugthart, S. (2010, september 22). EVI 1 in acute myeloide leukemie. EUR (239 pag.). Prom./coprom.: Prof. Dr. B. Lowenberg & Prof. Dr. H.R. Delwel. Artikel/Letter to the editor Abbas, S., Lugthart, S., Kavelaars, F.G., Schelen, A.M., Koenders, J.E., Zeilemaker, A., Putten, W.L.J. van, Rijneveld, A.W., Lowenberg, B. & Valk, P.J.M. (2010). Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value. Blood, 116(12), 2122-2126. Abbas, S., Erpelinck - Verschuren, C.A.J., Goudswaard, C.S., Lowenberg, B. & Valk, P.J.M. (2010). Mutant Wilms' tumor 1 (WT1) mRNA with premature termination codons in acute myeloid leukemia (AML) is sensitive to nonsense-mediated RNA decay (NMD). Leukemia, 24(3), 660-663. Agrawal-Singh, S, Koschmieder, S, Gelsing, S, Stocking, C., Stehling, M., Thiede, C, Thoennissen, NH, Kohler, G, Valk, P.J.M., Delwel, H.R., Mills, K, Baumer, N, Tickenbrock, L, Hansen, K, Berdel, WE, Muller-Tidow, C & Serve, H (2010). Pim2 cooperates with PML-RAR alpha to induce acute myeloid leukemia in a bone marrow transplantation model. Blood, 115(22), 4507-4516. Balgobind, B.V., Lugthart, S., Hollink, I.H.I.M., Peters, T.C.J.M., Wering, E.R. van, Graaf, S.S.N. de, Reinhardt, D., Creutzig, U., Kaspers, G.J.L., Bont, E.S.J.M. de, Stary, J., Trka, J., Zimmermann, M., Beverloo, H.B., Pieters, R., Delwel, H.R., Zwaan, C.M. & Heuvel-Eibrink, M.M. van den (2010). EV11 overexpression in distinct subtypes of pediatric acute myeloid leukemia. Leukemia, 24, 942-949. Balgobind, B.V., Hollink, I.H.I.M., Reinhardt, D., Wering, E.R. van, Graaf, S.S.N. de, Baruchel, A, Stary, J., Beverloo, H.B., Greef, G.E. de, Pieters, R., Zwaan, C.M. & Heuvel-Eibrink, M.M. van den (2010). Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique. European Journal of Cancer, 46, 1892-1899. Beekman, R. & Touw, I.P. (2010). G-CSF and its receptor in myeloid malignancy. Blood, 115(25), 5131-5136. Broyl, A., Hose, D, Lokhorst, H., Knegt, Y. de, Peeters, J., Jauch, A, Bertsch, U, Sonneveld, P., Buijs, A, Stevens-Kroef, M., Beverloo, H.B., Vellenga, E., Zweegman, S., Kersten, MJ, Holt, B. van der, Jarari, L el, Mulligan, G, Goldschmidt, H. & Duin, M. van (2010). Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood, 116(14), 2543-2553. Broyl, A., Corthals, S.L., Jongen, J.L.M., Holt, B. van der, Kuiper, R., Knegt, Y. de, Duin, M. van, Jarari, L el, Bertsch, U, Lokhorst, H.M., Durie, B.G., Goldschmidt, H. & Sonneveld, P. (2010). Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON65/GMMG-HD4 trial. Lancet Oncology, 11(11), 1057-1065. Cervera, J, Montesinos, P, Hernandez-Rivas, JM, Calasanz, MJ, Aventin, A, Ferro, MT, Luno, E, Sanchez, J, Vellenga, E., Rayon, C, Milone, G, Serna, J de la, Rivas, C, Gonzalez, JD, Tormo, M, Amutio, E, Gonzalez, M., Brunet, S, Lowenberg, B. & Sanz, M.A. (2010). Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Haematologica, 95(3), 424-431. Deenik, W., Janssen, J.J.W.M., Holt, B. van der, Verhoef, G.E.G., Smit, WM, Kersten, MJ, Daenen, S.M.G.J., Verdouck, LF, Ferrant, A., Schattenberg, A.V.M.B., Sonneveld, P., Kooy, MV, Wittebol, S., Willemze, R., Wijermans, P.W., Beverloo, H.B., Lowenberg, B., Valk, P.J.M., Ossenkoppele, G.J. & Cornelissen, J.J. (2010). Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. Haematologica, 95(6), 914-921. 99 < back to index Deenik, W., Holt, B. van der, Janssen, J.J.W.M., Chu, IWT, Valk, P.J.M., Ossenkoppele, G.J., Heiden, I.P. van der, Sonneveld, P., Schaik, R.H.N. van & Cornelissen, J.J. (2010). Polymorphisms in the multidrug resistance gene MDR1 (ABCB1) predict for molecular resistance in patients with newly diagnosed chronic myeloid leukemia receiving high-dose imatinib. Blood, 116(26), 6144-6145. Delforge, M., Blade, J., Dimopoulos, MA, Facon, T., Kropff, M, Ludwig, H., Palumbo, A., Damme, P. van, San-Miguel, JF & Sonneveld, P. (2010). Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncology, 11(11), 1086-1095. Dimopoulos, MA, Terpos, E, Chanan-Khan, A, Leung, N, Ludwig, H., Jagannath, S, Niesvizky, R, Giralt, S, Fermand, JP, Blade, J., Comenzo, RL, Sezer, O, Palumbo, A., Harousseau, JL, Richardson, PG, Barlogie, B, Anderson, KC, Sonneveld, P., Tosi, P, Cavo, M., Rajkumar, SV, Durie, BGM & Miguel, J San (2010). Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group. Journal of Clinical Oncology, 28(33), 4976-4984. Dohner, H., Estey, E.H., Amadori, S, Appelbaum, F.R., Buchner, T, Burnett, AK, Dombret, H., Fenaux, P, Grimwade, D., Larson, R.A., Lo-Coco, F, Naoe, T, Niederwieser, D., Ossenkoppele, G.J., Sanz, M.A., Sierra, J., Tallman, M.S., Lowenberg, B. & Bloomfield, C.D. (2010). Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood, 115(3), 453-474. Figueroa, ME, Lugthart, S., Li, YS, Erpelinck - Verschuren, C.A.J., Deng, XT, Christos, PJ, Schifano, E, Booth, J, Putten, W.L.J. van, Skrabanek, L, Campagne, F, Mazumdar, M, Greally, JM, Valk, P.J.M., Lowenberg, B., Delwel, H.R. & Melnick, A (2010). DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia. Cancer Cell, 17(1), 13-27. Figueroa, ME, Abdel-Wahab, O, Lu, C, Ward, PS, Patel, J., Shih, A, Li, YS, Bhagwat, N, Vasanthakumar, A, Fernandez, HF, Tallman, M.S., Sun, ZX, Wolniak, K, Peeters, J.K., Liu, W., Choe, SE, Fantin, VR, Paietta, E., Lowenberg, B., Licht, J.D., Godley, LA, Delwel, H.R., Valk, P.J.M., Thompson, CB, Levine, RL & Melnick, A (2010). Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation. Cancer Cell, 18(6), 553-567. Groschel, S, Lugthart, S., Schlenk, R.F., Valk, P.J.M., Eiwen, K, Goudswaard, C.S., Putten, WJL van, Kayser, S, Verdonck, L.F., Lubbert, M, Ossenkoppele, G.J., Germing, U, Schmidt-Wolf, I, Schlegelberger, B, Krauter, J, Ganser, A, Dohner, H., Lowenberg, B., Dohner, K & Delwel, H.R. (2010). High EVI1 Expression Predicts Outcome in Younger Adult Patients With Acute Myeloid Leukemia and Is Associated With Distinct Cytogenetic Abnormalities. Journal of Clinical Oncology, 28(12), 2101-2107. Janssen, J.J.W.M., Denkers, F., Valk, P.J.M., Cornelissen, J.J., Schuurhuis, G.J. & Ossenkoppele, G.J. (2010). Methylation patterns in CD34 positive chronic myeloid leukemia blast crisis cells. Haematologica, 95(6), 1036-1037. Jonge, HJM de, Valk, P.J.M., Veeger, NJGM, Elst, A. ter, Boer, M.L. den, Cloos, J, Haas, V. de, Heuvel-Eibrink, M.M. van den, Kaspers, G.J.L., Zwaan, C.M., Kamps, W.A., Lowenberg, B. & Bont, E.S.J.M. de (2010). High VEGFC expression is associated with unique gene expression profiles and predics adverse prognosis in pediatric and adult acute myeloid leukemia. Blood, 116(10), 1747-1754. Khandanpour, C, Thiede, C, Valk, P.J.M., Sharif-Askari, E, Nuckel, H, Lohmann, D, Horsthemke, B., Siffert, W, Neubauer, A., Grzeschik, KH, Bloomfield, C.D., Marcucci, G, Maharry, K, Slovak, M.L., Reijden, B.A. van der, Jansen, J.H., Schackert, HK, Afshar, K, Schnittger, S., Peeters, J.K., Kroschinsky, F, Ehninger, G, Lowenberg, B., Duhrsen, U & Moroy, T (2010). A variant allele of Growth Factor Independence 1 (GFI1) is associated with acute myeloid leukemia. Blood, 115(12), 2462-2472. Kyle, R.A., Durie, BGM, Rajkumar, SV, Landgren, O, Blade, J., Merlini, G, Kroger, N, Einsele, H, Vesole, DH, Dimopoulos, M, Miguel, J San, Avet-Loiseau, H, Hajek, R., Chen, WM, Anderson, KC, Ludwig, H., Sonneveld, P., Pavlovsky, S, Palumbo, A., Richardson, PG, Barlogie, B, Greipp, P, Vescio, R, Turesson, I., Westin, J & Boccadoro, M. (2010). Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia, 24(6), 1121-1127. Kyriakou, C, Canals, C, Cornelissen, J.J., Socie, G, Willemze, R., Ifrah, N, Greinix, HT, Blaise, D., Deconinck, E, Ferrant, A., Schattenberg, A., Harousseau, JL, Sureda, A & Schmitz, N. (2010). Allogeneic Stem-Cell Transplantation in Patients With Waldenstrom Macroglobulinemia: Report From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology, 28(33), 4926-4934. Lokhorst, H.M., Holt, B. van der, Zweegman, S., Vellenga, E., Croockewit, S, Oers, MH van, Borne, PV, Wijermans, P., Schaafsma, R., Weerdt, O de, Wittebol, S., Delforge, M., Berenschot, H, Bos, GM, Jie, KSG, Sinnige, H, Marwijk-Kooy, M van, Joosten, P., Minnema, M.C., Ammerlaan, A.H.M. & Sonneveld, P. (2010). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood, 115(6), 1113-1120. Lowenberg, B., Beck, J., Graux, C., Putten, W.L.J. van, Schouten, H.C., Verdonck, L.F., Ferrant, A., Sonneveld, P., JongenLavrencic, M., Lilienfeld-Toal, M von, Biemond, BJ, Vellenga, E., Breems, D. den, Muijnck, H de, Schaafsma, R., Verhoef, G., Dohner, H., Gratwohl, A., Pabst, T, Ossenkoppele, GL & Maertens, J. (2010). Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood, 115(13), 2586-2591. Lowenberg, B., Morgan, G., Ossenkoppele, G.J., Burnett, AK, Zachee, P, Duhrsen, U, Dierickx, D, Muller-Tidow, C, Sonneveld, P., Krug, U, Bone, E, Flores, N, Richardson, AF, Hooftman, L, Jenkins, C, Zweegman, S. & Davies, F (2010). Phase I/II Clinical Study of Tosedostat, an Inhibitor of Aminopeptidases, in Patients With Acute Myeloid Leukemia and Myelodysplasia. Journal of Clinical Oncology, 28(28), 4333-4338. Ludwig, H., Beksac, M., Blade, J., Boccadoro, M., Cavenagh, J, Cavo, M., Dimopoulos, M, Drach, J, Einsele, H, Facon, T., Goldschmidt, H., Harousseau, JL, Hess, U., Ketterer, N, Kropff, M, Mendeleeva, L, Morgan, G., Palumbo, A., Plesner, T, Miguel, J San, Shpilberg, O, Sondergeld, P, Sonneveld, P. & Zweegman, S. (2010). Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective. Oncologist, 15(1), 6-25. 100 < back to index Ludwig, H., Bolejack, V, Crowley, J, Blade, J., Miguel, J San, Kyle, R.A., Rajkumar, SV, Shimizu, K., Turesson, I., Westin, J, Sonneveld, P., Cavo, M., Boccadoro, M., Palumbo, A., Tosi, P, Harousseau, JL, Attal, M, Barlogie, B, Stewart, AK & Durie, B (2010). Survival and Years of Life Lost in Different Age Cohorts of Patients With Multiple Myeloma. Journal of Clinical Oncology, 28(9), 1599-1605. Lugthart, S., Groschel, S, Beverloo, H.B., Kayser, S, Valk, P.J.M., Zelderen-Bhola, SL Van, Ossenkoppele, G.J., Vellenga, E., Ruiter, E. de, Schanz, U, Verhoef, G., Vandenberghe, P., Ferrant, A., Koohne, CH, Pfreundschuh, M, Horst, HA, Koller, E, Lilienfeld-Toal, M von, Bentz, M, Ganser, A, Schlegelberger, B, Jotterand, M, Krauter, J, Pabst, T, Theobald, M., Schlenk, R.F., Delwel, H.R., Doohner, K, Lowenberg, B. & Dohner, H. (2010). Clinical, Molecular, and Prognostic Significance of WHO Type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia. Journal of Clinical Oncology, 28(24), 3890-3898. Montesinos, P, Gonzalez, JD, Gonzalez, J, Rayon, C, Lisa, E de, Amigo, ML, Ossenkoppele, G.J., Penarrubia, MJ, PerezEncinas, M, Bergua, J, Deben, G, Sayas, MJ, Serna, J de la, Ribera, J.M., Bueno, J, Milone, G, Rivas, C, Brunet, S, Lowenberg, B. & Sanz, M (2010). Therapy-Related Myeloid Neoplasms in Patients With Acute Promyelocytic Leukemia Treated With AllTrans-Retinoic Acid and Anthracycline-Based Chemotherapy. Journal of Clinical Oncology, 28(24), 3872-3879. Petzold, A, Mondria, T., Kuhle, J, Rocca, MA, Cornelissen, J.J., Boekhorst, PT, Lowenberg, B., Giovannoni, G, Filippi, M., Kappos, L. & Hintzen, R.Q. (2010). Evidence for Acute Neurotoxicity after Chemotherapy. Annals of Neurology, 68(6), 806-815. Posthuma, HLA, Skoda, RC, Jacob, FA, Maas, APC van der, Valk, P.J.M. & Posthuma, EFM (2010). Hereditary thrombocytosis not as innocent as thought? Development into acute leukemia and myelofibrosis. Blood, 116(17), 3375-3376. Sanz, M.A., Montesinos, P, Rayon, C, Holowiecka, A, Serna, J de la, Milone, G, Lisa, E de, Brunet, S, Rubio, V, Ribera, J.M., Rivas, C, Krsnik, I, Bergua, J, Gonzalez, J, Diaz-Mediavilla, J, Rojas, R, Manso, F, Ossenkoppele, G., Gonzalez, JD & Lowenberg, B. (2010). Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood, 115(25), 5137-5146. Schuurmans, M., Bromberg, J.E.C., Doorduijn, J.K., Poortmans, P, Taphoorn, M.J.B., Seute, T, Enting, R, Imhoff, G. van, Norden, Y. van & Bent, M.J. van den (2010). Primary central nervous system lymphoma in the elderly: a multicentre retrospective analysis. British Journal of Haematology, 151(2), 179-184. Slobbe, L., Doorduijn, J.K., Lugtenburg, P.J., Barzouhi, A el, Boersma, E., Leeuwen, W.B. van & Rijnders, B.J.A. (2010). Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial. PLoS One, 5(5). Sonneveld, P. (2010). More force or more smart? Blood, 115(10), 1859-1860. Terpos, E, Dimopoulos, MA, Sezer, O, Roodman, D., Abildgaard, N, Vescio, R, Tosi, P, Garcia-Sanz, R., Davies, F, ChananKhan, A, Palumbo, A., Sonneveld, P., Drake, MT, Harousseau, JL, Anderson, KC & Durie, BGM (2010). The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia, 24(10), 1700-1712. Wijermans, P., Schaafsma, M, Termorshuizen, F., Ammerlaan, R van, Wittebol, S., Sinnige, H, Zweegman, S., Kooy, MV, Griend, R van der, Lokhorst, H. & Sonneveld, P. (2010). Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: The HOVON 49 Study. Journal of Clinical Oncology, 28(19), 3160-3166. Octrooi Jongen-Lavrencic, M., Lowenberg, B., Sun, S.M. & Valk, P.J.M. (). Method for the treatment of acute myeloid leukemia. no PCT/EP2010/055355. 101 < back to index EMC MM-02-41-04 - Hematopoiesis: regulation of the proliferation and differentiation of hematopoietic progenitor cells Programme in brief design In this program we investigate the regulation of blood cell formation, i.e. hematopoiesis, in health and disease. Hematopoiesis is differentially regulated at the levels of primitive stem cells and more differentiated progenitor cell subsets and we study specifically the intrinsic characteristics of hematopoietic stem/progenitor cells and the extrinsic interactions with cells of the tissue microenvironment. The studies on hematopoietic and lymphoid development and intrinsic characteristics of stem/progenitor cells include the analysis of genetic determinants that control replication, replicative senescence, differentiation commitment, maturation, cellular dependence on humoral and stromal regulators and expression of specific hematopoietic growth factor receptors and differentiation specific genes. The focus of the experimental stem cell transplantation program is on improving immune reconstitution and induction of allo-antigen specific tolerance following transplantation. Specific projects deal with the development of tools and conditions that allow efficient gene transfer into the most primitive stem cells with long-term in vivo repopulation ability, eventually for the development of gene therapy, presently focused on inherited disorders, including immunodeficiencies, inherited anemias and metabolic diseases. In direct connection to the studies on hematopoiesis in healthy circumstances, the program has a focus on hematopoiesis in disease conditions. These diseases are characterized by quantitatively insufficient hematopoiesis resulting from disturbances at intrinsic or extrinsic levels of regulation in stem/progenitor cells. Conditions studied include idiopathic and congenital neutropenia and accelerated aging of stem cells following cytotoxic treatment. Models that include transgenic mice and subhuman primates have been developed to allow for the dissection of these conditions at the molecular level. Key figures Department hematology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 4,28 10,9 0,25 3,67 19,1 4,28 10,9 0,25 3,67 19,1 3 0 0 3 10 0 0 13 Thesis Brugman, M.H. (2010, juni 17). Insertional oncogenesis after retroviral gene transfer in hematopoietic stem cells. EUR (224 pag.). Prom./coprom.: Prof. Dr. G. Wagemaker. Bruinsma, M. (2010, maart 03). Regulatory T cells and immune tolerance after allogeneic hematopoietic stem cell transplantation. EUR (132 pag.). Prom./coprom.: Prof. Dr. J.J. Cornelissen & Prof. Dr. B. Lowenberg. Kaya, F.S.F. (2010, juni 16). Radioprotective agents stimulating hematopoietic stem cell reconstruction ¿ A translational approach. EUR (262 pag.). Prom./coprom.: Prof. Dr. G. Wagemaker. Artikel/Letter to the editor Borg, J, Papadopoulos, P., Georgitsi, M., Gutierrez Gutierrez, L., Grech, G., Fanis, P., Phylactides, M, Verkerk, A.J.M.H., Spek, P.J. van der, Scerri, CA, Cassar, W, Galdies, R, Ijcken, W.F.J. van, Ozgur, Z., Gillemans, C.H.A.M., Hou, J., Bugeja, M, Grosveld, F.G., Lindern, M.M. von, Felice, AE, Patrinos, GP & Philipsen, J.N.J. (2010). Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nature Genetics, 42(9), 801-U100. Bruin, A.M. de, Buitenhuis, M., Sluijs, KF van der, Gisbergen, KPJM van, Boon, L. & Nolte, MA (2010). Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-gamma. Blood, 116(14), 2559-2569. Crellin, NK, Trifari, S, Kaplan, CD, Cupedo, T. & Spits, H. (2010). Human NKp44(+)IL-22(+) cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. Journal of Experimental Medicine, 207(2), 281-290. Dijk, T.B. van, Gillemans, N, Pourfarzad, F., Lom, K. van, Lindern, M.M. von, Grosveld, F.G. & Philipsen, J.N.J. (2010). Fetal globin expression is regulated by Friend of Prmt1. Blood, 116(20), 4349-4352. Gratama, J.W., Boeckh, M, Nakamura, R, Cornelissen, J.J., Brooimans, R.A., Zaia, JA, Forman, SJ, Gaal, K, Bray, KR, Gasior, GH, Boyce, CS, Sullivan, LA & Southwick, PC (2010). Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study. Blood, 116(10), 1655-1662. Kerkhoffs, JLH, Putten, W.L.J. van, Novotny, VMJ, Boekhorst, P.A.W. te, Schipperus, MR, Zwaginga, JJ, Pampus, LCM van, Greef, G.E. de, Luten, M., Huijgens, P.C., Brand, A. & Rhenen, D.J. van (2010). Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction. British Journal of Haematology, 150(2), 209-217. Rasmussen, KD, Simmini, S, Abreu-Goodger, C, Bartonicek, N, Giacomo, M Di, Bilbao-Cortes, D, Horos, R., Lindern, M.M. von, Enright, AJ & O'Carroll, D (2010). The miR-144/451 locus is required for erythroid homeostasis. Journal of Experimental Medicine, 207(7), 1351-1358. Til, N.P. van, Stok, M., Aerts, F.S.F., Waard, M.C. de, Farahbakhshian, E., Visser, T.P., Kroos, M.A., Jacobs, E.H., Willart, M.A., Wegen, C.G. van der, Scholte, B.J., Lambrecht, B.N.M., Duncker, D.J.G.M., Ploeg, A.T. van der, Reuser, A.J.J., Verstegen, M.M.A. & Wagemaker, G. (2010). Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood, 115(26), 5329-5337. 102 < back to index Vroegindeweij, E., Crobach, A.S.L.P., Itoi, M, Satoh, R, Zuklys, S, Happe, C, Germeraad, WTV, Cornelissen, J.J., Cupedo, T., Hollander, GA, Kawamoto, H. & Ewijk, W van (2010). Thymic cysts originate from Foxn1 positive thymic medullary epithelium. Molecular Immunology, 47(5), 1106-1113. Wolfler, A., Oorschot, AADV, Haanstra, J.R., Valkhof, M.G., Bodner, C, Vroegindeweij, E., Strien, P.M.H. van, Novak, A., Cupedo, T. & Touw, I.P. (2010). Lineage-instructive function of C/EBP alpha in multipotent hematopoietic cells and early thymic progenitors. Blood, 116(20), 4116-4125. 103 < back to index EMC MM-02-54-03 - Molecular determinants of therapy response and outcome in childhood cancer Programme in brief design This translational research programme is focussed on the role of molecular genetic abnormalities on leukemogensis and outcome in childhood malignancies, especially leukemia. Specific goals are: · Molecular classification of childhood leukemias to redefine leukemias into biological subclasses. This is done by genome-wide screening techniques at the DNA level, extensive gene expression profiling by micro-array analysis and protein expression profiling. · Identification of (epi)genetic abnormalities important for develoment of childhood leukemias and lymphomas. Expression of tumor suppressor genes and oncogenes in various types of childhood leukemias and lymphomas are studied. The value of epigenetic silencing mechanisms such as methylation are studied. · Identification of molecules associated with cellular drug resistance and clinical therapy response. New resistance genes for specific classes of cytotoxic drugs are identified by micro-array analyses of drug resistant and sensitive patients and confirmed by other techniques. New strategies to modulate these new resistance genes are developed. · Identification of new targets for therapeutic intervention. New specific targets are detected in specific genetic subgroups of childhood leukemia by micro-array expression analysis. The presence of potential new drug targets is confirmed by other techniques and validation studies are performed. RNAi is being developed for ALL cells for this purpose. New agents directed against the newly discovered targets are evaluated in preclinical models for their activity in childhood leukemias. · Development of new treatment protocols: the targets and new compounds studied in the preclinical setting as described above are used in phase I/II studies. Central goal of the clinical program is the development of targeted therapies for children with hematological malignancies. · The clinical part of the research programme also studies: (1) Effectiveness of therapy in paediatric oncology, which are mainly done in national and international collaborations; (2) Improvements in supportive care in paediatric oncology, which are essential because of the high intensity of most treatment protocols; (3) Late effects of disease and treatment, which is important in the light of the improved cure rates of children with cancer. Key figures Department pediatrics pediatrics-hematology pediatrics-other Total SP1 2 2,4 0,4 4,8 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0 6,28 0,89 9,17 0 2,39 0 4,79 4 24,78 0 29,18 4 33,45 0,89 43,14 1 0 0 1 56 1 9 67 Thesis Beek, R.D. van (2010, maart 17). Endocrine effects of the treatment for acute lymphoblastic leukemia and Hodgkin's lymphoma in childhood. EUR (191 pag.) (Ridderkerk: Ridderprint B.V.). Prom./coprom.: Prof. Dr. R. Pieters, Dr. M.M. van den HeuvelEibrink & S.M.P.F. Muinck Keizer-Schrama. Artikel/Letter to the editor Adank, M..A., Segers, H., Mil, SE van, Helsdingen, Y.M. van, Ameziane, N., Ouweland, A.M.W. van den, Wagner, A., MeijersHeijboer, EJ, Kool, M., Kraker, J. de, Waisfisz, Q. & Heuvel-Eibrink, M.M. van den (2010). Fanconi anemia gene mutations are not involved in sporadic Wilms tumor. Pediatric Blood & Cancer, 55, 742-744. Arico, M., Schrappe, M., Hunger, S.P., Carroll, W.L., Conter, V., Galimberti, S., Manabe, A., Saha, V., Baruchel, A, Vettenranta, K., Horibe, K, Benoit, Y., Pieters, R., Escherich, G, Silverman, L.B., Pui, C-H. & Valsecchi, M.G. (2010). Clinical outcome of children with newly diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia treated between 1995 and 2005. Journal of Clinical Oncology, 28(31), 4755-4761. Bachas, C., Schuurhuis, G.J., Hollink, I.H.I.M., Kwidama, Z.J., Goemans, BF, Zwaan, C.M., Heuvel-Eibrink, M.M. van den, Bont, E.S.J.M. de, Reinhardt, D., Creutzig, U., Haas, V. de, Assaraf, Y.G., Kaspers, G.J.L. & Cloos, J (2010). High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine. Blood, 116(15), 2752-2758. Balgobind, B.V., Lugthart, S., Hollink, I.H.I.M., Peters, T.C.J.M., Wering, E.R. van, Graaf, S.S.N. de, Reinhardt, D., Creutzig, U., Kaspers, G.J.L., Bont, E.S.J.M. de, Stary, J., Trka, J., Zimmermann, M., Beverloo, H.B., Pieters, R., Delwel, H.R., Zwaan, C.M. & Heuvel-Eibrink, M.M. van den (2010). EV11 overexpression in distinct subtypes of pediatric acute myeloid leukemia. Leukemia, 24, 942-949. Balgobind, B.V., Zwaan, C.M., Reinhardt, D., Peters, T.C.J.M., Hollink, I.H.I.M., Haas, V. de, Kaspers, G.J.L., Bont, E.S.J.M. de, Baruchel, A, Stary, J., Meyer, C., Marschalek, R, Creutzig, U., Boer, M.L. den, Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). High BRE expression in pediatric MLL-rearranged AML is associated with favorable outcome. Leukemia, 24, 2048-2055. Balgobind, B.V., Hollink, I.H.I.M., Reinhardt, D., Wering, E.R. van, Graaf, S.S.N. de, Baruchel, A, Stary, J., Beverloo, H.B., Greef, G.E. de, Pieters, R., Zwaan, C.M. & Heuvel-Eibrink, M.M. van den (2010). Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique. European Journal of Cancer, 46, 1892-1899. Batz, C., Hasle, H., Bergstrasser, E., Heuvel-Eibrink, M.M. van den, Zecca, M., Niemeyer, C.M. & Flotho, C. (2010). Does SPRED1 contribute to leukomogenesis in juvenile myelomonocytic leukemia (JMML) ? Blood, 115(12), 2557-2558. 104 < back to index Bekkering, W.P., Vlieland, TPMV, Koopman, H.M., Schaap, G.R., Schreuder, H.W.B., Beishuizen, A., Tissing, W.J.E., Hoogerbrugge, P.M., Anninga, J.K. & Taminiau, AHM (2010). Quality of life in young patients after bone tumor surgery around the knee joint and comparison with healthy controls. Pediatric Blood & Cancer, 54, 738-745. Boot, A.M., Ridder, M.A.J. de, Sluis, I.M. van der, Slobbe, I.M. van, Krenning, E.P. & Muinck Keizer-Schrama, S.M.P.F. (2010). Peak bone mineral density, lean body mass and fractures. Bone, 46(2), 336-341. Bruggemann, M, Schrauder, A, Raff, T., Pfeifer, H., Dworzak, M, Ottmann, O.G., Asnafi, V, Baruchel, A, Bassan, R., Benoit, Y., Biondi, A., Cave, H., Dombret, H., Fielding, A.K., Foa, R., Gokbuget, N., Goldstone, A.H., Goulden, N., Henze, G., Hoelzer, D., Janka-Schaub, G.E., Macintyre, E.A., Pieters, R., Rambaldi, A., Ribera, J.M., Schmiegelow, K., Spinelli, O., Stary, J., Stackelberg, A, Kneba, M., Schrappe, M. & Dongen, J.J.M. van (2010). Standardized MRD quantification in European ALL trials: proceedings of the second international symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. Leukemia, 24, 521-535. Buitenkamp, T.D., Mathot, R.A.A., Haas, V. de, Pieters, R. & Zwaan, C.M. (2010). Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia. Haematologica, 95(7), 1106-1113. Cnossen, M.H., Aarsen, F.K., Akker, L.J. van den, Danen, R., Appel, I.M., Steyerberg, E.W. & Catsman-Berrevoets, C.E. (2010). Paediatric arterial ischaemic stroke: functional outcome and risk factors. Developmental Medicine & Child Neurology, 52, 394-399. Coenen, E.A., Zwaan, C.M., Meyer, C., Marschalek, R, Pieters, R., Veken, L.T.J.N. van der, Beverloo, H.B. & Heuvel-Eibrink, M.M. van den (2010). KIAA1524: a novel MLL translocation partner in acute myeloid leukemia. Leukemia Research, 35, 133135. Dalen, EC van, Michiels, E.M.C., Caron, H.N. & Kremer, LCM (2010). Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Systematics Review, 12(5). Eden, T.O.B., Pieters, R. & Richards, S. (2010). Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia - an individual patient data meta-analysis involving 5659 chlidren. British Journal of Haematology, 149, 722-733. Ehlers, S., Herbst, C., Zimmermann, M., Scharn, N., Germeshausen, M, Neuhoff, N. von, Zwaan, C.M., Reinhardt, K., Hollink, I.H.I.M., Klusmann, J.H., Lehrnbecher, T., Roettgers, S., Stary, J., Dworzak, M, Welte, K., Creutzig, U. & Reinhardt, D. (2010). Granulocyte Colony-Stimulating Factor (G-CSF) treatmant of childhood acute myeloid leukemias that overexpress the differentiation-defective G-CSF receptor Isoform IV is associated with a higher incidence of relapse. Journal of Clinical Oncology, 28(15), 2591-2597. Faaij, C.M.J.M., Willemze, A.J., Revesz, T, Balzarolo, M., Tensen, T.N.J., Hoogeboom, M, Vermeer, M.H., Wering, E. van, Zwaan, C.M., Kaspers, G.J.L., Story, C., Halteren, A.G.S. van, Vossen, J.M., Egeler, R.M., Tol, M.J.D. van & Annels, N.E. (2010). Chemokine/Chemokine Receptor Indications in extramedullary leukaemia of the skin in childhood AML: differential roles for CCR2, CCR5, CXCR4 and CXCR7. Pediatric Blood & Cancer, 55, 344-348. Flotho, C., Batz, C., Hasle, H., Bergstrasser, E., Heuvel-Eibrink, M.M. van den, Zecca, M., Niemeyer, C.M. & Zenker, M. (2010). Mutational analysis of SHOC2, a novel gene for Noonan-like syndrome, in JMML. Blood, 115(4), 913. Goemans, BF, Zwaan, C.M., Cloos, J, Lange, D. de, Loonen, A.H., Reinhardt, D., Hahlen, K., Gibson, BES, Creutzig, U. & Kaspers, G.J.L. (2010). FLT3 and KIT mutated pediatric acute myeloid leukemia (AML) samples are sensitive in vitro to the tyrosine kinase inhibitor SU11657. Leukemia Research, 34, 1302-1307. Gohring, G., Michalova, K, Beverloo, H.B., Betts, D., Harbott, J., Haas, O.A., Kerndrup, G., Sainati, L., Bergstraesser, E., Hasle, H., Stary, J., Trebo, M., Heuvel-Eibrink, M.M. van den, Zecca, M., Wering, E.R. van, Fischer, A., Noellke, P., Strahm, B, Locatelli, F., Niemeyer, C.M. & Schlegelberger, B (2010). Complex karotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood, 116(19), 3766-3769. Gooskens, S.L.M., Oranje, A.P., Adrichem, L.N.A. van, Waard- van der Spek, F.B. de, Hollander, J.C. den, Ven, C.P. van de & Heuvel-Eibrink, M.M. van den (2010). Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP). Pediatric Blood & Cancer, 55, 369-373. Gooskens, S.L.M., Oranje, A.P., Adrichem, L.N.A. van, Waard- van der Spek, F.B. de, Hollander, J.C. den, Ven, C.P. van de & Heuvel-Eibrink, M.M. van den (2010). Dermatofibrosarcoma protuberans (DFSP) bij kinderen. Oncollectie, 3, 8-15. Gravendeel, L.A.M., Kloosterhof, N.K., Bralten, L.B.C., Marion, R. van, Dubbink, H.J., Dinjens, W.N.M., Bleeker, FE, Hoogenraad, C.C., Michiels, E.M.C., Kros, J.M., Bent, M.J. van den, Sillevis Smitt, P.A.E. & French, P.J. (2010). Segregation of Non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Human Mutation, 31, 1186-1199. Hagemans, M.L.C., Stigter, R.L., Capelle, C.I. van, Beek, N.A.M.E. van der, Winkel, L.P.F., Vliet, L. van, Hop, W.C.J., Reuser, A.J.J., Beishuizen, A. & Ploeg, A.T. van der (2010). PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease. Journal of Inherited Metabolic Disease, 33, 133-139. Hartman, A, Schaik, R.H.N. van, Heiden, I.P. van der, Broekhuis, M.J.C., Meier, M., Boer, M.L. den & Pieters, R. (2010). Polymorphisms in genes involved in vincritine pharmacokinetics or pharmacokinetics of pharmacodynamics are nog related to impaired motor performance in children with leukemia. Leukemia Research, 34, 154-159. Hempel, G., Relling, M.V., Rossi, G. de, Stary, J., Lorenzo, P de, Valsecchi, M.G., Barisone, E., Boos, J. & Pieters, R. (2010). Pharmacokinetics of Daunorubicin and Daunorubicinol in infants with leukemia treated in the Interfant 99 Protocol. Pediatric Blood & Cancer, 54, 355-360. 105 < back to index Heuvel-Eibrink, M.M. van den, Dohle, G.R., Muinck Keizer-Schrama, S.M.P.F., Laven, J.S.E. & Neggers, S.J.C.M.M. (2010). Late effecten van kankerbehandeling bij kinderen. Deel 3: endocriene effecten. Oncollectie, 2, 2-7. Hollink, I.H.I.M., Heuvel-Eibrink, M.M. van den, Zimmerman, M., Balgobind, B.V., Peters, T.C.J.M., Alders, M., Willasch, A.M., Kaspers, G.J.L., Trka, J., Baruchel, A, Creutzig, U., Pieters, R., Reinhardt, D. & Zwaan, C.M. (2010). No prognostic impact of the WT1 gene single nucleotide polymorphism rs16754 in pediatric acute myeloid leukemia. Journal of Clinical Oncology, 28(28), 523-526. Horton, T.M., Sposto, R., Brown, P., Reynolds, C.P., Hunger, S.P., Winick, N.J., Raetz, E.A., Carroll, W.L., Arceci, R.J., Borowitz, M.J., Gaynon, PS, Gore, L., Jeha, S., Maurer, B.J., Siegel, S.E., Biondi, A., Kearns, P.R., Narendran, A., Silverman, L.B., Smith, M.A., Zwaan, C.M. & Whitlock, J.A. (2010). Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimes for pediatric Acute Lymphocytic Leukemia (ALL): review from an international consensus conference. Pediatric Blood & Cancer, 54, 872-878. Jonge, HJM de, Valk, P.J.M., Veeger, NJGM, Elst, A. ter, Boer, M.L. den, Cloos, J, Haas, V. de, Heuvel-Eibrink, M.M. van den, Kaspers, G.J.L., Zwaan, C.M., Kamps, W.A., Lowenberg, B. & Bont, E.S.J.M. de (2010). High VEGFC expression is associated with unique gene expression profiles and predics adverse prognosis in pediatric and adult acute myeloid leukemia. Blood, 116(10), 1747-1754. Jung, R., Krumbolz, M., Langer, T, Keller, T, Lorenzo, P de, Valsecchi, M.G., Velden, V.H.J. van der, Moericke, A., Stanulla, M., Teigler-Schlegel, A, Panzer-Grümayer, E.R., Dongen, J.J.M. van, Schrappe, M., Boer, M.L. den, Pieters, R., Rascher, W. & Metzler, M. (2010). Bidomal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment. Leukemia, 24, 903-907. Kamps, W.A., Pal-de Bruin, K.M. van der, Veerman, A.J.P., Fiocco, M., Bierings, M. & Pieters, R. (2010). Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia, 24, 309319. Keersmaecker, K. de, Real, P.J., Della Gatta, G., Palomero, T., Sulis, M.L., Tosello, V., Vlierberghe, P. van, Barnes, K., Castillo, M., Sole, X., Hadler, M., Lenz, J., Aplan, P.D., Kelliher, M., Kee, B.L., Pandolfi, P.P., Kappes, D., Gounari, F., Petrie, H., Meulen, J. van der, Speleman, F., Paietta, E., Recevskis, J., Wiernik, P.H., Rowe, J.M., Soulier, J., Avran, D., Cave, H., Dastugue, N., Raimondi, S., Meijerink, J.P.P., Cordon-Cardo, C., Califano, A. & Ferrando, A.A. (2010). The TLX1 oncogene drives aneuploidy in T cell transformation. Nature Medicine, 16(11), 1321-1327. Kleppe, M., Lahortiga, I., Chaar, T. el, Keersemaecker, K. de, Mentens, N., Graux, C., Roosbroeck, K. van, Ferrando, A.A., Langerak, A.W., Meijerink, J.P.P., Sigaux, F, Haferlach, T, Wlodarska, I., Vandenberghe, P., Soulier, J. & Cools, J. (2010). Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nature Genetics, 42(6), 530535. Landlinger, C., Preuner, S., Baskova, L., Grotel, M. van, Hartwig, N.G., Dworzak, M, Mann, G., Attarbaschi, A., Kager, L., Peters, C., Matthes-Martin, S., Lawitschka, A., Heuvel-Eibrink, M.M. van den & Lion, T. (2010). Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients. Leukemia, 24, 2032-2038. Lie Fong, S., Heuvel-Eibrink, M.M. van den, Eijkemans, M.J.C., Schipper, I., Hukkelhoven, C.W.P.M. & Laven, J.S.E. (2010). Pregnancy outcome in female childhood cancer survivors. Human Reproduction, 25(5), 1206-1212. Lijster, M.S. de, Bergevoet, R.M., Dalen, EC van, Michiels, E.M.C., Caron, H.N., Kremer, LCM & Aronson, D.C. (2010). Minimally invasive surgery versus open surgery for the treatment of solid abdominal and thoracic neoplasms in children. Cochrane Database Systematics Review, 17(3). Linden, M.H. van der, Seslija, L., Schneider, P., Pieters, R. & Stam, R.W. (2010). Establishing direct targets of MLL-AF4 fusion proteins in t(4;11)-positive acute lymphoblastic leukemia in infants. Daniel den Hoed Cancer News, 2, 25-26. Mann, G., Attarbaschi, A., Schrappe, M., Lorenzo, P de, Peters, C., Hann, I., Rossi, G. de, Felice, M., Lausen, B., Leblanc, T., Szczepanski, T., Ferster, A., Janka-Schaub, G., Rubnitz, J., Silverman, L.B., Stary, J., Campbell, M., Li, C.K, Suppiah, R., Biondi, A., Vora, A., Valsecchi, M.G. & Pieters, R. (2010). Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL) rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood, 116(15), 2644-2650. Meijerink, J.P.P. (2010). Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia. Best Practice & Research Clinical Haematology, 23, 307-318. Mouravieva, A., Escher, J.C., Kessel, I. van, Beishuizen, A., Vanheusden, K. & Wagner, A. (2010). Familiaire adenomateuze polyposis coli op de kinderleeftijd. Tijdschrift voor Kindergeneeskunde, 78(1), 28-33. Niemeyer, C.M., Kang, M.W., Shin, D.H., Furlan, I., Erlacher, M., Bunin, N.J., Bunda, S., Finklestein, J.Z., Sakomoto, K.M., Gorr, T.A., Mehta, P., Schmid, I., Kropshofer, G., Corbacioglu, S., Lang, P.J., Klein, C., Schlegel, P.G., Heinzmann, A., Schneider, M., Stary, J., Heuvel-Eibrink, M.M. van den, Hasle, H., Locatelli, F., Sakai, D.S., Archambeault, S., Chen, L., Russell, R.C., Sybingco, S.S., Ohh, M., Braun, B.S., Flotho, C. & Loh, M.L. (2010). Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nature Genetics, 9, 794-800. Pieters, R. (2010). Behandeling van acute lymfatische leukemie bij kinderen en adolescenten. Nederlands Tijdschrift voor Geneeskunde, 154(35), 1644-1649. Pieters, R. & Carroll, W.L. (2010). Biology and treatment of acute lymphoblastic leukemia. Hematology-Oncology Clinics of North America, 24, 1-18. 106 < back to index Pieters, R. (2010). Childhood leukaemia: towards improved tailored therapy. Lancet Oncology, 11, 403-404. Pieters, R. (2010). Acute lymfatische leukemie bij kinderen en adolescenten. Nederlands Tijdschrift voor Hematologie, 7(5), 177-186. Raadt, B. de, Wijers, E. & Beishuizen, A. (2010). Ouders en een ernstig ziek kind. Tijdschrift Kinderverpleegkunde, 3, 22-25. Raadt, B. de (2010). Veerkracht en moederschap. Beeld versus gedrag van moeder met stervend kind. Maatwerk, 11(1), 6. Raadt, B. de, Rijkschroeff, J.B.G. & Heuvel-Eibrink, M.M. van den (2010). Zorg op maat. Kinderpalliatieve zorg vanuit ouderbegeleidend perspectief. Maatwerk, 11(1), 9-11. Schotte, D., Turenhout, E.A.M., Stumpel, D.J.P.M., Stam, R.W., Gladdines, J.G.C.A.M., Meijerink, J.P.P., Pieters, R. & Boer, M.L. den (2010). Expression of miR-196b is not exclusively MLL-driven but is especially linked to activation of HOXA genes in pediatric acute lymphoblastic leukemia. Haematologica, 95(10), 1675-1682. Schrappe, M., Nachman, J., Hunger, S.P., Schmiegelow, K., Conter, V., Masera, G., Pieters, R. & Pui, C-H. (2010). Educational symposium on long-term results of large prospective clinical trials for childhood acute lymphoblastic leukemia (1985-2000). Leukemia, 24, 253-254. Smetsers, S.E., Zwaan, C.M., Sonnevelt, M.C., Brakenhoff, R.H., Smiers, F.J.W., Best, J.D., Joenje, H. & Bierings, M.B. (2010). Fanconi-anemie: uit de kinderschoenen. Nederlands Tijdschrift voor Hematologie, 7(6), 230-240. Stam, R.W., Boer, M.L. den, Schneider, P., Boer, J. de, Hagelstein, J.A.P., Valsecchi, M.G., Lorenzo, P de, Sallan, S.E., Brady, H.J.M., Armstrong, S.A. & Pieters, R. (2010). Association high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia. Blood, 115(5), 1018-1025. Stam, R.W., Schneider, P., Hagelstein, J.A.P., Linden, M.H. van der, Stumpel, D.J.P.M., Menezes, R.X. de, Lorenzo, P de, Valsecchi, M.G. & Pieters, R. (2010). Gene expression profiling-based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants. Blood, 115(14), 2835-2844. Vlierberghe, P. van, Palomero, T., Khiabanian, H., Meulen, J. van der, Castillo, M., Roy, N. van, Moerloose, B. de, Philippe, J, Conzalez-Garcia, S., Toribio, M.L., Taghon, T., Zuurbier, L.C., Cauwelier, B., Harrison, C.J., Schwab, C., Pisecker, M., Strehl, S, Langerak, A.W., Gecz, J., Sonneveld, E., Pieters, R., Paietta, E., Rowe, J., Wiernik, P.H., Benoit, Y., Soulier, J., Poppe, B., Yao, X., Cordon-Cardo, C., Meijerink, J.P.P., Rabadan, R., Speleman, F. & Ferrando, A.A. (2010). PHF6 mutations in T-cell lymphoblastic leukemia. Nature Genetics, 42(4), 338-342. Vries, A.C.H. de, Zwaan, C.M. & Heuvel-Eibrink, M.M. van den (2010). Molecular basis of juvenile myelomonocytic leukemia. Haematologica, 95(2), 179-182. Waas, M. van, Neggers, S.J.C.M.M., Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Components of the metabolic syndrome in 500 adult long-term survivors of childhood cancer. Annals of Oncology, 21, 1121-1126. Waas, M. van, Neggers, S.J.C.M.M., Lelij, A.J. van der, Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). The metabolic syndrome in adult survivors of childhood cancer, a review. Journal of Pediatric Hematology Oncology, 32(3), 171-179. Winkel, M.L. te, Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Future perspectives on minimizing bone density reduction in pediatric acute lymphoblastic leukemia. Personalized Medicine, 7(5), 469-471. Winkel, M.L. te, Sluis, I.M. van der, Lequin, M.H., Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Letter to editor in response to "Prospective bone ultrasound patterns during childhood acute lymphoblastic leukemia" by Mussa et al. Bone, 47, 835-836. Winkel, M.L. te, Beek, R.D. van, Muinck Keizer-Schrama, S.M.P.F., Uitterlinden, A.G., Hop, W.C.J., Pieters, R. & HeuvelEibrink, M.M. van den (2010). Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia. Haematologica, 95(5), 752-758. Winkel, M.L. te, Lequin, M.H., Bruyn, J.R. de, Ven, C.P. van de, Krijger, R.R. de, Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Self-limiting sternal tumors of childhood (SELSTOC). Pediatric Blood & Cancer, 55, 81-84. Zuurbier, L.C., Homminga, I., Calvert, V., Winkel, M.L. te, Gladdines, J.G.C.A.M., Kooi, C., Smits, W.K., Sonneveld, E., Veerman, A.J.P., Kamps, W.A., Horstmann, M, Petricoin, E.F., Pieters, R. & Meijerink, J.P.P. (2010). NOTCH1 and/or FBXW7 mutations predict for initial good prednisone response but not for improved outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on DCOG of COALL protocols. Leukemia, 24, 2014-2022. Zwaan, C.M., Reinhardt, D., Hitzler, J. & Vyas, P (2010). Acute leukemias in children with Down Syndrome. HematologyOncology Clinics of North America, 24, 19-34. Zwaan, C.M., Reinhardt, D., Zimmerman, M., Hasle, H., Stary, J., Stark, B., Dworzak, M, Creutzig, U. & Kaspers, G.J.L. (2010). Salvage treatment for children with refractory first of second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase II study. British Journal of Haematology, 148, 768-776. Zwaan, C.M., Kearns, P.R., Caron, H.N., Verschuur, A., Riccardi, R., Boos, J., Doz, F., Geoerger, B & Vassal, G (2010). The role of the 'innovative therapies for children with cancer' (ITCC) European consortium. Cancer Treatment Reviews, 36, 328-334. 107 < back to index EMC MM-02-72-01 - Lymphoid differentiation and immunodeficiencies Programme in brief design One of the most intriguing features of the specific immune system is the generation of mature B and T lymphocytes that carry immunoglobulin (Ig) molecules and T-cell receptors (TCR), which are highly specific for antigens, even when these cells have not encountered the antigens before. The generation and selection of a diverse and flexible specificity repertoire by lymphocytes is dependent on a series of developmental cell fate decisions, including the induction and regulation of Ig and TCR gene rearrangements. These decisions are implemented by the activity of specific transcription factors and enzyme systems and occur at specific checkpoints, controlled by signaling pathways downstream of antigen receptors and their immature forms. In particular, the research aims of this program comprise: - To study the role of lymphoid-specific transcription factors that control the in vivo developmental program of lymphoid cells. - To investigate signal transduction routes that are crucial to stem cell self-renewal and differentiation into lymphoid cells. - To unravel the essential steps in the induction and execution of Ig/TCR gene rearrangements in precursor-B and -T cells, e.g. using immunodeficiencies as model. - To characterize the signal transduction pathways downstream of the antigen receptors, which are essential for survival, selection and developmental progression of lymphoid cells. - To investigate how defects in the regulation of differentiation and proliferation steps during lymphoid development result in immunodeficiencies or lymphoid malignancies. - To translate the obtained knowledge on normal lymphoid differentiation and gene defects into novel diagnostics and opportunities for gene therapy in patients with primary immunodeficiencies (PID). Key figures Department immunology internal medicine pediatricsimmuno/infection pediatrics-other Total SP1 SP2 SP3 SP4 Sptot T1 4,56 2,13 0,75 1 8,44 0,03 0 0 0 0,03 0,03 0,03 4,65 0 0 2,13 0 0 0,75 0 0 1 0,03 0,03 8,53 4 T2 T3 0 0 Ttot 4 IS 38 FS 3 OP 11 Ptot 56 Thesis Khan, N.A. (2010, mei 26). Immunoregulatory properties of break down products of human choriogonadotropin. EUR. Prom./coprom.: Prof. Dr. R. Benner. Luis, T.C. (2010, november 17). Fine-tuning hematopoieses. Microenvironmental factors regulating self-renewal and differentiation of hematopoietic stem cells. EUR. Prom./coprom.: Prof. Dr. J.J.M. van Dongen & Dr. F.J.T. Staal. Ta, T.B.V. (2010, december 15). Role of pre-B cell receptor signaling molecules in B cell differentiation and tumor suppression. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden, Prof. Dr. R. Benner & Dr. R.W. Hendriks. Zee, M. van der (2010, oktober 13). Regulation of inflammatory responses in shock-related syndromes by synthetic oligopeptides and steroids. EUR. Prom./coprom.: Prof. Dr. R. Benner & W.A. Dik. Artikel/Letter to the editor Artac, H, Reisli, I., Kara, R, Knijnenburg, I., Adin-Cinar, S, Pekcan, S, Zijde, CM Jol-van der, Tol, M.J.D. van, Bakker-Jonges, L.E., Dongen, J.J.M. van, Burg, M. van der & Zelm, M.C. van (2010). B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele. Genes and Immunity, 11(7), 523-530. Artac, H, Gokturk, B, Bozdemir, SE, Toy, H, Burg, M. van der, Santisteban, I, Hershfield, M & Reisli, I. (2010). Late-onset adenosine deaminase deficiency presenting with Heck's disease. European Journal of Pediatrics, 169(8), 1033-1036. Bongers, T.N., Emonts, M., Maat, M.P.M. de, Groot, R. de, Lisman, T., Hazelzet, J.A. & Leebeek, F.W.G. (2010). Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome. 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Directly Transfected Langerin(+) Dermal Dendritic Cells Potentiate CD8(+) T Cell Responses following Intradermal Plasmid DNA Immunization. Journal of Immunology, 185(6), 3463-3471. Furmanov, K, Elnekave, M, Lehmann, D, Clausen, B.E., Kotton, DN & Hovav, AH (2010). The Role of Skin-Derived Dendritic Cells in CD8(+) T Cell Priming Following Immunization with Lentivectors. Journal of Immunology, 184(9), 4889-4897. Ginhoven, T.M. van, Berg, J.W. van den, Dik, W.A., Ijzermans, J.N.M. & Bruin, R.W.F. de (2010). Preoperative Dietary Restriction Reduces Hepatic Tumor Load by Reduced E-Selectin-Mediated Adhesion in Mice. Journal of Surgical Oncology, 102(4), 348-353. Ginhoven, T.M. van, Berg, J.W. van den, Dik, W.A., Ijzermans, J.N.M. & Bruin, R.W.F. de (2010). Preoperative fasting induces protection against renal ischemia/reperfusion injury by a corticosterone-independent mechanism. Transplant International, 23(11), 1171-1178. Haase, H, Ober-Blobaum, J., Engelhardt, G., Hebel, S & Rink, L (2010). Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation. Toxicology Letters, 198(2), 152-158. Hanson, J., Gille, A, Zwykiel, S, Lukasova, M, Clausen, B.E., Ahmed, K, Tunaru, S, Wirth, A & Offermanns, S (2010). Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. Journal of Clinical Investigation, 120(8), 2910-2919. Kautz-Neu, K, Meyer, RG, Clausen, B.E. & Stebut, E von (2010). Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. Experimental Dermatology, 19(8), 760-771. Kel, J.M., Girard-Madoux, MJH, Reizis, B & Clausen, B.E. (2010). TGF-beta Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis. 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Luis, T.C., Naber, B.A.E., Fibbe, W.E., Dongen, J.J.M. van & Staal, F.J.T. (2010). Wnt3a nonredundantly controls hematopoietic stem cell function and its deficiency results in complete absence of canonical Wnt signaling. Blood, 116(3), 496-497. Mellman, I & Clausen, B.E. (2010). beta-Catenin Balances Immunity. Science, 329(5993), 767-769. Ng, Y.Y., Baert, M.R.M., Pike - Overzet, K, Rodijk, M., Brugman, M.H., Schambach, A, Baum, C., Hendriks, R.W., Dongen, J.J.M. van & Staal, F.J.T. (2010). Correction of B-cell development in Btk-deficient mice using lentiviral vectors with codonoptimized human BTK. Leukemia, 24(9), 1617-1630. Noordegraaf, M., Flacher, V, Stoitzner, P & Clausen, B.E. (2010). Functional Redundancy of Langerhans Cells and Langerin(+) Dermal Dendritic Cells in Contact Hypersensitivity. Journal of Investigative Dermatology, 130(12), 2752-2759. Ober-Blobaum, J., Engelhardt, G., Hebel, S, Rink, L & Haase, H (2010). Cadmium ions promote monocytic differentiation of human leukemia HL-60 cells treated with 1 alpha,25-dihydroxyvitamin D3. Biological Chemistry, 391(11), 1295-1303. Romani, N., Clausen, B.E. & Stoitzner, P (2010). Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunological Reviews, 234, 120-141. Schwarz, A, Noordegraaf, M., Maeda, A, Torii, K, Clausen, B.E. & Schwarz, T (2010). Langerhans Cells Are Required for UVRInduced Immunosuppression. Journal of Investigative Dermatology, 130(5), 1419-1427. Verkaik, N.J., Dauwalder, O, Antri, K, Boubekri, I, Vogel, C.P. de, Badiou, C, Bes, M, Vandenesch, F, Tazir, M, Hooijkaas, H., Verbrugh, H.A., Belkum, A. van, Etienne, J., Lina, G, Ramdani-Bouguessa, N & Wamel, W.J.B. van (2010). Immunogenicity of Toxins during Staphylococcus aureus Infection. Clinical Infectious Diseases, 50(1), 61-68. 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DNA Repair, 9(9), 1003-1010. Zee, H.H. van der, Prens, E.P. & Boer, J. de (2010). Deroofing: A tissue-saving surgical technique for the treatment of mild to moderate hidradenitis suppurativa lesions. Journal of the American Academy of Dermatology, 63(3), 475-480. Zee, H.H. van der, Woude, C.J. van der, Florencia, E.F.I.I.I. & Prens, E.P. (2010). Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. British Journal of Dermatology, 162(1), 195-197. Zee, M. van der, Dik, W.A., Kap, Y.S., Dillon, M.J., Benner, R., Leenen, P.J.M., Khan, N.A. & Drevets, D.A. (2010). Synthetic Human Chorionic Gonadotropin-Related Oligopeptides Impair Early Innate Immune Responses to Listeria monocytogenes in Mice. Journal of Infectuous Diseases, 201(7), 1072-1080. Zee, M. van der, Berg, J.W. van den, Holten-Neelen, C van & Dik, W.A. (2010). 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Dongen, J.J.M. van & Burg, M. van der (2010). Inleiding primaire immunodeficiënties. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 247-268). Rotterdam: Erasmus MC, afdeling immunologie. Hamann, J., Veninga, H, Groot, D.M. de, Visser, L., Hofstra, C.L., Tak, P.P., Laman, J.D., Boots, AM & Eenennaam, H. van (2010). CD97 in leukocyte trafficking. In Adhesion-GPCRs: structure to function. Landes Biosciences and Springer Science+Business Media.. Ijspeert, H., Lankester, A.C., Tezcan, I., Verkaik, N.S., Gent, D.C. van, Dongen, J.J.M. van & Burg, M. van der (2010). Identificatie van nieuwe gendefecten bij T-B--SCID. In Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 279-291). Rotterdam: Erasmus MC, afdeling immunologie. Khan, N.A., Dik, W.A. & Benner, R. (2010). Regulatie van ontsteking door kleine peptiden die gebaseerd zijn op de aminozuursequentie van het zwangerschapshormoon hCG. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 227-244). Rotterdam: Erasmus MC, afdeling immunologie. 110 < back to index Lubberts, E. (2010). T-celsubsets en regulatie van ontstekingsprocessen. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 139-146). Rotterdam: Erasmus MC, afdeling immunologie. Pike - Overzet, K, Dongen, J.J.M. van & Staal, F.J.T. (2010). Gentherapie voor immunodeficiënties. In Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 307-315). Rotterdam: Erasmus MC, afdeling immunologie. Wind, H.K., Leenders, M., Homburg, C, Preijers, F. & Velden, V.H.J. van der (2010). Immunodiagnostiek van paroxismale nachtelijke hemoglobinurie (PNH). In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 481-498). Rotterdam: Erasmus MC, afdeling immunologie. Zelm, M.C. van, Burg, M. van der, Reisli, I., Artac, H, Mascart, F, Smet, J, Franco, J.L., Kanegane, H, Tol, M.J.D. van, Jol - van der Zijde, C.M. & Dongen, J.J.M. van (2010). CD19-complexdeficiënties. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 293-305). Rotterdam: Erasmus MC, afdeling immunologie. 111 < back to index EMC MM-02-72-02 - Immune regulation and autoimmunity Programme in brief design The department of Immunology focuses on lymphatic and myeloid differentiation, immune regulation and inflammation. Chronic inflammation and autoimmune disease are leading causes of morbidity, psychosiocal burden and economic loss in Western societies. In view of the central role of innate and adaptive immunity in these diseases, detailed insight into immune regulation is a requirement for elucidation of immunopathogenesis, and the rational development of diagnosis and (immuno)therapy. The Postgraduate School Molecular Medicine has an extensive and active program in immune regulation and autoimmunity, consisting of a close collaboration between clinical and pre-clinical departments. Chronic inflammatory diseases of interest are type I diabetes, thyroiditis, affective disorders and schizophrenia (all having a major immuno-neuro-endocrine component), rheumatoid arthritis (RA) and the related disorder Sjögren¿s syndrome, psoriasis, and the demyelinating diseases multiple sclerosis (MS) and Guillain-Barré syndrome (GBS). The general premise is that the immune mechanisms driving the multifactorial pathophysiology in these different diseases of interest are highly analogous. The fundamental immunological concepts we address within the frame of these diseases are:- immune (de)regulation by antigen presenting cells, notably dendritic cells and macrophages- functional T and B lymphocyte subsets- influences of the neuroendocrine system on leukocyte-target organ interaction- microbial compounds driving chronic inflammation- molecular mimicry and antibody neurotoxicityDevelopment of innovative animal models including conditional and cell type-specific transgenesis is integral part of this approach.Research topics include basic immunopathogenic mechanisms (e.g. molecular mimicry in GBS and MS); immuneendocrine interactions (e.g. in the pathogenesis of postpartum thyroiditis and post partum psychosis and in the linked amelioration of MS, thyroiditis and RA during pregnancy); molecular signaling pathways in chronic autoimmune inflammation (e.g. transcription factors in psoriasis and major psychiatric diseases, inflammatory gene signature expressions in monocytes in major psychiatric diseases, epi-genetic regulation of these various genes); experimental immunotherapy (e.g. antibodies against costimulatory molecules and cytokines); immune regulation by external factors (e.g. UV irradiation and skin inflammation, infection and MS activity); immune function and disease activity in MS; and an immune deregulation by an aberrant development and activity of antigen presenting cells (e.g. in diabetes, Sjögren¿s syndrome, thyroiditis, atherosclerosis, affective disorders, schizophrenia and histiocytosis).Close collaboration with clinical researchers who are well-trained in immunology allows joint elaboration of scientifically relevant research questions, construction of well-characterized patient cohorts, and evaluation of experimental (immuno)therapy. Specifically, the departments of Neurology (workgroup leaders Prof. Dr. R.Q. Hintzen, Dr. B.C. Jacobs, Prof. Dr. P.A. van Doorn), Dermatology (Prof. Dr. H.A.M. Neuman, Prof. Dr. E.P. Prens), Rheumatology (Prof. Dr. J.M.W. Hazes, Dr. E. Lubberts, Dr. R.J.E.M. Dolhain) and Internal Medicine (Dr. P.M. van Hagen) have structurally integrated their immune research groups within the department of Immunology. There is additional close collaboration on the role of microbial compounds in immune regulation with the departments of Virology (Prof. Dr. A.D.M.E. Osterhaus), Medical Microbiology and Infectious Diseases (Prof. Dr. H.A. Verbrugh, Dr. H.P. Endtz, Prof. Dr. A. van Belkum). Furthermore, the departments of Internal Medicine (Prof. Dr. A.J. van der Lelij, Prof. Dr. T.J. Visser) and Immunology collaborate on thyroid autoimmune disease and diabetes in schizophrenia, and the department of Psychiatry (Prof. Dr. M.W. Hengeveld, Prof. Dr. S. Kushner, Dr. V. Bergink, Dr. J.M. van Beveren) and Immunology on immune aberrancies in major affective disorders and schizophrenia. Combining researchers with different backgrounds (e.g. the clinic, molecular biology, cellular immunology) working on these different diseases in a single integrated team significantly stimulates scientific discussion and output. The joint expertise allows coverage of a broad area of approaches and technology, ranging from patient cohort studies via functional in vitro and genetic analyses of patient material to several animal disease models in rodents and nonhuman primates. The MS research is organized in the MS Centre ErasMS (head Prof. Dr. R.Q. Hintzen), supported by a 4 year program grant from the Dutch MS Research Foundation. The Biomedical Primate Research Centre (Dr. B.A. `t Hart and colleagues, Rijswijk) participates in this MS Centre.The research on inflammation as one of the causal factors of major psychiatric disorders is supported by a large scale EU-KP-7 grant (MOODINFLAME, 19 partners in 11 countries, coordinator ErasmusMC) and a NWO-TOP program grant. In this work there is extensive collaboration with Prof. Dr. W.A. Nolen (Dept of Psychiatry, Groningen) en Prof. Dr. R.S. Kahn (Dept of Psychiatry, Utrecht). Diabetes research is supported by a grant from the DFN and the JDRF. Key figures Department dermatology immunology neurology rheumatology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,06 0 0 0 0,06 4,13 5,25 0,8 0 10,18 0,12 0 0,4 0 0,52 0,09 0 0 0 0,09 4,4 5,25 1,2 0 10,85 2 0 0 2 33 8 13 56 Thesis Islam, Z. (2010, september 01). Campylobacter infection and Guillain-Barré syndrome in Bangladesh: Clinical epidemiology and comparative microbial genomics. EUR. Prom./coprom.: Prof. Dr. H.P. Endtz, Prof. Dr. A. van Belkum & Dr. B.C. Jacobs. Kap, Y.S. (2010, oktober 06). A primate view on multiple sclerosis. EUR. Prom./coprom.: Prof. Dr. R. Benner, Prof. Dr. J.D. Laman & B.A. 't Hart. Artikel/Letter to the editor Ang, C.W., Dijkstra, J.R., Klerk, M.A. de, Endtz, H.P., Doorn, P.A. van, Jacobs, B.C., Jeurissen, S.H.M. & Wagenaar, J.A. (2010). Host Factors Determine Anti-GM1 Response Following Oral Challenge of Chickens with Guillain-Barre Syndrome Derived Campylobacter jejuni Strain GB11. PLoS One, 5(3). Beyan, H, Drexhage, R.C., Nieuwenhuijsen, LV, Wit, H.J. de, Padmos, R.C., Schloot, N.C., Drexhage, H.A. & Leslie, RD (2010). Monocyte Gene-Expression Profiles Associated With Childhood-Onset Type 1 Diabetes and Disease Risk: A Study of Identical Twins. Diabetes, 59(7), 1751-1755. 112 < back to index Brkic, Z., Olthof, E.D., Drexhage, H.A. & Versnel, M.A. (2010). Monocyte gene expression signatures in rheumatic diseases: biomarkers for disease acitivity and tools. Open Arthritis Journal, 3, 13-17. Broekhoven, M.J.P. van, Graaf, M.T. de, Bromberg, J.E., Hooijkaas, H., Bent, M.J. van den, Beukelaar, J.W. de, Khan, N.A., Gratama, J.W., Geest, J.N. van der, Frens, M.A., Benner, R. & Sillevis Smitt, P.A.E. (2010). Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurological syndromes. Journal of Neurology Neurosurgery and Psychiatry, 81(12), 1341-1344. Broen, JCA, Wolvers-Tettero, I.L.M., Bon, L van, Vonk, MC, Coenen, MJH, Lafyatis, R, Radstake, TRDJ & Langerak, A.W. (2010). Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis. Annals of the Rheumatic Diseases, 69(12), 2213-2216. Cassani, B, Poliani, PL, Marrella, V, Schena, F, Sauer, AV, Ravanini, M, Strina, D, Busse, CE, Regenass, S, Wardemann, H, Martini, A, Facchetti, F, Burg, M. van der, Rolink, A.G., Vezzoni, P, Grassi, F, Traggiai, E & Villa, A (2010). Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome. Journal of Experimental Medicine, 207(7), 1525-1540. Cats, E.A., Pol, WL van der, Piepers, S, Franssen, H., Jacobs, B.C., Berg-Vos, R.M. van den, Kuks, J.B., Doorn, P.A. van, Engelen, BG van, Verschuuren, J.J., Wokke, JH, Veldink, J.H. & Berg, L.H. van den (2010). Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology, 75(9), 818-825. Cats, E.A., Jacobs, B.C., Yuki, N., Tio-Gillen, A.P., Piepers, S, Franssen, H., Asseldonk, JT van, Berg, L.H. van den & Pol, WL van der (2010). Multifocal motor neuropathy Association of anti-GM1 IgM antibodies with clinical features. Neurology, 75(22), 1961-1967. Cheng, C., Noorderloos, M, Deel, E.D. van, Tempel, D., Dekker, W. den, Wagtmans, K, Duncker, D.J.G.M., Soares, MP, Laman, J.D. & Duckers, H.J. (2010). Dendritic Cell Function in Transplantation Arteriosclerosis Is Regulated by Heme Oxygenase 1. Circulation Research, 106(10), 1656-1666. Colin, E.M., Asmawidjaja, P.S., Hamburg, J.P. van, Mus, A.M.C., Driel, M. van, Hazes, J.M.W., Leeuwen, J.P.T.M. van & Lubberts, E. (2010). 1,25-Dihydroxyvitamin D-3 Modulates Th17 Polarization and Interleukin-22 Expression by Memory T Cells From Patients With Early Rheumatoid Arthritis. Arthritis & Rheumatism, 62(1), 132-142. Dik, W.A., Laman, J.D., Hooijkaas, H. & Velden, V.H.J. van der (2010). Therapeutic antibodies and fusion proteins: what are they and how do they work. EJHP Practice, 16, 21-25. Dongen, J.J.M. van (2010). Antibody-based treatment: challenges for companion diagnostics and personalised medicine. EJHP Practice, 16, 17-18. Doorn, P.A. van, Kuitwaard, K., Walgaard, C., Koningsveld, R. van, Ruts, L. & Jacobs, B.C. (2010). IVIG Treatment and Prognosis in Guillain-Barr, Syndrome. Journal of Clinical Immunology, 30, S74-S78. Drexhage, H.A., Drexhage, R.C., Nieuwenhuijsen, L., Padmos, R.C., Weigelt, K., Beumer, W., Bergink, V., Burgerhout, K.M., Knijff, E.M., Versnel, M.A. & Leenen, P.J.M. (2010). De monocyt als potentieel diagnosticum. Het geactiveerde MPS bij stemmingsstoornissen, schizofrenie en autoimmuunziekten. Bi-logical, 3, 42-50. Drexhage, R.C., Heul-Nieuwenhuijsen, L., Padmos, R.C., Beveren, N. van, Cohen, D., Versnel, M.A., Nolen, W.A. & Drexhage, H.A. (2010). Inflammatory gene expression in monocytes of patients with schizophrenia: overlap and difference with bipolar disorder. A study in naturalistically treated patients. International Journal of Neuropsychopharmacology, 13(10), 1369-1381. Drexhage, R.C., Knijff, E.M., Padmos, R.C., Heul-Nieuwenhuijsen, L., Beumer, W., Versnel, M.A. & Drexhage, H.A. (2010). The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder. Expert Review of Neurotherapeutics, 10(1), 59-76. Eijk, M. van, Aust, G, Brouwer, MSM, Meurs, M. van, Voerman, J.S.A., Dijke, I.E., Pouwels, W, Sandig, I, Wandel, E, Aerts, J.M.F.G., Boot, R.G., Laman, J.D. & Hamann, J. (2010). Differential expression of the EGF-TM7 family members CD97 and EMR2 in lipid-laden macrophages in atherosclerosis, multiple sclerosis and Gaucher disease. Immunology Letters, 129(2), 6471. Faaij, CM, Annels, N.E., Ruigrok, G, Burg, M. van der, Ball, LM, Bredius, RG, Tol, M.J. van & Lankester, A.C. (2010). Decrease of Skin Infiltrating and Circulating CCR10+T Cells Coincides with Clinical Improvement after Topical Tacrolimus in Omenn Syndrome. Journal of Investigative Dermatology, 130(1), 308-311. Heidbrink, C, Hausler, SFM, Buttmann, M, Ossadnik, M, Strik, HM, Keller, A, Buck, D, Verbraak, E., Meurs, M. van, Krockenberger, M, Mehling, M, Mittelbronn, M, Laman, J.D., Wiendl, H & Wischhusen, J (2010). Reduced cortisol levels in cerebrospinal fluid and differential distribution of 11 beta-hydroxysteroid dehydrogenases in multiple sclerosis: Implications for lesion pathogenesis. Brain Behavior & Immunity, 24(6), 975-984. Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), 4227-4234. Heul-Nieuwenhuijsen, L., Padmos, R.C., Drexhage, R.C., Wit, H.J. de, Berghout, A. & Drexhage, H.A. (2010). An Inflammatory Gene-Expression Fingerprint in Monocytes of Autoimmune Thyroid Disease Patients. Journal of Clinical Endocrinology and Metabolism, 95(4), 1962-1971. 113 < back to index Islam, Z., Jacobs, B.C., Belkum, A. van, Mohammad, QD, Islam, MB, Herbrink, P., Diorditsa, S, Luby, SP, Talukder, KA & Endtz, H.P. (2010). Axonal variant of Guillain-Barre syndrome associated with Campylobacter infection in Bangladesh. Neurology, 74(7), 581-587. Islam, Z., Mohammad, QD, Endtz, H.P., Jacobs, B.C. & Belkum, A. van (2010). AXONAL VARIANT OF GUILLAIN-BARRE SYNDROME ASSOCIATED WITH CAMPYLOBACTER INFECTION IN BANGLADESH Reply. Neurology, 75(2), 194-195. Jagessar, S.A., Kap, Y.S., Heijmans, N, Driel, N van, Straalen, L van, Bajramovic, J.J., Brok, H.P.M., Blezer, ELA, Bauer, J., Laman, J.D. & Hart, B.A. 't (2010). Induction of Progressive Demyelinating Autoimmune Encephalomyelitis in Common Marmoset Monkeys Using MOG(34-56) Peptide in Incomplete Freund Adjuvant. Journal of Neuropathology and Experimental Neurology, 69(4), 372-385. Kamphuis, L.S.J., Laar, J.A.M. van, Kuipers, R.W.A.M., Missotten, T.O.A.R., Thio, H.B. & Hagen, P.M. van (2010). Sarcoïdose: verandering in therapeutische inzichten. Nederlands Tijdschrift voor Geneeskunde, 154, 1685. Kap, Y.S., Laman, J.D. & Hart, B.A. 't (2010). Experimental Autoimmune Encephalomyelitis in the Common Marmoset, a Bridge Between Rodent EAE and Multiple Sclerosis for Immunotherapy Development. Journal of neuroimmune pharmacology, 5(2), 220-230. Kap, Y.S., Driel, N van, Blezer, E., Parren, PWHI, Bleeker, WK, Laman, J.D., Craigen, JL & Hart, B.A. 't (2010). Late B Cell Depletion with a Human Anti-Human CD20 IgG1 kappa Monoclonal Antibody Halts the Development of Experimental Autoimmune Encephalomyelitis in Marmosets. Journal of Immunology, 185(7), 3990-4003. Kersseboom, R., Kil, L.P., Flierman, R, Zee, M. van der, Dingjan, G.M., Middendorp, S., Maas, A. & Hendriks, R.W. (2010). Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells. European Journal of Immunology, 40(9), 2643-2654. Lubberts, E. (2010). Th17 cytokines and arthritis. Seminars in Immunopathology, 32(1), 43-53. Man, Y.A. de, Bakker-Jonges, L.E., Goorbergh, CM Dufour-van den, Tillemans, S.P.R., Hooijkaas, H., Hazes, J.M.W. & Dolhain, R.J.E.M. (2010). Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy. Annals of the Rheumatic Diseases, 69(2), 420-423. Mus, A.M.C., Cornelissen, F.H.J., Asmawidjaja, P.S., Hamburg, J.P. van, Boon, L., Hendriks, R.W. & Lubberts, E. (2010). Interleukin-23 Promotes Th17 Differentiation by Inhibiting T-bet and FoxP3 and Is Required for Elevation of Interleukin-22, but Not Interleukin-21, in Autoimmune Experimental Arthritis. Arthritis & Rheumatism, 62(4), 1043-1050. Neuteboom, R.F., Verbraak, E., Wierenga-Wolf, A.F., Meurs, M. van, Steegers, E.A.P., Groot, C.J.M. de, Laman, J.D. & Hintzen, R.Q. (2010). Pregnancy-induced fluctuations in functional T-cell subsets in multiple sclerosis patients. Multiple Sclerosis, 16(9), 1073-1078. Oosten, M.J.M. van, Dolhain, R.J.E.M., Koper, F.J.W., Rossum, E.F.C. van, Emonts, M., Han, KH, Wouters, J.M.G.W., Hazes, J.M.W., Lamberts, S.W.J & Feelders, R.A. (2010). Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Research & Therapy, 12(4). Philippens, IHCHM, Hart, B.A. 't & Torres, G (2010). The MPTP marmoset model of Parkinsonism: a multi-purpose non-human primate model for neurodegenerative diseases. Drug Discovery Today, 15(23-24), 985-990. Racz, E., Leeuw, J. de, Baerveldt, E.M., Kant, M., Neumann, H.A.M., Fits, L van der & Prens, E.P. (2010). Cellular and Molecular Effects of Pulsed Dye Laser and Local Narrow-Band UVB Therapy in Psoriasis. Lasers in Surgery and Medicine, 42(3), 201-210. Ruts, L., Drenthen, J., Jacobs, B.C. & Doorn, P.A. van (2010). Distinguishing acute-onset CIDP from fluctuating Guillain-Barre syndrome A prospective study. Neurology, 74(21), 1680-1686. Ruts, L., Drenthen, J., Jongen, J.L.M., Hop, W.C.J., Visser, G.H., Jacobs, B.C. & Doorn, P.A. van (2010). Pain in Guillain-Barre syndrome A long-term follow-up study. Neurology, 75(16), 1439-1447. Steensel, L. van, Paridaens, A.D.A., Dingjan, G.M., Daele, P.L.A. van, Hagen, P.M. van, Kuijpers, R.W.A.M., Bosch, W.A. van den, Drexhage, H.A., Hooijkaas, H. & Dik, W.A. (2010). Platelet-Derived Growth Factor-BB: A Stimulus for Cytokine Production by Orbital Fibroblasts in Graves' Ophthalmopathy. Investigative Ophthalmology & Visual Science, 51(2), 1002-1007. Steensel, L. van & Dik, W.A. (2010). The orbital fibroblast: a key player and target for therapy in Graves' ophthalmopathy. Orbit, 29, 202-206. Vierboom, MPM, Breedveld, E., Kondova, I & Hart, B.A. 't (2010). Collagen-induced arthritis in common marmosets: a new nonhuman primate model for chronic arthritis. Arthritis Research & Therapy, 12(5). Walgaard, C., Lingsma, H.F., Ruts, L., Drenthen, J., Koningsveld, R van, Garssen, MJP, Doorn, P.A. van, Steyerberg, E.W. & Jacobs, B.C. (2010). Prediction of Respiratory Insufficiency in Guillain-Barre Syndrome. Annals of Neurology, 67(6), 781-787. Zwam, M. van, Wierenga-Wolf, A.F., Melief, J.A.M., Schrijver, B., Laman, J.D. & Boven, L.A. (2010). Myelin ingestion by macrophages promotes their motility and capacity to recruit myeloid cells. Journal of Neuroimmunology, 225(1-2), 112-117. 114 < back to index Part of book - abstract Daele, P.L.A. van (2010). Systemische sclerose: kliniek en behandeling. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 51-60). Rotterdam: Erasmus MC afdeling immunologie. Drexhage, H.A., Drexhage, R.C., Nieuwenhuijsen, L., Padmos, R.C., Weigelt, K., Beumer, W., Bergink, V., Burgerhout, K.M., Knijff, E.M., Versnel, M.A. & Leenen, P.J.M. (2010). De monocyt als potentieel diagnosticum. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 31-49). Rotterdam: Erasmus MC afdeling immunologie. Hagen, P.M. van & Velden, V.H.J. van der (2010). Biologicals: specifieke targeting in het immuunsysteem. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 175-186). Rotterdam: Erasmus MC afdeling immunologie. Hooijkaas, H. (2010). Biologicals; nieuwe ontwikkelingen en toepassingen. In PJE Bindels, AJ van der Lelij, LW van der Meer, BNM van der Poel & AD de Vries (Eds.), Ontwikkelingen in de Geneeskunde 2010 (pp. 22-30). Rotterdam: Erasmus MCCongresbureau. Hooijkaas, H. & Dufour - van den Goorbergh, B.C.M. (2010). Detectie van autoantistoffen bij systemische auto-immuunziekten. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 15-29). Rotterdam: Erasmus MC afdeling immunologie. Hooijkaas, H. (2010). Inleiding auto-immuunziekten. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 13-14). Rotterdam: Erasmus MC afdeling immunologie. Jacobs, B.C. (2010). Moleculaire mimicry in het Guillain-Barré syndroom. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 77-89). Rotterdam: Erasmus MC afdeling immunologie. Laar, J.A.M. van, Hagen, P.M. van & Kappen, J.H. (2010). Ziekte van Behçet. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 195-204). Rotterdam: Erasmus MC afdeling immunologie. Laman, J.D., Hintzen, R.Q. & Hart, B.A. 't (2010). Multipele sclerose. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 91-111). Rotterdam: Erasmus MC afdeling immunolgie. Onderdijk, A.J. & Prens, E.P. (2010). Psoriasis. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 187-194). Rotterdam: Erasmus MC afdeling immunologie. Sillevis Smitt, P.A.E. & Hooijkaas, H. (2010). Diagnostiek van paraneoplastische neurologische syndromen. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 127-134). Rotterdam: Erasmus MC afdeling immunologie. Versnel, M.A., Brkic, Z., Helden - Meeuwsen, C.G. van & Merwe, J.P. van de (2010). Het syndroom van Sjögren. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 113-125). Rotterdam: Erasmus MC afdeling immunologie. 115 < back to index EMC MM-02-72-03 - Diagnosis, classification and treatment evaluation of leukemias and malignant lymphomas Programme in brief design This research program focusses on the diagnosis and classification of leukemias and malignant lymphomas as well as on the evaluation of treatment effectiveness during follow-up via detection of low frequencies of malignant cells, i.e. detection of `minimal residual disease¿ (MRD). The research program combines molecular and cellular studies on normal and malignant hematopoiesis, particularly focusing on immature lymphoid differentiation. The research program consists of three main projects: Normal and aberrant V(D)J recombination in leukemias and malignant lymphomas: basic aspects and diagnostic applications. Project leader: A.W. Langerak. One of the key processes during early lymphoid differentiation concerns the rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. This so-called V(D)J recombination process is tightly regulated. Nevertheless, aberrant V(D)J recombination activity can induce aberrant Ig/TCR gene rearrangements, which involve oncogenes. Insight into normal and oncogenic rearrangements can be translated into better diagnosis and classification of lymphoid malignancies. Immunobiology of acute leukemia and treatment evaluation. Project leader: V.H.J. van der Velden. Although most patients with acute leukemia achieve remission according to cytomorphological and clinical criteria, many patients relapse and die from their disease. Therefore sensitive techniques are needed to monitor the patients for the presence of MRD during and after treatment in order to obtain better insight into the in vivo effectiveness of treatment, with flow cytometric immunophenotyping using aberrant marker expression and detection of tumor-associated proteins or with molecular MRD techniques via PCR analysis of Ig/TCR gene rearrangements and chromosome aberrations. Gene expression profiles in immature lymphoid cells and acute lymphoblastic leukemias. Project leader: F.J.Th. Staal. Gene expression profiles determine the differentiation lineage, developmental stage, and activation stage of the involved cells. Just like in any other cell type, regulation of gene expression in lymphocytes is largely controlled at the level of transcriptional initiation by transcription factors and transcriptional repressors. The study focusses on transcription factors and signaling routes that are controlling the most immature steps of lymphoid differentiation. In parallel, the abnormal regulation of gene expression in acute lymphoblastic leukemias is extensively studied and compared to corresponding normal immature T and B cell subpopulations. Results of these comparative studies will be exploited for developing new diagnostic tools. Key figures Department immunology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,39 0,75 2,8 0 3,94 0,39 0,75 2,8 0 3,94 0 0 0 0 18 1 12 31 Artikel/Letter to the editor Bruggemann, M, Schrauder, A, Raff, T., Pfeifer, H., Dworzak, M, Ottmann, O.G., Asnafi, V, Baruchel, A, Bassan, R., Benoit, Y., Biondi, A., Cave, H., Dombret, H., Fielding, A.K., Foa, R., Gokbuget, N., Goldstone, A.H., Goulden, N., Henze, G., Hoelzer, D., Janka-Schaub, G.E., Macintyre, E.A., Pieters, R., Rambaldi, A., Ribera, J.M., Schmiegelow, K., Spinelli, O., Stary, J., Stackelberg, A, Kneba, M., Schrappe, M. & Dongen, J.J.M. van (2010). Standardized MRD quantification in European ALL trials: proceedings of the second international symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. Leukemia, 24, 521-535. Conter, V., Bartram, C.R., Valsecchi, M.G., Schrauder, A, Panzer-Grumayer, R., Moricke, A., Arico, M., Zimmermann, M., Mann, G., Rossi, G. de, Stanulla, M., Locatelli, F., Basso, G., Niggli, F, Barisone, E., Henze, G., Ludwig, WD, Haas, O.A., Cazzaniga, G., Koehler, R, Silvestri, D, Bradtke, J, Parasole, R, Beier, R, Dongen, J.J.M. van, Biondi, A. & Schrappe, M. (2010). Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood, 115(16), 3206-3214. Costa, ES, Pedreira, CE, Barrena, S, Lecrevisse, Q, Flores, J, Quijano, S, Almeida, J., Garcia-Macias, MD, Bottcher, S, Dongen, J.J.M. van & Orfao, A. (2010). Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping. Leukemia, 24(11), 1927-1933. Costa, ES, Peres, RT, Almeida, J., Lecrevisse, Q, Arroyo, ME, Teodosio, C, Pedreira, CE, Dongen, J.J.M. van & Orfao, A. (2010). Harmonization of Light Scatter and Fluorescence Flow Cytometry Profiles Obtained After Staining Peripheral Blood Leucocytes for Cell Surface-Only Versus Intracellular Antigens with the Fix & Perm (TM) Reagent. Cytometry Part B-Clinical Cytometry, 78B(1), 11-20. Dekking, E, Velden, V.H.J. van der, Bottcher, S, Bruggemann, M, Sonneveld, E., Koning-Goedheer, A, Boeckx, N., Lucio, P., Sedek, L, Szczepanski, T., Kalina, T., Kovac, M, Evans, P, Hoogeveen, P.G., Flores-Montero, J, Orfao, A., Comans-Bitter, W.M., Staal, F.J.T. & Dongen, J.J.M. van (2010). Detection of fusion genes at the protein level in leukemia patients via the flow cytometric immunobead assay. Best Practice & Research Clinical Haematology, 23(3), 333-345. Jung, R., Krumbolz, M., Langer, T, Keller, T, Lorenzo, P de, Valsecchi, M.G., Velden, V.H.J. van der, Moericke, A., Stanulla, M., Teigler-Schlegel, A, Panzer-Grümayer, E.R., Dongen, J.J.M. van, Schrappe, M., Boer, M.L. den, Pieters, R., Rascher, W. & Metzler, M. (2010). Bidomal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment. Leukemia, 24, 903-907. Kleppe, M., Lahortiga, I., Chaar, T. el, Keersemaecker, K. de, Mentens, N., Graux, C., Roosbroeck, K. van, Ferrando, A.A., Langerak, A.W., Meijerink, J.P.P., Sigaux, F, Haferlach, T, Wlodarska, I., Vandenberghe, P., Soulier, J. & Cools, J. (2010). Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nature Genetics, 42(6), 530535. 116 < back to index Kuiper, RP de, Waanders, E., Velden, V.H.J. van der, Reijmersdal, SV van, Venkatachalam, R, Scheijen, B, Sonneveld, E., Dongen, J.J.M. van, Veerman, A.J.P., Leeuwen, FN van, Kessel, A.G. van & Hoogerbrugge, P.M. (2010). IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL. Leukemia, 24(7), 1258-1264. Lankester, A.C., Bierings, M.B., Wering, E.R. van, Wijkhuijs, AJM, Weger, R.A. de, Wijnen, J.T., Vossen, J.M., Versluys, B, Egeler, R.M., Tol, M.J.D. van, Putter, H., Revesz, T, Dongen, J.J.M. van, Velden, V.H.J. van der & Schilham, M.W. (2010). Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation. Leukemia, 24(8), 1462-1469. Nieto, WG, Teodosio, C, Lopez, A, Rodriguez-Caballero, A, Romero, A, Barcena, P, Gutierrez, ML, Langerak, A.W., FernandezNavarro, P, Orfao, A. & Almeida, J. (2010). Non-CLL-like Monoclonal B-Cell Lymphocytosis in the General Population: Prevalence and Phenotypic/Genetic Characteristics. Cytometry Part B-Clinical Cytometry, 78B, S24-S34. Perez-Andres, M, Paiva, B, Nieto, WG, Caraux, A, Schmitz, A, Almeida, J., Vogt, RF, Marti, G.E., Rawstron, AC, Zelm, M.C. van, Dongen, J.J.M. van, Johnsen, H.E., Klein, B. & Orfao, A. (2010). Human Peripheral Blood B-Cell Compartments: A Crossroad in B-Cell Traffic. Cytometry Part B-Clinical Cytometry, 78B, S47-S60. Pott, C., Hoster, E, Delfau-Larue, MH, Beldjord, K, Bottcher, S, Asnafi, V, Plonquet, A., Siebert, R., Callet-Bauchu, E, Andersen, N, Dongen, J.J.M. van, Klapper, W, Berger, F, Ribrag, V, Hoof, AL van, Trneny, M, Walewski, J, Dreger, P, Unterhalt, M, Hiddemann, W., Kneba, M., Kluin-Nelemans, H.C., Hermine, O, Macintyre, E. & Dreyling, M (2010). Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood, 115(16), 3215-3223. Staal, F.J.T., Ridder, D. de, Szczepanski, T., Schonewille, T., Linden, ECE van der, Wering, E.R. van, Velden, V.H.J. van der & Dongen, J.J.M. van (2010). Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype. Leukemia, 24(3), 491-499. Szczepanski, T., Harrison, C.J. & Dongen, J.J.M. van (2010). Genetic aberrations in paediatric acute leukaemias and implications for management of patients. Lancet Oncology, 11(9), 880-889. Ta, T.B.V., Bruijn, J.W. de, Brugge, P.J. ter, Hamburg, J.P. van, Diepstraten, H.J.A., Loo, P.F. van, Kersseboom, R. & Hendriks, R.W. (2010). Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway. Blood, 115(7), 1385-1393. Velden, V.H.J. van der, Sluijs-Geling, A van der, Gibson, BES, Marvelde, J.G. te, Hoogeveen, P.G., Hop, W.C.J., Wheatley, K., Bierings, M.B., Schuurhuis, G.J., Graaf, S.S.N. de, Wering, E.R. van & Dongen, J.J.M. van (2010). Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol. Leukemia, 24(9), 1599-1606. Vlierberghe, P. van, Palomero, T., Khiabanian, H., Meulen, J. van der, Castillo, M., Roy, N. van, Moerloose, B. de, Philippe, J, Conzalez-Garcia, S., Toribio, M.L., Taghon, T., Zuurbier, L.C., Cauwelier, B., Harrison, C.J., Schwab, C., Pisecker, M., Strehl, S, Langerak, A.W., Gecz, J., Sonneveld, E., Pieters, R., Paietta, E., Rowe, J., Wiernik, P.H., Benoit, Y., Soulier, J., Poppe, B., Yao, X., Cordon-Cardo, C., Meijerink, J.P.P., Rabadan, R., Speleman, F. & Ferrando, A.A. (2010). PHF6 mutations in T-cell lymphoblastic leukemia. Nature Genetics, 42(4), 338-342. Vries, J.F. de, Marvelde, J.G. te, Wind, H.K., Dongen, J.J.M. van & Velden, V.H.J. van der (2010). The potential use of basigin (CD147) as a prognostic marker in B-cell precursor acute lymphoblastic leukaemia. British Journal of Haematology, 150(5), 624626. Part of book - abstract Bottcher, S, Rawstron, AC, Lucio, P., Macintyre, E., Lima, M., Velden, V.H.J. van der, Dongen, J.J.M. van, Orfao, A. & Kneba, M. (2010). Diagnosis and classification of mature B-cell malignancies. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 355-371). Rotterdam: Erasmus MC, afdeling immunologie. Dekking, E, Velden, V.H.J. van der, Bottcher, S, Bruggemann, M, Sonneveld, E., Sluijs, AJ van der, Boeckx, N., Lucio, P., Sedek, L, Szczepanski, T., Kalina, T., Kovac, M, Evans, P, Hoogeveen, P.G., Flores-Montero, J, Orfao, A., Comans-Bitter, W.M., Staal, F.J.T. & Dongen, J.J.M. van (2010). Aantonen van fusiegenen op eiwitniveau bij leukemiepatiënten met behulp van de flowcytometrische immunobead assay. In Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 429-442). Rotterdam: Erasmus MC, afdeling immunologie. Dongen, J.J.M. van & Velden, V.H.J. van der (2010). Detection of minimal residual disease in acute lymphoblastic leukemia. In B Agarwal, G Calaminus, L Diller & M Egeler (Eds.), SIOP Education Book 2010 (pp. 43-50). Boston: International Society of Paediatric Oncology. Dongen, J.J.M. van & Orfao, A. (2010). Het EuroFlow programma. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 325-340). Erasmus MC, afdeling immunologie. Langerak, A.W., Gastel - van Mol, E.J., Verhaaf, B., Wolvers-Tettero, I.L.M. & Dongen, J.J.M. van (2010). Antigeenspecificiteit in chronische lymfatytische leukemie. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 443-458). Rotterdam: Erasmus MC, afdeling immunologie. Langerak, A.W., Tielemans, D., Missotten, T.O.A.R., Baarsma, G.S., Vermeulen, J., Spek, A. van der, Martin-Martin, L, Almeida, J., Flores-Montero, J, Cullen, M, Mejstrikova, E, Wind, H.K., Velden, V.H.J. van der, Orfao, A. & Dongen, J.J.M. van (2010). Flowcytometrische analyse van 'small samples'. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas 117 < back to index (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 413-428). Rotterdam: Erasmus MC, afdeling immunologie. Lecrevisse, Q, Costa, ES, Pedreira, CE, Martin, M., Hernandez, J, Munoz, M, Flores, J, Almeida, J., Dongen, J.J.M. van & Orfao, A. (2010). Infinicyt : Mulitidimensional analysis of flowcytometric data. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 341-354). Rotterdam: Erasmus MC, afdeling immunologie. Leenen, P.J.M., Laar, J.A.M. van & Egeler, R.M. (2010). Histiocytaire syndromen. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 205-225). Rotterdam: Erasmus MC, afdeling immunologie. Lhermitte, L, Asnafi, V, Flores-Montero, J, Lecrevisse, Q, Sedek, L, Szczepanski, T., Bottcher, S, Bruggemann, M, Mejstrikova, E, Kalina, T., Mendonca, A. De, Lucio, P., Cullen, M, Richards, S., Marvelde, J.G. te, Wind, H.K., Velden, V.H.J. van der, Sluijs, AJ van der, Vidriales, M.B., Hernandez, J, Costa, ES, Macintyre, E., Dongen, J.J.M. van & Orfao, A. (2010). Diagnosis and classification of acute lymphoblastic leukemia. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 373-383). Erasmus MC, afdeling immunologie. Velden, V.H.J. van der, Schoot, C.E. van der, Pieters, R., Haas, V. de & Dongen, J.J.M. van (2010). Evaluatie van therapieeffectiviteit bij kinderen met acute lymfatische leukemie middels detectie van ¿minimal residual disease¿ (MRD). In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 459-480). Rotterdam: Erasmus MC, afdeling immunologie. Velden, V.H.J. van der, Marvelde, J.G. te, Cullen, M, Mejstrikova, E, Flores-Montero, J, Sedek, L, Richards, S., Hrusek, O, Szczepanski, T., Evans, P, Kalina, T., Wind, H.K., Orfao, A. & Dongen, J.J.M. van (2010). Flowcytometrische immunofenotypering van acute myeloïde leukemieën en myelodysplastisch syndroom. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 385-411). Rotterdam: Erasmus MC, afdeling immunologie. Velden, V.H.J. van der & Langerak, A.W. (2010). Inleiding leukemieën en lymfomen. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 319-323). Rotterdam: Erasmus MC, afdeling immunologie. Boekredactie Dongen, J.J.M. van, Dik, W.A., Langerak, A.W., Velden, V.H.J. van der & Hooijkaas, H. (Eds.). (2010). Nieuwe ontwikkelingen in de Medische Immunologie 2010. Rotterdam: Erasmus MC, Universitair Medisch Centrum Rotterdam. 118 < back to index EMC MM-03-24-01 - Solid tumors between bench and bed Programme in brief design The department of Pathology is the backbone of the Josephine Nefkens Institute (JNI), and thereby committed to translational research of human solid tumors. The focus of the department is to unravel the pathogenesis of solid cancers combining advanced morphological and molecular methods on human tumor material, and animal models. Leading themes are the molecular and (epi)genetic basis of cancer, tumor stem cell biology, and tumor-host interactions. Results are used to develop objective criteria for diagnosis, response prediction and prognosis of human cancers, which will then be implemented in topreferral and routine clinical pathology. This is implemented and stimulated by coupling basic scientists with clinical pathologists around specific cancer types. These activities are also meant to facilitate other Erasmus MC departments¿ research programs by making available its morphologic expertise and giving access to human pathology specimens through the Erasmus MC tissue bank (Dr. P.H. Riegman). The research program of the department forms a substantial part of Main Theme 3, ¿Solid Tumors¿ of the Postgraduate Schools Molecular Medicine. Collaborations within Erasmus MC are formalized in the Postgraduate Schools Molecular Medicine, MGC and NIHES. Here below, the research program of the Department of Pathology is briefly summarized per research group: - Group Dr. W.N.M. Dinjens: molecular diagnosis of solid cancers; - Group Prof.dr. R. Fodde: Cancer stemness in tumor onset, progression and metastasis. - Group Dr. A.B. Houtsmuller: kinetics of molecules involved in DNA-repair, and (androgen dependent) transcription, studied in vivo using fluorescent-labeled proteins; - Group Prof.dr. J.M. Kros: molecular markers for diagnosis and response prediction in gliomas; - Group Dr. R.R. De Krijger: molecular markers for diagnosis and progression in pheochromocytoma; - Group Prof.dr. L.H.J. Looijenga and Prof.dr. J.W. Oosterhuis: pathogenesis of germ cell tumors, and cancer risk of various types of gonadal dysgenesis; - Group Prof.dr. J. Trapman and Dr. G.J.L.H. van Leenders: molecular mechanisms of origin and progression of prostate cancer; role of prostate (cancer) stem cells; - Group Prof.dr. E.C. Zwarthoff: biology and molecular diagnosis of bladder cancer; function of the leukemia-associated MN1TEL fusion gene; molecular pathogenesis of meningioma. For more extensive descriptions of the work carried out in our department, the reader is referred to the ‘Application for Renewal of the Erasmus Postgraduate School Molecular Medicine 2003’ (www.molmed.nl), ‘Oncological Research at the Erasmus MC University Medical Center Rotterdam, Annual Reports 2000-2004’, and recent issues of , Daniel den Hoed Cancer News. Key figures Department genetics pathology Total SP1 0 11,16 11,16 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,75 0 0 0,75 6,34 5,2 2,24 24,94 7,09 5,2 2,24 25,69 6 0 0 6 103 6 0 115 Thesis Biermann, K. (2010, maart 05). Pathogenesis of testicular germ cell tumors from a developmental point of view. EUR. Prom./coprom.: Prof. Dr. J.W. Oosterhuis. Casteren, N.J. van (2010, december 07). Aspects of early detection of testicular cancer and cancer related. EUR. Prom./coprom.: Prof. Dr. L.H.J. Looijenga, Prof. Dr. C.H. Bangma & G.R. Dohle. Gaal, J. (2010, november 10). Identifying Genes Involved in Paraganglioma Genesis. EUR (188 pag.). Prom./coprom.: Prof. Dr. R.R. de Krijger. Nederveen, F.H. van (2010, juni 11). Molecular Pathology of Pheochromocytoma and Paraganglioma Development. EUR (205 pag.). Prom./coprom.: Prof. Dr. J.W. Oosterhuis & Prof. Dr. R.R. de Krijger. Petri, B.J. (2010, december 07). Pheochromocytomas & Paragangliomas From DNA to the daily clinical practice. EUR (119 pag.). Prom./coprom.: Prof. Dr. R.R. de Krijger & Prof. Dr. C.H.J. van Eijck. Wolters, T. (2010, april 28). Improving screening strategies for prostate cancer. EUR (185 pag.). Prom./coprom.: Prof.Dr. F.H. Schroder & Prof. Dr. C.H. Bangma. Artikel/Letter to the editor Aa, M.N.M. van der, Steyerberg, E.W., Bangma, C.H., Rhijn, B.W.G. van, Zwarthoff, E.C. & Kwast, T.H. van der (2010). Cystoscopy revisited as the gold standard for detecting bladder cancer recurrence: diagnostic review bias in the randomized, prospective CEFUB trial. Journal of Urology, 183(1), 76-80. Agthoven, T. van, Sieuwerts, A.M., Meijer, D., Meijer-Gelder, M.E. van, Sarwari, R., Sleijfer, S., Foekens, J.A. & Dorssers, L.C.J. (2010). Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response. Endocrine-Related Cancer, 17(1), 215-230. Alataki, D, Triantafyllidis, A, Gaal, J., Rodiou, C, Vouros, J, Papathanasiou, A, Papanicolaou, A, Rombis, V & Krijger, R.R. de (2010). A non-catecholamine-producing sympathetic paraganglioma of the spermatic cord: the importance of performing candidate gene mutation analysis. Virchows Archiv. An International Journal of Pathology, 457(5), 619-622. 119 < back to index Albuquerque, C, Baltazar, C, Filipe, B, Penha, F, Pereira, T, Smits, M.J.M., Cravo, M, Lage, P, Fidalgo, P, Claro, I, Rodrigues, P, Veiga, I, Ramos, JS, Fonseca, I, Leitao, CN & Fodde, R. (2010). Colorectal Cancers Show Distinct Mutation Spectra in Members of the Canonical WNT Signaling Pathway According to Their Anatomical Location and Type of Genetic Instability. Genes Chromosomes & Cancer, 49(8), 746-759. Bakker, M.A. den, Willemsen, S.P., Grunberg, K, Noorduijn, L.A., Oosterhout, MFM van, Suylen, R.J. van, Timens, W., Vrugt, B, Tilburg, A. van & Thunnissen, F.B.J.M. (2010). Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability. Histopathology, 56(3), 356-363. Banez, LL, Sun, L, Leenders, G.J.L.H. van, Wheeler, TM, Bangma, C.H., Freedland, SJ, Ittmann, MM, Lark, AL, Madden, JF, Hartman, A, Weiss, G. & Castanos-Velez, E (2010). Multicenter Clinical Validation of PITX2 Methylation as a Prostate Specific Antigen Recurrence Predictor in Patients With Post-Radical Prostatectomy Prostate Cancer. Journal of Urology, 184(1), 149156. Bayley, JP, Kunst, HPM, Cascon, A, Sampietro, ML, Gaal, J., Korpershoek, E., Hinojar-Gutierrez, A, Timmers, HJLM, Hoefsloot, LH, Hermsen, M.A., Suarez, C, Hussain, A.K., Vriends, AHJT, Hes, FJ, Jansen, JC, Tops, CM, Corssmit, EP, Knijff, P. de, Lenders, J.W.M., Cremers, CWRJ, Devilee, P., Dinjens, W.N.M., Krijger, R.R. de & Robledo, M (2010). SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncology, 11(4), 366-372. Been, J.V., Rours, G.I.J.G., Kornelisse, R.F., Jonkers, F., Krijger, R.R. de & Zimmermann, L.J.I. (2010). Chorioamnionitis alters the response to surfactant in preterm infants. Journal of Pediatrics, 156, 10-15. 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Seasonal and Pandemic Human Influenza Viruses Attach Better to Human Upper Respiratory Tract Epithelium than Avian Influenza Viruses. American Journal of Pathology, 176(4), 1614-1618. Rijckborst, V., Borg, M.J. ter, Cakaloglu, Y, Ferenci, P, Tabak, F, Akdogan, M, Simon, K, Raptopoulou-Gigi, M, Ormeci, N, Zondervan, P.E., Hart, E., Vuuren, A.J. van, Hansen, B.E. & Janssen, H.L.A. (2010). A Randomized Trial of Peginterferon alpha-2a With or Without Ribavirin for HBeAg-Negative Chronic Hepatitis B. American Journal of Gastroenterology, 105(8), 1762-1769. Robanus-Maandag, EC, Koelink, PJ, Breukel, C., Salvatori, DCF, Jagmohan-Changur, SC, Bosch, CAJ, Verspaget, H.W., Devilee, P., Fodde, R. & Smits, M.J.M. (2010). A new conditional Apc-mutant mouse model for colorectal cancer. Carcinogenesis, 31(5), 946-952. Roobol, M.J., Bangma, C.H., Bouazzaoui, S el, Franken-Raab, C.G. & Zwarthoff, E.C. (2010). Feasibility study of screening for bladder cancer with urinary molecular markers (the BLU-P project). Urologic Oncology-Seminars and Original Investigations, 28(6), 686-690. Roobol, M.J., Schroder, F.H., Leenders, G.J.L.H. van, Hessels, D, Bergh, R.C.N. van den, Wolters, T. & Leeuwen, P.J. van (2010). Performance of Prostate Cancer Antigen 3 (PCA3) and Prostate-Specific Antigen in Prescreened Men: Reproducibility and Detection Characteristics for Prostate Cancer Patients with High PCA3 Scores (>= 100). European Urology, 58(6), 893-899. Schmoll, HJ, Jordan, K, Huddart, R., Pes, MPL, Horwich, A., Fizazi, K. & Kataja, V. (2010). Testicular non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21, v147-v154. Schmoll, HJ, Jordan, K, Huddart, R., Pes, MPL, Horwich, A., Fizazi, K. & Kataja, V. (2010). Testicular seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21, v140-v146. Schouten, J.N.L., Verheij, J. & Janssen, H.L.A. (2010). Niet-cirrotische portale hypertensie. Nederlands Tijdschrift voor Geneeskunde, 154, 1276. Schroten-Loef, C., Kraaij, R., Veldhoven, JLM, Berrevoets, C.A., Bakker, M.A. den, Ma, QZ, Sadelain, M, Bangma, C.H., Willemsen, R.A. & Debets, J.E.M.A. (2010). T cell activation upon exposure to patient-derived tumor tissue: A functional assay to select patients for adoptive T cell therapy. Journal of Immunological Methods, 359(1-2), 11-20. 123 < back to index Shahid, M, Dhillon, VS, Khalil, HS, Haque, S, Batra, S, Husain, SA & Looijenga, L.H.J. (2010). A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient. BMC Medical Genetics, 11. Sie, M.P.S., Wiel, HE van der, Smedts, F.M.M. & Boer, A.C. (2010). Human recombinant insulin and amyloidosis: an unexpected association. Netherlands Journal of Medicine, 68(3), 138-140. Smedts, F.M.M., Schrik, M, Horn, T. & Hopman, AHN (2010). Diagnostic Value of Processing Cytologic Aspirates of Renal Tumors in Agar Cell (Tissue) Blocks. Acta Cytologica, 54(4), 587-594. Smedts, F.M.M., Ramaekers, F.C.S. & Hopman, AHN (2010). The Two Faces of Cervical Adenocarcinoma In Situ. International Journal of Gynecological Pathology, 29(4), 378-385. Soest, G. van, Goderie, T, Regar, E.S., Koljenovic, S., Leenders, G.J.L.H. van, Gonzalo Lopez, M.N., Noorden, S van, Okamura, T., Bouma, BE, Tearney, GJ, Oosterhuis, J.W., Serruys, P.W.J.C. & Steen, A.F.W. van der (2010). Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging. Journal of Biomedical Optics, 15(1). Tanner, TM, Denayer, S, Geverts, B., Tilborgh, N Van, Kerkhofs, S, Helsen, C, Spans, L, Dubois, V, Houtsmuller, A.B., Claessens, F & Haelens, A (2010). A (RKLKK633)-R-629 motif in the hinge region controls the androgen receptor at multiple levels. Cellular and Molecular Life Sciences, 67(11), 1919-1927. Vanzyl, B, Planas, R, Ye, Y, Foulis, A, Krijger, R.R. de, Vives-Pi, M & Gillespie, KM (2010). Why are levels of maternal microchimerism higher in type 1 diabetes pancreas? Chimerism, 1(2), 45-50. Veder, L.L., Kerrebijn, J.D.F., Smedts, F.M.M. & Bakker, M.A. den (2010). DIAGNOSTIC ACCURACY OF FINE-NEEDLE ASPIRATION CYTOLOGY IN WARTHIN TUMORS. Head & Neck-Journal for the Sciences and Specialties of the Head and Neck, 32(12), 1635-1640. Veenma, D.C.M., Beurskens, L.W.J.E., Douben, J.C.W., Eussen, B.H.J., Noomen, P., Govaerts, L.C.P., Grijseels, E.W.M., Lequin, M.H., Krijger, R.R. de, Tibboel, D., Klein, A. de & Opstal, D. van (2010). Comparable Low-Level Mosaicism in Affected and Non Affected Tissue of a Complex CDH Patient. PLoS One, 5(12), e15348. Verdijk, R.M., Bakker, M.A. den, Dubbink, H.J., Hop, W.C.J., Dinjens, W.N.M. & Kros, J.M. (2010). TP53 Mutation Analysis of Malignant Peripheral Nerve Sheath Tumors. Journal of Neuropathology and Experimental Neurology, 69(1), 16-26. Viti, F., Merelli, I, Timmermans, M., Bakker, M.A. den, Beltrame, F, Riegman, P.H.J. & Milanesi, L (2010). Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study. Bmc Bioinformatics, 11. Vledder, M.G. van, Hage, J.A. van der, Kirkels, W.J., Verhoef, C., Oosterhuis, J.W. & Wilt, J.H.W. de (2010). Cervical Lymph Node Dissection for Metastatic Testicular Cancer. Annals of Surgical Oncology, 17, S104-S104. Weber, S., Eckert, D, Nettersheim, D, Gillis, A.J.M., Schafer, S, Kuckenberg, P, Ehlermann, J, Werling, U, Biermann, K., Looijenga, L.H.J. & Schorle, H (2010). Critical Function of AP-2gamma/TCFAP2C in Mouse Embryonic Germ Cell Maintenance. Biology of Reproduction, 82, 214-223. Weening, J.J. & Remuzzi, G (2010). Exciting times for renal medicine. Lancet (UK), 375(9722), 1227-1228. Wermann, H., Stoop, H., Gillis, A.J.M., Honecker, F., Gurp, R.J.H.L.M. van, Ammerpohl, O, Richter, J., Oosterhuis, J.W., Bokemeyer, C. & Looijenga, L.H.J. (2010). Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance. Journal of Pathology, 221(4), 433-442. Wessels, M.W., Kuchinka, B., Heydanus, R., Smit, B.J., Dooijes, D., Krijger, R.R. de, Lequin, M.H., Jong, E.M. de, Husen, M, Willems, P..J. & Casey, B. (2010). Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder? Journal of Medical Genetics, 47(5), 351-355. Wijngaart, D.J. van de, Molier, M., Lusher, SJ, Hersmus, R., Jenster, G.W., Trapman, J. & Dubbink, H.J. (2010). Systematic Structure-Function Analysis of Androgen Receptor Leu(701) Mutants Explains the Properties of the Prostate Cancer Mutant L701H. Journal of Biological Chemistry, 285(7), 5097-5105. Winkel, M.L. te, Lequin, M.H., Bruyn, J.R. de, Ven, C.P. van de, Krijger, R.R. de, Pieters, R. & Heuvel-Eibrink, M.M. van den (2010). Self-limiting sternal tumors of childhood (SELSTOC). Pediatric Blood & Cancer, 55, 81-84. Wolters, T., Kwast, T.H. van der, Vissers, C.J., Bangma, C.H., Roobol-Bouts, M.J., Schroder, F.H. & Leenders, G.J.L.H. van (2010). False-negative Prostate Needle Biopsies: Frequency, Histopathologic Features, and Follow-up. American Journal of Surgical Pathology, 34(1), 35-43. Wolters, T., Roobol, M.J., Leeuwen, P.J. van, Bergh, R.C.N. van den, Hoedemaeker, R.F., Leenders, G.J.L.H. van, Schroder, F.H. & Kwast, T.H. van der (2010). Should Pathologists Routinely Report Prostate Tumour Volume? The Prognostic Value of Tumour Volume in Prostate Cancer. European Urology, 57(5), 821-829. Wolters, T., Vissers, KJ, Bangma, C.H., Schroder, F.H. & Leenders, G.J.L.H. van (2010). The value of EZH2, p27kip1, BMI-1 and MIB-1 on biopsy specimens with low-risk prostate cancer in selecting men with significant prostate cancer at prostatectomy. Bju International, 106(2), 280-286. 124 < back to index You, JF, Buhard, O, Ligtenberg, M.J.L., Kets, CM, Niessen, RC, Hofstra, R.M.W., Wagner, A., Dinjens, W.N.M., Colas, C, Lascols, O, Collura, A, Flejou, JF, Duval, A & Hamelin, R (2010). Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats. British Journal of Cancer, 103(12), 1840-1845. Zheng, P. & Kros, J.M. (2010). Challenge of the gap between the current mania of cancer stem cells and the therapeutic strategy for patients with cancer. International Journal of Cancer, 126(6), 1529-1530. Zheng, P., Severijnen, E.A.W.F.M., Willemsen, R. & Kros, J.M. (2010). Different Patterns of Circulatory Shunting in Zebrafish Caldesmon Morphants: A Digital Motion Analysis. Heart lung and curculation, 19(4), 251-252. Zheng, P., Romme, E., Spek, P.J. van der, Dirven, C.M.F., Willemsen, R. & Kros, J.M. (2010). Glut1/SLC2A1 Is Crucial for the Development of the Blood-Brain Barrier In Vivo. Annals of Neurology, 68(6), 835-844. Zuiverloon, T.C.M., Aa, M.N.M. van der, Kwast, T.H. van der, Steyerberg, E.W., Lingsma, H.F., Bangma, C.H. & Zwarthoff, E.C. (2010). Fibroblast Growth Factor Receptor 3 Mutation Analysis on Voided Urine for Surveillance of Patients with Low-Grade Non-Muscle-Invasive Bladder Cancer. Clinical Cancer Research, 16(11), 3011-3018. Zuiverloon, T.C.M., Abas, C.S., Keur, K.A. van der, Vermeij, M., Tjin, S.S.K., Tilborg, A.G. van, Busstra, M.B. & Zwarthoff, E.C. (2010). In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: a case report. BMC Urology, 10, 5. 125 < back to index EMC MM-03-32-04 - Improving accuracy and therapeutic ratio in radiation oncology Programme in brief design A key field of research in radiotherapy is the clinical application of conformal radiotherapy, and intensity modulated radiotherapy (IMRT), where the treated volume is made to conform to the target volume, thereby limiting the volume of irradiated normal critical tissue. By reducing the probability of normal tissue toxicity, this approach allows for sparing of critical organs and/or radiation dose escalation and improved local tumor control. In collaboration with the AvL in Amsterdam, a randomized clinical trial of dose escalation for prostate cancer is currently underway. Phase II studies of intensity modulated conformal radiotherapy are underway for long cancer and head and neck cancer (to limit damage to the salivary glands and escalate dose). Studies of stereotactic irradiation for eye and brain tumors have been activated. The intraoperative brachytherapy research is focused on the treatment of tumors of the rectum, head and neck, and lung. A program of Ultrasound and CT-assisted bbrachytherapy for prostate cancer is underway. In collaboration with the Toraxcenter of the University Hospital Rotterdam, patients are being treated with endovascular brachytherapy in the context of ongoing clinical trials. In addition, two trials of radiotherapy for peripheral vascular disease and arteriovenous shunts are rapidly accruing patients. Finally for a number of clinical tumor sites radiation with concomitant chemotherapy radiation protectors is being studied. The current research in clinical physics is focused on the development and application of tools for conformal intensity modulated therapy. Improved electronic portal imaging (EPI) techniques are being developed and EPI has been clinical implemented for patient set-up verification and correction, in-vivo dosimetry during conformal treatments and for quality assurance measurements of intensity modulated photon beams produced with dynamic multileaf collimation. A program has been started to use implanted radio opaque markers for set-up verification instead of the bony anatomy. The optimization of dose distributions by intensity modulated radiotherapy beams is being actively pursued and algorithm is being developed for automated beam orientation selection. The research activities of molecular radiobiology are geared gaining an improved understanding of the mechanisms and biology relevance of double-strand. DNA breaks repair in relation to genomic instability, carcinogenisis and DNA end joining. In a Dutch Cancer Society funded project, the phenotype of mice with defective homologous recombination repair is currently being analyzed. Recently, dr. Kanaar has been granted a subsidy in the prestigious Pioneer program coordinated by the Netherlands Research Council. Key figures Department genetics radiotherapy Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,5 0 0 0 0,5 5,6 0,5 1 2,15 9,25 6,1 0,5 1 2,15 9,75 5 0 0 5 32 3 1 41 Thesis Al-Mamgani, A. (2010, oktober 08). The Dynamics of Dose Escalation of Radiotherapy for Localized Prostate Cancer. EUR. Prom./coprom.: Prof. Dr. P.C. Levendag. Eppink, B. (2010, juni 11). The Cellular Process of Hoologous Recombination and its Applications in Cancer Biology. EUR. Prom./coprom.: Prof. Dr. R. Kanaar & Prof. Dr. J.H.J. Hoeijmakers. Teguh, D.N. (2010, december 22). Morbidity (Dysphagia) in Head and Neck cancer after Radiohterapy using various Treatment Techniques. EUR. Prom./coprom.: Prof. Dr. P.C. Levendag. Warmerdam, D.O. (2010, september 24). Bological and Functional Analysis of the ATR Checkpoint Pathway. EUR. Prom./coprom.: Prof. Dr. R. Kanaar & Prof. Dr. J.H.J. Hoeijmakers. Wielen, G.J. van der (2010, februari 03). Erectile dysfunction after external beam radiotherapy for porstate cancer. EUR (124 pag.). Prom./coprom.: Prof. Dr. P.C. Levendag & Prof. Dr. C.H. Bangma. Artikel/Letter to the editor Al-Mamgani, A., Lebesque, J.V., Heemsbergen, W.D., Tans, L., Kirkels, W.J., Levendag, P.C. & Incrocci, L. (2010). Controversies in the Treatment of High-Risk Prostate Cancer-what Is the Optimal Combination of Hormonal Therapy and Radiotherapy: A Review of Literature. Prostate, 70(7), 701-709. Al-Mamgani, A., Heemsbergen, W.D., Levendag, P.C. & Lebesque, J.V. (2010). Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial. Radiotherapy and Oncology, 96(1), 13-18. 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Nederlands Tijdschrift voor Urologie, 18(1), 2730. 126 < back to index Basson, R, Rees, P. van, Wang, R., Montejo, AL & Incrocci, L. (2010). Sexual Function in Chronic Illness. Journal of Sexual Medicine, 7(1), 374-388. Bondar, L, Hoogeman, M.S., Osorio, EMV & Heijmen, B.J.M. (2010). A symmetric nonrigid registration method to handle large organ deformations in cervical cancer patients. Medical Physics, 37(7), 3760-3772. Chu, WK, Hanada, K., Kanaar, R. & Hickson, ID (2010). BLM has early and late functions in homologous recombination repair in mouse embryonic stem cells. Oncogene, 29(33), 4705-4714. Dijk, T.B. van, Gillemans, N, Stein, C, Fanis, P., Demmers, J.A.A., Corput, M.P.C. van de, Essers, J., Grosveld, F.G., Bauer, UM & Philipsen, J.N.J. (2010). Friend of Prmt1, a Novel Chromatin Target of Protein Arginine Methyltransferases. Molecular and Cellular Biology, 30(1), 260-272. Dzyubachyk, O., Cappellen, W.A. van, Essers, J., Niessen, W.J. & Meijering, H.W. (2010). Advanced Level-Set-Based Cell Tracking in Time-Lapse Fluorescence Microscopy. IEEE Transactions on Medical Imaging, 29(3), 852-867. Dzyubachyk, O., Essers, J., Cappellen, W.A. van, Baldeyron, C., Inagaki, A., Niessen, W.J. & Meijering, H.W. (2010). Automated analysis of time-lapse fluorescence microscopy images: from live cell images to intracellular foci. Bioinformatics, 26(19), 2424-2430. Grofsmid, D, Dirkx, M, Marijnissen, H, Woudstra, E. & Heijmen, B.J.M. (2010). Dosimetric validation of a commercial Monte Carlo based IMRT planning system. Medical Physics, 37(2), 540-549. Heemsbergen, W.D., Al-Mamgani, A., Witte, MG, Herk, M van, Pos, FJ & Lebesque, J.V. (2010). URINARY OBSTRUCTION IN PROSTATE CANCER PATIENTS FROM THE DUTCH TRIAL (68 GY VS. 78 GY): RELATIONSHIPS WITH LOCAL DOSE, ACUTE EFFECTS, AND BASELINE CHARACTERISTICS. International Journal of Radiation Oncology Biology Physics, 78(1), 19-25. Holthausen, J.T., Wyman, C.L. & Kanaar, R. (2010). Regulation of DNA strand exchange in homologous recombination. DNA Repair, 9(12), 1264-1272. Incrocci, L. (2010). Re: Time of Decline in Sexual Function After External Beam Radiotherapy for Prostate Cancer. European Urology, 57(5), 916-916. Kaijzel, EL, Heijningen, P.M. van, Wielopolski, P.A., Vermeij, M., Koning, G.A., Cappellen, W.A. van, Que, I., Chan, A.J.K., Dijkstra, J., Ramnath, N.W.M., Hawinkels, LJAC, Bernsen, M.R., Lowik, C.W.G.M. & Essers, J. (2010). Multimodality Imaging Reveals a Gradual Increase in Matrix Metalloproteinase Activity at Aneurysmal Lesions in Live Fibulin-4 Mice. Circulation Cardiovascular Imaging, 3(5), 567-577. Montorsi, F, Adaikan, G, Becher, E, Giuliano, F, Khoury, S, Lue, TF, Sharlip, I, Althof, S.E., Andersson, KE, Brock, G, Broderick, G, Burnett, A., Buvat, J, Dean, J, Donatucci, C, Eardley, I, Fugl-Meyer, K.S., Goldstein, I, Hackett, G, Hatzichristou, D, Hellstrom, W, Incrocci, L., Jackson, G., Kadioglu, A, Levine, L, Lewis, R.W., Maggi, M, McCabe, M, McMahon, CG, Montague, D, Montorsi, P, Mulhall, J, Pfaus, J, Porst, H, Ralph, D, Rosen, R, Rowland, D, Sadeghi-Nejad, H, Shabsigh, R, Stief, C, Vardi, Y, Wallen, K & Wasserman, M (2010). Summary of the Recommendations on Sexual Dysfunctions in Men. Journal of Sexual Medicine, 7(11), 3572-3588. Moolenburgh, S.E., Mac Lennan, L.M., Levendag, P.C., Munte, K., Scholtemeijer, M., Hofer, S.O.P. & Mureau, M.A.M. (2010). Nasal Reconstruction after Malignant Tumor Resection: An Algorithm for Treatment. Plastic and Reconstructive Surgery, 126(1), 97-105. Nout, RA, Smit, VTHBM, Putter, H., Juergenliemk-Schulz, IM, Jobsen, J.J., Lutgens, L.C.H.W., Steen-Banasik, E.M. van de, Mens, J.W.M., Slot, A., Kroese, MCS, Bunningen, BNFM van, Ansink, A.C., Putten, W.L.J. van & Creutzberg, C.L. (2010). Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet (UK), 375(9717), 816-823. Pool, A.E.M. van der, Mendez Romero, A.M., Wunderink, W., Heijmen, B.J.M., Levendag, P.C., Verhoef, C. & Ijzermans, J.N.M. (2010). Stereotactic body radiation therapy for colorectal liver metastases. British Journal of Surgery, 97(3), 377-382. Sadovsky, R, Basson, R, Krychman, M, Morales, AM, Schover, L, Wang, R. & Incrocci, L. (2010). Cancer and Sexual Problems. Journal of Sexual Medicine, 7(1), 349-373. Sanchez, H, Kanaar, R. & Wyman, C.L. (2010). Molecular recognition of DNA-protein complexes: A straightforward method combining scanning force and fluorescence microscopy. Ultramicroscopy, 110(7), 844-851. Sun, JY, Oma, Y, Harata, M, Kono, K, Shima, H, Kinomura, A, Ikura, T, Suzuki, H., Mizutani, S., Kanaar, R. & Tashiro, S (2010). ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot. PLoS One, 5(10). Vlaminck, I De, Vidic, I., Loenhout, MTJ van, Kanaar, R., Lebbink, J.H.G. & Dekker, C. (2010). Torsional regulation of hRPAinduced unwinding of double-stranded DNA. Nucleic Acids Research, 38(12), 4133-4142. Voort van Zyp, N.C.M.G. van der, Hoogeman, M.S., Water, S. van de, Levendag, P.C., Holt, B. van der, Heijmen, B.J.M. & Nuyttens, J.J. (2010). Clinical introduction of Monte Carlo treatment planning: A different prescription dose for non-small cell lung cancer according to tumor location and size. Radiotherapy and Oncology, 96(1), 55-60. 127 < back to index Voort van Zyp, N.C.M.G. van der, Prevost, J.G.H.G., Holt, B. van der, Braat, C., Klaveren, R.J. van, Pattynama, P.M.T., Levendag, P.C. & Nuyttens, J.J. (2010). Quality of life after stereotactic radiotherapy forstage I non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 77(1), 31-37. Voort van Zyp, N.C.M.G. van der, Holt, B. van der, Klaveren, R.J. van, Pattynama, P.M.T., Maat, A. van de & Nuyttens, J.J. (2010). Stereotactic body radiotherapy using real-time tumor tracking in octogenarians with non-small cell lung cancer. Lung Cancer, 69(3), 296-301. Wang, HY, Zhang, XM, Wang, P, Yu, XY, Essers, J., Chen, D, Kanaar, R., Takeda, S. & Wang, Y. (2010). Characteristics of DNA-binding proteins determine the biological sensitivity to high-linear energy transfer radiation. Nucleic Acids Research, 38(10), 3245-3251. Warmerdam, D.O. & Kanaar, R. (2010). Dealing with DNA damage: Relationships between checkpoint and repair pathways. Mutation Research. Reviews in Mutation Research, 704(1-3), 2-11. Witte, MG, Heemsbergen, W.D., Bohoslavsky, R, Pos, FJ, Al-Mamgani, A., Lebesque, J.V. & Herk, M van (2010). RELATING DOSE OUTSIDE THE PROSTATE WITH FREEDOM FROM FAILURE IN THE DUTCH TRIAL 68 GY VS. 78 GY. International Journal of Radiation Oncology Biology Physics, 77(1), 131-138. Wolbers, J.G., Mendez Romero, A.M., Linge, A. van, Dallenga, A.H.G. & Nowak, P.J.C.M. (2010). The most efficient intervention for vestibular schwannoma. Nederlands Tijdschrift voor Geneeskunde, 154(26), 714. Wunderink, W., Romero, AM, Seppenwoolde, Y., Boer, H., Levendag, P.C. & Heijmen, B.J.M. (2010). POTENTIALS AND LIMITATIONS OF GUIDING LIVER STEREOTACTIC BODY RADIATION THERAPY SET-UP ON LIVER-IMPLANTED FIDUCIAL MARKERS. International Journal of Radiation Oncology Biology Physics, 77(5), 1573-1583. Xu, HL, Balakrishnan, K., Malaterre, J, Beasley, M, Yan, YQ, Essers, J., Appeldoorn, E., Thomaszewski, JM, Vazquez, M, Verschoor, S, Lavin, MF, Bertonchello, I, Ramsay, RG & McKay, MJ (2010). Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice. PLoS One, 5(8). Zijtveld, M. van, Dirkx, M, Breuers, M, Kuipers, R. & Heijmen, B.J.M. (2010). Evaluation of the 'dose of the day' for IMRT prostate cancer patients derived from portal dose measurements and cone-beam CT. Radiotherapy and Oncology, 96(2), 172177. Part of book - abstract Eppink, B., Essers, J. & Kanaar, R. (2010). Interplay and quality control of DNA damage repair mechanisms. In K Rippe (Ed.), In genome organization and function in the cell nucleus. Weinheim: Wiley-VCH. Levendag, P.C., Teguh, D.N. & Schmitz, P.I.M. (2010). Interstitial Radiation Therapy in Cancer of the Orophayrnx and Oral Cavity. In J Bernier (Ed.), Head and Neck Cancer: Multimodality Management. Springer. 128 < back to index EMC MM-03-32-05 - Hyperthermia: a treatment for cancer Programme in brief design Hyperthermia (HT), i.e. heating tissue to 39 - 44 °C for 60 to 90 minutes, results in a cascade of effects, which all can be exploited to improve tumor response to radiotherapy (RT) and chemotherapy (CT). Currently known effects are: inhibition of radiation-induced damage repair, changes in perfusion, re-oxygenation, effects on macromolecular and nanoparticle delivery, induction of the heat shock response and immunological stimulation. Generally, normal tissue tolerates a hyperthermic treatment of 1 hour up to 44 °C without relevant clinical damage. This makes HT an ideal complementary treatment to both RT and CT. Consequently, HT is always implemented as part of a multimodal, oncological strategy. Its efficacy to improve clinical outcome of radiotherapy and chemotherapy has been demonstrated in multiple randomized phase III trials. At present, HT is part of standard therapy for several tumor pathologies in the Netherlands. The medical program is directed towards the development of the clinical application of HT as adjuvant to RT and CT. The group is internationally recognized for its coordination of the Dutch Deep Hyperthermia Trial, which was also of major importance for the recognition of hyperthermia as regular health care within the frame of the Dutch National Health Service. Currently, we coordinate a national phase III trial investigating RT+HT versus RT+CT in advanced cervical cancer. In close collaboration with the MD¿s of the departments of Radiation Oncology, Gynecology and Medical Oncology, we explore the feasibility of new clinical studies for tumor sites where treatment with regular RT or CT schedules does not result in a satisfactory probability of local control. The research in hyperthermia physics aims at improvement and assurance of the quality of the technical application of the hyperthermia treatment. The group has an international recognized guiding position in translating hyperthermia treatment planning towards clinical application. As strong focus of the research program is on the assessment of critical parameters for the application of 3-dimensional treatment planning on-line during loco-regional deep and superficial heating. In direct association to this objective we also invest in research aiming at (quantitative) validation of our treatment planning models for each individual applicator, including the development of new, accurate QA tools and procedures. Additionally, research is directed on the development of new hyperthermia systems to allow application of hyperthermia at tumor sites, which at this moment cannot be treated. The recent development of the HyperCollar for heating head and neck tumors is an compelling example of our work in this area. Finally, to enable prediction of treatment outcome it is important to perform extensive analysis of the relationship between thermal dose and tumor response. Eventually, this information will enable optimization of the treatment based on a probability of a successful treatment outcome. Key figures Department radiotherapy Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,84 0,74 4 0 6,58 1,84 0,74 4 0 6,58 1 0 0 1 10 1 1 13 Thesis Franckena, M. (2010, september 03). Hyperthermia for the treatment of locally advanced cervix cancer. EUR. Prom./coprom.: Prof. Dr. P.C. Levendag. Artikel/Letter to the editor Bakker, J.F., Paulides, M.M., Christ, A, Kuster, N & Rhoon, G.C. van (2010). Assessment of induced SAR in children exposed to electromagnetic plane waves between 10 MHz and 5.6 GHz. Physics in Medicine and Biology, 55(11), 3115-3130. Bakker, J.F., Paulides, M.M., Westra, A.H., Schippers, H. & Rhoon, G.C. van (2010). Design and test of a 434 MHz multichannel amplifier system for targeted hyperthermia applicators. International Journal of Hyperthermia, 26(2), 158-170. Bruijne, M. de, Holt, B. van der, Rhoon, G.C. van & Zee, J. van der (2010). Evaluation of CEM43 degrees CT90 Thermal Dose in Superficial Hyperthermia. Strahlentherapie und Onkologie, 186(8), 436-443. Drizdal, T., Togni, P., Visek, L & Vrba, J (2010). Comparison of Constant and Temperature Dependent Blood Perfusion in Temperature Prediction for Superficial Hyperthermia. Radioengineering, 19(2), 281-289. Franckena, M., Canters, R., Termorshuizen, F., Zee, J. van der & Rhoon, G.C. van (2010). Clinical implementation of hyperthermia treatment planning guided steering: A cross over trial to assess its current contribution to treatment quality. International Journal of Hyperthermia, 26(2), 145-157. Franckena, M. & Zee, J. van der (2010). Use of combined radiation and hyperthermia for gynecological cancer. Current Opinion in Obstetrics & Gynecology, 22(1), 9-14. Li, L., Hagen, T.L.M. ten, Schipper, D., Wijnberg, T.M., Rhoon, G.C. van, Eggermont, A.M.M., Lindner, L.H. & Koning, G.A. (2010). Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia. Journal of Controlled Release, 143(2), 274-279. Lutgens, L, Zee, J. van der, Pijls-Johannesma, M, Haas-Kock, DFM De, Buijsen, J, Mastrigt, GAPG van, Lammering, G, Ruysscher, DKM De & Lambin, P (2010). Combined use of hyperthermia and radiation therapy for treating locally advanced cervix carcinoma. Cochrane Database Systematics Review. Paulides, M.M., Bakker, J.F., Linthorst, M., Zee, J.A. van der, Rijnen, Z., Neufeld, E, Pattynama, P.M.T., Jansen, P.P., Levendag, P.C. & Rhoon, G.C. van (2010). The clinical feasibility of deep hyperthermia treatment in the head and neck: new challenges for positioning and temperature measurement. Physics in Medicine and Biology, 55(9), 2465-2480. 129 < back to index Zee, J. van der, Bruijne, M. de, Mens, J.W.M., Ameziane, A., Broekmeyer-Reurink, M.P., Drizdal, T., Linthorst, M. & Rhoon, G.C. van (2010). Reirradiation combined with hyperthermia in breast cancer recurrences: Overview of experience in Erasmus MC. International Journal of Hyperthermia, 26(7), 638-648. Part of book - abstract Christen, M, Schenk, O, Neufeld, E, Paulides, M.M. & Burkhart, H (2010). Scientific Computing with Multicore and Accelerators. In Bader, Dongarra, Kurzak, Chapman & Hall (Eds.), CRC Computational Science. Rapport Rhoon, G.C. van, Aernsbergen, L.M. van, Brussaard, G., Kelfkens, G., Kromhout, H., Leeuwen, F.E. van, Leonhard, H.K., Wadman, W.J., Weerdt, D.H.J. van de, Zwamborn, A.P.M. & Rongen, E. van (2010). Gezondheidsraad: Commissie Elektromagnetische velden Langetermijneffecten van radiofrequente elektromagnetische velden. Den Haag: Gezondheidsraad. 130 < back to index EMC MM-03-32-09 - Photodynamic therapy Programme in brief design Main objective of the research programme is to study the interaction between light and living tissue with the purpose of understanding, optimising and further developing applications of light for diagnosis and treatment of disease. In contrast to other physical modalities used for diagnostic or therapeutic purposes, such as ionising radiation, light has only shallow penetration in living tissue. This apparent limitation renders it excellently suitable for diagnosis and treatment of superficial disease. Fueled by rapid developments in optoelectronics, lasers and fiber optic technology, these techniques can be applied in vivo, in a noninvasive or minimally invasive manner. Research activities comprise ex vivo and animal experiments, as well as clinical studies. Current research activities are centered around two strongly interrelated research lines: photodynamic therapy (PDT) and optical dignostics (OD). PDT:Photodynamic therapy is a therapeutic technique that is based on the interaction of a light sensitive drug with light. PDT has been under study for several decades and is now an emerging treatment modality for a range of primarily malignant conditions. It is under clinical investigation for the treatment of cancers of head and neck, bladder, lung, prostate, oesophagus, brain, and skin and several non-malignant indications. For age-related macula degeneration (AMD) and non-melanoma skin cancer PDT is now the gold standard therapy. In the last decade PDT research in my group has focussed on the mechanisms of action of different photosensitisers, light dosimetry, light fractionation and the development of clinical applications. Research activities comprised preclinical work on animal models, phantom studies, theory development, clinical experimentation and clinical pilot studies. Greatest achievements of the reseach group is the improvement of ALA-PDT for basal cell carcinoma to a level at which it outperforms surgery using light fractionation and the development of a very successful approach for PDT of nasopharyngeal cancer. OD: Early attemps to use optical techniques for detecting cancer date from more than a century ago and were partly inspired by the fluorescent emission from the drugs used in early photodynamic therapy. The dramatic technological developments in optics and optoelectronics that have started a decade ago have enabled the use of a large number of new non invasive non destructive optical sampling techniques to probe inside the body. Sofar, my research group has a history in fluorescence imaging and spectroscopy as well as diffuse reflection spectroscopy. These techniques have been investigated for the diagnosis of cancer and are currently being used routinely in monitorring photodynamic therapy. Over the last few years Differential Pathlength Spectroscopy has been developed in my group, which is a special form of reflection spectroscopy. This technique has been used sucesfully in the bronchoscopic classification of early cancers, and is currently iunder investigation for diagnosis of cancer in the esophagus, the oral cavity, the brain and breast. A spin off company has been set up to enable further commercialisation of this technology. In collaboration with Utrecht University we are developing a new in vivo microscopic technique: Non-linear Spectral Imaging. Key figures Department radiotherapy Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 2,3 3,33 0 1 6,63 2,3 3,33 0 1 6,63 1 0 0 1 9 2 0 12 Thesis Kruijt, B. (2010, januari 15). In vivo monitoring of PDT: from lab to clinic. EUR. Prom./coprom.: Prof. Dr. Ir. H.J.C.M. Sterenborg. Artikel/Letter to the editor Amelink, A., Haringsma, J. & Sterenborg, H.J.C.M. (2010). Differential path-length spectroscopy: a tool for quantitative assessment of blood oxygen saturation in microvessels. Gastrointestinal Endoscopy, 71(6), 1100-1100. Kanick, S.C., Leest, K.H. van der, Djamin, RS, Janssens, AM, Hoogsteden, H.C., Sterenborg, H.J.C.M., Amelink, A. & Aerts, J.G.J.V. (2010). Characterization of Mediastinal Lymph Node Physiology In Vivo by Optical Spectroscopy during Endoscopic Ultrasound-Guided Fine Needle Aspiration. Journal of Thoracic Oncology, 5(7), 981-987. Kanick, S.C., Leest, K.H. van der, Aerts, J.G.J.V., Hoogsteden, H.C., Kascakova, S., Sterenborg, H.J.C.M. & Amelink, A. (2010). Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes. Journal of Biomedical Optics, 15(1). Kruijt, B., Snoek, E.M. van der, Sterenborg, H.J.C.M., Amelink, A. & Robinson, D.J. (2010). A dedicated applicator for light delivery and monitoring of PDT of intra-anal intraepithelial neoplasia. Photodiagnosis and Photodynamic Therapy, 7(1), 3-9. Middelburg, T.A., Zaane, F. van, Bruijn, H.S. de, Ploeg- van den Heuvel, A., Sterenborg, H.J.C.M., Neumann, H.A.M., Haas, E.R.M. de & Robinson, D.J. (2010). Fractionated Illumination at Low Fluence Rate Photodynamic Therapy in Mice. Photochemistry and Photobiology, 86(5), 1140-1146. Nachabe, R., Hendriks, BHW, Desjardins, AE, Voort, M. van der, Mark, M.B. van der & Sterenborg, H.J.C.M. (2010). Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600 nm. Journal of Biomedical Optics, 15(3). Robinson, D.J., Karakullukcu, MB, Kruijt, B., Kanick, S.C., Veen, RPL van, Amelink, A., Sterenborg, H.J.C.M., Witjes, M.J.H. & Tan, I.B. (2010). Optical Spectroscopy to Guide Photodynamic Therapy of Head and Neck Tumors. IEEE Journal of Selected Topics in Quantum Electronics, 16(4), 854-862. Robinson, D.J. & Sterenborg, H.J.C.M. (2010). Photodynamic Therapy- Clinical Applications. European Journal of Hospital Pharmacy Practice, 16, 56-58. Sterenborg, H.J.C.M., Rovers, J.P. & Robinson, D.J. (2010). Photodynamic therapy / basic principles. European Journal of Hospital Pharmacy Practice, 16, 58-60. 131 < back to index Ungureanu, C, Amelink, A., Rayavarapu, RG, Sterenborg, H.J.C.M., Manohar, S & Leeuwen, T.G. van (2010). Differential Pathlength Spectroscopy for the Quantitation of Optical Properties of Gold Nanoparticles. ACS Nano, 4(7), 4081-4089. Zaane, F. van, Subbaiyan, D, Ploeg- van den Heuvel, A., Bruijn, H.S. de, Balbas, EM, Pandraud, G, Sterenborg, H.J.C.M., French, P.J. & Robinson, D.J. (2010). A Telemetric light delivery system for metronomic photodynamic therapy (mPDT) in rats. Journal of Biophotonics, 3(5-6), 347-355. 132 < back to index EMC MM-03-44-06 - Neuro-oncology and pain Programme in brief design The overall aim of this scientific program is to study various aspects of cancer involving the nervous system, in close collaboration with many departments, including the departments of Pathology, Immunology, Medical Oncology and Radiotherapy. The program focuses on the following three main topics: 1. Primary Brain Tumors. 1.1 Identify molecular markers predicting treatment response in glial tumors using large scale analysis (genomics, transcriptomics, methylomics, metabolomics) and high-end mass spectrometry. 1.2 Develop experimental gene therapy modality for treatment of primary brain tumors. 1.3 Establish an effective treatment for patients with primary brain tumors. The department participates in phase I trials and is coordinator/initiator of several large international phase II-III trials. 2. Paraneoplastic disorders. 2.1 Identify the association between paraneoplastic autoantibodies, antigen specific T lymphocytes, clinical neurological syndrome and associated tumor. 2.2 Clone the target antigen of newly identified paraneoplastic autoantibodies. 2.3 Study the role of the paraneoplastic autoimmune response in anti-tumor immunity and neurological dysfunction. 3. Pain. 3.1 Study the role of neurotrophic factors in pain transmission in the superficial dorsal horn in animal models. 3.2 Establish an effective treatment for patients with cancer pain, focusing on neuropathic cancer pain and breakthrough pain. The department has initiated several clinical pain studies and coordinates an international randomized study to evaluate a new treatment modality for breakthrough pain. Key figures Department neurology neurosurgery pathology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 5,29 2,45 1,13 2,66 11,53 1,91 0 0 0 1,91 1,3 0,83 0 0 2,13 8,5 3,28 1,13 2,66 15,57 1 0 0 1 43 2 0 46 Thesis Stoop, M.P. (2010, februari 11). Cerebrospinal fluid proteomics of multiple sclerosis patients. EUR. Prom./coprom.: Prof. Dr. R.Q. Hintzen & Dr. T.M. Luider. Artikel/Letter to the editor Alves, R., Eijken, M, Swagemakers, S.M.A., Chiba, H., Titulaer, M.K., Burgers, P.C., Luider, T.M. & Leeuwen, J.P.T.M. van (2010). Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation. Journal of Proteome Research, 9(9), 4688-4700. Bent, M.J. van den, Dubbink, H.J., Marie, Y, Brandes, A.A., Taphoorn, M.J.B., Wesseling, P., Frenay, M., Tijssen, C.C., Lacombe, D., Idbaih, A, Marion, R. van, Kros, J.M., Dinjens, W.N.M., Gorlia, T. & Sanson, M (2010). IDH1 and IDH2 Mutations Are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clinical Cancer Research, 16(5), 1597-1604. Bent, M.J. van den (2010). Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathologica, 120(3), 297-304. Bon, E., Steegers-Theunissen, R.P.M., Steegers, E.A.P., Ursem, N.T.C., Charif, H., Burgers, P.C., Luider, T.M. & Dekker, L.J.M. (2010). Proteomic Analyses of the Developing Chicken Cardiovascular System. Journal of Proteome Research, 9(1), 268-274. Bralten, L.B.C., Kloosterhof, N.K., Gravendeel, L.A.M., Sacchetti, A., Duijm, EJ, Kros, J.M., Bent, M.J. van den, Hoogenraad, C.C., Sillevis Smitt, P.A.E. & French, P.J. (2010). Integrated Genomic Profiling Identifies Candidate Genes Implicated in GliomaGenesis and a Novel LEO1-SLC12A1 Fusion Gene. Genes Chromosomes & Cancer, 49(6), 509-517. Bralten, L.B.C., Gravendeel, A.M., Kloosterhof, N.K., Sacchetti, A., Vrijenhoek, T, Veltman, J.A., Bent, M.J. van den, Kros, J.M., Hoogenraad, C.C., Sillevis Smitt, P.A.E. & French, P.J. (2010). The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma. Oncogene, 29(46), 6138-6148. Brandes, A.A., Stupp, R., Hau, P, Lacombe, D., Gorlia, T., Tosoni, A., Mirimanoff, RO, Kros, J.M. & Bent, M.J. van den (2010). EORTC study 26041-22041: Phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma. European Journal of Cancer, 46(2), 348-354. Broekhoven, M.J.P. van, Graaf, M.T. de, Bromberg, J.E., Hooijkaas, H., Bent, M.J. van den, Beukelaar, J.W. de, Khan, N.A., Gratama, J.W., Geest, J.N. van der, Frens, M.A., Benner, R. & Sillevis Smitt, P.A.E. (2010). Human chorionic gonadotropin treatment of anti-Hu-associated paraneoplastic neurological syndromes. Journal of Neurology Neurosurgery and Psychiatry, 81(12), 1341-1344. 133 < back to index Costa, D. de, Broodman, I., Duijn, M.M. van, Stingl, C., Dekker, L.J.M., Burgers, P.C., Hoogsteden, H.C., Sillevis Smitt, P.A.E., Klaveren, R.J. van & Luider, T.M. (2010). Sequencing and Quantifying IgG Fragments and Antigen-Binding Regions by Mass Spectrometry. Journal of Proteome Research, 9(6), 2937-2945. Dammers, R., Schouten, J.W., Haitsma, I.K., Vincent, A.J.P.E., Kros, J.M. & Dirven, C.M.F. (2010). Towards improving the safety and diagnostic yield of stereotactic biopsy in a single centre. Acta Neurochirurgica, 152(11), 1915-1921. Dekker, L.J.M., Burgers, P.C., Charif, H., Rijswijk, A.L.C.T. van, Titulaer, M.K., Jenster, G.W., Bischoff, R., Bangma, C.H. & Luider, T.M. (2010). Differential expression of protease activity in serum samples of prostate carcinoma patients with metastases. Proteomics, 10(12), 2348-2358. Dhermain, FG, Hau, P, Lanfermann, H, Jacobs, AH & Bent, M.J. van den (2010). Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurology, 9(9), 906-920. Dos Santos Rubio, E.J., Harhangi, B.S., Kros, J.M., Vincent, A.J.P.E. & Dirven, C.M.F. (2010). A Primary Extraosseous Ewing Sarcoma in the Cerebellopontine Angle of a Child: Review of Relevant Literature and Case Report. Neurosurgery, 67(6), E1852E1856. Edvinsson, L., Chan, K.Y., Eftekhari, S, Nilsson, E, Vries, R.D. de, Saveland, H, Dirven, C.M.F., Danser, A.H.J. & Maassen van den Brink, A. (2010). Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries. Cephalalgia, 30(10), 1233-1240. Graaf, M.T. de, Beukelaar, J.W.K. de, Haasnoot, GW, Levering, W.H.B.M., Rogemond, V, Didelot, A, Honnorat, J., Gratama, J.W. & Sillevis Smitt, P.A.E. (2010). HLA-DQ2(+) individuals are susceptible to Hu-Ab associated paraneoplastic neurological syndromes. Journal of Neuroimmunology, 226(1-2), 147-149. Gravendeel, L.A.M., Kloosterhof, N.K., Bralten, L.B.C., Marion, R. van, Dubbink, H.J., Dinjens, W.N.M., Bleeker, FE, Hoogenraad, C.C., Michiels, E.M.C., Kros, J.M., Bent, M.J. van den, Sillevis Smitt, P.A.E. & French, P.J. (2010). Segregation of Non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Human Mutation, 31, 1186-1199. Grisariu, S, Avni, B, Batchelor, TT, Bent, M.J. van den, Bokstein, F, Schiff, D, Kuittinen, O, Chamberlain, M.C., Roth, P, Nemets, A, Shalom, E, Ben-Yehuda, D & Siegal, T (2010). Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report. Blood, 115(24), 5005-5011. Hollestelle, A., Nagel, J.H.A., Smid, M., Lam, S, Elstrodt, F., Wasielewski, M., Ng, S.S., French, P.J., Peeters, J.K., Rozendaal, MJ, Riaz, M., Koopman, D.G., Hagen, T.L.M. ten, Leeuw, BHCGM de, Zwarthoff, E.C., Teunisse, A, Spek, P.J. van der, Klijn, J.G.M., Dinjens, W.N.M., Ethier, SP, Clevers, H, Jochemsen, A.G., Bakker, M.A. den, Foekens, J.A., Martens, J.W.M. & Schutte, M. (2010). Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Research and Treatment, 121(1), 53-64. Hoorn, E.J., Laar, J.A.M. van, Hollander, J.G. den, Kros, J.M. & Brusse, E. (2010). Pulmonary puzzle Three diagnoses become one: a woman with ground-glass attenuation develops fever. Thorax, 65(3), 214-+. Idema, S, Dirven, C.M.F., Beusechem, VW van, Carette, JE, Planque, R, Noskel, DP, Lamfers, M.L.M. & Vandertop, W.P. (2010). Objective determination of the oncolytic potency of conditionally-replicating adenoviruses using mathematical modeling. Journal of Gene Medicine, 12(7), 564-571. Jonge, R. de, Brouwer, R., Graaf, M.T. de, Luitwieler, RL, Fleming, C, Frankrijker-Merkestijn, M. de, Sillevis Smitt, P.A.E., Boonstra, J.G. & Lindemans, J. (2010). Evaluation of the new body fluid mode on the Sysmex XE-5000 for counting leukocytes and erythrocytes in cerebrospinal fluid and other body fluids. Clinical Chemistry and Laboratory Medicine, 48(5), 665-675. Kampen, J.J.A. van, Reedijk, M.L., Burgers, P.C., Dekker, L.J.M., Hartwig, N.G., Ende, M.E. van der, Groot, R. de, Osterhaus, A.D.M.E., Burger, D, Luider, T.M. & Gruters, R.A. (2010). Ultra-fast analysis of plasma and intracellular levels of HIV protease inhibitors in children: a clinical application of MALDI Mass Spectometry. PLoS One, 5(7), e11409. Kuijf, M.L., Samsom, J.N., Rijs, W. van, Bax, M., Huizinga, R, Heikema, A.P., Doorn, P.A. van, Belkum, A. van, Kooyk, Y. van, Burgers, P.C., Luider, T.M., Endtz, H.P., Nieuwenhuis, E.E.S. & Jacobs, B.C. (2010). TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation. Journal of Immunology, 185, 748-755. Marignier, R, Chenevier, F, Rogemond, V, Sillevis Smitt, P.A.E., Renoux, C, Cavillon, G, Androdias, G, Vukusic, S, Graus, F., Honnorat, J. & Confavreux, C (2010). Metabotropic Glutamate Receptor Type 1 Autoantibody-Associated Cerebellitis A Primary Autoimmune Disease? Archives of Neurology, 67(5), 627-630. Meesters, R.J.W., Cornelissen, R., Klaveren, R.J. van, Jonge, R. de, Boer, E., Lindemans, J. & Luider, T.M. (2010). A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients. Analytical and Bioanalytical Chemistry, 398(7-8), 2943-2948. Meesters, R.J.W., Kampen, J.J.A. van, Reedijk, M.L., Scheuer, R.D., Dekker, L.J.M., Burger, D.M., Hartwig, N.G., Osterhaus, A.D.M.E., Luider, T.M. & Gruters, R.A. (2010). Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots. Analytical and Bioanalytical Chemistry, 398, 319-328. Mischak, H, Allmaier, G, Apweiler, R., Attwood, T, Baumann, M., Benigni, A, Bennett, SE, Bischoff, R., Bongcam-Rudloff, E, Capasso, G, Coon, JJ, D'Haese, P, Dominiczak, AF, Dakna, M, Dihazi, H, Ehrich, JH, Fernandez-Llama, P, Fliser, D, Frokiaer, J, Garin, J, Girolami, M, Hancock, WS, Haubitz, M, Hochstrasser, D, Holman, RR, Ioannidis, JPA, Jankowski, J, Julian, BA, Klein, JB, Kolch, W, Luider, T., Massy, Z, Mattes, WB, Molina, F, Monsarrat, B, Novak, J., Peter, K, Rossing, P., Sanchez- 134 < back to index Carbayo, M, Schanstra, JP, Semmes, OJ, Spasovski, G, Theodorescu, D, Thongboonkerd, V, Vanholder, R, Veenstra, TD, Weissinger, E, Yamamoto, T & Vlahou, A (2010). Recommendations for Biomarker Identification and Qualification in Clinical Proteomics. Science translational medicine, 2(46). Mustafa, D.A., Weiden, M.M. van der, Zheng, P.P., Nigg, A.L., Luider, T.M. & Kros, J.M. (2010). Expression sites of colligin 2 in glioma blood vessels. Brain Pathology, 20, 50-65. Mustafa, D.A.M., Sieuwerts, A.M., Zheng, P.P. & Kros, J.M. (2010). Overexpression of Colligin 2 in glioma vasculature is associated with overexpression of heat shock factor 2. Gene Regulation and Systems Biology, 4, 103-107. Putten, H.P. van, Dirven, C.M.F., Bent, M.J. van den & Lamfers, M.L.M. (2010). Sitimagene ceradenovec: a gene-based drug for the treatment of operable high-grade glioma. Future Oncology, 6(11), 1691-1710. Schuurmans, M., Bromberg, J.E.C., Doorduijn, J.K., Poortmans, P, Taphoorn, M.J.B., Seute, T, Enting, R, Imhoff, G. van, Norden, Y. van & Bent, M.J. van den (2010). Primary central nervous system lymphoma in the elderly: a multicentre retrospective analysis. British Journal of Haematology, 151(2), 179-184. Stoop, M.P., Singh, V., Dekker, L.J.M., Titulaer, M.K., Stingl, C., Burgers, P.C., Sillevis Smitt, P.A.E., Hintzen, R.Q. & Luider, T.M. (2010). Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis. PLoS One, 5(8). Stoop, M.P., Coulier, L, Rosenling, T, Shi, S, Smolinska, AM, Buydens, L, Ampt, K, Stingl, C., Dane, A, Muilwijk, B, Luitwieler, RL, Sillevis Smitt, P.A.E., Hintzen, R.Q., Bischoff, R., Wijmenga, SS, Hankemeier, T, Gool, A.J. van & Luider, T.M. (2010). Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples. Molecular & Cellular Proteomics, 9(9), 2063-2075. Tabatabai, G, Stupp, R., Bent, M.J. van den, Hegi, ME, Tonn, JC, Wick, W & Weller, M (2010). Molecular diagnostics of gliomas: the clinical perspective. Acta Neuropathologica, 120(5), 585-592. Taphoorn, M.J.B., Claassens, L, Aaronson, N.K., Coens, C., Mauer, M., Osoba, D, Stupp, R., Mirimanoff, RO, Bent, M.J. van den & Bottomley, A. (2010). An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. European Journal of Cancer, 46(6), 1033-1040. VanDuijn, MM, Dekker, L.J.M., Zeneyedpour, L., Sillevis Smitt, P.A.E. & Luider, T.M. (2010). Immune Responses Are Characterized by Specific Shared Immunoglobulin Peptides That Can Be Detected by Proteomic Techniques. Journal of Biological Chemistry, 285(38), 29247-29253. Verdijk, R.M., Bakker, M.A. den, Dubbink, H.J., Hop, W.C.J., Dinjens, W.N.M. & Kros, J.M. (2010). TP53 Mutation Analysis of Malignant Peripheral Nerve Sheath Tumors. Journal of Neuropathology and Experimental Neurology, 69(1), 16-26. Weller, M, Stupp, R., Reifenberger, G., Brandes, A.A., Bent, M.J. van den, Wick, W & Hegi, ME (2010). MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nature Reviews Neurology, 6(1), 39-51. Wen, PY, Macdonald, DR, Reardon, D.A., Cloughesy, TF, Sorensen, AG, Galanis, E, DeGroot, J., Wick, W, Gilbert, MR, Lassman, AB, Tsien, C, Mikkelsen, T, Wong, ET, Chamberlain, M.C., Stupp, R., Lamborn, K.R., Vogelbaum, MA, Bent, M.J. van den & Chang, SM (2010). Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in NeuroOncology Working Group. Journal of Clinical Oncology, 28(11), 1963-1972. Wick, W, Weller, M, Bent, M.J. van den & Stupp, R. (2010). Bevacizumab and Recurrent Malignant Gliomas: A European Perspective. Journal of Clinical Oncology, 28(12), E188-E189. Wick, W, Puduvalli, VK, Chamberlain, M.C., Bent, M.J. van den, Carpentier, A.F., Cher, LM, Mason, W., Weller, M, Hong, S, Musib, L, Liepa, AM, Thornton, DE & Fine, HA (2010). 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Protein and peptide markers for chemotherapy resistance in breast cancer. no. 135 < back to index EMC MM-03-47-02-A - Pathophysiological aspects and treatment of gastro-intestinal diseases Programme in brief design A major objective of this project is to investigate the impact of recently developed modalities for the diagnosis and treatment of gastro-intestinal diseases. The etiology of functional disorders such as constipation, disordered defecation and fecal incontinence will be evaluated using new diagnostic tools such as conventional anorectal manometry, 24-hours ambulant anorectal manometry, electromyography, barostat-measurements and laser Doppler flowmetry. New immuno-histochemical techniques using monoclonal antibodies will be used to investigate the histopathological characteristics of slow transit constipation. The efficacy of new therapeutic options such as anterior rectopexy, enterocele repair and sacral neuromodulation will be evaluated in clinical trials. Treatment of fecal incontinence and obstructed defecation by means of neuromodulation with pacemakers is a major topic for the next years. Medical treatment of anal fissures by local application of drugs, such as exogenous NO-donors and botulin-toxin, will also be evaluated. New surgical procedures, such as the Iwadare-technique, will be implemented in the treatment of complex, high transsphincteric fistulas. Pathofysiological aspects of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis will be studied. Another objective of this project is to evaluate the functional results following ileo-anal anastomosis in patients with IBD and FAP and following colo-anal anastomosis in patients with rectal cancer. New radiological tools such as endorectal ultrasound and magnetic resonance imaging of the anal sphincters and pelvic floor using an endo-anal coil, will be used for the preoperative localisation and classification of perianal fistulas, sphincter defects and rectal cancer. The role of laparoscopic techniques will be evaluated in patiens with acute peritonitis and colorectal cancer. The potential benefit of endoscopic intersection of the splanchnic nerves for patients with severe abdominal pain due to chronic pancreatitis will be studied. Key figures Department immunology surgery Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,2 0 0 0 1,2 3,82 0 0 0 3,82 5,02 0 0 0 5,02 5 0 0 5 69 10 0 84 Thesis Grotenhuis, B.A. (2010, december 01). The mischellaneous mystery of esophageal cancer: new pathogenetic and clinical insights. EUR. Prom./coprom.: Prof. Dr. R. Fodde & Prof. Dr. J.J.B. van Lanschot. Hartog, D. den (2010, september 22). Incisional hernia. EUR. Prom./coprom.: Prof. Dr. J.F. Lange. Petri, B.J. (2010, december 07). Pheochromocytomas & Paragangliomas From DNA to the daily clinical practice. EUR (119 pag.). Prom./coprom.: Prof. Dr. R.R. de Krijger & Prof. Dr. C.H.J. van Eijck. Vermeulen, J. (2010, december 07). Strategies in perforated diverticulitis. EUR. Prom./coprom.: Prof. Dr. J.F. Lange. Wijsmuller, A.R. (2010, december 08). Inguinal hernia management: focus on pain. EUR. Prom./coprom.: Prof.Dr. J. Jeekel & Prof. Dr. J.F. Lange. Artikel/Letter to the editor Bakker, OJ, Go, P.M., Puylaert, JB, Kazemier, G. & Heij, HA (2010). Guideline on diagnosis and treatment of acute appendicitis: imaging prior to appendectomy is recommended. Nederlands Tijdschrift voor Geneeskunde, 154, 303. Bertleff, M.J.O.E. & Lange, J.F. (2010). Laparoscopic correction of perforated peptic ulcer: first choice? A review of literature. Surgical Endoscopy-Ultrasound and Interventional Techniques, 24(6), 1231-1239. Bertleff, MJOE & Lange, J.F. (2010). Perforated Peptic Ulcer Disease: A Review of History and Treatment. Digestive Surgery, 27(3), 161-169. Bommel, J. van, Jonge, J. de, Buise, M.P., Specht, P.A.C., Genderen, M van & Gommers, D. (2010). The effects of intravenous nitroglycerine and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstruction. Surgery, 148(1), 71-77. Boonstra, J.J., Marion, R. van, Beer, DG, Lin, L., Chaves, P, Ribeiro, C, Pereira, AD, Roque, L, Darnton, S.J., Altorki, NK, Schrump, DS, Klimstra, D.S., Tang, LH, Eshleman, JR, Alvarez, H, Shimada, Y, Dekken, H. van, Tilanus, H.W. & Dinjens, W.N.M. (2010). Verification and Unmasking of Widely Used Human Esophageal Adenocarcinoma Cell Lines. Journal of the National Cancer Institute, 102(4), 271-274. Bosma, B.M., Metselaar, H.J., Gerrits, J.H., Besouw, N.M. van, Mancham, S., Groothuismink, Z.M.A., Boor, P.P.C., Laan, L.J.W. van der, Tilanus, H.W., Kuipers, E.J. & Kwekkeboom, J. (2010). Migration of Allosensitizing Donor Myeloid Dendritic Cells into Recipients After Liver Transplantation. Liver Transplantation, 16(1), 12-22. Bruynzeel, J.A., Feelders, R.A., Groenland, T.H.N., Meiracker, A.H. van den, Eijck, C.H.J. van, Lange, J.F., Herder, W.W. de & Kazemier, G. (2010). Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 95(2), 678-685. 136 < back to index Cijs, TM, Verhoef, C., Steyerberg, E.W., Koppert, L.B., Tran, T.C.K., Wijnhoven, B.P.L., Tilanus, H.W. & Jonge, J. de (2010). Outcome of Esophagectomy for Cancer in Elderly Patients. Annals of Thoracic Surgery, 90(3), 900-907. Claassen, M.A.A., Knegt, R.J. de, Tilanus, H.W., Janssen, H.L.A. & Boonstra, P.A. (2010). Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. Journal of Hepatology, 52(3), 315321. Eshuis, WJ, Gaag, N.A. van der, Rauws, E.A.J., Eijck, C.H.J. van, Bruno, M.J., Kuipers, E.J., Coene, P.P., Kubben, FJGM, Gerritsen, JJGM, Greve, J.W., Gerhards, MF, Hingh, IHJT de, Klinkenbijl, J.H., Nio, CY, Castro, SMM de, Busch, O.R.C., Gulik, T.M., Bossuyt, P.M.M. & Gouma, D.J. (2010). Therapeutic Delay and Survival After Surgery for Cancer of the Pancreatic Head With or Without Preoperative Biliary Drainage. Annals of Surgery, 252(5), 840-848. Gaag, N.A. van der, Rauws, E.A.J., Eijck, C.H.J. van, Bruno, M.J., Harst, E. van der, Kubben, FJGM, Gerritsen, JJGM, Greve, J.W., Gerhards, MF, Hingh, IHJT de, Klinkenbijl, JHG, Nio, CY, Castro, SMM de, Busch, O.R.C., Gulik, T.M., Bossuyt, PM & Gouma, D.J. (2010). Preoperative Biliary Drainage for Cancer of the Head of the Pancreas. New England Journal of Medicine, 362(2), 129-137. Ginneken, B.T.J. van, Berg-Emons, H.J.G. van den, Metselaar, H.J., Tilanus, H.W., Kazemier, G. & Stam, H.J. (2010). Effects of a rehabilitation programme on daily functioning, participation, health-related quality of life, anxiety and depression in liver transplant recipients. Disability & Rehabilitation, 32(25), 2107-2112. Ginneken, B.T.J. van, Berg-Emons, H.J.G. van den, Windt, A.E. van der, Tilanus, H.W., Metselaar, H.J., Stam, H.J. & Kazemier, G. (2010). Persistent fatigue in liver transplant recipients: a two-year follow-up study. Clinical Transplantation, 24(1), E10-E16. Goede, B. de, Eker, H.H., Metselaar, H.J., Tilanus, H.W., Lange, J.F. & Kazemier, G. (2010). RE: Emergency liver transplantation after umbilical hernia repair: A case report. Transplantation Proceedings, 42(7), 2823-2823. Gooszen, H.G. (2010). The PROPATRIA trial: best practices at the time were followed. Lancet (UK), 375(9722), 1249-1250. Grotenhuis, B.A., Dinjens, W.N.M., Wijnhoven, B.P.L., Sonneveld, P., Sacchetti, A., Franken, P.F., Dekken, H. van, Tilanus, H.W., Lanschot, J.J.B. van & Fodde, R. (2010). Barrett's oesophageal adenocarcinoma encompasses tumour-initiating cells that do not express common cancer stem cell markers. Journal of Pathology, 221(4), 379-389. Grotenhuis, B.A., Hagen, P. van, Wijnhoven, B.P.L., Spaander, M.C.W., Tilanus, H.W. & Lanschot, J.J.B. van (2010). Delay in Diagnostic Workup and Treatment of Esophageal Cancer. Journal of Gastrointestinal Surgery, 14(3), 476-483. Grotenhuis, B.A., Heijl, M. van, Kate, F.J.W. ten, Biermann, K., Offerhaus, G.J.A., Wijnhoven, B.P.L., Henegouwen, MIV, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Inter- and intraobserver variation in the histopathological evaluation of early oesophageal adenocarcinoma. Journal of Clinical Pathology, 63(11), 978-981. Grotenhuis, B.A., Heijl, M. van, Wijnhoven, B.P.L., Henegouwen, MIV, Biermann, K., Kate, F.J.W. ten, Busch, O.R.C., Dinjens, W.N.M., Tilanus, H.W. & Lanschot, J.J.B. van (2010). Lymphatic Micrometastases in Patients With Early Esophageal Adenocarcinoma. Journal of Surgical Oncology, 102(7), 863-867. Grotenhuis, B.A., Wijnhoven, B.P.L., Grune, F., Bommel, J. van, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Preoperative Risk Assessment and Prevention of Complications in Patients With Esophageal Cancer. Journal of Surgical Oncology, 101(3), 270278. Grotenhuis, B.A., Wijnhoven, B.P.L., Hotte, GJ, Stok, EP van der, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Prognostic Value of Body Mass Index on Short-Term and Long-Term Outcome after Resection of Esophageal Cancer. World Journal of Surgery, 34(11), 2621-2627. Grotenhuis, B.A., Heijl, M. van, Zehetner, J, Moons, J, Wijnhoven, B.P.L., Henegouwen, MIV, Tilanus, H.W., DeMeester, TR, Lerut, T. & Lanschot, J.J.B. van (2010). Surgical Management of Submucosal Esophageal Cancer Extended or Regional Lymphadenectomy? Annals of Surgery, 252(5), 823-829. Grotenhuis, B.A., Wijnhoven, B.P.L., Dekken, H. van & Lanschot, J.J.B. van (2010). THE MURINE MONOCLONAL ANTIBODY ANTI-CYTOKERATIN CAM 5.2 IS SPECIFIC FOR INTRACELLULAR CYTOKERATIN 8, NOT CYTOKERATIN 18 Reply. Journal of Thoracic and Cardiovascular Surgery, 139(6), 1675-1675. Grotenhuis, B.A., Lanschot, J.J.B. van, Dinjens, W.N.M. & Wijnhoven, B.P.L. (2010). The pathogenesis of Barrett's metaplasia and the progression to esophageal adenocarcinoma. Recent Results in Cancer Research, 182, 39-63. Grotenhuis, B.A., Hagen, P. van, Reitsma, JB, Lagarde, SM, Wijnhoven, B.P.L., Henegouwen, MIV, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Validation of a Nomogram Predicting Complications After Esophagectomy for Cancer. Annals of Thoracic Surgery, 90(3), 920-926. Harinck, F., Poley, J.W., Kluijt, I., Fockens, P. & Bruno, M.J. (2010). Is Early Diagnosis of Pancreatic Cancer Fiction? Surveillance of Individuals at High Risk for Pancreatic Cancer. Digestive Diseases, 28(4-5), 670-678. Harlaar, J.J., Ramshorst, G.H. van, Jeekel, H & Lange, J.F. (2010). Effect of Stitch Length on Wound Complications. Archives of Surgery, 145(6), 599-599. Hartog, D. den, Eker, H.H., Tuinebreijer, W.E., Kleinrensink, G.J., Stam, H.J. & Lange, J.F. (2010). Isokinetic strength of the trunk flexor muscles after surgical repair for incisional hernia. Hernia, 14(3), 243-247. 137 < back to index Heijl, M. van, Omloo, JM, Henegouwen, MIV, Lanschot, J.J.B. van, Sloof, G.W. & Boellaard, R. (2010). Influence of ROI definition, partial volume correction and SUV normalization on SUV-survival correlation in oesophageal cancer. Nuclear Medicine Communications, 31(7), 652-658. Heijl, M. van, Wijngaarden, AKS van, Lagarde, SM, Busch, O.R.C., Lanschot, J.J.B. van & Henegouwen, MIV (2010). Intrathoracic manifestations of cervical anastomotic leaks after transhiatal and transthoracic oesophagectomy. British Journal of Surgery, 97(5), 726-731. Heijl, M. van, Lanschot, J.J.B. van, Blom, RL, Bergman, J.J., Kate, F.J.C. ten, Busch, O.R.C., Reitsma, J.B. & Obertop, H. (2010). Outcomes of 16 years of oesophageal surgery: low postoperative mortality and improved long-term survival. Nederlands Tijdschrift voor Geneeskunde, 154, 1156. Heijl, M. van, Gooszen, JA, Fockens, P., Busch, OR, Lanschot, J.J.B. van & Henegouwen, MIV (2010). Risk Factors for Development of Benign Cervical Strictures After Esophagectomy. Annals of Surgery, 251(6), 1064-1069. Hoogduijn, M.J., Popp, FC, Grohnert, A, Crop, M.J., Rhijn, M. van, Rowshani, T., Eggenhofer, E, Renner, P, Reinders, ME, Rabelink, T.J., Laan, L.J.W. van der, Dor, F.J.M.F., Ijzermans, J.N.M., Genever, PG, Lange, C, Durrbach, A, Houtgraaf, H.J., Christ, B, Seifert, M, Shagidulin, M, Donckier, V, Deans, R, Ringden, O, Perico, N, Remuzzi, G, Bartholomew, A, Schlitt, HJ, Weimar, W., Baan, C.C. & Dahlke, MH (2010). Advancement of Mesenchymal Stem Cell Therapy in Solid Organ Transplantation (MISOT). Transplantation, 90(2), 124-126. Hoven, B. van der, Pelt, H van, Swart, EL, Bonthuis, F., Tilanus, H.W., Bakker, J. & Gommers, D. (2010). Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model. American Journal of Physiology-Gastrointestinal and Liver Physiology, 298(2), G177-G181. Jeurnink, S.M., Steyerberg, E.W., Hooft, JE van, Eijck, C.H.J. van, Schwartz, MP, Vleggaar, F.P., Kuipers, E.J. & Siersema, P.D. (2010). Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointestinal Endoscopy, 71(3), 490-499. Jong, K. de, Nio, CY, Hermans, J.J., Dijkgraaf, MG, Gouma, D.J., Eijck, C.H.J. van, Heel, E van, Klass, G, Fockens, P. & Bruno, M.J. (2010). High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations. Clinical Gastroenterology and Hepatology, 8(9), 806-811. Joosse, A., Vries, E. de, Eijck, C.H.J. van, Eggermont, A.M.M., Nijsten, T.E.C. & Coebergh, J.W.W. (2010). Reactive oxygen species and melanoma: an explanation for gender differences in survival? Pigment Cell & Melanoma Research, 23(3), 352-364. Keereweer, S., Sewnaik, A., Kerrebijn, J.D.F., Meeuwis, C.A., Tilanus, H.W. & Wilt, J.H.W. de (2010). Dysphagia after an Lshaped reconstruction technique of the free jejunum graft. Journal of Plastic, Reconstructive & Aesthetic Surgery, 63(11), 18201824. Keereweer, S., Wilt, J.H.W. de, Sewnaik, A., Meeuwis, C.A., Tilanus, H.W. & Kerrebijn, J.D.F. (2010). Early and long-term morbidity after total laryngopharyngectomy. European Archives of Oto-Rhino-Laryngology, 267(9), 1437-1444. Keereweer, S., Sewnaik, A., Kerrebijn, J.D.F., Meeuwis, C.A., Tilanus, H.W. & Wilt, J.H.W. de (2010). Salvage or what follows the failure of a free jejunum transfer for reconstruction of the hypopharynx? Journal of Plastic, Reconstructive & Aesthetic Surgery, 63(6), 976-980. Klijn, E., Niehof, S., Jonge, J. de, Gommers, D., Ince, C. & Bommel, J. van (2010). The Effect of Perfusion Pressure on Gastric Tissue Blood Flow in an Experimental Gastric Tube Model. Anesthesia & Analgesia, 110(2), 541-546. Koljenovic, S., Eijck, C.H.J. van & Bakker, M.A. den (2010). Pigmented black neuroendocrine tumour of the pancreas diagnosed by fine needle aspiration cytology. Cytopathology, 21(4), 270-272. Koop, K, Akkermans, F.L., Mennema-Vastenhout, TH, Schouten, W.R., Dam, J.H. & Collet, G.J. (2010). Subcutaneous emphysema of the neck after colectomy. International Journal of Colorectal Disease, 25(7), 917-918. Kwekkeboom, D.J., Herder, W.W. de, Eijck, C.H.J. van, Kam, B.L.R., Essen, M. van, Teunissen, J.J.M. & Krenning, E.P. (2010). Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors. Seminars in Nuclear Medicine, 40(2), 78-88. Kwekkeboom, D.J., Kam, B.L.R., Essen, M. van, Teunissen, J.J.M., Eijck, C.H.J. van, Valkema, R., Jong, M. de, Herder, W.W. de & Krenning, E.P. (2010). Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancer, 17(1), R53-R73. Laan, L.J.W. van der, Hudson, M, McPherson, S, Zondervan, P.E., Thomas, RC, Kwekkeboom, J., Lindsay, AS, Burt, AD, Kazemier, G., Tilanus, H.W., Bassendine, MF & Metselaar, H.J. (2010). Results of a Two-Center Study Comparing Hepatic Fibrosis Progression in HCV-positive Liver Transplant Patients Receiving Cyclosporine or Tacrolimus. Transplantation Proceedings, 42(10), 4573-4577. Lagarde, SM, Vrouenraets, B.C., Stassen, L.P.S. & Lanschot, J.J.B. van (2010). Evidence-Based Surgical Treatment of Esophageal Cancer: Overview of High-Quality Studies. Annals of Thoracic Surgery, 89(4), 1319-1326. Leeuwenburgh, I., Scholten, P., Alderliesten, J., Tilanus, H.W., Looman, C.W.N., Steijerberg, EW & Kuipers, E.J. (2010). LongTerm Esophageal Cancer Risk in Patients With Primary Achalasia: A Prospective Study. American Journal of Gastroenterology, 105(10), 2144-2149. 138 < back to index Menke, V., Es, JH van, Lau, W de, Born, M van den, Kuipers, E.J., Siersema, P.D., Bruin, R.W.F. de, Kusters, J.G. & Clevers, H (2010). Conversion of metaplastic Barrett's epithelium into post-mitotic goblet cells by gamma-secretase inhibition. Disease Models & Mechanisms, 3(1-2), 104-110. Mitalas, LE, Wijk, J.J. van, Gosselink, M.P., Doornebosch, P, Zimmerman, D.D.E. & Schouten, W.R. (2010). Seton drainage prior to transanal advancement flap repair: useful or not? International Journal of Colorectal Disease, 25(12), 1499-1502. Mitalas, LE, Onkelen, R.S. van, Gosselink, M.P., Zimmerman, D.D.E. & Schouten, W.R. (2010). The anal fistula plug as an adjunct to transanal advancement flap repair. Diseases of the Colon & Rectum, 53(12), 1713. Morak, M.J.M., Pek, C.J., Kompanje, E.J.O., Hop, W.C.J., Kazemier, G. & Eijck, C.H.J. van (2010). Quality of Life After Adjuvant Intra-Arterial Chemotherapy and Radiotherapy Versus Surgery Alone in Resectable Pancreatic and Periampullary Cancer A Prospective Randomized Controlled Study. Cancer, 116(4), 830-836. Moroso, V., Metselaar, H.J., Mancham, S., Tilanus, H.W., Eissens, D, Meer, A van der, Laan, L.J.W. van der, Kuipers, E.J., Joosten, I. & Kwekkeboom, J. (2010). Liver Grafts Contain a Unique Subset of Natural Killer Cells that Are Transferred into the Recipient After Liver Transplantation. Liver Transplantation, 16(7), 895-908. Noord, D. van, Biermann, K., Moons, L.M.G., Pattynama, P.M.T., Verhagen, H.J.M., Kuipers, E.J. & Mensink, P.B.F. (2010). Histological changes in patients with chronic upper gastrointestinal ischaemia. Histopathology, 57(4), 615-621. Oom, D.M.J., Steensma, A.B., Zimmerman, D.D.E. & Schouten, W.R. (2010). Anterior Sphincteroplasty for Fecal Incontinence: Is the Outcome Compromised in Patients With Associated Pelvic Floor Injury? Diseases of the Colon & Rectum, 53(2), 150-155. Oom, D.M.J., Steensma, A.B., Lanschot, J.J.B. van & Schouten, W.R. (2010). Is Sacral Neuromodulation for Fecal Incontinence Worthwhile in Patients With Associated Pelvic Floor Injury? Diseases of the Colon & Rectum, 53(4), 422-427. Pan, Q., Metselaar, H.J., Ruiter, P.E. de, Kwekkeboom, J., Tilanus, H.W., Janssen, H.L.A. & Laan, L.J.W. van der (2010). Calcineurin Inhibitor Tacrolimus Does Not Interfere with the Suppression of Hepatitis C Virus Infection by Interferon-alpha. Liver Transplantation, 16(4), 520-526. Pool, S.E., Krenning, E.P., Koning, G.A., Eijck, C.H.J. van, Teunissen, J.J.M., Kam, B.L.R., Valkema, R., Kwekkeboom, D.J. & Jong, M. de (2010). Preclinical and Clinical Studies of Peptide Receptor Radionuclide Therapy. Seminars in Nuclear Medicine, 40(3), 209-218. Ramshorst, G.H. van, Nieuwenhuizen, J., Hop, W.C.J., Arends, P., Boom, J., Jeekel, J. & Lange, J.F. (2010). Abdominal Wound Dehiscence in Adults: Development and Validation of a Risk Model. World Journal of Surgery, 34(1), 20-27. Ramshorst, G.H. van, Eker, H.H., Harlaar, J.J., Nijens, K.J.J., Jeekel, J. & Lange, J.F. (2010). Therapeutic alternatives for burst abdomen. Surgical Technology International, 19, 111-119. Santvoort, H.C. van, Besselink, M.G., Bakker, OJ, Hofker, HS, Boermeester, M.A., DeJong, C.H., Goor, H. van, Schaapherder, AF, Eijck, C.H.J. van, Bollen, T.L., Ramshorst, B. van, Nieuwenhuijs, V.B., Timmer, R., Lameris, J.S., Kruyt, PM, Manusama, E.R., Harst, E. van der, Schelling, G.P. van der, Karsten, T, Hesselink, E.J., Laarhoven, C.J. van, Rosman, C., Bosscha, K., Wit, R.J. de, Houdijk, AP, Leeuwen, MS van, Buskens, E. & Gooszen, H.G. (2010). A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis. New England Journal of Medicine, 362(16), 1491-1502. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Dam, T.B. van, Ijzermans, J.N.M., Weimar, W. & Baan, C.C. (2010). Characterization of Rabbit Antithymocyte Globulins-Induced CD25(+) Regulatory T Cells From Cells of Patients With End-Stage Renal Disease. Transplantation, 89(6), 655-666. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Mol, W.M., Weimar, W. & Baan, C.C. (2010). The calcineurin inhibitor tacrolimus allows the induction of functional CD4+CD25+regulatory T cells by rabbit antithymocyte globulins. Clinical & Experimental Immunology, 161(2), 364-377. Sewgobind, V.D.K.D., Quaedackers, M.E., Laan, L.J.W. van der, Kraaijeveld, R., Korevaar, S.S., Chan, G, Weimar, W. & Baan, C.C. (2010). The Jak Inhibitor CP-690,550 Preserves the Function of CD4+CD25brightFoxP3+Regulatory T Cells and Inhibits Effector T Cells. American Journal of Transplantation, 10(8), 1785-1795. Steensma, A.B., Oom, D.M.J., Burger, C.W. & Schouten, W.R. (2010). Assessment of posterior compartment prolapse: a comparison of evacuation proctography and 3D transperineal ultrasound. Colorectal Disease, 12(6), 533-539. Swank, H.A., Vermeulen, J., Lange, J.F., Mulder, I.M.E., Hoeven, JAB van der, Stassen, L.P.S., Crolla, RMPH, Sosef, M.N., Nienhuijs, SW, Bosker, RJI, Boom, MJ, Kruyt, PM, Swank, D.J., Steup, W.H., Graaf, EJR de, Weidema, W.F., Pierik, E.G.J.M., Prins, H.A., Stockmann, H.B., Tollenaar, R.A.E.M., Wagensveld, B.A. van, Coene, PPLO, Slooter, G.D., Consten, E.C., Duyn, E.B. van, Gerhards, MF, Hoofwijk, A.G.M., Karsten, T.M., Neijenhuis, PA, Blanken-Peeters, C.F.J.M., Cense, H.A., Mannaerts, G.H.H., Bruin, S.C., Eijsbouts, Q.A.J., Wiezer, M.J., Hazebroek, E.J., Geloven, A. van, Maring, J.K., D'Hoore, A, Kartheuser, A., Remue, C., Grevenstein, W.M.U. van, Konsten, J.L., Peet, D.L. van der, Govaert, M.J.P.M., Engel, A.F., Reitsma, JB & Bemelman, W.A. (2010). The Ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037). BMC Surgery, 10(1), 29. Tjon, S.W.A., Sint Nicolaas, J., Kwekkeboom, J., Man, R.A. de, Kazemier, G., Tilanus, H.W., Hansen, B.E., Laan, L.J.W. van der, Tha-In, T.H. & Metselaar, H.J. (2010). Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C-2 Monitoring and Recipient Age. Liver Transplantation, 16(7), 837-846. 139 < back to index Unlu, C., Korte, N. de, Daniels, L., Consten, E.C., Cuesta, M.A., Gerhards, MF, Geloven, A. van, Zaag, E.S. van der, Hoeven, J.A. van der, Klicks, R., Cense, H.A., Roumen, RM, Eijsbouts, Q.A.J., Lange, J.F., Fockens, P., Borgie, CA de, Bemelman, W.A., Reitsma, JB, Stockmann, H.B., Vrouenraets, B.C. & Boermeester, M.A. (2010). A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial). BMC Surgery, 10, 23. Vermeulen, J., Gosselink, M.P., Busschbach, J.J. van & Lange, J.F. (2010). Avoiding or Reversing Hartmann's Procedure Provides Improved Quality of Life After Perforated Diverticulitis. Journal of Gastrointestinal Surgery, 14(4), 651-657. Vermeulen, J., Harst, E. van der & Lange, J.F. (2010). Pathophysiology and prevention of diverticulitis and perforation. Netherlands Journal of Medicine, 68(10), 303-309. Vermeulen, J. & Lange, J.F. (2010). Treatment of Perforated Diverticulitis with Generalized Peritonitis: Past, Present, and Future. World Journal of Surgery, 34(3), 587-593. Wauben, L.S.G.L., Goossens, R.H.M. & Lange, J.F. (2010). Evaluation of Operative Notes Concerning Laparoscopic Cholecystectomy: Are Standards Being Met? World Journal of Surgery, 34(5), 903-909. Wessem, KJP van, Plaisier, P.W. & Lange, J.F. (2010). Letter to the Editor: "Incidence of contralateral occult inguinal hernia found at the time of laparoscopic trans-abdominal pre-peritoneal (TAPP) repair" by Griffin et al. (Hernia 14:345-349, 2010). Hernia, 14(6), 669-669. Wijnhoven, B.P.L. & Dejong, CHC (2010). Fate of manuscripts declined by the British Journal of Surgery. British Journal of Surgery, 97(3), 450-454. Wijnhoven, B.P.L., Hussey, DJ, Watson, DI, Tsykin, A, Smith, CM & Michael, MZ (2010). MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma. British Journal of Surgery, 97(6), 853-861. Witjes, C.D.M., Man, R.A. de, Eskens, F.A.L.M., Dwarkasing, R.S., Zondervan, P.E., Verhoef, C. & Ijzermans, J.N.M. (2010). Hepatocellular carcinoma: the significance of cirrhosis for treatment and prognosis- retrospective study. Nederlands Tijdschrift voor Geneeskunde, 154, 1747. Xu, HL, Balakrishnan, K., Malaterre, J, Beasley, M, Yan, YQ, Essers, J., Appeldoorn, E., Thomaszewski, JM, Vazquez, M, Verschoor, S, Lavin, MF, Bertonchello, I, Ramsay, RG & McKay, MJ (2010). Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice. PLoS One, 5(8). Zee, J.A. van der, Hagen, T.L.M. ten, Hop, W.C.J., Dekken, H. van, Dicheva, B.M., Seynhaeve, A.L.B., Koning, G.A., Eggermont, A.M.M. & Eijck, C.H.J. van (2010). Differential expression and prognostic value of HMGA1 in pancreatic head and periampullary cancer. European Journal of Cancer, 46(18), 3393-3399. Part of book - abstract Pan, Q. & Laan, L.J.W. van der (2010). Hepatitis C: new insights and therapeutics by RNAi. In M.A. Martinez (Ed.), RNA interference and viruses: current innovations and future. --: Caister Academic Press. 140 < back to index EMC MM-03-47-06-A - Surgical trauma and the development of tumour recurrence Programme in brief design Locoregional or distant tumour recurrence of gastrointestinal carcinoma remains as important complication after potentially curative surgical resection. Prevention of this affliction remains the goal of many clinical and experimental studies. Excessive production of reactive oxygen species (ROS) and related tissue injury play a fundamental role in a wide variety of disease processes. Besides chronic inflammatory diseases, ROS are also produced after surgical trauma. The main producers of ROS are inflammatory cells (PMNs) entering damaged tissue after surgical trauma. The purpose of these cell products is to destroy invading organisms and damaged tissue. Despite this beneficial effect, the overwhelming oxidative potential can result in additional tissue destruction, which enables tumour cells to adhere. This programme aims at Characterisation of the adhesion of human tumour cells to meso- and endothelial cells and investigating the influence of growth factors and cytokines. Identifying pathways of enhanced tumour cell adhesion after surgical trauma and to elucidate the role of PMNs and ROS for this process. Prevention of tumor recurrence of human pancreatic tumor in nude mice using scavengers and interferons Insight in the mechanism of enhanced tumour recurrence after surgical trauma and the role of PNMs and ROS in this process may lead to the development of tools, such as scavengers and/or interferons to prevent this common pathway of tumour recurrence in most gastro-enterologic cancers Key figures Department surgery Total SP1 SP2 SP3 SP4 Sptot T1 4,95 0 0 0 4,95 4,95 0 0 0 4,95 0 T2 T3 0 0 Ttot 0 IS 16 FS 4 OP 0 Ptot 20 Artikel/Letter to the editor Cijs, TM, Verhoef, C., Steyerberg, E.W., Koppert, L.B., Tran, T.C.K., Wijnhoven, B.P.L., Tilanus, H.W. & Jonge, J. de (2010). Outcome of Esophagectomy for Cancer in Elderly Patients. Annals of Thoracic Surgery, 90(3), 900-907. Dols, L.F.C., Kok, N.F.M., Terkivatan, T., Tran, T.C.K., d'Ancona, F.C., Langenhuijsen, J.F., Mertens zur Borg, I.R.A.M., Alwayn, I.P.J., Hendriks, M.P., Dooper, IM, Weimar, W. & Ijzermans, J.N.M. (2010). Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial. BMC Surgery, 10, 11. Dols, L.F.C., Kok, N.F.M. & Ijzermans, J.N.M. (2010). Live donor nephrectomy: a review of evidence for surgical techniques. Transplant International, 23(2), 121-130. Eshuis, WJ, Gaag, N.A. van der, Rauws, E.A.J., Eijck, C.H.J. van, Bruno, M.J., Kuipers, E.J., Coene, P.P., Kubben, FJGM, Gerritsen, JJGM, Greve, J.W., Gerhards, MF, Hingh, IHJT de, Klinkenbijl, J.H., Nio, CY, Castro, SMM de, Busch, O.R.C., Gulik, T.M., Bossuyt, P.M.M. & Gouma, D.J. (2010). Therapeutic Delay and Survival After Surgery for Cancer of the Pancreatic Head With or Without Preoperative Biliary Drainage. Annals of Surgery, 252(5), 840-848. Ginhoven, T.M. van, Berg, J.W. van den, Dik, W.A., Ijzermans, J.N.M. & Bruin, R.W.F. de (2010). Preoperative Dietary Restriction Reduces Hepatic Tumor Load by Reduced E-Selectin-Mediated Adhesion in Mice. Journal of Surgical Oncology, 102(4), 348-353. Grotenhuis, B.A., Wijnhoven, B.P.L., Grune, F., Bommel, J. van, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Preoperative Risk Assessment and Prevention of Complications in Patients With Esophageal Cancer. Journal of Surgical Oncology, 101(3), 270278. Grotenhuis, B.A., Wijnhoven, B.P.L., Hotte, GJ, Stok, EP van der, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Prognostic Value of Body Mass Index on Short-Term and Long-Term Outcome after Resection of Esophageal Cancer. World Journal of Surgery, 34(11), 2621-2627. Grotenhuis, B.A., Heijl, M. van, Zehetner, J, Moons, J, Wijnhoven, B.P.L., Henegouwen, MIV, Tilanus, H.W., DeMeester, TR, Lerut, T. & Lanschot, J.J.B. van (2010). Surgical Management of Submucosal Esophageal Cancer Extended or Regional Lymphadenectomy? Annals of Surgery, 252(5), 823-829. Grotenhuis, B.A., Hagen, P. van, Reitsma, JB, Lagarde, SM, Wijnhoven, B.P.L., Henegouwen, MIV, Tilanus, H.W. & Lanschot, J.J.B. van (2010). Validation of a Nomogram Predicting Complications After Esophagectomy for Cancer. Annals of Thoracic Surgery, 90(3), 920-926. Heijl, M. van, Lanschot, J.J.B. van, Blom, RL, Bergman, J.J., Kate, F.J.C. ten, Busch, O.R.C., Reitsma, J.B. & Obertop, H. (2010). Outcomes of 16 years of oesophageal surgery: low postoperative mortality and improved long-term survival. Nederlands Tijdschrift voor Geneeskunde, 154, 1156. Heijl, M. van, Sprangers, M.A.G., Boer, AGEM de, Lagarde, SM, Reitsma, HB, Busch, O.R.C., Tilanus, H.W., Lanschot, J.J.B. van & Henegouwen, MIVB (2010). Preoperative and Early Postoperative Quality of Life Predict Survival in Potentially Curable Patients with Esophageal Cancer. Annals of Surgical Oncology, 17(1), 23-30. Keereweer, S., Wilt, J.H.W. de, Sewnaik, A., Meeuwis, C.A., Tilanus, H.W. & Kerrebijn, J.D.F. (2010). Early and long-term morbidity after total laryngopharyngectomy. European Archives of Oto-Rhino-Laryngology, 267(9), 1437-1444. 141 < back to index Lalmahomed, Z.S., Kraan, J., Gratama, J.W., Mostert, B., Sleijfer, S. & Verhoef, C. (2010). Circulating Tumor Cells and Sample Size: The More, the Better. Journal of Clinical Oncology, 28(17), E288-E289. Langeveld, H.R., Riet, M. van 't, Weidema, W.F., Stassen, L.P.S., Steyerberg, E.W., Bonjer, H.J., Lange, J.F. & Jeekel, J. (2010). Total Extraperitoneal Inguinal Hernia Repair Compared With Lichtenstein (the LEVEL-Trial) A Randomized Controlled Trial. Annals of Surgery, 251(5), 819-824. Pool, A.E.M. van der, Wilt, J.H.W. de, Lalmahomed, Z.S., Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases. British Journal of Surgery, 97(3), 383-390. Pool, A.E.M. van der, Lalmahomed, Z.S., Wilt, J.H.W. de, Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Trends in Treatment for Synchronous Colorectal Liver Metastases: Differences in Outcome Before and After 2000. Journal of Surgical Oncology, 102(5), 413-418. Ramshorst, G.H. van, Nieuwenhuizen, J., Hop, W.C.J., Arends, P., Boom, J., Jeekel, J. & Lange, J.F. (2010). Abdominal Wound Dehiscence in Adults: Development and Validation of a Risk Model. World Journal of Surgery, 34(1), 20-27. Ramshorst, G.H. van, Eker, H.H., Harlaar, J.J., Nijens, K.J.J., Jeekel, J. & Lange, J.F. (2010). Therapeutic alternatives for burst abdomen. Surgical Technology International, 19, 111-119. Swank, H.A., Vermeulen, J., Lange, J.F., Mulder, I.M.E., Hoeven, JAB van der, Stassen, L.P.S., Crolla, RMPH, Sosef, M.N., Nienhuijs, SW, Bosker, RJI, Boom, MJ, Kruyt, PM, Swank, D.J., Steup, W.H., Graaf, EJR de, Weidema, W.F., Pierik, E.G.J.M., Prins, H.A., Stockmann, H.B., Tollenaar, R.A.E.M., Wagensveld, B.A. van, Coene, PPLO, Slooter, G.D., Consten, E.C., Duyn, E.B. van, Gerhards, MF, Hoofwijk, A.G.M., Karsten, T.M., Neijenhuis, PA, Blanken-Peeters, C.F.J.M., Cense, H.A., Mannaerts, G.H.H., Bruin, S.C., Eijsbouts, Q.A.J., Wiezer, M.J., Hazebroek, E.J., Geloven, A. van, Maring, J.K., D'Hoore, A, Kartheuser, A., Remue, C., Grevenstein, W.M.U. van, Konsten, J.L., Peet, D.L. van der, Govaert, M.J.P.M., Engel, A.F., Reitsma, JB & Bemelman, W.A. (2010). The Ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037). BMC Surgery, 10(1), 29. Voit, C., Akkooi, A.C.J. van, Schafer-Hesterberg, G, Schoengen, A, Kowalczyk, K, Roewert, JC, Sterry, W & Eggermont, A.M.M. (2010). Ultrasound Morphology Criteria Predict Metastatic Disease of the Sentinel Nodes in Patients With Melanoma. Journal of Clinical Oncology, 28(5), 847-852. 142 < back to index EMC MM-03-47-11 - Innovative tumor model development/tumor vasculature/tumor targeting/locoregional control Programme in brief design The Problem: Surgical treatment of primary tumors, recurrences or metasta¬ses may be technically impossible or insufficient to achieve local tumor control. Combination of surgery with infusion or perfusions techniques of organs or extremities, or a combination with peroperative insertion of catheters for peroperative radiotherapy or afterloading can improve the surgical re¬sults. The possi¬bility to translate the success of isolated limb perfusi¬ons with TNF¿ + cyt¬ostatic drugs in patients with irresectable extremity tumors into its application in new regional perfusion settings (pelvis, liver) is under investigation. Moreover a genetherapy program using various vectors has been developed investigating the efficacy of isolated perfusion and regional infusion techniques for these new treatment modalities. The development of treating metastatic disease with tumortargeting devices such as liposomal encapsu¬lation of TNF + cytostatic or other antiangiogenic drugs is another arm in the overall program. Opti¬malisa¬tion of pre- and per¬ope¬rative diagnostic procedures as well as induction chemo- / radiation therapy may improve the resec¬tability of tumors and improve the quality of life. These aspects are investigated in precli¬nical animal models and in clini¬cal trial protocols. An important development is the intravital microscopy models and new in vitro tumor cell mobility assays and innovative invivo tumor models developed in our laboratory as well as the structural participation in the OIC ¿Optical Imaging Center¿of the ErasmusMC. Regional isola¬ted perfusion or infusion of cytokines, in particular TNF¿ or other "antistromal agents" in combination with cytosta¬tic drugs are the central research item in this approach of biochemotherapy targeting both structural elements of neoplasms. Key figures Department surgery Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 3,9 3,37 2,4 4,09 13,76 3,9 3,37 2,4 4,09 13,76 0 0 0 0 59 5 4 68 Artikel/Letter to the editor Akkooi, A.C.J. van, Verhoef, C. & Eggermont, A.M.M. (2010). Importance of tumor load in the sentinel node in melanoma: clinical dilemmas. Nature Reviews Clinical Oncology, 7(8), 446-454. Akkooi, A.C.J. van, Voit, CA, Verhoef, C. & Eggermont, A.M.M. (2010). 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Pool, A.E.M. van der, Wilt, J.H.W. de, Lalmahomed, Z.S., Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases. British Journal of Surgery, 97(3), 383-390. Pool, A.E.M. van der, Mendez Romero, A.M., Wunderink, W., Heijmen, B.J.M., Levendag, P.C., Verhoef, C. & Ijzermans, J.N.M. (2010). Stereotactic body radiation therapy for colorectal liver metastases. British Journal of Surgery, 97(3), 377-382. Pool, A.E.M. van der, Lalmahomed, Z.S., Wilt, J.H.W. de, Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Trends in Treatment for Synchronous Colorectal Liver Metastases: Differences in Outcome Before and After 2000. Journal of Surgical Oncology, 102(5), 413-418. Pool, S.E., Krenning, E.P., Koning, G.A., Eijck, C.H.J. van, Teunissen, J.J.M., Kam, B.L.R., Valkema, R., Kwekkeboom, D.J. & Jong, M. de (2010). Preclinical and Clinical Studies of Peptide Receptor Radionuclide Therapy. Seminars in Nuclear Medicine, 40(3), 209-218. Pool, S.E., Koning, G.A., Kam, B.L.R., Koelewijn, S.J., Eggermont, A.M.M., Eijck, C.H.J. van, Krenning, E.P., Hagen, T.L.M. ten & Jong, M. de (2010). Optimizing peptice receptor radionuclide therapy of neuro endocrine tumors. Daniel den Hoed Cancer News, 2, 36-37. Rijnsburger, A.J., Obdeijn, A.I.M., Kaas, R., Tilanus-Linthorst, M.M.A., Boetes, C., Loo, CE, Wasser, M.N.J.M., Bergers, E, Kok, T. de, Muller, S.H., Peterse, H., Tollenaar, R.A.E.M., Hoogerbrugge, N., Meijer, S, Bartels, C.C.M., Seynaeve, C., Hooning, M.J., Kriege, M., Schmitz, P.I.M., Oosterwijk, J.C., Koning, H.J. de, Rutgers, EJT & Klijn, J.G.M. (2010). BRCA1-Associated Breast Cancers Present Differently From BRCA2-Associated and Familial Cases: Long-Term Follow-Up of the Dutch MRISC Screening Study. Journal of Clinical Oncology, 28(36), 5265-5273. Rutkowski, P, Nowecki, ZI, Akkooi, A.C.J. van, Kulik, J, Wanda, M, Siedlecki, JA, Eggermont, A.M.M. & Ruka, W. (2010). Multimarker Reverse Transcriptase-Polymerase Chain Reaction Assay in Lymphatic Drainage and Sentinel Node Tumor Burden. Annals of Surgical Oncology, 17(12), 3314-3323. Santvoort, H.C. van, Besselink, M.G., Bakker, OJ, Hofker, HS, Boermeester, M.A., DeJong, C.H., Goor, H. van, Schaapherder, AF, Eijck, C.H.J. van, Bollen, T.L., Ramshorst, B. van, Nieuwenhuijs, V.B., Timmer, R., Lameris, J.S., Kruyt, PM, Manusama, E.R., Harst, E. van der, Schelling, G.P. van der, Karsten, T, Hesselink, E.J., Laarhoven, C.J. van, Rosman, C., Bosscha, K., Wit, R.J. de, Houdijk, AP, Leeuwen, MS van, Buskens, E. & Gooszen, H.G. (2010). A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis. New England Journal of Medicine, 362(16), 1491-1502. Spatz, A., Batist, G & Eggermont, A.M.M. (2010). The biology behind prognostic factors of cutaneous melanoma. Current Opinion in Oncology, 22(3), 163-168. Tjon, S.W.A., Sint Nicolaas, J., Kwekkeboom, J., Man, R.A. de, Kazemier, G., Tilanus, H.W., Hansen, B.E., Laan, L.J.W. van der, Tha-In, T.H. & Metselaar, H.J. (2010). Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C-2 Monitoring and Recipient Age. Liver Transplantation, 16(7), 837-846. Vledder, M.G. van, Hage, J.A. van der, Kirkels, W.J., Verhoef, C., Oosterhuis, J.W. & Wilt, J.H.W. de (2010). Cervical Lymph Node Dissection for Metastatic Testicular Cancer. Annals of Surgical Oncology, 17, S104-S104. Voit, C., Akkooi, A.C.J. van, Schafer-Hesterberg, G, Schoengen, A, Kowalczyk, K, Roewert, JC, Sterry, W & Eggermont, A.M.M. (2010). Ultrasound Morphology Criteria Predict Metastatic Disease of the Sentinel Nodes in Patients With Melanoma. Journal of Clinical Oncology, 28(5), 847-852. Voit, CA, Akkooi, A.C.J. van & Eggermont, A.M.M. (2010). Role of Ultrasound in the Assessment of the Sentinel Node of Melanoma Patients. American Journal of Roentgenology, 195(6), W474-W475. Voit, CA, Akkooi, AJC van, Schafer-Hesterberg, G, Sterry, W & Eggermont, A.M.M. (2010). The value of preoperative ultrasound (after lymphoscintigraphy) in conjunction with pre-sentinel lymph node biopsy fine-needle aspiration outweighs the usage of ultrasound alone in conjunction with lymphoscintigraphy: the need for an algorithm. Melanoma Research, 20(4), 357359. 146 < back to index Witjes, C.D.M., Man, R.A. de, Eskens, F.A.L.M., Dwarkasing, R.S., Zondervan, P.E., Verhoef, C. & Ijzermans, J.N.M. (2010). Hepatocellular carcinoma: the significance of cirrhosis for treatment and prognosis- retrospective study. Nederlands Tijdschrift voor Geneeskunde, 154, 1747. Xu, HL, Balakrishnan, K., Malaterre, J, Beasley, M, Yan, YQ, Essers, J., Appeldoorn, E., Thomaszewski, JM, Vazquez, M, Verschoor, S, Lavin, MF, Bertonchello, I, Ramsay, RG & McKay, MJ (2010). Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice. PLoS One, 5(8). Zee, J.A. van der, Hagen, T.L.M. ten, Hop, W.C.J., Dekken, H. van, Dicheva, B.M., Seynhaeve, A.L.B., Koning, G.A., Eggermont, A.M.M. & Eijck, C.H.J. van (2010). Differential expression and prognostic value of HMGA1 in pancreatic head and periampullary cancer. European Journal of Cancer, 46(18), 3393-3399. 147 < back to index EMC MM-03-49-01 - Clinical and experimental aspects of urological tumors Programme in brief design The clinical and experimental aspects of urological malignancies are a central issue within the research programme of the Department of Urology, Erasmus MC. The research is concentrated towards identification and characterization of molecular mechanisms that are responsible for cancer development and progression, improvement of the (molecular) diagnostic procedures, aspects of epidemiology and prevention, the development of prognostic factors and the development of innovative approaches to treatment, especially with respect to cancer derived from the prostate, kidney and urinary bladder. Research related to prostate cancer is most developed at this time. The clinical research programme shows much interaction with the more basically oriented research efforts and offers an opportunity to introduce recent developments in the laboratory directly into early clinical research. The research programme benefits from a large database of prostate cancer patients and of their clinical course, which was set up 20 years ago together with a tissue and serum bank. Some international projects fall within this programme: The European Randomized Study of Screening for Prostate Cancer (KWF/EUR 98-1657, EMCR 2002-2722; Quality of Life: KWF-EUR-2000-2329, Preventiefonds 0028-22820, ZONMw 22000106; ERSPC) is co-ordinated nationally and internationally by the Department of Urology. The programme includes participation and co-ordination of multiple clinical trials (EORTC, etc.). Furthermore, an international project on the Development of Prostate Cancer Gene Therapy is incorporated in the 6th Framework Programme (FP6) project GIANT. Funding of this research topic was recently expanded by a grant from the ZonMw Translationeel Gentherapeutisch Onderzoek programme. In collaboration with the ERSPC, the value of PCA3 as first line screening test is analysed and a PRIAS project on active surveillance initiated. Elucidation of the mechanisms of androgen-regulated growth and loss of hormonal responsiveness of prostate cancer cells is a major goal of this project. A panel of xenografts and in vitro cell lines, comprising sublines that are different with respect to their hormone responsiveness, are analyzed for differential gene expression in order to identify the various genes involved in these processes. The study also includes the investigation of the possible role of intercellular interactions, epithelial-stromal as well as epithelial-epithelial. A further aspect is the investigation of the role of the androgen receptor in prostate development and prostate cancer. Within these fields of basic and translational research, we coordinate and manage two Marie Curie ITN projects which were merged into one PRO-NEST programme (coordinator G. Jenster and manager E. Schenk-Braat). Within PRONEST, the 17 partners will train 20 PhD students and 4 postdocs for a career in prostate cancer research. Translational research within the fields of prostate cancer biomarker and imaging has been initiated by a CTMM funded project called `Prostate Cancer Molecular Medicine¿ (PCMM) (coordinator C.H. Bangma and manager E. Schenk-Braat). Besides translational research, a tissue bank and clinical database will be build up for marker and imaging validation and for development of clinical decision support systems. The prostate cancer xenografts and human serum bank are also being utilized for our search for novel diagnostic and prognostic markers. Using Fourier Transform mass spectrometry, we have identified serum proteins associated with presence of prostate cancer and serum proteins derived from xenografts. As far as carcinoma of the kidney and bladder is concerned, the activities are concentrating on clinical studies. Regarding bladder cancer, molecular diagnostics and non-invasive spectrometry are a focus. Together with the department of Pathology Erasmus MC, marker research is performed in the context of KWF and FP7 programs. BLadder Cancer Urine marker Project (BLUP) is a bladder cancer screening feasibility study of our department (www.blu-project.org). These and other studies should lead to new diagnostic and therapeutic clinical applications. Key figures Department urology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 7,58 4,13 1 0 12,71 7,58 4,13 1 0 12,71 3 0 0 3 86 2 8 99 Thesis Casteren, N.J. van (2010, december 07). Aspects of early detection of testicular cancer and cancer related. EUR. Prom./coprom.: Prof. Dr. L.H.J. Looijenga, Prof. Dr. C.H. Bangma & G.R. Dohle. Wielen, G.J. van der (2010, februari 03). Erectile dysfunction after external beam radiotherapy for porstate cancer. EUR (124 pag.). Prom./coprom.: Prof. Dr. P.C. Levendag & Prof. Dr. C.H. Bangma. Wolters, T. (2010, april 28). Improving screening strategies for prostate cancer. EUR (185 pag.). Prom./coprom.: Prof.Dr. F.H. Schroder & Prof. Dr. C.H. Bangma. Artikel/Letter to the editor Aa, M.N.M. van der, Steyerberg, E.W., Bangma, C.H., Rhijn, B.W.G. van, Zwarthoff, E.C. & Kwast, T.H. van der (2010). Cystoscopy revisited as the gold standard for detecting bladder cancer recurrence: diagnostic review bias in the randomized, prospective CEFUB trial. Journal of Urology, 183(1), 76-80. Al-Mamgani, A., Lebesque, J.V., Heemsbergen, W.D., Tans, L., Kirkels, W.J., Levendag, P.C. & Incrocci, L. (2010). Controversies in the Treatment of High-Risk Prostate Cancer-what Is the Optimal Combination of Hormonal Therapy and Radiotherapy: A Review of Literature. Prostate, 70(7), 701-709. Aluwini, S., Rooij, P.H.E. van, Hoogeman, M, Bangma, C.H., Kirkels, W.J., Incrocci, L. & Kolkman-Deurloo, I.K. (2010). CyberKnife Stereotactic Radiotherapy as Monotherapy for Low- to Intermediate-Stage Prostate Cancer: Early Experience, Feasibility, and Tolerance. Journal of Endourology, 24(5), 865-869. Banez, LL, Sun, L, Leenders, G.J.L.H. van, Wheeler, TM, Bangma, C.H., Freedland, SJ, Ittmann, MM, Lark, AL, Madden, JF, Hartman, A, Weiss, G. & Castanos-Velez, E (2010). Multicenter Clinical Validation of PITX2 Methylation as a Prostate Specific Antigen Recurrence Predictor in Patients With Post-Radical Prostatectomy Prostate Cancer. Journal of Urology, 184(1), 149156. 148 < back to index Bangma, C.H. (2010). Indolent prostate cancer and active surveillance. eGrandRound, European School of Oncology. Cancer World, 15-21. Bangma, C.H., Schaik, R.H.N. van, Blijenberg, B.G., Roobol, M.J., Lilja, H. & Stenman, UH (2010). On the use of prostatespecific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer. European Journal of Cancer, 46(17), 3109-3119. Bangma, C.H. (2010). Onderzoekers tekort gedaan? Urograaf, 7, 1-2. Bangma, C.H. & Roobol-Bouts, M.J. (2010). PRIAS: active surveillance study. Urology Today, 22, 1. Bangma, C.H. (2010). PSA-screening deugt. Huisarts en Wetenschap, 53, 503. Bergh, R.C.N. van den, Vugt, H.A. van, Korfage, I.J., Steyerberg, E.W., Roobol, M.J., Schroder, F.H. & Essink-Bot, M.L. (2010). Disease insight and treatment perception of men on active surveillance for early prostate cancer. Bju International, 105(3), 322328. Bergh, R.C.N. van den, Essink-Bot, M.L., Roobol, M.J., Schroder, F.H., Bangma, C.H. & Steyerberg, E.W. (2010). Do Anxiety and Distress Increase During Active Surveillance for Low Risk Prostate Cancer? Journal of Urology, 183(5), 1786-1791. Bergh, R.C.N. van den, Steyerberg, E.W., Khatami, A, Aus, G, Pihl, CG, Wolters, T., Leeuwen, P.J. van, Roobol, M.J., Schroder, F.H. & Hugosson, J. (2010). Is Delayed Radical Prostatectomy in Men With Low-Risk Screen-Detected Prostate Cancer Associated With a Higher Risk of Unfavorable Outcomes? Cancer, 116(5), 1281-1290. Bergh, R.C.N. van den (2010). Outcome of Primary Versus Deferred Radical Prostatectomy in the National Prostate Cancer Register of Sweden Follow-Up Study EDITORIAL COMMENT. Journal of Urology, 184(4), 1327-1327. Bergh, R.C.N. van den (2010). Re: Radical Prostatectomy Findings in Patients in Whom Active Surveillance of Prostate Cancer Fails. European Urology, 57(3), 540-541. Bergh, R.C.N. van den, Vasarainen, H, Poel, HG van der, Vis-Maters, JJ, Rietbergen, JB, Pickles, T, Cornel, E.B., Valdagni, R, Jaspars, JJ, Hoeven, J van der, Staerman, F, Oomens, EHGM, Rannikko, A, Roemeling, S., Steyerberg, E.W., Roobol, M.J., Schroder, F.H. & Bangma, C.H. (2010). Short-term outcomes of the prospective multicentre 'Prostate Cancer Research International: Active Surveillance' study. Bju International, 105(7), 956-962. Boevee, SJ, Venderbos, L.D.F., Tammela, T.L.J., Nelen, V., Ciatto, S., Kwiatkowski, M, Paez, A., Malavaud, B, Hugosson, J. & Roobol, M.J. (2010). Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer. European Journal of Cancer, 46(17), 3082-3089. Boormans, J.L., Hermans, K.G.L., Made, A.C.J. van der, Leenders, G.J.L.H. van, Wildhagen, M.F., Collette, L., Schroder, F.H., Trapman, J. & Verhagen, P.C.M.S. (2010). Expression of the Androgen-Regulated Fusion Gene TMPRSS2-ERG Does Not Predict Response to Endocrine Treatment in Hormone-Naive, Node-Positive Prostate Cancer. European Urology, 57(5), 830835. Boormans, J.L., Korsten, H., Made, A.C.J. van der, Leenders, G.J.L.H. van, Verhagen, P.C.M.S. & Trapman, J. (2010). E17K substitution in AKT1 in prostate cancer. British Journal of Cancer, 102(10), 1491-1494. Both, M.I., Overvest, M.A., Wildhagen, M.F., Golding, J. & Wildschut, H.I.J. (2010). The association of daily physical activity and birth outcome: a population-based cohort study. European Journal of Epidemiology, 25(6), 421-429. Carsin, AE, Drummond, FJ, Black, A, Leeuwen, P.J. van, Sharp, L, Murray, L.J., Connolly, D, Egevad, L, Boniol, M., Autier, P., Comber, H & Gavin, A (2010). Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland. Cancer Causes & Control, 21(9), 1523-1531. Chun, FKH, Epstein, JI, Ficarra, V, Freedland, SJ, Montironi, R., Montorsi, F, Shariat, SF, Schroder, F.H. & Scattoni, V (2010). Optimizing Performance and Interpretation of Prostate Biopsy: A Critical Analysis of the Literature. European Urology, 58(6), 851-864. Cremers, RGHM, Karim-Kos, H.E., Houterman, S, Verhoeven, RHA, Schroder, F.H., Kwast, T.H. van der, Kil, P.J.M., Coebergh, J.W.W. & Kiemeney, L.A.L.M. (2010). Prostate cancer: Trends in incidence, survival and mortality in the Netherlands, 19892006. European Journal of Cancer, 46(11), 2077-2087. Crop, M.J., Rijke, Y.B. de, Verhagen, P.C.M.S., Cransberg, K. & Zietse, R. (2010). Diagnostic Value of Urinary Dysmorphic Erythrocytes in Clinical Practice. Nephron Clinical Practice, 115(3), C203-C212. Dekker, L.J.M., Burgers, P.C., Charif, H., Rijswijk, A.L.C.T. van, Titulaer, M.K., Jenster, G.W., Bischoff, R., Bangma, C.H. & Luider, T.M. (2010). Differential expression of protease activity in serum samples of prostate carcinoma patients with metastases. Proteomics, 10(12), 2348-2358. Dubbelman, Y., Wildhagen, M.F., Schroder, F.H., Bangma, C.H. & Dohle, G. (2010). Orgasmic Dysfunction After Open Radical Prostatectomy: Clinical Correlates and Prognostic Factors. Journal of Sexual Medicine, 7(3), 1216-1223. Dubbelman, Y., Groen, J., Wildhagen, M., Rikken, B. & Bosch, J.L.H.R. (2010). The recovery of urinary continence after radical retropubic prostatectomy: a randomized trial comparing the effect of physiotherapist-guided pelvic floor muscle exercises with guidance by an instruction folder only. Bju International, 106(4), 515-522. 149 < back to index Elzinga-Tinke, J.E., Sirre, ME, Looijenga, L.H.J., Casteren, N.J. van, Wildhagen, M.F. & Dohle, G.R. (2010). The predictive value of testicular ultrasound abnormalities for carcinoma in situ of the testis in men at risk for testicular cancer. International Journal of Andrology, 33(4), 597-603. Gupta, A., Roobol, M.J., Savage, CJ, Peltola, M, Pettersson, K., Scardino, P.T., Vickers, AJ, Schroder, F.H. & Lilja, H. (2010). A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands. British Journal of Cancer, 103(5), 708-714. Hendriks, A.E.J., Boellaard, W.P.A., Casteren, N.J. van, Romijn, J.C., Jong, F.H. de, Boot, A.M. & Drop, S.L.S. (2010). Fatherhood in tall men treated with high-dose sex steroids during adolescence. Journal of Clinical Endocrinology and Metabolism, 95(12), 5233-5240. Hofland, J., Weerden, W.M. van, Dits, N.F.J., Steenbergen, J., Leenders, G.J.L.H. van, Jenster, G.W., Schroder, F.H. & Jong, F.H. de (2010). Evidence of Limited Contributions for Intratumoral Steroidogenesis in Prostate Cancer. Cancer Research, 70(3), 1256-1264. Hofland, J., Weerden, W.M. van, Jenster, G.W., Schroder, F.H. & Jong, F.H. de (2010). Intraprostatic Steroidogenic Enzymes Response. Cancer Research, 70(20), 8249-8250. Horwich, A., Parker, C, Bangma, C.H. & Kataja, V. (2010). Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21, v129-v133. Hsu, CY, Wildhagen, M.F., Poppel, H. van & Bangma, C.H. (2010). Prognostic factors for and outcome of locally advanced prostate cancer after radical prostatectomy. Bju International, 105(11), 1536-1540. Jansen, F.H., Schaik, R.H.N. van, Kurstjens, J, Horninger, W, Klocker, H, Bektic, J, Wildhagen, M.F., Roobol, M.J., Bangma, C.H. & Bartsch, G. (2010). Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection. European Urology, 57(6), 921-927. Kattan, M.W. & Schroder, F.H. (2010). What Patients Newly Diagnosed With Clinically Localized Prostate Cancer Need to See: An Editorial Dialogue. European Urology, 58(2), 258-260. Kekelidze, M., Dwarkasing, R.S., Dijkshoorn, M.L., Sikorska, K., Verhagen, P.C.M.S. & Krestin, G.P. (2010). Kidney and Urinary Tract Imaging: Triple-Bolus Multidetector CT Urography as a One-Stop Shop-Protocol Design, Opacification, and Image Quality Analysis. Radiology, 255(2), 508-516. Kerkhof, M., Roobol, M.J., Cuzick, J., Sasieni, P., Roemeling, S., Schroder, F.H. & Steyerberg, E.W. (2010). Effect of the correction for noncompliance and contamination on the estimated reduction of metastatic prostate cancer within a randomized screening trial (ERSPC section Rotterdam). International Journal of Cancer, 127(11), 2639-2644. Korfage, I.J., Bergh, R.C.N. van den & Essink-Bot, M.L. (2010). Deciding on PSA-screening - Quality of current consumer information on the Internet. European Journal of Cancer, 46(17), 3073-3081. Laurila, M, Kwast, T.H. van der, Bubendorf, L., Lollo, S. Di, Pihl, CG, Ciatto, S., Hugosson, J., Maattanen, L, Roobol, M.J. & Kujala, PM (2010). Detection rates of cancer, high grade PIN and atypical lesions suspicious for cancer in the European Randomized Study of Screening for Prostate Cancer. European Journal of Cancer, 46(17), 3068-3072. Leeuwen, P.J. van, David, C, Tammela, T.L.J., Auvinen, A., Kranse, R., Roobol, M.J., Schroder, F.H. & Gavin, A (2010). Balancing the Harms and Benefits of Early Detection of Prostate Cancer. Cancer, 116(20), 4857-4865. Leeuwen, P.J. van, Kranse, R., Hakulinen, T., Roobol, M.J., Koning, H.J. de, Bangma, C.H. & Schroder, F.H. (2010). Diseasespecific mortality may underestimate the total effect of prostate cancer screening. Journal of Medical Screening, 17(4), 204-210. Leeuwen, P.J. van, Connolly, D, Gavin, A, Roobol, M.J., Black, A, Bangma, C.H. & Schroder, F.H. (2010). Prostate cancer mortality in screen and clinically detected prostate cancer: Estimating the screening benefit. European Journal of Cancer, 46(2), 377-383. Leeuwen, P.J. van (2010). Re: Comparative Effectiveness of Minimally Invasive vs Open Radical Prostatectomy. European Urology, 57(3), 539-540. Leeuwen, P.J. van & Schroder, F.H. (2010). RISK FACTORS Increased risk of suicide after prostate cancer diagnosis. Nature reviews urology, 7(7), 369-370. Leeuwen, P.J. van, Vugt, H.A. van & Bangma, C.H. (2010). The implementation of screening for prostate cancer. Prostate Cancer and Prostatic Diseases, 13(3), 218-227. Maitland, N, Chambers, K, Georgopoulos, L, Simpson-Holley, M, Leadley, R, Evans, H, Essand, M, Danielsson, A, Weerden, W.M. van, Ridder, C.M.A. de, Kraaij, R. & Bangma, C.H. (2010). Gene Transfer Vectors Targeted to Human Prostate Cancer: Do We Need Better Preclinical Testing Systems? Human Gene Therapy, 21(7), 815-827. Marques, RB, Dits, N.F.J., Erkens-Schulze, S., Weerden, W.M. van & Jenster, G.W. (2010). Bypass Mechanisms of the Androgen Receptor Pathway in Therapy-Resistant Prostate Cancer Cell Models. PLoS One, 5(10). Nelen, V., Thys, G., Hermans, A., D'Hooge, K, Dourcy-Belle-Rose, B., Coebergh, J.W.W., Roobol-Bouts, M.J. & Denis, L. (2010). Interval cancers in the Antwerp European randomised study of screening for prostate cancer study, using a 6 year screening interval. European Journal of Cancer, 46(17), 3090-3094. 150 < back to index Otto, S.J., Leeuwen, P.J. van, Hoekstra, J.W., Merckelbach, JW, Blom, J.H.M., Schroder, F.H., Roobol, M.J. & Koning, H.J. de (2010). Blinded and uniform causes of death verification in cancer screening: A major influence on the outcome of a prostate cancer screening trial? European Journal of Cancer, 46(17), 3061-3067. Otto, S.J., Moss, S.M., Maattanen, L, Roobol-Bouts, M.J., Zappa, M., Nelen, V., Kwiatkowski, M, Villers, A., Hugosson, J., Sanchez, AB & Koning, H.J. de (2010). PSA levels and cancer detection rate by centre in the European Randomized Study of Screening for Prostate Cancer. European Journal of Cancer, 46(17), 3053-3060. Rhijn, B.W.G. van, Zuiverloon, T.C.M., Vis, A.N., Radvanyi, F., Leenders, G.J.L.H. van, Ooms, BCM, Kirkels, W.J., Lockwood, GA, Boeve, E.R., Jobsis, AC, Zwarthoff, E.C. & Kwast, T.H. van der (2010). Molecular Grade (FGFR3/MIB-1) and EORTC Risk Scores Are Predictive in Primary Non-Muscle-Invasive Bladder Cancer. European Urology, 58(3), 433-441. Rhijn, B.W.G. van, Kwast, T.H. van der, Kakiashvili, DM, Fleshner, NE, Aa, M.N.M. van der, Alkhateeb, S, Bangma, C.H., Jewett, M.A.S. & Zlotta, A.R. (2010). Pathological stage review is indicated in primary pT1 bladder cancer. Bju International, 106(2), 206-210. Rhijn, B.W.G. van, Leenders, G.J.L.H. van, Ooms, BCM, Kirkels, W.J., Zlotta, A.R., Boeve, E.R., Jobsis, AC & Kwast, T.H. van der (2010). The Pathologist's Mean Grade Is Constant and Individualizes the Prognostic Value of Bladder Cancer Grading. European Urology, 57(6), 1052-1057. Roobol, M.J., Steyerberg, E.W., Kranse, R., Wolters, T., Bergh, R.C.N. van den, Bangma, C.H. & Schroder, F.H. (2010). A RiskBased Strategy Improves Prostate-Specific Antigen-Driven Detection of Prostate Cancer. European Urology, 57(1), 79-85. Roobol, M.J., Bangma, C.H., Bouazzaoui, S el, Franken-Raab, C.G. & Zwarthoff, E.C. (2010). Feasibility study of screening for bladder cancer with urinary molecular markers (the BLU-P project). Urologic Oncology-Seminars and Original Investigations, 28(6), 686-690. Roobol, M.J. (2010). Initial Prostate Specific Antigen 1.5 ng/ml or Greater in Men 50 Years Old or Younger Predicts Higher Prostate Cancer Risk EDITORIAL COMMENT. Journal of Urology, 183(3), 950-950. Roobol, M.J., Schroder, F.H., Leenders, G.J.L.H. van, Hessels, D, Bergh, R.C.N. van den, Wolters, T. & Leeuwen, P.J. van (2010). Performance of Prostate Cancer Antigen 3 (PCA3) and Prostate-Specific Antigen in Prescreened Men: Reproducibility and Detection Characteristics for Prostate Cancer Patients with High PCA3 Scores (>= 100). European Urology, 58(6), 893-899. Roobol, M.J., Schroder, F.H., Leeuwen, P.J. van, Wolters, T., Bergh, R.C.N. van den, Leenders, G.J.L.H. van & Hessels, D (2010). Performance of the Prostate Cancer Antigen 3 (PCA3) Gene and Prostate-Specific Antigen in Prescreened Men: Exploring the Value of PCA3 for a First-line Diagnostic Test. European Urology, 58(4), 475-481. Roobol, M.J. & Schroder, F.H. (2010). Re: Estimating the Benefits of PSA Screening. European Urology, 57(1), 175-176. Roobol, M.J. & Schroder, F.H. (2010). Reply from Authors re: Vincenzo Ficarra, Giacomo Novara, Filiberto Zattoni, The role of the prostate cancer antigen 3 (PCA3) test for the diagnosis of prostate cancer in the era of opportunistic prostate-specific antigen screening, Eur Urol 2010;58:482-4. European Urology, 58(4), 484-485. Schenk-Braat, E.A.M., Essand, M & Bangma, C.H. (2010). Clinical Adenoviral Gene Therapy for Prostate Cancer. Human Gene Therapy, 21(7), 807-813. Schenk-Braat, E.A.M. (2010). Re: Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSATargeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer. European Urology, 58(4), 632-633. Schenk-Braat, E.A.M. & Bangma, C.H. (2010). Het `Prostate Cancer Molecular Medicine¿ project. Urograaf. Schroder, F.H., Tombal, B, Miller, K, Boccon-Gibod, L., Shore, ND, Crawford, ED, Moul, J., Olesen, TK & Persson, BE (2010). Changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or leuprolide: results from a 12month, comparative, phase III study. Bju International, 106(2), 182-187. Schroder, F.H. & Roobol, M.J. (2010). Dutasteride and Prostate Cancer. New England Journal of Medicine, 363(8), 793-794. Schroder, F.H., Bergh, R.C.N. van den, Wolters, T., Leeuwen, P.J. van, Bangma, C.H., Kwast, T.H. van der & Roobol, M.J. (2010). Eleven-Year Outcome of Patients with Prostate Cancers Diagnosed During Screening After Initial Negative Sextant Biopsies. European Urology, 57(2), 256-266. Schroder, F.H., Denis, L. & Roobol, M.J. (2010). Epilogue: Different approaches for prostate cancer screening in the EU? European Journal of Cancer, 46(17), 3120-3125. Schroder, F.H. & Roobol, M.J. (2010). ERSPC and PLCO Prostate Cancer Screening Studies: What Are the Differences? European Urology, 58(1), 46-52. Schroder, F.H. (2010). Prostate cancer around the world. An overview. Urologic Oncology-Seminars and Original Investigations, 28(6), 663-667. Schroder, F.H. & Roobol, M.J. (2010). The REDUCE Trial. European Urology, 58(2), 253-255. Schroeder, R.P.J., Muller, C.M., Reneman, S., Melis, M.L., Breeman, W.A.P., Blois, E. de, Bangma, C.H., Krenning, E.P., Weerden, W.M. van & Jong, M. de (2010). A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues. European Journal of Nuclear Medicine and Molecular Imaging, 37(7), 1386-1396. 151 < back to index Schroeder, R.P.J., Visser, M., Weerden, W.M. van, Ridder, C.M.A. de, Reneman, S., Melis, M.L., Breeman, W.A.P., Krenning, E.P. & Jong, M. de (2010). Androgen-regulated gastrin-releasing peptide receptor expression in androgen-dependent human prostate tumor xenografts. International Journal of Cancer, 126(12), 2826-2834. Schroten-Loef, C., Kraaij, R., Veldhoven, JLM, Berrevoets, C.A., Bakker, M.A. den, Ma, QZ, Sadelain, M, Bangma, C.H., Willemsen, R.A. & Debets, J.E.M.A. (2010). T cell activation upon exposure to patient-derived tumor tissue: A functional assay to select patients for adoptive T cell therapy. Journal of Immunological Methods, 359(1-2), 11-20. Schuit, M.R.H. & Bangma, C.H. (2010). De behandeling van gemetastaseerd prostaatcarcinoom. Farmacotherapie Online. Suikki, HE, Kujala, PM, Tammela, T.L.J., Weerden, W.M. van, Vessella, RL & Visakorpi, T. (2010). Genetic Alterations and Changes in Expression of Histone Demethylases in Prostate Cancer. Prostate, 70(8), 889-898. Sylvester, R.J., Brausi, MA, Kirkels, W.J., Hoeltl, W., Silva, FC Da, Powell, PH, Prescott, S., Kirkali, Z., Beek, C. van, Gorlia, T. & Reijke, T.M. de (2010). Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Guerin, and Bacillus Calmette-Guerin plus Isoniazid in Patients with Intermediate- and High-Risk Stage Ta T1 Urothelial Carcinoma of the Bladder. European Urology, 57(5), 766-773. Verhagen, P.C.M.S., Schroder, F.H., Collette, L. & Bangma, C.H. (2010). Does Local Treatment of the Prostate in Advanced and/or Lymph Node Metastatic Disease Improve Efficacy of Androgen-Deprivation Therapy? A Systematic Review. European Urology, 58(2), 261-269. Vickers, A, Cronin, A, Roobol-Bouts, M.J., Savage, C, Peltola, M, Pettersson, K., Scardino, P.T., Schroder, F.H. & Lilja, H. (2010). Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication. Journal of Clinical Oncology, 28(15), 2493-2498. Vickers, AJ, Cronin, AM, Roobol, M.J., Savage, CJ, Peltola, M, Pettersson, K., Scardino, P.T., Schroder, F.H. & Lilja, H. (2010). A Four-Kallikrein Panel Predicts Prostate Cancer in Men with Recent Screening: Data from the European Randomized Study of Screening for Prostate Cancer, Rotterdam. Clinical Cancer Research, 16(12), 3232-3239. Vickers, AJ, Wolters, T., Savage, CJ, Cronin, AM, O'Brien, MF, Roobol, M.J., Aus, G, Scardino, P.T., Hugosson, J., Schroder, F.H. & Lilja, H. (2010). Prostate Specific Antigen Velocity Does Not Aid Prostate Cancer Detection in Men With Prior Negative Biopsy. Journal of Urology, 184(3), 907-912. Vickers, AJ, Cronin, AM, Roobol, M.J., Hugosson, J., Jones, JS, Kattan, M.W., Klein, E., Hamdy, F, Neal, D, Donovan, J, Parekh, DJ, Ankerst, D, Bartsch, G., Klocker, H, Horninger, W, Benchikh, A, Salama, G, Villers, A., Freedland, SJ, Moreira, DM, Schroder, F.H. & Lilja, H. (2010). The Relationship between Prostate-Specific Antigen and Prostate Cancer Risk: The Prostate Biopsy Collaborative Group. Clinical Cancer Research, 16(17), 4374-4381. Vledder, M.G. van, Hage, J.A. van der, Kirkels, W.J., Verhoef, C., Oosterhuis, J.W. & Wilt, J.H.W. de (2010). Cervical Lymph Node Dissection for Metastatic Testicular Cancer. Annals of Surgical Oncology, 17, S104-S104. Vrij, J. de, Willemsen, R.A., Lindholm, L & Hoeben, R.C. (2010). Adenovirus-Derived Vectors for Prostate Cancer Gene Therapy. Human Gene Therapy, 21(7), 795-805. Vugt, H.A. van, Roobol, M.J., Venderbos, L.D.F., Zwanenburg, E Joosten-van, Essink-Bot, M.L., Steyerberg, E.W., Bangma, C.H. & Korfage, I.J. (2010). Informed decision making on PSA testing for the detection of prostate cancer: An evaluation of a leaflet with risk indicator. European Journal of Cancer, 46(3), 669-677. Vugt, H.A. van, Bangma, C.H. & Roobol, M.J. (2010). Should prostate-specific antigen screening be offered to asymptomatic men? Expert Review of Anticancer Therapy, 10(7), 1043-1053. Wever, E.M., Draisma, G., Heijnsdijk, E.A.M., Roobol, M.J., Boer, R., Otto, S.J. & Koning, H.J. de (2010). Prostate-Specific Antigen Screening in the United States vs in the European Randomized Study of Screening for Prostate Cancer-Rotterdam. Journal of the National Cancer Institute, 102(5), 352-355. Wijngaart, D.J. van de, Molier, M., Lusher, SJ, Hersmus, R., Jenster, G.W., Trapman, J. & Dubbink, H.J. (2010). Systematic Structure-Function Analysis of Androgen Receptor Leu(701) Mutants Explains the Properties of the Prostate Cancer Mutant L701H. Journal of Biological Chemistry, 285(7), 5097-5105. Wolters, T., Kwast, T.H. van der, Vissers, C.J., Bangma, C.H., Roobol-Bouts, M.J., Schroder, F.H. & Leenders, G.J.L.H. van (2010). False-negative Prostate Needle Biopsies: Frequency, Histopathologic Features, and Follow-up. American Journal of Surgical Pathology, 34(1), 35-43. Wolters, T., Roobol, M.J., Leeuwen, P.J. van, Bergh, R.C.N. van den, Hoedemaeker, R.F., Leenders, G.J.L.H. van, Schroder, F.H. & Kwast, T.H. van der (2010). Should Pathologists Routinely Report Prostate Tumour Volume? The Prognostic Value of Tumour Volume in Prostate Cancer. European Urology, 57(5), 821-829. Wolters, T., Roobol, M.J., Steyerberg, E.W., Bergh, R.C.N. van den, Bangma, C.H., Hugosson, J., Ciatto, S., Kwiatkowski, M, Villers, A., Lujan, M, Nelen, V., Tammela, T.L.J. & Schroder, F.H. (2010). The effect of study arm on prostate cancer treatment in the large screening trial ERSPC. International Journal of Cancer, 126(10), 2387-2393. Wolters, T., Vissers, KJ, Bangma, C.H., Schroder, F.H. & Leenders, G.J.L.H. van (2010). The value of EZH2, p27kip1, BMI-1 and MIB-1 on biopsy specimens with low-risk prostate cancer in selecting men with significant prostate cancer at prostatectomy. Bju International, 106(2), 280-286. 152 < back to index Zhu, X., Roobol-Bouts, M.J. & Schroder, F.H. (2010). Screening for porstate cancer: have we resolved the controsversy? Current Opinion in Supportive and Palliative Care, 4(3), 352-355. Zuiverloon, T.C.M., Aa, M.N.M. van der, Kwast, T.H. van der, Steyerberg, E.W., Lingsma, H.F., Bangma, C.H. & Zwarthoff, E.C. (2010). Fibroblast Growth Factor Receptor 3 Mutation Analysis on Voided Urine for Surveillance of Patients with Low-Grade Non-Muscle-Invasive Bladder Cancer. Clinical Cancer Research, 16(11), 3011-3018. Part of book - abstract Bangma, C.H. (2010). Bloedonderzoek bij urologische problemen inde huisartsenpraktijk. In JLHR Bosch & A Prins (Eds.), Praktische Huisartsengeneeskunde (leerboek) (pp. 109-117). Houten: Bohn Stafleu van Loghum. Bangma, C.H. (2010). Prostaatbiopsie. In .JLHR Bosch & A Prins (Eds.), Praktische Huisartsengeneeskunde (leerboek) (pp. 161-169). Houten: Bohn Stafleu van Loghum. Boekredactie Bul, M. & Bangma, C.H. (Eds.). (2010). Is screening naar prostaatkanker zinvol? Urologie spreekuur. Houten: Bohn Stafleu van Loghum. 153 < back to index EMC MM-03-52-02-A - Gynaecological oncology; basics, epidemiology and clinical aspects Programme in brief design Elevated levels of steroid hormones like estradiol and progesterone are important factors in the development of endometrial, breast and probably also ovariancancer. nevertheless, some medical interventions like hormone treatment for In Vitro Fertilization (IVF), Hormone replacement Therapy (HRT) after menopause, and tamoxifen-treatment of breast cancer casue significant increases in steroid signaling. Questions we are trying to answer are: Is temporarily administration of gonadotropins significantly correlated with an increased risk of ovarian, endometrial, breast and thyroid cancer in women treated with In Vitro Fertilization? Furthermore, are women who have a poor response to IVF more prone for gynaecological and breast cancer?Furthermore, in our laboratory we are investigating the molecular mechanism behind the question why steroids are sometimes causing cancer development (increases estrogen signaling can cause endometrial cancer), while in other cases steroids seem to protect against cancer growth (progesterone inhibits estrogen induced carcinogenesis in the endometrium). In these investigations Wnt signaling plays an important role. The life-time risk for infection with HPV is around 80%. Fortunately most women are able to clear this infection, and less than 10% of women infected with a high-risk HPV develop a persistent infection, which is one of the leading causes of preneoplastic and neoplastic lesions in the female genital tract, including cervical and vulvar intraepithelial neoplasia( CIN and VIN). Acquisition and clearing of HPV infection, viral load and persistence, T-cell response, cytokine expression, changes in cellular genome, viral oncogene proteins E6 and E7, role of human tumor suppressor genes p53 and Rb, loss of heterozygosity and telomerase activation are all factors that are studied to understand HPV-induced carcinogenesis. In addition to these molecular studies we are also investigating clinical aspects like the consequences of a national based primary screening program for cervical cancer and the role of HPV testing in the management of women with premalignant cervical lesions. Furthermore, in a number a randomized clinical trials alternative treatments,to otherwise mutilating surgery for VIN, are evaluated Key figures Department gynaecology/obstetrics reproduction and development Total SP1 SP2 SP3 SP4 Sptot T1 3,4 2,1 0 0 5,5 0,9 4,3 0 2,1 0 0 0 0 0,9 6,4 1 T2 T3 0 0 Ttot 1 IS 25 FS 0 OP 1 Ptot 27 Thesis Gerestein, C.G. (2010, maart 05). Value of prediction models in determining treatment strategies in patients with advanced stage epithelial. EUR. Prom./coprom.: Prof. Dr. C.W. Burger. Artikel/Letter to the editor Aa, MA van der, Helmerhorst, T.J.M., Siesling, S, Riemersma, S & Coebergh, J.W. (2010). Vaginal and (Uncommon) Cervical Cancers in the Netherlands, 1989-2003. International Journal of Gynecological Cancer, 20(4), 638-645. Baalbergen, A., Veenstra, Y, Stalpers, LL & Ansink, A.C. (2010). Primary surgery versus primary radiation therapy with or without chemotherapy for early adenocarcinoma of the uterine cervix. Cochrane Database Systematics Review. Beekhuizen, H.J. van, Joosten, I., Lotgering, F.K., Bulten, J & Kempen, LC van (2010). Natural Killer Cells and HLA-G Expression in the Basal Decidua of Human Placenta Adhesiva. Placenta, 31(12), 1078-1084. Bekker- Grob, E.W. de, Hofman, R., Donkers, B., Ballegooijen, M. van, Helmerhorst, T.J.M., Raat, H. & Korfage, I.J. (2010). Girls' preferences for HPV vaccination: A discrete choice experiment. Vaccine, 28(41), 6692-6697. Berkhof, J, Coupe, VM, Bogaards, JA, Kemenade, F.J. van, Helmerhorst, T.J.M., Snijders, PJ & Meijer, C.J. (2010). The health and economic effects of HPV DNA screening in the Netherlands. International Journal of Cancer, 127(9), 2147-2158. Gerestein, C.G., Nieuwenhuyzen-de Boer, G.M., Eijkemans, M.J.C., Kooi, G.S. & Burger, C.W. (2010). Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer. European Journal of Cancer, 46(1), 102-109. Gerestein, C.G. (2010). Waarde voorspellingsmodellen bij het bepalen van behandelstrategieën gevorderd stadium eierstokkanker. Oncologie Up-to-Date, 1, 10-11. Groenen, S.M.A., Timmers, P.J. & Burger, C.W. (2010). Recurrence Rate in Vulvar Carcinoma in Relation to Pathological Margin Distance. International Journal of Gynecological Cancer, 20(5), 869-873. Haadsma, ML, Mooij, TM, Groen, H., Burger, C.W., Lambalk, C.B., Broekmans, F.J.M., Leeuwen, F.E. van, Bouman, K. & Hoek, A. (2010). A reduced size of the ovarian follicle pool is associated with an increased risk of a trisomic pregnancy in IVF-treated women. Human Reproduction, 25(2), 552-558. Haadsma, ML, Groen, H., Mooij, TM, Burger, C.W., Broekmans, F.J.M., Lambalk, C.B., Leeuwen, F.E. van & Hoek, A. (2010). Miscarriage risk for IVF pregnancies in poor responders to ovarian hyperstimulation. Reproductive Biomedicine OnLine, 20(2), 191-200. Helleman, J., Jansen, M.P.H.M., Burger, C.W., Burg, M.E.L. van der & Berns, P.M.J.J. (2010). Integrated genomics of chemotherapy resistant ovarian cancer: A role for extracellular matrix, TGFbeta and regulating microRNAs. International Journal of Biochemistry & Cell Biology, 42(1), 25-30. 154 < back to index Hove, M.C.P. ten, Pool-Goudzwaard, A.L., Eijkemans, M.J.C., Steegers-Theunissen, R.P.M., Burger, C.W. & Vierhout, M.E. (2010). Prevalence of Double Incontinence, Risks and Influence on Quality of Life in a General Female Population. Neurourology and Urodynamics, 29(4), 545-550. Nout, RA, Smit, VTHBM, Putter, H., Juergenliemk-Schulz, IM, Jobsen, J.J., Lutgens, L.C.H.W., Steen-Banasik, E.M. van de, Mens, J.W.M., Slot, A., Kroese, MCS, Bunningen, BNFM van, Ansink, A.C., Putten, W.L.J. van & Creutzberg, C.L. (2010). Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet (UK), 375(9717), 816-823. Oom, D.M.J., Steensma, A.B., Zimmerman, D.D.E. & Schouten, W.R. (2010). Anterior Sphincteroplasty for Fecal Incontinence: Is the Outcome Compromised in Patients With Associated Pelvic Floor Injury? Diseases of the Colon & Rectum, 53(2), 150-155. Oom, D.M.J., Steensma, A.B., Lanschot, J.J.B. van & Schouten, W.R. (2010). Is Sacral Neuromodulation for Fecal Incontinence Worthwhile in Patients With Associated Pelvic Floor Injury? Diseases of the Colon & Rectum, 53(4), 422-427. Oonk, MH, Hemel, BM van, Hollema, H., Hullu, J.A. de, Ansink, A.C., Vergote, I., Verheijen, RH, Maggioni, A., Gaarenstroom, KN, Baldwin, PJ, Dorst, EB Van, Velden, J. van der, Hermans, RH, Putten, HW van der, Drouin, P, Runnebaum, IB, Sluiter, WJ & Zee, AG van der (2010). Size of sentinel-node metastasis and chances of non-sentinel-node involvement and survival in early stage vulvar cancer: results from GROINSS-V, a multicentre observational study. Lancet Oncology, 11(7), 646-652. Popp, SL, Abele, IS, Buck, MB, Stope, MB, Blok, L.J., Hanifi-Moghaddam, P., Burger, C.W., Fritz, P & Knabbe, C (2010). Microsomal epoxide hydrolase expression in the endometrial uterine corpus is regulated by progesterone during the menstrual cycle. Journal of Molecular Histology, 41(2-3), 111-119. Rustin, GJS, Burg, M.E.L. van der, Griffin, CL, Guthrie, D, Lamont, A, Jayson, GC, Kristensen, G, Mediola, C, Coens, C., Qian, WD, Parmar, MKB & Swart, AM (2010). Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet (UK), 376(9747), 1155-1163. Santegoets, L.A.M., Helmerhorst, T.J.M. & Meijden, W.I. van der (2010). A Retrospective Study of 95 Women With a Clinical Diagnosis of Genital Lichen Planus. Journal of lower genital tract disease, 14(4), 323-328. Steensma, A.B., Oom, D.M.J., Burger, C.W. & Schouten, W.R. (2010). Assessment of posterior compartment prolapse: a comparison of evacuation proctography and 3D transperineal ultrasound. Colorectal Disease, 12(6), 533-539. Steensma, A.B., Konstantinovic, ML, Burger, C.W., Ridder, D. de, Timmerman, D & Deprest, J (2010). Prevalence of major levator abnormalities in symptomatic patients with an underactive pelvic floor contraction. International Urogynecology Journal and Pelvic Floor Dysfunction, 21(7), 861-867. Terlou, A., Seters, M. van, Kleinjan, A., Heijmans-Antonissen, C., Santegoets, L.A.M., Beckmann, I., Beurden, M. van, Helmerhorst, T.J.M. & Blok, L.J. (2010). Imiquimod-induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia. International Journal of Cancer, 127(12), 2831-2840. Terlou, A., Blok, L.J., Helmerhorst, T.J.M. & Beurden, M. van (2010). Premalignant epithelial disorders of the vulva: squamous vulvar intraepithelial neoplasia, vulvar Paget's disease and melanoma in situ. Acta Obstetricia et Gynecologica Scandinavica, 89(6), 741-U4. Timmermans, A., Opmeer, B.C., Khan, KS, Bachmann, LM, Epstein, E, Clark, TJ, Gupta, JK, Bakour, SH, Bosch, T. van den, Doorn, H.C. van, Cameron, ST, Giusa, MG, Dessole, S, Dijkhuizen, FPHLJ, Riet, G. ter & Mol, B.W.J. (2010). Endometrial Thickness Measurement for Detecting Endometrial Cancer in Women With Postmenopausal Bleeding A Systematic Review and Meta-Analysis. Obstetrics and Gynecology, 116(1), 160-167. Vergote, I., Trope, CG, Amant, F, Kristensen, GB, Ehlen, T, Johnson, N, Verheijen, R.H.M., Burg, M.E.L. van der, Lacave, A.J., Panici, PB, Kenter, G.G., Casado, A, Mendiola, C., Coens, C., Verleye, L, Stuart, GCE, Pecorelli, S & Reed, NS (2010). Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer. New England Journal of Medicine, 363(10), 943-953. Verloop, J., Leeuwen, F.E. van, Helmerhorst, T.J.M., Boven, HH van & Rookus, MA (2010). Cancer risk in DES daughters. Cancer Causes & Control, 21(7), 999-1007. 155 < back to index EMC MM-03-54-04-A - Developmental biology; pathophysiology of the newborn Programme in brief design Growth and development of the fetus, the transition of the fetus to the newbom and growth . and development of the newbom infant are among the most critical periods in human lire. Pertubations of the normal development in these critical periods can cause temporary or persistent effects. Knowledge of the normal development is essential fOT the evaluation of an abnormal pattem of development. Abnormal growth and development is mainly gene in groups of infants like preterm infants. Our research therefore focusses on these infants, but also on normal and sick term infants and infants with inherited metabolic disease. 1. Substrate utilization, metabolism, nutrition and body composition of the preterm and term newbom. 2. Intestinal development in rodents, mammals and preterm infants 3. Neonatal neuroimaging, neurology and long term-development 4. Neonatal lung development and surfactant metabolism. 5. Neonatal pharmacology; developmental and neonatal pharmacology. Key figures Department pediatrics pediatrics-hematology pediatrics-IC/N pediatrics-IC/P pediatrics-other Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,02 0 0 0,11 1,13 0 1 0 0 1 0,11 0 1 3 4,11 0 0 0,58 0 0,58 1 0 3 2,3 6,3 2,13 1 4,58 5,41 13,12 5 0 0 5 36 3 2 46 Thesis Dudink, J. (2010, september 01). Diffusion weighted imaging of the neonatal brain. EUR (238 pag.) (Rotterdam: Print Partners Ipskamp). Prom./coprom.: Prof. Dr. J.B. van Goudoever, dr. P. Govaert & Dr. M.H. Lequin. Paassen, N. van (2010, december 01). Guts! Dietary modulation of innate defense. EUR (242 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. J.B. van Goudoever, Prof.Dr. H.J.G. Boehm & Dr. I.B. Renes. Puiman, P.J. (2010, december 22). Lumen Illuminated. Intestinal defense mechanism in the neonate. EUR (207 pag.) (Rptterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. J.B. van Goudoever, Prof.Dr. H.J.G. Boehm & Dr. I.B. Renes. Swarte, R.M.C.. The clinical value of intensive monitoring in term asphyxiated newborns. EUR (146 pag.) (Rotterdam: Drukkerij Verloop). Prom./coprom.: Prof. Dr. J.B. van Goudoever, dr. P. Govaert, Dr. M.H. Lequin & Dr. G.H. Visser. Verbruggen, S.C.A.T. (2010, december 22). Protein, energy and their interaction in critically ill children. EUR (235 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. J.B. van Goudoever & Dr. K.F.M. Joosten. Artikel/Letter to the editor Akker, C.H.P. van den, Vlaardingerbroek, H. & Goudoever, J.B. van (2010). Nutritional support for extremely low-birth weight infants: abandoning catabolism in neonatal intensive care unit. Current Opinion in Clinical Nutrition and Metabolic Care, 13, 327335. Akker, C.H.P. van den & Goudoever, J.B. van (2010). Recent advances in our outstanding of protein and amino acid metabolism in the human fetus. Current Opinion in Clinical Nutrition and Metabolic Care, 13, 75-80. Been, J.V., Rours, G.I.J.G., Kornelisse, R.F., Jonkers, F., Krijger, R.R. de & Zimmermann, L.J.I. (2010). Chorioamnionitis alters the response to surfactant in preterm infants. Journal of Pediatrics, 156, 10-15. Berfelo, F.J., Kersbergen, K.J., Ommen, C.H. van, Govaert, P., Straaten, HLM van, Poll-The, B.T., Wezel-Meijler, G. van, Vermeulen, R.J., Groenendaal, F., Vries, L.S. de & Haan, T.R. de (2010). Neonatal cerebral sinovenous thrombosis from symptom to outcome. Stroke, 41, 1382-1388. Boer, J. de & Smit, B.J. (2010). De positie van maagsondes en accumulatie van lucht in de maag bij pasgeborenen op de Intensive Care Neonatologie. Tijdschrift voor Vroedvrouwen, 16(2), 97-103. Braegger, C., Decsi, T, Dias, JA, Hartman, C.A., Kolacek, S, Koletzko, S, Mihatsch, W., Moreno, L., Puntis, J., Shamir, R., Szajewska, H., Turck, D. & Goudoever, J.B. van (2010). Practical approach to paediatric enteral nutrition: a comment by the ESPGHAN Committee on Nutrition. Journal of Pediatric Gastroenterology and Nutrition, 51(1), 110-122. Coenraad, S., Goedegebure, A., Goudoever, J.B. van & Hoeve, L.J. (2010). Risk factors for sensorineural haering loss in NICU infants compared to normal hearing NICU controls. International Journal of Pediatric Otorhinolaryngology, 74, 99-102. Corpeleijn, W.E., Riedijk, M.A., Zhou, Y., Schierbeek, H., Huang, Y., Chen, C & Goudoever, J.B. van (2010). Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants. Clinical Nutrition, 29, 341-346. Corpeleijn, W.E. & Goudoever, J.B. van (2010). Early nutrient supply and the preterm infant. Journal of Pediatric Gastroenterology and Nutrition, 51(suppl 3), S141-S142. 156 < back to index Corpeleijn, W.E., Vermeulen, M.J., Vliet, I. van, Kruger, C & Goudoever, J.B. van (2010). Human Milk-Banking-facts and issues to resolve. Nutrients, 2, 762-769. Dijk, M. van, Poley, M.J., Gischler, S.J., Mazer, P., Meijers-IJsselstijn, H., Tibboel, D. & Latour, J.M. (2010). Parental satisfaction with follow-up services for children with major anatomical congenital anomalies. Child Care Health & Development, 36(1), 101109. Dudink, J., Buijs, J., Govaert, P., Zwol, A.L. van, Conneman, H.N.L., Goudoever, J.B. van & Lequin, M.H. (2010). Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants. Pediatric Radiology, 40, 1397-1404. Ecury-Goossen, G.M., Dudink, J., Lequin, M.H., Roon, M., Horsch, S. & Govaert, P. (2010). The clinical presentation of preterm cerebellar haemorrhage. European Journal of Pediatrics, 169, 1249-1253. Govaert, P. (2010). Neonatal brain arteriopathies. Developmental Medicine & Child Neurology, 52, 117-118. Heesch, M.M.J. van, Bonsel, G.J., Dumoulin, J, Evers, J.L.H., Hoeven, M.A.H.B.M van der, Severens, J.L., Dijkgraaf, R.H.M., Veen, F. van der, Tonch, N., Nelen, WLDM, Zonneveld, P. van, Goudoever, J.B. van, Tamminga, P., Steiner, K., Esseboom, C., Beijsterveldt, C.E.M. van, Boomsma, D.I., Snellen, D. & Dirksen, C.D. (2010). Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study. BMC Pediatrics, 10(75), 1-11. Helder, O.K., Brug, J., Looman, C.W.N., Goudoever, J.B. van & Kornelisse, R.F. (2010). The impact of an education program on hand hygiene compliance and nosocomial infection incidence in an urban Neonatal Intensieve Care Unit: an intervention study with before and after comparison. International Journal of Nursing Studies, 47, 1245-1252. Helder, O.K. & Latour, J.M. (2010). Undergraduate nurse students' education in infection prevention: is it effective to change the attitude and compliance with hand hygiene? Nursing in Critical Care, 15(1), 39-40. Herba, C.M., Roza, S.J., Govaert, P., Rossum, J van, Hofman, A., Jaddoe, V.W.V.K., Verhulst, F.C. & Tiemeier, H.W. (2010). Infant Brain Development and Vulnerability to Later Internalizing Difficulties: The Generation R Study. Journal of the American Academy Child Adolescent Psychiatry, 49(10), 1053-1063. Hira, V., Sluijter, M., Goessens, W.H.F., Ott, A., Groot, R. de, Hermans, P.W.M. & Kornelisse, R.F. (2010). Coagulase-negative Staphylococcal skin carriage among neonatal intensive care unit personnel: from population to infection. Journal of Clinical Microbiology, 48(11), 3876-3881. Horsch, S., Skiold, B., Hallberg, B., Nordell, B., Mosskin, M., Lagercrantz, H., Aden, U. & Blennow, M. (2010). Cranial ultrasound and MRI at term age in extremely perterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition, 95, F310-F314. Horsch, S., Kutz, P. & Roll, C. (2010). Late germinal matrix hemorrhage-like lesions in very preterm infants. Journal of Child Neurology, 25(7), 809-814. Ista, W.G. & Helder, O.K. (2010). Samen werken aan een protocol. Nederlands Tijdschrift voor Evidence Based Practice, 2010(1), 20-23. Jedeloo, S., Staa, A.L. van, Latour, J.M. & Exel, N.J.A. van (2010). Preferences for health care and self-management among Dutch adolescents with chronic conditions: A Q-methodological investigation. International Journal of Nursing Studies, 47, 593603. Kaam, A.H. van, Rimensberger, P.C., Borensztajn, D., Jaegere, A.P.M.C. de & Neovent Study Group, The (2010). Ventilation practices in the neonatal intensive care unit: a cross-sectional study. Journal of Pediatrics, 157, 767-771. Kroon, A.A., Wang, J., Huang, Z, Cao, Z., Kuliszewski, M & Post, M. (2010). Inflammatory response to oxygen and endotoxin in newborn rat lung ventilated with low tidal volume. Pediatric Research, 68(1), 63-69. Labree, L.J.W., Foets, M.M.E. & Weisglas-Kuperus, N. (2010). Continuity and coordination of care during and after neonatal intensive care. Jounal of Child Health Care, 14(3), 239-249. Latour, J.M., Hazelzet, J.A., Duivenvoorden, H.J. & Goudoever, J.B. van (2010). Perceptions of parents, nurses and physicians on neonatal intensiver care practices. Journal of Pediatrics, 157(2), 215-220. Mercier, J-C., Hummler, E., Durrmeyer, X., Sanchez-Luna, M., Carnielli, V.P., Field, D., Greenough, A, Overmeire, B. van, Jonsson, B., Hallman, M.D. & Baldassarre, J. (2010). Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial. Lancet (UK), 376, 346-354. Moens, C.S.H., Oosterlaan, J., Duivenvoorden, H.J., Goudoever, J.B. van & Weisglas-Kuperus, N. (2010). Development of preschool and academic skills in children born very preterm. Journal of Pediatrics, 158(1), 51-56. Naghib, S., Starre, C. van der, Gischler, S.J., Joosten, K.F.M. & Tibboel, D. (2010). Mortality in very long-stay pediatric intensive care unit patients and incidence of withdrawal of treatment. Intensive Care Medicine, 36, 131-136. Olieman, J.F., Poley, M.J., Gischler, S.J., Penning, C., Escher, J.C., Hoonaard, T.L. van den, Goudoever, J.B. van, Bax, N.M.A., Tibboel, D. & Meijers-IJsselstijn, H. (2010). Interdisciplinary management of infantile short bowel syndrome: resource consumption, growth, and nutrition. Journal of Pediatric Surgery, 45, 490-498. Puiman, P.J., Stoll, B., Goudoever, J.B. van & Burrin, D.G. (2010). Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs. Journal of Nutrition, 141, 63-70. 157 < back to index Rook, D., Braake, F.W.J. te, Schierbeek, H., Longini, M., Buonocore, G. & Goudoever, J.B. van (2010). Glutathione synthesis rates in early postnatal life. Pediatric Research, 67(4), 407-411. Schoor, S.R.D. van der, Schierbeek, H., Bet, P.M., Vermeulen, M.J., Lafeber, H.N., Goudoever, J.B. van & Elburg, R.M. van (2010). Majority of dietary glutamine is utilized in first pass in preterm infants. Pediatric Research, 67(2), 194-199. Skiold, B., Horsch, S., Hallberg, B., Engstrom, M., Nagy, Z., Mosskin, M., Blennow, M. & Aden, U. (2010). White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study. Acta Paediatrica, 99, 842-849. Spek, I.L. van der, Franken, M.C.J.P., Wieringa, M.H. & Weisglas-Kuperus, N. (2010). Phonological development in very-lowbirthweight children: an exploratory study. Developmental Medicine & Child Neurology, 52, 541-546. Staa, A.L. van, Jedeloo, S, Latour, J.M. & Trappenburg, M.J. (2010). Exciting but exhausting: experiences with participatory research with chronically ill adolescents. Health Expectations, 13(1), 95-107. Szajewska, H., Guandalini, S., Morelli, L., Goudoever, J.B. van & Walker, A.J. (2010). Effect of Bifidobacterium animalis subsp lactis supplementation in preterm infants: a systematic review of randomized controlled trials. Journal of Pediatric Gastroenterology and Nutrition, 51(2), 203-209. Valkenburg, A.J., Dijk, M. van, Klein, A. de, Anker, J.N. van den & Tibboel, D. (2010). PAIN MANAGEMENT IN INTELLECTUALLY DISABLED CHILDREN: ASSESSMENT, TREATMENT, AND TRANSLATIONAL RESEARCH. Developmental disabilities research reviews, 16(3), 248-257. Verbruggen, S.C.A.T., Sy, J., Arrivillaga, A., Joosten, K.F.M., Goudoever, J.B. van & Castillo, L. (2010). Parenteral amino acid intakes in critically 1ll children: a matter of convenience. Journal of Parenteral and Enteral Nutrition, 34(3), 329-340. Boekredactie Govaert, P. & Vries, L.S. de (Eds.). (2010). An atlas of neonatal brain sonography. London: Mac Keith Press. 158 < back to index EMC MM-03-61-05-A - Experimental therapeutical approaches in inflammatory dermatoses and cutaneous oncology Programme in brief design The Department of Dermatology will focus its scientific efforts on inflammatory dermatoses and cutaneous oncology. At present time we are exploring clinically related basic research possibilities. Our first step towards the research target consists mainly of in vivo, ex vivo and in vitro studies of psoriasis and non-melanoma skin cancer. With these studies we aim at gaining more insight in the molecular and immunopathological aspects of psoriasis and the protective immunological mechanisms during tumor growth of basal cell carcinoma. In addition various therapeutic approaches in psoriasis and in non-melanoma skin cancers will be investigated regarding to their mode of action and immunomodulatory potential. Key figures Department dermatology immunology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,43 0 0 2,5 3,93 0,4 0 0 1 1,4 1,83 0 0 3,5 5,33 1 0 0 1 34 9 18 62 Thesis Wakkee, M. (2010, april 15). Psoriasis comorbidity & treatment. EUR (184 pag.). Prom./coprom.: Prof. Dr. H.A.M. Neumann, T.E.C. Nijsten & Dr. R.M.C. Herings. Artikel/Letter to the editor Amzayyb, M, Bos, R.R. van den, Kodach, VM, Bruin, DM de, Nijsten, T.E.C., Neumann, H.A.M. & Gemert, M.J.C. (2010). Carbonized blood deposited on fibres during 810, 940 and 1,470 nm endovenous laser ablation: thickness and absorption by optical coherence tomography. Lasers in Medical Science, 25(3), 439-447. Baerveldt, E.M. & Prens, E.P. (2010). Is er een verband tussen `erosive pustular dermatosis¿ en interne medicatie? Dermatologie Spreekuur, 1, 1-3. Biemans, A.A.M., Bos, R.R. van den & Nijsten, T.E.C. (2010). Endovenous therapies of varicose veins: indications, procedures, efficacy and safety. Giornale Italiano di dermatologia e venereologia, 145(2), 161-174. Bos, R. van den, Milleret, R, Kockaert, M.A., Neumann, H.A.M. & Nijsten, T.E.C. (2010). Stoomablatie: een nieuwe thermische endoveneuze behandeling van varices. Tijdschrift voor Geneeskunde (België), 20(11). Enzler, MA & Bos, R.R. van den (2010). A New Gold Standard for Varicose Vein Treatment? European Journal of Vascular and Endovascular Surgery, 39(1), 97-98. Essers, B.A.B., Dirksen, C.D., Prins, MH & Neumann, H.A.M. (2010). Assessing the Public's Preference for Surgical Treatment of Primary Basal Cell Carcinoma: A Discrete-Choice Experiment in the South of The Netherlands. Dermatologic Surgery, 36(12), 1950-1955. Flohil, S.C., Vries, E. de, Meurs, J.B.J. van, Fang, Y., Stricker, B.H.C., Uitterlinden, A.G. & Nijsten, T.E.C. (2010). Vitamin Dbinding protein polymorphisms are not associated with development of (multiple) basal cell carcinomas. Experimental Dermatology, 19(12), 1103-1105. Geer-Rutten, S. van der, Reijers, H & Krekels, G.A.M. (2010). How to run an effective and efficient dermato-oncology unit: a Dutch approach. Journal der Deutschen Dermatologischen Gesellschaft, 8(1), 15-18. Geer-Rutten, S. van der, Reijers, HA, Tuijl, H.F.J.M., Vries, H de & Krekels, G.A.M. (2010). Need for a New Skin Cancer Management Strategy. Archives of Dermatology, 146(3), 332-336. Geld, CWM van der, Bos, R.R. van den, Ruijven, PWM van, Nijsten, T.E.C., Neumann, H.A.M. & Gemert, M.J.C. (2010). The heat-pipe resembling action of boiling bubbles in endovenous laser ablation. Lasers in Medical Science, 25(6), 907-909. Gho, C.G. & Neumann, H.A.M. (2010). Donor hair follicle preservation by partial follicular unit extraction. A method to optimize hair transplantation. Journal of Dermatological Treatment, 21(6), 337-349. Gooskens, S.L.M., Oranje, A.P., Adrichem, L.N.A. van, Waard- van der Spek, F.B. de, Hollander, J.C. den, Ven, C.P. van de & Heuvel-Eibrink, M.M. van den (2010). Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP). Pediatric Blood & Cancer, 55, 369-373. Haar, N.M. van der, Gotz, H.M., Goessens, W.H.F. & Snoek, E.M. van der (2010). Atypische, ulceratieve presentatie syfilis. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20, 686-689. Haas, E.R.M. de, Nijsten, T.E.C. & Vries, E. de (2010). Population Education in Preventing Skin Cancer: From Childhood to Adulthood. Journal of Drugs in Dermatology, 9(2), 112-116. Habbema, L. (2010). Efficacy of tumescent local anesthesia with variable lidocaine concentration in 3430 consecutive cases of liposuction. Journal of the American Academy of Dermatology, 62(6), 988-994. 159 < back to index Hajdarbegovic, E., Leest, R.J.T. van der, Snoek, E.M. van der & Thio, H.B. (2010). Herpes simplex lymfangitis. Nederlands Tijdschrift voor Dermatologie & Venereologie. Holterhues, C., Vries, E. de, Louwman, MW, Koljenovic, S. & Nijsten, T.E.C. (2010). Incidence and Trends of Cutaneous Malignancies in the Netherlands, 1989-2005. Journal of Investigative Dermatology, 130(7), 1807-1812. Husson, O., Holterhues, C., Mols, F, Nijsten, T.E.C. & Poll-Franse, L.V. van de (2010). Melanoma survivors are dissatisfied with perceived information about their diagnosis, treatment and follow-up care. British Journal of Dermatology, 163(4), 879-881. Joosse, A., Vries, E. de, Eijck, C.H.J. van, Eggermont, A.M.M., Nijsten, T.E.C. & Coebergh, J.W.W. (2010). Reactive oxygen species and melanoma: an explanation for gender differences in survival? Pigment Cell & Melanoma Research, 23(3), 352-364. Kamphuis, L.S.J., Laar, J.A.M. van, Kuipers, R.W.A.M., Missotten, T.O.A.R., Thio, H.B. & Hagen, P.M. van (2010). Sarcoïdose: verandering in therapeutische inzichten. Nederlands Tijdschrift voor Geneeskunde, 154, 1685. Kiiski, V, Vries, E. de, Flohil, S.C., Bijl, M.J., Hofman, A., Stricker, B.H.C. & Nijsten, T.E.C. (2010). Risk Factors for Single and Multiple Basal Cell Carcinomas. Archives of Dermatology, 146(8), 848-855. Koomen, ER, Vries, E. de, Kempen, LC van, Akkooi, A.C.J. van, Guchelaar, HJ, Louwman, W.J., Nijsten, T.E.C. & Coebergh, J.W.W. (2010). Epidemiology of Extracutaneous Melanoma in the Netherlands. Cancer Epidemiology Biomarkers & Prevention, 19(6), 1453-1459. Krol, CG, Geer-Rutten, S. van der, Thio, H.B., Janssen, MJ & Jonkers, GJ (2010). Acrodermatitis chronica atrophicans: late manifestatie van lymeborreliose. Nederlands Tijdschrift voor Geneeskunde, 154, 2012. Kruijt, B., Snoek, E.M. van der, Sterenborg, H.J.C.M., Amelink, A. & Robinson, D.J. (2010). A dedicated applicator for light delivery and monitoring of PDT of intra-anal intraepithelial neoplasia. Photodiagnosis and Photodynamic Therapy, 7(1), 3-9. Kuiper, E.M.M., Erpedum, KJ van, Beuers, U, Hansen, B.E., Thio, H.B., Man, R.A. de, Janssen, H.L.A. & Buuren, H.R. van (2010). The Potent Bile Acid Sequestrant Colesevelam Is Not Effective in Cholestatic Pruritus: Results of a Double-Blind, Randomized, Placebo-Controlled Trial. Hepatology, 52(4), 1334-1340. Lanjouw, E., Ossewaarde, J.M., Stary, A., Boag, F & Meijden, W.I. van der (2010). 2010 European guideline for the management of Chlamydia trachomatis infections. International Journal of Std & Aids, 21(11), 729-737. Leeuw, J. de, Beek, N. van der, Bjerring, P. & Neumann, H.A.M. (2010). Photodynamic therapy of acne vulgaris using 5aminolevulinic acid 0.5% liposomal spray and intense pulsed light in combination with topical keratolytic agents. Journal of the European Academy of Dermatology and Venereology, 24(4), 460-469. Meijden, W.A.G. van der, Bruchem-Visser, R.L. van, Thio, H.B. & Cammen, T.J.M. van der (2010). Melanomen bij ouderen ernstiger. Nederlands Tijdschrift voor Geneeskunde, 154, 1535. Middelburg, T.A., Zaane, F. van, Bruijn, H.S. de, Ploeg- van den Heuvel, A., Sterenborg, H.J.C.M., Neumann, H.A.M., Haas, E.R.M. de & Robinson, D.J. (2010). Fractionated Illumination at Low Fluence Rate Photodynamic Therapy in Mice. Photochemistry and Photobiology, 86(5), 1140-1146. Mols, F, Holterhues, C., Nijsten, T.E.C. & Poll-Franse, L.V. van de (2010). Personality is associated with health status and impact of cancer among melanoma survivors. European Journal of Cancer, 46(3), 573-580. Munte, K. (2010). Basaloid follicular hamartoma. Nederlands Tijdschrift voor Dermatologie & Venereologie. Nijsten, T.E.C. & Bergstresser, PR (2010). Patient Advocacy Groups: Let's Stick Together. Journal of Investigative Dermatology, 130(7), 1757-1759. Oranje, A.P. (2010). Management of urticaria and angioedema in children: new trends. Giornale Italiano di dermatologia e venereologia, 145(6), 771-774. O'Regan, GM, Kemperman, P.M.J.H., Sandilands, A, Chen, HJ, Campbell, LE, Kroboth, K, Watson, R, Rowland, M, Puppels, G.J., McLean, W.H.I., Caspers, P.J. & Irvine, AD (2010). Raman profiles of the stratum corneum define 3 filaggrin genotypedetermined atopic dermatitis endophenotypes. Journal of Allergy and Clinical Immunology, 126(3), 574-U270. Prens, E.P. (2010). Reageren en overreageren. Het huidimmuunsysteem, allergieën en ontstekingen. Derma Novum, 10, 4-10. Racz, E., Leeuw, J. de, Baerveldt, E.M., Kant, M., Neumann, H.A.M., Fits, L van der & Prens, E.P. (2010). Cellular and Molecular Effects of Pulsed Dye Laser and Local Narrow-Band UVB Therapy in Psoriasis. Lasers in Surgery and Medicine, 42(3), 201-210. Ruiter, R. de, Visser, L.E., Eijgelsheim, M., Rodenburg, E.M., Hofman, A., Coebergh, J.W.W., Nijsten, T.E.C. & Stricker, B.H.C. (2010). High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study. European Journal of Cancer, 46(13), 2467-2472. Schelke, L.W., Elzen, H.J. van den, Erkamp, PPM & Neumann, H.A.M. (2010). Use of Ultrasound to Provide Overall Information on Facial Fillers and Surrounding Tissue. Dermatologic Surgery, 36(3), 1843-1851. Snoek, E.M. van der (2010). Condylomata acuminata and anal dysplasia. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20, 64-69. 160 < back to index Snoek, E.M. van der & Loon, A.M. van (2010). Herpes zoster in het anogenitaal gebied. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20, 16-18. Snoek, E.M. van der (2010). Seksueel Overdraagbare aandoeningen, is er nieuws onder de zon? Nederlands Militair Geneeskundig Tijdschrift, 63, 145-152. Snoek, E.M. van der & Couwenberg, S.M. (2010). Zon op je huid, waarom wel en wanneer niet? De Onderofficier, 52, 22-27. Spuls, P.I., Lecluse, LLA, Poulsen, MLNF, Bos, J.D., Stern, RS & Nijsten, T.E.C. (2010). 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Journal of the European Academy of Dermatology and Venereology, 24(8), 867-874. Waalboer, R., Steenwinkel, J.E.M. de, Biemans, A.A.M. & Thio, H.B. (2010). Cutane scedosporiose. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20(9), 586-587. Wakkee, M., Herings, R.M.C. & Nijsten, T.E.C. (2010). Psoriasis May Not be an Independent Risk Factor for Acute Ischemic Heart Disease Hospitalizations: Results of a Large Population-Based Dutch Cohort. Journal of Investigative Dermatology, 130(4), 962-967. Wentel, T.D. (2010). Rood. Nederlands Tijdschrift voor Dermatologie & Venereologie. Willemse-Erix, DFM, Jachtenberg, J.W., Schut, TB, Leeuwen, W.B. van, Belkum, A. van, Puppels, G.J. & Maquelin, K. (2010). Towards Raman-based epidemiological typing of Pseudomonas aeruginosa. Journal of Biophotonics, 3(8-9), 506-511. Willemse-Erix, H.F.M., Jachtenberg, J, Barutci, H., Puppels, G.J., Belkum, A. van, Vos, M.C. & Maquelin, K. (2010). 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In WB van Leeuwen, E van Pelt-Verkuil, MF van Berlo, A van Belkum & HGM Niesters (Eds.), Moleculaire diagnostiek, 2nd edition (pp. 149-170). Heron Reeks. Mortimer, PS, Burnand, KG & Neumann, H.A.M. (2010). Diseases of the Veins and Arteries: leg Ulcers. In SM Breathnach, NH Cox & CEM Griffiths (Eds.), Rook¿s Textbook of Dermatology, 8th Edition. Onderdijk, A.J. & Prens, E.P. (2010). Psoriasis. In JJM van Dongen, WA Dik, AW Langerak, VHJ van der Velden & H Hooijkaas (Eds.), Nieuwe ontwikkelingen in de Medische Immunologie 2010 (pp. 187-194). Rotterdam: Erasmus MC afdeling immunologie. Sholkina, M.A., Puppels, G.J. & Bakker Schut, T.C. (2010). The current state of Raman Imaging in clinical applications. In G Srinivasan (Ed.), Vibrational Spectroscopic Imaging for Biomedical Applications (pp. 265-293). Mc Graw-Hill. Willemse-Erix, H.F.M., Belkum, A. van & Maquelin, K. (2010). Raman spectroscopy for bacterial strain typing. In Molecular Microbiology; Diagnostic Principles and Practice, 2nd edition (pp. 313-324). ASM Press. Boekredactie Snoek, E.M. van der, Schouten, W.R., Muris, J & Thio, H.B. (Eds.). (2010). Anale klachten, diagnostiek en behandeling. Amsterdam: Elsevier gezondheidszorg. 161 < back to index EMC MM-03-86-01 - Translational genomics and proteomics of cancer Programme in brief design The overall aim of the section of Translational Cancer Genomics & Proteomics is to investigate the cell biological and genetic factors involved in the development of sporadic and hereditary breast and ovarian cancer, to investigate the processes of tumor progression and treatment failure, and to come to tailored treatments (for subgroups of patients) that are based on risk factors and cell biological phenotypes of individual tumors and circulating tumor cells. To carry out our research programs involving clinical, translational and mechanistic genomics and proteomics studies on sporadic and hereditary cancer our laboratories have available a database on over 3,000 families with familial and hereditary breast cancer, breast and ovarian tissue (>15,000 samples stored in liquid nitrogen) and serum banks (>50,000 samples), 60 well-characterized breast and ovarian cancer cell lines, and various metastasizing and non-metastasizing rat and mouse tumor models. In our clinic, phase I, II and III trails with various (targeted) drugs are performed. The research is carried out in 3 different, but extensively collaborating, research groups: - Breast Cancer Genomics & Proteomics - Integrated Genomics of Breast and Ovarian Cancer - Hereditary Cancer Syndromes Key figures Department medical oncology neurology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 7,57 5,94 2,19 2,95 18,65 0 0 0 1 1 7,57 5,94 2,19 3,95 19,65 0 0 0 0 58 0 1 59 Artikel/Letter to the editor Agthoven, T. van, Sieuwerts, A.M., Meijer, D., Meijer-Gelder, M.E. van, Sarwari, R., Sleijfer, S., Foekens, J.A. & Dorssers, L.C.J. (2010). Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response. Endocrine-Related Cancer, 17(1), 215-230. Antoniou, AC, Beesley, J, McGuffog, L., Sinilnikova, O.M., Healey, S, Neuhausen, S.L., Ding, YC, Rebbeck, TR, Weitzel, JN, Lynch, H.T., Isaacs, C., Ganz, PA, Tomlinson, G, Olopade, OI, Couch, F.J., Wang, XS, Lindor, NM, Pankratz, VS, Radice, P., Manoukian, S, Peissel, B, Zaffaroni, D, Barile, M, Viel, A, Allavena, A, Dall'Olio, V, Peterlongo, P, Szabo, C.I., Zikan, M, Claes, K, Poppe, B., Foretova, L, Mai, PL, Greene, M.H., Rennert, G., Lejbkowicz, F, Glendon, G, Ozcelik, H, Andrulis, I.L., Thomassen, M., Gerdes, AM, Sunde, L., Cruger, D, Jensen, UB, Caligo, M, Friedman, E., Kaufman, B, Laitman, Y, Milgrom, R, Dubrovsky, M, Cohen, S., Borg, A, Jernstrom, H, Lindblom, A, Rantala, J, Stenmark-Askmalm, M, Melin, B, Nathanson, K, Domchek, S, Jakubowska, A, Lubinski, J., Huzarski, T, Osorio, A., Lasa, A, Duran, M., Tejada, MI, Godino, J, Benitez, J., Hamann, U., Kriege, M., Hoogerbrugge, N., Luijt, R.B. van der, Asperen, C.J. van, Devilee, P., Meijers-Heijboer, E.J., Blok, MJ, Aalfs, C.M., Hogervorst, F., Rookus, M, Cook, M., Oliver, C, Frost, D, Conroy, D, Evans, D.G., Lalloo, F, Pichert, G, Davidson, R., Cole, T., Cook, J., Paterson, J, Hodgson, S, Morrison, PJ, Porteous, ME, Walker, L, Kennedy, MJ, Dorkins, H, Peock, S, Godwin, AK, Stoppa-Lyonnet, D., Pauw, A de, Mazoyer, S, Bonadona, V, Lasset, C., Dreyfus, H., Leroux, D, Hardouin, A, Berthet, P, Faivre, L, Loustalot, C, Noguchi, T, Sobol, H., Rouleau, E, Nogues, C, Frenay, M., Venat-Bouvet, L, Hopper, J.L., Daly, M.B., Terry, MB, John, EM, Buys, S.S., Yassin, Y, Miron, A, Goldgar, D., Singer, CF, Dressler, AC, Gschwantler-Kaulich, D, Pfeiler, G, Hansen, TVO, Jnson, L, Agnarsson, BA, Kirchhoff, T., Offit, K., Devlin, V, Dutra-Clarke, A, Piedmonte, M, Rodriguez, GC, Wakeley, K, Boggess, JF, Basil, J, Schwartz, PE, Blank, SV, Toland, AE, Montagna, M, Casella, C, Imyanitov, E, Tihomirova, L, Blanco, I, Lazaro, C, Ramus, SJ, Sucheston, L, Karlan, BY, Gross, J, Schmutzler, R, Wappenschmidt, B, Engel, C, Meindl, A, Lochmann, M, Arnold, N, Heidemann, S, Varon-Mateeva, R, Niederacher, D, Sutter, C, Deissler, H., Gadzicki, D, Preisler-Adams, S, Kast, K, Schonbuchner, I, Caldes, T, Hoya, M de la, Aittomaki, K, Nevanlinna, H., Simard, J., Spurdle, A.B., Holland, H, Chen, XQ, Platte, R, Chenevix-Trench, G. & Easton, D.F. 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Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. Cancer Epidemiology Biomarkers & Prevention, 19(11), 2859-2868. Ernesto Godinho, M.F., Sieuwerts, A.M., Look, M.P., Meijer, D., Foekens, J.A., Dorssers, L.C.J. & Agthoven, T. van (2010). Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. British Journal of Cancer, 103(8), 1284-1291. 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(2010). Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls. Cancer Epidemiology Biomarkers & Prevention, 19(9), 2143-2151. 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Schilder, CM, Seynaeve, C., Beex, LV, Boogerd, W., Linn, SC, Gundy, CM, Huizenga, HM, Nortier, JW, Velde, CJV De, Dam, FS Van & Schagen, SB (2010). Effects of Tamoxifen and Exemestane on Cognitive Functioning of Postmenopausal Patients With Breast Cancer: Results From the Neuropsychological Side Study of the Tamoxifen and Exemestane Adjuvant Multinational Trial. Journal of Clinical Oncology, 28(8), 1294-1300. Schilder, CM, Seynaeve, C., Linn, SC, Boogerd, W., Gundy, CM, Beex, LV, Dam, FS Van & Schagen, SB (2010). The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy. Psycho-Oncology, 19(4), 415-422. Schilder, CMT, Seynaeve, C., Linn, SC, Boogerd, W., Beex, L.V.A.M., Gundy, CM, Nortier, J.W.R., Velde, C.J.H. van de, Dam, F.S.A.M. & Schagen, SB (2010). 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The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI). European Journal of Cancer, 46(12), 2206-2215. Sieuwerts, A.M., Ansems, M, Look, M.P., Span, P.N., Weerd, V. de, Galen, A van, Foekens, J.A., Adema, G.J. & Martens, J.W.M. (2010). Clinical significance of the nuclear receptor co-regulator DC-SCRIPT in breast cancer: an independent retrospective validation study. Breast cancer research, 12(6). Sleijfer, S., Quali, M, Glabbeke, M. van, Krarup-Hansen, A, Rodenhuis, S., Cesne, A. le, Hogendoorn, P.C.W., Verweij, J. & Blay, J.Y. (2010). Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas An exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). European Journal of Cancer, 46(1), 72-83. Stacey, SN, Sulem, P, Zanon, C, Gudjonsson, SA, Thorleifsson, G, Helgason, A, Jonasdottir, A, Besenbacher, S, Kostic, JP, Fackenthal, JD, Huo, D, Adebamowo, C, Ogundiran, T, Olson, JE, Fredericksen, ZS, Wang, XS, Look, M.P., Sieuwerts, A.M., Martens, J.W.M., Pajares, I, Garcia-Prats, MD, Ramon-Cajal, JM, Juan, A de, Panadero, A, Ortega, E, Aben, K.K.H., Vermeulen, SH, Asadzadeh, F, Engelenburg, KCA van, Margolin, S, Shen, CY, Wu, PE, Forsti, A, Lenner, P, Henriksson, R, Johansson, R, Enquist, K, Hallmans, G, Jonsson, T, Sigurdsson, H, Alexiusdottir, K, Gudmundsson, J, Sigurdsson, A, Frigge, ML, Gudmundsson, L, Kristjansson, K, Halldorsson, BV, Styrkarsdottir, U, Gulcher, JR, Hemminki, K, Lindblom, A, Kiemeney, LA, Mayordomo, JI, Foekens, J.A., Couch, F.J., Olopade, OI, Gudbjartsson, DF, Thorsteinsdottir, U, Rafnar, T, Johannsson, OT & Stefansson, K (2010). Ancestry-Shift Refinement Mapping of the C6orf97-ESR1 Breast Cancer Susceptibility Locus. PLoS Genetics, 6(7). Strijbos, M.H., Gratama, J.W., Schmitz, P.I.M., Rao, C, Onstenk, W., Doyle, GV, Miller, MC, Wit, R. de, Terstappen, LWMM & Sleijfer, S. (2010). Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. European Journal of Cancer, 46(11), 2027-2035. Strijbos, M.H., Snijder, C.A., Kraan, J., Lamers, C.H.J., Gratama, J.W. & Duvekot, J.J. (2010). Levels of Circulating Endothelial Cells in Normotensive and Severe Preeclamptic Pregnancies. Cytometry Part B-Clinical Cytometry, 78B(6), 382-386. Tuna, M, Smid, M., Zhu, DK, Martens, J.W.M. & Amos, CI (2010). Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer. PLoS One, 5(11). Turnbull, C, Ahmed, S., Morrison, J, Pernet, D, Renwick, A., Maranian, M, Seal, S., Ghoussaini, M, Hines, S, Healey, CS, Hughes, D., Warren-Perry, M, Tapper, W, Eccles, D., Evans, D.G., Hooning, M.J., Schutte, M., Ouweland, A.M.W. van den, 165 < back to index Houlston, R., Ross, G., Langford, C., Pharoah, PDP, Stratton, M.R., Dunning, A.M., Rahman, N. & Easton, D.F. (2010). Genome-wide association study identifies five new breast cancer susceptibility loci. Nature Genetics, 42(6), 504-U47. Vermaat, JS, Tweel, I. van der, Mehra, N, Sleijfer, S., Haanen, JB, Roodhart, JM, Engwegen, JY, Korse, C.M., Langenberg, MH, Kruit, W.H.J., Groenewegen, G., Giles, R.H., Schellens, JH, Beijnen, J.H. & Voest, E.E. (2010). Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models. Annals of Oncology, 21(7), 1472-1481. Wang, XS, Pankratz, VS, Fredericksen, Z, Tarrell, R, Karaus, M, McGuffog, L., Pharaoh, PD, Ponder, BA, Dunning, A.M., Peock, S, Cook, M., Oliver, C, Frost, D, Sinilnikova, O.M., Stoppa-Lyonnet, D., Mazoyer, S, Houdayer, C., Hogervorst, FBL, Hooning, M.J., Ligtenberg, M.J., Spurdle, A, Chenevix-Trench, G., Schmutzler, RK, Wappenschmidt, B, Engel, C, Meindl, A, Domchek, SM, Nathanson, K.L., Rebbeck, TR, Singer, CF, Gschwantler-Kaulich, D, Dressler, C, Fink, A, Szabo, C.I., Zikan, M, Foretova, L, Claes, K, Thomas, G., Hoover, RN, Hunter, DJ, Chanock, SJ, Easton, D.F., Antoniou, AC & Couch, F.J. (2010). Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers. Human Molecular Genetics, 19(14), 2886-2897. Wasielewski, M., Out, AA, Vermeulen, J., Nielsen, M, Ouweland, A.M.W. van den, Tops, CMJ, Wijnen, J.T., Vasen, H.F.A., Weiss, M.M., Klijn, J.G.M., Devilee, P., Hes, FJ & Schutte, M. (2010). Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer. Breast Cancer Research and Treatment, 124(3), 635-641. Part of book - abstract Eskens, F.A.L.M., Jonge, M.J.A. de & Sleijfer, S. (2010). Principes van systemische antikankerbehandeling. In JJM van der Hoeven, DTTh Wagener & JPh Dalmeijer (Eds.), Het Oncologie Formularium (pp. 301-326). Houten: Bohn Stafleu van Loghum. 166 < back to index EMC MM-03-86-08 - Translational pharmacology Programme in brief design The programme Translational Pharmacology covers a broad range of topics with clinical trials involving patients on one hand and pharmacological and biological approaches using preclinical models on the other hand. In the clinic cancer patients are treated with new classes of anticancer agents e.g. receptor tyrosine kinase inhibitors, angiogenesis inhibitors and cell cycle inhibitors, or new combinations of anticancer drugs to establish their toxicity profile and efficacy. Linked to these early (phase I and II) and late (phase III) clinical trials is an extensive translational research program addressing the pharmacokinetics and pharmacodynamics of the investigational drugs as well as the pharmacogenetics that influences these pharmacological parameters. Special attention is given to identify pre-treatment patient characteristics that influence the distribution - and hence the efficacy and/or toxicity - of anticancer agents in order to develop genotype and/or phenotype based dosing approaches to correct for interpatient variation. In addition research is carried out to elucidate the molecular mechanisms of carcinogenesis and the ways (cancer) cells respond to various kinds of stress such as exposure to chemo and immune therapeutic agents and/or DNA damaging conditions. The overall aim is to improve the systemic therapy of cancer either through the use of novel anticancer agents and/or novel combinations of chemo and immune therapies, the tailoring of existing treatments for specific patient populations and the discovery and development of novel therapeutic targets. The research program is carried out by five closely interacting research groups: - Molecular Pharmacodynamics (dr. E.A.C. Wiemer) - Personalized Medicine (dr. A.H.J. Mathijssen) - Early Clinical Trials (dr. M.J.A. de Jonge) - Experimental Systemic Therapy of Urogenital Tumours (prof. dr. R. de Wit) - Experimental Tumor Immunology (dr. J.E.M.A. Debets) Key figures Department medical oncology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 6,16 3,8 1,83 4,1 15,89 6,16 3,8 1,83 4,1 15,89 1 0 0 1 42 3 2 48 Thesis Pouw, N.M.C. (2010, juni 23). Towards effective TCR gene therapy: preclinical requirements. EUR. Prom./coprom.: Prof. Dr. J. Verweij. Artikel/Letter to the editor Armstrong, AJ, Garrett-Mayer, E, Wit, R. de, Tannock, I & Eisenberger, M (2010). Prediction of Survival following First-Line Chemotherapy in Men with Castration-Resistant Metastatic Prostate Cancer. Clinical Cancer Research, 16(1), 203-211. Armstrong, AJ, Tannock, I.F., Wit, R. de, George, DJ, Eisenberger, M & Halabi, S (2010). The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival. European Journal of Cancer, 46(3), 517-525. Belt-Dusebout, A.W. van den, Aleman, B.M.P., Gietema, J.A., Wit, R. de, Veer, M.B. van t, Lugtenburg, P.J., Krol, ADG & Leeuwen, F.E. van (2010). Langetermijncomplicaties na behandeling voor zaadbalkanker en hodgkinlymfoom. Nederlands Tijdschrift voor Geneeskunde, 154, 2229. Bendle, GM, Linnemann, C, Hooijkaas, AI, Bies, L, Witte, MA de, Jorritsma, A, Kaiser, ADM, Pouw, N.M.C., Debets, J.E.M.A., Kieback, E, Uckert, W, Song, JY, Haanen, JBAG & Schumacher, TNM (2010). Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nature Medicine, 16(5), 565-U98. Bol, J.M. van der, Mathijssen, R.H.J., Creemers, GJM, Planting, A.S.T., Loos, W.J., Wiemer, E.A.C., Friberg, L.E., Verweij, J., Sparreboom, A. & Jong, F.A. de (2010). A CYP3A4 Phenotype-Based Dosing Algorithm for Individualized Treatment of Irinotecan. Clinical Cancer Research, 16(2), 736-742. Bol, J.M. van der, Jong, F.A. de, Schaik, R.H.N. van, Sparreboom, A., Fessem, M.A.C. van, Geijn, F.E. van de, Daele, P.L.A. van, Verweij, J., Sleijfer, S. & Mathijssen, R.H.J. (2010). Effects of Mannose-Binding Lectin Polymorphisms on IrinotecanInduced Febrile Neutropenia. Oncologist, 15(10), 1063-1072. Bruijn, P. de, Sleijfer, S., Lam, M.H., Mathijssen, R.H.J., Wiemer, E.A.C. & Loos, W.J. 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Myelosuppression by sunitinib is flt-3 genotype dependent. British Journal of Cancer, 103(5), 757-758. Franke, RM, Kosloske, AM, Lancaster, CS, Filipski, KK, Hu, CX, Zolk, O, Mathijssen, RH & Sparreboom, A. (2010). Influence of Oct1/Oct2-Deficiency on Cisplatin-Induced Changes in Urinary N-Acetyl-beta-D-Glucosaminidase. Clinical Cancer Research, 16(16), 4198-4206. Glabbeke, M. van (2010). Comparison of Two Doses of Imatinib for the Treatment of Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Meta-Analysis of 1,640 Patients. Journal of Clinical Oncology, 28(7), 1247-1253. Govers, C.C.F.M., Sebestyen, Z., Coccoris, M., Willemsen, R.A. & Debets, J.E.M.A. (2010). T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends in Molecular Medicine, 16(2), 77-87. Guttman-Yassky, E, Mita, A, Jong, M. de, Matthews, L, McCarthy, S, Iwata, KK, Verweij, J., Rowinsky, E.K. & Krueger, JG (2010). Characterisation of the cutaneous pathology in non-small cell lung cancer (NSCLC) patients treated with the EGFR tyrosine kinase inhibitor erlotinib. European Journal of Cancer, 46(11), 2010-2019. Hamberg, A.P., Steeghs, N., Loos, W.J., Biessen, A.J. van der, Hollander, M., Tascilar, M., Verweij, J., Gelderblom, H. & Sleijfer, S. (2010). Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies. British Journal of Cancer, 102(12), 1699-1706. Hamberg, A.P., Ratain, MJ, Lesaffre, E.M.E.H. & Verweij, J. (2010). Dose-escalation models for combination phase I trials in oncology. European Journal of Cancer, 46(16), 2870-2878. Hamberg, A.P., Verweij, J. & Sleijfer, S. (2010). (Pre-)Clinical Pharmacology and Activity of Pazopanib, a Novel Multikinase Angiogenesis Inhibitor. Oncologist, 15(6), 539-547. Hawkins, RE, Gilham, DE, Debets, J.E.M.A., Eshhar, Z., Taylor, N., Abken, H. & Schumacher, TN (2010). Development of Adoptive Cell Therapy for Cancer: A Clinical Perspective. Human Gene Therapy, 21(6), 665-672. Herpen, C.M.L. van, Eskens, F.A.L.M., Jonge, M.J.A. de, Desar, I, Hooftman, L, Bone, EA, Timmer-Bonte, JNH & Verweij, J. (2010). A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours. British Journal of Cancer, 103(9), 1362-1368. Issels, RD, Lindner, L.H., Verweij, J., Wust, P., Reichardt, P., Schem, BC, Abdel-Rahman, S, Daugaard, S., Salat, C, Wendtner, CM, Vujaskovic, Z, Wessalowski, R, Jauch, K.W., Durr, HR, Ploner, F, Baur-Melnyk, A, Mansmann, U, Hiddemann, W., Blay, J.Y. & Hohenberger, P. (2010). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk softtissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncology, 11(6), 561-570. Jaarsveld, M.T.M. van, Helleman, J., Berns, P.M.J.J. & Wiemer, E.A.C. (2010). MicroRNAs in ovarian cancer biology and therapy resistance. International Journal of Biochemistry & Cell Biology, 42(8), 1282-1290. Jonge, M.J.A. de, Slingerland, M., Loos, W.J., Wiemer, E.A.C., Burger, H., Mathijssen, R.H.J., Kroep, JR, Hollander, MAG den, Biessen, A.J. van der, Lam, M.H., Verweij, J. & Gelderblom, H. (2010). Early cessation of the clinical development of LiPlaCis, a liposomal cisplatin formulation. European Journal of Cancer, 46(16), 3016-3021. Kitzen, J.J., Puozzo, C, Jonge, M.J.A. de, Brandely, M & Verweij, J. (2010). Mild to moderate liver dysfunction does not require dose reduction of oral or intravenous vinorelbine: Results of a pharmacokinetic study. European Journal of Cancer, 46(2), 266269. Kitzen, J.J.E.M., Jonge, M.J.A. de & Verweij, J. (2010). Aurora kinase inhibitors. Critical Reviews in Oncology/Hematology, 73(2), 99-110. Konings, I.R.H.M., Jonge, M.J.A. de, Burger, H., Gaast, A. van der, Beijsterveldt, LEC van, Winkler, H, Verweij, J., Yuan, Z., Hellemans, P & Eskens, F.A.L.M. (2010). Phase I and pharmacological study of the broad-spectrum tyrosine kinase inhibitor JNJ-26483327 in patients with advanced solid tumours. British Journal of Cancer, 103(7), 987-992. Konings, I.R.H.M., Gaast, A. van der, Wijk, LJ van der, Jongh, F.E. de, Eskens, F.A.L.M. & Sleijfer, S. (2010). The addition of pravastatin to chemotherapy in advanced gastric carcinoma: A randomised phase II trial. European Journal of Cancer, 46(18), 3200-3204. Lammers, L.A., Mathijssen, R.H.J., Gelder, T. van, Bijl, M.J., Graan, A.M. de, Seynaeve, C., Fessem, M. van, Berns, E.M.J.J., Vulto, A.G. & Schaik, R.H.N. van (2010). The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. British Journal of Cancer, 103(6), 765-771. Lancaster, CS, Hu, CX, Franke, RM, Filipski, KK, Orwick, SJ, Chen, ZY, Zuo, ZL, Loos, W.J. & Sparreboom, A. (2010). Cisplatin-Induced Downregulation of OCTN2 Affects Carnitine Wasting. Clinical Cancer Research, 16(19), 4789-4799. Novelli, M, Rossi, S, Rodriguez-Justo, M, Taniere, P, Seddon, B, Toffolatti, L, Sartor, C, Hogendoorn, P.C.W., Sciot, R., Glabbeke, M. van, Verweij, J., Blay, J.Y., Hohenberger, P., Flanagan, A. & Tos, AP Dei (2010). DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology, 57(2), 259-270. Pander, J, Wessels, J.A.M., Mathijssen, R.H.J., Gelderblom, H. & Guchelaar, HJ (2010). Pharmacogenetics of tomorrow: the 1+1=3 principle. Pharmacogenomics, 11(7), 1011-1017. 168 < back to index Pouw, N.M.C., Treffers-Westerlaken, E, Kraan, J., Wittink, F, Hagen, T.L.M. ten, Verweij, J. & Debets, J.E.M.A. (2010). Combination of IL-21 and IL-15 enhances tumour-specific cytotoxicity and cytokine production of TCR-transduced primary T cells. Cancer Immunology Immunotherapy, 59(6), 921-931. Pouw, N.M.C., Treffers-Westerlaken, E, Mondino, A, Lamers, C.H.J. & Debets, J.E.M.A. (2010). TCR gene-engineered T cell: Limited T cell activation and combined use of IL-15 and IL-21 ensure minimal differentiation and maximal antigen-specificity. Molecular Immunology, 47(7-8), 1411-1420. Schroten-Loef, C., Kraaij, R., Veldhoven, JLM, Berrevoets, C.A., Bakker, M.A. den, Ma, QZ, Sadelain, M, Bangma, C.H., Willemsen, R.A. & Debets, J.E.M.A. (2010). T cell activation upon exposure to patient-derived tumor tissue: A functional assay to select patients for adoptive T cell therapy. Journal of Immunological Methods, 359(1-2), 11-20. Sleijfer, S., Ouali, M, Glabbeke, M. van, Krarup-Hansen, A, Rodenhuis, S., Cesne, A. le, Hogendoorn, P.C.W., Verweij, J. & Blay, J.Y. (2010). Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas An exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). European Journal of Cancer, 46(1), 72-83. Strijbos, M.H., Gratama, J.W., Schmitz, P.I.M., Rao, C, Onstenk, W., Doyle, GV, Miller, MC, Wit, R. de, Terstappen, LWMM & Sleijfer, S. (2010). Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. European Journal of Cancer, 46(11), 2027-2035. Strijbos, M.H., Krimpen, B.A. van, Debets, J.E.M.A., Kraan, J., Sleijfer, S., Gratama, J.W. & Lamers, C.H.J. (2010). mRNA levels of CD31, CD144, CD146 and von Willebrand factor do not serve as surrogate markers for circulating endothelial cells. Thrombosis and Haemostasis, 104(2), 318-326. Surmont, V., Smit, E.F., Jonge, M.J.A. de, Aerts, J.G.J.V., Nackaerts, K, Vernhout, R, Gras, J, Wijk, A Van, Phernambucq, ECJ, Meerbeeck, J.P.A.M. van, Senan, S., Kraaij, CJ, Chouaki, N, Praag, J.O. & Klaveren, R.J. van (2010). Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies. Lung Cancer, 69(3), 302-306. Trimbos, B, Timmers, P, Pecorelli, S, Coens, C., Ven, K. van der, Burg, M.E.L. van der & Casado, A (2010). Surgical Staging and Treatment of Early Ovarian Cancer: Long-term Analysis From a Randomized Trial. Journal of the National Cancer Institute, 102(13), 982-987. Vergote, I., Trope, CG, Amant, F, Kristensen, GB, Ehlen, T, Johnson, N, Verheijen, R.H.M., Burg, M.E.L. van der, Lacave, A.J., Panici, PB, Kenter, G.G., Casado, A, Mendiola, C., Coens, C., Verleye, L, Stuart, GCE, Pecorelli, S & Reed, NS (2010). Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian Cancer. New England Journal of Medicine, 363(10), 943-953. Verweij, J. & Baker, L.H. (2010). Future treatment of soft tissue sarcomas will be driven by histological subtype and molecular abberations. European Journal of Cancer, 46(5), 863-868. Verweij, J., Disis, ML & Cannistra, SA (2010). Phase I Studies of Drug Combinations. Journal of Clinical Oncology, 28(30), 4545-4546. Vos, F.Y.F.L. de, Middelburg, T.A., Seynaeve, C. & Jonge, M.J.A. de (2010). Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy. Journal of infection and chemotherapy, 16(1), 59-61. Witjes, C.D.M., Man, R.A. de, Eskens, F.A.L.M., Dwarkasing, R.S., Zondervan, P.E., Verhoef, C. & Ijzermans, J.N.M. (2010). Hepatocellular carcinoma: the significance of cirrhosis for treatment and prognosis- retrospective study. Nederlands Tijdschrift voor Geneeskunde, 154, 1747. Wooldridge, L, Clement, M, Lissina, A, Edwards, ESJ, Ladell, K, Ekeruche, J, Hewitt, RE, Laugel, B, Gostick, E, Cole, DK, Debets, J.E.M.A., Berrevoets, C.A., Miles, JJ, Burrows, SR, Price, DA & Sewell, AK (2010). MHC Class I Molecules with Superenhanced CD8 Binding Properties Bypass the Requirement for Cognate TCR Recognition and Nonspecifically Activate CTLs. Journal of Immunology, 184(7), 3357-3366. Zubakov, D., Boersma, A.W.M., Choi, H.Y., Kuijk, P.F. van, Wiemer, E.A.C. & Kayser, M. (2010). MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation. International Journal of Legal Medicine, 124(3), 217-226. Part of book - abstract Eskens, F.A.L.M., Jonge, M.J.A. de & Sleijfer, S. (2010). Principes van systemische antikankerbehandeling. In JJM van der Hoeven, DTTh Wagener & JPh Dalmeijer (Eds.), Het Oncologie Formularium (pp. 301-326). Houten: Bohn Stafleu van Loghum. Wijnhoven, B.P.L., Gaast, A. van der, Rij, C.M. van & Lanschot, J.J.B. van (2010). Slokdarmcarcinoom. In JJM van der Hoeven, DTTh Wagener & JPh Dalmeijer (Eds.), Het Oncologie Formularium (pp. 157-166). Houten: Bohn Stafleu van Loghum. 169 < back to index EMC MM-04-20-01 - Neoplastic lesions and chronic inflammatation of the gastrointestinal tract Programme in brief design The research of the Department of Gastroenterology & Hepatology is centered around the themes premalignant lesions and chronic inflammatory processes of the gastrointestinal epithelium. The main focus is on molecular, immunological and optical detection of the development, the diagnosis, and treatment of chronic inflammatory and neoplastic diseases of 1) esophagus, 2) stomach, and 3) colon. Ad 1) Esophagus: Reflux induced chronic inflammation is thought to be the main initiating factor for the development of Barrett's esophagus, a precursor lesion for adenocarcinoma of the esophagus. Concerning Barrett's esophagus, the investigations aim at: a) the understanding of the inflammatory inducing factors in reflux esophagitis and Barrett¿s esophagus; b) the determination of prognostic parameters in Barrett's epithelium, that predict development of malignancy. c) uncovering of optical and molecular techniques for detection of dysplasia in Barrett¿s esophagus, and d) development of minimal invasive treatment strategies for early malignancy. Ad 2) Stomach: endoscopic surveillance of patients with pre-malignant gastric lesions may provide a basis for gastric cancer prevention. current surveillance in routine practice often relies on histological assessment of random biopsies obtained during conventional endoscopy. however, the appropriate biopsy strategy is unclear. Research aims to: a) improve detection of precursor lesions that precede development of early gastric cancer; b) to assess the predictive value of clinical, histological and serological parameters c) to develop guidelines for clinical management of patients at increased risk for gastric cancer Ad 3) Colon: Colon research concerns effective screening, and intervention strategies in sporadic colorectal cancer (CRC), familial and hereditary cancer syndromes. The investigations aim at: a) to develop and compare resection techniques for neoplasms of the colon b) uncovering of optical and molecular techniques for detection of dysplasia in members of familial and hereditary coloncancer families c) to develop strategies for population based screening for colorectal cancer Key figures Department gastroenterology & hepatology Total SP1 16,21 16,21 SP2 0,1 0,1 SP3 SP4 0 0 Sptot 7 7 23,31 23,31 T1 T2 T3 5 0 0 Ttot IS 5 107 FS 3 OP 0 Ptot 115 Thesis Baars, J.E. (2010, november 05). Complications of inflammatory Bowel Disease Revisited. EUR (242 pag.). Prom./coprom.: Prof. Dr. E.J. Kuipers & Drs. C.J. van der Woude. Capelle, L.G. (2010, september 03). Helicobacter Pylori-associated malignancies. EUR (178 pag.). Prom./coprom.: Prof. Dr. E.J. Kuipers. Hol, L. (2010, april 13). Population-based screening for colorectal cancer. EUR. Prom./coprom.: Prof. Dr. E.J. Kuipers, Prof.Dr. J.D.F. Habbema & Dr. M.E. van Leerdam. Hunfeld, N.G.M. (2010, september 24). Clinical effects of proton pump inhibitors; focus on pharmacogenetics, kinetics and dynamics. EUR (164 pag.). Prom./coprom.: Prof. Dr. E.J. Kuipers. Mulder, S. (2010, december 10). Screening and surveillance for colorectal cancer. EUR (149 pag.). Prom./coprom.: Prof. Dr. E.J. Kuipers. Mulder, S.A. (2010, december 10). Studies on screening and surveillance for colorectal cancer. EUR. Prom./coprom.: Prof. Dr. E.J. Kuipers. Artikel/Letter to the editor Aktas, H., Ridder, L. de, Haringsma, J., Kuipers, E.J. & Mensink, P.B.F. (2010). Complications of single-balloon enteroscopy: a prospective evaluation of 166 procedures. Endoscopy, 42, 365-368. Albuquerque, C, Baltazar, C, Filipe, B, Penha, F, Pereira, T, Smits, M.J.M., Cravo, M, Lage, P, Fidalgo, P, Claro, I, Rodrigues, P, Veiga, I, Ramos, JS, Fonseca, I, Leitao, CN & Fodde, R. (2010). Colorectal Cancers Show Distinct Mutation Spectra in Members of the Canonical WNT Signaling Pathway According to Their Anatomical Location and Type of Genetic Instability. Genes Chromosomes & Cancer, 49(8), 746-759. Al-Lahham, SH, Peppelenbosch, M.P., Roelofsen, H., Vonk, RJ & Venema, K. (2010). Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 1801(11), 1175-1183. Amelink, A., Haringsma, J. & Sterenborg, H.J.C.M. (2010). Differential path-length spectroscopy: a tool for quantitative assessment of blood oxygen saturation in microvessels. Gastrointestinal Endoscopy, 71(6), 1100-1100. 170 < back to index Arends, J.E., Claassen, M.A.A., Berg, CHSB van den, Nanlohy, NM, Erpecum, K.J. van, Baak, BC, Hoepelman, A.I.M., Boonstra, P.A. & Baarle, D. van (2010). T-cell responses at baseline and during therapy with peginterferon-alpha and ribavirin are not associated with outcome in chronic hepatitis C infected patients. Antiviral Research, 87(3), 353-360. Baars, J.E., Vogelaar, L., Wolfhagen, FNJ, Biermann, K., Kuipers, E.J. & Woude, C.J. van der (2010). A short course of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation in inflammatory bowel disease patients: Results from a randomized controlled trial. Journal of Crohn's and Colitis, 4(6), 661-668. Baars, J.E., Siegel, CA, Spijker, A. van t, Markus, T, Kuipers, E.J. & Woude, C.J. van der (2010). Inflammatory bowel diseasepatients are insufficiently educated about the basic characteristics of their disease and the associated risk of colorectal cancer. Digestive and Liver Disease, 42(11), 777-784. Baars, J.E., Markus, T, Kuipers, E.J. & Woude, C.J. van der (2010). Patients' Preferences regarding Shared Decision-Making in the Treatment of Inflammatory Bowel Disease: Results from a Patient-Empowerment Study. Digestion. International Journal of Gastroenterology, 81(2), 113-119. Barkun, AN, Adam, V, Sung, JJY, Kuipers, E.J., Mossner, J, Jensen, D, Stuart, R, Lau, JY, Naucler, E, Kilhamn, J, Granstedt, H, Liljas, B & Lind, T (2010). Cost Effectiveness of High-Dose Intravenous Esomeprazole for Peptic Ulcer Bleeding. Pharmacoeconomics, 28(3), 217-230. Barkun, AN, Bardou, M, Kuipers, E.J., Sung, J, Hunt, RH, Martel, M & Sinclair, P (2010). International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding. Annals of Internal Medicine, 152(2), 101-+. Bekker- Grob, E.W. de, Hol, L., Donkers, B., Dam, L. van, Habbema, J.D.F., Leerdam, M.E. van, Kuipers, E.J., Essink-Bot, M.L. & Steyerberg, E.W. (2010). Labeled versus Unlabeled Discrete Choice Experiments in Health Economics: An Application to Colorectal Cancer Screening. Value in Health, 13(2), 315-323. Boparai, KS, Mathus-Vliegen, EMH, Koornstra, JJ, Nagengast, F.M., Leerdam, M.E. van, Noesel, C.J.M. van, Houben, M., Cats, A., Hest, L.P. van, Fockens, P. & Dekker, E (2010). Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: a multicentre cohort study. Gut, 59(8), 1094-1100. Bosma, B.M., Metselaar, H.J., Gerrits, J.H., Besouw, N.M. van, Mancham, S., Groothuismink, Z.M.A., Boor, P.P.C., Laan, L.J.W. van der, Tilanus, H.W., Kuipers, E.J. & Kwekkeboom, J. (2010). Migration of Allosensitizing Donor Myeloid Dendritic Cells into Recipients After Liver Transplantation. Liver Transplantation, 16(1), 12-22. Bultman, E., Kuipers, E.J. & Woude, C.J. van der (2010). Systematic review: steroid withdrawal in anti-TNF-treated patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 32(3), 313-323. Calvet, X, Barkun, A, Bardou, M, Sung, J & Kuipers, E.J. (2010). High-Dose vs Non-High-Dose PPIs After Endoscopic Treatment in Patients With Bleeding Peptic Ulcer: Current Evidence Is Insufficient to Claim Equivalence. Archives of Internal Medicine, 170(18), 1698-1699. Capelle, L.G., Haringsma, J., Vries, A.C. de, Steyerberg, E.W., Biermann, K., Dekken, H. van & Kuipers, E.J. (2010). Narrow Band Imaging for the Detection of Gastric Intestinal Metaplasia and Dysplasia During Surveillance Endoscopy. Digestive Diseases & Sciences, 55(12), 3442-3448. Capelle, L.G., Grieken, N.C.T. van, Lingsma, H.F., Steyerberg, E.W., Klokman, W.J., Bruno, M.J., Vasen, H.F.A. & Kuipers, E.J. (2010). Risk and Epidemiological Time Trends of Gastric Cancer in Lynch Syndrome Carriers in The Netherlands. Gastroenterology, 138(2), 487-492. Capelle, L.G., Vries, A.C. de, Haringsma, J., Borg, F. ter, Vries, R.A. de, Bruno, M.J., Dekken, H. van, Meijer, J., Grieken, N.C.T. van & Kuipers, E.J. (2010). The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointestinal Endoscopy, 71(7), 1150-1158. Claassen, M.A.A., Knegt, R.J. de, Tilanus, H.W., Janssen, H.L.A. & Boonstra, P.A. (2010). Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. Journal of Hepatology, 52(3), 315321. Colombel, JF, Sandborn, WJ, Reinisch, W, Mantzaris, GJ, Kornbluth, A, Rachmilewitz, D, Lichtiger, S, D'Haens, G, Diamond, RH, Broussard, DL, Tang, KL, Woude, C.J. van der & Rutgeerts, P (2010). Infliximab, Azathioprine, or Combination Therapy for Crohn's Disease. New England Journal of Medicine, 362(15), 1383-1395. Dam, L. van, Kuipers, E.J. & Leerdam, M.E. van (2010). Performance improvements of stool-based screening tests. Best Practice & Research in Clinical Gastroenterology, 24(4), 479-492. Dam, L. van, Hol, L., Bekker- Grob, E.W. de, Steyerberg, E.W., Kuipers, E.J., Habbema, J.D.F., Essink-Bot, M.L. & Leerdam, M.E. van (2010). What determines individuals' preferences for colorectal cancer screening programmes? A discrete choice experiment. European Journal of Cancer, 46(1), 150-159. Deprez, PH, Bergman, J.J., Meisner, S, Ponchon, T, Repici, A, Dinis-Ribeiro, M & Haringsma, J. (2010). Current practice with endoscopic submucosal dissection in Europe: position statement from a panel of experts. Endoscopy, 42(10), 854-859. Dieren, J.M. van, Lambers, M.E.H., Kuipers, E.J., Samsom, J.N., Woude, C.J. van der & Nieuwenhuis, E.E.S. (2010). Local immune regulation of mucosal inflammation by Tacrolimus. Digestive Diseases & Sciences, 55, 2514-2519. 171 < back to index Dinjens, W.N.M., Leerdam, M.E. van & Wagner, A. (2010). On the advent of MSI testing of all colorectal cancers and a substantial part of other Lynch syndrome-related neoplasms. Expert Review of Molecular Diagnosis, 10(4), 381-384. Dotan, I, Rachmilewitz, D, Schreiber, S., Eliakim, R, Woude, C.J. van der, Kornbluth, A, Buchman, AL, Bar-Meir, S, Bokemeyer, B, Goldin, E, Maaser, C, Mahadevan, U, Seidler, U, Hoffman, JC, Homoky, D, Plasse, T, Powers, B, Rutgeerts, P & Hommes, D (2010). A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease. Gut, 59(6), 760-766. Eshuis, WJ, Gaag, N.A. van der, Rauws, E.A.J., Eijck, C.H.J. van, Bruno, M.J., Kuipers, E.J., Coene, P.P., Kubben, FJGM, Gerritsen, JJGM, Greve, J.W., Gerhards, MF, Hingh, IHJT de, Klinkenbijl, J.H., Nio, CY, Castro, SMM de, Busch, O.R.C., Gulik, T.M., Bossuyt, P.M.M. & Gouma, D.J. (2010). Therapeutic Delay and Survival After Surgery for Cancer of the Pancreatic Head With or Without Preoperative Biliary Drainage. Annals of Surgery, 252(5), 840-848. Festen, EAM, Stokkers, P.C.F., Diemen, CC van, Bodegraven, A.A. van, Boezen, H.M., Crusius, BJA, Hommes, DW, Woude, C.J. van der, Balschun, T, Verspaget, H.W., Schreiber, S., Jong, DJ de, Franke, A, Dijkstra, G., Wijmenga, C. & Weersma, RK (2010). Genetic Analysis in A Dutch Study Sample Identifies More Ulcerative Colitis Susceptibility Loci and Shows Their Additive Role in Disease Risk (vol 105, pg 395, 2010). American Journal of Gastroenterology, 105(2), 479-479. Fuhler, G.M., Baanstra, M, Chesik, D, Somasundaram, R., Seckinger, A, Hose, D, Peppelenbosch, M.P. & Bos, N.A. (2010). Bone marrow stromal cell interaction reduces Syndecan-1 expression and induces kinomic changes in myeloma cells. Experimental Cell Research, 316(11), 1816-1828. Gaag, N.A. van der, Rauws, E.A.J., Eijck, C.H.J. van, Bruno, M.J., Harst, E. van der, Kubben, FJGM, Gerritsen, JJGM, Greve, J.W., Gerhards, MF, Hingh, IHJT de, Klinkenbijl, JHG, Nio, CY, Castro, SMM de, Busch, O.R.C., Gulik, T.M., Bossuyt, PM & Gouma, D.J. (2010). Preoperative Biliary Drainage for Cancer of the Head of the Pancreas. New England Journal of Medicine, 362(2), 129-137. Gao, H., Lier, M.G.F. van, Poley, J.W., Kuipers, E.J., Leerdam, M.E. van & Mensink, P.B. (2010). Endoscopic therapy of smallbowel polyps by double-balloon enteroscopy in patients with Peutz-Jeghers syndrome. Gastrointestinal Endoscopy, 71(4), 768773. Geenen, EJM van, Boer, NKH de, Stassen, P, Linskens, RK, Bruno, M.J., Mulder, C.J.J., Stegeman, CA & Bodegraven, A.A. van (2010). Azathioprine or mercaptopurine-induced acute pancreatitis is not a disease-specific phenomenon. Alimentary Pharmacology & Therapeutics, 31(12), 1322-1329. Geenen, EJM van, Mulder, C.J.J., Peet, D.L. van der, Fockens, P. & Bruno, M.J. (2010). Endoscopic treatment of acute biliary pancreatitis: A national survey among Dutch gastroenterologists. Scandinavian Journal of Gastroenterology, 45(9), 1116-1120. Geenen, EJM van, Peet, D.L. van der, Bhagirath, P, Mulder, C.J.J. & Bruno, M.J. (2010). Etiology and diagnosis of acute biliary pancreatitis. Nature reviews - gastroenterology & hepatology, 7(9), 495-502. Groenen, M.J.M., Buuren, H.R. van, Henegouwen, GPV, Fockens, P., Lei, J. van der, Stuifbergen, WNHM, Schaar, PJ Van der, Kuipers, E.J. & Ouwendijk, RJT (2010). Validation study of automatically generated codes in colonoscopy using the endoscopic report system Endobase (R). Scandinavian Journal of Gastroenterology, 45(9), 1121-1126. Harinck, F., Poley, J.W., Kluijt, I., Fockens, P. & Bruno, M.J. (2010). Is Early Diagnosis of Pancreatic Cancer Fiction? Surveillance of Individuals at High Risk for Pancreatic Cancer. Digestive Diseases, 28(4-5), 670-678. Harinck, F., Canto, MI, Schulick, R, Goggins, M, Poley, J.W., Fockens, P., Kluijt, I. & Bruno, M.J. (2010). Surveillance in individuals at high risk of pancreatic cancer: too early to tell? Gut, 59(7), 1005-1006. Haringsma, J., Heel, N.C.M. van & Kuipers, E.J. (2010). Are we making progress in diagnosing and preventing gastrointestinal cancers? Therapeutic Advances in Gastroenterology, 3(4), 213-220. Haver, VG, Slart, RHJA, Zeebregts, CJ, Peppelenbosch, M.P. & Tio, R.A. (2010). Rupture of Vulnerable Atherosclerotic Plaques: MicroRNAs Conducting the Orchestra? Trends in Cardiovascular Medicine, 20(2), 65-71. Haycock, A, Koch, A.D., Familiari, P, Delft, F van, Dekker, E, Petruzziello, L, Haringsma, J. & Thomas-Gibson, S (2010). Training and transfer of colonoscopy skills: a multinational, randomized, blinded, controlled trial of simulator versus bedside training. Gastrointestinal Endoscopy, 71(2), 298-307. Heel, N.C.M. van, Haringsma, J., Spaander, V.M.C.W., Bruno, M.J. & Kuipers, E.J. (2010). Esophageal stents for the relief of malignant dysphagia due to extrinsic compression. Endoscopy, 42(7), 536-540. Heel, N.C.M. van, Haringsma, J., Spaander, V.M.C.W., Bruno, M.J. & Kuipers, E.J. (2010). Short-Term Esophageal Stenting in the Management of Benign Perforations. American Journal of Gastroenterology, 105(7), 1515-1520. Hoed, C.M. den & Kuipers, E.J. (2010). Esomeprazole for the treatment of peptic ulcer bleeding. Expert Review of Gastroenterology and Hepatology, 4(6), 679-695. Hol, L., Bekker-Grob, EW de, Dam, L. van, Donkers, B., Kuipers, E.J., Habbema, J.D.F., Steyerberg, E.W., Leerdam, M.E. van & Essink-Bot, M.L. (2010). Preferences for colorectal cancer screening strategies: a discrete choice experiment. British Journal of Cancer, 102(6), 972-980. Hol, L., Jonge, V. de, Leerdam, M.E. van, Ballegooijen, M. van, Looman, C.W.N., Vuuren, A.J. van, Reijerink, JCIY, Habbema, J.D.F., Essink-Bot, M.L. & Kuipers, E.J. (2010). Screening for colorectal cancer: Comparison of perceived test burden of guaiac- 172 < back to index based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy. European Journal of Cancer, 46(11), 2059-2066. Hol, L., Leerdam, M.E. van, Ballegooijen, M. van, Vuuren, A.J. van, Dekken, H. van, Reijerink, JCIY, Togt, A van der, Habbema, J.D.F. & Kuipers, E.J. (2010). Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut, 59(1), 62-68. Homs, M.Y.V., Gaast, A. van der, Siersema, P.D., Steyerberg, E.W. & Kuipers, E.J. (2010). Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction (Withdrawn paper. 2010, art. no. CD004063). Cochrane Database Systematics Review. Hoogduijn, M.J., Popp, FC, Grohnert, A, Crop, M.J., Rhijn, M. van, Rowshani, T., Eggenhofer, E, Renner, P, Reinders, ME, Rabelink, T.J., Laan, L.J.W. van der, Dor, F.J.M.F., Ijzermans, J.N.M., Genever, PG, Lange, C, Durrbach, A, Houtgraaf, H.J., Christ, B, Seifert, M, Shagidulin, M, Donckier, V, Deans, R, Ringden, O, Perico, N, Remuzzi, G, Bartholomew, A, Schlitt, HJ, Weimar, W., Baan, C.C. & Dahlke, MH (2010). Advancement of Mesenchymal Stem Cell Therapy in Solid Organ Transplantation (MISOT). Transplantation, 90(2), 124-126. Hoorn, E.J., Hoek, J. van der, Man, R.A. de, Kuipers, E.J., Bolwerk, C & Zietse, R. (2010). A Case Series of Proton Pump Inhibitor-Induced Hypomagnesemia. American Journal of Kidney Diseases, 56(1), 112-116. Hunfeld, N.G.M., Touw, D.J., Mathot, R.A.A., Mulder, P.G.H., Schaik, R.H.N. van, Kuipers, E.J., Kooiman, J.C. & Geus, W.P. (2010). A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism. Alimentary Pharmacology & Therapeutics, 31, 150-159. Jeurnink, S.M., Polinder, S., Steyerberg, E.W., Kuipers, E.J. & Siersema, P.D. (2010). Cost comparison of gastrojejunostomy versus duodenal stent placement for malignant gastric outlet obstruction. Journal of Gastroenterology, 45(5), 537-543. Jeurnink, S.M., Steyerberg, E.W., Hooft, JE van, Eijck, C.H.J. van, Schwartz, MP, Vleggaar, F.P., Kuipers, E.J. & Siersema, P.D. (2010). Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointestinal Endoscopy, 71(3), 490-499. Jong, K. de, Nio, CY, Hermans, J.J., Dijkgraaf, MG, Gouma, D.J., Eijck, C.H.J. van, Heel, E van, Klass, G, Fockens, P. & Bruno, M.J. (2010). High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations. Clinical Gastroenterology and Hepatology, 8(9), 806-811. Jonge, P.J.F. de, Blankenstein, M. van, Looman, C.W.N., Casparie, M.K., Meijer, G.A. & Kuipers, E.J. (2010). Risk of Colorectal Cancer in Patients With Barrett's Esophagus: A Dutch Population-Based Study. American Journal of Gastroenterology, 105(1), 77-83. Jonge, P.J.F. de, Blankenstein, M. van, Looman, C.W.N., Casparie, M.K., Meijer, G.A. & Kuipers, E.J. (2010). Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study. Gut, 59(8), 1030-1036. Jonge, V. de, Sint Nicolaas, J., Lalor, EA, Wong, C.K., Walters, B, Bala, A, Kuipers, E.J., Leerdam, M.E. van & Zanten, SJOV van (2010). A prospective audit of patient experiences in colonoscopy using the Global Rating Scale: A cohort of 1187 patients. Canadian Journal of Gastroenterology, 24(10), 607-613. Kanwal, F, Barkun, A, Gralnek, IM, Asch, SM, Kuipers, E.J., Bardou, M, Sung, J, Enns, R, Agreus, L, Armstrong, D & Spiegel, BMR (2010). Measuring Quality of Care in Patients With Nonvariceal Upper Gastrointestinal Hemorrhage: Development of an Explicit Quality Indicator Set. American Journal of Gastroenterology, 105(8), 1710-1718. Kuipers, E.J. (2010). Barrett's oesophagus, proton pump inhibitors and gastrin: the fog is clearing. Gut, 59(2), 148-149. Kuipers, E.J. (2010). ENDOSCOPY Risk assessment in upper gastrointestinal bleeding. Nature reviews - gastroenterology & hepatology, 7(9), 480-482. Laan, L.J.W. van der, Hudson, M, McPherson, S, Zondervan, P.E., Thomas, RC, Kwekkeboom, J., Lindsay, AS, Burt, AD, Kazemier, G., Tilanus, H.W., Bassendine, MF & Metselaar, H.J. (2010). Results of a Two-Center Study Comparing Hepatic Fibrosis Progression in HCV-positive Liver Transplant Patients Receiving Cyclosporine or Tacrolimus. Transplantation Proceedings, 42(10), 4573-4577. Laar, L. van der, Bosch, A. van den, Kooij, SW van der, Janssen, H.L.A., Coffer, P.J., Kooten, C. van & Woltman, A.M. (2010). A Nonredundant Role for Canonical NF-kappa B in Human Myeloid Dendritic Cell Development and Function. Journal of Immunology, 185(12), 7252-7261. Laar, L. van der, Buitenhuis, M, Wensveen, FM, Janssen, H.L.A., Coffer, P.J. & Woltman, A.M. (2010). Human CD34-Derived Myeloid Dendritic Cell Development Requires Intact Phosphatidylinositol 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling. Journal of Immunology, 184(12), 6600-6611. Laine, L, Spiegel, B, Rostom, A, Moayyedi, P, Kuipers, E.J., Bardou, M, Sung, J & Barkun, AN (2010). Methodology for Randomized Trials of Patients With Nonvariceal Upper Gastrointestinal Bleeding: Recommendations From an International Consensus Conference. American Journal of Gastroenterology, 105(3), 540-550. Leeuwenburgh, I., Gerrits, M.M., Capello, A., Bogert, B. van den, Dekken, H. van, Steyerberg, E.W., Siersema, P.D. & Kuipers, E.J. (2010). Expression of p53 as predictor for the development of esophageal cancer in achalasia patients. Diseases of the Esophagus, 23(6), 506-511. 173 < back to index Lems, W.F. & Kuipers, E.J. (2010). Preventie en NSAID-gastropathie: verschil tussen een coxib en toevoeging van een PPI. Nederlands Tijdschrift voor Geneeskunde, 154, 2663. Li, Y., Haar, C. de, Chen, M., Deuring, J.J., Gerrits, M.M., Smits, M.J.M., Xia, B, Kuipers, E.J. & Woude, C.J. van der (2010). Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut, 59(2), 227-235. Liedenbaum, MH, Vries, AH de, Rijn, AF van, Dekker, H.M., Willemssen, F.E.J.A., Leerdam, M.E. van, Marrewijk, C.J. van, Fockens, P., Bipat, S, Bossuyt, P.M.M. & Stoker, J.. (2010). CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population. Abdominal Imaging, 35(6), 661-668. Liedenbaum, MH, Vries, AH de, Gouw, CIBF, Rijn, AF van, Bipat, S, Dekker, E & Stoker, J. (2010). CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes. European Radiology, 20(2), 367-376. Lier, M.G.F. van, Wagner, A., Leerdam, M.E. van, Biermann, K., Kuipers, E.J., Steyerberg, E.W., Dubbink, H.J. & Dinjens, W.N.M. (2010). A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory. Journal of Cellular and Molecular Medicine, 14(1-2), 181-197. Lier, M.G.F. van, Wagner, A., Mathus-Vliegen, EMH, Kuipers, E.J., Steyerberg, E.W. & Leerdam, M.E. van (2010). High Cancer Risk in Peutz-Jeghers Syndrome: A Systematic Review and Surveillance Recommendations. American Journal of Gastroenterology, 105(6), 1258-1264. Lier, M.G.F. van, Mathus-Vliegen, EMH, Leerdam, M.E. van, Kuipers, E.J., Looman, C.W.N., Wagner, A. & Vanheusden, K. (2010). Quality of life and psychological distress in patients with Peutz-Jeghers syndrome. Clinical Genetics, 78(3), 219-226. Menke, V., Es, JH van, Lau, W de, Born, M van den, Kuipers, E.J., Siersema, P.D., Bruin, R.W.F. de, Kusters, J.G. & Clevers, H (2010). Conversion of metaplastic Barrett's epithelium into post-mitotic goblet cells by gamma-secretase inhibition. Disease Models & Mechanisms, 3(1-2), 104-110. Mensink, P.B.F., Aktas, H., Detkova, Z., West, R.L., Kuipers, E.J. & Woude, C.J. van der (2010). Impact of double-balloon enteroscopy findings on the management of Crohn's disease. Scandinavian Journal of Gastroenterology, 45(4), 483-489. Moroso, V., Metselaar, H.J., Mancham, S., Tilanus, H.W., Eissens, D, Meer, A van der, Laan, L.J.W. van der, Kuipers, E.J., Joosten, I. & Kwekkeboom, J. (2010). Liver Grafts Contain a Unique Subset of Natural Killer Cells that Are Transferred into the Recipient After Liver Transplantation. Liver Transplantation, 16(7), 895-908. Mulder, S.A., Soest, E.M. van, Dieleman, J.P., Rossum, LGM van, Ouwendijk, RJT, Leerdam, M.E. van & Kuipers, E.J. (2010). Exposure to colorectal examinations before a colorectal cancer diagnosis: a case-control study. European Journal of Gastroenterology & Hepatology, 22(4), 437-443. Noord, D. van, Biermann, K., Moons, L.M.G., Pattynama, P.M.T., Verhagen, H.J.M., Kuipers, E.J. & Mensink, P.B.F. (2010). Histological changes in patients with chronic upper gastrointestinal ischaemia. Histopathology, 57(4), 615-621. Pan, Q., Metselaar, H.J., Ruiter, P.E. de, Kwekkeboom, J., Tilanus, H.W., Janssen, H.L.A. & Laan, L.J.W. van der (2010). Calcineurin Inhibitor Tacrolimus Does Not Interfere with the Suppression of Hepatitis C Virus Infection by Interferon-alpha. Liver Transplantation, 16(4), 520-526. Queiroz, KCS, Ruela-de-Sousa, RR, Fuhler, G.M., Aberson, HL, Ferreira, CV, Peppelenbosch, M.P. & Spek, CA (2010). Hedgehog signaling maintains chemoresistance in myeloid leukemic cells. Oncogene, 29(48), 6314-6322. Ramsoekh, D., Haringsma, J., Poley, J.W., Putten, P. van, Dekken, H. van, Steyerberg, E.W., Leerdam, M.E. van & Kuipers, E.J. (2010). A back-to-back comparison of white light video endoscopy with autofluorescence endoscopy for adenoma detection in high-risk subjects. Gut, 59(6), 785-793. Redford, PS, Boonstra, P.A., Read, S, Pitt, J, Graham, C, Stavropoulos, E, Bancroft, GJ & O'Garra, A (2010). Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung. European Journal of Immunology, 40(8), 2200-2210. Rijckborst, V., Hansen, B.E., Cakaloglu, Y, Ferenci, P, Tabak, F, Akdogan, M, Simon, K, Akarca, US, Flisiak, R, Hart, E., Vuuren, A.J. van, Boucher, C.A.B., Borg, M.J. ter & Janssen, H.L.A. (2010). Early On-Treatment Prediction of Response to Peginterferon Alfa-2a for HBeAg-Negative Chronic Hepatitis B Using HBsAg and HBV DNA Levels. Hepatology, 52(2), 454-461. Robanus-Maandag, EC, Koelink, PJ, Breukel, C., Salvatori, DCF, Jagmohan-Changur, SC, Bosch, CAJ, Verspaget, H.W., Devilee, P., Fodde, R. & Smits, M.J.M. (2010). A new conditional Apc-mutant mouse model for colorectal cancer. Carcinogenesis, 31(5), 946-952. Ruela-de-Sousa, RR, Queiroz, KCS, Peppelenbosch, M.P. & Fuhler, G.M. (2010). Reversible phosphorylation in haematological malignancies: Potential role for protein tyrosine phosphatases in treatment? Biochimica et Biophysica Acta-Reviews on Cancer, 1806(2), 287-303. Santvoort, H.C. van, Besselink, M.G., Bakker, OJ, Hofker, HS, Boermeester, M.A., DeJong, C.H., Goor, H. van, Schaapherder, AF, Eijck, C.H.J. van, Bollen, T.L., Ramshorst, B. van, Nieuwenhuijs, V.B., Timmer, R., Lameris, J.S., Kruyt, PM, Manusama, E.R., Harst, E. van der, Schelling, G.P. van der, Karsten, T, Hesselink, E.J., Laarhoven, C.J. van, Rosman, C., Bosscha, K., Wit, R.J. de, Houdijk, AP, Leeuwen, MS van, Buskens, E. & Gooszen, H.G. (2010). A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis. New England Journal of Medicine, 362(16), 1491-1502. 174 < back to index Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Dam, T.B. van, Ijzermans, J.N.M., Weimar, W. & Baan, C.C. (2010). Characterization of Rabbit Antithymocyte Globulins-Induced CD25(+) Regulatory T Cells From Cells of Patients With End-Stage Renal Disease. Transplantation, 89(6), 655-666. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Mol, W.M., Weimar, W. & Baan, C.C. (2010). The calcineurin inhibitor tacrolimus allows the induction of functional CD4+CD25+regulatory T cells by rabbit antithymocyte globulins. Clinical & Experimental Immunology, 161(2), 364-377. Sewgobind, V.D.K.D., Quaedackers, M.E., Laan, L.J.W. van der, Kraaijeveld, R., Korevaar, S.S., Chan, G, Weimar, W. & Baan, C.C. (2010). The Jak Inhibitor CP-690,550 Preserves the Function of CD4+CD25brightFoxP3+Regulatory T Cells and Inhibits Effector T Cells. American Journal of Transplantation, 10(8), 1785-1795. Sikkema, M., Jonge, P.J.F. de, Steyerberg, E.W. & Kuipers, E.J. (2010). Risk of Esophageal Adenocarcinoma and Mortality in Patients With Barrett's Esophagus: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology, 8(3), 235-244. Sikkens, E.C.M., Cahen, D.L., Kuipers, E.J. & Bruno, M.J. (2010). Pancreatic enzyme replacement therapy in chronic pancreatitis. Best Practice & Research in Clinical Gastroenterology, 24(3), 337-347. Silva, MAS da, Tee, JM, Paridaen, J, Brouwers, A., Runtuwene, V, Zivkovic, D., Diks, SH, Guardavaccaro, D & Peppelenbosch, M.P. (2010). Essential Role for the d-Asb11 cul5 Box Domain for Proper Notch Signaling and Neural Cell Fate Decisions In Vivo. PLoS One, 5(11). Sint Nicolaas, J., Tjon, S.W.A., Metselaar, H.J., Kuipers, E.J., Man, R.A. de & Leerdam, M.E. van (2010). Colorectal Cancer in Post-Liver Transplant Recipients. Diseases of the Colon & Rectum, 53(5), 817-821. Sint Nicolaas, J., Jonge, V. de, Steyerberg, E.W., Kuipers, E.J., Leerdam, M.E. van & Zanten, SJO Veldhuyzen-van (2010). Risk of Colorectal Carcinoma in Post-Liver Transplant Patients: A Systematic Review and Meta-analysis. American Journal of Transplantation, 10(4), 868-876. Stoof, J., Kuipers, E.J. & Vliet, A.H.M. van (2010). Characterization of NikR-responsive promoters of urease and metal transport genes of Helicobacter mustelae. Biometals, 23(1), 145-159. Tapirdamaz, O., Mancham, S., Laan, L.J.W. van der, Kazemier, G., Thielemans, K., Metselaar, H.J. & Kwekkeboom, J. (2010). Detailed Kinetics of the Direct Allo-Response in Human Liver Transplant Recipients: New Insights from an Optimized Assay. PLoS One, 5(12). Tee, JM & Peppelenbosch, M.P. (2010). Anchoring skeletal muscle development and disease: the role of ankyrin repeat domain containing proteins in muscle physiology. Critical Reviews in Biochemistry and Molecular Biology, 45(4), 318-330. Teshima, C.W. & Poley, J.W. (2010). Endoscopic ultrasonography. Endoscopy, 42(11), 944-949. Teshima, C.W., Aktas, H., Haringsma, J., Kuipers, E.J. & Mensink, P.B.F. (2010). Single-balloon-assisted colonoscopy in patients with previously failed colonoscopy. Gastrointestinal Endoscopy, 71(7), 1319-1323. Tha-In, T.H., Metselaar, H.J., Bushell, AR, Kwekkeboom, J. & Wood, K.J. (2010). Intravenous Immunoglobulins Promote Skin Allograft Acceptance by Triggering Functional Activation of CD4(+)Foxp3(+) T cells. Transplantation, 89(12), 1446-1455. Tjon, S.W.A., Sint Nicolaas, J., Kwekkeboom, J., Man, R.A. de, Kazemier, G., Tilanus, H.W., Hansen, B.E., Laan, L.J.W. van der, Tha-In, T.H. & Metselaar, H.J. (2010). Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C-2 Monitoring and Recipient Age. Liver Transplantation, 16(7), 837-846. Uitdehaag, M.J., Siersema, P.D., Spaander, M.C.W., Vleggaar, F.P., Verschuur, E.M.L., Steyerberg, E.W. & Kuipers, E.J. (2010). A new fully covered stent with antimigration properties for the palliation of malignant dysphagia: a prospective cohort study. Gastrointestinal Endoscopy, 71(3), 600-605. Valkhoff, V.E., Soest, E.M. van, Sturkenboom, M.C.J.M. & Kuipers, E.J. (2010). Time-trends in gastroprotection with nonsteroidal anti-inflammatory drugs (NSAIDs). Alimentary Pharmacology & Therapeutics, 31(11), 1218-1228. Vasen, H.F.A., Abdirahman, M, Brohet, R., Langers, AMJ, Kleibeuker, JH, Kouwen, M van, Koornstra, JJ, Boot, HJ, Cats, A., Dekker, E, Sanduleanu, S, Poley, J.W., Hardwick, JCH, Cappel, WHDT, Jong, A.E. de, Tan, T.G., Jacobs, MAJM, Mohamed, FLA, Boer, SY de, Meeberg, P.C. van de, Verhulst, ML, Salemans, JM, Bentem, N Van, Westerveld, B.D., Vecht, J & Nagengast, F.M. (2010). One to 2-Year Surveillance Intervals Reduce Risk of Colorectal Cancer in Families With Lynch Syndrome. Gastroenterology, 138(7), 2300-2306. Vries, A.C. de, Haringsma, J., Vries, R.A. de, Borg, F. ter, Grieken, N.C.T. van, Meijer, G.A., Dekken, H. van & Kuipers, E.J. (2010). Biopsy Strategies for Endoscopic Surveillance of Pre-malignant Gastric Lesions. Helicobacter, 15(4), 259-264. Vries, A.C. de & Kuipers, E.J. (2010). Helicobacter pylori infection and Nonmalignant Diseases. Helicobacter, 15, 29-33. Vrolijk, J.M., Noord, D. van, Verhagen, H.J.M., Pattynama, P.M.T. & Mensink, P.B. (2010). A giant antral ulceration evoked by a rare cause of single-vessel chronic GI ischemia. Gastrointestinal Endoscopy, 72(1), 211-213. Wijkerslooth, TR de, Haan, MC de, Stoop, E.M., Deutekom, M, Fockens, P., Bossuyt, P.M.M., Thomeer, M.G.J., Ballegooijen, M. van, Essink-Bot, M.L., Leerdam, M.E. van, Kuipers, E.J., Dekker, E & Stoker, J.. (2010). Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial. BMC Gastroenterology, 10. 175 < back to index Woltman, A.M., Boonstra, P.A. & Janssen, H.L.A. (2010). Dendritic cells in chronic viral hepatitis: victims or guardian angels? Gut, 59, 115-125. Woude, C.J. van der, Stokkers, P., Bodegraven, A.A. van, Assche, G van, Hebzda, Z, Paradowski, L, D'Haens, G, Ghosh, S, Feagan, B, Rutgeerts, P, Dijkstra, G.J.J., Jong, DJ de, Oldenburg, B, Farhan, M, Richard, T, Dean, Y & Hommes, D.W. (2010). Phase I, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study of NI-0401 (a Fully Human Anti-CD3 Monoclonal Antibody) in Patients with Moderate to Severe Active Crohn's Disease. Inflammatory Bowel Diseases, 16(10), 17081716. Zee, H.H. van der, Woude, C.J. van der, Florencia, E.F.I.I.I. & Prens, E.P. (2010). Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study. British Journal of Dermatology, 162(1), 195-197. Zelinkova-Detkova, Z, Mensink, P.B.F., Dees, J., Kuipers, E.J. & Woude, C.J. van der (2010). Reproductive wish represents an important factor influencing therapeutic strategy in inflammatory bowel diseases. Scandinavian Journal of Gastroenterology, 45(1), 46-50. 176 < back to index EMC MM-04-20-02-A - Liverspecific immunopathology; mechanism and therapeutic modulation Programme in brief design The mission of the research program is to unravel the mechanisms underlying inadequate immunological reactions which lead to liver damage, and the development of effective diagnosis and treatment of these disorders. On the one hand, an insufficient immune response to hepatitis viruses causes persistence of the viruses leading to chronic hepatitis and hepatocellular carcinoma, on the other hand over-reactivity of the host immune system to antigens presented in the liver is the primary cause of hepatobiliary auto-immune diseases and of rejection after liver transplantation. The program is performed by integrated preclinical and clinical research. The pre-clinical research is focused on intra-hepatic immunological reactions between AntigenPresenting Cells and T-cells in the liver of patients. The clinical research is focused on medicinal modulation of these interactions by cytokines, anti-viral-, and immunosuppressive drugs. Cohorts of patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrosis, primary sclerosing cholangitis and vascular liver disease are the basis from which investigator-initiated randomised controlled trials are organised. Numerous global multicenter studies on antiviral therapy in chronic viral hepatitis have been coordinated by the liver group. The effects of these treatments on the intrahepatic immune reactivity are studied by sophisticated methods developed in the laboratory, such as the fine needle liver aspiration biopsy Key figures Department gastroenterology & hepatology Total SP1 11,65 11,65 SP2 0,86 0,86 SP3 SP4 0 0 9,97 9,97 Sptot 22,48 22,48 T1 T2 T3 7 0 0 Ttot 7 IS 42 FS 5 OP 5 Ptot 59 Thesis Brouw, M.L. op den (2010, maart 17). Dendritic cells in Hepatitis B virus infection: Host-pathogen interaction and immune modulation. EUR. Prom./coprom.: Prof. Dr. H.L.A. Janssen. Hansen, B.E. (2010, november 19). Statistical models of treatment effects in chronic hepatitis B and C. EUR (267 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen. Hoekstra, J. (2010, december 17). Etiology and clinical outcome of Budd-Chiari syndrome and portal vein thrombosis. EUR (179 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen & Prof. Dr. F.W.G. Leebeek. Kuiper, E.M.M. (2010, november 24). Primary biliary cirrhosis: diagnostic and therapeutic aspects. EUR (141 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen & H.R. van Buuren. Reijnders, J.G.P. (2010, november 24). Optimizing treatment strategies using nucleos(t)ide analogues for patients with chronic hepatitis. EUR (158 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen. Spaander, M.C.W. (2010, december 17). Portal vein thromobsis in non cirrhotic patients. EUR (107 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen. Vries - Sluijs, T.E.M.S. de (2010, december 01). Prevention and treatment of hepatitis B virus infection in HIV-infected patients. EUR (109 pag.). Prom./coprom.: Prof. Dr. H.L.A. Janssen, Dr. M.E. van der Ende & R.A. de Man. Artikel/Letter to the editor Aalten, S.M. van, Terkivatan, T., Man, R.A. de, Windt, D.J. van der, Kok, N.F.M., Dwarkasing, R.S. & Ijzermans, J.N.M. (2010). Diagnosis and Treatment of Hepatocellular Adenoma in the Netherlands: Similarities and Differences. Digestive Surgery, 27(1), 61-67. Bommel, F van, Man, R.A. de, Wedemeyer, H, Deterding, K, Petersen, J, Buggisch, P, Erhardt, A, Huppe, D, Stein, K, Trojan, J, Sarrazin, C, Bocher, WO, Spengler, U., Wasmuth, HE, Reinders, J.G., Moller, B, Rhode, P, Feucht, HH, Wiedenmann, B. & Berg, T (2010). Long-Term Efficacy of Tenofovir Monotherapy for Hepatitis B Virus-Monoinfected Patients After Failure of Nucleoside/Nucleotide Analogues. Hepatology, 51(1), 73-80. Bosma, B.M., Metselaar, H.J., Gerrits, J.H., Besouw, N.M. van, Mancham, S., Groothuismink, Z.M.A., Boor, P.P.C., Laan, L.J.W. van der, Tilanus, H.W., Kuipers, E.J. & Kwekkeboom, J. (2010). Migration of Allosensitizing Donor Myeloid Dendritic Cells into Recipients After Liver Transplantation. Liver Transplantation, 16(1), 12-22. Bruijne, J de, Bergmann, J.F., Reesink, H.W., Weegink, C.J., Molenkamp, R, Schinkel, J, Tong, XA, Li, J., Treitel, MA, Hughes, EA, Lier, JJ van, Vliet, AA van, Janssen, H.L.A. & Knegt, R.J. de (2010). Antiviral Activity of Narlaprevir Combined with Ritonavir and Pegylated Interferon in Chronic Hepatitis C Patients. Hepatology, 52(5), 1590-1599. Bruijne, J de, Bergmann, J.F., Weegink, C.J., Nieuwkerk, C.M.J. van, Knegt, R.J. de, Komoda, Y, Rooij, JJV de, Vliet, A. van, Jansen, P.L.M., Molenkamp, R, Schinkel, J, Reesink, H & Janssen, H.L.A. (2010). Safety and antiviral activity of JTK-652: a novel HCV infection inhibitor. Antiviral Therapy, 15(5), 765-773. Claassen, M.A.A., Knegt, R.J. de, Tilanus, H.W., Janssen, H.L.A. & Boonstra, P.A. (2010). Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. Journal of Hepatology, 52(3), 315321. Dubbeld, J, Hoekstra, H, Farid, W.R.R., Ringers, J, Porte, R.J., Metselaar, H.J., Baranski, AG, Kazemier, G., Berg, A.P van de & Hoek, B. van (2010). Similar liver transplantation survival with selected cardiac death donors and brain death donors. British Journal of Surgery, 97(5), 744-753. 177 < back to index Ginneken, B.T.J. van, Berg-Emons, H.J.G. van den, Windt, A.E. van der, Tilanus, H.W., Metselaar, H.J., Stam, H.J. & Kazemier, G. (2010). Persistent fatigue in liver transplant recipients: a two-year follow-up study. Clinical Transplantation, 24(1), E10-E16. Godeschalk, M.F.P., Mensink, P.B.F., Buuren, H.R. van & Kuipers, E.J. (2010). Primary Balloon-assisted Enteroscopy in Patients With Obscure Gastrointestinal Bleeding Findings and Outcome of Therapy. Journal of Clinical Gastroenterology, 44(9), E195-E200. Groenen, M.J.M., Buuren, H.R. van, Henegouwen, GPV, Fockens, P., Lei, J. van der, Stuifbergen, WNHM, Schaar, PJ Van der, Kuipers, E.J. & Ouwendijk, RJT (2010). Validation study of automatically generated codes in colonoscopy using the endoscopic report system Endobase (R). Scandinavian Journal of Gastroenterology, 45(9), 1121-1126. Grunfeld, J.P., Hwu, WL, Chien, YH, Lee, N., Chiang, S, Dobrovolny, R., Huang, A., Yeh, H.N., Chao, M., Lin, SB, Kitagawa, T, Desnick, R.J., Hsu, L., Keimpema, L van, Nevens, F., Vanslembrouck, R, Oijen, G. van, Hoffmann, A.L., Dekker, H., Man, R.A. de, Drenth, J., Alamovitch, S, Plaisier, E, Favrole, P, Prost, C, Chen, Z, Agrmael, T van, Marro, B, Ronco, P., Zivna, M, Hulkova, H, Matignon, M, Hodanova, K, Vylet'al, P, Kalbacova, M, Baresova, V, Sikora, J., Blazkova, H, Zivny, J, Ivanek, R, Stranecky, V, Sovova, J, Claes, K, Lerut, E, Fryns, J.-P., Hart, P., Hart, T, Adams, J., Pawtowski, A, Clemessy, M, Gasc, JM, Gubler, M, Antignac, C, Elleder, M., Kapp, K, Grimbert, P, Bleyer, A, Kmoch, S, Brown, E, Schlondorff, J, Becker, Dj, Tsukaguchi, H, Uschinki, A, Higgs, H, Henderson, J. & Pollak, M (2010). More on clinical renal genetics. Clinical Journal of the American Society of Nephrology, 5, 563-567. Gutteling, J.J., Duivenvoorden, H.J., Busschbach, J.J. van, Man, R.A. de & Darlington - Molkenboer, A.S. (2010). Psychological Determinants of Health-Related Quality of Life in Patients With Chronic Liver Disease. Psychosomatics, 51(2), 157-165. Hansen, B.E., Buster, E.H.C.J., Steyerberg, E.W., Lesaffre, E.M.E.H. & Janssen, H.L.A. (2010). Prediction of the Response to Peg-Interferon-Alfa in Patients With HBeAg Positive Chronic Hepatitis B Using Decline of HBV DNA During Treatment. Journal of Medical Virology, 82(7), 1135-1142. Hoekstra, J., Guimaraes, A.H.C., Leebeek, F.W.G., Darwish Murad, S., Malfliet, J.J.M.C., Plessier, A, Hernandez-Guerra, M, Langlet, P, Elias, E., Trebicka, J, Primignani, M., Garcia-Pagan, JC, Valla, DC, Rijken, D.C. & Janssen, H.L.A. (2010). Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome. Blood, 115(2), 388-395. Hoorn, E.J., Hoek, J. van der, Man, R.A. de, Kuipers, E.J., Bolwerk, C & Zietse, R. (2010). A Case Series of Proton Pump Inhibitor-Induced Hypomagnesemia. American Journal of Kidney Diseases, 56(1), 112-116. Koedijk, FDH, Houdt, R van, Hahne, SJM, Veldhuijzen, I.K., Man, R.A. de, Coutinho, R.A., Bruisten, S.M. & Boot, HJ (2010). Afname in meldingen van acute hepatitis B in Nederland. Nederlands Tijdschrift voor Geneeskunde, 154, 900. Komarek, A, Hansen, B.E., Kuipers, E.J., Buuren, H.R. van & Lesaffre, E.M.E.H. (2010). Discriminant analysis using a multivariate linear mixed model with a normal mixture in the random effects distribution. Statistics in Medicine, 29, 3267-3283. Kremer, AE, Martens, JJWW, Kulik, W., Rueff, F, Kuiper, E.M.M., Buuren, H.R. van, Erpecum, K.J. van, Kondrackiene, J, Prieto, J, Rust, C, Geenes, VL, Williamson, C, Moolenaar, WH, Beuers, U & Elferink, RPJO (2010). Lysophosphatidic Acid Is a Potential Mediator of Cholestatic Pruritus. Gastroenterology, 139(3), 1008-U399. Kuiper, E.M.M., Zondervan, P.E. & Buuren, H.R. van (2010). Paris Criteria Are Effective in Diagnosis of Primary Binary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome. Clinical Gastroenterology and Hepatology, 8(6), 530-534. Kuiper, E.M.M., Erpedum, KJ van, Beuers, U, Hansen, B.E., Thio, H.B., Man, R.A. de, Janssen, H.L.A. & Buuren, H.R. van (2010). The Potent Bile Acid Sequestrant Colesevelam Is Not Effective in Cholestatic Pruritus: Results of a Double-Blind, Randomized, Placebo-Controlled Trial. Hepatology, 52(4), 1334-1340. Kuiper, E.M.M., Hansen, B.E., Metselaar, H.J., Man, R.A. de, Haagsma, E.B., Hoek, B. van & Buuren, H.R. van (2010). Trends in liver transplantation for primary biliary cirrhosis in the Netherlands 1988-2008. BMC Gastroenterology, 10, 144. Laar, L. van der, Bosch, A. van den, Kooij, SW van der, Janssen, H.L.A., Coffer, P.J., Kooten, C. van & Woltman, A.M. (2010). A Nonredundant Role for Canonical NF-kappa B in Human Myeloid Dendritic Cell Development and Function. Journal of Immunology, 185(12), 7252-7261. Laar, L. van der, Buitenhuis, M, Wensveen, FM, Janssen, H.L.A., Coffer, P.J. & Woltman, A.M. (2010). Human CD34-Derived Myeloid Dendritic Cell Development Requires Intact Phosphatidylinositol 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling. Journal of Immunology, 184(12), 6600-6611. Moroso, V., Metselaar, H.J., Mancham, S., Tilanus, H.W., Eissens, D, Meer, A van der, Laan, L.J.W. van der, Kuipers, E.J., Joosten, I. & Kwekkeboom, J. (2010). Liver Grafts Contain a Unique Subset of Natural Killer Cells that Are Transferred into the Recipient After Liver Transplantation. Liver Transplantation, 16(7), 895-908. Pan, Q., Metselaar, H.J., Ruiter, P.E. de, Kwekkeboom, J., Tilanus, H.W., Janssen, H.L.A. & Laan, L.J.W. van der (2010). Calcineurin Inhibitor Tacrolimus Does Not Interfere with the Suppression of Hepatitis C Virus Infection by Interferon-alpha. Liver Transplantation, 16(4), 520-526. Plessier, A, Darwish Murad, S., Hernandez-Guerra, M, Consigny, Y, Fabris, F., Trebicka, J, Heller, J, Morard, I, Lasser, L, Langlet, P, Denninger, MH, Vidaud, D, Condat, B, Hadengue, A., Primignani, M., Garcia-Pagan, JC, Janssen, H.L.A. & Valla, D. (2010). Acute Portal Vein Thrombosis Unrelated to Cirrhosis: A Prospective Multicenter Follow-up Study. Hepatology, 51(1), 210-218. 178 < back to index Reijnders, J.G.P., Deterding, K, Petersen, J, Zoulim, F, Santantonio, T, Buti, M, Bommel, F van, Hansen, B.E., Wedemeyer, H & Janssen, H.L.A. (2010). Antiviral effect of entecavir in chronic hepatitis B: Influence of prior exposure to nucleos(t)ide analogues. Journal of Hepatology, 52(4), 493-500. Reijnders, J.G.P., Perquin, M.J., Zhang, N., Hansen, B.E. & Janssen, H.L.A. (2010). Nucleos(t)ide Analogues Only Induce Temporary Hepatitis B e Antigen Seroconversion in Most Patients With Chronic Hepatitis B. Gastroenterology, 139(2), 491-498. Rijckborst, V., Borg, M.J. ter, Cakaloglu, Y, Ferenci, P, Tabak, F, Akdogan, M, Simon, K, Raptopoulou-Gigi, M, Ormeci, N, Zondervan, P.E., Hart, E., Vuuren, A.J. van, Hansen, B.E. & Janssen, H.L.A. (2010). A Randomized Trial of Peginterferon alpha-2a With or Without Ribavirin for HBeAg-Negative Chronic Hepatitis B. American Journal of Gastroenterology, 105(8), 1762-1769. Rijckborst, V., Hansen, B.E., Cakaloglu, Y, Ferenci, P, Tabak, F, Akdogan, M, Simon, K, Akarca, US, Flisiak, R, Hart, E., Vuuren, A.J. van, Boucher, C.A.B., Borg, M.J. ter & Janssen, H.L.A. (2010). Early On-Treatment Prediction of Response to Peginterferon Alfa-2a for HBeAg-Negative Chronic Hepatitis B Using HBsAg and HBV DNA Levels. Hepatology, 52(2), 454-461. Rijckborst, V. & Janssen, H.L.A. (2010). The role of interferon in hepatitis B therapy. Current Hepatitis Reports, 9, 231-238. Roomer, R., Hansen, B.E., Janssen, H.L.A. & Knegt, R.J. de (2010). Risk Factors for Infection During Treatment with Peginterferon alfa and Ribavirin for Chronic Hepatitis C. Hepatology, 52(4), 1225-1231. Roomer, R., Hansen, B.E., Janssen, H.L.A. & Knegt, R.J. de (2010). Thrombocytopenia and the risk of bleeding during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. Journal of Hepatology, 53(3), 455-459. Schouten, J.N.L., Verheij, J. & Janssen, H.L.A. (2010). Niet-cirrotische portale hypertensie. Nederlands Tijdschrift voor Geneeskunde, 154, 1276. Schramm, C, Bubenheim, M, Adam, R, Karam, V, Buckels, J, O'Grady, JG, Jamieson, N, Pollard, S, Neuhaus, P, Manns, MM, Porte, R., Castaing, D, Paul, A, Traynor, O, Garden, J, Friman, S, Ericzon, BG, Fischer, L., Vitko, S., Krawczyk, M, Metselaar, H.J., Foss, A, Kilic, Murat, Rolles, K, Burra, P., Rogiers, X & Lohse, AW (2010). Primary Liver Transplantation for Autoimmune Hepatitis: A Comparative Analysis of the European Liver Transplant Registry. Liver Transplantation, 16(4), 461-469. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Dam, T.B. van, Ijzermans, J.N.M., Weimar, W. & Baan, C.C. (2010). Characterization of Rabbit Antithymocyte Globulins-Induced CD25(+) Regulatory T Cells From Cells of Patients With End-Stage Renal Disease. Transplantation, 89(6), 655-666. Sint Nicolaas, J., Tjon, S.W.A., Metselaar, H.J., Kuipers, E.J., Man, R.A. de & Leerdam, M.E. van (2010). Colorectal Cancer in Post-Liver Transplant Recipients. Diseases of the Colon & Rectum, 53(5), 817-821. Sneitz, N, Bakker, CT, Knegt, R.J. de, Halley, D.J.J., Finel, M & Bosma, P.J. (2010). Crigler-Naijar Syndrome in The Netherlands: Identification of Four Novel UGT1A1 Alleles, Genotype-Phenotype Correlation, and Functional Analysis of 10 Missense Mutants. Human Mutation, 31(1), 52-59. Sonneveld, M.J., Rijckborst, V., Boucher, C.A.B., Hansen, B.E. & Janssen, H.L.A. (2010). Prediction of Sustained Response to Peginterferon Alfa-2b for Hepatitis B e Antigen Positive Chronic Hepatitis B Using On-Treatment Hepatitis B Surface Antigen Decline. Hepatology, 52(4), 1251-1257. Sonneveld, M.J. & Janssen, H.L.A. (2010). Pros and cons of peg-interferon versus nucleos(t)ide analogues for treatment of chronic hepatitis B. Current Hepatitis Reports, 9, 91-98. Spaander, V.M.C.W., Buuren, H.R. van, Hansen, B.E. & Janssen, H.L.A. (2010). Ascites in patients with noncirrhotic nonmalignant extrahepatic portal vein thrombosis. Alimentary Pharmacology & Therapeutics, 32(4), 529-534. Tha-In, T.H., Metselaar, H.J., Bushell, AR, Kwekkeboom, J. & Wood, K.J. (2010). Intravenous Immunoglobulins Promote Skin Allograft Acceptance by Triggering Functional Activation of CD4(+)Foxp3(+) T cells. Transplantation, 89(12), 1446-1455. Tjon, S.W.A., Sint Nicolaas, J., Kwekkeboom, J., Man, R.A. de, Kazemier, G., Tilanus, H.W., Hansen, B.E., Laan, L.J.W. van der, Tha-In, T.H. & Metselaar, H.J. (2010). Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C-2 Monitoring and Recipient Age. Liver Transplantation, 16(7), 837-846. Toorenenbergen, A.W. van, Heerde, M.J. van & Buuren, H.R. van (2010). Potential Value of Serum Total IgE for Differentiation between Autoimmune Pancreatitis and Pancreatic Cancer. Scandinavian Journal of Immunology, 72(5), 444-448. Veldhuijzen, I.K., Toy, M., Hahne, SJM, Wit, G.A. de, Schalm, S.W., Man, R.A. de & Richardus, J.H. (2010). Screening and Early Treatment of Migrants for Chronic Hepatitis B Virus Infection Is Cost-Effective. Gastroenterology, 138(2), 522-530. Vries - Sluijs, T.E.M.S. de, Reijnders, J.G.P., Hansen, B.E., Zaaijer, H.L, Prins, J.M., Pas, S.D., Schutten, M., Hoepelman, A.I.M., Richter, C., Mulder, J.W., Man, R.A. de, Janssen, H.L.A. & Ende, M.E. van der (2010). Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus. Gastroenterology, 139(6), 1934-1941. Woltman, A.M., Boonstra, P.A. & Janssen, H.L.A. (2010). Dendritic cells in chronic viral hepatitis: victims or guardian angels? Gut, 59, 115-125. Part of book - abstract 179 < back to index Buuren, H.R. van (2010). Primaire biliaire cirrose. In Cursus Klinische Hepatologie (pp. 57-62). Amsterdam: Nederlandse vereniging voor hepatologie. Janssen, H.L.A. & Zoutendijk, R. (2010). HBV, huidige standaardbehandeling. In Cursus Klinische Hepatologie, (pp. 87-92). Amsterdam: Nederlandse vereniging voor hepatologie. Janssen, H.L.A. & Buuren, H.R. van (2010). Ziekten van lever en galwegen. In J. van der Meer, CDA Stedehouwer & RP Koopmans (Eds.), Leerboek interne geneeskunde (pp. 717-768). Houten: Bohn Stafleu van Loghum. Metselaar, H.J. (2010). Indicatie, selectie en prioritering voor levertransplantaties. In Cursus Klinische Hepatologie, (pp. 99-102). Amsterdam: Nederlandse vereniging voor hepatologie. Roomer, R. & Knegt, R.J. de (2010). HCV, huidige standaardbehandeling. In Cursus Klinische Hepatologie (pp. 79-86). Amsterdam: Nederlandse vereniging voor hepatologie. 180 < back to index EMC MM-04-27-01 - Human virus infections: immunity, therapy and epidemiology Programme in brief design The role of virus specific immune responses in the (immune) pathogenesis of, and protection against virus infections is studied in humans and in animal models for human virus infections. Special attention is paid to infections with morbilli-, lenti-, herpes-, influenza- and hepatitis viruses. The role of virus specific antibodies in neutralization and/or enhancement of virus infectivity and the kinetics of the emergence of these antibodies, is subject of study in different systems. Similarly, also the evaluation of the role of virus specific T helper- and cytotoxic T cells is carried out. The knowledge generated in this way is used to design novel strategies of intervention in viral spreading and pathogenesis, like e.g. vaccination, diagnosis and post-exposure treatment. In this framework novel antiviral therapeutic strategies , based on immunological and non-immunological principles, are also developed. Finally, epidemilogical research questions, related to infections with the aforemeentioned viruses and "exotic" viruses, are adressed. Besides the continuation of the above mentioned activities, studies concerning the epidemiology and epizootiology of influenza viruses of man and animals will be extended in the next year, with a special emphasis on possibly emerging influenza pandemics. Research concerning the possible development of an HIV vaccine based on the use of Rev and Tat will be intensified. This will also be the case for research concerning the immunopathogenesis of chronic infections with HBV, HCV, EBV, CMV and HIV, with special attention for problems with multiple infections and infections in immunocompromised and transplantation patients. Finally, a focus will be on virus infections if wild and threatened animal species as well as exotic and zoonotic virus infections. Morbillivirus, lentivirus, herpesvirus, hepatitis virus, pathogenesis, immunopathogenesis, neutralizing antibody, enhancement, cytotoxic T cell, T cell phenotype, antiviral, epidemiology, zoonosis Key figures Department internal medecine pharmacy virology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,75 0 0 0 0,75 0,5 0 0 0 0,5 18,9 26,11 2,25 2,99 50,25 20,15 26,11 2,25 2,99 51,5 2 1 1 4 84 5 1 94 Thesis Keawcharoen, J.. Highly pathogenic avian influenza A (H5N1) virus in wildlife. Universiteit van Utrecht. Prom./coprom.: Prof. Dr. A.D.M.E. Osterhaus. Riel, D.A.J. van (2010, september 23). "A critical role of cell tropism for the pathogenesis of influenza". EUR. Prom./coprom.: Prof. Dr. T. Kuiken & Prof. Dr. A.D.M.E. Osterhaus. Siebenga, J.J. (2010, november 17). Towards a study of norovirus molecular epidemiology. EUR. Prom./coprom.: Prof. Dr. M.P.G. Koopmans. Wijngaard, C.C. van der (2010, december 09). Is this an outbreak? A retrospecitve evaluation of syndromic surveillance for emerging infectious disease. EUR. Prom./coprom.: Prof. Dr. M.P.G. Koopmans. Artikel/Letter to the editor Aardema, H., Tulleken, JE, Biggelaar, RJ van den, Wolters, BA, Jager, CM de, Boucher, C.A.B. & Riezebos-Brilman, A (2010). Fatal pneumonitis due to oseltamivir-resistant new influenza A(H1N1) in het case of an intensive care patient. Nederlands Tijdschrift voor Geneeskunde, 154, 1634. Alsio, A, Christensen, P.B., Farkkila, M, Langeland, N, Buhl, MR, Pedersen, C, Morch, K, Haagmans, B.L., Westin, J, Hellstrand, K, Norkrans, G & Lagging, M (2010). Nonresponder Patients with Hepatitis C Virus Genotype 2/3 Infection: A Question of Low Systemic Interferon Concentrations? Clinical Infectious Diseases, 50(4), E22-E25. Anderson, T, Capua, I, Dauphin, G, Donis, R, Fouchier, R.A.M., Mumford, E, Peiris, M, Swayne, D & Thiermann, A (2010). FAO-OIE-WHO Joint Technical Consultation on Avian Influenza at the Human-Animal Interface. INFLUENZA AND OTHER RESPIRATORY VIRUSES, 4, 1-29. Bezemer, D., Sighem, A. van, Lukashov, V.V., Hoek, L. van den, Back, N., Schuurman, R., Boucher, C.A.B., Claas, E.C.J., Boerlijst, M.C., Coutinho, R.A., Wolf, F. de & ATHENA study group, - (2010). Transmission networks of HIV-1 among men having sex with men in the Netherlands. Aids, 24, 271-282. Bodewes, R., Kreijtz, J.H.C.M., Amerongen, G. van, Geelhoed-Mieras, M.M., Verburgh, R.J., Heldens, JGM, Bedwell, J, Brand, J.M.A. van den, Kuiken, T., Baalen, C.A. van, Fouchier, R.A.M., Osterhaus, A.D.M.E. & Rimmelzwaan, G.F. (2010). A Single Immunization with CoVaccine HT-Adjuvanted H5N1 Influenza Virus Vaccine Induces Protective Cellular and Humoral Immune Responses in Ferrets. Journal of Virology, 84(16), 7943-7952. Bodewes, R., Rimmelzwaan, G.F. & Osterhaus, A.D.M.E. (2010). Animal models for the preclinical evaluation of candidate influenza vaccines. Expert Review of Vaccines, 9(1), 59-72. Bodewes, R., Osterhaus, A.D.M.E. & Rimmelzwaan, G.F. (2010). Targets for the Induction of Protective Immunity Against Influenza A Viruses. VIRUSES-BASEL, 2(1), 166-188. 181 < back to index Bodewes, R., Kreijtz, J.H.C.M., Hillaire, M.L.B., Geelhoed-Mieras, M.M., Fouchier, R.A.M., Osterhaus, A.D.M.E. & Rimmelzwaan, G.F. (2010). Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8(+) T-cell responses in mice. Journal of General Virology, 91, 1743-1753. 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European Journal of Clinical Microbiology & Infectious Diseases, 29(6), 677-682. Svraka, S., Vennema, H., Veer, B. ter, Hedlund, KO, Thorhagen, M, Siebenga, J.J., Duizer, E & Koopmans, M. (2010). Epidemiology and Genotype Analysis of Emerging Sapovirus-Associated Infections across Europe. Journal of Clinical Microbiology, 48(6), 2191-2198. Svraka, S., Rosario, K, Duizer, E, Avoort, H van der, Breitbart, M & Koopmans, M. (2010). Metagenomic sequencing for virus identification in a public-health setting. Journal of General Virology, 91, 2846-2856. Vijver, D.A.M.C. van de & Boucher, C.A.B. (2010). The risk of HIV drug resistance following implementation of pre-exposure prophylaxis. Current Opinion in Infectious Diseases, 23(6), 621-627. Vries, E. van der, Stelma, F.F. & Boucher, C.A.B. (2010). Emergence of a Multidrug-Resistant Pandemic Influenza A (H1N1) Virus. New England Journal of Medicine, 363(14), 1381-1382. Vries, E. van der, Jonges, M., Herfst, S., Maaskant, J., Linden, A. van der, Guldemeester, J., Aron, GI, Bestebroer, T.M., Koopmans, M., Meijer, A., Fouchier, R.A.M., Osterhaus, A.D.M.E., Boucher, C.A.B. & Schutten, M. (2010). Evaluation of a rapid molecular algorithm for detection of pandemic influenza A (H1N1) 2009 virus and screening for a key oseltamivir resistance (H275Y) substitution in neuraminidase. Journal of Clinical Virology, 47(1), 34-37. Vries, E. van der & Schutten, M. (2010). Satisfying the need for rapid diagnosis of new variant influenza A H1N1. Expert Review of Molecular Diagnosis, 10(3), 251-253. Vries, R.D. de, Lemon, K, Ludlow, M., McQuaid, S, Yuksel, S., Amerongen, G. van, Rennick, LJ, Rima, BK, Osterhaus, A.D.M.E., Swart, R.L. de & Duprex, WP (2010). In Vivo Tropism of Attenuated and Pathogenic Measles Virus Expressing Green Fluorescent Protein in Macaques. Journal of Virology, 84(9), 4714-4724. Vries, R.D. de, Yuksel, S., Osterhaus, A.D.M.E. & Swart, R.L. de (2010). Specific CD8(+) T-lymphocytes control dissemination of measles virus. European Journal of Immunology, 40(2), 388-395. Vries - Sluijs, T.E.M.S. de, Reijnders, J.G.P., Hansen, B.E., Zaaijer, H.L, Prins, J.M., Pas, S.D., Schutten, M., Hoepelman, A.I.M., Richter, C., Mulder, J.W., Man, R.A. de, Janssen, H.L.A. & Ende, M.E. van der (2010). Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus. Gastroenterology, 139(6), 1934-1941. Wildschut, E.D., Hoog, M. de, Ahsman, M.J., Tibboel, D., Osterhaus, A.D.M.E. & Fraaij, P.L.A. (2010). Plasma concentrations of oseltamivir and oseltamivir corboxylate in critically ill children on extracorporeal membrane oxygenation support. PLoS One, 5(6), e10938. 185 < back to index Wit, E. de, Munster, V.J., Riel, D.A.J. van, Beyer, W.E.P., Rimmelzwaan, G.F., Kuiken, T., Osterhaus, A.D.M.E. & Fouchier, R.A.M. (2010). Molecular Determinants of Adaptation of Highly Pathogenic Avian Influenza H7N7 Viruses to Efficient Replication in the Human Host. Journal of Virology, 84(3), 1597-1606. Ye, JQ, Shao, HX, Hickman, D, Angel, M, Xu, KM, Cai, YB, Song, HC, Fouchier, R.A.M., Qin, AJ & Perez, DR (2010). Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice. Clinical and Vaccine Immunology, 17(9), 1363-1370. 186 < back to index EMC MM-04-28-01 - Infections due to bacteria, fungi and parasites: diagnosis, molecular mechanisms, epidemiology, therapy and prevention Programme in brief design The project is focused on the infectious complications caused by bacteria, fungi and parasites related to recent developments in clinical medicine, such as new therapeutic modalities or resistance, an increased use of medical devices, frequent diagnostic and therapeutic intervention, and an increasing number of immunocompromised patients. As a consequence, a growing number of patients are prone to severe (nosocomial) infections that are often difficult to treat. These infections are a major cause of morbidity and mortality in these patients, which is partially enforced by failure of antibiotic treatment despite the availability of potent antibiotics. The focus of this programme is on the molecular mechanism of infection, the epidemiology, the early diagnosis using molecular techniques, the preven¬tion of infections, as well as treatment using alternative methods. The approach is partly fundamental/animal-experimental and partly clinical/epidemiological. Key figures Department clinical microbiology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 7,42 3,99 0 0,85 12,26 7,42 3,99 0 0,85 12,26 5 0 0 5 56 8 5 74 Thesis Islam, Z. (2010, september 01). Campylobacter infection and Guillain-Barré syndrome in Bangladesh: Clinical epidemiology and comparative microbial genomics. EUR. Prom./coprom.: Prof. Dr. H.P. Endtz, Prof. Dr. A. van Belkum & Dr. B.C. Jacobs. Khan, M.A. (2010, maart 17). Antimicrobial resistance spread and the role of mobile genetic elements. EUR (143 pag.). Prom./coprom.: Prof. Dr. A. van Belkum & Dr. J.P. Hays. Rours, G.I.J.G. (2010, juni 11). Chlamydia trachomatis. Infections during pregnancy. EUR (208 pag.) (Rotterdam: Haveka BV). Prom./coprom.: Prof. Dr. H.A. Verbrugh, Prof.Dr. R. de Groot & Dr. R.P.A.J. Verkooijen. Slobbe, L. (2010, juni 16). Infectious complications in hematology patients: a clinical focus on prevention. EUR (169 pag.). Prom./coprom.: Prof. Dr. H.A. Verbrugh, Dr. B.J.A. Rijnders & Dr. J.K. Doorduijn. Verkaik, N.J. (2010, oktober 07). The human antibody response to Staphylococcus aureus in colonization and infection. EUR (128 pag.). Prom./coprom.: Prof. Dr. A. van Belkum & Dr. W.J.B. van Wamel. Artikel/Letter to the editor Ang, C.W., Dijkstra, J.R., Klerk, M.A. de, Endtz, H.P., Doorn, P.A. van, Jacobs, B.C., Jeurissen, S.H.M. & Wagenaar, J.A. (2010). Host Factors Determine Anti-GM1 Response Following Oral Challenge of Chickens with Guillain-Barre Syndrome Derived Campylobacter jejuni Strain GB11. PLoS One, 5(3). Been, J.V., Rours, G.I.J.G., Kornelisse, R.F., Jonkers, F., Krijger, R.R. de & Zimmermann, L.J.I. (2010). Chorioamnionitis alters the response to surfactant in preterm infants. Journal of Pediatrics, 156, 10-15. Bode, L.G.M., Kluytmans, J.A.J.W., Wertheim, H.F.L., Bogaers, D, Vandenbroucke-Grauls, C.M.J.E., Roosendaal, R., Troelstra, A., Box, ATA, Voss, A., Tweel, I. van der, Belkum, A. van, Verbrugh, H.A. & Vos, M. (2010). Preventing Surgical-Site Infections in Nasal Carriers of Staphylococcus aureus. New England Journal of Medicine, 362(1), 9-17. Budding, AE, Vandenbroucke-Grauls, C.M.J.E., Melles, D.C., Duijkeren, E van, Kluytmans, JA & Savelkoul, PHM (2010). Binary IS Typing for Staphylococcus aureus. PLoS One, 5(10). Buijtels, P.C.A.M., Sande, MAB van der, Parkinson, S, Verbrugh, H.A., Petit, P.L.C. & Soolingen, D. van (2010). Isolation of non-tuberculous mycobacteria at three rural settings in Zambia; a pilot study. Clinical Microbiology and Infection, 16(8), 11421148. Chai, LYA, Veerdonk, F van de, Marijnissen, RJ, Cheng, SC, Khoo, AL, Hectors, M, Lagrou, K, Vonk, A.G., Maertens, J., Joosten, LAB, Kullberg, B.J. & Netea, MG (2010). Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology, 130(1), 46-54. Chai, LYA, Netea, MG, Sugui, J, Vonk, A.G., Sande, W.W.J. van de, Warris, A., Kwon-Chung, KJ & Kullberg, B.J. (2010). Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response. Immunobiology, 215(11), 915-920. Chai, LYA, Netea, MG, Teerenstra, S, Earnest, A, Vonk, A.G., Schlamm, HT, Herbrecht, R., Troke, PF & Kullberg, B.J. (2010). Early Proinflammatory Cytokines and C-Reactive Protein Trends as Predictors of Outcome in Invasive Aspergillosis. Journal of Infectuous Diseases, 202(9), 1454-1462. Duijkeren, E van, Moleman, M, Oldruitenborgh-Oosterbaan, MMS van, Multem, J, Troelstra, A., Fluit, AC, Wamel, W.J.B. van, Houwers, DJ, Neeling, A.J. de & Wagenaar, J.A. (2010). Methicillin-resistant Staphylococcus aureus in horses and horse personnel: An investigation of several outbreaks. Veterinary Microbiology, 141(1-2), 96-102. Erasmus, V., Kuperus, M.N., Richardus, J.H., Vos, M.C., Oenema, A. & Beeck, E.F. van (2010). Improving hand hygiene behaviour of nurses using action planning: a pilot study in the intensive care unit and surgical ward. Journal of Hospital Infection, 76(2), 161-164. 187 < back to index Erasmus, V., Daha, TJ, Brug, J., Richardus, J.H., Behrendt, M.D. & Vos, M. (2010). Systematic Review of Studies on Compliance with Hand Hygiene Guidelines in Hospital Care. Infection Control & Hospital Epidemiology, 31(3), 283-294. Ghaznavi-Rad, E, Shamsudin, MN, Sekawi, Z, Belkum, A. van & Neela, V (2010). A simplified multiplex PCR assay for fast and easy discrimination of globally distributed staphylococcal cassette chromosome mec types in meticillin-resistant Staphylococcus aureus. Journal of Medical Microbiology, 59(10), 1135-1139. Ghaznavi-Rad, E, Ghasemzadeh-Moghaddam, H, Shamsudin, MN, Hamat, RA, Sekawi, Z, Aziz, MN, Tavakol, M., Belkum, A. van & Neela, V (2010). Environmental Contamination in the Hospital as a Possible Source for Nosocomial Infection with Methicillin-Resistant Staphylococcus aureus. Infection Control & Hospital Epidemiology, 31(12), 1302-1303. Ghaznavi-Rad, E, Shamsudin, MN, Sekawi, Z, Khoon, LY, Aziz, MN, Hamat, RA, Othman, N, Chong, PP, Belkum, A. van, Ghasemzadeh-Moghaddam, H & Neela, V (2010). Predominance and Emergence of Clones of Hospital-Acquired MethicillinResistant Staphylococcus aureus in Malaysia. Journal of Clinical Microbiology, 48(3), 867-872. Haar, N.M. van der, Gotz, H.M., Goessens, W.H.F. & Snoek, E.M. van der (2010). Atypische, ulcertieve presentatie syfilis. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20, 686-689. Heikema, A.P., Bergman, M.P., Richards, H, Crocker, P.R., Gilbert, M., Samsom, J.N., Wamel, W.J.B. van, Endtz, H.P. & Belkum, A. van (2010). Characterization of the specific interaction between Sialoadhesin and Sialylated Campylobacter jejuni lipoologosaccharides. Infection & Immunity, 78(7), 3237-3246. Hellemond, J.J. van & Genderen, P.J.J. van (2010). Apenmalaria in Nederland bij een reiziger uit Maleisië. Nederlands Tijdschrift voor Geneeskunde, 154, 1353. Hira, V., Sluijter, M., Goessens, W.H.F., Ott, A., Groot, R. de, Hermans, P.W.M. & Kornelisse, R.F. (2010). Coagulase-negative Staphylococcal skin carriage among neonatal intensive care unit personnel: from population to infection. Journal of Clinical Microbiology, 48(11), 3876-3881. Islam, Z., Jacobs, B.C., Belkum, A. van, Mohammad, QD, Islam, MB, Herbrink, P., Diorditsa, S, Luby, SP, Talukder, KA & Endtz, H.P. (2010). Axonal variant of Guillain-Barre syndrome associated with Campylobacter infection in Bangladesh. Neurology, 74(7), 581-587. Islam, Z., Mohammad, QD, Endtz, H.P., Jacobs, B.C. & Belkum, A. van (2010). AXONAL VARIANT OF GUILLAIN-BARRE SYNDROME ASSOCIATED WITH CAMPYLOBACTER INFECTION IN BANGLADESH Reply. Neurology, 75(2), 194-195. Jongste, A.H.C. de, Tilanus, A.M.R., Bax, H, Willems, M.H.A., Feltz, M. van der & Hellemond, J.J. van (2010). New insights in diagnosing Schistosoma myelopathy. Journal of Infection, 60(3), 244-247. Kaan, J.A., Troelstra, A. & Vos, M.C. (2010). Opleiding tot ziekenhuishygiënist. Nederlands Tijdschrift voor Medische Microbiologie, 18, 27-28. Khan, M.A., Northwood, JB, Levy, F., Verhaegh, S.J.C., Farrell, DJ, Belkum, A. van & Hays, J.P. (2010). bro beta-lactamase and antibiotic resistances in a global cross-sectional study of Moraxella catarrhalis from children and adults. Journal of Antimicrobial Chemotherapy, 65(1), 91-97. Khan, M.A., Northwood, JB, Loor, R.G.J., Tholen, A.T.R., Riera, E, Falcon, M, Belkum, A. van, Westreenen, M. van & Hays, J.P. (2010). High prevalence of ST-78 infection-associated vancomycin-resistant Enterococcus faecium from hospitals in Asuncion, Paraguay. Clinical Microbiology and Infection, 16(6), 624-627. Klein, J.., Huisman, I, Menon, A.G., Leenders, C.M., Eeghem, K.H.A. van, Vos, M.C. & Dorresteijn, J.J. (2010). Postoperatieve infectie door gecontamineerde propofol. Nederlands Tijdschrift voor Geneeskunde, 154, 234-236. Kuhn, G, Koessler, T, Melles, D.C., Francois, P, Huyghe, A, Dunman, P, Vos, M., Zanetti, G, Schrenzel, J, Belkum, A. van & Blanc, D.S. (2010). Comparative genomics of epidemic versus sporadic Staphylococcus aureus strains does not reveal molecular markers for epidemicity. Infection, Genetics and Evolution, 10(1), 89-96. Kuijf, M.L., Samsom, J.N., Rijs, W. van, Bax, M., Huizinga, R, Heikema, A.P., Doorn, P.A. van, Belkum, A. van, Kooyk, Y. van, Burgers, P.C., Luider, T.M., Endtz, H.P., Nieuwenhuis, E.E.S. & Jacobs, B.C. (2010). TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation. Journal of Immunology, 185, 748-755. Lebon, A., Moll, H.A., Tavakol, M., Wamel, W.J.B. van, Jaddoe, V.W.V.K., Hofman, A., Verbrugh, H.A. & Belkum, A. van (2010). Correlation of bacterial colonization status between mother and child: the Generation R Study. Journal of Clinical Microbiology, 48(3), 960-962. Lestari, ES, Duerink, DO, Hadi, U, Severin, J.A., Nagelkerke, N.J.D., Kuntaman, K, Wahjono, H, Gardjito, W, Soejoenoes, A, Broek, P.J.. van den, Keuter, M., Gyssens, IC & Verbrugh, H.A. (2010). Determinants of carriage of resistant Staphylococcus aureus among S. aureus carriers in the Indonesian population inside and outside hospitals. Tropical Medicine and International Health, 15(10), 1235-1243. Menezes, G.A., Khan, M.A. & Hays, J.P. (2010). Important methodological considerations with respect to differentiation of CTXM-15 and CTX-M-28 extended-spectrum beta-lactamases. Indian Journal of Medical Microbiology, 28, 81-82. Menezes, G.A., Khan, M.A., Harish, BN, Parija, SC, Goessens, W.H.F., Vidyalakshmi, K, Baliga, S. & Hays, J.P. (2010). Molecular characterization of antimicrobial resistance in non-typhoidal salmonellae associated with systemic manifestations from India. Journal of Medical Microbiology, 59, 1477-1483. 188 < back to index Mollema, F.P.N., Severin, J.A., Nouwen, J.L., Ott, A., Verbrugh, H.A. & Vos, M. (2010). Successful Treatment for Carriage of Methicillin-Resistant Staphylococcus aureus and Importance of Follow-Up. Antimicrobial Agents & Chemotherapy, 54(9), 40204025. Mollema, F.P.N., Richardus, J.H., Behrendt, M.D., Vaessen, N., Lodder, W, Hendriks, W., Verbrugh, H.A. & Vos, M. (2010). Transmission of Methicillin-Resistant Staphylococcus aureus to Household Contacts. Journal of Clinical Microbiology, 48(1), 202-207. Muller, A.E., Huisman, I, Roos, P.J., Rietveld, A.P., Klein, J., Harbers, JBM, Dorresteijn, J.J., Steenbergen, J.E. van & Vos, M. (2010). Outbreak of severe sepsis due to contaminated propofol: lessons to learn. Journal of Hospital Infection, 76(3), 225-230. Muller, A.E., Mouton, J.W., Oostvogel, P.M., Dorr, PJ, Voskuyl, RA, DeJongh, J, Steegers, E.A.P. & Danhof, M (2010). Pharmacokinetics of Clindamycin in Pregnant Women in the Peripartum Period. Antimicrobial Agents & Chemotherapy, 54(5), 2175-2181. Neela, V, Moghaddam, HG, Belkum, A. van, Horst-Kreft, D.E., Mariana, NS & Rad, EG (2010). First report on methicillinresistant Staphylococcus aureus of Spa type T037, Sequence type 239, SCCmec type III/IIIA in Malaysia. European Journal of Clinical Microbiology & Infectious Diseases, 29(1), 115-117. Ruimy, R, Angebault, C, Djossou, F, Dupont, C., Epelboin, L, Jarraud, S, Lefevre, LA, Bes, M, Lixandru, BE, Bertine, M, Miniai, A El, Renard, M, Bettinger, RM, Lescat, M, Clermont, O, Peroz, G, Lina, G, Tavakol, M., Vandenesch, F, Belkum, A. van, Rousset, F & Andremont, A (2010). Are Host Genetics the Predominant Determinant of Persistent Nasal Staphylococcus aureus Carriage in Humans? Journal of Infectuous Diseases, 202(6), 924-934. Sande, W.W.J. van de, Fahal, A.H., Bakker-Woudenberg, I.A.J.M. & Belkum, A. van (2010). Madurella mycetomatis Is Not Susceptible to the Echinocandin Class of Antifungal Agents. Antimicrobial Agents & Chemotherapy, 54(6), 2738-2740. Sande, W.W.J. van de, Lo-Ten-Foe, JR, Belkum, A. van, Netea, MG, Kullberg, B.J. & Vonk, A.G. (2010). Mycoviruses: future therapeutic agents of invasive fungal infections in humans? European Journal of Clinical Microbiology & Infectious Diseases, 29(7), 755-763. Sande, W.W.J. van de, Fahal, A., Tavakol, M. & Belkum, A. van (2010). Polymorphisms in catechol-O-methyltransferase and cytochrome p450 subfamily 19 genes predispose towards Madurella mycetomatis-induced mycetoma susceptibility. Medical Mycology, 48(7), 959-968. Sande, W.W.J. van de, Tavakol, M., Vianen, W. van & Bakker-Woudenberg, I.A.J.M. (2010). The effects of antifungal agents to conidial and hyphal forms of Aspergillus fumigatus. Medical Mycology, 48(1), 48-55. Severin, J.A. & Lestari, ES (2010). Antimicrobial resistance in Indonesia: prevalence, determinants and genetic basis. Medicus Tropicus Bulletin of the Netherlands Society for Tropical Medicine & International Health, 48, 3-4. Severin, J.A., Mertaniasih, NM, Kuntaman, K, Lestari, ES, Purwanta, M, Toom, N Lemmens-den, Duerink, DO, Hadi, U, Belkum, A. van, Verbrugh, H.A. & Goessens, W.H.F. (2010). Molecular characterization of extended-spectrum beta-lactamases in clinical Escherichia coli and Klebsiella pneumoniae isolates from Surabaya, Indonesia. Journal of Antimicrobial Chemotherapy, 65(3), 465-469. Severin, J.A., Lestari, ES, Kuntaman, K, Pastink, M, Snijders, S.V., Toom, N Lemmens-den, Horst-Kreft, D.E., Hadi, U, Duerink, DO, Goessens, W.H.F., Fluit, AC, Wamel, W.J.B. van, Belkum, A. van & Verbrugh, H.A. (2010). Nasal Carriage of MethicillinResistant and Methicillin-Sensitive Strains of Staphylococcus sciuri in the Indonesian Population. Antimicrobial Agents & Chemotherapy, 54(12), 5413-5417. Severin, J.A. & Lestari, ES (2010). Antimicrobiële resistentie in Indonesië: prevalentie, determinanten en genetische basis. Nederlands Tijdschrift voor Medische Microbiologie, 18, 39-40. Slobbe, L., Doorduijn, J.K., Lugtenburg, P.J., Barzouhi, A el, Boersma, E., Leeuwen, W.B. van & Rijnders, B.J.A. (2010). Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial. PLoS One, 5(5). Steenwinkel, J.E.M. de, Knegt, G.J. de, Kate, M.T. ten, Belkum, A. van, Verbrugh, H.A., Kremer, K., Soolingen, D. van & Bakker-Woudenberg, I.A.J.M. (2010). Time-kill kinetics of anti-tuberculosis drugs, and emergence of resistance, in relation to metabolic activity of Mycobacterium tuberculosis. Journal of Antimicrobial Chemotherapy, 65(12), 2582-2589. Tiel, FH van, Buiting, A.G.M., Meessen, N.E.L., Voss, A. & Vos, M.C. (2010). Is ultraschone lucht in de operatiekamer zorgen voor een grotere veiligheid? Nederlands Tijdschrift voor Geneeskunde, 154, 1598. Tielens, A.G.M., Grinsven, KWA van, Henze, K, Hellemond, J.J. van & Martin, W. (2010). Acetate formation in the energy metabolism of parasitic helminths and protists. International Journal for Parasitology, 40(4), 387-397. Tims, S., Wamel, W.J.B. van, Endtz, H.P., Belkum, A. van & Kayser, M. (2010). Microbial DNA fingerprinting of human fingerprints: dynamic colonization of fingertip microflora challenges human host inferences for forensic purposes. International Journal of Legal Medicine, 124(5), 477-481. Trijp, M.J.C.A. van, Melles, D.C., Snijders, S.V., Wertheim, H.F.L., Verbrugh, H.A., Belkum, A. van & Wamel, W.J.B. van (2010). Genotypes, superantigen gene profiles, and presence of exfoliative toxin genes in clinical methicillin-susceptible Staphylococcus aureus isolates. Diagnostic Microbiology & Infectious Disease, 66(2), 222-224. 189 < back to index Verhaegh, S.J.C., Lebon, A., Saarloos, J.A., Verbrugh, H.A., Jaddoe, V.W.V.K., Hofman, A., Hays, J.P., Moll, H.A. & Belkum, A. van (2010). Determinants of Moraxella catarrhalis colonization in healthy Dutch children during the first 14 months of life. Clinical Microbiology and Infection, 16(7), 992-997. Verkaik, N.J., Boelens, H.A.M., Vogel, C.P. de, Tavakol, M., Bode, L.G.M., Verbrugh, H.A. & Belkum, A. van (2010). Heterogeneity of the humoral immune response following Staphylococcus aureus bacteremia. European Journal of Clinical Microbiology & Infectious Diseases, 29(5), 509-518. Verkaik, N.J., Dauwalder, O, Antri, K, Boubekri, I, Vogel, C.P. de, Badiou, C, Bes, M, Vandenesch, F, Tazir, M, Hooijkaas, H., Verbrugh, H.A., Belkum, A. van, Etienne, J., Lina, G, Ramdani-Bouguessa, N & Wamel, W.J.B. van (2010). Immunogenicity of Toxins during Staphylococcus aureus Infection. Clinical Infectious Diseases, 50(1), 61-68. Verkaik, N.J., Lebon, A., Vogel, C.P. de, Hooijkaas, H., Verbrugh, H.A., Jaddoe, V.W.V.K., Hofman, A., Moll, H.A., Belkum, A. van & Wamel, W.J.B. van (2010). Induction of antibodies by Staphylococcus aureus nasal colonization in young children. Clinical Microbiology and Infection, 16(8), 1312-1317. Verkaik, N.J., Wamel, W.J.B. van & Belkum, A. van (2010). De humane antilichaamrespons tegen Staphylococcus aureus tijdens kolonisatie en infectie. Nederlands Tijdschrift voor Medische Microbiologie, 18, 38-39. Vries, SPW de, Hijum, SAFT van, Schueler, W, Riesbeck, K, Hays, J.P., Hermans, P.W.M. & Bootsma, H.J. (2010). Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen. Journal of Bacteriology, 192(14), 35743583. Waalboer, R., Steenwinkel, J.E.M. de, Biemans, A.A.M. & Thio, H.B. (2010). Cutane scedosporiose. Nederlands Tijdschrift voor Dermatologie & Venereologie, 20(9), 586-587. Wamel, W.J.B. van, Manaskova, SH, Fluit, AC, Verbrugh, H.A., Neeling, A.J. de, Duijkeren, E van & Belkum, A. van (2010). Short term micro-evolution and PCR-detection of methicillin-resistant and -susceptible Staphylococcus aureus sequence type 398. European Journal of Clinical Microbiology & Infectious Diseases, 29(1), 119-122. Westreenen, M. van & Tiddens, H.A.W.M. (2010). New antimibrobial strategies in Cystic Fibrosis. Paediatric Drugs, 12(6), 343352. Willemse-Erix, DFM, Jachtenberg, J.W., Schut, TB, Leeuwen, W.B. van, Belkum, A. van, Puppels, G.J. & Maquelin, K. (2010). Towards Raman-based epidemiological typing of Pseudomonas aeruginosa. Journal of Biophotonics, 3(8-9), 506-511. Willemse-Erix, H.F.M., Jachtenberg, J, Barutci, H., Puppels, G.J., Belkum, A. van, Vos, M.C. & Maquelin, K. (2010). Proof of Principle for Successful Characterization of Methicillin-Resistant Coagulase-Negative Staphylococci Isolated from Skin by Use of Raman Spectroscopy and Pulsed-Field Gel Electrophoresis. Journal of Clinical Microbiology, 48(3), 736-740. Witt, R. te, Belkum, A. van, MacKay, WG, Wallace, PS & Leeuwen, W.B. van (2010). External quality assessment of the molecular diagnostics and genotyping of meticillin-resistant Staphylococcus aureus. European Journal of Clinical Microbiology & Infectious Diseases, 29(3), 295-300. Witt, R. te, Belkum, A. van & Leeuwen, W.B. van (2010). Molecular diagnostics and genotyping of MRSA: an update. Expert Review of Molecular Diagnosis, 10(4), 375-380. Witt, R. te, Wolfswinkel, M.E. van, Petit, PL, Hellemond, J.J. van, Koelewijn, R., Belkum, A. van & Genderen, P.J.J. van (2010). Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria. Malaria Journal, 9. Witt, R. te, Leeuwen, W.B. van & Belkum, A. van (2010). Specific Diagnostic Tests for Atypical Respiratory Tract Pathogens. Infectious Disease Clinics of North America, 24(1), 229-+. Wultanska, D, Banaszkiewicz, A, Radzikowski, A, Obuch-Woszczatynski, P., Mlynarczyk, G, Brazier, JS, Pituch, H. & Belkum, A. van (2010). Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease. European Journal of Clinical Microbiology & Infectious Diseases, 29(10), 1265-1270. Part of book - abstract Hackstein, J.H.P. & Tielens, A.G.M. (2010). Hydrogenosomes. In JHP Hackstein (Ed.), (Endo) symbiotic methanogenic archaea, Microbiology Monographs. Heidelberg: Springer Verlag. Leeuwen, W. van & Belkum, A. van (2010). Molecular detection and identification of methicillin-resistant Staphylococcus aureus. In DA Persing (Ed.), Molecular Microbiology: diagnostics and practice (pp. 463-477). ASM Press. 190 < back to index EMC MM-04-28-04 - Clinical research in infectious diseases in adults Programme in brief design The programme focuses on problems of diagnosis, prevention and therapy of infections in immunocompromised adult patients including HIV, and co-infections such as hepatitis B. Inpatients are mainly studied in the department of haematology and in the intensive care setting. Catheter-related infections, infections in neutropenic patients and HIV-infected patients are topics of specific interest. The programme explores the value of novel tools like vibrational spectroscopy in the diagnosis of infections by bacteria and fungi. In these infections that are often difficult-to-treat, new management strategies of antimicrobial drugs or inflammation modulators are expected to result in a better outcome. Key figures Department clinical microbiology internal medicine virology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,75 0 0 0 0,75 0,8 0 0 0,65 1,45 0,3 0 0 0 0,3 1,85 0 0 0,65 2,5 0 0 0 0 16 0 0 16 Artikel/Letter to the editor Bezemer, D., Sighem, A. van, Lukashov, V.V., Hoek, L. van den, Back, N., Schuurman, R., Boucher, C.A.B., Claas, E.C.J., Boerlijst, M.C., Coutinho, R.A., Wolf, F. de & ATHENA study group, - (2010). Transmission networks of HIV-1 among men having sex with men in the Netherlands. Aids, 24, 271-282. Burger, D.M., Magis-Escurra, C, Berk, GEL van den & Gelinck, L.B.S. (2010). Pharmacokinetics of double-dose raltegravir in two patients with HIV infection and tuberculosis. Aids, 24(2), 328-330. Gelinck, L.B.S. & Burger, D.M. (2010). Switching from Efavirenz to Nevirapine. Clinical Infectious Diseases, 51(3), 365-365. Jongste, A.H.C. de, Tilanus, A.M.R., Bax, H, Willems, M.H.A., Feltz, M. van der & Hellemond, J.J. van (2010). New insights in diagnosing Schistosoma myelopathy. Journal of Infection, 60(3), 244-247. Kampen, J.J.A. van, Reedijk, M.L., Burgers, P.C., Dekker, L.J.M., Hartwig, N.G., Ende, M.E. van der, Groot, R. de, Osterhaus, A.D.M.E., Burger, D, Luider, T.M. & Gruters, R.A. (2010). Ultra-fast analysis of plasma and intracellular levels of HIV protease inhibitors in children: a clinical application of MALDI Mass Spectometry. PLoS One, 5(7), e11409. Lodwick, RK, Sabin, C.A., Porter, K, Ledergerber, B., Sighem, A. van, Cozzi-Lepri, A, Khaykin, P, Mocroft, A., Jacobson, L, Wit, S. de, Obel, N, Castagna, A, Wasmuth, JC, Gill, J., Klein, MB, Gange, S, Riera, M, Mussini, C, Gutierrez, F, Touloumi, G, Carrieri, P, Guest, JL, Brockmeyer, NH & Phillips, AN (2010). Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per mu L in Europe and North America: a pooled cohort observational study. Lancet (UK), 376(9738), 340-345. Luin, M van, Ende, M.E. van der, Richter, C., Visser, M., Faraj, D, Ven, A. van de, Gelinck, L.B.S., Kroon, F., Wit, FW, Schaik, R.H.N. van, Kuks, PFM & Burger, D.M. (2010). Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. Aids, 24(8), 1223-1226. Mollema, F.P.N., Severin, J.A., Nouwen, J.L., Ott, A., Verbrugh, H.A. & Vos, M. (2010). Successful Treatment for Carriage of Methicillin-Resistant Staphylococcus aureus and Importance of Follow-Up. Antimicrobial Agents & Chemotherapy, 54(9), 40204025. Rijnders, B.J.A. & Slobbe, L. (2010). Bronchoalveolar Lavage Fluid Galactomannan for Diagnosis of Invasive Pulmonary Aspergillosis. Clinical Infectious Diseases, 50(7), 1070-1070. Rijnders, B.J.A. (2010). Replacement of intravascular catheters to prevent infection: Evidence still missing while the question may become irrelevant. Critical Care Medicine, 38(4), 1208-1209. Sighem, A. van, Gras, L., Reiss, P., Brinkman, K., Wolf, F. de & ATHENA study group, - (2010). Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of unifected individuals. Aids, 24, 1527-1535. Slobbe, L., Doorduijn, J.K., Lugtenburg, P.J., Barzouhi, A el, Boersma, E., Leeuwen, W.B. van & Rijnders, B.J.A. (2010). Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial. PLoS One, 5(5). Tilanus, A.M.R., Geus, H.R.H. de, Rijnders, B.J.A., Dwarkasing, R.S., Hoven, B. van der & Bakker, J. (2010). Severe group A streptococcal toxic shock syndrome presenting as primary peritonitis: a case report and brief review of the literature. International Journal of Infectious Diseases, 14, E208-E212. Verbon, A. & Prins, J.M. (2010). Shoulder pain in two HIV-seropositive patients. Netherlands Journal of Medicine, 68(10), 322-+. Verweij, KE, Kamerik, AR, Ingen, J. van, Dijk, J.H. van, Sikwangala, P., Thuma, P, Nouwen, J.L. & Soolingen, D. van (2010). Application of modern microbiological diagnostic methods for tuberculosis in Macha, Zambia. International Journal of Tuberculosis and Lung Disease, 14(9), 1127-1131. 191 < back to index Vries - Sluijs, T.E.M.S. de, Reijnders, J.G.P., Hansen, B.E., Zaaijer, H.L, Prins, J.M., Pas, S.D., Schutten, M., Hoepelman, A.I.M., Richter, C., Mulder, J.W., Man, R.A. de, Janssen, H.L.A. & Ende, M.E. van der (2010). Long-term Therapy With Tenofovir Is Effective for Patients Co-Infected With Human Immunodeficiency Virus and Hepatitis B Virus. Gastroenterology, 139(6), 1934-1941. 192 < back to index EMC MM-04-39-05 - Renal insufficiency and organ transplantation Programme in brief design This program concerns various methods of renal replacement: Therapy: haemodialysis, peritoneal dialysis and transplantation. In the clinical setting we try to find optimal treatment modalities for acute renal failure i.e. continuous dialysis techniques (CAVHD,CVVH) and for haemodynamic instability during intermittent dialysis. In CAPD patients we study the effect of dialysis fluids on nutrition, while in patient on hemodialysis we characterize their inherent immuno deficiency. The main topic of the program is immunological monitoring of kidney- and heart transplant recipients. We study the cascades of immunological factors that lead to acute and chronic rejection. In attempt to find strategies to prevent and treat these processes. Key figures Department internal medicine Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 11,75 0 1 0 12,75 11,75 0 1 0 12,75 4 0 0 4 32 3 0 39 Thesis Crop, M.J. (2010, november 03). Mesenchymal stem cells in organ transplantation. EUR (176 pag.). Prom./coprom.: Prof. Dr. W. Weimar. Gerrits, J.H. (2010, januari 08). Donor-reactive T-cell responses after HLA-identical living-related kidney transplantation. EUR (175 pag.). Prom./coprom.: Prof. Dr. W. Weimar. Klerk, M. de (2010, april 22). The Dutch living donor kidney exchange program. EUR (116 pag.). Prom./coprom.: Prof. Dr. W. Weimar. Sewgobind, V.D.K.D. (2010, juni 08). Immunosuppressive drugs and immune regulation in organ transplantation. EUR (209 pag.). Prom./coprom.: Prof. Dr. W. Weimar. Artikel/Letter to the editor Baan, C.C. (2010). iTregs by vitamins: commentary on 'Retinoic acid attenuates acute heart rejection by increasing regulatory T cell and repressing differentiation of Th17 in the presence of TGF-beta'. Transplant International, 23(10), 984-985. Betjes, M.G.H., Wit, EEA de, Weimar, W. & Litjens, N.H.R. (2010). Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients. Nephrology Dialysis Transplantation, 25(11), 36403646. Borra, L.C.P., Roodnat, J.I., Kal, JA, Mathot, R.A.A., Weimar, W. & Gelder, T. van (2010). High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation. Nephrology Dialysis Transplantation, 25(8), 2757-2763. Bosma, B.M., Metselaar, H.J., Gerrits, J.H., Besouw, N.M. van, Mancham, S., Groothuismink, Z.M.A., Boor, P.P.C., Laan, L.J.W. van der, Tilanus, H.W., Kuipers, E.J. & Kwekkeboom, J. (2010). Migration of Allosensitizing Donor Myeloid Dendritic Cells into Recipients After Liver Transplantation. Liver Transplantation, 16(1), 12-22. Buren, M.C. van, Massey, EK, Maasdam, L., Zuidema, W.C., Hilhorst, M.T., IJzermans, J.N. & Weimar, W. (2010). For Love or Money? Attitudes Toward Financial Incentives Among Actual Living Kidney Donors. American Journal of Transplantation, 10(11), 2488-2492. Crop, M.J., Baan, C.C., Korevaar, S.S., Ijzermans, J.N.M., Weimar, W. & Hoogduijn, M.J. (2010). Human Adipose TissueDerived Mesenchymal Stem Cells Induce Explosive T-Cell Proliferation. Stem Cells and Development, 19(12), 1843-1853. Crop, M.J., Baan, C.C., Korevaar, S.S., Ijzermans, J.N.M., Pescatori, M., Stubbs, A.P., Ijcken, W.F.J. van, Dahlke, MH, Eggenhofer, E, Weimar, W. & Hoogduijn, M.J. (2010). Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clinical & Experimental Immunology, 162(3), 474-486. Dols, L.F.C., Kok, N.F.M., Terkivatan, T., Tran, T.C.K., d'Ancona, F.C., Langenhuijsen, J.F., Mertens zur Borg, I.R.A.M., Alwayn, I.P.J., Hendriks, M.P., Dooper, IM, Weimar, W. & Ijzermans, J.N.M. (2010). Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial. BMC Surgery, 10, 11. Dols, L.F.C., Ijzermans, J.N.M., Wentink, N., Tran, T.C.K., Zuidema, W.C., Dooper, IM, Weimar, W. & Kok, N.F.M. (2010). LongTerm Follow-up of a Randomized Trial Comparing Laparoscopic and Mini-Incision Open Live Donor Nephrectomy. American Journal of Transplantation, 10(11), 2481-2487. Dols, L.F.C., Kok, N.F.M., Terkivatan, T., Tran, T.C.K., Alwayn, I.P.J., Weimar, W. & Ijzermans, J.N.M. (2010). Optimizing leftsided live kidney donation: hand-assisted retroperitoneoscopic as alternative to standard laparoscopic donor nephrectomy. Transplant International, 23(4), 358-363. Gelder, T. van & Hesselink, D.A. (2010). Dosing Tacrolimus Based on CYP3A5 Genotype: Will It Improve Clinical Outcome? Clinical Pharmacology & Therapeutics, 87(6), 640-641. 193 < back to index Gelder, T. van, Silva, HT, Fijter, J.W. de, Budde, K, Kuypers, D, Arns, W, Soulillou, JP, Kanellis, J, Zelvys, A, Ekberg, H, Holzer, H, Rostaing, L & Mamelok, RD (2010). Renal Transplant Patients at High Risk of Acute Rejection Benefit From Adequate Exposure to Mycophenolic Acid. Transplantation, 89(5), 595-599. Gelder, T. van (2010). TDM for Mycophenolic Acid at No Extra Cost. Transplantation, 89(10), 1176-1177. Gensburger, O, Schaik, R.H.N. van, Picard, N., Meur, Y. Le, Rousseau, A, Woillard, JB, Gelder, T. van & Marquet, P (2010). Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil. Pharmacogenetics Genomics, 20(9), 537-543. Geus, H.R.H. de, Betjes, M.G.H. & Bakker, J. (2010). Neutrophil gelatinase-associated lipocalin clearance during veno-venous continuous renal replacement therapy in critically ill patients. Intensive Care Medicine, 36(12), 2156-2157. Groot, C.J.M. de, Mast, B.J. van der, Visser, W., Kuiper, P. de, Weimar, W. & Besouw, N.M. van (2010). Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens. American Journal of Obstetrics and Gynecology, 203(5). Ham, S.M. van, Heutinck, KM, Jorritsma, T, Bemelman, FJ, Strik, MCM, Vos, W. van der, Muris, JJF, Florquin, S, Berge, IJM ten & Rowshani, AT (2010). Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients. Kidney International, 78(10), 1033-1040. Hesselink, D.A., Bouamar, R. & Gelder, T. van (2010). The Pharmacogenetics of Calcineurin Inhibitor-Related Nephrotoxicity. Therapeutic Drug Monitoring, 32(4), 387-393. Hoogduijn, M.J., Popp, FC, Grohnert, A, Crop, M.J., Rhijn, M. van, Rowshani, T., Eggenhofer, E, Renner, P, Reinders, ME, Rabelink, T.J., Laan, L.J.W. van der, Dor, F.J.M.F., Ijzermans, J.N.M., Genever, PG, Lange, C, Durrbach, A, Houtgraaf, H.J., Christ, B, Seifert, M, Shagidulin, M, Donckier, V, Deans, R, Ringden, O, Perico, N, Remuzzi, G, Bartholomew, A, Schlitt, HJ, Weimar, W., Baan, C.C. & Dahlke, MH (2010). Advancement of Mesenchymal Stem Cell Therapy in Solid Organ Transplantation (MISOT). Transplantation, 90(2), 124-126. Hoogduijn, M.J., Popp, F, Verbeek, R., Masoodi, M, Nicolaou, A, Baan, C.C. & Dahlke, MH (2010). The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. International Immunopharmacology, 10(12), 1496-1500. Klerk, M. de, Deijl, WM van der, Witvliet, M.D., Haase-Kromwijk, BJJM, Claas, F.H.J. & Weimar, W. (2010). The optimal chain length for kidney paired exchanges: an analysis of the Dutch program. Transplant International, 23(11), 1120-1125. Kuypers, DRJ, Meur, Y. Le, Cantarovich, M, Tredger, MJ, Tett, SE, Cattaneo, D, Tonshoff, B., Holt, D.W., Chapman, J & Gelder, T. van (2010). Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation. Clinical Journal of the American Society of Nephrology, 5(2), 341-358. Lammers, L.A., Mathijssen, R.H.J., Gelder, T. van, Bijl, M.J., Graan, A.M. de, Seynaeve, C., Fessem, M. van, Berns, E.M.J.J., Vulto, A.G. & Schaik, R.H.N. van (2010). The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer. British Journal of Cancer, 103(6), 765-771. Massey, E., Kranenburg, L.W., Zuidema, W.C., Hak, G., Erdman, R.A.M., Hilhorst, M.T., Ijzermans, J.N.M., Busschbach, J.J. van & Weimar, W. (2010). Encouraging Psychological Outcomes After Altruistic Donation to a Stranger. American Journal of Transplantation, 10(6), 1445-1452. Roodnat, J.I., Zuidema, W., Wetering, J. van de, Klerk, M. de, Erdman, R.A.M., Massey, E., Hilhorst, M.T., Ijzermans, J.N.M. & Weimar, W. (2010). Altruistic Donor Triggered Domino-Paired Kidney Donation for Unsuccessful Couples from the KidneyExchange Program. American Journal of Transplantation, 10(4), 821-827. Roodnat, J.I., Wetering, J. van de, Zuidema, W., Noord, MAA van, Kal-van Gestel, J.A., Ijzermans, J.N.M. & Weimar, W. (2010). Ethnically Diverse Populations and Their Participation in Living Kidney Donation Programs. Transplantation, 89(10), 1263-1269. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Dam, T.B. van, Ijzermans, J.N.M., Weimar, W. & Baan, C.C. (2010). Characterization of Rabbit Antithymocyte Globulins-Induced CD25(+) Regulatory T Cells From Cells of Patients With End-Stage Renal Disease. Transplantation, 89(6), 655-666. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Mol, W.M., Weimar, W. & Baan, C.C. (2010). The calcineurin inhibitor tacrolimus allows the induction of functional CD4+CD25+regulatory T cells by rabbit antithymocyte globulins. Clinical & Experimental Immunology, 161(2), 364-377. Sewgobind, V.D.K.D., Quaedackers, M.E., Laan, L.J.W. van der, Kraaijeveld, R., Korevaar, S.S., Chan, G, Weimar, W. & Baan, C.C. (2010). The Jak Inhibitor CP-690,550 Preserves the Function of CD4+CD25brightFoxP3+Regulatory T Cells and Inhibits Effector T Cells. American Journal of Transplantation, 10(8), 1785-1795. Sijs, H. van der, Bouamar, R., Gelder, T. van, Aarts, J.E.C.M., Berg, M. & Vulto, A.G. (2010). Functionality test for drug safety alerting in computerized physician order entry systems. International Journal of Medical Informatics, 79(4), 243-251. Sijs, H. van der, Gelder, T. van, Vulto, A., Berg, M. & Aarts, J.E.C.M. (2010). Understanding Handling of Drug Safety Alerts: a Simulation Study. International Journal of Medical Informatics, 79, 361-369. Wetering, J. van de, Roodnat, J.I., Hemke, AC, Hoitsma, A.J. & Weimar, W. (2010). Patient Survival After the Diagnosis of Cancer in Renal Transplant Recipients: A Nested Case-Control Study. Transplantation, 90(12), 1542-1546. 194 < back to index Winter, B.C.M. de, Mathot, R.A.A., Sombogaard, F., Neumann, I, Hest, R.M. van, Doorduijn, J.K. & Gelder, T. van (2010). Differences in Clearance of Mycophenolic Acid Among Renal Transplant Recipients, Hematopoietic Stem Cell Transplant Recipients, and Patients With Autoimmune Disease. Therapeutic Drug Monitoring, 32(5), 606-614. Part of book - abstract Klerk, M. de, Zuidema, W.C., Ijzermans, J.N.M. & Weimar, W. (2010). On chain lengths, domino-paired and unbalanced altruistic kidney donations. In JM Cecka & PI Terasaki (Eds.), Clinical Transplants. Los Angeles: Terasaki Foundation Laboratory. Weimar, W. (2010). Les dons croisés, les << bons samaritains>>, l¿expérience des Pays-Bas. In Réflexion éthiques sur la pénurie d¿organes en Europe. Paris: L'Hermattan. 195 < back to index EMC MM-04-42-02 - Cell biological and pathophysiological investigations on pulmonary diseases Programme in brief design Investigations of immunological, cell biological processes in inflammation, infection, transplantation and malignancies in the lungs are performed to get insight into the contribution of inflammatory cells and mediators. Emphasis is on I) the antigen presenting cell as a major contributor to the inflammatory process in obstructive and interstitial pulmonary diseases and as target and tool for therapy II) the role of transcription factors and signal transduction pathways that are essential for development and function of lymphocytes. Pathophysiological investigations are performed to increase our understanding of structure function relationships in the lungs. In this programme investigations are done in animal models and in humans. The effects of therapeutic interventions on cell biological processes and structural and functional properties of the lungs are also under investigation. Key figures Department medical psychology & psychotherapy pediatrics-pulmonology pulmonology Total SP1 0,4 0,03 5,9 6,33 SP2 0 0 0,4 0,4 SP3 SP4 0 0 2 2 Sptot 0 0 0 0 0,4 0,03 8,3 8,73 T1 T2 T3 6 0 0 Ttot 6 IS 42 FS OP 3 Ptot 0 51 Thesis Hou, J. (2010, januari 13). Gene Expression Profiling of Early Stage Non-Small Cell lung Cancer. EUR (198 pag.). Prom./coprom.: Prof. Dr. J.N.J. Philipsen, Prof. Dr. F.G. Grosveld & Dr. J.G.J.V. Aerts. Leest, K.H. van der (2010, mei 28). Optical and functional imaging in lung cancer. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden & Dr. J.G.J.V. Aerts. Ribeiro de Almeida, C.A. (2010, november 17). CTCF a crucial regulator of gene expression in lymphocytes. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden & Prof. Dr. R.W. Hendriks. Surmont, V.F.M. (2010, januari 07). Treatment advances in locally advanced and metastatic non-small cell lung cancer. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden, Dr. J.G.J.V. Aerts & Dr. R.J. van Klaveren. Ta, T.B.V. (2010, december 15). Role of pre-B cell receptor signaling molecules in B cell differentiation and tumor suppression. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden, Prof. Dr. R. Benner & Dr. R.W. Hendriks. Veltman, J.D. (2010, december 08). Targeting immune suppression to refine dendritic cell-based immunotherapy in mesothelioma. EUR. Prom./coprom.: Prof. Dr. H.C. Hoogsteden, Dr. J.G.J.V. Aerts & Ing. J.P.J.J. Hegmans. Artikel/Letter to the editor Aalst, C.M. van der, Klaveren, R.J. van & Koning, H.J. de (2010). Does participation to screening unintentionally influence lifestyle behaviour and thus lifestyle-related morbidity? Best Practice & Research in Clinical Gastroenterology, 24(4), 465-478. Aalst, C.M. van der, Bergh, K.A.M. van den, Willemsen, MC, Koning, H.J. de & Klaveren, R.J. van (2010). Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial. Thorax, 65(7), 600-605. Baecke, E., Koning, H.J. de, Otto, S.J., Iersel, C.A. van & Klaveren, R.J. van (2010). Limited contamination in the Dutch-Belgian randomized lung cancer screening trial (NELSON). Lung Cancer, 69(1), 66-70. Bergh, K.A.M. van den, Essink-Bot, M.L., Borsboom, G.J.J.M., Scholten, ET, Prokop, M, Koning, H.J. de & Klaveren, R.J. van (2010). Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON). British Journal of Cancer, 102(1), 27-34. Boros, P.W., Enright, P.L., Quanjer, P.H., Borsboom, G.J.J.M., Wesolowski, S.P. & Hyatt, R.E. (2010). Impaired lung compliance and Dl,co but no restrictive ventilatory defect in sarcoidosis. European Respiratory Journal, 36, 1315-1322. Costa, D. de, Broodman, I., Duijn, M.M. van, Stingl, C., Dekker, L.J.M., Burgers, P.C., Hoogsteden, H.C., Sillevis Smitt, P.A.E., Klaveren, R.J. van & Luider, T.M. (2010). Sequencing and Quantifying IgG Fragments and Antigen-Binding Regions by Mass Spectrometry. Journal of Proteome Research, 9(6), 2937-2945. Drogat, B, Kalucka, J, Gutierrez Gutierrez, L., Hammad, H, Goossens, S, Ghahremani, MF, Bartunkova, S, Haigh, K, Deswarte, K, Nyabi, O, Naessens, M, Ferrara, N, Klingmuller, U, Lambrecht, B.N.M., Nagy, A., Philipsen, J.N.J. & Haigh, JJ (2010). Vegf regulates embryonic erythroid development through Gata1 modulation. Blood, 116(12), 2141-2151. Fulambarker, A., Copur, A.S., Cohen, M.E., Patel, M., Gill, S., Schultz, S.T. & Quanjer, P.H. (2010). Comparison of pulmonary function in immigrant vs US-born Asian Indians. Chest, 137(6), 1398-1404. Gietema, HA, Zanen, P, Schilham, A, Ginneken, B van, Klaveren, R.J. van, Prokop, M & Lammers, JWJ (2010). Distribution of emphysema in heavy smokers: Impact on pulmonary function. Respiratory Medicine, 104(1), 76-82. 196 < back to index Hammad, H, Plantinga, M, Deswarte, K, Pouliot, P, Willart, MAM, Kool, M., Muskens, A.M. & Lambrecht, B.N.M. (2010). Inflammatory dendritic cells-not basophils-are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. Journal of Experimental Medicine, 207(10), 2097-2111. Hegmans, J.P.J.J., Veltman, J.D., Lambers, M.E., Vries, IJM de, Figdor, C.G., Hendriks, R.W., Hoogsteden, H.C., Lambrecht, B.N.M. & Aerts, J.G.J.V. (2010). Consolidative Dendritic Cell-based Immunotherapy Elicits Cytotoxicity against Malignant Mesothelioma. American Journal of Respiratory and Critical Care Medicine, 181(12), 1383-1390. Hoek, R.A.S. & Eerden, M.M. van der (2010). A man with exercise related shortness of breath. Nederlands Tijdschrift voor Geneeskunde, 154, 1102. Hoop, B de, Gietema, H, Vorst, S van de, Murphy, K, Klaveren, R.J. van & Prokop, M (2010). Pulmonary Ground-Glass Nodules: Increase in Mass as an Early Indicator of Growth. Radiology, 255(1), 199-206. Hoop, B de, Schaefer-Prokop, C, Gietema, HA, Jong, P.A. de, Ginneken, B.T.J. van, Klaveren, R.J. van & Prokop, M (2010). Screening for Lung Cancer with Digital Chest Radiography: Sensitivity and Number of Secondary Work-up CT Examinations. Radiology, 255(2), 629-637. Hou, J., Aerts, J.G.J.V., Hamer, B. den, Ijcken, W.F.J. van, Bakker, M.A. den, Riegman, P.H.J., Leest, K.H. van der, Spek, P.J. van der, Foekens, J.A., Hoogsteden, H.C., Grosveld, F.G. & Philipsen, J.N.J. (2010). Gene Expression-Based Classification of Non-Small Cell Lung Carcinomas and Survival Prediction. PLoS One, 5(4), 10312. Jacobs, PC, Prokop, M, Graaf, Y. van der, Gondrie, MJ, Janssen, KJ, Koning, H.J. de, Isgum, I, Klaveren, R.J. van, Oudkerk, M.., Ginneken, B van & Mali, WP (2010). Comparing coronary artery calcium and thoracic aorta calcium for prediction of allcause mortality and cardiovascular events on low-dose non-gated computed tomography in a high-risk population of heavy smokers. Atherosclerosis, 209(2), 455-462. Kanick, S.C., Leest, K.H. van der, Djamin, RS, Janssens, AM, Hoogsteden, H.C., Sterenborg, H.J.C.M., Amelink, A. & Aerts, J.G.J.V. (2010). Characterization of Mediastinal Lymph Node Physiology In Vivo by Optical Spectroscopy during Endoscopic Ultrasound-Guided Fine Needle Aspiration. Journal of Thoracic Oncology, 5(7), 981-987. Kanick, S.C., Leest, K.H. van der, Aerts, J.G.J.V., Hoogsteden, H.C., Kascakova, S., Sterenborg, H.J.C.M. & Amelink, A. (2010). Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes. Journal of Biomedical Optics, 15(1). Kersseboom, R., Kil, L.P., Flierman, R, Zee, M. van der, Dingjan, G.M., Middendorp, S., Maas, A. & Hendriks, R.W. (2010). Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells. European Journal of Immunology, 40(9), 2643-2654. Klein Wolterink, R.G.J., Garcia-Ojeda, ME, Vosshenrich, C.A.J., Hendriks, R.W. & Santo, J.P. di (2010). The intrathymic crossroads of T and NK cell differentiation. Immunological Reviews, 238, 126-137. Kleinjan, A., Willart, M., Nimwegen, M. van, Leman, K., Hoogsteden, H.C., Hendriks, R.W. & Lambrecht, B.N.M. (2010). United airways: circulating Th2 effector cells in an allergic rhinitis model are responsible for promoting lower airways inflammation. Clinical & Experimental Allergy, 40(3), 494-504. Lambrecht, B.N.M. & Hammad, H. (2010). The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lancet (UK), 376(9743), 835-843. Lambrechts, D, Buysschaert, I, Zanen, P, Coolen, J., Lays, N, Cuppens, H., Groen, H.J.M., Dewever, W, Klaveren, R.J. van, Verschakelen, J, Wijmenga, C., Postma, D.S., Decramer, M. & Janssens, W (2010). The 15q24/25 Susceptibility Variant for Lung Cancer and Chronic Obstructive Pulmonary Disease Is Associated with Emphysema. American Journal of Respiratory and Critical Care Medicine, 181(5), 486-493. Meesters, R.J.W., Cornelissen, R., Klaveren, R.J. van, Jonge, R. de, Boer, E., Lindemans, J. & Luider, T.M. (2010). A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients. Analytical and Bioanalytical Chemistry, 398(7-8), 2943-2948. Mus, A.M.C., Cornelissen, F.H.J., Asmawidjaja, P.S., Hamburg, J.P. van, Boon, L., Hendriks, R.W. & Lubberts, E. (2010). Interleukin-23 Promotes Th17 Differentiation by Inhibiting T-bet and FoxP3 and Is Required for Elevation of Interleukin-22, but Not Interleukin-21, in Autoimmune Experimental Arthritis. Arthritis & Rheumatism, 62(4), 1043-1050. Ng, Y.Y., Baert, M.R.M., Pike - Overzet, K, Rodijk, M., Brugman, M.H., Schambach, A, Baum, C., Hendriks, R.W., Dongen, J.J.M. van & Staal, F.J.T. (2010). Correction of B-cell development in Btk-deficient mice using lentiviral vectors with codonoptimized human BTK. Leukemia, 24(9), 1617-1630. Noord, C. van, Eijgelsheim, M. & Stricker, B.H.C. (2010). Drug- and non-drug-associated QT interval prolongation. British Journal of Clinical Pharmacology, 70(1), 16-23. Noord, C. van, Sturkenboom, M.C.J.M., Straus, S.M.J.M., Hofman, A., Kors, J.A., Witteman, J.C.M. & Stricker, B.H.C. (2010). Serum glucose and insulin are associated with QTc and RR intervals in nondiabetic elderly. European Journal of Endocrinology, 162(2), 241-248. Noord, C. van, Dorr, M, Sturkenboom, M.C.J.M., Straus, S.M.J.M., Reffelmann, T, Felix, SB, Hofman, A., Kors, J.A., Haring, R, Jong, F.H. de, Nauck, M., Uitterlinden, A.G., Wallaschofski, H., Witteman, J.C.M., Volzke, H & Stricker, B.H.C. (2010). The association of serum testosterone levels and ventricular repolarization. European Journal of Epidemiology, 25(1), 21-28. 197 < back to index Plantinga, M, Hammad, H & Lambrecht, B.N.M. (2010). Origin and functional specializations of DC subsets in the lung. European Journal of Immunology, 40(8), 2112-2118. Quanjer, P.H., Stanojevic, S., Stocks, J., Hall, G.L., Prasad, K.V.V., Cole, T.J., Rosenthal, M., Perez-Padilla, R., Hankinson, J.L., Falaschetti, E, Golshan, M., Brunekreef, B., Al-Rawas, O., Kuhr, J., Trabelsi, Y & Ip, M.S.M. (2010). Changes in the FEV1/FVC ratio during childhood and adolescence: an intercontinental study. European Respiratory Journal, 36, 1391-1399. Quanjer, P.H. (2010). Open letter to the members of the GOLD Committee. Respiration, 80, 265-268. Quanjer, P.H. & Enright, P.L. (2010). Should we use 'lung age'? Primary Care Respiratory Journal, 19(3), 197-199. Quanjer, P.H. (2010). Submitting a manuscript. European Respiratory Journal, 35(3), 699. Quanjer, P.H., Enright, P.L., Miller, MR, Stocks, J., Swanney, MP, Crapo, RO, Pedersen, O.F. & Schouten, JP (2010). The need to change the method for defining mild airway obstruction. Primary Care Respiratory Journal, 19(3), 288-291. Shirinbak, S, Taher, YA, Maazi, H, Gras, R, Esch, BCAM van, Henricks, PAJ, Samsom, J.N., Verbeek, JS, Lambrecht, B.N.M., Oosterhout, A.J.M. van & Nawijn, MC (2010). Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice. Journal of Immunology, 185(7), 3857-3865. Surmont, V., Aerts, J.G.J.V., Klaveren, R.J. van, Tournoy, K, Tan, K.Y., Vernhout, R.M., Schmitz, P.I.M., Legrand, C., Hoogsteden, H.C. & Meerbeeck, J.P.A.M. van (2010). A Randomized Phase II Study Comparing Two Schedules of the 21-Day Regimen of Gemcitabine and Carboplatin in Advanced Non-Small Cell Lung Cancer. Oncology (Basel), 78(3-4), 267-270. Surmont, V., Smit, E.F., Jonge, M.J.A. de, Aerts, J.G.J.V., Nackaerts, K, Vernhout, R, Gras, J, Wijk, A Van, Phernambucq, ECJ, Meerbeeck, J.P.A.M. van, Senan, S., Kraaij, CJ, Chouaki, N, Praag, J.O. & Klaveren, R.J. van (2010). Pemetrexed and cisplatin with concurrent radiotherapy for locally advanced non-small cell and limited disease small cell lung cancer: Results from 2 phase I studies. Lung Cancer, 69(3), 302-306. Ta, T.B.V., Bruijn, J.W. de, Brugge, P.J. ter, Hamburg, J.P. van, Diepstraten, H.J.A., Loo, P.F. van, Kersseboom, R. & Hendriks, R.W. (2010). Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway. Blood, 115(7), 1385-1393. Til, N.P. van, Stok, M., Aerts, F.S.F., Waard, M.C. de, Farahbakhshian, E., Visser, T.P., Kroos, M.A., Jacobs, E.H., Willart, M.A., Wegen, C.G. van der, Scholte, B.J., Lambrecht, B.N.M., Duncker, D.J.G.M., Ploeg, A.T. van der, Reuser, A.J.J., Verstegen, M.M.A. & Wagemaker, G. (2010). Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood, 115(26), 5329-5337. Veltman, J.D., Lambers, M.E.H., Nimwegen, M. van, Hendriks, R.W., Hoogsteden, H.C., Aerts, J.G.J.V. & Hegmans, J.P.J.J. (2010). COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. Bmc Cancer, 10. Veltman, J.D., Lambers, M.E.H., Nimwegen, M. van, Hendriks, R.W., Hoogsteden, H.C., Hegmans, J.P.J.J. & Aerts, J.G.J.V. (2010). Zoledronic acid impairs myeloid differentiation to tumour-associated macrophages in mesothelioma. British Journal of Cancer, 103(5), 629-641. Voort van Zyp, N.C.M.G. van der, Prevost, J.G.H.G., Holt, B. van der, Braat, C., Klaveren, R.J. van, Pattynama, P.M.T., Levendag, P.C. & Nuyttens, J.J. (2010). Quality of life after stereotactic radiotherapy forstage I non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 77(1), 31-37. Voort van Zyp, N.C.M.G. van der, Holt, B. van der, Klaveren, R.J. van, Pattynama, P.M.T., Maat, A. van de & Nuyttens, J.J. (2010). Stereotactic body radiotherapy using real-time tumor tracking in octogenarians with non-small cell lung cancer. Lung Cancer, 69(3), 296-301. Wang, Y., Bock, G.H. de, Klaveren, R.J. van, Ooyen, P van, Tukker, W, Zhao, YJ, Dorrius, MD, Proenca, RV, Post, W.J. & Oudkerk, M.. (2010). Volumetric measurement of pulmonary nodules at low-dose chest CT: effect of reconstruction setting on measurement variability. European Radiology, 20(5), 1180-1187. 198 < back to index EMC MM-04-44-02 - Neuromuscular and Neuroinflammatory Disorders Programme in brief design Research questions of the programme This research programme aims to study various aspects of immune-mediated of the central (multiple sclerosis, encephalitis, epilepsy) and peripheral (Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, mitochondrial myopathy, Pompe¿s disease) nervous system. Studies are conducted in close collaboration in particular with the Departments of Immunology, Medical Microbiology and Infectious diseases, Virology, Genetics, Epidemiology, Rehabilitation of the Erasmus MC, as well as with neurological, neuroimmunological and genetic centers around the world. Clinical neurophysiological research focuses on the development and application of non-invasive EMG techniques to assess motor unit function in neuromuscular disorders. The Rotterdam MS center ¿ErasMS¿ for MS and CNS inflammation integrates research and care. The department is actively involved in the Center lysosomal and metabolic diseases ¿Pompe center¿. The Paediatric Neurology Department coordinates the long-term follow-up of the Dutch Study of Epilepsy in Childhood and participates in the `Generation R¿ project, and in national and international collaborative groups for the identification of genes and genotype-phenotype correlations in mitochondrial disorders, malformations of cortical development (MCD) and epilepsy. The programme is focused on the following topics: Neuromuscular disorders / neuroimmunology - peripheral nervous system. 1. Immunological, viral, microbiological and genetic determinants and pathogenesis of Guillain-Barré syndrome (GBS). 2. Prognostic modelling of the GBS and chronic inflammatory demyelinating polyneuropathy (CIDP). 3. National surveillance of GBS after vaccinations. 4. Clinical trials and laboratory studies with intravenous immunoglobulin (IVIg) and other immunomodulatory drugs in GBS and the chronic inflammatory demyelinating polyneuropathy (CIDP). 5. Clinimetric evaluation of assessment scales in immune-mediated neuropathies (Perinoms study) 6. Non-invasive EMG techniques to monitor changes in motor unit function. 7. Electrophysiological studies in immune-mediated neuropathies. 8. Enzyme replacement therapy, assessment of longterm-outcome and prognostic modelling in Pompe disease. 9. Mitochondrial disorders leading to neuromuscular disorders, visual system disorders and encephalopathies. 10. Gene discovery in families with mitochondrial encephalomyopathies 11. Protein profiles in PBMC in Leber¿s Hereditary Optic Neuropathy patients Multiple sclerosis/ neuroimmunology - central nervous system. 1. Immunological, genetic and infectious determinants on the disease course in Multiple Sclerosis (MS) and Acute Disseminated Encephalomyelitis (ADEM). 2. Determinants of ADEM and MS in childhood. 3. Gene discovery in MS families. 4. Immunomodulatory treatment of central nervous system (CNS) inflammatory disease. 5. The Rotterdam `ErasMS¿ multiple sclerosis center, including research in animal models. 6. Retinal measurements as a tool to monitor CNS inflammation. Epilepsy and other neurological disorders in childhood 1. Incidence and determinants of epilepsy and other paroxysmal disorders in childhood (¿Generation R¿ study). 2. Course of childhood epilepsy in cohort studies with prospective long-term follow-up, developing prognostic models and evaluating modified treatment strategies. 3. Initiating and conducting therapeutic trials in childhood epilepsy (anti-epileptic drugs, ketogenic diet). 4. Genes and genetic mechanisms in childhood epilepsy and in families with epilepsy. 5. Monitoring techniques, diagnosis and treatment modalities in neonatal seizures. 6. Genes causing cortical migration disorders and their relation with seizures. 7. Molecular genetics and cognitive aspects of cerebellar dysfunction in Williams syndrome. 8. Treatment of migraine and other headaches in childhood. 9. Hereditary causes of mental retardation, epilepsy and neurological syndromes. 10. Continuous EEG monitoring in neonatal asphyxia. 11. Cognitive functioning and its treatment in children with neurofibromatosis type 1. 12. Cognitive functioning and epilepsy in children with tuberous sclerosis. Key figures Department immunology neurology Total SP1 0 6,65 6,65 SP2 0 1,9 1,9 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 0,5 0 0,5 5,45 3,45 17,45 5,95 3,45 17,95 4 0 0 4 72 2 1 79 Thesis Bruijn, J.J. de (2010, september 29). Quality of life and psychological functioning in observational and intervention studies in childhood migraine. EUR. Prom./coprom.: Prof. Dr. W.F.M. Arts & Prof.Dr. J. Passchier. Perumpillichira, J.C. (2010, september 02). Improvements in neonatal brain monitoring after perinatal asphyxia. EUR. Prom./coprom.: Prof. Dr. W.F.M. Arts. Ruts, L. (2010, juni 17). Pain, autonomic dysfunction, and course of disease in Guillain-Barre Syndrome. EUR. Prom./coprom.: Prof. Dr. P.A. van Doorn. 199 < back to index Wit, M.C.Y. de (2010, september 10). Malformations of the human cerebral cortex. EUR. Prom./coprom.: Prof. Dr. W.F.M. Arts, Prof. Dr. F.G. Grosveld, Dr. I.F.M. de Coo & Dr. G.M.S. Mancini. Artikel/Letter to the editor Ang, C.W., Dijkstra, J.R., Klerk, M.A. de, Endtz, H.P., Doorn, P.A. van, Jacobs, B.C., Jeurissen, S.H.M. & Wagenaar, J.A. (2010). Host Factors Determine Anti-GM1 Response Following Oral Challenge of Chickens with Guillain-Barre Syndrome Derived Campylobacter jejuni Strain GB11. PLoS One, 5(3). Azzouzi, H el, Oort, RJ van, Nagel, R van der, Sluiter, W., Bergmann, MW & Windt, LJ De (2010). MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload. European Journal of Heart Failure, 12(1), 4-12. Bakkers, M., Faber, C.G., Drent, M., Hermans, MCE, Nes, S.I. van, Lauria, G, Baets, M De & Merkies, I.S.J. (2010). Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy. Journal of Neurology, 257(12), 2086-2090. Berg, L.E.M. van den, Zandbergen, A.A.M., Capelle, C.I. van, Vries, J.M. de, Hop, W.C.J., Hout, J.M.P. van den, Reuser, A.J.J., Zillikens, M.C. & Ploeg, A.T. van der (2010). Low bone mass in Pompe disease. Muscular strength as a predictor of bone mineral density. Bone, 47, 649-7. Bergh, PYK Van den, Hadden, RDM, Bouche, P, Cornblath, DR, Hahn, A, Illa, I., Koski, CL, Leger, JM, Nobile-Orazio, E., Pollard, J, Sommer, C, Doorn, P.A. van & Schaik, IN van (2010). European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision. European Journal of Neurology, 17(3), 356-363. Blok, J.H., Dijk, J.P. van, Drenthen, J., Maathuis, E.M. & Stegeman, D.F. (2010). Size does matter: The influence of motor unit potential size on statistical motor unit number estimates in healthy subjects. Clinical Neurophysiology, 121(10), 1772-1780. Bok, LA, Maurits, NM, Willemsen, MA, Jakobs, C., Teune, LK, Poll-The, B.T., Coo, I.F.M. de, Toet, MC, Hagebeuk, EE, Brouwer, O.F., Hoeven, J.H. van der & Sival, DA (2010). The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. Epilepsia, 51(12), 2406-2411. Brouwer, APM de, Bokhoven, H. van, Nabuurs, SB, Arts, W.F.M., Christodoulou, J & Duley, J (2010). PRPS1 Mutations: Four Distinct Syndromes and Potential Treatment. American Journal of Human Genetics, 86(4), 506-518. Bruijn, J.A., Locher, H., Passchier, J., Dijkstra, N. & Arts, W.F.M. (2010). Psychopathology in Children and Adolescents With Migraine in Clinical Studies: A Systematic Review. Pediatrics, 126(2), 323-332. Bruijn, J.J. de, Duivenvoorden, H.J., Passchier, J., Locher, H., Dijkstra, N. & Arts, W.F.M. (2010). Medium-dosed riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, doubleblind corss-over trial. Cephalalgia, 30(12), 1426-1434. Brusse, I.A., Peters, N.C.J., Steegers, E.A.P., Duvekot, J.J. & Visser, G.H. (2010). Electroencephalography During Normotensive and Hypertensive Pregnancy: A Systematic Review. Obstetrical and Gynecological Survey, 65(12), 794-803. Callenbach, P.M.C., Bouma, PAD, Geerts, A.T., Arts, W.F.M., Stroink, H., Peeters, E.A.J., Donselaar, C.A. v, Peters, A.C.B. & Brouwer, O.F. (2010). Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch Study of Epilepsy in Childhood. Seizure, 19(8), 501-506. Capelle, C.I. van, Beek, N.A.M.E. van der, Hagemans, M.L.C., Arts, W.F.M., Hop, W.C.J., Lee, P., Jaeken, J., Frohn-Mulder, I.M.E., Merkus, P.J.F.M., Corzo, D, Puga, A.C., Reuser, A.J.J. & Ploeg, A.T. van der (2010). Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. Neuromuscular Disorders, 20, 775-782. Cats, E.A., Pol, WL van der, Piepers, S, Franssen, H., Jacobs, B.C., Berg-Vos, R.M. van den, Kuks, J.B., Doorn, P.A. van, Engelen, BG van, Verschuuren, J.J., Wokke, JH, Veldink, J.H. & Berg, L.H. van den (2010). Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology, 75(9), 818-825. Cats, E.A., Jacobs, B.C., Yuki, N., Tio-Gillen, A.P., Piepers, S, Franssen, H., Asseldonk, JT van, Berg, L.H. van den & Pol, WL van der (2010). Multifocal motor neuropathy Association of anti-GM1 IgM antibodies with clinical features. Neurology, 75(22), 1961-1967. Catsman-Berrevoets, C.E. & Aarsen, F.K. (2010). The spectrum of neurobehavioural deficits in the Posterior Fossa Syndrome in children after cerebellar tumour surgery. Cortex, 46(7), 933-946. Cnossen, M.H., Aarsen, F.K., Akker, L.J. van den, Danen, R., Appel, I.M., Steyerberg, E.W. & Catsman-Berrevoets, C.E. (2010). Paediatric arterial ischaemic stroke: functional outcome and risk factors. Developmental Medicine & Child Neurology, 52, 394-399. Cornips, EMJ, Razenberg, FGEM, Rhijn, L.W. van, Soudant, DLHM, Raak, EPM van, Weber, JW, Robben, SG, Fock, J.M., Catsman-Berrevoets, C.E. & Vles, J.S.H. (2010). The lumbosacral angle does not reflect progressive tethered cord syndrome in children with spinal dysraphism. Childs Nervous System, 26(12), 1757-1764. Deburchgraeve, W, Cherian, P.J., Vos, M., Swarte, R.M.C., Blok, J.H., Visser, G.H., Govaert, P. & Huffel, S Van (2010). Time Varying Neonatal Seizure Localization. Methods of Information in Medicine, 49(5), 473-478. Donofrio, PD, Bril, V, Dalakas, MC, Deng, C, Hanna, K, Hartung, H.P., Hughes, R, Latov, N, Merkies, I.S.J. & Doorn, P.A. van (2010). Safety and Tolerability of Immune Globulin Intravenous in Chronic S Inflammatory Demyelinating Polyradiculoneuropathy. Archives of Neurology, 67(9), 1082-1088. 200 < back to index Doorn, P.A. van, Kuitwaard, K., Walgaard, C., Koningsveld, R. van, Ruts, L. & Jacobs, B.C. (2010). IVIG Treatment and Prognosis in Guillain-Barr, Syndrome. Journal of Clinical Immunology, 30, S74-S78. Geerts, A.T., Arts, W.F.M., Stroink, H., Peeters, E, Brouwer, O, Peters, B, Laan, L.J.W. van der & Donselaar, C van (2010). Course and outcome of childhood epilepsy: A 15-year follow-up of the Dutch Study of Epilepsy in Childhood. Epilepsia, 51(7), 1189-1197. Ghezzi, A, Banwell, B, Boyko, A, Amato, MP, Anlar, B, Blinkenberg, M, Boon, M., Filippi, M., Jozwiak, S., Ketelslegers, I, Kornek, B, Lim, M, Lindstrom, E, Nadj, C, Neuteboom, R., Rocca, MA, Rostasy, K, Tardieu, M, Wassmer, E, CatsmanBerrevoets, C.E. & Hintzen, R.Q. (2010). The management of multiple sclerosis in children: a European view. Multiple Sclerosis, 16(10), 1258-1267. Gorson, KC, Schaik, IN van, Merkies, I.S.J., Lewis, RA, Barohn, RJ, Koski, CL, Cornblath, DR, Hughes, R.A.C., Hahn, AF, Baumgarten, M, Goldstein, J., Katz, J, Graves, M, Parry, G & Doorn, P.A. van (2010). Chronic inflammatory demyelinating polyneuropathy disease activity status: recommendations for clinical research standards and use in clinical practice. Journal of the Peripheral Nervous System, 15(4), 326-333. Griffith, KA, Merkies, I.S.J., Hill, EE & Cornblath, DR (2010). Measures of chemotherapy-induced peripheral neuropathy: a systematic review of psychometric properties. Journal of the Peripheral Nervous System, 15(4), 314-325. Hagemans, M.L.C., Stigter, R.L., Capelle, C.I. van, Beek, N.A.M.E. van der, Winkel, L.P.F., Vliet, L. van, Hop, W.C.J., Reuser, A.J.J., Beishuizen, A. & Ploeg, A.T. van der (2010). PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease. Journal of Inherited Metabolic Disease, 33, 133-139. Hermans, MCE, Pinto, Y.M., Merkies, I.S.J., Die-Smulders, C.E.M. de, Crijns, H.J.G.M. & Faber, C.G. (2010). Hereditary muscular dystrophies and the heart. Neuromuscular Disorders, 20(8), 479-492. Hermans, MCE, Faber, C.G., Baets, M.H. de, Die-Smulders, C.E.M. de & Merkies, I.S.J. (2010). Rasch-built myotonic dystrophy type 1 activity and participation scale (DM1-Activ). Neuromuscular Disorders, 20(5), 310-318. Hoorn, E.J., Laar, J.A.M. van, Hollander, J.G. den, Kros, J.M. & Brusse, E. (2010). Pulmonary puzzle Three diagnoses become one: a woman with ground-glass attenuation develops fever. Thorax, 65(3), 214-+. Hughes, R.A.C., Swan, A.V. & Doorn, P.A. van (2010). Corticosteroids for Guillain-Barre syndrome. Cochrane Database Systematics Review. Hughes, R.A.C., Swan, A.V. & Doorn, P.A. van (2010). Intravenous immunoglobulin for Guillain-Barre syndrome. Cochrane Database Systematics Review. Islam, Z., Jacobs, B.C., Belkum, A. van, Mohammad, QD, Islam, MB, Herbrink, P., Diorditsa, S, Luby, SP, Talukder, KA & Endtz, H.P. (2010). Axonal variant of Guillain-Barre syndrome associated with Campylobacter infection in Bangladesh. Neurology, 74(7), 581-587. Jafari, N., Broer, L., Hoppenbrouwers, I.A., Duijn, C.M. van & Hintzen, R.Q. (2010). Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis. Multiple Sclerosis, 16(11), 1303-1307. Jafari, N., Nierop, G.P. van, Verjans, G.M.G.M., Osterhaus, A.D.M.E., Middeldorp, J.M. & Hintzen, R.Q. (2010). No evidence for intrathecal IgG synthesis to Epstein Barr virus nuclear antigen-1 in multiple sclerosis. Journal of Clinical Virology, 49(1), 26-31. Kappers, M.H.W., Esch, J.H.M. van, Sluiter, W., Sleijfer, S., Danser, A.H.J. & Meiracker, A.H. van den (2010). Hypertension Induced by the Tyrosine Kinase Inhibitor Sunitinib Is Associated With Increased Circulating Endothelin-1 Levels. Hypertension, 56(4), 675-U216. Ketelslegers, I.A., Neuteboom, R.F., Boon, M., Catsman-Berrevoets, C.E. & Hintzen, R.Q. (2010). A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology, 74(18), 1412-1415. Ketelslegers, I.A., Catsman-Berrevoets, C.E., Boon, M., Eikelenboom, MJ, Stroink, H., Neuteboom, R.F., Aarsen, F.K., Putte, EM van de & Hintzen, R.Q. (2010). Fatigue and depression in children with multiple sclerosis and monophasic variants. European Journal of Paediatric Neurology, 14(4), 320-325. Korsten, A., Coo, I.F.M. de, Spruijt, L, Wit, L.E.A. de, Smeets, H.J.M. & Sluiter, W. (2010). Patients with Leber hereditary optic neuropathy fail to compensate impaired oxidative phosphorylation. Biochimica et Biophysica Acta-Bioenergetics, 1797(2), 197203. Kuijf, M.L., Samsom, J.N., Rijs, W. van, Bax, M., Huizinga, R, Heikema, A.P., Doorn, P.A. van, Belkum, A. van, Kooyk, Y. van, Burgers, P.C., Luider, T.M., Endtz, H.P., Nieuwenhuis, E.E.S. & Jacobs, B.C. (2010). TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation. Journal of Immunology, 185, 748-755. Kuitwaard, K., Berg, L.H. van den, Vermeulen, M., Brusse, E., Cats, E.A., Kooi, A.J. van der, Notermans, N.C., Pol, WL van der, Schaik, IN van, Nes, S.I. van, Hop, W.C.J. & Doorn, P.A. van (2010). Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy. Journal of Neurology Neurosurgery and Psychiatry, 81(12), 1374-1379. 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Neuteboom, R.F., Verbraak, E., Wierenga-Wolf, A.F., Meurs, M. van, Steegers, E.A.P., Groot, C.J.M. de, Laman, J.D. & Hintzen, R.Q. (2010). Pregnancy-induced fluctuations in functional T-cell subsets in multiple sclerosis patients. Multiple Sclerosis, 16(9), 1073-1078. Oegema, R., Klein, A. de, Verkerk, A.J.M.H., Schot, R., Dumee, B.C., Douben, J.C.W., Eussen, B.J., Dubbel, R.J.M., Poddighe, P.J., Laar, I.M.B.H. van de, Dobyns, WB, Spek, P.J. van der, Lequin, M.H., Coo, I.F.M. de, Wit, M.C. de, Wessels, M.W. & Mancini, G.M.S. (2010). Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A. Molecular Syndromology, 1(3), 113-120. Oegema, R., Schot, R., Wit, M.C.Y. de, Lequin, M.H., Oostenbrink, R., Coo, I.F.M. de & Mancini, G.M.S. (2010). KBG syndrome associated with periventricular nodular heterotopia. Clinical Dysmorphology, 19(3), 164-165. Peferoen, LAN, Lamers, F, Lodder, LNR, Gerritsen, WH, Huitinga, I, Melief, J.A.M., Giovannoni, G, Meier, U, Hintzen, R.Q., Verjans, G.M.G.M., Nierop, G.P. van, Vos, W. van der, Peferoen-Baert, RMB, Middeldorp, J.M., Valk, P.J.M. & Amor, S. (2010). Epstein Barr virus is not a characteristic feature in the central nervous system in established multiple sclerosis. Brain, 133. Ploeg, A.T. van der, Clemens, P.R., Corzo, D, Escolar, D.M., Florence, J., Groeneveld, G.J., Herson, S., Kishnani, PS, Laforet, P, Lake, S., Lange, D.J., Leshner, R.T., Morgan, C., Nozaki, K., Park, D.J., Pestronk, A., Rosenbloom, B., Skrinar, A., Capelle, C.I. van, Beek, N.A. van der, Wasserstein, M. & Zivkovic, S.A. (2010). A randomized study of alglucosidase alfa in late-onset Pompe's disease. New England Journal of Medicine, 362, 1396-1406. Ruts, L., Drenthen, J., Jacobs, B.C. & Doorn, P.A. van (2010). Distinguishing acute-onset CIDP from fluctuating Guillain-Barre syndrome A prospective study. Neurology, 74(21), 1680-1686. Ruts, L., Drenthen, J., Jongen, J.L.M., Hop, W.C.J., Visser, G.H., Jacobs, B.C. & Doorn, P.A. van (2010). Pain in Guillain-Barre syndrome A long-term follow-up study. Neurology, 75(16), 1439-1447. Schaik, IN van, Eftimov, F., Doorn, P.A. van, Brusse, E., Berg, L.H. van den, Pol, WL van der, Faber, C.G., Oostrom, JCH van, Vogels, OJM, Hadden, RDM, Kleine, BU, Norden, AGW van, Verschuuren, J.J.G.M., Dijkgraaf, MG & Vermeulen, M. (2010). Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial. Lancet Neurology, 9(3), 245-253. Sellner, J, Boggild, M, Clanet, M., Hintzen, R.Q., Illes, Z, Montalban, X, Pasquier, RA Du, Polman, C.H., Sorensen, PS & Hemmer, B (2010). EFNS guidelines on diagnosis and management of neuromyelitis optica. European Journal of Neurology, 17(8), 1019-E61. Siepman, T.A.M., Bettink-Remeijer, M.W. & Hintzen, R.Q. (2010). Retinal nerve fiber layer thickness in subgroups of multiple sclerosis, measured by optical coherence tomography and scanning laser polarimetry. Journal of Neurology, 257(10), 16541660. 202 < back to index Stoop, M.P., Singh, V., Dekker, L.J.M., Titulaer, M.K., Stingl, C., Burgers, P.C., Sillevis Smitt, P.A.E., Hintzen, R.Q. & Luider, T.M. (2010). Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis. PLoS One, 5(8). Stoop, M.P., Coulier, L, Rosenling, T, Shi, S, Smolinska, AM, Buydens, L, Ampt, K, Stingl, C., Dane, A, Muilwijk, B, Luitwieler, RL, Sillevis Smitt, P.A.E., Hintzen, R.Q., Bischoff, R., Wijmenga, SS, Hankemeier, T, Gool, A.J. van & Luider, T.M. (2010). Quantitative Proteomics and Metabolomics Analysis of Normal Human Cerebrospinal Fluid Samples. Molecular & Cellular Proteomics, 9(9), 2063-2075. Teunissen, CE, Petzold, A, Bennett, JL, Berven, FS, Brundin, L, Comabella, M, Franciotta, D, Federiksen, JL, Fleming, JO, Furlan, R, Hintzen, R.Q., Hughes, SG, Johnson, MH, Krasulova, E, Kuhle, J, Magnone, MC, Rajda, C, Rejdak, K, Schmidt, HK, Pesch, V van, Waubant, E, Wolf, C, Giovannoni, G, Deisenhammer, F, Hegen, H, Hemmer, B & Tumani, HT (2010). A consensus protocol for the standardisation of cerebrospinal fluid collection and biobanking. Laboratoriumsmedizin-Journal of laboratory medicine, 34(1), 1-12. Teunissen, CE, Tumani, HT, Bennett, JL, Berven, FS, Brundin, L, Comabella, M, Franciotta, D, Federiksen, JL, Fleming, JO, Furlan, R, Hintzen, R.Q., Hughes, SG, Johnson, MH, Krasulova, E, Kuhle, J, Magnone, MC, Petzold, A, Rajda, C, Rejdak, K, Schmidt, HK, Pesch, V van, Waubant, E, Wolf, C, Hemmer, B, Deisenhammer, F & Giovannoni, G (2010). Short commentary on 'a consensus protocol for the standardization of cerebrospinal fluid collection and biobanking'. Multiple Sclerosis, 16(2), 129132. Vanhoutte, EK, Faber, C.G. & Merkies, I.S.J. (2010). Statistical significance or clinical relevance? Nederlands Tijdschrift voor Geneeskunde, 154(48), 2516. Verkerk, A.J.M.H., Schot, R., Waterschoot, L. van, Douben, J.C.W., Poddighe, P.J., Lequin, M.H., Vries, L.S. de, Terhal, P, Hahnemann, JMD, Coo, I.F.M. de, Wit, M.C.Y. de, Wafelman, L.S., Garavelli, L, Dobyns, WB, Spek, P.J. van der, Klein, A. de & Mancini, G.M.S. (2010). Unbalanced der(5)t(5;20) Translocation Associated With Megalencephaly, Perisylvian Polymicrogyria, Polydactyly and Hydrocephalus. American Journal of Medical Genetics Part A, 152A(6), 1488-1497. Vermeulen, R.C.W., Kurk, RM, Visser, F.C., Sluiter, W. & Scholte, H.R. (2010). Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. Journal of Translational Medicine, 8. Visser, A.M., Jaddoe, V.W.V.K., Hofman, A., Moll, H.A., Steegers, E.A.P., Tiemeier, H.W., Raat, H., Breteler, M.M.B. & Arts, W.F.M. (2010). Fetal Growth Retardation and Risk of Febrile Seizures. Pediatrics, 126(4), E919-E925. Visser, A.M., Jaddoe, V.W.V.K., Arends, L.R., Tiemeier, H.W., Hofman, A., Moll, H.A., Steegers, E.A.P., Breteler, M.M.B. & Arts, W.F.M. (2010). Paroxysmal disorders in infancy and their risk factors in a population-based cohort: the Generation R Study. Developmental Medicine & Child Neurology, 52(11), 1014-1020. Vries, J.M. de, Hagemans, M.L.C., Bussmann, J.B.J., Ploeg, A.T. van der & Doorn, P.A. van (2010). Fatigue in neuromuscular disorders: focus on Guillain-Barr, syndrome and Pompe disease. Cellular and Molecular Life Sciences, 67(5), 701-713. Vries, J.M. de, Beek, N.A.M.E. van der, Kroos, M.A., Ozkan, L., Doorn, P.A. van, Richards, S.M., Sung, C.C.C., Brugma, J.C., Zandbergen, A.A.M., Ploeg, A.T. van der & Reuser, A.J.J. (2010). High antibody titer in an adult with Pompe disease affects treatment with alglucosidase alfa. Molecular Genetics and Metabolism, 101, 338-345. Walgaard, C., Lingsma, H.F., Ruts, L., Drenthen, J., Koningsveld, R van, Garssen, MJP, Doorn, P.A. van, Steyerberg, E.W. & Jacobs, B.C. (2010). Prediction of Respiratory Insufficiency in Guillain-Barre Syndrome. Annals of Neurology, 67(6), 781-787. Wit, M.C.Y. de, Schippers, HM, Coo, I.F.M. de, Arts, W.F.M., Lequin, M.H., Brooks, A, Visser, G.H. & Mancini, G.M.S. (2010). Absence epilepsy and periventricular nodular heterotopia. Seizure, 19(7), 450-452. Wit, M.C.Y. de, Coo, I.F.M. de, Schot, R., Hoogeboom, A.J.M., Lequin, M.H., Verkerk, A.J.M.H. & Mancini, G.M.S. (2010). Periventricular Nodular Heterotopia and Distal Limb Deficiency: A Recurrent Association. American Journal of Medical Genetics Part A, 152A(4), 954-959. Part of book - abstract Ketelslegers, I.A. & Catsman-Berrevoets, C.E. (2010). Multiple sclerose op de kinderleeftijd. In Handboek Multiple Sclerose. Utrecht: De Tijdstroom. 203 < back to index EMC MM-04-47-07 - Organ transplantation Programme in brief design Ischemia reperfusion injury, chronic transplant dysfunction after transplantation, and hepatic steatosis are the main focus of the experimental studies on liver surgery and allotransplantation. Effects of ischemia reperfusion injury are studied in small animal models, including well defined renal, lung and hepatic models. Current experimental research focuses on the molecular mechanisms by which ischemia reperfusion injury leads to organ failure and, in the kidney allotransplantation model, to chronic transplant dysfunction. In addition, the contribution of ageing to this process is being studied. Accumulation of oxidative damage to DNA is thought to play a major role in organismal aging by compromising cellular function, triggering cell death and limiting the proliferative capacity of regenerative tissues. Clinical observations suggest an inverse relationship between ischemia time and long-term transplant success, leading to the hypothesis that this injury leads to processes also activated during premature aging of organs. Use of knockout mice that are defective in DNA repair pathways are used to study the effects of ischemia reperfusion injury after liver resection and organ transplantation. Transcriptional profiling will be used to understand the molecular basis of the injury process. These studies are being conducted in close collaboration with the Department of Cell Biology (Prof. Dr. J. Hoeijmakers) and the Department of Immunology (Prof. Dr. R. Benner). The role of the angiotensin system in renal ischemic damage is studied in collaboration with Dr. T. Walther of the Department of Pharmacology, University Hospital Charité, Berlin, Germany. Ischemia reperfusion injury in the lung is used to study therapeutic options to ameliorate reperfusion injury with the aim to decrease the incidence of acute respiratory distress syndrome and chronic deterioration of lung function following lung transplantation. This is done in collaboration with Prof. Dr. B. Lachmann, Department of Experimental Anaesthesiology, and Prof. Dr. B. Lambrecht, Department of Pulmonary Diseases. Additional studies on hepatic steatosis in relation to resection and transplantation are being studied in close collaboration with Prof. Dr. J. Folkman. Department of Surgery, Childrens Hospital, Harvard Medical School, Boston, USA. Specifically, the roles of matrixmetalloproteinases in the process of hepatic lipid metabolism are being evaluated in rodent models of dietary-induced hepatic steatosis. Research on xenotransplantation has been hampered by potential risks of viral transmission from the animal donor to the human recipient. Progress has been made on genetic modification of donor animals, including elimination of Gal-epitopes and introduction of complement-regulating factors. Using larger animal models the effects of these modifications are being studied in collaboration with Prof. Dr. D. Cooper at the Thomas Starzl Transplantation Institute, Pittsburgh, USA. Studies involving the induction of immunological tolerance are conducted in close collaboration with Prof. Dr. D. Sachs, Transplantation Biology Research Center, Harvard Medical School, Boston, USA Key figures Department gastroenterology & hepatology internal medicine surgery Total SP1 0,5 0,5 5,6 6,6 SP2 SP3 0 0 0 0 SP4 0 0 2 2 Sptot 0 0 2 2 0,5 0,5 9,6 10,6 T1 T2 T3 1 0 0 Ttot 1 IS 40 FS 4 OP 0 Ptot 45 Thesis Susa, D. (2010, november 03). Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury. EUR. Prom./coprom.: Prof. Dr. J.N.M. Ijzermans. Artikel/Letter to the editor Aalten, S.M. van, Terkivatan, T., Man, R.A. de, Windt, D.J. van der, Kok, N.F.M., Dwarkasing, R.S. & Ijzermans, J.N.M. (2010). Diagnosis and Treatment of Hepatocellular Adenoma in the Netherlands: Similarities and Differences. Digestive Surgery, 27(1), 61-67. Bakker, OJ, Go, P.M., Puylaert, JB, Kazemier, G. & Heij, HA (2010). Guideline on diagnosis and treatment of acute appendicitis: imaging prior to appendectomy is recommended. Nederlands Tijdschrift voor Geneeskunde, 154, 303. Bosma, B.M., Metselaar, H.J., Gerrits, J.H., Besouw, N.M. van, Mancham, S., Groothuismink, Z.M.A., Boor, P.P.C., Laan, L.J.W. van der, Tilanus, H.W., Kuipers, E.J. & Kwekkeboom, J. (2010). Migration of Allosensitizing Donor Myeloid Dendritic Cells into Recipients After Liver Transplantation. Liver Transplantation, 16(1), 12-22. Bruynzeel, J.A., Feelders, R.A., Groenland, T.H.N., Meiracker, A.H. van den, Eijck, C.H.J. van, Lange, J.F., Herder, W.W. de & Kazemier, G. (2010). Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 95(2), 678-685. Crop, M.J., Baan, C.C., Korevaar, S.S., Ijzermans, J.N.M., Weimar, W. & Hoogduijn, M.J. (2010). Human Adipose TissueDerived Mesenchymal Stem Cells Induce Explosive T-Cell Proliferation. Stem Cells and Development, 19(12), 1843-1853. Crop, M.J., Baan, C.C., Korevaar, S.S., Ijzermans, J.N.M., Pescatori, M., Stubbs, A.P., Ijcken, W.F.J. van, Dahlke, MH, Eggenhofer, E, Weimar, W. & Hoogduijn, M.J. (2010). Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clinical & Experimental Immunology, 162(3), 474-486. Dols, L.F.C., Kok, N.F.M., Terkivatan, T., Tran, T.C.K., d'Ancona, F.C., Langenhuijsen, J.F., Mertens zur Borg, I.R.A.M., Alwayn, I.P.J., Hendriks, M.P., Dooper, IM, Weimar, W. & Ijzermans, J.N.M. (2010). Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial. BMC Surgery, 10, 11. 204 < back to index Dols, L.F.C., Kok, N.F.M. & Ijzermans, J.N.M. (2010). Live donor nephrectomy: a review of evidence for surgical techniques. Transplant International, 23(2), 121-130. Dols, L.F.C., Ijzermans, J.N.M., Wentink, N., Tran, T.C.K., Zuidema, W.C., Dooper, IM, Weimar, W. & Kok, N.F.M. (2010). LongTerm Follow-up of a Randomized Trial Comparing Laparoscopic and Mini-Incision Open Live Donor Nephrectomy. American Journal of Transplantation, 10(11), 2481-2487. Dols, L.F.C., Kok, N.F.M., Terkivatan, T., Tran, T.C.K., Alwayn, I.P.J., Weimar, W. & Ijzermans, J.N.M. (2010). Optimizing leftsided live kidney donation: hand-assisted retroperitoneoscopic as alternative to standard laparoscopic donor nephrectomy. Transplant International, 23(4), 358-363. Dor, F.J.M.F., Ramirez, ML, Down, J.D. & Cooper, D.K.C. (2010). The Spleen as a Site for Hematopoiesis. Transplantation, 90(9), 1040-1041. Dubbeld, J, Hoekstra, H, Farid, W.R.R., Ringers, J, Porte, R.J., Metselaar, H.J., Baranski, AG, Kazemier, G., Berg, A.P van de & Hoek, B. van (2010). Similar liver transplantation survival with selected cardiac death donors and brain death donors. British Journal of Surgery, 97(5), 744-753. Eijkemans, M.J.C., Houdenhoven, M. van, Nguyen, T., Boersma, E., Steyerberg, E.W. & Kazemier, G. (2010). Predicting the Unpredictable A New Prediction Model for Operating Room Times Using Individual Characteristics and the Surgeon's Estimate. Anesthesiology, 112(1), 41-49. Ginhoven, T.M. van, Berg, J.W. van den, Dik, W.A., Ijzermans, J.N.M. & Bruin, R.W.F. de (2010). Preoperative Dietary Restriction Reduces Hepatic Tumor Load by Reduced E-Selectin-Mediated Adhesion in Mice. Journal of Surgical Oncology, 102(4), 348-353. Ginhoven, T.M. van, Huisman, T.M., Berg, J.W. van den, Ijzermans, J.N.M., Delhanty, P.J.D. & Bruin, R.W.F. de (2010). Preoperative fasting induced protection against renal ischemia/reperfusion injury is independent of ghrelin in mice. Nutrition Research, 30(12), 865-869. Ginhoven, T.M. van, Berg, J.W. van den, Dik, W.A., Ijzermans, J.N.M. & Bruin, R.W.F. de (2010). Preoperative fasting induces protection against renal ischemia/reperfusion injury by a corticosterone-independent mechanism. Transplant International, 23(11), 1171-1178. Ginneken, B.T.J. van, Berg-Emons, H.J.G. van den, Metselaar, H.J., Tilanus, H.W., Kazemier, G. & Stam, H.J. (2010). Effects of a rehabilitation programme on daily functioning, participation, health-related quality of life, anxiety and depression in liver transplant recipients. Disability & Rehabilitation, 32(25), 2107-2112. Ginneken, B.T.J. van, Berg-Emons, H.J.G. van den, Windt, A.E. van der, Tilanus, H.W., Metselaar, H.J., Stam, H.J. & Kazemier, G. (2010). Persistent fatigue in liver transplant recipients: a two-year follow-up study. Clinical Transplantation, 24(1), E10-E16. Goede, B. de, Eker, H.H., Metselaar, H.J., Tilanus, H.W., Lange, J.F. & Kazemier, G. (2010). RE: Emergency liver transplantation after umbilical hernia repair: A case report. Transplantation Proceedings, 42(7), 2823-2823. Hoogduijn, M.J., Popp, FC, Grohnert, A, Crop, M.J., Rhijn, M. van, Rowshani, T., Eggenhofer, E, Renner, P, Reinders, ME, Rabelink, T.J., Laan, L.J.W. van der, Dor, F.J.M.F., Ijzermans, J.N.M., Genever, PG, Lange, C, Durrbach, A, Houtgraaf, H.J., Christ, B, Seifert, M, Shagidulin, M, Donckier, V, Deans, R, Ringden, O, Perico, N, Remuzzi, G, Bartholomew, A, Schlitt, HJ, Weimar, W., Baan, C.C. & Dahlke, MH (2010). Advancement of Mesenchymal Stem Cell Therapy in Solid Organ Transplantation (MISOT). Transplantation, 90(2), 124-126. Laan, L.J.W. van der & Dogterom, M (2010). In Vitro Assays to Study Force Generation at Dynamic Microtubule Ends. Methods in Cell Biology, 95, 617-639. Laan, L.J.W. van der, Hudson, M, McPherson, S, Zondervan, P.E., Thomas, RC, Kwekkeboom, J., Lindsay, AS, Burt, AD, Kazemier, G., Tilanus, H.W., Bassendine, MF & Metselaar, H.J. (2010). Results of a Two-Center Study Comparing Hepatic Fibrosis Progression in HCV-positive Liver Transplant Patients Receiving Cyclosporine or Tacrolimus. Transplantation Proceedings, 42(10), 4573-4577. Massey, E., Kranenburg, L.W., Zuidema, W.C., Hak, G., Erdman, R.A.M., Hilhorst, M.T., Ijzermans, J.N.M., Busschbach, J.J. van & Weimar, W. (2010). Encouraging Psychological Outcomes After Altruistic Donation to a Stranger. American Journal of Transplantation, 10(6), 1445-1452. Meijer, V.E. de, Kalish, BT, Puder, M & Ijzermans, J.N.M. (2010). Systematic review and meta-analysis of steatosis as a risk factor in major hepatic resection. British Journal of Surgery, 97(9), 1331-1339. Menke, V., Es, JH van, Lau, W de, Born, M van den, Kuipers, E.J., Siersema, P.D., Bruin, R.W.F. de, Kusters, J.G. & Clevers, H (2010). Conversion of metaplastic Barrett's epithelium into post-mitotic goblet cells by gamma-secretase inhibition. Disease Models & Mechanisms, 3(1-2), 104-110. Mitchell, J.R., Verweij, M., Brand, K., Ven, M. van der, Goemaere, N.N.T., Engel, S. van den, Chu, T, Forrer, F., Muller, C., Jong, M. de, Ijcken, W.F.J. van, Ijzermans, J.N.M., Hoeijmakers, J.H.J. & Bruin, R.W.F. de (2010). Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell, 9(1), 40-53. Morak, M.J.M., Pek, C.J., Kompanje, E.J.O., Hop, W.C.J., Kazemier, G. & Eijck, C.H.J. van (2010). Quality of Life After Adjuvant Intra-Arterial Chemotherapy and Radiotherapy Versus Surgery Alone in Resectable Pancreatic and Periampullary Cancer A Prospective Randomized Controlled Study. Cancer, 116(4), 830-836. 205 < back to index Moroso, V., Metselaar, H.J., Mancham, S., Tilanus, H.W., Eissens, D, Meer, A van der, Laan, L.J.W. van der, Kuipers, E.J., Joosten, I. & Kwekkeboom, J. (2010). Liver Grafts Contain a Unique Subset of Natural Killer Cells that Are Transferred into the Recipient After Liver Transplantation. Liver Transplantation, 16(7), 895-908. Pan, Q., Metselaar, H.J., Ruiter, P.E. de, Kwekkeboom, J., Tilanus, H.W., Janssen, H.L.A. & Laan, L.J.W. van der (2010). Calcineurin Inhibitor Tacrolimus Does Not Interfere with the Suppression of Hepatitis C Virus Infection by Interferon-alpha. Liver Transplantation, 16(4), 520-526. Pool, A.E.M. van der, Wilt, J.H.W. de, Lalmahomed, Z.S., Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases. British Journal of Surgery, 97(3), 383-390. Pool, A.E.M. van der, Mendez Romero, A.M., Wunderink, W., Heijmen, B.J.M., Levendag, P.C., Verhoef, C. & Ijzermans, J.N.M. (2010). Stereotactic body radiation therapy for colorectal liver metastases. British Journal of Surgery, 97(3), 377-382. Pool, A.E.M. van der, Lalmahomed, Z.S., Wilt, J.H.W. de, Eggermont, A.M.M., Ijzermans, J.N.M. & Verhoef, C. (2010). Trends in Treatment for Synchronous Colorectal Liver Metastases: Differences in Outcome Before and After 2000. Journal of Surgical Oncology, 102(5), 413-418. Roodnat, J.I., Zuidema, W., Wetering, J. van de, Klerk, M. de, Erdman, R.A.M., Massey, E., Hilhorst, M.T., Ijzermans, J.N.M. & Weimar, W. (2010). Altruistic Donor Triggered Domino-Paired Kidney Donation for Unsuccessful Couples from the KidneyExchange Program. American Journal of Transplantation, 10(4), 821-827. Roodnat, J.I., Wetering, J. van de, Zuidema, W., Noord, MAA van, Kal-van Gestel, J.A., Ijzermans, J.N.M. & Weimar, W. (2010). Ethnically Diverse Populations and Their Participation in Living Kidney Donation Programs. Transplantation, 89(10), 1263-1269. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Dam, T.B. van, Ijzermans, J.N.M., Weimar, W. & Baan, C.C. (2010). Characterization of Rabbit Antithymocyte Globulins-Induced CD25(+) Regulatory T Cells From Cells of Patients With End-Stage Renal Disease. Transplantation, 89(6), 655-666. Sewgobind, V.D.K.D., Laan, L.J.W. van der, Kho, M.M.L., Kraaijeveld, R., Korevaar, S.S., Mol, W.M., Weimar, W. & Baan, C.C. (2010). The calcineurin inhibitor tacrolimus allows the induction of functional CD4+CD25+regulatory T cells by rabbit antithymocyte globulins. Clinical & Experimental Immunology, 161(2), 364-377. Sewgobind, V.D.K.D., Quaedackers, M.E., Laan, L.J.W. van der, Kraaijeveld, R., Korevaar, S.S., Chan, G, Weimar, W. & Baan, C.C. (2010). The Jak Inhibitor CP-690,550 Preserves the Function of CD4+CD25brightFoxP3+Regulatory T Cells and Inhibits Effector T Cells. American Journal of Transplantation, 10(8), 1785-1795. Snoeijs, MG, Schaubel, DE, Hene, R, Hoitsma, A.J., Idu, M.M., Ijzermans, J.N.M., Ploeg, R.J., Ringers, J, Christiaans, MH, Buurman, W.A. & Heurn, L.W.E. van (2010). Kidneys from Donors after Cardiac Death Provide Survival Benefit. Journal of the American Society of Nephrology, 21(6), 1015-1021. Tapirdamaz, O., Mancham, S., Laan, L.J.W. van der, Kazemier, G., Thielemans, K., Metselaar, H.J. & Kwekkeboom, J. (2010). Detailed Kinetics of the Direct Allo-Response in Human Liver Transplant Recipients: New Insights from an Optimized Assay. PLoS One, 5(12). Tjon, S.W.A., Sint Nicolaas, J., Kwekkeboom, J., Man, R.A. de, Kazemier, G., Tilanus, H.W., Hansen, B.E., Laan, L.J.W. van der, Tha-In, T.H. & Metselaar, H.J. (2010). Increased Incidence of Early De Novo Cancer in Liver Graft Recipients Treated with Cyclosporine: An Association with C-2 Monitoring and Recipient Age. Liver Transplantation, 16(7), 837-846. Windt, D.J. van der, Smetanka, C, Macedo, C, He, J, Lakomy, R, Bottino, R, Ekser, B, Echeverri, GJ, Metes, D, Ijzermans, J.N.M., Trucco, M, Cooper, D.K.C. & Lakkis, FG (2010). Investigation of Lymphocyte Depletion and Repopulation Using Alemtuzumab (Campath-1H) in Cynomolgus Monkeys. American Journal of Transplantation, 10(4), 773-783. Witjes, C.D.M. & Kazemier, G. (2010). An immunocompromised host with a fever. Nederlands Tijdschrift voor Geneeskunde, 154, 1500. Witjes, C.D.M., Man, R.A. de, Eskens, F.A.L.M., Dwarkasing, R.S., Zondervan, P.E., Verhoef, C. & Ijzermans, J.N.M. (2010). Hepatocellular carcinoma: the significance of cirrhosis for treatment and prognosis- retrospective study. Nederlands Tijdschrift voor Geneeskunde, 154, 1747. 206 < back to index EMC MM-04-49-03-A - Genitourinary tract disorders in children Programme in brief design Experimental and clinical investigation of normal and pathological function and recovery of the urinary tract and reproductive tract. Antenatal diagnostics, detection of congenital disorders before birth and the resulting postnatal evaluation and treatment. Bladder dysfunction, neurogenic and structural. The mechanisms that connect loss of bladder and renal function to changes in bladder structure plus new treatments are investigated in an animal model for infravesical obstruction. Raman spectroscopy is applied for in vitro and in vivo analysis of the bladder wall-structure (also in bladder cancer). In co-operation with the centre for optical diagnostics and therapy, Dr. G.J. Puppels. Gonadal dysgenesis. The chromosal changes occuring in gonadal tissue of patients with gonadal dysgenesis are studied to improve its diagnosis, to gain insight into its development and to discover early markers of testicular cancer. Joint KWF project with the laboratory of experimental pathology and oncology, Dr. L.H.J. Looijenga. Hypospadia, possible causes of hypospadias like androgen receptor and the effect of hypospadias correction on urodynamics are investigated. Inborn errors predisposing to stone formation. The role of inborn errors in renal metabolite handling for urinary stone formation is studied. Obstruction and reflux, of the pyelo-ureteric junction, ureter with (functional) obstructions, vesicoureteric reflux and infravesical obstruction in prospective studies. In co-operation with the department of Nuclear Medicine, Prof. Dr. H.Y. Oei. Urinary tract infection. Proteomics and bacterial DNA analysis are used to study bacterial populations in the urinary tract and to improve diagnosis of UTI. Specific complications like bladder stone formation are analysed. New bladder rinsing fluids are developed. In co-operation with departments of medical microbiology and infectious diseases, Prof. Dr. A van Belkum, Center for Biomics, Dr. T.M. Luider and obstetrics, Dr. T Schneider. Urodynamic investigations, in connection to the other projects the value of urodynamic evaluations is investigated in cooperation with FURORE. Key figures Department urology Total SP1 SP2 SP3 SP4 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1,2 0 0 0 1,2 1,2 0 0 0 1,2 0 0 0 0 4 0 0 4 Artikel/Letter to the editor Hafezi, F, Moesen, I, Carels, G, Mooy, C & Paridaens, A.D.A. (2010). Waldenstrom's macroglobulinaemia of the lacrimal gland in a patient with sarcoidosis. Ophthalmologe, 107(1), 60-+. Kok, R.C., Timmerman, M.A., Wolffenbuttel, K.P., Drop, S.L.S. & Jong, F.H. de (2010). Isolated 17,20-Lyase deficiency due to the cytochrome b5 mutation W27X. Journal of Clinical Endocrinology and Metabolism, 95(3), 994-999. Looijenga, L.H.J., Hersmus, R., Leeuw, H.C.G.M. de, Stoop, H., Cools, MBC, Oosterhuis, J.W., Drop, S.L.S. & Wolffenbuttel, K.P. (2010). Gonadal tumours and DSD. Best Practice & Research Clinical Endocrinology & Metabolism, 24, 391-310. Pleskacova, J., Hersmus, R., Oosterhuis, J.W., Setyawati, B.A., Faradz, SMH, Cools, M.B.C., Wolffenbuttel, K.P., Lebl, J., Drop, S.L.S. & Looijenga, L.H.J. (2010). Tumor risk in disorders of sex development. Sexual Development, 4, 259-269. 207 < back to index EMC MM-04-54-07 - Disorders of the gastrointestinal tract in childhood Programme in brief design The digestive tract is under constant attack by bacteria, viruses and other noxious agents in the lumen of the gastrointestinal tract. The gastrointestinal mucosa, consisting of the epithelium and the underlying immune cells in the lamina propria, forms an important line of defence against these potential harmful agents. Mucosal damage may lead to malabsorption and diarrhea, since the gastrointestinal epithelium is essential for the digestion and uptake of nutrients and for the maintenance of the liquid balance in the human body. Many types of gastrointestinal diseases lead to mucosal damage. The mission of the research program is to unravel the mechanisms underlying normal function and disorders of the gastrointestinal tract including the liver, in childhood by means of integrated pre-clinical and clinical research. This research aims at the development of strategies for prevention, diagnosis, and treatment of gastrointestinal diseases. In particular, research is focussed on mechanisms responsible for damage and subsequent regeneration of the gastrointestinal tract in 1. Inflammatory bowel diseases (Crohn and ulcerative colitis), 2. Infectious diseases (rotavirus or norovirus, E. coli) 3. Inherited diseases (cystic fibrosis, CrigIer Najjar), and 4. after chemotherapy. The relevance is perhaps best illustrated by the high incidence of each of the studied diseases. Possibilities are evaluated of intervention using dietary components, probiotics, or drugs, either to prevent mucosal damage or to stimulate the recovery of mucosal functions after an insult. Key figures Department pediatrics pediatrics-other Total SP1 SP2 0 2 2 SP3 0 0 0 SP4 1 3 4 0 0 0 Sptot T1 T2 T3 Ttot IS FS OP Ptot 1 5 6 2 1 0 3 18 3 3 27 Thesis Beuling, E.A. (2010, december 02). GATA transcription factors and the regulation of intestinal development, differentation and function. EUR (202 pag.) (Rotterdam). Prom./coprom.: Prof.Dr. H.A. Buller, R.J. Grand & S.D. Krasinski. Damen, G.M. (2010, april 14). Pediatric Inflammatory Bowel Disease. EUR (134 pag.) (Breda: NPN drukkers B.V.). Prom./coprom.: Prof.dr. A.J. van der Heijden, E.E.S. Nieuwenhuis, Dr. J.C. Escher & Dr. J.N. Samsom. Lierop, P.P.E. van (2010, september 15). The role of the innate immune system in inflammatory bowel disease. EUR (172 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. A.J. van der Heijden, E.E.S. Nieuwenhuis, Dr. J.N. Samsom & Dr. J.C. Escher. Artikel/Letter to the editor Aktas, H., Ridder, L. de, Haringsma, J., Kuipers, E.J. & Mensink, P.B.F. (2010). Complications of single-balloon enteroscopy: a prospective evaluation of 166 procedures. Endoscopy, 42, 365-368. Assche, G van, Dignass, A., Woude, C.J. van der, Oldenburg, B, D'Haens, G, Gionchetti, P., Vucelic, B., Soderholm, J., Escher, J.C., Koletzko, S, Lukas, M., Tilg, H., Vermeire, S, Cole, A, Stange, E. & Travis, S. (2010). The second European evidencebased consensus on the diagnosis and management of Crohn's disease: special situations. Journal of Crohn's and Colitis, 4, 63-101. Damen, G.M., Krieken, H. van, Hoppenreijs, E.P.A.H., Os, E. van, Tolboom, J.J.M., Warris, A., Yntema, J.B.L., Nieuwenhuis, E.E.S. & Escher, J.C. (2010). Overlap, common features and essential differences in pediatric granulomatous inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition, 51, 690-697. Dieren, J.M. van, Lambers, M.E.H., Kuipers, E.J., Samsom, J.N., Woude, C.J. van der & Nieuwenhuis, E.E.S. (2010). Local immune regulation of mucosal inflammation by Tacrolimus. Digestive Diseases & Sciences, 55, 2514-2519. Heikema, A.P., Bergman, M.P., Richards, H, Crocker, P.R., Gilbert, M., Samsom, J.N., Wamel, W.J.B. van, Endtz, H.P. & Belkum, A. van (2010). Characterization of the specific interaction between Sialoadhesin and Sialylated Campylobacter jejuni lipoologosaccharides. Infection & Immunity, 78(7), 3237-3246. Horsthuis, K, Ridder, L. de, Smets, AMJB, Leeuwen, MS van, Benninga, M.A., Houwen, R.H.J., Littooij, A.S., Nievelstein, R.A.J. & Stoker, J. (2010). Magnetic resonance enterography for suspected inflammatory bowel disease in a pediatric population. Journal of Pediatric Gastroenterology and Nutrition, 51(5), 603-609. Hulst, J.M., Zwart, H., Hop, W.C.J. & Joosten, K.F.M. (2010). Dutch national survey to test the STRONGkids nutritional risk screening tool in hospitalized children. Clinical Nutrition, 29, 106-111. Jong, J.C. de, Escher, J.C., Arends, L.R., Jaddoe, V.W.V.K., Hofman, A., Raat, H. & Moll, H.A. (2010). Infant nutritional factors and functional constipation in childhood: The Generation R Study. American Journal of Gastroenterology, 105, 940-945. Joosten, K.F.M., Zwart, H., Hop, W.C.J. & Hulst, J.M. (2010). National malnutrition screening days in hospitalised children in The Netherlands. Archives of Disease in Childhood, 95, 141-145. Joosten, K.F.M., Zwart, H., Hop, W.C.J. & Hulst, J.M. (2010). Ondervoeding bij eenvijfde van kinderen opgenomen in Nederlandse ziekenhuizen. Nederlands Tijdschrift voor Geneeskunde, 154, A1641. 208 < back to index Kuijf, M.L., Samsom, J.N., Rijs, W. van, Bax, M., Huizinga, R, Heikema, A.P., Doorn, P.A. van, Belkum, A. van, Kooyk, Y. van, Burgers, P.C., Luider, T.M., Endtz, H.P., Nieuwenhuis, E.E.S. & Jacobs, B.C. (2010). TLR4-mediated sensing of Campylobacter jejuni by dendritic cells is determined by sialylation. Journal of Immunology, 185, 748-755. Lee, JJ, Essers, J.B., Kugathasan, S., Escher, J.C., Lettre, G., Butler, J.L., Stephens, M.C., Ramoni, M.F., Grand, R.J. & Hirschhorn, J. (2010). Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study. Annals of Human Genetics, 74, 489-497. Lee, JJ, Escher, J.C., Shuman, M.J., Forbes, P.W., Delemarre, L.C., Harr, B.W., Kruijer, M., Moret, M., Allende-Richter, S. & Grand, R.J. (2010). Final adult height of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score. Inflammatory Bowel Diseases, 16(10), 1669-1677. Lierop, P.P.E. van, Haar, C.G. de, Lindenbergh-Kortleve, D.J, Simons-Oosterhuis, Y., Rijt, L.S. van, Lambrecht, B.N.M., Escher, J.C., Samsom, J.N. & Nieuwenhuis, E.E.S. (2010). T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model. Inflammatory Bowel Diseases, 16(3), 442-451. Mouravieva, A., Escher, J.C., Kessel, I. van, Beishuizen, A., Vanheusden, K. & Wagner, A. (2010). Familiaire adenomateuze polyposis coli op de kinderleeftijd. Tijdschrift voor Kindergeneeskunde, 78(1), 28-33. Olieman, J.F., Penning, C., IJsselstijn, H., Escher, J.C., Joosten, K.F.M., Hulst, J.M. & Tibboel, D. (2010). Enteral nutrition in children with short-bowel syndrome: current evidence and recommendations for the clinician. Journal of the American Dietetic Association, 110, 420-426. Olieman, J.F., Poley, M.J., Gischler, S.J., Penning, C., Escher, J.C., Hoonaard, T.L. van den, Goudoever, J.B. van, Bax, N.M.A., Tibboel, D. & Meijers-IJsselstijn, H. (2010). Interdisciplinary management of infantile short bowel syndrome: resource consumption, growth, and nutrition. Journal of Pediatric Surgery, 45, 490-498. Ridder, L. de, Rings, E.H.H.M. & Escher, J.C. (2010). Richtlijn 'Diagnostiek en behandeling van inflammatoire darmziekte bij kinderen'. Nederlands Tijdschrift voor Geneeskunde, 154, A1898. Ridder, L. de & Groeneweg, M. (2010). Accidentele ingestie van een etsend middel op de kinderleeftijd: is endoscopie altijd nodig? Praktische Pediatrie, 2, 112-115. Shirinbak, S, Taher, YA, Maazi, H, Gras, R, Esch, BCAM van, Henricks, PAJ, Samsom, J.N., Verbeek, JS, Lambrecht, B.N.M., Oosterhout, A.J.M. van & Nawijn, MC (2010). Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice. Journal of Immunology, 185(7), 3857-3865. Smits, S.L., Leeuwen, M. van, Eijk, A.A. van der, Fraaij, P.L.A., Escher, J.C., Simon, J.H. & Osterhaus, A.D.M.E. (2010). Human astrovirus in a patient with new-onset celiac disease. Journal of Clinical Microbiology, 48(9), 3416-3418. Strijbosch, R.A.M., Hoonaard, T.L. van den, Olieman, J.F., Escher, J.C., Alwayn, I.P.J. & Meijers-IJsselstijn, H. (2010). Visolie bij langdurige parenterle voeding bij kinderen. Nederlands Tijdschrift voor Geneeskunde, 154, A2003. Wauben, M.H.M., Toes, R.E.M., Bos, N.A., Damoiseaux, J., Ham, S.M. van, Loosdrecht, AA van de & Samsom, J.N. (2010). Sending and signaling by the immune system NVVI-Dutch Society for Immunology Course, April 2-3, 2009. Immunology Letters, 128, 1-3. 209 < back to index EMC MM-04-54-08-A - Clinical, epidemiological and basic research of infectious diseases and immunological diseases in children Programme in brief design This programme aims to enhance the understanding of the (molecular) pathogenesis, pathobiology, epidemiology, diagnosis, therapy and prevention of infectious diseases and immunological disorders in children by means of clinical and basic research. Infectious diseases are the major cause of morbidity in children and contribute substantially towards mortality in children needing topclinical care including those with AIDS, meningococcal sepsis and immunocompromised children with sepsis. Primary and secondary (acquired) immunodeficiencies as well as immunodysregulations, in particular auto-immunity, are frequent diagnostic and therapeutic challenges and often complicated by (serious) infections. The studies carried out within this project aim to increase the understanding of interactions between host and micro-organisms and to improve the diagnostic, therapeutic and preventive modalities of infectious diseases and immunological disorders. Key figures Department neurology pediatrics pediatricsimmuno/infection pediatrics-other Total SP1 SP2 SP3 SP4 0 1,89 0 0 1 1 0 0,67 2 1 4,89 0 2,3 2,3 0 0,44 2,44 0 5,9 6,57 Sptot T1 1 3,56 2 9,64 16,2 5 T2 T3 1 0 Ttot 6 IS 75 FS 6 OP 7 Ptot 94 Thesis Hendriksen, W.T. (2010, mei 25). Gene regulaton in Streptococcus pneumoniae: interplay between nutrition and virulence. EUR (221 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Dr. P.W.M. Hermans, Prof.Dr. R. de Groot & H.J. Bootsma. Labout, J.A.M. (2010, december 22). Bacterial carriage in infancy. Risk factors and consequences. EUR (150 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof.Dr. H.A. Moll & Dr. P.W.M. Hermans. Mook-Kanamori, D.O. (2010, november 24). Genetic and environmental influences on early growth. The Generation R Study. EUR (241 pag.) (Rotterdam: Optima Grafische Communicatie). Prom./coprom.: Prof. Dr. A. Hofman, Prof. Dr. E.A.P. Steegers & Dr. V.W.V.K. Jaddoe. Rakhmanina, N.Y. (2010, december 21). Optimizing antiretroviral therapy in children and adolescents with HIV infection. EUR (226 pag.). Prom./coprom.: Prof.Dr. R. de Groot & Prof.Dr. D. Tibboel. Rours, G.I.J.G. (2010, juni 11). Chlamydia trachomatis. Infections during pregnancy. EUR (208 pag.) (Rotterdam: Haveka BV). Prom./coprom.: Prof. Dr. H.A. Verbrugh, Prof.Dr. R. de Groot & Dr. R.P.A.J. Verkooijen. Veen, M. (2010, april 16). The Manchester Triage System in paediatric emergency care. EUR (168 pag.) (Enschede: Ipskamp Drukkers). Prom./coprom.: Prof. Dr. H.A. Moll & Prof. Dr. E.W. Steyerberg. Artikel/Letter to the editor Albers, H.M., Brinkman, D.M.C., Kamphuis, S.S.M., Suijlekom-Smit, L.W.A. van, Rossum, M.A.J. van, Hoppenreijs, E.P.A.H., Girschick, H.J., Wouters, C.H., Saurenmann, R.K., Houwing-Duistermaat, J.J., Huizinga, T.W.J., Schilham, M.W. & Cate, R. ten (2010). Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis. Arthritis Care & Research, 62(2), 204-212. Bakker, R., Pluimgraaff, L.E., Steegers, E.A.P., Raat, H., Tiemeier, H.W., Hofman, A. & Jaddoe, V.W.V.K. (2010). Associations of light and moderate maternal alcohol consumption with fetal growth characteristics in different periods of pregnancy: The Generation R Study. International Journal of Epidemiology, 39(3), 777-789. Bakker, R., Steegers, E.A.P., Obradov, A, Raat, H., Hofman, A. & Jaddoe, V.W.V.K. (2010). Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: the Generation R Study. American Journal of Clinical Nutrition, 91(6), 1691-1698. Bakker, R., Steegers, E.A.P., Mackenbach, J.P., Hofman, A. & Jaddoe, V.W.V.K. (2010). Maternal smoking and blood pressure in different trimesters of pregnancy: The Generation R Study. Journal of Hypertension, 28(11), 2210-2218. Batenburg-Eddes, T. van, Groot, L. de, Steegers, E.A.P., Hofman, A., Jaddoe, V.W.V.K., Verhulst, F.C. & Tiemeier, H.W. (2010). Fetal Programming of Infant Neuromotor Development: The Generation R Study. Pediatric Research, 67(2), 132-137. Been, J.V., Rours, G.I.J.G., Kornelisse, R.F., Jonkers, F., Krijger, R.R. de & Zimmermann, L.J.I. (2010). Chorioamnionitis alters the response to surfactant in preterm infants. Journal of Pediatrics, 156, 10-15. Bezemer, D., Sighem, A. van, Lukashov, V.V., Hoek, L. van den, Back, N., Schuurman, R., Boucher, C.A.B., Claas, E.C.J., Boerlijst, M.C., Coutinho, R.A., Wolf, F. de & ATHENA study group, - (2010). Transmission networks of HIV-1 among men having sex with men in the Netherlands. Aids, 24, 271-282. 210 < back to index Blom, E.A., Jansen, P.W., Verhulst, F.C., Hofman, A., Raat, H., Jaddoe, V.W.V.K., Coolman, M., Steegers, E.A.P. & Tiemeier, H.W. (2010). Perinatal complications increase the risk of postpartum depression. The Generation R Study. Bjog-An International Journal of Obstetrics and Gynaecology, 117(11), 1390-1398. Bongers, T.N., Emonts, M., Maat, M.P.M. de, Groot, R. de, Lisman, T., Hazelzet, J.A. & Leebeek, F.W.G. (2010). Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome. Blood Coagulation & Fibrinolysis, 103, 1181-1187. Burg, M. van der, Pac, M, Berkowska, M.A., Goryluk-Kozakiewicz, B., Wakulinska, A., Dembowska-Balginska, B., Gregorek, H., Barendregt, B.H., Krajewska-Walasek, M., Bernatowska, E., Dongen, J.J.M. van, Chrzanowska, K.H. & Langerak, A.W. (2010). Loss of juxtaposition of RAG-induced immunoglobulin DNA ends is implicated in the precursor B-cell differentiation defect in NBS patients. Blood, 115(23), 4770-4777. Coolman, M., Groot, C.J.M. de, Jaddoe, V.W.V.K., Hofman, A., Raat, H. & Steegers, E.A.P. (2010). Medical record validation of maternally reported history of preeclampsia. Journal of Clinical Epidemiology, 63(8), 932-937. Davila, S, Wright, V.J., Khor, C.C., Sim, K.S., Binder, A., Breunis, W.B., Inwald, D., Nadel, S., Betts, H., Carrol, E.D., Groot, R. de, Hermans, P.W.M., Hazelzet, J.A., Emonts, M., Lim, C.C., Kuijpers, T.W., Martinon-Torres, F., Salas, A., Zenz, W., Levin, M. & Hibberd, M.L. (2010). Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nature Genetics, 42(9), 772-U63. Duijts, L., Jaddoe, V.W.V.K., Hofman, A. & Moll, H.A. (2010). Prolonged and Exclusive Breastfeeding Reduces the Risk of Infectious Diseases in Infancy. Pediatrics, 126(1), E18-E25. Durmus, B., Mook-Kanamori, D.O., Holzhauer, S., Hofman, A., Beek, E.M. van der, Boehm, G., Steegers, E.A.P. & Jaddoe, V.W.V.K. (2010). Growth in foetal life and infancy is associated with abdominal adiposity at the age of 2 years: The Generation R Study. Clinical Endocrinology, 72(5), 633-640. Elfrink, M.E.C., Schuller, AA, Veerkamp, J.S.J., Poorterman, J.H.G., Moll, H.A. & Cate, B.J.M. ten (2010). Factors increasing the caries risk of second primary molars in 5-year-old Dutch children. International Journal of Paediatric Dentistry, 20, 151-157. Emonts, M., Vermont, C.L.V., Houwing-Duistermaat, J.J., Haralambous, E., Gaast-de Jongh, C.E., Hazelzet, J.A., Faust, S.N., Betts, H., Hermans, P.W.M., Levin, M. & Groot, R. de (2010). Polymorphisms in PARP, IL1B, IL4, C1INH, DEFB1 and DEFA4 in meningococcal disease in three populations. Shock, 34(1), 17-22. Fraaij, P.L.A., Houmes, R.J.M., Geukers, V.M., Gesink - van der Veer, B.J., Kneyber, M.C.J. & Tibboel, D. (2010). Acute respiratory distress syndrome¿ (ARDS) als ernstige complicatie van influenza. Nederlands Tijdschrift voor Geneeskunde, 153, 1640. Fraaij, P.L.A. & Osterhaus, A.D.M.E. (2010). the epidemiology of influenza viruses in humans. Hot Topics in Respiratory Medicine, 5(13), 7-14. Freathy, RM, Mook-Kanamori, D.O., Sovio, U, Prokopenko, I, Timpson, NJ, Berry, DJ, Warrington, NM, Widen, E, Hottenga, J.J., Kaakinen, M, Lange, LA, Bradfield, JP, Kerkhof, M., Marsh, JA, Magi, R, Chen, C.M., Lyon, HN, Kirin, M, Adair, LS, Aulchenko, Y.S., Bennett, AJ, Borja, JB, Bouatia-Naji, N, Charoen, P, Coin, LJM, Cousminer, DL, Geus, E.J.C. de, Deloukas, P, Elliott, P, Evans, DM, Froguel, P, Glaser, B., Groves, CJ, Hartikainen, AL, Hassanali, N, Hirschhorn, JN, Hofman, A., Holly, J.M.P., Hypponen, E, Kanoni, S, Knight, BA, Laitinen, J, Lindgren, CM, McArdle, WL, O'Reilly, PF, Pennell, CE, Postma, D.S., Pouta, A, Ramasamy, A, Rayner, NW, Ring, SM, Rivadeneira, F., Shields, BM, Strachan, DP, Surakka, I, Taanila, A, Tiesler, C, Uitterlinden, A.G., Duijn, C.M. van, Wijga, A.H., Willemsen, G, Zhang, HT, Zhao, JH, Wilson, JF, Steegers, E.A.P., Hattersley, A.T., Eriksson, JG, Peltonen, L., Mohlke, KL, Grant, S.F.A., Hakonarson, H, Koppelman, G.H., Dedoussis, GV, Heinrich, J., Gillman, MW, Palmer, LJ, Frayling, T.M., Boomsma, D.I., Smith, G.D., Power, C, Jaddoe, V.W.V.K., Jarvelin, MR & McCarthy, MI (2010). Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nature Genetics, 42(5), 430U73. Geelhoed, J.J.M. & Jaddoe, V.W.V.K. (2010). Early influences on cardiovascular and renal development. European Journal of Epidemiology, 25, 677-692. Geelhoed, J.J.M., Taal, H.R., Steegers, E.A., Arends, L.R., Lequin, M., Moll, H.A., Hofman, A., Heijden, A.J. van der & Jaddoe, V.W.V.K. (2010). Kidney growth curves in healthy children from the third trimester of pregnancy until the age of two years. The Generation R Study. Pediatric Nephrology, 25(2), 289-298. Geelhoed, M.J.J., Steegers, E.A.P., Koper, J.W., Rossum, E.F.C. van, Moll, H.A., Raat, H., Tiemeier, H.W., Hofman, A. & Jaddoe, V.W.V.K. (2010). Glucocoricoid receptor gene polymorphisms do not affect growth in fetal and early postnatal life. The Generation R Study. BMC Medical Genetics, 11(39). Groen, E. de, Mohangoo, A.D., Jongste, J.C. de, Wouden, J.C. van der, Moll, H.A., Jaddoe, V.W.V.K., Hofman, A., Koning, H.J. de & Raat, H. (2010). Early detection and counselling intervention of asthma symptoms in preschool children: study design of a cluster randomised controlled trial. Bmc Public Health, 10, 555. Henrichs, J., Schenk, JJ, Barendregt, C.S., Schmidt, H.G., Steegers, E.A.P., Hofman, A., Jaddoe, V.W.V.K., Moll, H.A., Verhulst, F.C. & Tiemeier, H.W. (2010). Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study. Developmental Medicine & Child Neurology, 52(7), 644-651. Henrichs, J., Schenk, J.J.A.M., Roza, S.J., Berg, M.P. van den, Schmidt, H.G., Steegers, E.A.P., Hofman, A., Jaddoe, V.W.V.K., Verhulst, F.C. & Tiemeier, H.W. (2010). Maternal psychological distress and fetal growth trajectories: The Generation R Study. Psychological Medicine, 40(4), 633-643. 211 < back to index Henrichs, J., Schokking, J.J., Schenk, JJ, Ghassabian, A., Schmidt, H.G., Visser, T.J., Hooijkaas, H., Muinck Keizer-Schrama, S.M.P.F., Hofman, A., Jaddoe, V.W.V.K., Visser, W., Steegers, E.A.P., Verhulst, F.C., Rijke, Y.B. de & Tiemeier, H.W. (2010). Maternal Thyroid Function during Early Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study. Journal of Clinical Endocrinology and Metabolism, 95(9), 4227-4234. Herba, C.M., Roza, S.J., Govaert, P., Rossum, J van, Hofman, A., Jaddoe, V.W.V.K., Verhulst, F.C. & Tiemeier, H.W. (2010). Infant Brain Development and Vulnerability to Later Internalizing Difficulties: The Generation R Study. Journal of the American Academy Child Adolescent Psychiatry, 49(10), 1053-1063. Hernan, M.A. (2010). The effect of combined antiretrovirl therapy on the overall mortality of HIV-infected individuals. The HIVCAUSAL Collaboration. Aids, 24, 123-137. Hira, V., Sluijter, M., Goessens, W.H.F., Ott, A., Groot, R. de, Hermans, P.W.M. & Kornelisse, R.F. (2010). Coagulase-negative Staphylococcal skin carriage among neonatal intensive care unit personnel: from population to infection. Journal of Clinical Microbiology, 48(11), 3876-3881. Immerzeel, TD van, Gilst, R.M. van & Hartwig, N.G. (2010). Beneficial use of immunoglobulins in the treatment of Sydenham chorea. European Journal of Pediatrics, 169, 1151-1154. Jaddoe, V.W.V.K., Duijn, C.M. van, Heijden, A.J. van der, Mackenbach, J.P., Moll, H.A., Steegers, E.A.P., Tiemeier, H.W., Uitterlinden, A.G., Verhulst, F.C. & Hofman, A. (2010). The Generation R Study: design and cohort update 2010. European Journal of Epidemiology, 25(11), 823-841. Jansen, P.W., Tiemeier, H.W., Verhulst, F.C., Burdorf, A., Jaddoe, V.W.V.K., Hofman, A., Moll, H.A., Verburg, B.O., Steegers, E.A.P., Mackenbach, J.P. & Raat, H. (2010). Employment status and the risk of pregnancy complications: the Generation R Study. Occupational and Environmental Medicine, 67, 387-394. Jansen, P.W., Raat, H., Mackenbach, J.P., Jaddoe, V.W.V.K., Hofman, A., Oort, F.V.A. van, Verhulst, F.C. & Tiemeier, H.W. (2010). National Origin and Behavioural Problems of Toddlers: The Role of Family Risk Factors and Maternal Immigration Characteristics. Journal of Abnormal Child Psychology, 38(8), 1151-1164. Jong, J.C. de, Escher, J.C., Arends, L.R., Jaddoe, V.W.V.K., Hofman, A., Raat, H. & Moll, H.A. (2010). Infant nutritional factors and functional constipation in childhood: The Generation R Study. American Journal of Gastroenterology, 105, 940-945. Jonge, L.L. de, Osch-Gevers, M. van, Geelhoed, J.J.M., Hofman, A., Steegers, E.A.P., Helbing, W.A. & Jaddoe, V.W.V.K. (2010). Breastfeeding is not associated with left cardiac structures and blood pressure during the first two years of life. The Generation R Study. Early Human Development, 86(8), 463-468. Kampen, J.J.A. van, Reedijk, M.L., Burgers, P.C., Dekker, L.J.M., Hartwig, N.G., Ende, M.E. van der, Groot, R. de, Osterhaus, A.D.M.E., Burger, D, Luider, T.M. & Gruters, R.A. (2010). Ultra-fast analysis of plasma and intracellular levels of HIV protease inhibitors in children: a clinical application of MALDI Mass Spectometry. PLoS One, 5(7), e11409. Knaap, L.C. van der & Jaarsveld, van -Bakker, de, P.W. (2010). Avondspreekuur voor hiv-geinfecteerde jongeren. Tijdschrift voor Verpleegkundigen, 3, 25-27. Knaap, L.C. van der & Jaarsveld, van -Bakker, de, P.W. (2010). Hiv in de zorg. TvZ. Tijdschrift voor Verpleegkunde, 6, 20. Kort, S.W.K. de, Mook-Kanamori, D.O., Jaddoe, V.W.V.K. & Hokken-Koelega, A.C.S. (2010). Interactions between TCF7L2 genotype and growth hormone-induced changes in glucose homeostatis in small for gestational age children. Clinical Endocrinology, 72, 47-52. Krul, M., Wouden, J.C. van der, Schellevis, F.G., Suijlekom-Smit, L.W.A. van & Koes, B.W. (2010). Nursemaid's elbow: its diagnostic clues and preferred means of reduction. Journal of Family Practice, 59(1), E5-E7. Landlinger, C., Preuner, S., Baskova, L., Grotel, M. van, Hartwig, N.G., Dworzak, M, Mann, G., Attarbaschi, A., Kager, L., Peters, C., Matthes-Martin, S., Lawitschka, A., Heuvel-Eibrink, M.M. van den & Lion, T. (2010). Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients. Leukemia, 24, 2032-2038. Lebon, A., Moll, H.A., Tavakol, M., Wamel, W.J.B. van, Jaddoe, V.W.V.K., Hofman, A., Verbrugh, H.A. & Belkum, A. van (2010). Correlation of bacterial colonization status between mother and child: the Generation R Study. Journal of Clinical Microbiology, 48(3), 960-962. Li, Y., He, Y, Qi, L., Jaddoe, V.W.V.K., Feskens, E.J.M., Yang, XJ, Ma, G. & Hu, FB (2010). Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood. Diabetes, 59, 2400-2406. Louwers, E.C.F.M., Affourtit, M.J., Moll, H.A., Koning, H.J. de & Korfage, I.J. (2010). Screening for child abuse at emergency departments: a systemic review. Archives of Disease in Childhood, 95, 214-218. Luijk, P.C.M., Saridjan, N.S., Tharner, A., Ijzendoorn, MH van, Bakermans-Kranenburg, MJ, Jaddoe, V.W.V.K., Hofman, A., Verhulst, F.C. & Tiemeier, H.W. (2010). Attachment, Depression, and Cortisol: Deviant Patterns in Insecure-Resistant and Disorganized Infants. Developmental Psychobiology, 52(5), 441-452. Luijk, P.C.M., Velders, F.P., Tharner, A., IJzerdoorn, MH, Bakermans-Kranenburg, MJ, Jaddoe, V.W.V.K., Hofman, A., Verhulst, F.C. & Tiemeier, H.W. (2010). FKBP5 and resistant attachment predict cortisol reactivity in infants: Gene-environment interaction. Psychoneuroendocrinology, 35(10), 1454-1461. 212 < back to index Maas, A.J.B.M., Mook-Kanamori, D.O., Ay, L., Steegers, E.A.P., Duijn, C.M. van, Hofman, A., Hokken-Koelega, A.C.S. & Jaddoe, V.W.V.K. (2010). Insulin VNTR and IGF-1 promotor region polymorphisms are not associated with body composition in early childhood: The Generation R Study. Hormone Research, 73, 120-127. Marroun El, H., Tiemeier, H.W., Steegers, E.A.P., Roos-Hesselink, J.W., Jaddoe, V.W.V.K., Hofman, A., Verhulst, F.C., Brink, W van den & Huizink, A.C. (2010). A prospective study on intrauterine cannabis exposure and fetal blood flow. Early Human Development, 86(4), 231-236. Meesters, R.J.W., Kampen, J.J.A. van, Reedijk, M.L., Scheuer, R.D., Dekker, L.J.M., Burger, D.M., Hartwig, N.G., Osterhaus, A.D.M.E., Luider, T.M. & Gruters, R.A. (2010). Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots. Analytical and Bioanalytical Chemistry, 398, 319-328. Mohangoo, A.D., Koning, H.J. de, Groen, E. de, Wouden, J.C. van der, Jaddoe, V.W.V.K., Moll, H.A., Hofman, A., Mackenbach, J.P., Jongste, J.C. de & Raat, H. (2010). A comparison of parent-reported wheezing of shortness of breath among infants as assessed bij questonnaire and physician-interview: The Generation R Study. Pediatric Pulmonology, 45, 500-507. Moll, H.A. (2010). Challenges in the validation of triage systems at emergency departments. Journal of Clinical Epidemiology, 63, 384-388. Mook-Kanamori, D.O., Steegers, E.A.P., Eilers, PH, Raat, H., Hofman, A. & Jaddoe, V.W.V.K. (2010). Risk Factors and Outcomes Associated With First-Trimester Fetal Growth Restriction. Jama - Journal of the American Medical Association, 303(6), 527-534. Moorthy, L.N., Peterson, M.G.E., Baratelli, M.J., Hasset, A.L., Lehman, T.J.A. & Suijlekom-Smit, L.W.A. van (2010). Preliminary cross-cultural adaption of a new pediatric health-related quality of life scale in children with systemic lupus erythematosus: an international effort. Lupus, 19, 83-88. Nijman, R.G., Oostenbrink, R., Dons, E.M., Bouwhuis, C.B. & Moll, H.A. (2010). 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