METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
Use of Foreground and Dissemination Activities during Period 3: 1.2.2011 - 31.1.2012
General comments concerning patenting related to METOXIA:
During the 3rd period an international patent application (PCT) was published which involves the work on the CAIXinhibitors where we have a product patent filed and involves several partners. While 1/UIO, 2/MAASTRO,
8/UNIMAN, and 9/UNIFI are patent owners, also 3/UEDIN, 4/RUNMC, 6/AUH,AS, 18/IVSAS, 20/GROW-UM and
21/OU-Lyng are today participating in this development with models of specific value for this translational work. In
addition 1/UIO is working on a patent on priming effects of low dose-rate radiation and the protective effect of
this priming for development of resistance against certain toxic chemicals.
Individual partner’s dissemination:
1/UIO:
 14th April 2011 METOXIA sub-group meeting on the theme “Patent situation and strategy to demonstrate
therapeutic and diagnostic proof-of-principle” in Munich, Germany. Speaker Erik O. Pettersen: Patent situation
and strategy to follow-up the PCT-application on our patented CA-IX inhibitors. Objective: To reach a
conclusion regarding the strategy for commercialization of our patented CAIX-inhibitor compounds. Target:
Participants of the CAIXi-sub-group of METOXIA.
 20th -22th June 2011 the Biannual Meeting of the Norwegian Physical Society, University of Oslo, Department of
Physics, Norway. Speaker: Nina Jeppesen Edin: Molecular mechanisms for induction of sustained elimination of
low dose hyper-radiosensitivity. Objective: To discuss our results with colleagues within the Physical Society
Target: International research scientists within physics.
 22nd-24th June 2011, European Carbonic Anhydrase Meeting, Montecatini Terme, Italy, Chair: Erik O. Pettersen:
Coumarins as inhibitors of zink containing enzymes. Objective: Discuss data on METOXIA-patented CAIXinhibitors with international expertise. Target: International experts on Carbonic Anhydrase.
 28th August – 1st September 201;1 14th International Congress of Radiation Research, Warsaw, Poland.
Speaker: Nina Jeppesen Edin: Molecular mechanisms for induction of sustained elimination of low dose hyperradiosensitivity. Objective: To discuss our results with colleagues within the Radiation Research Society
Target: International scientists within Radiation Research.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Nina Jeppesen Edin: The mechanism by which reoxygenation and low dose-rate radiation turn off
hyper-radiosensitivity. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners
of METOXIA.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Erik O. Pettersen: A short resume of to what extent METOXIA in its first two years reached its goals; an
outline of where there are pressing problems for the project as a whole. Objective: To sum up the situation for
METOXIA at Mid-Term as seen by the co-ordinator. Target: All partners of METOXIA.
 14th November 2011 Internal seminar at The Norwegian Radiation Protection Authority, Bærum, Norway.
Speaker Nina Jeppesen Edin: Low dose-rate gamma irradiation can protect against subsequent high dose-rate
irradiation. Objective: To discuss our results with colleagues within the radiation protection. Target:
International research scientists within radiation protection.
Scientific articles with acknowledgement for METOXIA-support:
 Pettersen EO: METOXIA: Tumour micro-environment for new specific cancer treatment. In: Public
Service Review: European Union: Issue 23 (In press).
 Edin NJ, Olsen DR, Sandvik JA, Malinen E, Pettersen EO.: Low dose hyper-radiosensitivity is eliminated
during exposure to cycling hypoxia but returns after reoxygenation. Int J. Radiat. Biol. PMID:
22132723. Epub 2012 Jan 6 ahead of print.
2/MAASTRO
METOXIA Foreground and Dissemination Activities
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 20th – 21st March 2011 Prediction, Recognition, Evaluation and Eradication of Normal Tissue Effects, ESTROmeeting, Brussels, Belgium. Speaker Philippe Lambin: Isotoxic individualized radical thoracic radiotherapy based
on normal tissue complications probability: from dose constraints to multifactorial predictors. Objective: To
improve Prediction, Recognition, Evaluation and Eradication of Normal Tissue Effects. Target group:
International research scientists within oncology.
 8th -12th May 2011 ESTRO International Oncology Forum; Clinical perspectives in radiation oncology, London,
UK. Speaker Philippe Lambin: Imaging of residual disease in NSCLC: Towards dose painting by volumes.
Objective: Translating molecular imaging into the clinic: From mouse to man. Target: International research
scientists within oncology.
 22nd-24th June 2011 CAIX satellite meeting, Montecatini Terme, Italy. Speaker Ludwig Dubois: CA IX
sulf(on)amides: Applications in imaging and therapy. Objective: To discuss MAASTRO findings on new
patented CAIX-inhibitors with the international CA-expertise. Target: International research scientists within
oncology.
 31st July - 3rd Aug 2011 Joint meeting The American Association of Physicists in Medicine (AAPM) and Canadian
Organization of Medical Physicists (COMP), Vancouver, Canada. Speaker Philippe Lambin: FDG for Dose
Painting: A Rational Choice. Objective: To improve Prediction, Recognition, Evaluation and Eradication.
Target: International research scientists within oncology.
 8th Sept 2011 3rd meeting of the EORTC and 4th Langendorff-Symposium - Pros and Cons on Imaging in
Radiation Oncology. Speaker: Hugo Alerts: Innovative molecular imaging approaches for radiation oncology:
new PET biomarkers and “Radiomics". Objective: To improve Prediction, Recognition, Evaluation and
Eradication. Target: International research scientists within oncology.
 23rd-26th Sept 2011, European Multidisciplinary Cancer Congress, ECCO-ESMO, Stockholm, Sweden. Authors: A.
Dingemans, G. Bootsma, A. van Baardwijk, B. Reijmen, R. Wanders, M. Hochstenbag, A. van Belle, R. Houben, P.
Lambin, D. de Ruysscher: Determination of Standard Dose Cetuximab Together With Concurrent Individualised,
Isotoxic Accelerated Radiotherapy (RT) and Cisplatin-vinorelbine for Patients (pts) With Stage III Non-small Cell
Lung Cancer (NSCLC) - a Phase I Study (NCT00522886).
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Ludwig Dubois: Isogenic tumour models and importance of individual sensors of the UPR and the 4
main downstream pathways for hypoxia tolerance and phenotype. Objective: To discuss last year progress in
2/MAASTRO within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for EUROXY/METOXIA-support:
 Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, Zegers CM, Gillies R,
Boellard R, Dekker A, Aerts HJ. Radiomics: Extracting more information from medical images using
advanced feature analysis. Eur J Cancer. 2012 Jan 16. [Epub ahead of print]
 Dubois, L. Peeters S, Lieuwes NG, Geusens N, Thiry A, Wigfield S, Carta F, McIntyre A, Scozzafava A,
Dogné JM, Supuran CT, Harris AL, Masereel B, Lambin P. Specific inhibition of carbonic anhydrase IX
activity enhances the in vivo therapeutic effect of tumor irradiation. Radiother Oncol 99; 424-431,
(2011).
 Dubois LJ, Lieuwes NG, Janssen MH, Peeters WJ, Windhorst AD, Walsh JC, Kolb HC, Ollers MC,
Bussink J, van Dongen GA, van der Kogel A, Lambin P.: Preclinical evaluation and validation of
[18F]HX4, a promising hypoxia marker for PET imaging. Proc Natl Acad Sci U S A. 2011 Aug
30;108(35):14620-5. Epub 2011 Aug 23.
 Quero L, Dubois L, Lieuwes NG, Hennequin C, Lambin P.: miR-210 as a marker of chronic hypoxia, but
not a therapeutic target in prostate cancer. Radiother Oncol. 2011 Oct;101(1):203-8. Epub 2011 Jun
23.
3/UEDIN:
 5th April 2011 American Association of Cancer Research Meeting, Orlando, Florida. Speaker Michael Dornish:
Poster presentation: Spheroid growth in 3D alginate matrices . The work presented is in collaboration with
Partner 7/FMC.
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 14th April 2011 CAIX sub-group Meeting, Kempinski Hotel, Munchen, Germany. Speaker: Simon Langdon.
Antiproliferative effects of CA9 inhibitors against breast cancer cell lines. Target group: METOXIA partners of
the CAIXi sub-group.
 7th-9th June 2011 TERMIS-EU Meeting, Granada, Spain. Speaker: Simon Langdon. Experience with alginate 3D
cell culture of breast cancer cells.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speakers Carol Ward and Simon Langdon: CA9-inhibitors in combination with a sodium-proton exchanger in
pre-clinical models of breast cancer. Objective: To discuss last year progress in 3/UEDIN within METOXIA.
Target: All partners of METOXIA.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Stewart Smith: Monitoring O2, pH and temperature by use of a small chip multi-sensor. Possibility for
wireless transmission. Objective: To discuss last year progress in 3/UEDIN (technology group) within
METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Li DDU, Arlt J, Tyndall D, Walker R, Richardson J, Stoppa D: Video-rate fluorescence lifetime imaging
camera with CMOS single-photon avalanche diode arrays and high-speed imaging algorithm. J.
Biomedical Optics 16; (2011 Sept) 096012.
 Tyndall D, Rae D, Li DDU, Richardson J, Arlt J, Henderson R: A 100Mphoton/s time-resolved minisilicon photomultiplier with on-chip fluorescence lifetime estimation in 0.13μm CMOS imaging
technology. IEEE International Solid-State Circuits Conference, pp20-22, 2012.
4/RUNMC:
 24th-26th February 2011 3rd International Conference on Innovative Approaches in Head and Neck Oncology
(ICHNO), Barcelona, Spain. Speaker Hans Kaanders on behalf of the European Society for Therapeutic Radiology
and Oncology (ESTRO), the European Head and Neck Society (EHNS) and the European Society for Medical
Oncology (ESMO): Presentation on the results, including oxygenation status, of the ARCON phase III trial.
Objective: Translating molecular imaging into the clinic. Target: International research scientists within
oncology
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Hans Kaanders: Assessment of the predictive value of marker and marker combinations. Objective: To
discuss last year progress in 4/RUNMC within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Rademakers SE, Lok J, van der Kogel AJ, Bussink J, Kaanders JH: Metabolic markers in relation to
hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1
and MCT4. BMC Cancer. 12; (2011) 167-177.
 Hoogsteen IJ, Marres HAM, van den Hoogen FJA, et al. Expression of EGFR under tumor hypoxia:
Identification of a subpopulation of tumor cells responsible for aggressiveness and treatment
resistance. Int. J. Radiat. Oncol. Biol. Phys. (in press).
 Janssens GO, Rademakers SE, Terhaard CH, et al.: Accelerated radiotherapy with carbogen and
nicotinamide for laryngeal cancer: Results of a phase III randomized trial. J. Clin. Oncol. (in press).
5/UOXF.BP:
 11th Jan 201,1 MSc Radiation Biology, Wellcome Trust, Oxford, UK. Speaker Adrian L. Harris: Tumour
vasculature: angiogenesis and targeted therapy.
 11th Feb 2011, 1st International Conference in Genomic Medicine, Jeddah, Saudi Arabia. Speaker Adrian L.
Harris: Notch signalling: new pathways and mechanisms in tumour’s angiogenesis; targets for therapy.
Objective: Translating molecular imaging into the clinic. Target: International research scientists within
oncology
 4th March 2011, Manchester Breast Centre Annual Meeting 2011, Paterson Institute, Manchester, UK. Speaker
Adrian L. Harris: Novel pathways of tumour angiogenesis and mechanisms of resistance to anti-angiogenic
METOXIA Foreground and Dissemination Activities
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
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therapy. Objective: Translating molecular imaging into the clinic. Target: International research scientists
within oncology
30th March 2011, RNAi 2011 6th International Conference & Exhibition, Gene Regulation by Small RNAs, St
Hilda’s College, Oxford, UK. Speaker Adrian L. Harris: Hypoxia induced miRNAs: Mechanisms of effect,
prognostic factors and therapeutic targets. Objective: Translating molecular imaging into the clinic. Target:
International research scientists within oncology
20th June 2011, ICR Annual Conference, The Institute of Cancer Research, Sutton, London, UK. Speaker Adrian L.
Harris: Mechanisms of intrinsic and acquired resistance to anti-angiogenic therapy.
23rd June 2011, The 1st International Conference Notch Targeting in Cancer, Mykonos, Greece. Speaker Adrian
L. Harris: Role of notch signalling in human tumour angiogenesis.
30th June 2011, 2nd UK National Breast Cancer Meeting, UK Cancer Convention, London, UK. Speaker Adrian L.
Harris: Does anti-angiogenesis therapy have a future in breast cancer?
24th Sept 2011, 16th ECCO/36th ESMO Multidisciplinary Cancer Congress, Stockholm, Sweden. Speaker Adrian
L. Harris: Anti-Angiogenic Strategies for Cancer Introduction to session Chair.
28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Adrian Harris: Hypoxia induced kinase RIOK3, a key mediator of invasion and metastasis. Objective: To
discuss last year progress in 5/UOXF.BP within METOXIA. Target: All partners of METOXIA.
3rd Oct 2011, PET radiotracers for studying Tumour Hypoxia Meeting, NCRI PET Research Network, Aberdeen
University, UK. Speaker Adrian L. Harris: Pathology of tumour hypoxia.
22nd Nov 2011, Oxford Experimental cancer Medicine Centre (ECMC) Meeting. Speaker Adrian L. Harris:
Angiogenesis studies.
Scientific articles with acknowledgement for METOXIA-support:
 Jubb AM, Browning L, Campo L, Turley H, Steers G, Thurston G, Harris AL, Ansorge O: Expression of
vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma. Histopathology. Feb 1. (2012) doi:
10.1111/j.1365-2559.2011.04138.x. [Epub ahead of print].
 Liu SK, Bham SA, Fokas E, Beech J, Im J, Cho S, Harris AL, Muschel RJ: Delta-like ligand 4-notch
blockade and tumor radiation response. J Natl Cancer Inst. 103; (2011) 1778-1798. Epub 2011 Oct 18.
 Favaro E, Lord S, Harris AL, Buffa FM: Gene expression and hypoxia in breast cancer. Genome Med.
(2011) 55-67.
 Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, Taylor M, Harris AL, Ragoussis J:
microRNA-associated progression pathways and potential therapeutic targets identified by
integrated mRNA and microRNA expression profiling in breast cancer. Cancer Res. 71; (2011) 56355645. Epub 2011 Jul 7.
 Ghazoui Z, Buffa FM, Dunbier AK, Anderson H, Dexter T, Detre S, Salter J, Smith IE, Harris AL, Dowsett
M: Close and stable relationship between proliferation and a hypoxia metagene in aromatase
inhibitor-treated ER-positive breast cancer. Clin. Cancer Res. 17; (2011) 3005-3012. Epub 2011 Feb
15.
6/AUH,AS:
 26th-28th May 2011, Aarhus, Denmark. Speaker Jens Overgaard: Enhancement of radiation by heat, Mike
Horsman: Role of tumour vasculature in heat response.
 3rd June 2011, Highlighting video from ESTRO 2011: Speaker Jens Overgaard: Important factors influencing the
treatment of head and neck cancer
 9th Sept 2011, Ezcoller foundation – ECCO Recognition for Contribution to Oncology: The 2011 award is given to
Jens Overgaard in recognition of his leading role in experimental oncology and translational research in
radiation oncology as well as his outstanding contribution to promote multi-disciplinarity and evidence-based
approaches in oncology and more specifically innovative treatments for Head and neck and Breast cancer, as
well as the establishment of new therapeutic standards.
 23rd-27th Sept 2011, ECCO 16, ESMO 36, ESTRO 30 European Multidisciplinary Cancer Congress, Stockholm,
Sweden. Speaker: Jens Overgaard: Award lecture Ezcoller foundation – ECCO Recognition for Contribution to
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
Oncology. Objective: To discuss findings regarding experimental oncology with international scientific
expertise. Target: International scientists.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Morten Busk: Hypoxia (and FDG)-PET guided development of hypoxia targeting strategies as a means
to radiosensitize tumours. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Toustrup K, Sørensen BS, Nordsmark M, Busk M, Wiuf C, Alsner J, Overgaard J: Development of a hypoxia gene
expression classifier with predictive impact for hypoxic modification of radiotherapy in head and neck cancer.
Cancer Res. 71; (2011) 5923-5931.
 Busk M, Toustrup K, Sørensen BS, Alsner J, Horsman MR, Jakobsen S, Overgaard J: In vivo identification and
specificity assessment of mRNA markers of hypoxia in human and mouse tumors. BMC Cancer 2011;11:63.
 Busk M, Walenta S, Mueller-Klieser W, Steiniche T, Jakobsen S, Horsman MR, Overgaard J: Inhibition of tumor
lactate oxidation: consequences for the tumor microenvironment. Radiothe.r Oncol. 99; (2011) 404-411.
 Mortensen LS, Busk M, Nordsmark M, Jakobsen S, Theil J, Overgaard J, Horsman MR: Accessing radiation
response using hypoxia PET imaging and oxygen sensitive electrodes: a preclinical study. Radiother Oncol 99;
(2011) 418-423.
7/FMC:
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Mike Dornish: NovaMatrix-3DTM – 3D Cell Culture and Formation of Multi-Cellular Structures in
Alginate Foams. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners of
METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
8/UNIMAN:
 2nd-4th Feb 2011. The 22nd International LH Gray conference, Manchester UK. Authors: Natalie Burrows, Joseph
Williams, Julia Resch, Georg Brabant and Kaye Williams: The clinical PI3K inhibitor GDC-0941 radio-sensitizes
thyroid carcinoma cells by inhibiting both the PI3K and HIF-1 signaling pathways.
 2nd-6th April 2011. The 102nd American association of cancer research (AACR) conference. FL, USA Authors:
Natalie Burrows, Muhammad Babur, Sophie Ridsdale, Joseph Williams, Julia Resch, Georg Brabant and Kaye
Williams: Metastatic characteristics and radio-sensitivity dependent on PI3K and HIF-1 signaling in thyroid
carcinomas. Objective: To discuss findings regarding HIF-signalling with international scientific expertise.
Target: International scientists.
 11th-14th April 2011, The British Endocrine Society conference, Birmingham, UK, Speakers Natalie Burrows,
Muhammad Babur, Julia Resch, Sophie Ridsdale, Joseph Williams Georg Brabant & Kaye Williams: Metastatic
characteristics and radio-sensitivity depend on PI3K and HIF-1 signaling in thyroid carcinomas.
 4th-7th June 2011. ENDO Annual meeting, MA, USA. Authors: Natalie Burrows, Muhammad Babur, Julia Resch,
Sophie Ridsdale, Joseph Williams, Georg Brabant and Kaye Williams: Metastatic characteristics and
desensitisation to radiotherapy depends on PI3K and HIF-1 signaling in thyroid-carcinomas.
 22nd-24th June 2011, European Carbonic Anhydrase Meeting, Montecatini Terme, Italy, Speaker Kaye Williams:
CA-IX inhibition and the metastatic phenotype. Objective: Discuss data on METOXIA-patented CAIX-inhibitors
with international expertise. Target: International experts on Carbonic Anhydrase.
 29th June-1st July 2011, Association for Radiation Research and the UK Mutagen Society joint annual meeting,
Nottingham, UK, Speaker Kaye Williams: Metastatic characteristics and desensitisation to radiotherapy
depends on PI3K and HIF-signalling in thyroid carcinomas.
 10th Sept 2011, 35th Annual Meeting of the European Thyroid Association (ETA), Krakow Poland, Speakers
Natalie Burrows, Joseph Williams, Georg Brabant and Kaye Williams: The clinical PI3K inhibitor GDC-0941 radiosensitizes thyroid-carcinoma cells by inhibiting both the PI3K and HIF-1 signaling pathways.
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker Roben Gieling: Potential clinical use of CA9-inhibitors? Effects of patented CA9i compounds against
METOXIA Foreground and Dissemination Activities
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
metastasis in model systems. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
 2011. The British Institute of Radiology, London, UK. Speaker Nathalie Burrows: Metastatic characteristics and
desensitization to radiotherapy depends on PI3K and HIF-1 signaling in thyroid-carcinomas.
 4th-7th Nov 2011, 8th National Cancer Research Institute (NCRI) Cancer Conference, Liverpool, UK Authors:
Roben G. Gieling1, Muhammad Babur1, Brian A. Telfer1, Andrea Scozzafava2, Claudiu Supuran2, Kaye J.
Williams1. (1Hypoxia & Therapeutics Group, School of Pharmaceutical Sciences; University of Manchester, Manchester,
United Kingdom, 2University of Florence, Department of Chemistry, Florence, Italy): Carbonic Anhydrase IX inhibitor S4:
a potential new anti-metastatic drug in breast cancer.
 12th-16th Nov 2011. Molecular Targets and Cancer Therapeutics, AACR-NCI-EORTC International Conference, San
Francisco, CA, USA. Authors: Roben G. Gieling1, Muhammad Babur1, Brian A. Telfer1, Steve Williams2, Karen
Davies2, Andrea Scozzafava3, Claudiu Supuran3, Kaye J. Williams1: (1Hypoxia & Therapeutics Group, School of
Pharmaceutical Sciences; 2Imaging Science and Biomedical Engineering University of Manchester, Manchester,
United Kingdom; 3University of Florence, Department of Chemistry, Florence, Italy): Anticancer effects of S4, a
new carbonic anhydrase inhibitor, on MDA-MB-231 and HCT116 tumours.
Scientific articles with acknowledgement for METOXIA-support:
 Ali M, Kamjoo M, Thomas HD, Kyle S, Pavlovska I, Babur M, Telfer BA, Curtin NJ, Williams KJ. The
clinically active PARP inhibitor AG014699 ameliorates cardiotoxicity but doesn’t enhance the efficacy
of doxorubicin, despite improving tumour perfusion and radiation response in mice. Mo.l Cancer
Therapeutics, 10, (2011) 2320-2329.
 Burrows N, Babur M, Resch J, Williams KJ, Brabant G.et al Hypoxia-Inducible Factor in Thyroid
Carcinoma J Thyroid Research 2011;2011:762905. Epub 2011 Jun 16.
 Burrows N, Babur M, Resch J, Ridsdale S, Mejin M, Rowling EJ, Brabant G, Williams KJ.: GDC-0941
Inhibits Metastatic Characteristics of Thyroid Carcinomas by Targeting both the Phosphoinositide-3
Kinase (PI3K) and Hypoxia-Inducible Factor-1_ (HIF-1_) Pathways. J Clin Endocrinol Metab. 2011
Dec;96(12):E1934-43. Epub 2011 Oct 12.
9/UNIFI:
 27th Jan-6th Feb 2011; Visit for collaboration with Prof. Ozlem Guzel of Istanbul University and with Prof. Birsen
Oksal of Akdeniz University (TUR) Claudiu Dupuran: Investigation of enzyme inhibitors for carbonic anhydrase in
hypoxic tumors.
 14th April 2011, CAIX-inhibitor sub-group meeting, Munich airport , Germany. Speaker Claudiu Supuran: Do we
have a lead compound? Objective: To discuss last progress of CAIX-inhobitor invention within METOXIA.
Target: METOXIA-partners of the CAIXi sub-group.
 5th-10th June 2011, XXIII International Conference on Coordination and Bioinorganic Chemistry, Smolenice
Slovakia, Speaker Andrea Scozzafava. Carbonic anhydrase inhibitor coated nanoparticles: New therapeutic
approaches. Objective: To discuss findings regarding HIF-signalling with international scientific expertise.
Target: International scientists.
 22nd-24th June 2011, European Carbonic Anhydrase Meeting, Montecatini Terme, Italy, Speaker Claudiu
Supuran: new drug targets and chemotypes for developing CAIs/CAAs. Objective: Discuss data on METOXIApatented CAIX-inhibitors with international expertise. Target: International experts on Carbonic Anhydrase.
 27th June-6th July 2011, 25th National Chemistry Congress with International Participation in Erzurum, Turkey.
Speaker Claudiu Supuran: Plenary lecture/dissemination of rsults on CA inhibition in hypoxic
tumors/metastasis. Objective: Collaboration with Hatay University (Prof . Ozen Ozensoy).
 28th – 30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speakers Claudiu Supuran and Andrea Scozzafava: : CA9 and -12 inhibitor molecules: Detailed characterization
of enzyme – inhibitor complexes by means of X-ray crystallography and kinetic methods. Objective: To discuss
last year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
 4th Nov 2011, The Italy/Japan Joint Meeting on Cancer Research, Kyoto, Japan. Speaker Claudiu Supuran:
Presentation of two seminars.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
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
2nd -5th Dec 2011, The 11th International Symposium on Applied Bioinorganic Chemistry, Barcelona Spain,
Speaker Andrea Scozzafava: Carbonic Anhydrase IX Inhibitor Coated Nanoparticles: new Diagnostic and
Therapeutic Approaches for Cancer Treatment. Objective: To discuss findings regarding HIF-signalling with
international scientific expertise. Target: International scientists.
Scientific articles with acknowledgement for METOXIA-support:
 Neri, D., Supuran, C.T.: Interfering with pH regulation in tumours as a therapeutic strategy. Nature
Rev. Drug Discov. 10; (2011) 767-777.
 Carta F, Aggarwal M, Maresca A, Scozzafava A, McKenna R, Masini E, Supuran CT. Dithiocarbamates
strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo. J Med Chem. Jan 26.
(2012) [Epub ahead of print].
 Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran
CT. Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: Xray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV. J.
Med. Chem. 54; (2011) 3977-3981.
 Mader P, Brynda J, Gitto R, Agnello S, Pachl P, Supuran CT, Chimirri A, Řezáčová P. Structural basis for
the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides. J.
Med. Chem. 54; (2011) 2522-2526.
 Davis RA, Hofmann A, Osman A, Hall RA, Mühlschlegel FA, Vullo D, Innocenti A, Supuran CT, Poulsen
SA. Natural product-based phenols as novel probes for mycobacterial and fungal carbonic
anhydrases. J. Med. Chem. 54; (2011) 1682-1692.
 Lopez M, Trajkovic J, Bornaghi LF, Innocenti A, Vullo D, Supuran CT, Poulsen SA. Design, synthesis,
and biological evaluation of novel carbohydrate-based sulfamates as carbonic anhydrase inhibitors. J.
Med. Chem. 54; (2011) 1481-1489.
 Saada MC, Montero JL, Vullo D, Scozzafava A, Winum JY, Supuran CT. Carbonic anhydrase activators:
gold nanoparticles coated with derivatized histamine, histidine, and carnosine show enhanced
activatory effects on several mammalian isoforms. J. Med. Chem. 54; (2011) 1170-1177.
 Carta F, Aggarwal M, Maresca A, Scozzafava A, McKenna R, Supuran CT. Dithiocarbamates: a new
class of carbonic anhydrase inhibitors. Crystallographic and kinetic investigations. Chem. Commun.
(Camb). 48; (2012) 1868-1870.
 Lopez M, Vu H, Wang CK, Wolf MG, Groenhof G, Innocenti A, Supuran CT, Poulsen SA. Promiscuity of
carbonic anhydrase II. Unexpected ester hydrolysis of carbohydrate-based sulfamate inhibitors. J.
Am. Chem. Soc. 133; (2011) 18452-18462.
 Rodríguez, OM. Maresca, A, Témpera, CA, Bravo, RD, Colinas, PA, Supuran CT: N-β-glycosyl
sulfamides are selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII.
Bioorg. Med. Chem. Lett. 21; (2011) 4447-4450.
 Ohradanova,A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ Wörheide G Supuran CT: Cloning,
characterization and sulfonamide inhibition studies of an -carbonic anhydrase from the living fossil
sponge Astrosclera willeyana. Bioorg. Med. Chem. 20; (2012) 1403-1410.
 Ohradanova,A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ Wörheide G Supuran CT: Anion
inhibition studies of an -carbonic anhydrase from the living fossil Astrosclera willeyana. Bioorg.
Med. Chem. Lett. 22; (2012) 1314-1316.
 Carta F, Innocenti A, Hall RA, Mühlschlegel FA, Scozzafava A, Supuran CT: Carbonic anhydrase
inhibitors. Inhibition of the -class enzymes from the fungal pathogens Candida albicans and
Cryptococcus neoformans with branched aliphatic-/aromatic carboxylates and their derivatives.
Bioorg. Med. Chem. Lett. 21; (2011) 2521-2526.
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 Knaus EE, Innocenti A, Scozzafava A, Supuran CT: Phenylethynylbenzenesulfonamide regioisomers
strongly and selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX
and XII over the cytosolic isoforms I and II. Bioorg. Med. Chem. Lett. 21; (2011) 5892-5896.
 Rami M, Innocenti A, Montero JL, Scozzafava A, Winum JY Supuran CT: Synthesis of rhodamine B –
benzenesulfonamide conjugates and their inhibitory activity against human - and bacterial/fungal
-carbonic anhydrases. Bioorg. Med. Chem. Lett. 21; (2011) 5210-5213.
 Salmon AJ, Williams ML, Maresca A, Supuran CT, Poulsen SA: Synthesis of glycoconjugate carbonic
anhydrase inhibitors by ruthenium-catalysed azide-alkyne 1,3-dipolar cycloaddition. Bioorg. Med.
Chem. Lett. 21; (2011) 6058-6061.
 Carta F, Garaj V, Maresca A, Wagner J, Avvaru BS, Robbins AH, Scozzafava A, McKenna R, Supuran CT:
Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic
anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: solution and X-ray
crystallographic studies. Bioorg. Med. Chem. 19; (2011) 3105-3119.
 Pala N, Dallocchio R, Dessì A, Brancale A, Carta F, Ihm S, Maresca A, Sechi M, Supuran CTL: Virtual
screening-driven identification of human carbonic anhydrase inhibitors incorporating an original new
pharmacophore. Bioorg. Med. Chem. Lett. 21; (2011) 2515-2520.
 Cincinelli A, Martellini T, Innocenti A, Scozzafava A, Supuran CT: Purification and inhibition studies
with anions and sulfonamides of an -carbonic anhydrase from the Antarctic seal Leptonychotes
weddellii. Bioorg. Med. Chem. 19; (2011) 1847-1851.
 Rami M, Maresca A, F-Zhora Smaine, Montero J-L, Scozzafava A Winum JY, Supuran CT: Sulfonamides
incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumorassociated carbonic anhydrase isoforms IX and XII. Bioorg. Med. Chem. Lett. 21; (2011) 2975-2979.
 Pacchiano F, Carta F, Vullo D, Scozzafava A, Supuran CT: Inhibition of -carbonic anhydrases with
ureido-substituted benzenesulfonamides. Bioorg. Med. Chem. Lett. 21; (2011) 102-105.
 Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A: Synthesis and biological
profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. Bioorg.
Med. Chem. 19; (2011) 7003-7007.
 Maresca A, Supuran CT: R)-/(S)-10-Camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides
selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg. Med. Chem. Lett. 21;
(2011) 1334-1337.
 Truppo E, Supuran CTY, Sandomenico A, Vullo D, Innocenti A, Di Fiore A, Alterio V, De Simone G,
Monti SM, Carbonic anhydrase VII is S-glutathionylated without loss of catalytic activity and affinity
for sulfonamide inhibitors. Bioorg. Med. Chem. Lett. 22; (2012) 1560-1564.
 Carta F, Maresca A, Scozzafava A, Supuran CT: 5- and 6-Membered (thio)lactones are prodrug type
carbonic anhydrase inhibitors. Bioorg. Med. Chem. Lett. 22; (2012) 267-270.
 Monti SM, Maresca A, Carta F, De Simone G, F.A. Mühlschlegel FA, Scozzafava A, Supuran CT:
Dithiocarbamates strongly inhibit the beta-class fungal carbonic anhydrases from Cryptococcus
neoformans, Candida albicans and Candida glabrata. Bioorg. Med. Chem. Lett. 22; (2012) 859-862.
 De Simone G, Supuran CT: (In)organic anions as carbonic anhydrase inhibitors. J. Inorg. Biochem.
2012, (in press).
10/KI:
 26th-29th June 2011, The 33th Naito Conference, Sapporo, japan. Speaker Lorenz Poellinger: Epigenetic
regulatory mechanism underlying the response to hypoxia. Objective: To give an over-view over the hypoxiaregulatory field. Target: International Scientists.
 21st-24th Sept 2011, 6th European Meeting for Vascular Biology and Medicine, Krakov, Poland. Speaker Lorenz
Poellinger: Mechanisms of gene regulation in hypoxia: role of hypoxia-inducible factors in regulation of the
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Grant Agreement No. HEALTH-F2-2009-222741






epigenetic landscape of target cells. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Lorenz Poellinger: The epigenetic landscape in hypoxia - hypoxia-dependent epigenetic regulatory mechanisms
for regulation of tumor growth and metastasis. Objective: To discuss last year progress in 10/KI-Poellinger
within METOXIA. Target: All partners of METOXIA.
23rd-26th Sept 2011, European Multidisciplinary Cancer Congress, ECCO-ESMO, Stockholm, Sweden. Authors: N.
Lajmi, S. Kobold, Y. Cao, T. Luetkens, H. Reinhard, C. Bokemeyer, N. Kröger, D. Atanackovic: Allogeneic Stem
Cell Transplantation Induces Autoantibodies Against Cancer Testis Antigens in Multiple Myeloma Patients.
28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Yihai Cao: On the role of hypoxia in lymphatic metastasis. Objective: To discuss last year progress in 10/KI-Cao
within METOXIA. Target: All partners of METOXIA.
9th-14th Oct 2011, HypoxiaNet Meeting Impact of Hypoxia on Cells, Mice and Men, Monte Verita, Ascona,
Switzerland. Speaker Lorenz Poellinger: Epigenetic regulatory mechanisms underlying the hypoxic response.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
10th-13th Dec 2011, 53rd American Society of Hematology (ASH) Annual Meeting and Exposition, Atlanta, USA.
Speaker Lorenz Poellinger: Physiologic Hypoxia Promotes Maintenance of CML Stem Cells Despite Effective
BCR-ABL Inhibition. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
9th-13 Jan 2012, Croucher Advanced Study Institute 2012, Tumour Microenvironment – New Concepts and
Molecular Mechanisms, Hong Kong. Speaker Lorenz Poellinger: Mechanisms of Gene Regulation in Hypoxia –
Relevance for Regulation of Tumor Growth and the Cell Differentiation Status. Objective: To give an over-view
over the hypoxia-regulatory field. Target: International Scientists.
Scientific articles with acknowledgement for METOXIA-support:
 Stiehl, DP, Bordoli, MR, Abreu-Rodrıguez, I, Wollenick, K, Schraml, P Gradin, K, Poellinger, L,
Kristiansen, G and Wenger, RH: Non-canonical HIF-2a function drives autonomous breast cancer cell
growth via an AREG–EGFR/ErbB4 autocrine loop. Oncogene (2011) 1–15; (advance online
publication, 19 September 2011; doi:10.1038/onc.2011.417.)
 Cao Y.: Antiangiogenic cancer therapy: why do mouse and human patients respond in a different way
to the same drug? Int J Dev Biol. 55 (4-5); (2011); 557-62.
 Cao Y, Arbiser J, D'Amato RJ, D'Amore PA, Ingber DE, Kerbel R, Klagsbrun M, Lim S, Moses MA, Zetter
B, Dvorak H, Langer R.: Forty-year journey of angiogenesis translational research. Science Transl Med.
2011 Dec 21;3(114):114rv3.
 Xue Y, Lim S, Yang Y, Wang Z, Jensen LD, Hedlund EM, Andersson P, Sasahara M, Larsson O, Galter D,
Cao R, Hosaka K, Cao Y.: PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing
erythropoietin production in stromal cells. Nature Medicine. 2011 Dec 4;18(1):100-10. doi:
10.1038/nm.2575.
 Lim S, Honek J, Xue Y, Seki T, Cao Z, Andersson P, Yang X, Hosaka K & Cao Y.: Cold-induced activation
of brown adipose tissue and adipose angiogenesis in mice. Nature Protocols, in press
11/MAD:
 8-12 January 2011 Davos, Switzerland Cost Action TD0901 Hypoxia Sensing, signaling and adaptation.
Luis del Peso presented a poster
 12th April 2011, University of Zurich. Luis del Peso gave a lunch seminar on hypoxia.
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Manuel Landazuri and Maria Calzada: Role of hypoxia in angiogenesis and metastasis: Regulation of Ephrin A3
and VCAM-1 by hypoxia. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 Martinez-Poveda B, Gomez V, Alcaide-German M, Perruca S, Vazquez S, Alba LE, Casanovas O, GarciaBermejo ML, Peso L, Jimenez B.: Non-invasive monitoring of hypoxia-inducible factor activation by
optical imaging during antiangiogenic treatment in a xenograft model of ovarian carcinoma. Int J
Oncol. 2011 Sep;39(3):543-52. doi: 10.3892/ijo.2011.1074. Epub 2011 Jun 9. PMID: 21667025.
 Tiana M, Villar D, Pérez-Guijarro E, Gómez-Maldonado L, Moltó E, Fernández-Miñán A, GómezSkarmeta JL, Montoliu L, Del Peso L.: A role for insulator elements in the regulation of gene
expression response to hypoxia. Nucleic Acids Res. 2011 Nov 25. [Epub ahead of print] PMID:
22067454.
 Tello D, Balsa E, Acosta-Iborra B, Fuertes-Yebra E, Elorza A, Ordóñez Á, Corral-Escariz M, Soro I,
López-Bernardo E, Perales-Clemente E, Martínez-Ruiz A, Enríquez JA, Aragonés J, Cadenas S,
Landázuri MO. Induction of the mitochondrial NDUFA4L2 protein by HIF-1α decreases oxygen
consumption by inhibiting Complex I activity. Cell Metab. 14; (2011) 768-79.
12/DHZM:
 26-29 March 2011: Annual meeting of the German Society of Physiology, Regensburg, Germany. Authors: D.
Kracun, I. Kanchev, F. Rie, J. Hess, A. Gorlach: Low dose dexamethasone treatment stimulates vascular
proliferative responses involving NADPH oxidases and the HIF system. Objective: To discuss HIF-regulatory
effects. Target group: International research scientists.
 26-29 March 2011: Annual meeting of the German Society of Physiology, Regensburg, Germany. Authors: D.
Kracun, I. Kanchev, F. Rie, J. Hess, A. Gorlach: Folic acid prevents uncoupling of NO synthase and pulmonary
vascular remodelling under hypoxia. Objective: To discuss HIF-regulatory effects. Target group: International
research scientists.
 7th June 2011: Austrian Academy of Sciences, Institute for Biomedical Ageing Research, Innsbruck, Austria.
Speaker?
 22nd-24th June 2011, European Carbonic Anhydrase Meeting, Montecatini Terme, Italy, Speaker Agnes Görlach:
ROS and CA inhibitors in tumors. Objective: To discuss progress in understanding CA IX function in hypoxic
cells. Target group: International research scientists and collaborators/METOXIA members.

17th-19th September 2011, Kloster Seeon, Germany. Speaker Agnes Görlach: The tumor-vessel
interface: Cellular and molecular mechanisms of tumor progression and metastasis.
 21st-24th Sept 2011, 6th European Meeting for Vascular Biology and Medicine, Krakov, Poland. Speaker Agnes
Görlach: NADPH oxidases and the HIF pathway: an emerging liaison in vascular cells. Objective: To give an overview over the hypoxia-regulatory field. Target: International Scientists.
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Agnes Görlach: ADAM17 regulation by hypoxia and ER stress: Gene signatures/protein profiles of
hypoxia/reoxygenation markers involved in invasion/metastasis. Objective: To discuss last year progress in
1/UIO within METOXIA. Target: All partners of METOXIA.
 9th-14th Oct 2011, HypoxiaNet Meeting Impact of Hypoxia on Cells, Mice and Men, Monte Verita, Ascona,
Switzerland. Speaker Agnes Görlach: ?
 14-17 October 2011: Meeting of the European Society for Microcirculation, Munich, Germany.
Authors : I. Diebold, A. Petry1, K. Sabrane, J. Hess, A. Görlach: The novel HIF1 target gene NOX2
induces angiogenesis by urotensin-II. Objective: To give an over-view over the hypoxia-regulatory
field. Target: International Scientists.
 9th Nov 2011, BioM4-Biotechnology Cluster, Munich, Germany. Meeting with Industry partners,
Speaker Agnes Görlach.
Scientific articles with acknowledgement for METOXIA-support:
 Schelter F, Halbgewachs B, Bäumler P, Neu C, Görlach A, Schrötzlmair F, Krüger A. Tissue inhibitor of
metalloproteinases-1-induced scattered liver metastasis is mediated by hypoxia-inducible factor-1α
Clin Exp Metastasis. 28; (2011) 91-99.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
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Grant Agreement No. HEALTH-F2-2009-222741
 Diebold I, Petry A, Burger M, Hess J, Görlach A. NOX4 mediates activation of FoxO3a and matrix
metalloproteinase 2 expression by urotensin-II; Mol Biol Cell. 22; (2011) 4424-4434.
 Rzymski T, Petry A, Kracun D, Pike L, Harris AL, Görlach A: The unfolded protein response controls
induction and activation of ADAM17/TACE by severe hypoxia and ER-stress, Oncogene. Nov 21.
(2011) [Epub ahead of print]
 Grunewald TG, Diebold I, Esposito I, Plehm S, Hauer K, Thiel U, da Silva-Buttkus P, Neff F, Unland R,
Müller-Tidow C, Zobywalski C, Lohrig K, Lewandrowski U, Sickmann A, da Costa OP, Görlach A,
Cossarizza A, Butt E, Richter GH, Burdach S: STEAP1 Is Associated with the Invasive and Oxidative
Stress Phenotype of Ewing Tumors. Mol Cancer Res. 10; (2012) 52-65.
 Diebold I, Petry A, Sabrane K, Djordjevic T, Hess J, Görlach A: The HIF1 Target Gene NOX2 Promotes
Angiogenesis by Urotensin-II, J. Cell. Sci., (in press)
13/CNRS:
 20th-21st Jan 2011, Plenary Lecture, Hypoxia colloquium of the Brain Society, Caën, France. Speaker: Jacques
Pouyssegur:
 25th Jan 2011, Colloque INCa-Translational Research Projects, Paris, France. Chair: Jacques Pouyssegur.
 4th- 5th Feb 2011, international colloquium “Genome, Cancer and Ageing”, Monaco, Speaker: Jackues
Pouyssegur.
 15th-21st feb 2011, International Meeting “Hypoxia & Cancer”, Lake Louise, Calgary, Alberta, Canada. Speaker:
Jacques Pouyssegur: Tumor hypoxia and metabolism: Towards novel anticancer approaches.
 31st May 2011, Translational Research European Hospital Georges Pompidou, Paris, Speaker: Jacques
Pouyssegur. Plenary lecture.
 14th-17th Sept 2011, ISP-International Symposium on Pheochromocytoma and Paraganglioma, Paris, France.
Speaker Jacques Pouyssegur: Tumor biology. Objective: To discuss findings regarding hypoxia-metabolism
with international scientific expertise. Target: International scientists.
 20th-23rd Sept 2011, 53e Réunion Annuelle du CRCQ Mont Gabriel, Quebec, Canada. Speaker: Jacques
Pouyssegur. Plenary lecture (Conférencier du président).
 23rd-26th Sept 2011, European Multidisciplinary Cancer Congress, ECCO-ESMO, Stockholm, Sweden. Speaker
Jacques Pouyssegur: Anticancer Approaches Based on Tumour Hypoxia and Metabolism. Objective: To discuss
findings regarding hypoxia-metabolism with international scientific expertise. Target: International scientists.
 23rd sept 2011, International symposium: Obesity, Diabetes, Cancer (23e Journée Dreyfus, Cochin), Speaker J.
Chiche)
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Jacques Pouyssegur: Involvement of CAIX in metastatic spread and mechanisms with clinical
potential.Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
 5th-8th Oct 2011, Lecture at Workshop of Hypoxia in Tumor microenvironment, Berder Island, Bretagny, France.
Speaker Jacques Pouyssegur.
 13th-14th Oct 2011, Lecture on New concepts through Targeted therapies, Lille, France. Speaker Jacques
Pouyssegur.
 14th-16th Oct 2011, Hypoxia and Vascular Biology Symposium, Berlin, Germany, Speaker Jacques Pouyssegur.
 27th Oct-2nd Nov 2011, International Meeting “Metformin and Cancer” Banbury, Cold Spring Harbor
Laboratory,USA. Speaker Jacques Pouyssegur.
 17th-18th Nov 2011, 2nd International Meeting of Society Proton Dynamics and Cancer (ISPDC), Nice, France.
Speaker Jacques Pouyssegur.
 24th Nov 2011, Lecture organized by Roche, Paris, France. Speaker Jacques Pouyssegur: Tumour invasion and
Metastasis.
 5th Dec 2011, Lecture “EMBL Symposium Targeted Genome Editing Using ZFN”, Heidelberg, Germany. Speaker
Jacques Pouyssegur:
 9th Dec 2011, Lecture International PhD course “ion Transport and Cancer”, Copenhagen Denmark. December 9
Speaker Jacques Pouyssegur.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
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Grant Agreement No. HEALTH-F2-2009-222741
Scientific articles with acknowledgement for METOXIA-support:
 Puissegur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand
K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouysségur J, Gounon P, Hofman P, Barbry
P, Mari B.: MiR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial
alterations associated with modulation of HIF-1 activity. Cell. Death Differ. 18; (2011) 465-478.
 Parks SK, Chiche J, & Pouysségur J: pH control mechanisms of tumor survival and growth. J Cell
Physiol 226 ; (2011) 299-308.
 Brahimi-Horn MC, Bellot G, & Pouysségur J: Hypoxia and energetic tumour metabolism. Curr Opin
Genet Dev 21; (2011) 67-72.
 Morris JC, Chiche J, Grellier C, Lopez M, Bornaghi LF, Maresca A, Supuran CT, Pouysségur J, Poulsen
SA: Targeting Hypoxic Tumor Cell Viability with Carbohydrate-Based Carbonic Anhydrase IX and XII
Inhibitors. J. Med Chem. 54; (2011) 6905-6918.
 Chiche J, Fur YL, Vilmen C, Frassineti F, Daniel L, Halestrap AP, Cozzone PJ, Pouysségur J, Lutz NW: In
vivo pH in metabolic-defective Ras-transformed fibroblast tumors: Key role of the monocarboxylate
transporter, MCT4, for inducing an alkaline intracellular pH. Int J Cancer (2011) doi:
10.1002/ijc.26125.
 Pelletier J, Dayan F, Durivault J, Ilc K, Pécou E, Pouysségur J, Mazure NM: The asparaginyl hydroxylase
factor-inhibiting HIF is essential for tumor growth through suppression of the p53-p21 axis.
Oncogene in press, (2011) doi: 10.1038/onc.2011.471.
 Le Floch R, Chiche J, Marchiq I, Naïken, Ilc K, Murray C, Critchlow S, Roux D, Simon MP and Pouysségur
J: CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics
and growth of glycolytic tumors. Proc. Natl. Acad. Sci (USA). 108; (2011) 16663-16668.
14/ALU-FR:
 7th-9th June 2011, Sensor + Test Conferences 2011, Nürnberg, Germany. Authors: J. Kieninger, K.
Aravindalochanan, B. Enderle, G. Urban, H. Flamm, A. Weltin: Chemical Sensors for Bio-Scientific Research –
From in vitro to in vivo. Objective: To discuss our progress with scientist and engineer experts. Target:
Engineering experts.
 27th-30th Sept 2011, Conference of Biomedical Engineering (BMT) and 45th Annual Meeting of the German
Association of Biomedical Engineering, Freiburgh, Germany. Authors: J. Kieninger, B. Enderle, Y. Tamari, J.
Sandvik, E. O. Pettersen, G. Urban: Metabolic pathways in tumor cell culture: Enhancement of the Sensing Cell
Culture Flask with biosensors. Objective: To discuss our progress with scientist and engineer experts. Target:
Engineering experts.
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Hubert Flamm: Progress on development of ROS sensors. and Speaker Jochen Kieninger: Sensing Cell Culture
Flask (SCCF). Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners of
METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
15/Jobst:
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid,
Spain. Speaker Gerhard Jobst: Convenient tools for in vitro cell culturing: Calibration free biosensors
for take/ use/ replace. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
16/VX:
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Jan Villadsen: Wireless data transfer in micro-environmental parameter recording. Objective: To discuss last
year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
17/UCL:
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Patrick Maxwell: Evaluation of arginine depletion with Arginine Deiminase as a therapeutic strategy. Objective:
To discuss last year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
 13th-16th Oct 2011. Oncology at the Limits, Stockholm, Sweden. Speaker Patrick Maxwell: Targeting
Tumor Hypoxia.
 14th-15th Nov 2011. British Association of Urological Surgeons, Section of Oncology Annual Meeting,
Royal College of Surgeons in London, UK. Speaker Patrick Maxwell: HIF ‐ the key to clear cell RCC.
Scientific articles with acknowledgement for METOXIA-support:
 Harten SK, Esteban MA, Shukla D, Ashcroft M, Maxwell PH: Inactivation of the von Hippel-Lindau tumour
suppressor gene induces Neuromedin U expression in renal cancer cells. Mol. Cancer. 26; (2011) 89-96.
 Khan MN, Bhattacharyya T, Andrikopoulos P, Esteban MA, Barod R, Connor T, Ashcroft M, Maxwell PH,
Kiriakidis S: Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1αmediated apoptosis. Br J Cancer. 104; (2011) 1151-1159.
 Maxwell PH. Seeing the smoking gun: a sensitive and specific method to visualize loss of the tumour
suppressor, fumarate hydratase, in human tissues. J Pathol. 225; (2011) 1-3.
18/IVSAS:
 18th Feb 2011, Institute of Cancer Biology, Copenhagen, Denmark, Invited lecture, Danish Cancer
Society. Speaker: Silvia Pastorekova: Tumor response to hypoxia and acidosis: role of carbonic
anhydrase IX. Objective: To discuss the significance of CA IX for adaptation of tumor cells to hypoxia
and acidosis. Target group: International research scientists.
 29th April 2011, Invited seminar at Academia Sinica, Genomics Research Center, Taipei, Taiwan:
Speaker: Silvia Pastorekova: Role of carbonic anhydrase IX in hypoxia-driven tumor progression.
Objective: To disseminate the knowledge on CA IX in the context of tumor hypoxia to biomedical
community in Taiwan. Target group: International research scientists.
 22nd-24th June 2011 CA satellite meeting, Montecatini Terme, Italy. Speaker Silvia Pastorekova: CA IX
as a functional component of the cell migration machinery. Objective: To discuss progress in
understanding CA IX function in hypoxic cells. Target group: International research scientists and
collaborators/METOXIA members.
 25th-30th June 2011, 10th Symposium on Catecholamines and Other Neurotransmitter in Stress,
Smolenice castle, Slovakia. Speaker: Silvia Pastorekova: Interplay Between Molecular Responses of
Tumor Cells to Hypoxia and Stress Mediated by Catecholamines. Objective: To discuss new data
related to functional regulation of CA IX in hypoxic cancer cells. Target group: International research
scientists.
 8th-10th Sept 2011, 6th EORTC Pathobiology Group Annual Meeting, Rotterdam, The Netherlands.
Speaker: Silvia Pastorekova, Martina Takacova: Expression of hypoxia-induced carbonic anhydrase IX
in medullary thyroid carcinoma. Objective: To discuss new data on CA IX crosstalk with oncogenic
pathways in medullary thyroid cancer. Target group: International research scientists.
 28th-30th Sept 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain.
Speaker: Silvia Pastorekova: Involvement of CA X in metastatic spread and mechanisms with clinical
potential. Objective: To discuss functional relevance of CA IX for epithelial-mesenchymal transition.
Target group: All partners of METOXIA.
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Grant Agreement No. HEALTH-F2-2009-222741
 18th-19th Nov 2011, 2nd ISPDC meeting “Proton dynamics and cancer”, Nice, France, Speaker Silvia
Pastorekova: Upstream regulation and downstream effects of carbonic anhydrase IX in the context of
hypoxic tumor phenotype. Objective: To discuss progress in understanding molecular mechanisms
regulating CA IX function in hypoxic cells. Target group: International research scientists.
Scientific articles with acknowledgement for METOXIA support:
 Svastova E, Witarski W, Csaderova L, Kosik I, Skvarkova L, Hulikova A, Zatovicova M, Barathova M,
Kopacek J, Pastorek J, Pastorekova S. Carbonic Anhydrase IX Interacts with Bicarbonate Transporters
in Lamellipodia and Increases Cell Migration via Its Catalytic Domain. J Biol Chem. 2012 Jan
27;287(5):3392-402. Epub 2011 Dec 14.
 Ditte P, Dequiedt F, Svastova E, Hulikova A, Ohradanova-Repic A, Zatovicova M, Csaderova L, Kopacek
J, Supuran CT, Pastorekova S, Pastorek J. Phosphorylation of carbonic anhydrase IX controls its ability
to mediate extracellular acidification in hypoxic tumors. Cancer Res. 2011 Dec 15;71(24):7558-67.
Epub 2011 Oct 28.
19/IBT:
 23rd-27th Aug 2011, Eucaryotic mRNA processing, Cold Spring Harbor Laboratory, USA. Speaker Arvydas
Kanopka: Hypoxia regulated pre-mRNA processing. Objective: To discuss progress in understanding molecular
mechanisms regulating mRNA splicing in hypoxic cells. Target group: International research scientists.
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Arvydas Kanopka: Role of the splicing factor U2AF65 in the reprogramming of cellular pre-mRNA splicing from
normoxic to hypoxic activity. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
20/GROW-UM:
 2nd-6th April 2011. The 102nd American association of cancer research (AACR) conference. FL, USA Speaker:
Bradly G Wouters: Meet the expert: Biological Responses to Tumor Hypoxia and Their Potential as Therapeutic
Targets. Objective: To discuss findings regarding HIF-signalling with international scientific expertise. Target:
International scientists.
 14th April 2011 METOXIA sub-group meeting on the theme “Patent situation and strategy to demonstrate
therapeutic and diagnostic proof-of-principle” in Munich, Germany. Speaker Brad G Wouters: Suggestions to
the discussion Objective: To reach a conclusion regarding the strategy for commercialization of our patented
CAIX-inhibitor compounds. Target: Participants of the CAIXi-sub-group of METOXIA.
 28th –30th September 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker
Ludwig Dubois: Isogenic tumour models and importance of individual sensors of the UPR and the 4 main
downstream pathways for hypoxia tolerance and phenotype. Objective: To discuss last year progress in 1/UIO
within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Ramaekers CH, van den Beucken T, Meng A, Kassam S, Thoms J, Bristow RG, Wouters BG. Hypoxia
disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of
UBE2T Radiother Oncol. 101; (2011) 190-197.
 Rouschop KM, Dubois L, Schaaf MB, van den Beucken T, Lieuwes N, Keulers TG, Savelkouls KG,
Bussink J, van der Kogel AJ, Koritzinsky M, Wouters BG.: Deregulation of cap-dependent mRNA
translation increases tumour radiosensitivity through reduction of the hypoxic fraction. Radiother
Oncol. 99; (2011) 385-391.
 Starmans MH, Chu KC, Haider S, Nguyen F, Seigneuric R, Magagnin MG, Koritzinsky M, Kasprzyk A, Boutros PC,
Wouters BG, Lambin P: The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression
signatures in breast cancer. Radiother Oncol. (2012) Mar;102(3):436-43. Epub 2012 Feb 20.
METOXIA Foreground and Dissemination Activities
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 van den Beucken T, Magagnin MG, Jutten B, Seigneuric R, Lambin P, Koritzinsky M, Wouters BG.
Translational control is a major contributor to hypoxia induced gene expression. Radiother Oncol. 99;
(2011) 379-384.
 Zanella VE, Cojocari D, Hilgendorf S, Vellanki RN, Chung S, Wouters BG, Koritzinsky M.: AMPK
regulates metabolism and survival in response to ionizing radiation. Radiother Oncol. 99; (2011) 293299.
21/OU:
 2nd-6th April 2011. The 102nd American association of cancer research (AACR) conference. FL, USA. Authors:
Saelen MG, Flatmark K, Folkvord S, de Wijn R, Rasmussen H, Fodstad O, Ree AH: Tumor kinome profiling of
early systemic disease dissemination in rectal cancer. Objective: To discuss findings regarding HIF-signalling
with international scientific expertise. Target: International scientists.
 23rd-27th Sept 2011, ECCO 16, ESMO 36, ESTRO 30 European Multidisciplinary Cancer Congress, Stockholm,
Sweden. Speaker: Røe, K: Protein kinase activity and therapy response. Objective: To discuss findings regarding
HIF-signalling with international scientific expertise. Target: International scientists.
 28th –30th Sept 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker for
21/OU-Lyng: Anne Hansen Ree: Tumour kinase activity and metabolic profiling of rectal cancer - radiotherapy
outcome and systemic dissemination. Objective: To discuss last year progress in 21/OU-Lyng within METOXIA.
Target: All partners of METOXIA. Kiranpreet Kaur:
 28th –30th Sept 2011 The 3rd General Assembly (Mid-Term Meeting) of METOXIA in Madrid, Spain. Speaker for
21/OU-Kragh: Kiranpret Kaur: Hematopoietic stem cells under Normoxia versus Hypoxia; preliminary results.
Objective: To discuss last year progress in 21/OU-Kragh within METOXIA. Target: All partners of METOXIA.
 27th Oct 2011, Amgen Nordic & Baltic Expert Group Workshop – Innovation in the treatment of GI cancer,
Copenhagen, Denmark. Speaker Anne Hansen Ree: Kinome profiling of tumors from rectal cancer patients for
identification of functional biomarkers of EGFR signaling pathway druggability. Objective: To discuss findings
regarding HIF-signalling with international scientific expertise. Target: International scientists.
 12th-16th Nov 2011, AACR-NCI-EORTC International Conference – Molecular Targets and Cancer Therapeutics,
San Francisco, CA, USA. Authors: Ree AH, Kristensen AT, Saelen MG, de Wijn R, Folkvord S, Abrahamsen TW,
Flatmark: Ex vivo kinome profiling of tumors from rectal cancer patients for possible identification of functional
biomarkers of EGFR signaling pathway druggability. Objective: To discuss findings regarding HIF-signalling with
international scientific expertise. Target: International scientists.
Scientific articles with acknowledgement for METOXIA-support:
 Røe K, Kakar M, Seierstad T, Ree AH, Olsen DR: Early prediction of response to radiotherapy and androgendeprivation therapy in prostate cancer by repeated functional MRI: a preclinical study. Radiation Oncol. 6;
(2011) 65-74.
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