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 2: 1.2.2010 - 31.1.2011
General comments concerning patenting related to METOXIA:
During 2nd period a sub-group has filed 2 patents and has also worked out a PCT-application (to be filed in 3rd
period). This involves the work on the CAIX-inhibitors where we have a product patent filed and involves
several partners, so far 1/UIO, 2/MAASTRO, 8/UNIMAN, 9/UNIFI and 18/IVSAS as patent owners. Later we
hope that also 3/UEDIN, 5/UOXF.BP, 12/DHZM, 13/CNRS and 20/GROW-UM can participate in this
development since they all may have 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:
 4th February 2010, patent Meeting, University of Florence Italy. Speaker 1 of 1/UIO: Erik Pettersen:
Introductory remarks concerning patenting in METOXIA and the scientific basis of the 2 patents so far in
question. Speaker 2 of 1/UIO: Katrine Rese Shadidi: Short Presentation of Birkeland Innovation and its role
in patenting and commercialization for METOXIA.
Objective: To compose a sub-group for development of CA9-inhibitors for therapy and diagnosis.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speakers Erik Pettersen and Nina Jeppesen Edin. Low dose-rate radiation as a priming factor and a
hypoxia-specific treatment. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Erik Pettersen: Leading the meeting and all discussions. Summing up from the former
sub-group meeting and a resume of the patent situation for CA9-inhibitors within METOXIA. Objective: To
discuss progress on non-invasive imaging using CA IX directed sulphonamides and combination
treatment. Target group: Research Scientists and collaborators/METOXIA members.
Scientific articles with acknowledgement for METOXIA-support:
 Pettersen, E.O.: METOXIA: The translation of new knowledge into cancer detection and treatment
processes. In: Public Service Review: European Union: Issue 20. pp: 188-189. http://edition.pagesuiteprofessional.co.uk/Launch.aspx?EID=fec3b902-efbb-461c-b74a-e9d2a03b0479
 Edin, N.J., Olsen, D.R., Sandvik, J.A., Malinen, E. and Pettersen, E.O.: Low dose hyper-radiosensitivity is
eliminated during exposure to cycling hypoxia but returns after reoxygenation. (Submitted).
 Cheng, C., Edin, J.F.J., Xiaoqun, G., Aspmodal, I., Cristoffersen, S., Jian, L., Storm-Mathisen, J., Pettersen,
E.O. and Bergersen, L.H.: Different alterations of different MCTs after hypoxia in brain and breast tumor
cells. (Submitted).
2/MAASTRO
 13t. January 2010 Nijmegen, The Netherlands: Speaker Ludwig Dubois. HX4: validation with pimonidazole.
Objective: Meeting to discuss progress on noninvasive imaging Target group: Research Scientists and
collaborators/METOXIA members.
 18th 20th March 2010 on First Molecular Imaging in Radiation Oncology, Brussels, Belgium: Speaker Ludwig
Dubois. Preclinical evaluation of [18F]HX4, a novel and promising hypoxia marker for PET imaging
Objective: To discuss progress on noninvasive imaging. Target group: Research Scientists.
 26th March 2010 7nd Antwerp Oncology day, Antwerp, Belgium: Speaker Ludwig Dubois. Evaluation of
hypoxia using non-invasive PET imaging. Objective: To discuss progress on non-invasive imaging. Target
group: Research Scientists
 9th April 2010 Research meeting Nice, France: Speaker Ludwig Dubois. The use of sulfonamides in targeting
CA IX for imaging and therapy purposes. Objective: To discuss progress on noninvasive imaging using CA IX
directed sulphonamides. Target group: Research Scientists and collaborators/METOXIA members.
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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
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker (Ludwig Dubois) Hypoxia and hypoxia response, a target for imaging and treatment: a
preclinical and clinical approach. Objective: To discuss last year progress in 2/MAASTRO within METOXIA.
Target: All partners of METOXIA.
 18th August 2010 Research meeting Nijmegen, The Netherlands: Speaker Ludwig Dubois. HX4: validation
with pimonidazole. Objective: To discuss progress on non-invasive imaging Target group: Research
Scientists
 7th September 2010 Pizza-meeting, Maastricht, The Netherlands: Speaker Ludwig Dubois. CA IX
sulfonamides: applications in imaging and therapy. Objective: To discuss progress on noninvasive imaging
using CA IX directed sulphonamides. Target group: Research Scientists.
 12th-16th September 2010 ESTRO 29 meeting, Barcelona, Spain: Speaker Ludwig Dubois. Preclinical
evaluation and validation of [18F]HX4, a novel and promising hypoxia marker for PET imaging. Objective: To
discuss progress on non-invasive imaging. Target group: Research Scientists.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Ludwig Dubois Possible models for testing of hypoxia imaging and metastasis
Objective: To discuss progress on non-invasive imaging using CA IX directed sulphonamides and
combination treatment. Target group: Research Scientists and collaborators/METOXIA members.
Scientific articles with acknowledgement for EUROXY/METOXIA-support:
 Akurathi, V., Dubois, L., Lieuwes, N.G., Chitneni, S.K., Cleynhens, B.J., Vullo, D., Supuran, C.T., Verbruggen,
A.M., Lambin, P. and Bormans, G.M.: Synthesis and biological evaluation of a 99mTc-labelled sulfonamide
conjugate for in vivo visualization of carbonic anhydrase IX expression in tumor hypoxia. Nuclear Med. Biol.
37; (2010) 557-564.
 Rouschop, K.M., van den Beucken, T., Dubois, L., Niessen, H., Bussink, J., Savelkouls, K., Keulers, T., Mujcic,
H., Landuyt, W., Voncken, J.W., Lambin, P., van der Kogel, A.J., Koritzinsky, M. and Wouters BG The
unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy
genes MAP1LC3B and ATG5 J. Clin. Invest. 120; (2010) 127–141.
3/UEDIN:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speakers Ian Kunkler and Simon Langdon: Short summing up of the 2/UEDIN METOXIA-activities
within medical research. New plan of delivery Objective: To discuss last year progress in 3/UEDIN within
METOXIA. Target: All partners of METOXIA.
 One abstract in collaboration with partner 7/FMC (Dr. Mike Dornish and colleagues) has been accepted for
presentation at the Annual AACR Meeting 2011. “Spheroid growth in 3D alginate matrices .” By JM Dornish,
T Andersen, H Heier-Baardson, C Markussen, C Ward, P Mullen, S Langdon, I Kunkler, D Harrison.
 October 2010 Oxford, UK, Workshop on the Tumour Microenvironment: Speaker Simon Langdon. Targeting
pH regulation in breast cancer. Presented at CTRad.
4/RUNMC:
 24th March 2010 University of Wisconsin USA: Speaker Albert J. van der Kogel. Imaging the heterogeneity
and dynamics of the tumor microenvironment. Medical Centre Grand Rounds presentation.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Hans Kaanders: Clinically relevant marker response patterns and critical subpopulations
of tumour cells Objective: To discuss last year progress in 4/RUNMC within METOXIA. Target: All partners
of METOXIA.
 20th -22nd June 2010 Washington, DC, USA: Speaker Albert J. van der Kogel. Imaging for Treatment
Assessment in Radiation Therapy. ITART (Imaging for Treatment Assessment in Radiation Therapy)
conference).
 September 2010 Barcelona, Spain (Keynote address): Speaker (J.H. Kaanders). ARCON: Results from a
randomized study in carcinoma of the larynx. 29th Annual Meeting of the European Society for
Therapeutic Radiology and Oncology.
Scientific articles with acknowledgement for METOXIA-support:
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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
 Hoogsteen, I.J., Marres, H.A.M., van den Hoogen, F.J.A., et al.: Expression of EGFR under tumor hypoxia:
Identification of a subpopulation of tumor cells responsible for aggressiveness and treatment resistance.
Submitted for publication.
 Rademakers, S., Lok, J., van der Kogel., et al.: Metabolic markers in relation to hypoxia; staining patterns
and colocalization of pimonidazole, HIF-1,
CAIX, LDH-5, GLUT-1, MCT1 and MCT4. Submitted for
publication.
5/UOXF.BP:
 16th March 2010, Keystone Symposium, Vancouver, Canada. Speaker Adrian Harris: pH Regulation &
Carbonic Anhydrase in Tumour Cells.
 26th March 2010, European Breast Cancer Conference (EBCC), Barcelona, Spain. Speaker Adrian Harris:
Angiogenesis and Hypoxia.
 3rd June 2010, Centre for Cancer Research & Cell Biology, Belfast, N-Ireland. Speaker Adrian Harris:
Mechanisms of Response and Resistance to Anti-Angiogenesis Therapy.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Adrian L. Harris: A comprehensive gene profile describing hypoxia, anoxia and
reoxygenation. Objective: To discuss last year progress in 5/UOXF.BP within METOXIA. Target: All partners
of METOXIA.
 14th June 2010, BACR 50th Anniversary Meeting, Edinburgh, Scotland. Speaker Adrian Harris: Role of
Hypoxia in Resistance to Anti-Angiogenic Therapy.
 27th September 2010, 4th International Conference Primary Systematic Treatment in the Management of
Breast Cancer: Cremona, Italy. Speaker Adrian Harris: Knowing Angiogenesis and the Environment.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Alan McIntyre: Spheroid models for use in CA9i-testing. Objective: To discuss
progress on non-invasive imaging using CA IX directed sulphonamides. Target group: Research Scientists
and collaborators/METOXIA members.
 24th January 2011, MSc Radiation Biology Course, Oxford, UK. Speaker Adrian Harris: Tumour vasculature:
angiogenesis and targeted therapy
Scientific articles with acknowledgement for METOXIA-support:
 Bridges, E.M., Harris, A.L.: The angiogenic process as a therapeutic target in cancer. Biochem Pharmacol.
(2011) Mar 4. [Epub ahead of print]
 Jubb, A.M., Miller, K.D., Rugo, H.S., Harris, A.L., Chen, D., Reimann, J.D., Cobleigh, M.A., Schmidt, M.,
Langmuir, V.K., Hillan, K.J., Chen, D.S. and Koeppen, H.: Impact of exploratory biomarkers on the treatment
effect of bevacizumab in metastatic breast cancer. Clin. Cancer Res. 17; (2011) 372-81; Epub 2011 Jan 11.
 Ghazoui, Z., Buffa, F.M., Dunbier, A.K., Anderson, H., Dexter, T., Detre, S., Salter, J., Smith, I.E., Harris, A.L.,
Dowsett, M. Close and stable relationship between proliferation and a hypoxia metagene in aromatase
inhibitor treated ER-positive breast cancer. Clin. Cancer Res., (2011) Feb 15 – [Epub ahead of print].
 Jubb, A.M., Buffa, F.M., Harris, A.L. Assessment of tumour hypoxia for prediction of response to therapy
and cancer prognosis. J. Cell. Mol. Med., 14; (2010) 18-29.
 Jubb, A.M., Soilleux, E.J, Turley, H., Steers, G., Parker, A., Low, I., Blades, J., Li, J.-L., Allen, P., Leek, R.,
Noguera-Troise, I., Gatter, K.C., Thurston, G. and Harris, A.L.: Expression of vascular notch ligand delta-like
4 and inflammatory markers in breast cancer. Am. J. Pathol., 176; (2010) 2019-28.
 Buffa, F.M., Harris, A.L., West, C.M. and Miller, C.J.: Large meta-analysis of multiple cancers reveals a
common, compact and highly prognostic hypoxia metagene. Br J Cancer, 102; (2010) 428-35.
 Jubb, A.M. and Harris, A.L.: Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet
Oncol. 11; (2010) 1172-83.
6/AUH.AS:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Morten Busk: Pre-clinical animal models for testing of hypoxia-related radio-therapeutic
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
strategies. Objective: To discuss last year progress in 6/AUH.AS within METOXIA. Target: All partners of
METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Busk, M., Munk, O.L., Jakobsen, S., Wang, T., Skals, M., Steiniche, T., Horsman, M.R. and Overgaard, J,:
Assessing hypoxia in animal tumor models based on pharmacokinetic analysis of dynamic FAZA-PET. Acta
Oncologica 49; (2010) 922–933
 Busk, M., Toustrup, K., Soerensen, B.S., Alsner, J., Horsman, M.R. Jakobsen, S. and Overgaard, J,: In vivo
identification and specificity assessment of mRNA markers of hypoxia in human and mouse tumors.
Accepted for publication in BMC Cancer 2011 Feb 9;11:63.
 Toustrup, K., Sørensen, B.S., Nordsmark, M., Busk, M., Wiuf, C., Alsner, J. And Overgaard, J.: Gene
expression classifier predicts for hypoxic modification of radiotherapy in Head and Neck cancer. Submitted.
7/FMC:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Mike Dornish: Bone-seeking -radiation of metastasis. Experience so far. Objective: To
discuss last year progress in 7/FMC within METOXIA. Target: All partners of METOXIA.
 26-29 June 2010. European Association for Cancer Research (EACR) meeting. An abstract entitled “Lack of
protective effect by hypoxia on alpha particle radiation from radium-223” was submitted and accepted for
presentation. The abstract reference is Eur. J. Cancer Suppl., 8, 216, 2010. A copy of the poster is attached
as Appendix 1.
 An abstract entitled “In situ immobilization in alginate foams – a novel 3D in vitro cell culture system” was
submitted and accepted for presentation at the European Association for Cancer Research (EACR) meeting
held 26-29 June 2010. The abstract reference is Eur. J. Cancer Suppl., 8, 136, 2010.
 An abstract entitled “Spheroid growth in 3D alginate matrices” was submitted and accepted for
presentation at the American Association for Cancer Research (AACR) meeting to be held in April 2011.
The work presented is in collaboration with the University of Edinburgh (Partner 3).
8/UNIMAN:
 Society for Endocrinology BES 2010, Investigating the role of HIF-1α in tumour growth and metastasis in an
in vivo model of thyroid cancer Endocrine Abstracts (2010) 21 P211 Poster presentation
 8th Feb 2010, The British Institute of Radiology, London. Speaker Kaye J. Williams. Investigating the role of
HIF-1a in tumour growth and metastasis in an in vivo model of thyroid carcinoma; Objective: Scientists in
training day.
 3-6 March 2010 Symposion der Deutschen Gesellschaft für Endokrinologie und Jahrestagung der
Slowakischen Gesellschaft für Endokrinologie, Leipzig. Speaker Kaye J. Williams. HIF-1α in tumour growth
and metastasis in an in vivo model of thyroid cancer.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Kaye J. Williams: Knock-out tumour models in the study of hypoxia-driven metastasis.
Objective: To discuss last year progress in 8/UNIMAN within METOXIA. Target: All partners of METOXIA.
 13-15th June 2010 Edinburgh, Scotland. Presenter Kaye J. Williams. A link between HIF-1a and PI3-Kinase
activity in the development of a metastatic phenotype in thyroid carcinomas? Poster presentation.
Objective Hallmarks of cancer: mechanisms to therapies, BACR
 28-30 June, Association for Radiation Research, St. Catherine's College, University of Oxford, UK. Invited
speaker Kaye J. Williams. HIF and hypoxic targets in radiobiology.
 11-16 September 2010, 14th International Thyroid Congress • Paris, Palais des Congrès. Speaker Kaye J.
Williams. Hypoxia-inducible factor-1α (hif-1α): An interacting role with the phosphoinositide 3-kinase (pi3k)
pathway in the development of a metastatic phenotype in thyroid carcinomas? oral communications.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Kaye J. Williams: Testing of patented CA9i on metastasis models in vivo and in vitro.
Objective: To discuss progress on non-invasive imaging using CA IX directed sulphonamides. Target group:
Research Scientists and collaborators/METOXIA members.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
Scientific articles with acknowledgement for METOXIA-support:
 Lunt, S.J., Cawthorne, C., Ali, M., Telfer, B.A., Babur, M., Smigova, A., Julyan, P.J., Price, P.M., Stratford, I.J.,
Bloomer, W.D., Papadopoulou, M.V. and Williams, K.J.: The hypoxia-selective cytotoxin NLCQ-1 (NSC
709257) controls metastatic disease when used as an adjuvant to radiotherapy. Br J Cancer, 103; (2010)
201-208.
 Burrows, N., Resch, J., Cowen, R.L., von Wasielewski, R., Hoang-Vu, C., West, C., Williams, K.J. and Brabant,
G.: Expression of hypoxia inducible factor 1α in thyroid carcinomas. Endocrine-Related Cancer, 17; (2010)
61-72.
9/UNIFI:
Dr. Claudiu T. Supuran presented seminars/conferences with the following occasions:
a) Collaboration with Universities of Montpellier and Nice, France, on the synthesis of CA IX inhibitors, visit in
the period 26 May – 05 June 2010
b) University of Padova, immunohistochemistry of CA IX in tumours, visit in the period 25 – 26 June 2010.
c) Invited lecture at the Medicinal Chemistry International Conference in Reims, France, 29 June – 3 July 2010
d) Collaboration with the Universities of Instanbul and Balikesir, Turkey, on the synthesis of CA IX inhibitors,
visit in the period 10-31 August 2010
e) Participation at the 1st Interntional Conference on Proton Dynamics, Rome, Italy, 26-28 September 2010,
with a plenary lòecture prsented (on CA IX inhibitors in cancer).
f) Seminar at the Italian Institute of Health (ISS), Rome, Italy, on October 15, 2010
g) Collaboration with Universities of Montpellier and Nice, France, on the synthesis of CA IX inhibitors, visit in
the period 25 October – 01 November 2010
h) Collaboration with the Universities of Antalya, Turkey, on the synthesis of CA IX/XII inhibitors, visit in the
period 2-9 November 2010 (and seminar on CA IX inhibition)
Other dissemination activities:
Dr. Peter Burghout of the Radboud University Nijmegen (NDL), participated to a conference entitled “Search
for bacterial genes contributing to pneumococcal pathogenesis: role for carbonic anhydrase”, in Florence, in
March 30, 2010
Prof. Reinhard Zeidler of the University Of Munchen (DEU), participated to the conference entitled
“Generation of New Tumor – reactive Antibodies against carbonic Anhydrase XII”, in Florence, October 13,
2010.
During my trips in France, Italy and Turkey I also had informal discussions with personalities in the anticancer
drug rsearch, which may be useful for the network. For example, with Dr. Stefamo Fais, head of the Italian
National Institte of Health, who is also a leader on the antitumor drug design, who was much interested in the
published METOXIA papers, or with Professors from Turkish Universities (O. Ozensoy, O. Guzel, O. Arslan, B.
Oksal) with whom we collaborate, and who have carbonic anhydrase inhibitor research projects.
 4th February 2010, patent Meeting, University of Florence Italy. Speaker 1 of 9/UNIFI: Andrea Scozzafava:
Introduction and wellcome. Speaker 2 of 9/UNIFI: Claudiu Supuran: CA9-inhibitors, chemical background
for the therapy patent.
Objective: To compose a sub-group for development of CA9-inhibitors for therapy and diagnosis.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Andrea Scozzafava. CA9 and -12-inhibitors to be tested: structures and their relationship
to the patent situation. Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All
partners of METOXIA.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Claudiu Supuran: Characteristics of a lead compound. Objective: To discuss progress
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
on non-invasive imaging using CA IX directed sulphonamides and combination treatment. Target group:
Research Scientists and collaborators/METOXIA members.
Scientific articles with acknowledgement for METOXIA-support:
 Carta, F., Innocenti, A., Hall, R.A., Mühlschlegel, F.A., Scozzafava, A. and Supuran, C.T.: Carbonic anhydrase
inhibitors. Inhibition of the β-class enzymes from the fungal pathogens Candida albicans and Cryptococcus
neoformans with branched aliphatic/aromatic carboxylates and their derivatives. Bioorg. Med. Chem. Lett.
2011 Feb 17. [Epub ahead of print].
 Durdagi, S., Şentürk, M., Ekinci, D., Balaydın, H.T., Göksu, S., Küfrevioğlu, O.I., Innocenti,
A., Scozzafava, A. and Supuran, C.T.: Kinetic and docking studies of phenol-based inhibitors of
carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site.
Bioorg. Med. Chem. 19; (2011) 1381-1389.
 Pacchiano, F., Carta, F., Vullo, D., Scozzafava, A. and Supuran, C.T.: Inhibition of -carbonic anhydrases with
ureido-substituted benzenesulfonamides. Bioorg. Med. Chem. Lett. 21; (2011) 102-105.
 Supuran, C.T.: Carbonic anhydrase inhibitors Bioorg. Med. Chem. Lett. 20; (2010) 20, 3467-3474.
 Pacchiano, F., Aggarwal, M., Avvaru, B.S., Robbins, A.H., Scozzafava, A., R McKenna, R. and Supuran, C.T.:
Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate
different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency. Chem. Comm. 46;
(2010) 8371-8373.
 Innocenti, A. and Supuran, C.T.: Paraoxon, 4-nitrophenyl phosphate and acetate are substrates of - but
not of -, - and -carbonic anhydrases Bioorg. Med. Chem. Lett. 20; (2010) 6208-6212.
 Innocenti, A., Scozzafava, A. and Supuran, C.T.: Carbonic anhydrase inhibitors. Inhibition of transmembrane
isoforms IX, XII and XIV with less investigated inorganic anions. Bioorg. Med. Chem. Lett. 20; (2010) 15481550.
 Maresca, A. and Supuran, C.T.: Coumarins incorporating hydroxy- and chloro- moieties
selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX
and XII over the cytosolic ones I and II. Bioorg. Med. Chem. Lett. 20; (2010) 4511-4514.
 Innocenti, A., Sarıkaya, S.B.Ö., Gülçin, I. and Supuran, C.T.: Carbonic anhydrase inhibitors.
Inhibition of mammalian isoforms I – XIV with a series of natural product polyphenols and
phenolic acids. Bioorg. Med. Chem. 18; (2010) 2159-2164.
 Ekinci, D., Çavdar, H., Talaz, O., Şentürk, M. and Supuran, C.T.: NO-releasing esters show
carbonic anhydrase inhibitory action against human isoforms I and II. Bioorg. Med.
Chem., 18; (2010) 3559-3563
 Avvaru, B.S., Wagner, J.M., Maresca, A., Scozzafava, A., Robbins, A.H., Supuran, C.T. and McKenna, R.:
Carbonic anhydrase inhibitors. The X-Ray crystal structure of human isoform II in adduct with an adamantyl
analogue of acetazolamide resides in a new hydrophobic binding pocket. Bioorg. Med. Chem. Lett. 20;
(2010) 4376-4381.
 Brzozowski, Z., Sławiński, J., Innocenti, A. and Supuran, C.T.: Carbonic anhydrase inhibitors. Regioselective
synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the
human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX, XII. Eur. J. Med.
Chem. 45; (2010) 3656-3661.
 Wagner, J., Avvaru, B.S., Robbins, A.H., Scozzafava, A., Supuran, C.T. and McKenna, R.: Coumarinylsubstituted sulfonamides strongly inhibit several human carbonic anhydrase isoforms: solution and
crystallographic investigations. Bioorg. Med. Chem. 18; (2010) 4873-4878.
 Maresca, A., Scozzafava, A. and Supuran, C.T.: 7,8-Disubstituted- but not 6,7-disubstituted coumarins
selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the
cytosolic ones I and II in the low nanomolar/subnanomolar range. Bioorg. Med. Chem. Lett. 20; (2010)
7255-7258.
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 Di Fiore, A., Monti, S.M., Innocenti, A., Winum, J.-Y., de Simone G. and Supuran, C.T.: Carbonic anhydrase
inhibitors. X-ray crystallographic and solution binding studies for the interaction of a boron containing
aromatic sulfamide with mammalian isoforms I-XV. Bioorg. Med. Chem. Lett. 20; (2010) 3601-3605.
 Gluszok, S., Frédérick, R., Supuran, C.T., Vullo, D., Scozzafava, A., Masereel, B., Depreux, P. and Goossens,
L.: Design, solid-phase synthesis and biological evaluation of novel 1,2-diarylpyrrole-3-carboxamides as
carbonic anhydrase IX inhibitors. Bioorg. Med. Chem., 18; (2010) 7392-7401.
 Esteves, M.A., Ortet, O., Capelo, A., Supuran, C.T., Marques, S.M., and Santos, M.A.: New
Hydroxypyrimidinone-containing Sulfonamides as Carbonic Anhydrase Inhibitors also acting as MMP
inhibitors. Bioorg. Med. Chem. Lett. 20; (2010) 3623-3627.
 Gavernet, L., Ramale, J.L., Bruno Blanch, L., Estiu, G., Maresca, A. and Supuran, C.T.: Affinity of sulfamates
and sulfamides to Carbonic Anhydrase II isoform: experimental and molecular modeling approaches. J.
Chem. Inform. Model. 20; (2010) 1113-1122.
 Marques, S.M., Enyedy, E.A., Supuran, C.T., Krupenko, N.I., Krupenko, S.A. and Santos, M.A.: PteridineSulfonamide Conjugates as Dual Inhibitors of Carbonic Anhydrases and Dihydrofolate Reductase with
Potential Antitumor Activity. Bioorg. Med. Chem. (2010) 5081-5089.
 Innocenti, A., Durdagi, S., Doostdar, N., Strom, T.A., Barron, A.R. and Supuran, C.T.: Nanoscale enzyme
inhibitors: Fullerenes inhibit carbonic anhydrase by occluding the active site entrance. Bioorg. Med. Chem.
28; (2010) 2822-2828.
 Innocenti, A., Gülçin, I., Scozzafava, A. and Supuran C.T.: Carbonic anhydrase inhibitors. Antioxidant
polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg. Med. Chem. Lett. 20; (2010) 5050-5053.
 Supuran, C.T.: Carbonic anhydrase inhibition/activation: trip of a scientist around the world in the search of
novel chemotypes and drug targets. Curr. Pharm. Des. 16; (2010) 3233-3245.
 Supuran, C.T., Di Fiore, A., Alterio, V., Monti, S.M. and De Simone, G.: Recent advances in structural studies
of the carbonic anhydrase family: The crystal structure of human CA IX and CA XIII. Curr. Pharm. Des. 16;
(2010) 3246-3254.
 Lopez, M., Salmon, A.J., Supuran, C.T. and Poulsen, S.-A.: Carbonic anhydrase inhibitors developed through
‘click tailing’. Curr. Pharm. Des., 16; (2010) 3277-3287.
 Carta, F., Temperini, C., Innocenti, A., Scozzafava, A., Kaila, K. and Supuran, C.T.: Polyamines inhibit
carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J. Med.Chem. 53; (2010) 55115522.
 Schulze Wischeler, J., Innocenti, A., Vullo, D., Agrawal, A., Cohen, S.M., Heine, A., Supuran, C.T. and Klebe,
G.: Bidentate Zinc Chelators for α-Carbonic Anhydrases that Produce a Trigonal Bipyramidal Coordination
Geometry. Chem. Med. Chem. 5; (2010) 1609-1615.
 Akurathi, V., Dubois, L., Lieuwes, N.G., Chitneni, S.K., Cleynhens, B.J., Vullo, D., Supuran, C.T., Verbruggen,
A.M., Lambin, P. and Bormans, G.M.: Synthesis and biological evaluation of a 99mTc-labelled sulfonamide
conjugate for in vivo visualization of carbonic anhydrase IX expression in tumor hypoxia. Nuclear Med. Biol.
37; (2010) 557-564.
 26. R. Gitto, S. Agnello, S. Ferro, D. Vullo, C.T. Supuran, A. Chimirri, . Identification of i potent and selective
human carbonic anhydrase VII (hCA II) inhibitors ChemMedChem 2010, 5, 823-826
 Lopez, M., Bornaghi, L.F., Innocenti, A., Vullo, D., Supuran, C.T. and Poulsen, S.-A.: Sulfonamide linked
neoglycoconjugates – a new class of inhibitors for cancer-associated carbonic anhydrases. J. Med. Chem.
53; (2010) 2913-2926.
 Gitto, R., Agnello, S., Ferro, S., Vullo, D., Brynda, J., Mader, P., Supuran, C.T. and Chimirri, A.: Identification
of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis,
Biological Evaluation and Enzyme-ligand X-ray studies. J. Med. Chem. 53; (2010) 2401-2408.
10/KI:
Presentation of METOXIA WP3 and WP4 research data were given at the following international conferences:
 19-24 january 2010, Keystone Symposia, Keystone, Colorado, USA, Lorenz Poellinger was invited plenary
speaker on the theme: Hypoxia: Molecular Mechanisms of Oxygen Sensing and Responsive Pathways.
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker 1: Lorenz Poellinger: Identification of common molecular targets for activated Notch and
HIF transcription factors during EMT. Speaker 2: Pegah Rouhi: Angiogenic factors in pre-clinical model
systems.
Objective: To discuss last year progress in 10/KI within METOXIA. Target: All partners of METOXIA.
 15-18 June 2010 Smolenice, Slovakia. Invited plenary speaker, Lorenz Poellinger: Oxygen in Health and
Disease. Objective: EU Cost Action: “Hypoxianet”.
 7-8 October 2010, Dublin, Ireland. Invited plenary speaker Lorenz Poellinger: Therapeutic Aspects of
hypoxia-dependent pathways. Objective: EU Cost Action: “Hypoxianet”.
 8-11 January 2011 Davos Congress, Davos, Switzerland. Speaker Lorenz Poellinger: “Hypoxia: Molecular
Mechanisms of Oxygen Sensing and Responsive Pathways”, Also attended by Poellinger research group
laboratory members: Drs. Katarina Gradin, Dr. Hideaki Nakamura, Dr. Norio Suzuki
Scientific articles with acknowledgement for METOXIA-support:
 Zhang, D., Hedlund, E.M., Lim, S., Chen, F., Zhang, Y., Sun, B., and Cao, Y.: Antiangiogenic agents
significantly improve survival in tumor-bearing mice by increasing tolerance to chemotherapy-induced
toxicity. Proc. Natl. Acad. Sci. U S A. 108; (2011) 4117-22. Epub 2011 Feb 18.
 Rouhi, P., Jensen, L.D., Cao, Z., Hosaka, K., Länne, T., Wahlberg, E., Steffensen, J.F. and Cao Y.: Hypoxiainduced metastasis model in embryonic zebrafish. Nat Protoc. 5; (2010) 1911-8. Epub 2010 Nov 4
 Cao, Y.: Off-tumor target--beneficial site for antiangiogenic cancer therapy? Nat. Rev. Clin. Oncol. 7; (2010)
604-8. Epub 2010 Aug 3.
 Cao, R. and Cao, Y.: Cancer-associated retinopathy: a new mechanistic insight on vascular remodeling. Cell
Cycle. 2010 May 15;9(10):1882-5. Epub 2010 May 15.
 Xue, Y., Lim, S., Bråkenhielm, E. and Cao Y.: Adipose angiogenesis: quantitative methods to study
microvessel growth, regression and remodeling in vivo. Nat Protoc. 5; (2010) 912-20. Epub 2010 Apr 22.
 Cao, Y.: Therapeutic angiogenesis for ischemic disorders: what is missing for clinical benefits? Discov. Med.
9; (2010) 179-84.
 Cao, Y.: Angiogenesis: What can it offer for future medicine? Exp Cell Res. 316; (2010) 1304-8. Epub 2010
Mar 3.
 Rouhi, P., Lee, S.L., Cao, Z., Hedlund, E.M., Jensen, L.D. and Cao, Y.: Pathological angiogenesis facilitates
tumor cell dissemination and metastasis. Cell Cycle. 9; (2010) 913-7. Epub 2010 Mar 6.
 Cao, Y.: Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev
Drug Discov. 9; (2010) 107-15.
11/MAD:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Luis del Peso: Identification of new targets relevant to the EMT and angiogenesis.
Objective: To discuss last year progress in 11/MAD within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Ortiz-Barahona, A., Villar, D., Pescador, N., Amigo, J. and del Peso, L.: Genome-wide identification of
hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcriptionprofiling data and in silico binding site prediction. Nucleic Acids Res. 38; (2010) 2332-45. Epub 2010 Jan 8.
12/DHZM:
 4th February 2010, patent Meeting, University of Florence Italy. Speaker Agnes Görlach: A short over-view
of potential models in their use which could be of particular relevance in the study of a hypoxia-specific
cell-killing substance. Objective: To compose a sub-group for development of CA9-inhibitors for therapy
and diagnosis.
 March 2010 Joint Meeting of the German and Danish Physiological Societies, Copenhagen, Denmark.
Speaker Agnes Görlach. Presented data related to METOXIA.
 March 2010, Pathology Department, Geneva Switzerland. Speaker Agens Görlach: Presented data related
to METOXIA.
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 May 2010, Vanderbilt University, Nashville, TE, USA. Speaker Agnes Görlach. Presented data related to
METOXIA
 15-18 June 2010 Smolenice, Slovakia. Speaker, Agnes Görlach. Presented data related to METOXIA.
Objective: EU Cost Action: “Hypoxianet”.
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Agnes Görlach: Regulation of NADPH oxidases by hypoxia. Objective: To discuss last year
progress in 12/DHZM within METOXIA. Target: All partners of METOXIA.
 July 2010 Annual Meeting of the Society of Microcirculation and Vascular Biology, Berlin, Germany Speaker
Agnes Görlach. Presented data related to METOXIA.
 7-8 October 2010, Dublin, Ireland. Speaker, Agnes Görlach. Presented data related to METOXIA. Objective:
EU Cost Action: “Hypoxianet”.

Scientific articles with acknowledgement for METOXIA-support:
 Schelter, F., Halbgewachs, B., Bäumler, P., Neu, C., Görlach, A., Schrötzlmair, F. and Krüger, A.: Tissue
inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by hypoxia-inducible
factor-1aClin Exp Metastasis. 28; (2011) 91–99.
 Diebold, I., Petry, A., Hess, J. and Görlach, A.: The NADPH oxidase subunit NOX4 is a new target gene of the
hypoxia-inducible factor-1. Mol. Biol. Cell 15; (2010) 2087-96.
 Diebold, I., Petry, A., Djordjevic, T., BelAiba, R.S., Fineman, J., Black, S., Schreiber, C., Fratz, S., Hess, J.,
Kietzmann, T. and Görlach, A.: Reciprocal regulation of Rac1 and PAK-1 by HIF-1α: A positive feed back loop
promoting pulmonary vascular remodeling Antioxid Redox Signal 13; (2010) 399-412.
 Su, Y., Loos, M., Giese, N., Hines, O.J., Diebold, I., Görlach, A., Metzen, E., Pastorekova, S., Friess, H. and
Büchler, P.: Identification of a survival-independent metastasis-enhancing role of hypoxia-inducible factor1alpha with a hypoxia-tolerant tumor cell line. J Biol Chem. 2010 Aug 20;285(34):26182-9. Epub 2010 Jun
21
13/CNRS:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Jacques Pouyssegur: Progress report in targeting CAIX, CAXII, Monocarboxylate
transporters MCTs and their chaperon Basigin/CD147. Objective: To discuss last year progress in 12/DHZM
within METOXIA. Target: All partners of METOXIA.
Meetings where Jacques Pouyssegur have been invited, and have lectured in 2010
 13th January 2010, Paris, France. 2nd Meeting Pasteur & Curie Institutes. Plenary Lecture.
 18th January 2010, Paris, France. Annual meeting of the French Cancer Society (SFC - Club facteur de
Croissance).
 22nd-23rd January 2010, Nice, France. Molecular Biology and Imaging in Oncology Workshop, Chairman &
Speaker.
 10th-13th March 2010, Regensburg, Germany. German Annual Cell biology Meeting and Melanoma
research.
 24th-25th March 2010, Bonn, Germany. 1st biennial International Cancer Conference on Tumor
microenvironment.
 27th-30th March 2010, Copenhagen, Denmark. Scandinavia and German Joint Physiological Society Meeting.
 15th April 2010, Paris, France. Lecture “ Biologie des Cancers, Bilan d’une décennie” SFC.
 23rd-24th April 2010, Barcelona, Spain. International Meeting on Functional Genomics SIGMA ZFN
technology.
 29th-30th April 2010, Dijon, France. Lecture plénière, Symposium Intercancéropole “Cancer, Métabolisme et
Nutrition”.
 11th May 2010, Zürich , Switzerland. Seminar at the Zürich Center for Integrative Physiology.
 3rd-4th June 2010, Helsinki, Finland. Symposium on “Molecular Insights into Cancer progression and
Invasion”.
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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
 15th-18th June 2010, Smolenice, Slovak Republic. Symposium “Oxygen in health and disease”. Objective: EU
Cost Action: “Hypoxianet”.
 22nd-24th June 2010, Paris, France. Eurocancer, Chair “Basic research session “and «Diabetes and Cancer
workshop».
 26th-30th June 2010, Oslo, Norway. European Association in Cancer Research (EACR 21).
 5th-7th July 2010, Moscow, Russia. Russian-French Colloqium “Molecular Biology of Mammalian cells”.
 6th-11th September 2010, Fondation des Treilles. International Symposium on “Mouse models in cancer”.
 10th-16th September 2010, Philadelphia, USA. AACR Meeting Conference “Metastasis and Tumor
microenvironment”.
 19th-21st September 2010, Edinburgh, Scotland. Meeting on “Cancer and Metabolism, Pathways to the
Future”.
 27th-28th September 2010, Rome Italy. International Symposium on Proton Dynamic and Cancer ISPDC.
 30th September-3rd October 2010, Oslo, Norway. FEBS Workshop on Spatiotemporal Dynamics of Cell
signalling.
 7th-8th October 2010, Dublin, Ireland. Therapeutic aspects of Hypoxia-sensitive Pathways. Objective: EU
Cost Action: “Hypoxianet”.
 23rd-26th October 2010, Capri, Italy. International Workshop “Therapeutic opportunities on Cancer
Metabolism and Cell death”.
 28th 31st October 2010, Mont St Odile, France. 35th Euro Symposium on Hormones and Cell regulation.
(replaced by C. Brahimi).
 27th-31st October 2010, Singapore. Singapore Biology Symposium and BBRC Annual meeting.
 31st October-5th November 2010, Ascona, Swizterland. 4th International Conference on Tumor-host
Interaction.
 5th-6th November 2010, Paris, France. Chair & Speaker INCa International Forum “Prospects in Future
Cancer Research”.
 8th-10th November 2010, Barcelona, Spain. Biomed Conference on “ Cancer Metabolism”.
 22nd November 2010, Maison de la Chimie, Paris, France. Lecture Congrès “Carrefour de la Pathologie
2010”.
 8th 10th December 2010, Lille, France. Chair & Speaker Symposium Scientifique de la Société Française de
Nutrition (SFN).
 17th December 2010, Marseilles, France. 2nd Scientific Meeting on “Metabolic Signature of Cancers and
Imaging”.
Scientific articles with acknowledgement for METOXIA-support:
 Brahimi-Horn, M.C. and Pouysségur, J.: Tumor Hypoxia and Energetic Metabolism. Curr Opin Genet Dev.
21; (2011) 67-72. Epub 2010 Nov 11.
 Puisségur, M.P., Mazure, N.M., Bertero, T., Pradelli, L., Grosso, S., Robbe-Sermesant, K., Maurin, T.,
Lebrigand, K., Cardinaud, B., Hofman, V., Fourre, S., Magnone, V., Ricci, J.E., Pouysségur, J., Gounon, P.,
Hofman, P., Barbry, P. and 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) 465-78.
Epub 2010 Oct 1.
 Parks, S., Chiche, J. and Pouysségur, J.: pH control mechanisms of tumor survival and growth. J Cell Physiol.
22; (2011) 299-308.
 Mazure, N.M., Pouysségur, J.: Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol.
22; (2010) 177-180.
 Chiche, J., Ilc, K., Brahimi-Horn, M.C. and Pouysségur, J.: Membrane-bound carbonic anhydrases are key pH
regulators controlling tumor growth and cell migration. Adv Enzyme Regul. 50; (2010) 20-33.
 Ilie, M., Mazure, N.M., Hofman, V., Ammadi, R.E., Ortholan, C., Bonnetaud, C., Havet, K., Venissac, N.,
Mograbi, B., Mouroux, J., Pouysségur, J. and Hofman, P.: High levels of carbonic anhydrase IX in tumour
tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J
Cancer. 102; (2010) 1627-35.
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 Chiche, J., Rouleau, M., Gounon, P., Brahimi-Horn, M.C., Pouysségur, J. and Mazure, N.M.: Hypoxic
enlarged mitochondria protect cancer cells from apoptotic stimuli. J Cell Physiol. 22; (2010) 648-57.
14/ALU-FR:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker 1: Jochen Kieninger: SCCF: application to hypoxic and "normoxic" cell culture - results
form joint measurement in Oslo. Speaker 2: Hubert Flamm: Development of super oxide sensors - actual
status and pitfalls. Objective: To discuss last year progress in 14/ALU-FR within METOXIA. Target: All
partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Kieninger, J. Sandvik, J.A., Pettersen, E.O., Jobst, G., Aravindalochanan, K. and Urban, G.A.:. Monitoring of
Peri-Cellular Oxygen Levels in Tumor Cell Cultures by Amperometric Oxygen Sensor Array. IEEE SENSORS
2010, Waikoloa, HI, USA, 2010.
 Pruszak, J., Döbrössy, M., Kieninger, J., Aravindalochanan, K., Urban, G.A. and Nikkhah. G.: Neural Stem
Cells: From Cell Fate and Metabolic Monitoring Toward Clinical Applications. In: G. M. Artmann, S. Minger,
J. Hescheler (Editors). Stem Cell Engineering. Springer-Verlag, Berlin Heidelberg, 2011.
15/Jobst:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Gerhard Jobst: Development of probes for detection and perfusion monitoring. Objective:
To discuss last year progress in 15/Jobst within METOXIA. Target: All partners of METOXIA.
16/VX:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Jan Villadsen: Vivox Feed back control of incubator. Objective: To discuss last year
progress in 16/VX within METOXIA. Target: All partners of METOXIA.
17/UCL:
 19th-24th January 2010 Keystone, Denver, Colorado, USA. Keystone Symposium on Hypoxia: Molecular
Mechanisms of Oxygen Sensing and Response Pathways. Invited speaker Patrick Maxwell: ‘The
VHL/PHD/HIF axis in kidney cancer’.
 February 2010: Royal Veterinary College, Camden Campus. Invited lecture, “Oxygen sensing: genetic
insights from worms through to humans”.
 March 2010: Division of Basic Medical Sciences, Molecular & Metabolic Signalling Centre, St George’s
University, London. Invited lecture: “ Genetic insights into oxygen sensing”.
 14th April 2010 New College, Oxford. Nordic and University of Oxford Science Exchange: Neuroendocrine
Tumours (NETs) Advances in Biology and Treatments. Invited speaker Patrick Maxwell: “HIF in
neuroendocrine tumouriogenesis”.
 15th-18th June 2010 Smolenice Castle, Slovakia. Meeting of COST Action TD0901 HypoxiaNet. Oxygen in
Health and Disease. Invited lecture by Patrick Maxwell: ‘Hypoxic response pathways in kidney cancer’.
 17th September 2010 Institute of Child Health, London. Symposium on Cardiovascular and Metabolic
Sciences: Processes, disease prevention and therapeutic strategies. Patrick Maxwell chairing discussion on:
“Experimental Medicine to Clinical Strategies”.
 27th-30th September 2010 Leh, Ladakh, India. International Symposium on Recent Trends and Future
Perspectives in High-Altitude Pulmonary Research. Invited speaker Patrick Maxwell: “Learning from genetic
variants in the oxygen response pathway in humans and mice”.
 5th October 2010, Bio Nano Consulting Road Show, San Francisco, USA. Nanotechnology in Drug Discovery
and Development. Patrick Maxwell on Radio Interview with Dr Moira Gunn on BioTech Nation.
 8th-10th October 2010, Dublin. HypoxiaNet Working Group Meeting on therapeutic aspects of hypoxiadependent pathways. Speaker Patrick Maxwell: “Hypoxic response pathways in kidney cancer”.
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 14th November 2010, Trinity Centre for Health Sciences, St James’s Hospital, Dublin: The 13th Annual
Meeting of the Institute of Molecular Medicine. Speaker Patrick Maxwell: “Confessions of a clinician
scientist – how oxygen turned me on”.
 17th November 2010, Institute of Child Health, London. Annual Lecture. Speaker Patrick Maxwell: “Oxygen
Sensing”.
 26th-27th November 2010, Nicosia, Cyprus. 2nd International Conference of the Cyprus Society of Human
Genetics.
 16th December 2010, London, UK. Seminar at UCL Cancer Institute: Speaker Patrick Maxwell: “Oxygen
sensing and Renal Cancer”.
 8-11 January 2011 Davos Congress, Davos, Switzerland. OXYGEN – HypoxiaNet Research Conference:
Patrick Maxwell was member of organising committee and session chair.
18/IVSAS:
 15th-18th June 2010 meeting of the COST Action TD0901 Hypoxianet. – Smolenice, Slovakia. Speaker 1: Silvia
Pastorekova: New insights into functional aspects of CA IX and their implications for cancer biology.
Presentation 2, poster: Ditte, P., Svastova, E., Zatovicova, M., Pastorekova, S., Dequiedt, F. and Pastorek, J.:
CA IX-mediated acidification of extracellular environment is dependent on Thr443 phosphorylation by PKA.
Presentation 3, poster: Takacova, M., Kopacek, J., Barathova, M., Ohradanova, A., Goliasova, T.,
Pastorekova, S. and Pastorek, J.: Complex view on the transcriptional regulation of CA IX. In Oxygen in
health and disease. Presentation 4, poster: Witarski, W., Hulikova, A., Zatovicova, M., Barathova, M.,
Kopacek, J., Pastorek, J., Pastorekova, S. and Svastova, E.: The role of carbonic anhydrase IX in cell
migration as a part of metastatic cascade. In Oxygen in health and disease. (In: “Oxygen in health and
disease”: Meeting of the COST Action TD0901 Hypoxianet. - Smolenice, 2010, p.40, 45, 60 and 62
respectively).
 6th-8th October 2010 meeting of the COST action TD0901 HypoxiaNet, Dublin. Speaker Silvia Pastorekova:
Therapeutic strategies based on CA IX-mediated targeting of tumor cells with hypoxic phenotype. (n:
Theraputic aspects of Hypoxia-inducible Pathways“, Meeting of the COST action TD0901 HypoxiaNet).
 25th September 2010, 10th Central European Meeting in Bratislava, Slovakia. Presentation, poster:
Pastorekova, S., Takacova, M., Zatovicova, M., Bartosová, M., Skvarkova, L., Vidlickova, I. and Breza, J.: A
study of the clinical significance of carbonic anhydrase IX (CA IX) in renal carcinomas. (In EAU 10th Central
European Meeting -book of abstracts. - Bratislava : [s.n.], 2010, p. 31).
Scientific articles with acknowledgement for METOXIA-support:
 Su, Y., Loos, M., Giese, N., Hines, O.J., Diebold, I., Görlach, A., Metzen, E., Pastorekova, S., Friess, H. and
Büchler, P.: Identification of a survival-independent metastasis-enhancing role of hypoxia-inducible factor1alpha with a hypoxia-tolerant tumor cell line. J. Biol. Chem. 2010 Aug 20;285(34):26182-9. Epub 2010 Jun
21.
 Pastorek, J. and Pastorekova, S.: Molelular mechanisms regulating expression and function of cancerassociated carbonic anhydrase IX. In: The tumor microenvironment (Ed. Bagley, RG), Humana Press, 2010,
pp-749, ISBN 978-1-1499-6614-8. pp: 59-90.
 Zatovicova, M., Jelenska, L., Hulikova, A., Ditte, Z., Ditte, P., Goliasova, T., Pastorek, J. and Pastorekova, S.:
Carbonic anhydrase IX as an anticancer therapy target: preclinical evaluation of internalizing monoclonal
antibody directed to catalytic domain. In Current Pharmaceutical Design, 2010, vol., no., p.. (4.414 IF2009). (2010 - Current Contents). ISSN 1381-6128.
19/IBT:
 14th-18th January 2011 Davos, Switzerland. Article published in relation to conference OXYGEN 2011:
Hypoxia sensing, signaling and adaptation. Jakubauskiene, E., R. Stasionyte, R., Makino, Y., Poellinger, L.,
Kanopka, A.: Role of 65 kDa protein in regulation of HIF-3α pre-mRNA splicing
20/GROW-UM:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Brad Wouters: Isogenic tumour models and targeting of hypoxia response pathways
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
including UPR, mTOR and HIF. Objective: To discuss last year progress in 20/GROW-UM within METOXIA.
Target: All partners of METOXIA.
 30th November 2010 CA IX sub-group meeting Sheraton Airport hotel, Schiphol, Amsterdam, The
Netherlands. Speaker Brad Wouters. A short over-view of potential models and their use which could be of
particular relevance in the study of a hypoxia-specific cell-killing substance Objective: To discuss progress
on non-invasive imaging using CA IX directed sulphonamides and combination treatment. Target group:
Research Scientists and collaborators/METOXIA members.
Scientific articles with acknowledgement for EUROXY/METOXIA-support:
 Rouschop, K.M., van den Beucken, T., Dubois, L., Niessen, H., Bussink, J., Savelkouls, K., Keulers, T., Mujcic,
H., Landuyt, W., Voncken, J.W., Lambin, P., van der Kogel, A.J., Koritzinsky, M. and Wouters BG The
unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy
genes MAP1LC3B and ATG5 J. Clin. Invest. 120; (2010) 127–141.
21/OU:
 10th-13th June 2010 The 2nd General Assembly of METOXIA on the Coastal Steamer Tromsø-Trondheim,
Norway. Speaker Anne Hansen Ree: Micrometastasis in rectal cancer - relevance of tumour kinase
signalling mediated by VEGFR and PI3K/AKT. Objective: To discuss last year progress in 21/OU within
METOXIA. Target: All partners of METOXIA.
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