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 5: 1.2.2013 - 31.7.2014
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 has 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. It could well be that some partners have patented
inventions during the 4th period which has not been managed through the management team of METOXIA, but in
that case no financing have been used by our “Other” –post on the METOXIA budget.
Individual partner’s dissemination:
1/UIO:
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speakers
a) Erik O. Pettersen: Short summing up on history and aim of today’s meeting. b) Jørund Sollid: How should we
best commercialize the METOXIA patent portfolio? Objective: To reach a conclusion regarding the further
strategy for commercialization of our patented CAIX-inhibitor compounds. Target: Participants of the CAIXisub-group of METOXIA.
 18th – 20th April 2013. International meeting on carbonic anhydrases titelsed: "Frontiers In CA research :
Dissemination activity of the EU project METOXIA” In Montecattini Terme, Italy. Speaker Erik O. Pettersen:
METOXIA – a successful network; Perspectives of continuation in the Horizon 2020 program. Objective: To
announce the possibility for new networks for continuation of the research performed during METOXIA.
Target: International experts on Carbonic Anhydrases..
 20th September 2013 METOXIA sub-group meeting on the theme: “How to best commercialize the METOXIA
CAIX patent portfolio”. Speakers a) Erik O. Pettersen: Short summing up on history and aim of today’s meeting.
Also a brief summing up of data produced so far by Cyprotex Discovery Ltd on compounds DTC-24a, Xanti-15a,
DH348, NKP60, DH307, DH338 and Acetazolamide. b) Jørund Sollied: Presentation of the ideas of Inven2
regarding further commercialization of CAIX-inhibitors for cancer treatment with focus on the road-map.
Objective: To reach a conclusion regarding the further strategy for commercialization of our patented CAIXinhibitor compounds. Target: Participants of the CAIXi-sub-group of METOXIA.
 3rd November 2013: METOXIA steering group meeting on the theme: “Points for the General Assembly for
termination of METOXIA and decisions” in Nice, France. Speaker Erik O. Pettersen: Should we invite the
METOXIA partners to co-author a final paper summing up the METOXIA achievements with participation of all
groups?” Objective: To get back-up from WP-leaders for this suggestion at the GA-meeting. Target: Work
Package leaders of METOXIA.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speakers: a) Erik O.
Pettersen: A short resume of to what extent METOXIA in its 4th (and partly its 5th) year reached its goals;
planning round-up of the METOXIA project. b) Stine Christoffersen: Combined effect of cyclic hypoxia and ultralow dose-rate low-LET radiation. Objective: To discuss last year progress of METOXIA and the finalization of
the project. Target: All partners of METOXIA.
 4th-8th April 2014. The 33rd ESTRO conference, Vienna, Austria. Invited speaker: Eirik Malinen: ”Accounting for
uncertainties in imaging and radiation delivery in dose painting trials.” Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within radiation oncology
Scientific articles with acknowledgement for METOXIA-support:
 Edin NJ, Sandvik JA, Cheng C, Vollan HS, Reger K, Görlach A, Pettersen EO. The role of nitric oxide radicals in
removal of hyper-radiosensitivity by priming irradiation. J Radiat Res 2013;54:1015-1028.
 Larsen BE, Karlsen J, Pettersen EO, Sandvik JA, Melvik JE. Oxygen consumption in T-47D cells immobilized in
alginate. Cell Prolif. 2013;46:469-481.
 Kieninger J, Aravindalochanan K, Sandvik JA, Pettersen EO, Urban GA. Pericellular oxygen monitoring with
integrated sensor chips for reproducible cell culture experiments. Cell Prolif 2014; 47:180-188.
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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

Edin NJ, Sandvik JA, Cheng C, Bergersen L, Pettersen EO. The roles of TGF-β3 and peroxynitrite in
removal of hyper-radiosensitivity by priming irradiation. Int J. Radiat Biol. 2014; 90;527-537.
PhD thesis:
 Lars Tore Gyland Mikalsen: “Solid Tumour vascular Quantification: A Histopathology Study of Tumour
Endothelium”. Faculty of Mathematics and Natural Sciences, The University of Oslo, Oslo, Norway, March 2014.
2/MAASTRO
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speaker
Philippe Lambin: Tumour models for preclinical effect-studies and eventual imaging. Objective: To reach a
conclusion regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds.
Target: Participants of the CAIXi-sub-group of METOXIA.
 8th June 2013. International oxygen conference in Oulu, Finland. Speaker Sarah Peeters.
 20th September 2013 METOXIA sub-group meeting on the theme: “How to best commercialize the METOXIA
CAIX patent portfolio”. Speaker Nicolas Geûens: History and road ahead for DualTpharma. Objective: To reach a
conclusion regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds.
Target: Participants of the CAIXi-sub-group of METOXIA.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Philippe
Lambin: Hypoxia-related clinical trials: New imaging biomarkers and new therapeutic interventions. Objective:
To discuss last year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
 4th-8th April 2014. The 33rd ESTRO conference, Vienna, Austria. Invited speakers: a) Philippe Lambin:
“Immunocytokines and radiotherapy: preclinical experience.” b) Philippe lambin: “Multi-factorial decision
support systems.” Objective: To give an over-view over the hypoxia-regulatory field. Target: International
research scientists within radiation oncology
Scientific articles with acknowledgement for EUROXY/METOXIA-support:
 Lambin P, van Stiphout RG, Starmans MH, Rios-Velazquez E, Nalbantov G, Aerts HJ, Roelofs E, van Elmpt W,
Boutros PC, Granone P, Valentini V, Begg AC, De Ruysscher D, Dekker A. Predicting outcomes in radiation
oncology--multifactorial decision support systems. Nat Rev Clin Oncol. 2013;10;27-40.
 Roelofs E, Persoon L, Nijsten S, Wiessler W, Dekker A, Lambin P. Benefits of a clinical data warehouse with
data mining tools to collect data for a radiotherapy trial. Radiother Oncol. 2013;108;174-179.
 Dubois L, Peeters SG, van Kuijk SJ, Yaromina A, Lieuwes NG, Saraya R, Biemans R, Rami M, Parvathaneni NK,
Vullo D, Vooijs M, Supuran CT, Winum JY, Lambin P. Targeting carbonic anhydrase IX by nitroimidazole
based sulfamides enhances the therapeutic effect of tumor irradiation: a new concept of dual targeting
drugs. Radiother Oncol 2013;108;523-538.
 Buijsen J, Lammering G, Jansen RL, Beets GL, Wals J, Sosef M, Den Boer MO, Leijtens J, Riedl RG, Theys J,
Lambin P. Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally
advanced rectal cancer. Radiother Oncol. 2013;107;184-188.
 Rami M, Dubois L, Parvathaneni NK, Alterio V, van Kuijk SJ, Monti SM, Lambin P, De Simone G, Supuran CT,
Winum JY. Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazolesulfonamides/sulfamides/sulfamates. J Med Chem 2013;56;8512-8520.
 Rouschop KM1, Dubois LJ, Keulers TG, van den Beucken T, Lambin P, Bussink J, van der Kogel AJ, Koritzinsky
M, Wouters BG. PERK/eIF2α signaling protects therapy resistant hypoxic cells through induction of
glutathione synthesis and protection against ROS. Proc Natl Acad Sci U S A. 2013;110;4622-4627.
 van Elmpt W, Das M, Hüllner M, Sharifi H, Zegers CM, Reymen B, Lambin P, Wildberger JE, Troost EG, VeitHaibach P, De Ruysscher D. Characterization of tumor heterogeneity using dynamic contrast enhanced CT
and FDG-PET in non-small cell lung cancer. Radiother Oncol. 2013;109;65-70.
 Leijenaar RT, Carvalho S, Velazquez ER, van Elmpt WJ, Parmar C, Hoekstra OS, Hoekstra CJ, Boellaard R,
Dekker AL, Gillies RJ, Aerts HJ, Lambin P. Stability of FDG-PET Radiomics features: an integrated analysis of
test-retest and inter-observer variability. Acta Oncol. 2013;52;1391-1397.
 Carvalho S, Leijenaar RT, Velazquez ER, Oberije C, Parmar C, van Elmpt W, Reymen B, Troost EG, Oellers M,
Dekker A, Gillies R, Aerts HJ, Lambin P. Prognostic value of metabolic metrics extracted from baseline
positron emission tomography images in non-small cell lung cancer. Acta Oncol. 2013;52;1398-1404.
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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
 Nalbantov G, Kietselaer B, Vandecasteele K, Oberije C, Berbee M, Troost E, Dingemans AM, van Baardwijk A,
Smits K, Dekker A, Bussink J, De Ruysscher D, Lievens Y, Lambin P. Cardiac comorbidity is an independent
risk factor for radiation-induced lung toxicity in lung cancer patients. Radiother Oncol. 2013;109;100-106.
 Zegers CM, van Elmpt W, Wierts R, Reymen B, Sharifi H, Öllers MC, Hoebers F, Troost EG, Wanders R, van
Baardwijk A, Brans B, Eriksson J, Windhorst B, Mottaghy FM, De Ruysscher D, Lambin P. Hypoxia imaging
with [¹⁸F]HX4 PET in NSCLC patients: defining optimal imaging parameters. Radiother Oncol. 2013;109;5864.
 Lambin P, Roelofs E, Reymen B, Velazquez ER, Buijsen J, Zegers CM, Carvalho S, Leijenaar RT, Nalbantov G,
Oberije C, Scott Marshall M, Hoebers F, Troost EG, van Stiphout RG, van Elmpt W, van der Weijden T,
Boersma L, Valentini V, Dekker A. 'Rapid Learning health care in oncology' - an approach towards decision
support systems enabling customised radiotherapy'. Radiother Oncol. 2013;109;159-64.
 Velazquez ER, Parmar C, Jermoumi M, Mak RH, van Baardwijk A, Fennessy FM, Lewis JH, De Ruysscher D,
Kikinis R, Lambin P, Aerts HJ. Volumetric CT-based segmentation of NSCLC using 3D-Slicer. Sci Rep. 2013 Dec
18;3:3529. doi: 10.1038/srep03529.
 Roelofs E, Dekker A, Meldolesi E, van Stiphout RG, Valentini V, Lambin P. International data-sharing for
radiotherapy research: an open-source based infrastructure for multicentric clinical data mining. Radiother
Oncol. 2014;110;370-374.
 Hoeben BA, Starmans MH, Leijenaar RT, Dubois LJ, van der Kogel AJ, Kaanders JH, Boutros PC, Lambin P,
Bussink J. Systematic analysis of 18F-FDG PET and metabolism, proliferation and hypoxia markers for
classification of head and neck tumors. BMC Cancer 2014 Feb 26;14:130. doi: 10.1186/1471-2407-14-130
 Fox NS, Starmans MH, Haider S, Lambin P, Boutros PC. Ensemble analyses improve signatures of tumour
hypoxia and reveal inter-platform differences. BMC Bioinformatics. 2014 Jun 6;15:170. doi: 10.1186/14712105-15-170.
 Parmar C, Rios Velazquez E, Leijenaar R, Jermoumi M, Carvalho S, Mak RH, Mitra S, Shankar BU, Kikinis R,
Haibe-Kains B, Lambin P, Aerts HJ. Robust Radiomics feature quantification using semiautomatic volumetric
segmentation. PLoS One. 2014 Jul 15;9(7):e102107. doi: 10.1371/journal.pone.0102107. eCollection 2014.
 Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Cavalho S, Bussink J, Monshouwer R, HaibeKains B, Rietveld D, Hoebers F, Rietbergen MM, Leemans CR, Dekker A, Quackenbush J, Gillies RJ, Lambin P.
Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat
Commun. 2014 Jun 3;5:4006. doi: 10.1038/ncomms5006.
 Buijsen J, van Stiphout RG, Menheere PP, Lammering G, Lambin P. Blood biomarkers are helpful in the
prediction of response to chemoradiation in rectal cancer: a prospective, hypothesis driven study on
patients with locally advanced rectal cancer. Radiother Oncol. 2014;111;237-242.
3/UEDIN:
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speaker
Simon Langdon: Novel CAIX inhibitors in preclinical breast cancer models (S4, FC9-403, FC9-398, FC9-396).
Objective: To reach a conclusion regarding the further strategy for commercialization of our patented CAIXinhibitor compounds. Target: Participants of the CAIXi-sub-group of METOXIA.
 18th-21st June 2013. Pathology Society Meeting, Edinburgh, UK. Speakers Carol Ward: An Ex-Vivo Tumour Model
Using Core Biopsy Explants Validate Carbonic Anhydrase IX (CAIX) as a Therapeutic Target in Breast Cancer.
James Meehan: A Comparison of the Effects of Novel Carbonic Anhydrase Inhibitors on the Growth and
Invasion of Breast and Ovarian Cancer Cells. Objective: To focus attention to the newly developed biological
models. Target: pathology experts
 September 2013. Edinburgh Radiation Research Meeting, Edinburgh, UK. Speakers: Simon Langdon and carol
Ward: Targeting the Hypoxic Microenvironment with CAIX inhibitors. Objective: To focus attention to the
hypoxic micro-environment. Target: Radiotherapy and radiobiology experts.
 October 2013. Scottish Radiotherapy Research Forum Meeting in Stirling University, UK. Speaker: Simon
Langdon: Targeting the Hypoxic Microenvironment. Objective: To focus attention to the hypoxic microenvironment. Target: Radiotherapy experts.
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
 4th October 2013. Perth Radiation Oncology, Perth, Australia. Speaker: Ian Kunkler: Biologically adapted
radiotherapy for breast cancer. Objective: To focus attention to the hypoxic micro-environment. Target:
Radiotherapy experts.
 10th October 2013. Royal Park Hotel, Sydney, Australia Speaker: Ian Kunkler: Biologically adapted radiotherapy
for breast cancer. Objective: To focus attention to the hypoxic micro-environment. Target: Radiotherapy
experts.
 14th October 2013. Radiation Oncology, Mater Centre, Brisbane, Australia Speaker: Ian Kunkler: Biologically
adapted radiotherapy for breast cancer. Objective: To focus attention to the hypoxic micro-environment.
Target: Radiotherapy experts.
 17th -20th October 2013. 64th RANZCR Annual Scientific Meeting Auckland, New Zealand Speaker: Ian Kunkler: .
Diagnostic and therapeutic radiology in treatment planning: marriage, divorce and second marriage. Objective:
To focus attention to the hypoxic micro-environment. Target: Radiotherapy experts.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Carol Ward:
CA9 inhibitors and radiation: A pre-clinical study using a breast tumour explant model. Objective: To discuss
last year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
 20th -22nd February 2014. Kyoto Breast Cancer Consensus Conference, Kyoto, Japan. Speaker Ian Kunkler:
Towards the personalisation of radiotherapy for breast cancer. Objective: To focus attention to the need for
personalized treatment. Target: Oncologists.
Scientific articles with acknowledgement for METOXIA-support:
 Ward C, Langdon SP, Mullen P, Harris AL, Harrison DJ, Supuran CT, Kunkler IH. New strategies for targeting
the hypoxic tumour microenvironment in breast cancer. Cancer Treat Rev 2013. 39: 171 – 179
 Ward, C., Meehan, J., Harrison, D. J., Kunkler, I. H. & Langdon, S. P. An Ex-Vivo Tumour Model Using Core
Biopsy Explants Validate Carbonic Anhydrase IX (CAIX) as a Therapeutic Target in Breast Cancer. J. pathol
2013; 231:24
 Meehan, J., Ward, C., Supuran, C., Langdon, S. P. & Kunkler, I. The Effects of Novel Carbonic Anhydrase
Inhibitors on the Proliferation and Invasion of Breast and Ovarian Cancer Cells. J. Pahol. 2013; 231;36
 Ward C, James Meehan, Peter Mullen, Claudiu Supuran, J Michael Dixon, Jeremy S Thomas, Jean-Yves
Winum Philippe Lambin, Ludwig Dubois, Nanda-Kumar Pavathaneni, Edward J Jarman, Lorna Renshaw,
InHwa Um, Charlene Kay, Ian H Kunkler, David J Harrison, Simon P Langdon. Evaluation of Carbonic
Anhydrase IX as a Therapeutic Target for Inhibition of Breast Cancer Invasion and Metastasis Using a Series
of in vitro Breast Cancer Models. Clin Cancer Res (submitted).
4/RUNMC:
 19th-23rd April 2013. European Society for Therapeutic Radiology and Oncology Annual Meeting (ESTRO-Forum),
Geneva, Switzerland. Speaker Hans Kaanders.
 10th-13th June 2013. Biological Image Guided Adaptive Radiotherapy Scientific Meeting, Aarhus, Denmark.
Speaker Hans Kaanders.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Johannes HAM
Kaanders: Early radiotherapy-induced changes in head and neck cancers. (Hans Kaanders got ill and could not
present his paper, but submitted conclusions to be included in the meeting report). Objective: To discuss last
year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
 4th-8th April 2014. 33rd European Society for Therapeutic Radiology and Oncology (ESTRO) Annual Meeting,
Vienna Austria. Speaker Jan Bussink: Is hypoxia an immunological niche? Bussink Objective: To give an overview over the hypoxia-regulatory field. Target: International research scientists within radiation oncology.
Scientific articles with acknowledgement for METOXIA-support:
 Rademakers SE, Hoogsteen IJ, Rijken PF, Terhaard CH, Doornaert PA, Langendijk JA, van den Ende P, van der
Kogel AJ, Bussink J, Kaanders JH. Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma:
Results of the Accelerated Radiotherapy with Carbogen Breathing and Nicotinamide phase III randomized
trial. Head Neck. 2013 Dec 17. doi: 10.1002/hed.23569. [Epub ahead of print]
 Rademakers SE, Hoogsteen IJ, Rijken PF, Oosterwijk E, Terhaard CH, Doornaert PA, Langendijk JA, van den
Ende P, Takes R, De Bree R, van der Kogel AJ, Bussink J, Kaanders JH. Pattern of CAIX expression is
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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
prognostic for outcome and predicts response to ARCON in patients with laryngeal cancer treated in a
phase III randomized trial. Radiother Oncol. 2013;108;517-522.
 Hypoxia, metabolism, and growth factor signaling in head and neck squamous cell carcinoma: Correlation
between primary and xenograft tumors. Stegeman H, Rademakers SE, Span PN, Takes RP, van der Kogel AJ,
Kaanders JH, Bussink J. Head Neck. 2014;36;1288-1295.
 Meijer TW, Bussink J, Zatovicova M, Span PN, Lok J, Supuran CT, Kaanders JH. Tumor microenvironmental
changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.
Submitted.
5/UOXF.BP:
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Dean Singleton:
Hypoxic regulation of RIOK3 promotes cell invasion through remodelling of the actin cytoskeleton. Objective:
To discuss last year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
International scientific meetings with Adrian Harris as speaker:
METOXIA Foreground and Dissemination Activities
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METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
Invited Lectures 2013 -2014
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
2013
15.01.13
‘Role of hypoxia metabolism resistance to bevacizumab’
Think Tank 23, Dominican Republic
13.03.13
‘Additional key angiogenesis processes: Dll4/Notch signalling pathway and beyond’
Neoangiogenesis in cancer Advisory Board, Zurich
26.03.13
‘The role of hypoxia microRNAs in cancer biology’
British Society for Matrix Biology, Oxford
17.04.13
‘New pathways to target Notch signalling in tumour angiogenesis’
Oxford Cancer Research Centre Symposium, Oxford
15.05.13
‘Tumour angiogenesis inhibition, can we do it rationally?’
Lowy Cancer Sumposium, Sydney, Australia
27.06.13
‘Targeting notch signalling by blocking antibodies to Jagged I and Dll4’
The 3rd International Conference 'Notch Targeting in Cancer’, Mykonos
07.10.13
‘Window of opportunity: new approach for studying drug-tumor interaction’
Cremona, Italy
05.11.13
‘Translational metabolic treatments for breast cancer’
National Cancer Research Institute, Liverpool
08.11.13
‘Induced essentiality of hypoxic metabolism provides new ways to enhance
antiangiogenic therapy’
Cancer Research UK Cambridge Institute Symposium 2013, Cambridge
12.12.13
‘Hypoxic metabolism in breast cancer - how to overcome resistance to anti-angiogenic
therapy’
San Antonio Breast Cancer Symposium, San Antonio
2014
14.01.14
‘The hypoxia transcriptome of breast cancer’
Think Tank 24, Bonaire
30.01.14
‘Role of glycogen metabolism in adaptation to hypoxia’
Metabolism 2014, Luxembourg
21.02.14
‘Tumour Angiogenesis & hypoxia’
ESPCA Oncogenesis and Translational Medicine, Ribeiro Preto, Brazil
26.02.14
‘Hypoxia signalling, mitochondria and cancer’
Mitochondria Energy Metabolism & Cancer, Institute for Child Health, London
19.03.14
‘Metabolic Response to Anti-Angiogenic Therapy’
Keystone Symposia on Metabolism and Angiogenesis, Canada
‘Synthetic Lethality Recruited for Therapeutic Effect’
AACR Annual Meeting, San Diego
‘Mechanisms of resistance to anti-angiogenic therapy and induced essentiality as a
therapy target’
European Institute of Oncology, Milan
‘New angiogenic pathways’
Cancer Centre Amsterdam, Netherlands
‘DLL4-NOTCH and FOXO1 regulate endothelial Fatty Acid Binding Protein 4
downstream of VEGFA’
Annual Oncology Student Symposium, Oxford
08.04.14
07.05.14
13.06.14
26.06.14
Scientific articles with acknowledgement for METOXIA-support:
 Eustace, A., Mani, N., Span, P.N., Irlam, J.J., Taylor, J., Betts, G.N., Denley, H., Miller, C.J., Homer, J.J., Rojas,
A.M., Hoskin, P.J., Buffa, F.M., Harris, A.L., Kaanders, J.H., and West, C.M. A 26-Gene Hypoxia Signature
Predicts Benefit from Hypoxia-Modifying Therapy in Laryngeal Cancer but Not Bladder Cancer. Clin Cancer
Res 2013;19;4879-4888.
 Gieling, R.G., Parker, C.A., De Costa, L.A., Robertson, N., Harris, A.L., Stratford, I.J., and Williams, K.J.
Inhibition of carbonic anhydrase activity modifies the toxicity of doxorubicin and melphalan in tumour cells
in vitro. J Enzyme Inhib Med Chem 2013;28;360-369.
 Kumar, K., Wigfield, S., Gee, H.E., Devlin, C.M., Singleton, D., Li, J.L., Buffa, F., Huffman, M., Sinn, A.L., Silver,
J., Turley, H., Leek, R., Harris, A.L., and Ivan, M. Dichloroacetate reverses the hypoxic adaptation to
bevacizumab and enhances its antitumor effects in mouse xenografts. J Mol Med (Berl) 2013;91;749-758.
 Singleton, D.C., and Harris, A.L. Microenvironmental induced essentiality of autophagy. Clin Cancer Res
2013;19;2791-2793.
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 Ward, C., Langdon, S.P., Mullen, P., Harris, A.L., Harrison, D.J., Supuran, C.T., and Kunkler, I.H. (2013). New
strategies for targeting the hypoxic tumour microenvironment in breast cancer. Cancer Treat Rev 39, 171179.
 Gómez-Maldonado L, Tiana M1, Roche O, Prado-Cabrero A, Jensen L, Fernandez-Barral A, Guijarro-Muñoz I,
Favaro E, Moreno-Bueno G, Sanz L4, Aragones J, Harris A, Volpert O, Jimenez B, Del Peso L. EFNA3 long
noncoding RNAs induced by hypoxia promote metastatic dissemination. Oncogene. 2014 Jul 14;0. doi:
10.1038/onc.2014.200. [Epub ahead of print]
 Singleton, DC, Rouhi, P, Haider, S, Li, JL, Kessler, B, Cao, Y, Harris, AL. Hypoxic regulation of RIOK3 is a major
mechanism for cancer cell invasion and metastasis. (submitted).
6/AUH,AS:
 6th-10th April 2013: AACR annual meeting, Walter E. Washington Convention Center, Washington DC, USA.
Speakers Morten Busk: AMPK as a target to overcome hypoxia-induced treatment resistance in tumors.
Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts.
 May 2013. 13th International Workshop on the Tumor Microenvironment : Hypoxia, angiogenesis and
vasculature, Miami, USA. Speaker: Morten Busk: AMPK as a target to overcome hypoxia-induced treatment
resistance in tumors. Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Morten Busk:
Preclinical and clinical studies on hypoxia-related molecular targets. Objective: To discuss last year progress of
METOXIA and the finalization of the project. Target: All partners of METOXIA.
 10th-14th February 2014. ICTR-PHE 2014, Uniting physics, biology and medicine for better healthcare, Geneva,
Switzerland. Speaker: Morten Busk: Do physiological relevant doses of biguanides have any role in cancer
treatment? Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts.
 4th-8th April 2014. ESTRO 33 Annual Meeting, Vienna Austria. Speaker: a) Morten Busk: “Targeting metabolism
and hypoxia to improve radiotherapy.” b) Jens Overgaard: “Robert Kienböck and Gottwald Schwarz - Pioneers
of radiobiology and clinical radiotherapy.” Objective: To focus attention to the hypoxic micro-environment.
Target: Cancer experts.
Scientific articles with acknowledgement for METOXIA-support:
 Busk M, Mortensen LS, Nordsmark M, Overgaard J, Jakobsen S, Hansen KV, Theil J, Kallehauge JF, D'Andrea
FP, Steiniche T, Horsman MR. PET hypoxia imaging with FAZA: reproducibility at baseline and during
fractionated radiotherapy in tumour-bearing mice. Eur J Nucl Med Mol Imaging. 2013;40;186-197.
 Busk M, Jakobsen S, Horsman MR, Mortensen LS, Iversen AB, Overgaard J, Nordsmark M, Ji X, Lee DY,
Raleigh JR. PET imaging of tumor hypoxia using 18F-labeled pimonidazole. Acta Oncol. 2013;52;1300-1307.
 Busk M, Horsman MR. Horsman MR, Relevance of hypoxia in radiation oncology: pathophysiology, tumor
biology and implications for treatment. Q J Nucl Med Mol Imaging. 2013;57;219-234.
 Sørensen BS1, Busk M, Olthof N, Speel EJ, Horsman MR, Alsner J, Overgaard J. Radiosensitivity and effect of
hypoxia in HPV positive head and neck cancer cells. Radiother Oncol. 2013;108;500-505.
 Nielsen T, Nielsen NC, Holm TH, Ostergaard L, Horsman MR, Busk M. Ultra-high field 1H magnetic resonance
imaging approaches for acute hypoxia. Acta Oncol. 2013;52;1287-1292.
 Winther M, Alsner J, Tramm T, Nordsmark M. Hypoxia-regulated gene expression and prognosis in locoregional gastroesophageal cancer. Acta Oncol 2013;52;1327-35.
7/FMC:
Scientific articles with acknowledgement for METOXIA-support:
 Larsen BE, Karlsen J, Pettersen EO, Sandvik JA, Melvik JE. Oxygen consumption in T-47D cells immobilized in
alginate. Cell Prolif. 2013;46:469-481.
 Andersen T, Markussen C, Dornish M, Heier-Baardson H, Melvik JE, Alsberg E, Christensen BE. In situ gelation for
cell immobilization and culture in alginate foam scaffolds. Tissue Eng Part A. 2014 Feb;20(3-4):600-10. doi:
10.1089/ten.TEA.2013.0223. Epub 2013 Nov 28.
8/UNIMAN:
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741

12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany.
Speaker Kaye Williams: Tumour models for preclinical effect-studies and eventual imaging. (Kaye was ill, but
sent the material so that Erik could present it). Objective: To reach a conclusion regarding the further
strategy for commercialization of our patented CAIX-inhibitor compounds. Target: Participants of the CAIXisub-group of METOXIA.
 20th September 2013 METOXIA sub-group meeting on the theme: “How to best commercialize the METOXIA
CAIX patent portfolio”. Speaker Kaye Williams: participated in discussion. Objective: To reach a conclusion
regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds. Target:
Participants of the CAIXi-sub-group of METOXIA.
 4th-5th November 2013. The 5th General Assembly Meeting of METOXIA in Nice, France. Speakers: Kaye Williams
and Roben Gieling: Updating on targeting CAIX and hypoxia signalling Objective: To discuss last year progress
of METOXIA and the finalization of the project. Target: All partners of METOXIA.
 4th-9th April 2014: AACR annual meeting, San Diego Convention Center San Diego, California, USA. Speakers
Jennifer L. Bryant, Suzanne L. Meredith, Roben G. Gieling, Brian A. Telfer, Muhammad Babur, Claudiu T.
Supuran, Kaye J. Williams, Anne White: Inhibiting carbonic anhydrase IX targets hypoxic small cell lung cancer
cells. Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts.
 5th-8th July 2014. 23rd Biennial Congress of the European Association for Cancer Research. Munich, Germany.
Speakers: Roben G Gieling, Muhammad Babur, Brian A Telfer, Kaye J Williams: CA IX inhibitor 4-(3'-(3″,5″dimethylphenyl)ureido)phenyl sulfamate (S4) as an adjuvant to doxorubicin chemotherapy reduces metastatic
dissemination. Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts
Scientific articles with acknowledgement for METOXIA-support:
 Cawthorne C1, Burrows N, Gieling RG, Morrow CJ, Forster D, Gregory J, Radigois M, Smigova A, Babur M,
Simpson K, Hodgkinson C, Brown G, McMahon A, Dive C, Hiscock D, Wilson I, Williams KJ. [18F]-FLT positron
emission tomography can be used to image the response of sensitive tumors to PI3-kinase inhibition with
the novel agent GDC-0941. Mol Cancer Ther. 2013;12;819-828.
 Gieling RG, Parker CA, De Costa LA, Robertson N, Harris AL, Stratford IJ, Williams KJ. Inhibition of carbonic
anhydrase activity modifies the toxicity of doxorubicin and melphalan in tumour cells in vitro. J Enzyme
Inhib Med Chem. 28; (2013) 360-369.
 Gieling RG, Williams KJ. Carbonic anhydrase IX as a target for metastatic disease. Bioorg Med Chem.
2013;21;1470-1476.
 Gieling RG, Babur M, Mamnani L, Burrows N, Telfer BA, Carta F, Winum JY, Scozzafava A, Supuran CT,
Williams KJ. Antimetastatic effect of sulfamate carbonic anhydrase IX inhibitors in breast carcinoma
xenografts. J Med Chem. 21; (2013) 1470-1476.
 Hammond EM, Asselin MC, Forster D, O'Connor JP, Senra JM, Williams KJ. The meaning, measurement and
modification of hypoxia in the laboratory and the clinic. Clin Oncol (R Coll Radiol). 2014;26;277-288.
 Burrows N, Telfer B, Brabant G, Williams KJ. Inhibiting the phosphatidylinositide 3-kinase pathway blocks
radiation-induced metastasis associated with Rho-GTPase and Hypoxia-inducible factor-1 activity. Radiother
Oncol. 2013;108;548-553.
9/UNIFI:
 7th March 2013. Conference on “Carbonic Anhydrases as drug targets” in Bucharest, Romania. Speaker Claudiu
Supuran: Design and biological testing in osteosarcoma models of CA-9 inhibitors syntheiszed in Florence.
Objective: To focus attention to the hypoxic micro-environment. Target: Cancer experts.
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speakers
Andrea Scozzafava, Claudiu Supuran: Discussion Objective: To reach a conclusion regarding the further
strategy for commercialization of our patented CAIX-inhibitor compounds. Target: Participants of the CAIXisub-group of METOXIA.
 18th – 20th April 2013. International meeting on carbonic anhydrases titelsed: "Frontiers In CA research :
Dissemination activity of the EU project METOXIA” In Montecattini Terme, Italy. Speaker Fabrisio Carta:
Nanoparticles with CA inhibitory activity. Objective: To announce the possibility for new networks for
METOXIA Foreground and Dissemination Activities
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
continuation of the research performed during METOXIA. Target: International experts on Carbonic
Anhydrases..
 18th – 20th April 2013. International meeting on carbonic anhydrases titelsed: "Frontiers In CA research :
Dissemination activity of the EU project METOXIA” In Montecattini Terme, Italy. Speaker Claudiu Supuran:
Exploiting the hydrophobic and hydrophilic sites of carbonic anhydrase for the drug design of novel classes of
inhibitors. Objective: To announce the possibility for new networks for continuation of the research
performed during METOXIA. Target: International experts on Carbonic Anhydrases..
 29th june-4th July 2013. European School of Medicinal Chemistry (XXXIV Advanced Course of Medicinal Chemistry
and “E. Duranti” National Seminar for PhD Students), Urbino, Italy. Participant Dr. Bozdag: Coumarin and
arylureido-substituted aromatic/heterocyclic sulfonamides as CAis. Objective: To focus attention to the
hypoxic micro-environment. Target: Cancer experts.
 1st-3rd September 2013. 2nd International Conference and Exibition “Drug Design 2013” in Oxford, UK. Speaker:
Andrea Scozzafava: Carbonic Anhydrase Inhibitors with dual activities. Objective: To focus attention to the
hypoxic micro-environment. Target: Cancer experts.
 10th-13th September 2013. XXII National Meeting on Medicinal Chemistry in Roma, Italy. Speaker: Claudiu
Supuran: Carbonic anhydrase inhibitors as anticancer and antimetastatic agents. Objective: To focus attention
to the hypoxic micro-environment. Target: Cancer experts.
 20th September 2013 METOXIA sub-group meeting on the theme: “How to best commercialize the METOXIA
CAIX patent portfolio”. Speakers Andrea Scozzafava and Claudiu Supuran: Discussion. Objective: To reach a
conclusion regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds.
Target: Participants of the CAIXi-sub-group of METOXIA.
 23rd-25th October 2013. 2nd CA satellite meeting in Naples, Italy. Speakers: a) Claudiu Supuran: What’s new in
the carbonic anhydrase field-An update of research from 2012 to 2013. b) Dr. Ceruso: Sulfonamides
incorporating fluorine 1,3,5-triazine moieties as inhibitors of human carbonic anhydrase isoforms I-XIV. c) Dr.
Vullo: Coumarin and arylureido-substituted aromatic/heterocyclic sulfonamides as CAIs. Objective: To focus
attention to the hypoxic micro-environment. Target: Cancer experts.
 4th-5th November 2013. The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Claudiu
Supuran and Andrea Scozzafava: CA9 and -12 as new cancer therapy targets: An over-view of the novel
classes of inhibitors discovered and international competition towards this goal. Objective: To discuss last
year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 D. Ekinci, L. Karagoz, D. Ekinci, M, Senturk, C.T. Supuran, Carbonic anhydrase inhibitors: in vitro inhibition of α
isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids J. Enzyme Inhib. Med. Chem. 2013, 28, 283-288.
 C. Alp, A. Maresca, N.A. Alp, M.S. Gültekin, D. Ekinci, A. Scozzafava, C.T. Supuran, Secondary/tertiary
benzenesulfonamides with inhibitory action against the cytosolic human carbonic anhydrase isoforms I and II. J.
Enzyme Inhib. Med. Chem. 2013, 28, 294-298
 A. Maresca, A. Scozzafava, D. Vullo, C.T. Supuran, Dihalogenated sulfanilamides and benzolamides are effective
-class carbonic anhydrases from Mycobacterium tuberculosis.J. Enzyme Inhib. Med.
Chem. 2013, 28, 384-387.
 A. Maresca, D. Vullo, A. Scozzafava, C.T. Supuran, Inhibition of the alpha- and beta- carbonic anhydrases from
the gastric pathogen Helycobacter pylori with anions J. Enzyme Inhib. Med. Chem. 2013, 28, 388-391.

-class carbonic anhydrases from
Mycobacterium tuberculosis with carboxylic acids.J. Enzyme Inhib. Med. Chem. 2013, 28, 392-396.
 A. Bonneau, A. Maresca, J.-Y. Winum, C.T. Supuran, Metronidazole-coumarin conjugates and 3-cyano-7hydroxy-coumarin act as isoform-selective carbonic anhydrase inhibitors J. Enzyme Inhib. Med. Chem. 2013, 28,
397-401.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741


















-class carbonic anhydrases
from Mycobacterium tuberculosis J. Enzyme Inhib. Med. Chem. 2013, 28, 407-411.
O. Koz, D. Ekinci, A. Perrone, S. Piacente, O. Alankus-Caliskan, E. Bedir, C.T. Supuran, Analysis of saponins and
phenolic compounds as inhibitors of α-carbonic anhydrase isoenzymes J. Enzyme Inhib. Med. Chem. 2013, 28,
412-417.
S. Del Prete, V. De Luca, A. Scozzafava, V. Carginale, C.T. Supuran, C. Capasso, Biochemical properties of a new
α-carbonic anhydrase from the human pathogenic bacterium Vibrio cholerae J. Enzyme Inhib. Med. Chem.
2014, 29, 23-27.
A. Sharma, M. Tiwari, C.T. Supuran, Novel coumarins and benzocoumarins acting as isoform-selective inhibitors
against the tumor-associated carbonic anhydrase IX J. Enzyme Inhib. Med. Chem. 2014, 29, 292-296
C. Capasso, C.T. Supuran, Sulfa and trimethoprim-like drugs - antimetabolites acting as carbonic anhydrase,
dihydropteroate synthase and dihydrofolate reductase inhibitors J. Enzyme Inhib. Med. Chem. 2014, 29, 379387.
S. Durdagi, G. Scozzafava, D. Vullo, H. Sahin, S. Kolayli, C.T. Supuran, Inhibition of mammalian carbonic anhydrases IXIV with grayanotoxin III: Solution and in silico studies J. Enzyme Inhib. Med. Chem. 2014, 29, 469-475.
S. Bilginer, E. Unluer, H.I. Gul, E. Mete, S. Isik, D. Vullo, S. Beyaztas, O. Ozensoy-Guler, C Capasso, C.T. Supuran,
Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties
strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase J. Enzyme Inhib. Med. Chem. 2014, 29, 495-499.
R.L. Arechederra, A. Waheed, W.S. Sly, C.T. Supuran, S.D. Minteer, Effect of Sulfonamides as Selective Carbonic
Anhydrase Va and Vb Inhibitors on Mitochondrial Metabolic Energy Conversion Bioorg. Med. Chem. 2013, 21,
1544-1548.
G. Compain, A. Martin-Mingot, A. Maresca, S. Thibaudeau, C.T. Supuran, Superacid synthesis of halogen containing
N-substituted-4-aminobenzene sulfonamides : new selective tumor-associated carbonic anhydrase inhibitors
Bioorg. Med. Chem. 2013, 21, 1555-1563.
F. Carta, D. Vullo, A. Maresca, A. Scozzafava, C.T. Supuran, Mono-/dihydroxybenzoic acid esters and phenol
pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV Bioorg.
Med. Chem. 2013, 21, 1564-1569.
F. Cottier, W. Leewattanapasuk, L.R. Kemp, M. Murphy, C.T. Supuran, O. Kurzai, F.A. Mühlschlegel, Carbonic
anhydrase regulation and CO2 sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog
Bioorg. Med. Chem. 2013, 21, 1549-1554
D. Vullo, V. De Luca, A. Scozzafava, V. Carginale, M. Rossi, C.T. Supuran, C. Capasso, The alpha-carbonic anhydrase
from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition
by sulfonamides. Bioorg. Med. Chem. 2013, 1534-1538.
R.A. Davis, D. Vullo, A Maresca, C.T. Supuran, S.A. Poulsen, Natural product coumarins that inhibit human carbonic
anhydrases. Bioorg. Med. Chem. 2013, 21, 1539-1543.
R. Demirdağ, V. Çomaklı, M. Şentürk, D. Ekinci, Ö.I. Küfrevioğlu, C.T. Supuran, Purification and characterization of
carbonic anhydrase from sheep kidney and effects of sulfonamides on enzyme activity Bioorg. Med. Chem. 2013,
21, 1522-1525.
L. Syrjanen, M.E.E. Tolvanen, M. Hilvo, D. Vullo, F. Carta, C.T. Supuran, S. Parkkila, Characterization, bioinformatic
analysis and dithiocarbamate inhibition studies of two new α-carbonic anhydrases, CAH1 and CAH2, from the fruit
fly Drosophila melanogaster Bioorg. Med. Chem. 2013, 21, 1516-1521.
T. Tuccinardi, S. Bertini, C. Granchi, G. Ortore, M. Macchia, F. Minutolo, A. Martinelli, C.T. Supuran, Salicylaldoxime
derivatives as new leads for the development of carbonic anhydrase inhibitors Bioorg. Med. Chem. 2013, 21, 15111515.
L.E. Riafrecha, O.M. Rodriguez, D. Vullo, C.T. Supuran, P.A. Colinas, Synthesis of C-cinnamoyl glycosides and their
inhibitory activity against mammalian carbonic anhydrasesBioorg. Med. Chem. 2013, 21, 1489-1494.
S. Singh, C.T. Supuran, Chemometric QSAR modeling and in silico design of carbonic anhydrase inhibition of a coral
secretory isoform by sulfonamideBioorg. Med. Chem. 2013, 21, 1495-1502.
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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
 V. De Luca, D. Vullo, A. Scozzafava, V. Carginale, M. Rossi, C.T. Supuran, C. Capasso, An α-carbonic anhydrase from
the thermophilic bacterium Sulphurihydrogenibium azorense is the fastest enzyme known for the CO2 hydration
reaction Bioorg. Med. Chem. 2013, 1465-1469.
 A. Alafeefy, S. Isik, H.A. Abdel-Aziz, A.E. Ashour, D. Vullo, N.A. Al-Jaber, C.T. Supuran, Carbonic anhydrase inhibitors.
Benzenesulfonamides incorporating cyanoacrylamide moieties are low nanomolar/subnanomolar inhibitors of the
tumor-associated isoforms IX and XII Bioorg. Med. Chem. 2013, 21, 1396-1403
 C. Ward, S.P. Langdon, P. Mullen, A.L. Harris, D.J. Harrison, C.T. Supuran, I. Kunkler, New strategies for targeting the
hypoxic tumour microenvironment in breast cancer Cancer Treatm. Rev. 2013, 39, 171-179.
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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
 N. Lounnas, C. Rosilio, M. Nebout, D. Mary, E. Griessinger, Z. Neffati, H. Spits, T. Hagenbeek, V. Asnafi, S.A. Poulsen,
C.T. Supuran, J.F. Peyron, V. Imbert, Pharmacological inhibition of carbonic anhydrase XII interferes with cell
proliferation and induces cell apoptosis in T-cell lymphomas. Cancer Lett. 2013, 333, 76-88.
 I. Nishimori, D. Vullo, T. Minakuchi, A. Scozzzafava, C. Capasso, C.T. Supuran, Restoring catalytic activity to the
human carbonic anhydrase (CA) related proteins VIII, X and XI affords isoforms with high catalytic efficiency and
susceptibility to anion inhibition Bioorg. Med. Chem. Lett. 2013, 23, 256-260.
 K. Tars, D. Vullo, A. Kazaks, J. Leitans, A. Lends, A. Grandane, R. Zalubovskis, A. Scozzafava, C.T. Supuran,
Sulfocoumarins (1,2-benzoxathiine 2,2-dioxides): a class of potent and isoform-selective inhibitors of tumorassociated carbonic anhydrases J. Med. Chem. 2013, 56, 293-300.
 D. Vullo, S. Isik, S. Del Prete, V. De Luca, V. Carginale, A. Scozzafava, C.T. Supuran, C. Capasso, Anion inhibition
-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae Bioorg. Med. Chem. Lett. 2013,
23, 1636-1638.
 T. Rogez-Florent, S. Meignan, C. Foulon, P Six, A. Gros, C. Bal-Mahieu, C.T. Supuran, A. Scozzafava, R, Frédérick, B.
Masereel, P. Depreux, A. Lansiaux, J.F. Goossens, S. Gluszok, L.Goossens, New selective carbonic anhydrase IX
inhibitors: Synthesis and pharmacological evaluation of diarylpyrazole-benzenesulfonamides.Bioorg. Med. Chem.
2013, 21, 1451-1464
 J.Y. Winum, P.A. Colinas, C.T. Supuran, Glycosidic carbonic anhydrase IX inhibitors: A sweet approach against
cancer.Bioorg. Med. Chem. 2013, 21, 1419-1426
 Ö. Güzel-Akdemir, A. Akdemir, S. Isik, D. Vullo, C.T. Supuran, o-Benzenedisulfonimido-sulfonamides are potent
inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII Bioorg. Med. Chem. 2013, 21,
1386-1391.
 A. Akdemir, D. Vullo, V. De Luca, A. Scozzafava, V. Carginale, M. Rossi, C.T. Supuran, C. Capasso, The extremo-αcarbonic anhydrase (CA) from Sulfurihydrogenibium azorense, the fastest CA known, is highly activated by amino
acids and amines Bioorg. Med. Chem. Lett. 2013, 23, 1087-1090.
 L. Gavernet, J.L. Gonzalez Funes, P.H. Palestro, L.E. Bruno Blanch,G.L. Estiu, A. Maresca, I. Barrios, C.T. Supuran,
Inhibition pattern of sulfamide-related compounds in binding to carbonic anhydrase isoforms I, II, VII, XII and XIV.
Bioorg. Med. Chem. 2013, 21, 1410-1418.
 S. Biswas, F. Carta, A. Scozzafava, R. McKenna, C.T. Supuran, Structural effect of phenyl ring compared to
thiadiazole based adamantly-sulfonamides on carbonic anhydrase inhibition Bioorg. Med. Chem. 2013, 21, 23142318.
 P. Pan, A.B. Vermelho, G. Capaci Rodrigues, A. Scozzafava, M.E. Tolvanen, S. Parkkila, C. Capasso, C.T. Supuran,
-carbonic anhydrase from Trypanosoma
cruzi, the causative agent of Chagas disease. J. Med. Chem. 2013, 56, 1761-1771.
 Ö. Güzel-Akdemir, A. Akdemir, P. Pan, A.B. Vermelho, S. Parkkila, A. Scozzafava, C. Capasso, C.T. Supuran, A class of
-carbonic anhydrase from Trypanosoma cruzi. J. Med.
Chem. 2013, 56, 5773–5781.
 H. Carreyre, J.M. Coustard, G. Carre, C. Vandebrouck, J. Bescond, M. Ouedraogo, J Marrot, D Vullo, C.T. Supuran, S.
Thibaudeau, Natural product hybrid and its superacid synthesized analogues: Dodonein and its derivatives show
selective inhibition of carbonic anhydrase isoforms I, III, XIII and XIV. Bioorg. Med. Chem. 2013, 21, 3790-3794.
 B. Métayer, A. Mingot, D. Vullo, C.T. Supuran, S. Thibaudeau, New superacid synthesized (fluorinated) tertiary
benzenesulfonamides acting as selective hCA IX inhibitors: toward a new mode of carbonic anhydrases inhibition by
sulfonamides. Chem. Commun. 2013, 49, 6015-6017.
 E. Masini, F. Carta, A. Scozzafava, C.T. Supuran, Antiglaucoma carbonic anhydrase inhibitors: A patent review.
Expert Opin. Ther. Pat. 2013, 23, 705-716.
 C. Capasso, C.T. Supuran, Antiinfective carbonic anhydrase inhibitors: A patent and literature review. Expert Opin.
Ther. Pat. 2013, 23, 693-704.
 F. Carta, C.T. Supuran, Diuretics with carbonic anhydrase inhibitory action: A patent and literature review (20052013). Expert Opin. Ther. Pat. 2013, 23, 681-691.
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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
 A. Akdemir, Ö. Güzel-Akdemir, A. Scozzafava, C. Capasso, C.T. Supuran, Inhibition of tumor-associated human
carbonic anhydrase isozymes IX and XII by a new class of substituted-phenylacetamido aromatic sulfonamides
Bioorg. Med. Chem. 2013, 21, 5228-5232.
 D. Vullo, W. Leewattanapasuk, F.A. Mühlschlegel, A. Mastrolorenzo, C. Capasso, C.T. Supuran, Carbonic anhydrase
-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides,
sulfamates and sulfamides Bioorg. Med. Chem. Lett. 2013, 23, 2647-2652.
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
 A.M. Alafeefy, S. Isik, N.A. Al-Jaber, D. Vullo, H.A. Abdel-Aziz, A.E. Ashour, A.S. Awaad, C. Capasso, C.T. Supuran,
Carbonic anhydrase inhibitors. Benzenesulfonamides incorporating cyanoacrylamide moieties strongly inhibit
Saccharomyces cerevisiae β-carbonic anhydrase Bioorg. Med. Chem. Lett. 2013, 23, 3570-3575.
 G. De Simone, V. Alterio, C.T. Supuran, Exploiting the hydrophobic and hydrophilic binding sites for designing
carbonic anhydrase inhibitors. Expert Opin. Drug Discov. 2013, 8, 793-810.
 S.M. Monti, C.T. Supuran, G. De Simone, Anticancer carbonic anhydrase inhibitors: A patent review (2008-2013).
Expert Opin. Ther. Pat. 2013, 23, 737-749.
 K. Aksu, M. Nar, M. Tanc, D. Vullo, İ. Gülçin, S. Göksu, F. Tümer, C.T. Supuran, Synthesis and carbonic anhydrase
inhibitory properties of sulfamides structurally related to dopamine Bioorg. Med. Chem. 2013, 21, 2925-2931.
 F. Carta, A. Akdemir, A. Scozzafava, E. Masini, C.T. Supuran, Xanthates and trithiocarbonates strongly inhibit
carbonic anhydrases and show antiglaucoma effects in vivo J. Med. Chem. 2013, 56, 4691-4700.
 D. Vullo, V. De Luca, A. Scozzafava, V. Carginale, M. Rossi, C.T. Supuran, C. Capasso, The extremo-alpha-carbonic
anhydrase from the thermophilic bacterium Sulfurihydrogenibium azorense is highly inhibited by sulfonamides.
Bioorg. Med. Chem. 2013, 21, 4521-4525.
 H.M. Said, C. Hagemann, F. Carta, A. Katzer, B. Polat, A. Staab, A. Scozzafava, J. Anacker, G.H. Vince, M. Flentje, C.T.
Supuran. Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including
acetazolamide in human glioblastoma. Bioorg. Med. Chem. 2013, 21, 3949-3957.
 M. Tanc, F. Carta, M. Bozdag, A. Scozzafava, C.T. Supuran, 7-Substituted-sulfocoumarins are isoform-selective,
potent carbonic anhydrase II inhibitors. Bioorg. Med. Chem. 2013, 21, 4502- 4510.
 M.C. Saada, J. Ombouma, J.L. Montero, C.T. Supuran, J.Y. Winum, Thiol-ene click chemistry for the synthesis of
highly effective glycosyl sulfonamide carbonic anhydrase inhibitors. Chem. Commun. (Camb.) 2013, 49, 5699-5701.
 L. Dubois, S. Peeters, S.J.A. van Kuijk, A. Yaromina, N.G Lieuwes, R. Saraya, R. Biemans, M. Rami, N.K. Parvathaneni,
D. Vullo, M. Vooijs, C.T. Supuran, J.Y. Winum, P. Lambin, Targeting of carbonic anhydrase IX by nitroimidazole based
sulfamide dual drugs enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting
drugs.Radiother. Oncol. 2013, 108, 523-528.
 J. Leitans, A. Sprudza, M. Tanc, I. Vozny, R. Zalubovskis, K. Tars, C.T. Supuran, 1-Substituted-(1,2,3-triazol-4yl)thiophene-2-sulfonamides strongly inhibit human carbonic anhydrases I, II, IX and XII: solution and X-ray
crystallographic studies Bioorg. Med. Chem. 2013, 21, 5130-5138.
 K.K. Sethi, S.M. Verma, M. Tanç, F. Carta, C.T. Supuran, Carbonic Anhydrase Inhibitors: Synthesis and Inhibition of
the cytosolic mammalian carbonic anhydrase isoforms I, II and VII with benzene sulfonamides incorporating 4,5,6,7tetrachlorophthalimide moiety. Bioorg. Med. Chem. 2013, 21, 5168-5174.
 G. Capaci Rodrigues, D. Ferreira Feijó, M. Torres Bozza, P. Pan, D. Vullo, S. Parkkila, C.T. Supuran, C. Capasso, A.
Palermo Aguiar, A.B. Vermelho, Design, Synthesis and Evaluation of Hydroxamic Acid Derivatives as Promising
Agents for the Management of Chagas' disease. J. Med. Chem. 2014, 57, 298-308.
 V. Akurathi, L. Dubois, S. Celen, N.G. Lieuwes, S.K. Chitneni, B.J. Cleynhens, A. Innocenti, C.T. Supuran, A. M.
Verbruggen, P. Lambin, G.M. Bormans, Development and biological evaluation of 99mTc-sulfonamide derivatives
for in vivo visualization of CA IX as surrogate tumor hypoxia markers. Eur. J. Med. Chem. 2014, 71, 374-384.
 S. Del Prete, D. Vullo, V. De Luca, V. Carginale, A. Scoz
carbonic anhydrase from the pathogenic anaerobe Porphyromonas gingivalis and its inhibition profile with anions
and small molecules Bioorg. Med. Chem. Lett. 2013, 23, 4067-4071.
 L. Syrjänen, A.B. Vermelho, I. de Almeida Rodrigues, S. Corte-Real, T. Salonen, P. Pan, D. Vullo, S. Parkkila, C.
Capasso, C.T. Supuran, Cloning, characterization and inhibition studies of a beta carbonic anhydrase from
Leishmania donovani chagasi, the protozoan parasite responsible of leishmaniasis J. Med. Chem. 2013, 56, 73727381.
 M. Rami, L. Dubois, N.K. Parvathaneni, V. Alterio, S. van Kuijk, S.M. Monti, P. Lambin, G. De Simone, C.T. Supuran,
J.Y. Winum, Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazolesulfonamide/sulfamide/sulfamate. J. Med. Chem. 2013, 56, 8512-8520.
 Ö. Güzel-Akdemir, S. Biswas, K. Lastra, R. McKenna, C.T. Supuran, Structural study of the location of the phenyl tail
of benzene sulfonamides and the effect on human carbonic anhydrase inhibition Bioorg. Med. Chem. 2013, 21,
6674-6680.
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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
 J. Sławiński, K. Szafrański, A. Kędzia, D. Vullo, C.T. Supuran, Carbonic anhydrase inhibitors. Synthesis of heterocyclic
4-substituted pyridine-3-sulfonamide derivatives and their inhibition of the human cytosolic isozymes I and II and
transmembrane cancer-associated isozymes IX and XII. Eur. J. Med. Chem. 2013, 69, 701-710.
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
 B. Métayer, A. Martin-Mingot, D. Vullo, C.T. Supuran, S. Thibaudeau, Superacid synthesized tertiary
benzenesulfonamides and benzofused sultams act as selective hCA IX inhibitors: toward the understanding of the
new mode of inhibition by sulfonamides. Org. Biomol. Chem. 2013, 11, 7540-7549.
 S. Biswas, R. McKenna, C.T. Supuran, Effect of incorporating a thiophene tail in the scaffold of acetazolamide on the
inhibition of human carbonic anhydrase isoforms I, II, IX and XII. Bioorg. Med. Chem. Lett. 2013, 23, 5646-5649.
 M. Ceruso, D. Vullo, A. Scozzafava, C.T. Supuran, Inhibition of human carbonic anhydrase isoforms I-XIV with
sulfonamides incorporating fluorine and 1,3,5-triazine moieties Bioorg. Med. Chem. 2013, 21, 6929-6936.
 K.K. Sethi, D. Vullo, S.M. Verma, M. Tanç, F. Carta, C.T. Supuran, Carbonic Anhydrase Inhibitors: Synthesis and
inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating
4,5,6,7-tetrabromophthalimide moiety Bioorg. Med. Chem. 2013, 21, 5973-5982.
 M. Bozdag, M. Ferraroni, E. Nuti, D. Vullo, A. Rossello, F. Carta, A. Scozzafava, C.T. Supuran, Combining the tail and
the ring approaches for obtaining potent and isoform-selective carbonic anhydrase inhibitors: solution and X-ray
crystallographic studies Bioorg Med. Chem. 2014, 22, 334-340.
 C.J. Carroux, G.M. Rankin, J. Moeker, L.F. Bornaghi, K. Katneni, S.A. Charman, D. Vullo, C.T. Supuran, S.A. Poulsen, A
prodrug approach towards cancer-related carbonic anhydrase inhibition J. Med. Chem. 2013, 56, 9623-9634.
 B. Żołnowska, J. Sławiński, A. Pogorzelska J. Chojnacki, D. Vullo, C.T. Supuran, Carbonic anhydrase inhibitors.
Synthesis, and molecular structure of novel series N-substituted N'-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl) guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumorassociated isozymes IX and XII Eur. J. Med. Chem. 2014, 71, 135-147.
 J. Sławiński, A. Pogorzelska, B. Żołnowska, K. Brożewicz, D. Vullo, C.T. Supuran, Carbonic anhydrase inhibitors.
Synthesis of a novel series of 5-substituted 2,4-dichlorobenzenesulfonamides and their inhibition of human
cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XIIEur. J. Med. Chem. 2014,
82, 47-55.
 S. Carradori, C. De Monte, M. D’Ascenzio, D. Secci, G. Celik, M. Ceruso, D. Vullo, A. Scozzafava, C.T. Supuran, Salen
and tetrahydrosalen derivatives act as effective inhibitors of the tumor-associated carbonic anhydrase XII - A new
scaffold for designing isoform-selective inhibitors Bioorg Med. Chem. Lett. 2013, 23, 6759-6763.
 SitaRam, G. Celik, P. Khloya, D. Vullo, C.T. Supuran, P.K. Sharma, Benzenesulfonamide bearing 1,2,4-triazole
scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII Bioorg. Med.
Chem. 2014, 22, 1873-1882.
 P. Khloya, G. Celik, SitaRam, D. Vullo, C.T. Supuran, P.K. Sharma, 4-Functionalized 1,3-diarylpyrazoles bearing
benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX
and XII Eur. J. Med. Chem., 2014, 76, 284-290.
 A.K. Saluja, M. Tiwari, D. Vullo, C.T. Supuran, Substituted benzene sulfonamides incorporating 1,3,5-triazinyl
moieties potently inhibit cytosolic and transmembrane human carbonic anhydrases II, IX and XII Bioorg. Med.
Chem. Lett. 2014, 24, 1310-1314.
 A. Grandane, M. Tanc, R. Zalubovskis, C.T. Supuran, Synthesis of 6-tetrazolyl-substituted sulfocoumarins acting as
highly potent and selective inhibitors of the tumor-associated carbonic anhydrase isoforms IX and XII Bioorg. Med.
Chem. 2014, 22, 1522-1528.
 K.K. Sethi, S.M. Verma, M. Tanç, G. Purper, G. Calafato, F. Carta, C.T. Supuran, Carbonic Anhydrase Inhibitors:
Synthesis and inhibition of the human carbonic anhydrase isoforms I, II, IX and XII with benzene sulfonamides
incorporating 4- and 3-nitrophthalimide moieties Bioorg. Med. Chem. 2014, 22, 1586-1595.
 A. Grandane, M. Tanc, R. Zalubovskis, C.T. Supuran, 6-Triazolyl-substituted sulfocoumarins are potent, selective
inhibitors of the tumor-associated carbonic anhydrases IX and XII Bioorg. Med. Chem. Lett. 2014, 24, 1256-1260.
 M. D’Ascenzio, S. Carradori, C. De Monte, D. Secci, M. Ceruso, C.T. Supuran, Design, synthesis and evaluation of Nsubstituted saccharin derivatives as selective inhibitors of tumor-associated carbonic anhydrase XII Bioorg. Med.
Chem. 2014, 22, 1821-1831.
 C.T. Supuran, A. Scozzafava, E. Masini, F. Carta, E.O. Pettersen, P. Ebbesen, Carbonic anhydrase inhibitor comprising
a dithiocarbamate. WO 2013/050426.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
10/KI:
 7th May 2013. Minisymposium: Epigenetic Aspects and Approaches on Cancer Biology and Stress Response.
Oulu, Finland. Speaker Lorenz Poellinger: Epigenetic mechanisms regulating the hypoxic response and stem cell
maintenance. Objective: To give an over-view over the hypoxia-regulatory field. Target: International research
scientists within oncology and Cancer biology.
 8th-12th June 2013. Hypoxianet Oulu 2013, Dealing with hypoxia: Regulatory aspects in cells, tissues and
organisms Oulu, Finland. Speaker Lorenz Poellinger: Epigenetic mechanisms of gene regulation in hypoxia.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International research scientists
within oncology and Cancer biology.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Katarina Gradin:
The role of activated forms of Notch and HIF transcription factors to regulate EMT under hypoxic conditions.
Objective: To discuss last year progress of METOXIA and the finalization of the project. Target: All partners of
METOXIA.
 7th-12th January 2014. Keystone Symposia:” Sensing and Signaling of Hypoxia: Interfaces with Biology and
Medicine (A1)”, Breckenridge, CO, USA. Speaker: Lorenz Poellinger: Regulation of the Cell Differentation Status
by Hypoxia. Objective: To give an over-view over the hypoxia-regulatory field. Target: International research
scientists within radiation oncology
 10th-13th May 2014. 7th international conference SUMO, Ubiquitin, UBL proteins. Implications for human
disease, Shanghai, China. Speaker Lorenz Poellinger: Regulation of the hypoxic response by the von HippelLindau E3 ubiquitin ligase. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within oncology and Cancer biology.
 15th-19th June 2014. 9th European Conference on Mathematical and Theoretical Biology, Gothenburg, Sweden.
Speaker Yihai Cao: Mechanisms of lymphangiogenesis and metastasis. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within oncology and Cancer biology.
Scientific articles with acknowledgement for METOXIA-support:
 Hedlund EM, Yang X, Zhang Y, Yang Y, Shibuya M, Zhong W, Sun B, Liu Y, Hosaka K, Cao Y. Tumor cellderived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs. Proc
Natl Acad Sci U S A. 2013;110;654-659.
 Cao Y. Erythropoietin in cancer: a dilemma in risk therapy. Trends Endocrinol Metab. 2013;24;190-199.
 Hosaka K, Yang Y, Seki T, Nakamura M, Andersson P, Rouhi P, Yang X, Jensen L, Lim S, Feng N, Xue Y, Li X,
Larsson O, Ohhashi T, Cao Y. Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs
on vascular remodelling and metastasis. Nat Commun. 2013;4:2129. doi: 10.1038/ncomms3129.
 Yang Y, Zhang Y, Cao Z, Ji H, Yang X, Iwamoto H, Wahlberg E, Länne T, Sun B, Cao Y. Anti-VEGF- and antiVEGF receptor-induced vascular alteration in mouse healthy tissues. Proc Natl Acad Sci U S A.
2013;110;12018-12023.
 Jensen LD, Cao Y. Clock controls angiogenesis. Cell Cycle. 2013;12;405-408.
 Yang X, Zhang Y, Yang Y, Lim S, Cao Z, Rak J, Cao Y. Vascular endothelial growth factor-dependent
spatiotemporal dual roles of placental growth factor in modulation of angiogenesis and tumor growth. Proc
Natl Acad Sci U S A. 2013;110;13932-13937.
 Cao Y. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin
sensitivity. Cell Metab. 2013;18;478-489.
 Cao Y. Multifarious functions of PDGFs and PDGFRs in tumor growth and metastasis. Trends Mol Med.
2013;19;460-473.
 Religa P1, Cao R, Religa D, Xue Y, Bogdanovic N, Westaway D, Marti HH, Winblad B, Cao Y. VEGF significantly
restores impaired memory behavior in Alzheimer's mice by improvement of vascular survival. Sci Rep.
2013;3:2053. doi: 10.1038/srep02053.
 Khalesi E, Nakamura H, Leong Lee K, Chandra Putra A, Fukazawa T, Kawahara Y, Makino Y, Poellinger L, Yuge
L, Tanimoto K. The Krüppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxiainducible factors via non-canonical mechanisms. Biochem Biophys Res Commun. 2013 Oct 25. pii: S0006291X(13)01764-6.
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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
 Cao Y. Angiogenesis as a therapeutic target for obesity and metabolic diseases. Chem Immunol Allergy.
2014;99:170-179.
 Ji H, Cao R, Yang Y, Iwamoto H, Lim S, Zhang Y, Nakamura M, Andersson P, Wang J, Sun Y, Yang X, Cao Y.
TNFR1-mediates TNF- -induced tumor inflammatory lymphangiogenesis and lymphatic metastasis by
orchestrating the VEGF-C–VEGFR3 signaling pathway., Nature Communications. 2014 (in press).
 Ng KP, Manjeri A, Lee KL, Huang W, Tan SY, Chuah CT, Poellinger L, Ong ST. Physiologic hypoxia promotes
maintenance of CML stem cells despite effective BCR-ABL1 inhibition. Blood. 2014;123;3316-3326.
 Ueda J, Ho JC2, Lee KL, Kitajima S, Yang H, Sun W, Fukuhara N, Zaiden N, Chan SL, Tachibana M, Shinkai Y,
Kato H, Poellinger L. The Hypoxia-Inducible Epigenetic Regulators Jmjd1a and G9a Provide a Mechanistic
Link between Angiogenesis and Tumor Growth. Mol Cell Biol. 2014 Jul 28. pii: MCB.00099-14. [Epub ahead
of print].
 Jakubauskiene E, , Vilys L, Makino Y, Poellinger L, Kanopka A. Cellular hypoxia changes alternative pre-mRNA
splicing by regulating SR protein phosphorylation levels. (Submitted).
11/MAD:
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speakers: María Calzada
and Luis del Peso: Modulation of the angiogenesis inhibitor Ephrin-A3 and the adhesion molecule VCAM-1 by
hypoxia. Implication in cancer metastasis Objective: To discuss last year progress of METOXIA and the
finalization of the project. Target: All partners of METOXIA.
 7th-12th January 2014. Keystone Symposia: “Sensing and Signaling of Hypoxia: Interfaces with Biology and
Medicine (A1)”, Breckenridge, CO, USA. Poster: Luis delPeso. Objective: To give an over-view over the hypoxiaregulatory field. Target: International research scientists within radiation oncology.
 21st March 2014. 1st Symposium on Biomedical research, Universidad Autónoma de Madrid, Madrid, Spain.
Speaker Luis del Peso: Regulation of gene expression by hipoxia. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within oncology and Cancer biology.
Scientific articles with acknowledgement for METOXIA-support:
 Gómez-Maldonado L, Tiana M1, Roche O, Prado-Cabrero A, Jensen L, Fernandez-Barral A, Guijarro-Muñoz I,
Favaro E, Moreno-Bueno G, Sanz L4, Aragones J, Harris A, Volpert O, Jimenez B, Del Peso L. EFNA3 long
noncoding RNAs induced by hypoxia promote metastatic dissemination. Oncogene. 2014 Jul 14;0. doi:
10.1038/onc.2014.200. [Epub ahead of print]
12/DHZM:
 2nd-5th March 2013. 92nd Annual Meeting of the DPG (German Physiological Society), Heidelberg, Germany.
Speaker: a) D. Kracun: Dexamethasone induces pulmonary vascular remodelling involving NOX and HIF. b) D.
Kracun: β3-endonexin as a novel negative regulator of the HIF-system. Objective: To give an over-view over
the hypoxia-regulatory field. Target: International research scientists within oncology and Cancer biology.
 3rd-6th April 2013. 79th Annual Meeting of the German Society for Cardiology, Mannheim, Germany. Speaker: a)
D. Kracun, I. Kanchev, F. Rieß, A. Görlach: Folic acid partially prevents hypoxia-induced pulmonary vascular
remodeling and right ventricular hypertrophy. b) D. Kracun, I. Kanchev, F. Rieß, A. Görlach; Dexamethasone
induces pulmonary vascular remodeling via activation of NADPH oxidases and the HIF system. c) F. Rieß, D.
Kracun, S. Bonello, M. Weitnauer, T. Kietzmann, A. Görlach: Reconciling the role of HIF3 : Inhibition of HIF2
activity in endothelial cells. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within cardiology and Cancer biology.
 8th-12th June 2013. Hypoxianet Oulu 2013, Dealing with hypoxia: Regulatory aspects in cells, tissues and
organisms Oulu, Finland. Speaker Agnes Görlach: Stress kinase signalling in hypoxic smooth muscle cells.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International research scientists
within oncology and Cancer biology.
 7th-12th January 2014. Keystone Symposia:” Sensing and Signaling of Hypoxia: Interfaces with Biology and
Medicine (A1)”, Breckenridge, CO, USA. Speaker: Agnes Görlach: The β3-integrin binding protein β3-endonexin
is anovel negative regulator of hypoxia-inducible factor-1 (HIF-1) Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within radiation oncology
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
 2nd-5th March 2013. 93rd Annual Meeting of the DPG (German Physiological Society), Heidelberg, Germany.
Speaker: a) D. Kracun: Dexamethasone induces pulmonary vascular remodelling involving NOX and HIF. b) D.
Kracun: β3-endonexin as a novel negative regulator of the HIF-system. Objective: To give an over-view over
the hypoxia-regulatory field. Target: International research scientists within oncology and Cancer biology.

 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speakers: Agnes Görlach:
Hypoxia-sensitive NADPH oxidases: from preclinical models to potential biomarkers. Objective: To discuss last
year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Edin NJ, Sandvik JA, Cheng C, Vollan HS, Reger K, Görlach A, Pettersen EO. The role of nitric oxide radicals in
removal of hyper-radiosensitivity by priming irradiation. J Radiat Res 2013;54:1015-1028.
 Kračun D1, Riess F, Kanchev I, Gawaz M, Görlach A. The β3-integrin binding protein β3-endonexin is a novel
negative regulator of hypoxia-inducible factor-1. Antioxid Redox Signal. 2014;20;1964-1976.
13/CNRS:
 12th-15th February 2013, First International Symposium of Cancer Research Center of Lyon (CRCL) Lyon
Convention Center,Lyon, France, Speaker Jacques Pouyssegur: Hypoxia & tumour metabolism: novel
therapeutic approaches”. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
 23rd February- 2nd March 2013, Keystone International Symposium X4 2013 “Tumor Metabolism”, Keystone
(USA), Speaker Jacques Pouyssegur: Hypoxia Signaling, pHi Regulation and Tumor Metabolism: Novel
Therapeutic Approaches. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
 4th-7th March 2013, 11th International Congress on Targeted Anticancer Therapies, Paris, France. Speaker
Jacques Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 14th 15th March 2013, Mediterranean Alp Cancer Conference, MACC8, Therapeutic Progress in Head and
Neck Cancer, Cuneo, Italy, Speaker Jacques Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel
Anticancer Approaches. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
 26th-28th March 2013, 90th Annual Meeting of Physiological Society of Japan, Tokyo, Japan, Speaker Jacques
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 24th-26th April 2013, INSERM workshop, "Genome targeting with artificial TALENs", Bordeaux, France.
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 24th-28th April 2013, The International Liver Congress™ 2013, Amsterdam, The Netherlands. Speaker Jacques
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 13th-15th may 2013, , Angiogenesis meeting, Siena, Italy. Keynote Lecture by Jacques Pouyssegur: Hypoxia
Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International Scientists.
 24th May 2013, Immunology Research Center, Pierre Fabre, St Julien, Genève, Switzerland, Speaker Jacques
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 8th-12th June 2013. Hypoxianet Oulu 2013, Dealing with hypoxia: Regulatory aspects in cells, tissues and
organisms Oulu, Finland. Speaker Nathalie mazure: How to survive in a hypoxic microenvironment. Objective:
To give an over-view over the hypoxia-regulatory field. Target: International research scientists within
oncology and Cancer biology
METOXIA Foreground and Dissemination Activities
Page 19
METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741

17th June 2013, International Scientific Advisory Board, Curie Institute, Paris, France. Speaker Jacques
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 27th-30th July 2013, The International IUPS Physiology Meeting, pH Symposium, Satellite meeting Oxford, UK.
Speaker Jacques Pouyssegur: pH versus hypoxia as key signals in cancer. Objective: To give an over-view
over the hypoxia-regulatory field. Target: International Scientists.
 27th September-1st October 2013, European Cancer Congress, 17th ECCO - ESMO – ESTRO, Amsterdam, the
Netherlands. Special Session chair: Jacques Pouyssegur: Autophagy in Cancer and Cancer Therapy.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 4th-9th October 2013, Banbury meeting: Metformine & Cancer, CSHL, New York, USA. Speaker Jacques
Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To give an
over-view over the hypoxia-regulatory field. Target: International Scientists.
 10th-12th October 2013, ISPDC Annual Meeting on “Proton Dynamic and Cancer”, Munich, Germany. Speaker
Jacques Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Jacques
Pouyssegur: Targeting Hypoxia-stimulated glycolysis in rapidly growing Tumours. Objective: To discuss last year
progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
 29th-31st January 2014, Alterations of the Metabolic pathways as Therapeutic Targets Luxemburg, Speaker
Jacques Pouyssegur: Hypoxia Signaling and Tumor Metabolism: Novel Anticancer Approaches. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 13th-15th March 2014, 93th Ann. Symposium German Physiology Soc. – Tumour Metabolism Symposium,
Mainz, Germany. Speaker Jacques Pouyssegur: Novel aspects of pH targeting in cancer biology. Objective:
To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 16th- 2nd March 2014, Keystone International Symposium X6 2014 “Tumor Metabolism”, Keystone (USA),
Whisler, Canada. Speaker Jacques Pouyssegur: Hypoxia Signaling, pHi Regulation and Tumor Metabolism: Novel
Therapeutic Approaches. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
 8th April 2014, Invitation Seminar, University of Cambridge, UK. Speaker Jacques Pouyssegur: Hypoxia Signaling,
pHi Regulation and Tumor Metabolism: Novel Therapeutic Approaches. Objective: To give an over-view over
the hypoxia-regulatory field. Target: International Scientists.
 14th-16th may 2014, Cancer metabolism and Hypoxia: Cancéropole Nord-Ouest, Deauville, France. Plenary
lecture: Jacques Pouyssegur: Novel aspects of pH targeting in cancer biology. Objective: To give an overview over the hypoxia-regulatory field. Target: International Scientists.
Scientific articles with acknowledgement for METOXIA-support:
 Parks SK, Chiche J, Pouysségur J. Disrupting proton dynamics and energy metabolism for cancer therapy.
Nat Rev Cancer 13; (2013) 611-23
 Parks SK, Mazure NM, Counillon L, Pouysségur J.: Hypoxia promotes tumor cell survival in acidic conditions
by preserving ATP levels. J Cell Physiol. 228; (2013) 1854-1862
 Doyen J, Trastour C, Ettore F, Peyrottes I, Toussant N, Gal J, Ilc K, Roux D, Parks SK, Ferrero JM, Pouysségur J.
Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative
breast cancer and correlates independently with clinical outcome. Biochem Biophys res Comm 451; (2014)
54-61
 Granja S, Marchiq I, Le Floch R, Moura CS, Baltazar F, Pouysségur J. Decrease lactic acid export via basigin
disruption sensitizes A549 cells to phenformin in both normoxic and hypoxic microenvironments.
Oncotarget (Submitted)
 Marchiq I, Le Floch R, Roux D, Simon MP, Pouysségu J. Genetic Disruption of Lactate/H+ Symporters (MCTs)
and their Subunit CD147/BASIGIN Sensitizes Glycolytic Tumor Cells to Phenformin. Cancer Research (2014,
Submitted).
14/ALU-FR:
METOXIA Foreground and Dissemination Activities
Page 20
METOXIA
Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Julia Marzioch:
Microsensor system for research on photodynamic therapy Objective: To discuss last year progress of
METOXIA and the finalization of the project. Target: All partners of METOXIA.
 26th-28th March 2014. 5th International BioNanoMED 2014, Krems, Austria. Speaker: Jochen Kieninger:
Electrochemical Characterization of Platinum Nanowire Electrodes Increasing Sensitivity and Selectivity in
Biosensors. Objective: Discuss improvement of biosensors. Target: Electro engineers within the biosensing
area.
 27th-30th May 2014. 24th Anniversary World Congress on Biosensors, Melbourne, Australia. Speakers a) Hubert
Flamm: Optimization of the ROS sensors. b) Julia Marzioch: Microsensors Systems for Cancer Research and
Photodynamic Therapy. Objective: Discuss improvement of biosensors. Target: Electro engineers within the
biosensing area.
Scientific articles with acknowledgement for METOXIA-support:
 Weltin A, Slotwinski K, Kieninger J, Moser I, Jobst G, Wego M, Ehret R, Urban GA. Cell culture monitoring for
drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem. Lab Chip.
2014;14;138-146
 Kieninger J, Aravindalochanan K, Sandvik JA, Pettersen EO, Urban GA. Pericellular oxygen monitoring with
integrated sensor chips for reproducible cell culture experiments. Cell Prolif 2014; 47:180-188.
15/Jobst:
 3rd-4th June 2013. BioTech 2013: Single-Use Technology in Biopharmaceutical Manufacturing Wädenswil,
Switzerland. Speaker Gerhard Jobst: Pre-calibrated glucose, lactate, glutamine biosensors for single-use
applications. Objective: Discuss improvement of biosensors. Target: Electro engineers within the biosensing
area
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Gerhard Jobst:
Cell-Nurse”: The personal life support system for cells. Objective: To discuss last year progress of METOXIA
and the finalization of the project. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Moser, I., Jost G. Pre-Calibrated Biosensors for Single-Use Applications. Chem. Ing. Tech. 2013, 85No. 1-2,
172-178.
 Marie Bléron. Bachelor's thesis (2014) “Licence Professionnelle de Biotechnologies” with the title
"Caractérisation de la performance d'une méthode définie du mini-analyseur pour la mesure du glucose,
lactate et glutamine". Bi-national (Alsace/ France, Germany) and dual education (University IUT de Colmar
and Company Jobst Technologies, Freiburg).
 Weltin A, Slotwinski K, Kieninger J, Moser I, Jobst G, Wego M, Ehret R, Urban GA. Cell culture monitoring for
drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem. Lab Chip.
2014;14;138-146.
Newspaper contributions:
 Company Profiles: Jobst Technologies GmbH, Biotech Guide Baden- Württemberg: Biotech Companies in
the South-West of Germany, (BIOPRO BW ed.), 2013, p. 92.
 Jobst Technologies, 2014. “Lab on Chip for Life Sciences”. Part 2 Innovations and Competencies of Companies
in Microsystems Technology in Germany 2014 (ISSN 2191-7183, trias Consult ed.), p. 86
16/VX:
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Jan A. Villadsen:
Challenges for maintaining sterility and aseptic conditions in a small enclosure for cell therapeutic products,
what is possible? Objective: To discuss last year progress of METOXIA and the finalization of the project.
Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
17/UCL:
 8th-12th June 2013. Hypoxianet Oulu 2013, Dealing with hypoxia: Regulatory aspects in cells, tissues and
organisms, Oulu, Finland. Speakers a) Margaret Ashcroft: Tumour progression: Adaptive by default? b) Patrick
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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
Maxwell: The HIF pathway and epithelial to mesenchymal transition. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within oncology and Cancer biology.
Scientific articles with acknowledgement for METOXIA-support:
 Yang OC, Maxwell PH, Pollard PJ. Renal cell carcinoma: translational aspects of metabolism and therapeutic
consequences. Kidney Int. 2013;84;667-681.
18/IVSAS:
 20th-24th April 2013. 7th Conference on Experimental and Translational Oncology, Portoroz, Slovenia. Speakers:
a) Silvia Pastorekova: Hypoxia-induced carbonic anhydrase IX as a clinically exploitable component of tumor
progression.
b) M. Zatovicova: Ectodomain shedding of the carbonic anhydrase IX: regulatory, biological and clinical
implications.
c) J. Kopacek: Uncovering the signaling role of the carbonic anhydrase IX through RNA interference and
gene profiling.
d) M. Takacova: Ret-mediated activation of HIF pathway explains expression pattern of carbonic anhydrase
IX in medullary thyroid carcinoma.
e) M.Takacova: Molecular mechanisms contributing to the expression and clinical significance of the
carbonic anhydrase IX in colorectal carcinoma.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International research scientists
within oncology and Cancer biology
 23rd-25th may 2013. 6th Annual World Cancer Congress, Theme: A New Era in Cancer Research and Therapy,
Xi´an, China. Speaker: Jaromir Pastorek: Molecular Mechanisms Regulating Expression and Function of Cancerassociated Carbonic Anhydrase IX. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within oncology and Cancer biology.
 8th-12th June 2013. Hypoxianet Oulu 2013, Dealing with hypoxia: Regulatory aspects in cells, tissues and
organisms, Oulu, Finland. Speakers: a) Silvia Pastorekova: CA IX as a hypoxia-directed actor in tumor biology: to
be or not to be acidic. b) E. Svastova: Dealing with hypoxia: Regulatory aspects in cells, tissues and organisms.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International research scientists
within oncology and Cancer biology.
 10th-12th October 2013. 4th Annual Meeting of the International Society for Proton Dynamics in Cancer (ISPDC),
Munich, Germany. Speaker: a) Silvia Pastorekova: CA IX role in pH regulation and signaling in cancer – a
subcellular context-related view. b) L. Csaderova: Beyond pH regulation: A role of CA IX in focal adhesion during
cell spreading and movement. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within oncology and Cancer biology.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Silvia
Pastorekova: CA IX role in tumour cells and stroma, and detection of CA IX-positive circulating cells and shed CA
IX ectodomain in serum samples. Objective: To discuss last year progress of METOXIA and the finalization of
the project. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA support:

Takacova M, Bartosova M, Skvarkova L, Zatovicova M, Vidlickova I, Csaderova L, Barathova M, Breza
J Jr, Bujdak P, Pastorek J, Breza J Sr, Pastorekova S. Carbonic anhydrase IX is a clinically significant tissue and
serum biomarker associated with renal cell carcinoma. Oncol Lett. 2013;5;191-197.

Radvak P, Repic M, Svastova E, Takacova M, Csaderova L, Strnad H, Pastorek J, Pastorekova S,
Kopacek J. Suppression of carbonic anhydrase IX leads to aberrant focal adhesion and decreased invasion of
tumor cells. Oncol Rep. 2013;29;1147-1153.

Svastova E, Pastorekova S. Carbonic anhydrase IX: a hypoxia-controlled "catalyst" of cell migration.
Cell Adh Migr. 2013;7;226-231.

Csaderova L, Debreova M, Radvak P, Stano M, Vrestiakova M, Kopacek J, Pastorekova S, Svastova E.
The effect of carbonic anhydrase IX on focal contacts during cell spreading and migration. Front Physiol.
2013 Oct 1;4:271. doi: 10.3389/fphys.2013.00271. PubMed PMID: 24101905; PubMed Central PMCID:
PMC3787331.
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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

Zatovičová M, Pastoreková S. Modulation of cell surface density of carbonic anhydrase IX by
shedding of the ectodomain and endocytosis. Acta Virol. 2013;57;257-264.

Sedlakova O, Svastova E, Takacova M, Kopacek J, Pastorek J, Pastorekova S. Carbonic anhydrase IX, a
hypoxia-induced catalytic component of the pH regulating machinery in tumors. Front Physiol 2014; 4; 400.
 Takacova M, Bullova P, Simko V, Skvarkova L, Poturnajova M, Feketeova L, Babal P, Kivela AJ, Kuopio T,
Kopacek J, Pastorek J, Parkkila S, and Pastorekova S. Expression pattern of carbonic anhydrase IX in
medullary thyroid carcinoma supports a role for RET-mediated activation of the HIF pathway. Am J Pathol
2014;184; 953-965.
 Syrjänen L, Luukkaala T, Leppilampi M, Kallioinen M, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila
S, Karttunen T. Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin
neoplasms. APMIS. 2014;122;880-890.
 Ditte Z, Ditte P, Labudova M, Simko V, Iuliano F, Zatovicova M, Csaderova L, Pastorekova S, Pastorek J.
Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa
tumor xenografts. BMC Cancer. 2014 May 22;14:358. doi: 10.1186/1471-2407-14-358.
 Pastorek J, Pastorekova S. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From
biology to clinical use. Semin Cancer Biol (2014), http://dx.doi.org/10.1016/j.semcancer.2014.08.002.
Book chapters:

Benej M, Pastorekova S, Pastorek J. Carbonic Anhydrase IX: Regulation and Role in Cancer. Subcell
Biochem. 2014;75:199-219. doi: 10.1007/978-94-007-7359-2_11. PubMed PMID: 24146381.
 Pastorekova C, Supuran CT. Carbonic Anhydrase IX: From Biology to Therapy. In: Hypoxia and Cancer.
Biological Implications and Therapeutic Opportunities (Ed. Melillo G.). Humana Press, Bristol-Myers Squibb
Princeton
New Jersey USA, Springer Science+Business Media New York 2014, p. 121-156.
19/IBT:
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Arvydas
Kanopka: Summing up on the 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 of METOXIA and the
finalization of the project. Target: All partners of METOXIA.
 7th-12th January 2014. Keystone Symposia: “Sensing and Signaling of Hypoxia: Interfaces with Biology and
Medicine (A1)”, Breckenridge, CO, USA. Speaker: Arvydas Kanopka: 65 kDa protein plays an important role in
hypoxia dependent pre-mRNA splicing regulation. Objective: To give an over-view over the hypoxia-regulatory
field. Target: International research scientists within radiation oncology.
 18th-20th June 2014. The XIIIth International Conference of Lithuanian Biochemical Society, Birstonas,
Lithuania. Speaker: Laurynas Vilys: The role of U2AF in hypoxia-dependant pre-mRNA splicing regulation. To
give an over-view over the hypoxia-regulatory field. Target: International research scientists within
radiation oncology.
Scientific articles with acknowledgement for METOXIA-support:
 Jakubauskiene E, , Vilys L, Makino Y, Poellinger L, Kanopka A. Cellular hypoxia changes alternative pre-mRNA
splicing by regulating SR protein phosphorylation levels. (Submitted).
20/GROW-UM:
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speaker
Brad Wouters: Tumour models for preclinical effect-studies and eventual imaging. Objective: To reach a
conclusion regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds.
Target: Participants of the CAIXi-sub-group of METOXIA.
 5th-6th September 2013. 2nd CR-UK/MRC Gray Institute Symposium, Oxford, UK. Speaker: Brad Wouters: An
epigenetic basis for the contribution of tumor hypoxia to stemness and metastasis. Objective: To give an overview over the hypoxia-regulatory field. Target: International research scientists within radiation oncology.
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Ludwig Dubois:
Hypoxia cancer treatment by use of novel CA9i compounds: A pre-clinical approach. Objective: To discuss last
year progress of METOXIA and the finalization of the project. Target: All partners of METOXIA.
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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
 7th-12th January 2014. Keystone Symposia: “Sensing and Signaling of Hypoxia: Interfaces with Biology and
Medicine (A1)”, Breckenridge, CO, USA. Speaker: Bradly G. Wouters: Hypoxia Promotes Stemness and Poor
Prognosis through Epigenetic Regulation of DICER: Objective: To give an over-view over the hypoxiaregulatory field. Target: International research scientists within radiation oncology.
 27th-29th March 2014. Workshop on Mathematical Oncology V: Heterogeneity and Plasticity in Cancer. Fields
Institute, Toronto, Canada. Speaker Brad Wouters: Hypoxic regulation of epigenetic state controls metastasis
and stemness in cancer. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within radiation oncology.
 4th-8th April 2014. The 33rd ESTRO conference, Vienna, Austria. Invited speaker: Brad Wouters: “The biological
rationale for targeting hypoxia - past, present, and future.” Objective: To give an over-view over the hypoxiaregulatory field. Target: International research scientists within radiation oncology
Scientific articles with acknowledgement for METOXIA-support:
 Dubois L, Peeters SG, van Kuijk SJ, Yaromina A, Lieuwes NG, Saraya R, Biemans R, Rami M, Parvathaneni NK,
Vullo D, Vooijs M, Supuran CT, Winum JY, Lambin P. Targeting carbonic anhydrase IX by nitroimidazole
based sulfamides enhances the therapeutic effect of tumor irradiation: a new concept of dual targeting
drugs. Radiother Oncol 2013;108;523-538.
 Rami M, Dubois L, Parvathaneni NK, Alterio V, van Kuijk SJ, Monti SM, Lambin P, De Simone G, Supuran CT,
Winum JY. Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazolesulfonamides/sulfamides/sulfamates. J Med Chem 2013;56;8512-8520.
 Koritzinsky M, Wouters BG. The roles of reactive oxygen species and autophagy in mediating the tolerance
of tumor cells to cycling hypoxia. Semin Radiat Oncol. 2013;23;252-261.
 Mujcic H, Nagelkerke A, Rouschop KM, Chung S, Chaudary N, Span PN, Clarke B, Milosevic M, Sykes J, Hill
RP, Koritzinsky M, Wouters BG. Hypoxic activation of the PERK/eIF2α arm of the unfolded protein response
promotes metastasis through induction of LAMP3. Clin Cancer Res. 2013;19;6126-6137.
 Rouschop KM1, Dubois LJ, Keulers TG, van den Beucken T, Lambin P, Bussink J, van der Kogel AJ, Koritzinsky
M, Wouters BG. PERK/eIF2α signaling protects therapy resistant hypoxic cells through induction of
glutathione synthesis and protection against ROS. Proc Natl Acad Sci U S A. 2013;110;4622-4627.
21/OU:
 28th February 2013, Oslo Cancer Cluster R&D Network meeting “Radiation Therapy and radiopharmaceuticals:
from Bench to bedside”, Oslo, Norway, Oral presentations by a) Heidi Lyng: “Targeting tumor
microenvironment for radiotherapy optimization” and b) Anne-Hansen Ree: “Histone deacetylase inhibitors in
radiotherapy – from preclinical concept to clinical therapy”. Objective: To give an over-view over the hypoxiaregulatory field. Target: International research scientists within radiation oncology.
 6th-10th April 2013 AACR Annual meeting, Washington DC, USA. Speaker Cathinka Halle Julin: HIF1α signaling
contributes to an aggressive hypoxic phenotype in cervical cancer. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within radiation oncology.
 12th April 2013 METOXIA sub-group meeting on the theme “The Cyprotex data on PK and PD: How do we
proceed with our biological testing to produce an optimal application to CR-UK.” in Munich, Germany. Speaker
Kjersti Flatmark: Tumour models for preclinical effect-studies and eventual imaging. Objective: To reach a
conclusion regarding the further strategy for commercialization of our patented CAIX-inhibitor compounds.
Target: Participants of the CAIXi-sub-group of METOXIA.
 22nd-24th June 2013. 13th International Wolfsberg Meeting on “Molecular Radiation Biology/Oncology”,
Ermatingen, Switzerland. Speakers :a) Cathinka Halle Julin: “Epigenetic changes associated with hypoxiarelated chemoradioresistance in cervical cancer”, b) Harald Bull Ragnum: “Micrometastases and
pimonidazole staining in a surgical cohort of prostate cancer”. Objective: To give an over-view over
treatment of colorectal cancer. Target: International oncology specialists.
 1st-5th September 2013. 40th Annual Meeting of the European Radiation Research Society, Dublin, Ireland.
Invited speaker: Anne-Hansen Ree: “Histone deacetylase (HDAC) inhibition – a targeted approach to hypoxic
tumor radiosensitization?” Objective: To give an over-view over radiosensitization. Target: International
radiation oncology specialists.
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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
 4th-5th November 2013 The 5th General Assembly Meeting of METOXIA in Nice, France. Speaker: Heidi Lyng:
Hypoxia signalling in prostate cancer. Objective: To discuss last year progress of METOXIA and the finalization
of the project. Target: All partners of METOXIA.
 22nd November 2013. Universita Cattolica del S Cuore, Facolta di Medicina e Chirurgia Agostino Gemelli,
Rome, Italy, Invited speaker: Anne-Hansen Ree: “Design and conduct of early-phase radiotherapy trials with
targeted therapeutics,” Objective: To give an over-view over radiosensitization. Target: International
radiation oncology specialists.
 18th-25th January 2014. The 29th CERRO meeting, Les Menuires, France. Speaker: Heidi Lyng: “Combined analysis
of pimonidazole staining and gene expression in prostate cancer. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International research scientists within radiation oncology
 28th March 2014. Seminar on “Current Topics in Cancer Biophysics” Oslo, Norway. Speaker: Harald Bull
Ragnum: “Radiosensitization of hypoxic prostate cancer cell lines by vorinostat.” Objective: To give an overview over radiosensitization. Target: International radiation oncology specialists.
 4th-8th April 2014. The 33rd ESTRO conference, Vienna, Austria. Invited speakers: a) Heidi Lyng: “Hypoxia
signaling in aggressive cancer revealed by DCE-MRI”, b) Anne Hansen Ree: “Trial design in personalised
radiation therapy - multiplicity and complexity”, speakers a) Harald Bull Ragnum: “Relationships between
pimonidazole immunostaining and gene expression in prostate cancer patients”, b) Christina Sæten Fjeldbo:
“HIF1 signaling in aggressive hypoxic cervical tumors”, c) Marte Jonsson: “Mitochondrial function of the
prognostic cell cycle regulatory gene CKS2 in cervical cancer.” d) Grete Hasvold: “G2 checkpoint signalling in
hypoxic cells.” Objective: To give an over-view over the hypoxia-regulatory field. Target: International
research scientists within radiation oncology.
 5th-9th April 2014. AACR Annual meeting, San Diego, California, USA. Speaker Merete Hektoen: “On the role of
experimental microenvironmental conditions in targeted inhibition of the pH-regulating carbonic anhydrase IX
in colorectal carcinoma cells.” Objective: To give an over-view over the hypoxia-regulatory field. Target:
International research scientists within radiation oncology.
 3rd-4th July 2014. IRCCS, Istituto Nazionale Tumori Conference: Histone Deacetylase Inhibitors – Lessons Learned
and Challenges for the Future, Napoli, Italy. Invited speaker: Anne-Hansen Ree: “The rationale and
opportunities for HDAC inhibitors in combination with radiotherapy”. Objective: To give an over-view over
radiosensitization. Target: International radiation oncology specialists.
Scientific articles with acknowledgement for METOXIA-support:

Ragnum HB, Røe K, Holm R, Vlatkovic L, Nesland JM, Aarnes E-K, Ree AH, Flatmark K,
Seierstad T, Lilleby W, Lyng H. Hypoxia-independent downregulation of hypoxia inducible factor 1 targets by
androgen deprivation therapy in prostate cancer. Int J Radiat Oncol Biol Phys. 2013;87;753-760.
Featured in “Issue Highlights”, Int J Radiat Oncol Bio Phys, 87, A16, 2013.
 Røe K, Bratland Å, Vlatkovic L, Ragnum HB, Saelen MG, Olsen DR, Marignol L, Ree AH. Hypoxic tumor kinase
signaling mediated by STAT5A in development of castration-resistant prostate cancer. PLoS One 8, e63723,
2013.
PhD theses:
 MG Sælen: Rectal cancer – functional molecular profiling and targeting of tumor hypoxia in radiation
response and metastasis. Faculty of Medicine, University of Oslo, Norway, 2014.
 HB Ragnum: Hypoxia in prostate cancer: gene expression profiling in relation to disease aggressiveness and
treatment interventions. Faculty of Medicine, University of Oslo, Norway, 2014.
***
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