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 4: 1.2.2012 - 31.1.2013
1/UIO:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker Erik O. Pettersen:
Introductory comments concerning our meeting with CR-UK and thoughts around further development of
patented compounds. 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.
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Erik O. Pettersen:
Short summing up on history and aim of today’s meeting. Objective: Follow-up of the sensor and 3D model
sub-group discussions in Madrid 30th September 2011 Target: Participants of the CAIXi-sub-group of METOXIA.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers Peter
Ebbesen and Nina Jeppesen Edin: Effect of small doses whole-body γ-radiation given at low dose-rate to mice
with normal micro-flora.
Also speaker: Erik Pettersen: A short resume of to what extent METOXIA in its third year reached its goals;
corrected direction determined by progress.
Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
 21st June 2012: Meeting of Inven2, Peter Ebbesen, Kaye Williams with Professor Herbert Newell in Manchester.
Objective: To inform about the METOXIA CAIX project and get guidance regarding the fulfilment of the CR-UK
list of activities to complete an application for NAC of CR-UK.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Erik O. Pettersen and Peter Ebbesen: NORMOXIA-EUROXY-METOXIA: The scientific frame-work for
this course and hypoxia and acidosis in human physiology and diseases.
Stine Christoffersen: Cell respiration, hypoxia and low dose-rate radiation.
Lars Tore Mikalsen: The prognostic properties of vascular hot-spot characteristics in breast cancer.
Target: Young PhD-students of partner organisations.
 15th- 19th October: 39th Meeting of the European Radiation Research Society at Vietri sul Mare, Italy. Speaker
Nina Frederike Jeppesen Edin: The role of TGFb3 and induced nitric oxide synthase activity in connection with
induced resistance against low dose hyper-radiosensitivity.
 12th-16th November 2012: Transatlantic Science Week, Rice University and MD Anderson Cancer Center,
Houston, Texas, USA.
Speakers: Erik O. Pettersen: Hypoxia within METOXIA, possible follow-up?
Nina Jeppesen Edin: Cycling hypoxia and inverse radiomodifying effects of oxygen at ultra-low radiation doses.
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:
 Pettersen EO: METOXIA: Tumour micro-environment for new specific cancer treatment. In: Public Service
Review: European Union: Issue 23 (2012) pp 222-223.
 Pettersen EO: Cell-cycle alterations by hypoxic microenvironment. In: “Tumour Hypoxia: Molecular Mechanisms
and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN 978-363163991-7. pp 195-216.
 Røe K, Mikalsen LT, van der Kogel AJ, Bussink J, Lyng H, Ree AH, Marignol L, Olsen DR.: Vascular responses
to radiotherapy and androgen-deprivation therapy in experimental prostate cancer. Radiat Oncol. 2012
May 23;7:75. doi: 10.1186/1748-717X-7-75.
 Edin NJ, Olsen DR, Sandvik JA, Malinen E, Pettersen EO.: Low dose hyper-radiosensitivity is eliminated during
exposure to cycling hypoxia but returns after reoxygenation. Int J. Radiat. Biol. 88; (2012) 311-319.
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
 Cheng C, Edin NJ, Lauritzen KH, Aspmodal I, Cristoffersen S, Liu J, Rasmussen L, Pettersen EO, Gao X, Bergersen
LH: Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells.
Cellular Oncology 35; (2012) 217-227.
2/MAASTRO
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speakers Philippe Lambin and
Ludwig Dubois: tumour models, possibility for toxicology studies and 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.
 19th-20th April 2012 in Noordwijkerhout, The Netherlands, NVRB (Dutch Society of Radiobiology), Speaker:
Sarah Peeters, Poster presentation.
 9th-13th May 2012 ESTRO meeting Barcelona, Spain. Speakers Philippe Lambin: Do our mothers' genes
influence radiation response?
C. Oberije: Development of a practical prediction model for overall survival from stage III lung cancer.
Target: International research scientists within radiation oncology
 14th May 2012 ESTRO meeting University Hospital Zurich, Schwitzerland. Speaker Philippe Lambin: From
population to voxel based Radiation Oncology: Exploiting inter and intra patient heterogeneity. Target:
International research scientists within radiation oncology
 30th May 2012 ESTRO meeting Maastricht, the Netherlands. Speaker Philippe Lambin: 5.000 patients in the
Biobank of MAASTRO: Past, present and future. Target: International research scientists within radiation
oncology
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speakers Ludwig Dubois: Hypoxia imaging and cancer treatment by use of novel CA9i compounds: A preclinical approach.
Also speaker: Philippe Lambin: Heterogenous versus homogenous irradiation and combination radiation
drugs in clinics.
Objective: To discuss last year progress in 2/MAASTRO within METOXIA. Target: All partners of METOXIA.
 3rd October 2012 Refereeravond Maastricht, the Netherlands, Speaker Sarah Peeters.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Philippe Lambin: Clinical imaging of hypoxia.
Sarah Peters: Non-invasive hypoxia PET-imaging: What tracer to use.
Marco Schaaf: ULK1 is required for autophagy-mediated hypoxic tolerance.
Target: Young PhD-students of partner organisations.
 8th November 2012 GROW Science Day, Maastricht, the Netherlands, Speaker Sarah Peeters
Scientific articles with acknowledgement for EUROXY/METOXIA-support:
 Peeters S, Lambin P, Dubois L: Noninvasive hypoxia imaging. In: “Tumour Hypoxia: Molecular Mechanisms and
Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN 978-3631-639917. pp 397-428.
 Reymen B, Lambin P: Hypoxia, hypoxia response and conventional anti-cancer therapy. In: “Tumour Hypoxia:
Molecular Mechanisms and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH
(2012) ISBN 978-3631-63991-7. pp 429-466.
 Rouschop KM, 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 Mar 7. [Epub ahead of
print].
 Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, Zegers CM, Gillies R, Boellard
R, Dekker A, Aerts HJ. Radiomics: Extracting more information from medical images using advanced feature
analysis. Eur J Cancer. 48; (2012) 441-446.
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
 Lambin P, van Stiphout RGPM, Starmans MHW, Rios-Velazquez E, Nalbantov G, Aerts HJWL, Roelofs E, van
Elmpt W, Boutros PC, Pierluigi Granone, Vincenzo Valentini, Adrian C. Begg, Dirk De Ruysscher and Andre
Dekke

Oberije C, Aerts H, Yu S, de Ruysscher D, Menheere P, Hilvo M, van der Weide H, Rao B, Lambin P.
Development and validation of a prognostic model using blood biomarker information for prediction of
survival of non-small cell lung cancer patients treated with combined chemotherapy and radiation or
radiotherapy alone (NCT00181519, NCT00573040, NCT00572325). Int J Radiat Oncol Biol Phys; 2011; 81(2):
360-368

Voets AM, Oberije C, Struijk RB, Reymen B, De Ruyck K, Thierens H, Vandecasteele K, De Neve W,
Houben R, De Ruysscher D, Smeets HJ, Lambin P. No association between TGF-β1 polymorphisms and
radiation-induced lung toxicity in a European cohort of lung cancer patients. Radiother Oncol. 2012
Dec;105(3):296-8. doi: 10.1016/j.radonc.2012.09.016. Epub 2012 Nov 3.
 Starmans MH, Pintilie M, John T, Der SD, Shepherd FA, Jurisica I, Lambin P, Tsao MS, Boutros PC: Exploiting
the noise: improving biomarkers with ensembles of data analysis methodologies. Genome Med. 2012 Nov
12;4(11):84. [Epub ahead of print].
 van der Heide UA, Houweling AC, Groenendaal G, Beets-Tan RG, Lambin P: Functional MRI for radiotherapy
dose painting. Magn Reson Imaging. 2012 Nov;30(9):1216-23. doi: 10.1016/j.mri.2012.04.010. Epub 2012
Jul 6.
 Starmans MH, Chu KC, Haider S, Nguyen F, Seigneuric R, Magagnin MG, Koritzinsky M, Kasprzyk A, Boutros
PC, Wouters BG, Lambin P: The prognostic value of temporal in vitro and in vivo derived hypoxia geneexpression signatures in breast cancer. Radiother Oncol. 2012 Mar;102(3):436-43. doi:
10.1016/j.radonc.2012.02.002. Epub 2012 Feb 20.
 Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, Zegers CM, Gillies R,
Boellard R, Dekker A, Aerts HJ: Radiomics: extracting more information from medical images using
advanced feature analysis. Eur J Cancer. 2012 Mar;48(4):441-6. doi: 10.1016/j.ejca.2011.11.036. Epub 2012
Jan 16.
3/UEDIN:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speakers: Simon Langdon: Tumour
models, possibility for toxicology studies and imaging. Also presenting: Carol Ward: New data from the UEDIN
breast tumour explant model. 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.
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIAproject of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Anthony
Walton: Multiplexed, Miniaturised Sensing Systems: Monitoring O2, pH and temperature by use of a small
chip multi-sensor. Possibility for wireless transmission Objective: Follow-up of the sensor and 3D model
sub-group discussions in Madrid 30th September 2011 Target: Participants of the CAIXi-sub-group of
METOXIA.
 27th-29th April 2012: Retreat & Collaborative Meeting between St Andrews, Abertay and Edinburgh
Universities at the Burn, Angus, Scotland.
 2nd May 2012 CTRad Biomarker Network Workshop, Microenvironment and Signal Transduction at Oxford
University, England. Invited speaker Carol Ward: Inhibition of CA IX and NHE-1; Targeting pH regulation in
breast cancer. Target: International research scientists within oncology
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speakers Ian Kunkler and Simon Langdon: Inhibition of CAIX in 2D and 3D Breast cancer Cultures. Objective:
To discuss last year progress in 3/UEDIN within METOXIA. Target: All partners of METOXIA.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH
Hotel Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From
Biology to Therapy III.
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
Speaker: James Meehan: A comparison of effects of novel CA inhibitors on the growth and invasion of
breast and ovarian cancer cells.
Target: Young PhD-students of partner organisations.
 1st-2nd November 2012 IGMM Symposium, John McIntyre Conference Centre, Edinburgh, Scotland. Speaker.
James Meehan: A comparison of the effects of novel carbonic anhydrase inhibitors on the growth and
invasion of breast and ovarian cancer cells. Target: International research scientists within oncology
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
 Winum JY, Carta F, Ward C, Mullen P, Harrison D, Langdon SP, Checchi A, Scozzafava A, Kunkler I, Supuran
CT. Ureido-substituted sulfamates show potent carbonic anhydrase IX inhibitory and antiproliferative
activities against breast cancer cell lines. Bioorg Med Chem Lett. 2012, 22:4681 – 4685
4/RUNMC:
 7th February 2012 Dept Radiation Oncology, University of Wisconsin, USA. Invited lecture. Speaker Hans
Kaanders Target: International research scientists within radiation oncology.
 27th February-2nd March 2012 International Congress on Translational Radiation Oncology (ICTR), Geneva,
Switzerland. Speakers: Hans Kaanders: Design and validation of the best therapies combining antiangiogenesis and blockers of pHi-regulating systems. Rademakers: Determine criteria for adding CA9
inhibitor to radiation therapy of larynx cancer. Target: International research scientists within radiation
oncology
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker: Ilse Hoogsteen:
Experiments planned at 4/RUNMC on xenografts with combined CAIXi and radiotherapy. 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.
 9th-13th May 2012 European Society for Therapeutic Radiology and Oncology Annual Meeting (ESTRO),
Barcelona, Spain Speakers: S Rademakers: Predictive value of CAIX expression and staining pattern in
patients treated in the phase III randomised ARCON trial.
H. Stegeman: EGFR-inhibition and radiotherapy in head and neck cancer xenografts: hypoxia, proliferation and tumor
growth delay. Target: International research scientists within radiation oncology.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: Ilse Hoogsteen: Design of molecular marker profiles for prediction of radiotherapy responsiveness
and metastatic behaviour and for selection of patients for new biology-based treatment strategies:
Objective: To discuss last year progress in 4/RUNMC within METOXIA. Target: All partners of METOXIA.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH
Hotel Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From
Biology to Therapy III.
Speaker: Hans Kaanders: Hypoxia as a target for personalized medicine
Marco Schaaf: ULK1 is required for autophagy-mediated hypoxic tolerance
Target: Young PhD-students of partner organisations.
 15th-16th November 2012 Latin American Association for Therapeutic Radiation Oncology Scientific Meeting,
Puerto Vallarte, Mexico. Speaker Hans Kaanders: To modulate level of oxygenation in radiotherapy. Target:
International research scientists within radiation oncology
Scientific articles with acknowledgement for METOXIA-support:
 Hoogsteen IJ, Marres HAM, van den Hoogen FJA, et al. Expression of EGFR under tumor hypoxia:
Identification of a subpopulation of tumor cells responsible for aggressiveness and treatment resistance.
Int. J. Radiat. Oncol. Biol. Phys. 84:807-814, 2012.
 Janssens GO, Rademakers SE, Terhaard CH, et al. Accelerated radiotherapy with carbogen and nicotinamide
for laryngeal cancer: Results of a phase III randomized trial. J. Clin Oncol. 30:1777-1783, 2012.
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
 Meijer TW, Kaanders JH, Span PN, Bussink J: Targeting hypoxia, HIF-1, and tumor glucose metabolism to
improve radiotherapy efficacy. Clin Cancer Res. 2012 Oct 15;18(20):5585-94. doi: 10.1158/1078-0432.CCR12-0858.
 Janssens GO, Rademakers SE, Terhaard CH, et al.: Accelerated radiotherapy with carbogen and
nicotinamide for laryngeal cancer: Results of a phase III randomized trial. J Clin Oncol. 2012 May
20;30(15):1777-83. doi: 10.1200/JCO.2011.35.9315. Epub 2012 Apr 16.
 Røe K, Mikalsen LT, van der Kogel AJ, Bussink J, Lyng H, Ree AH, Marignol L, Olsen DR.: Vascular responses
to radiotherapy and androgen-deprivation therapy in experimental prostate cancer. Radiat Oncol. 2012
May 23;7:75. doi: 10.1186/1748-717X-7-75.
5/UOXF.BP:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker: Adrian Harris: Discussing
how to perform pharmacokinetics for CR-UK application 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.
 31st March -4th April 2012 AACR 2012 Annual Meeting; Education Session, McCormic Place, Chicago II: Speaker
Adrian Harris: Current Clinical Strategies for targeting hypoxia cancer cells. Target: International research
scientists within oncology.
 3rd May 2012 Ontario Cancer Institute, Ontario, Canada, Speaker Adrian Harris: “Targeting tumour
adaptation to hypoxia & enhancement of anti-angiogenic therapy”. Target: International research scientists
within oncology.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: dean Singleton: Correlation of oxygen measurement in tumours with the extent hypoxia as
assessed by pimonidazole staining and blood markers Objective: To discuss last year progress in
5/UOXF.BP within METOXIA. Target: All partners of METOXIA.
 15th June 2012 Breast Cancer Nobel Symposia, Stockholm, Sweden. Speaker Adrian Harris: Tumour
angiogenesis and metabolism: interlocked targets for therapy. Target: International research scientists
within oncology.
 8th July 2012 Cell Press Conference, Leuven, Belgium. Speaker Adrian Harris: Mechanisms of resistance to
anti-VEGF treatment - new therapeutic strategies. Target: International research scientists within oncology.
 8th July 2012 EACR 22 Congress, Barcelona, Spain. Speaker Adrian Harris: Mechanisms of resistance to antiVEGF treatment - new therapeutic strategies. Target: International research scientists within oncology.
 7th September 2012 Immunocore Limited, Abingdon, Oxfordshire, UK Speaker Adrian Harris: Tumour
angiogenesis and metabolism: interlocked targets for therapy. Target: International research scientists
within oncology.
 5th October 2012 Tumour Microenviornent & cellular stress: Signalling, Imaging & Therapeutic Targets,
Crete, Greece Speaker Adrian Harris: Exploiting synthetic lethality of hypoxia induced metabolism to
enhance antiangiogenic therapy. Target: International research scientists within oncology.
 12th October 2012 HypOxyBridge Meeting, Oxford Unviersity, Wellcome Trust, Oxford, UK. Speaker Adrian
Harris: Therapeutic implications of in vivo induction of hypoxia during anti-angiogenic cancer therapy.
Target: International research scientists within oncology.
 15th January 2013 Think Tank 23, Dominican Republic, Speaker Adrian Harris: Role of hypoxia metabolism
resistance to bevacizumab. Target: International research scientists within oncology.
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 Apr;39(2):171-179.
 Jubb AM, Browning L, Campo L, Turley H, Steers G, Thurston G, Harris AL, Ansorge O: Expression of vascular
Notch ligands Delta-like 4 and Jagged-1 in glioblastoma. Histopathology. Feb 1. (2012) doi: 10.1111/j.13652559.2011.04138.x. [Epub ahead of print].
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
 Kumar K, Wigfield S, Gee HE, Devlin CM, Singleton D, Li JL, Buffa F, Huffman M, Sinn AL, Silver J, Turley H,
Leek R, Harris AL, Ivan M. Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its
antitumor effects in mouse xenografts. J. Mol. Med. (Berl) 2013 Jan 30. [Epub ahead of print].
 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. 2013 Apr;28(2):360-9. doi: 10.3109/14756366.2012.736979. Epub 2012 Nov 19.
6/AUH,AS:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker: Morten Busk: Experiments
planned at 6/AUK,AS on xenografts with combined CAIXi and radiotherapy. 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.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: Morten Busk: Defining optimal combinational therapies that target different aspects of hypoxia
prior to irradiation in pre-clinical models: Objective: To discuss last year progress in 6/AUH,AS within
METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Busk M, Mortensen LS, Nordsmark M, et al. PET hypoxia imaging with FAZA: reproducibility at baseline and
during fractionated radiotherapy in tumour-bearing mice. Eur J Nucl Med Mol Imaging 2013;40:186-97.
 Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J. Imaging hypoxia to improve radiotherapy
outcome. Nat Rev Clin Oncol 2012;9:674-87.
 Mortensen LS, Johansen J, Kallehauge J, et al. FAZA PET/CT hypoxia imaging in patients with squamous cell
carcinoma of the head and neck treated with radiotherapy: results from the DAHANCA 24 trial. Radiother
Oncol 2012;105:14-20.
7/FMC:
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Michael Dornish:
Development of Nova-Matrix 3D-models for cancer research and challenges for internal micro-environmental
recordings.Objective: Follow-up of the sensor and 3D model sub-group discussions in Madrid 30th September
2011 Target: Participants of the CAIXi-sub-group of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
8/UNIMAN:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker: Kaye Williams:
Experiments planned at 8/UNIMAN on xenografts with combined CAIXi and radiotherapy. 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.
 11th-15th April 2012. 9th International Conference on Carbonic Anhydrase, Antalya, Turkey Author: Kaye
Williams: Therapeutic opportunities in targeting tumour-associated CA-IX expression. Target: International
scientists within cancer research.
 30th April-3rd October 2012, Radiation Research Society Annual Meeting, Puerto Rico, USA Speaker Kaye
Williams: Inhibiting Oncogenic signalling to target hypoxia and metastasis. Target: International scientists
within cancer research.
 5th-9th May 2012. 15th International & 14th European Congress of Endocrinology, Florence, Italy. Speaker
Natalie Borrows: PI3K/HIF and ATM signalling in radio-resistance of thyroid-carcinoma. New therapeutic
implications? Target: International scientists within cancer research.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
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
Speakers: Kaye Williams and Roben Gieling: Updating on targeting CAIX and hypoxia signaling. Objective: To
discuss last year progress in 8/UNIMAN within METOXIA. Target: All partners of METOXIA.
 21st June 2012: Meeting of Kaye Williams, Inven2 of 1/UIO and Peter Ebbesen with Professor Herbert Newell in
Manchester. Objective: To inform about the METOXIA CAIX project and get guidance regarding the fulfilment of
the CR-UK list of activities to complete an application for NAC of CR-UK.
 8th-12 September 2012. 36th Annual Meeting of the European Thyroid Association, Pisa, Italy. Speaker Natalie
Burrows: HIF-2 expression correlates with clinically aggressive thyroid tumours. In vitro, hypoxia-modulated
targets are differentially regulated by HIF-1 and -2, and promote radio-resistance. Target: International
scientists within cancer research.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Kaye Williams: Bioreductive drugs and hypoxic cell sensitizers.
Kathryn Blount: Cancer and energetic
Emily Rowling: Effects of the SRC-inhibitor Saracatinib (AZD0530) on the cellular response to radiation
treatment in vitro.
Target: Young PhD-students of partner organisations.
Scientific articles with acknowledgement for METOXIA-support:
 Williams KJ, McKeown R: Targeting hypoxic cells with bioreductive drugs. In: “Tumour Hypoxia: Molecular
Mechanisms and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012)
ISBN 978-3631-63991-7. pp 467-490.
 Cawthorne C, Burrows N, Gieling RG, Morrow C, Forster D, Gregory J, Smigova A, Babur M, Hodgkinson C,
Dive C, 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; in press, Mol Cancer Therapeutics.
 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. 2012 Nov 19.
 Gieling RG, Williams KJ. Carbonic anhydrase IX as a target for metastatic disease. Bioorg Med Chem. 2012
Oct 11. doi:pii: S0968-0896(12)00796-1. 10.1016/ j.bmc.2012.09.062.
 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. 2012 Jun 14;55(11):5591-600.
Also notice that the following paper published at the end of the last reporting period was reported as
research highlight in Nature Reviews Endocrinology 8, 4 (2012):
 Burrows N, Babur M, Resch J, Ridsdale S, Mejin M, Rowling EJ, Brabant G, Williams KJ.: GDC-0941 Inhibits
Metastatic Characteristics of Thyroid Carcinomas by Targeting both the Phosphoinositide-3 Kinase (PI3K) and
Hypoxia-Inducible Factor-1_ (HIF-1_) Pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. Epub 2011
Oct 12.
9/UNIFI:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speakers: Andrea Scozzafava and
Fabrizio Carta: Up-dating the situation regarding chemical synthesis for in vivo experiments. 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 April 2012 Conference on CAIX and CAXII in Toulouse, France. Speaker Claudiu Supuran: Inhibition of
carbonic anhydrase IX and XII as a strategy to image and treat Hypoxic tumors. Target: International scientists
within cancer research.
 11th-15th April 2012 9th International Conference on CAs in Antalya Turkey. The organizer of the conference was
Claudiu Supuran. Target: International scientists within cancer research.
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 25th-27th May2012, the 15th Hellenic Symposium on Medicinal Chemistry in Athens, Greece. Speaker: Claudiu
Supuran: Plenary lecture on: Carbonic anhydrases as drug targets. Target: International scientists within cancer
research.
 1st-7th June 2012: Claudiu Supuran meeting with Dr. Atilla Akdemir of the Bezmialem Vakif University of Istanbul
Turkey for discussions and programming experiments on CA inhibitors.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speakers: Claudiu Supuran and Andrea Scozzafava: CA9 and -12 as new cancer therapy targets: An overview of the international competition towards this goal. Objective: To discuss last year progress in 9/UNIFI
within METOXIA. Target: All partners of METOXIA.
 26th-29th June 2012. 10th International Symposium on Pharmaceutical Sciences in Ankara, Turkey. Invited
speaker Claudiu Supuran: Inhibition of carbonic anhydrases as a new antitumor mechanism. Target:
International scientists within cancer research.
 17th-21st July 2012 21st Italian National Meeting on Medicinal Chemistry in Palermo. Invited speaker: Claudiu
Supuran: Carbonic anhydrases as drug targets. Target: International scientists within cancer research.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Claudiu Supran: Principles for 3D-fitting of molecules to an enzyme - measuring side-effects of drugs:
carbonic anhydrases as an example.
Muhammet Tanc: Sulfocoumarins as CA inhibitors.
Target: Young PhD-students of partner organisations.
Collaborative visits with METOXIA-themes for Andrea Scozzafava:
 21st-22nd February 2012: Collaboration with Dr. Giuseppina De Simone and Dr. C. Capasso of Italian National
Research Council CNR in Naples (ITA) on the crystallography of CA complexed with inhibitors.
Collaborative visits with METOXIA-themes for Claudiu Supuran:
 1st-7th June 2012: collaboration with Dr. Atilla Akdemir of the Bezmialem Vakif University of Istanbul, Tukey,
June 01 – 07, 2012 for discussions and programming experiments on CA inhibitors.
 29th August-2nd September 2012: Collaboration with Dr. C. Capasso of Italian National Research Council CNRInstitute of Protein Biochemistry in Naples (ITA), visit for cloning CA IX from its synthetic gene (procedure
developed by Dr Capasso).
 5th -26th August 2012. Collaboration with Dr. Ozlen Guzel of Istanbul University in Istanbul, Turkey for
discussions and programming experiments on CA inhibitors in the framework of the METOXIA project.
 2nd October 2012. Collaboration with Prof. N. Baldini of Istituto Ortopedico Rizzoli di Bologna-Laboratorio
di Fisiopatologia ortopedica e medicina rigenerativa in Bologna (ITA), investigations of CA inhibitors in
hypoxic osteosarcomas.
 21st-28th October 2012. Collaboration with Dr. Laura Badea of the University of Bucharest, Romania for
discussions in the framework of the METOXIA project.
 28th October-1st November 2012. Collaboration with Dr. G. De Simone of Italian National Research Council
CNR-Istituto di Biostrutture e Bioimmagini in Naples, Italy for discussions in the framework of the METOXIA
project, visit in the period.
 5th-10th November 2012. Collaboration with Dr. Jean-Francois Peyron of the Centre de Recherche
Mediterraéen de Médecine Moléculaire in Nice (FRA) for discussions and programming experiments on CA
inhibitors and hypoxic tumors in the framework of the METOXIA project.
 27th-29th November 2012. Collaboration with Dr. Sebastian Thibaudeau of the University of Poitiers, France
for giving a seminar and discussions in the framework of the METOXIA project and collaboration with Dr.
Bodgan-Iuliu Iorga of the Molecular Modelling and Structural Crystallography Institut de Chimie des
Substances Naturelles-CNRS for discussions and to give a seminar at that Institut in the period November
29th – December 01st, 2012.
Scientific articles with acknowledgement for METOXIA-support:
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EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 Supuran CT: New drugs interfering with pH regulation in hypoxic tumours In: “Tumour Hypoxia: Molecular
Mechanisms and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN
978-3631-63991-7. pp 517-542.
 Monti SM, Supuran CT, De Simone G.: Carbonic anhydrase IX as a target for designing novel anticancer drugs.
Curr Med Chem. 2012;19(6):821-830.
 Ekinci D, Cavdar H, Durdagi S, Talaz O, Sentürk M, Supuran CT.: Structure-activity relationships for the
interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase
isoforms I, II, III, IV and VI. Eur J Med Chem. 2012 Mar;49: 68-73.
 Carta F, Aggarwal M, Maresca A, Scozzafava A, McKenna R, Supuran CT.: Dithiocarbamates: a new class of
carbonic anhydrase inhibitors. Crystallographic and kinetic investigations. Chem Commun (Camb). 2012 Feb
11;48(13):1868-1870.
 Carta F, Aggarwal M, Maresca A, Scozzafava A, McKenna R, Masini E, Supuran CT. Dithiocarbamates strongly
inhibit carbonic anhydrases and show antiglaucoma action in vivo. J Med Chem. 2012 Feb 23;55(4):17211730.
 Truppo E, Supuran CT, Sandomenico A, Vullo D, Innocenti A, Di Fiore A, Alterio V, De Simone G, Monti SM.:
Carbonic anhydrase VII is S-glutathionylated without loss of catalytic activity and affinity for sulfonamide
inhibitors. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1560-1564.
 McDonald PC, Winum JY, Supuran CT, Dedhar S.: Recent developments in targeting carbonic anhydrase IX
for cancer therapeutics. Oncotarget. 2012 Jan;3(1):84-97.
 Can D, Spingler B, Schmutz P, Mendes F, Raposinho P, Fernandes C, Carta F, Innocenti A, Santos I, Supuran
CT, Alberto R.: [(Cp-R)M(CO)3] (M=Re or 99mTc) Arylsulfonamide, arylsulfamide, and arylsulfamate
conjugates for selective targeting of human carbonic anhydrase IX.: Angew Chem Int Ed Engl. 2012 Apr
2;51(14):3354-3357.
 Perez-Sayans M, Garcia-Garcia A, Scozzafava A, Supuran CT.: Inhibition of V-ATPase and carbonic
anhydrases as interference strategy with tumor acidification processes. Curr Pharm Des. 2012;18(10):14071413.
 Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT.: New chemotypes acting as isozyme-selective
carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoform II. Bioorg Med Chem Lett.
2012 Mar 15;22(6):2182-2185.
 Moeker J, Teruya K, Rossit S, Wilkinson BL, Lopez M, Bornaghi LF, Innocenti A, Supuran CT, Poulsen SA.:
Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases.
Bioorg Med Chem. 2012 Apr 1;20(7):2392-2404.
 Carta F, Maresca A, Scozzafava A, Supuran CT. Novel coumarins and 2-thioxo-coumarins as inhibitors of the
tumor-associated carbonic anhydrases IX and XII. Bioorg Med Chem. 2012 Apr 1;20(7):2266-2273.
 Parkkila S, Vullo D, Maresca A, Carta F, Scozzafava A, Supuran CT. Serendipitous fragment-based drug
discovery: ketogenic diet metabolites and statins effectively inhibit several carbonic anhydrases. Chem
Commun (Camb). 2012 Apr 11;48(29):3551-3553
 Turkoglu S, Maresca A, Alper M, Kockar F, Işık S, Sinan S, Ozensoy O, Arslan O, Supuran CT.: Mutation of
active site residues Asn67 to Ile, Gln92 to Val and Leu204 to Ser in human carbonic anhydrase II: influences
on the catalytic activity and affinity for inhibitors. Bioorg Med Chem. 2012 Apr 1;20(7):2208-2213.
 Pérez-Sayáns M, Supuran CT, Pastorekova S, Suárez-Peñaranda JM, Pilar GD, Barros-Angueira F, Gándara-Rey
JM, García-García A.: The role of carbonic anhydrase IX in hypoxia control in OSCC. J. Oral. Pathol. Med. 2013
Jan;42(1):1-8.
 Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezáčová P, Chimirri A.:
Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as
potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-3899.
 Supuran CT.: Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem. 2012
Dec;27(6):759-772.
 Pérez-Sayáns M, Suárez-Peñaranda JM, Pilar GD, Supuran CT, Pastorekova S, Barros-Angueira F, Gándara-Rey
JM, García-García A.: Expression of CA-IX is associated with advanced stage tumors and poor survival in oral
squamous cell carcinoma patients. J. Oral. Pathol. Med. 2012 Oct;41(9):667-674.
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Grant Agreement No. HEALTH-F2-2009-222741
 Balboni G, Congiu C, Onnis V, Maresca A, Scozzafava A, Winum JY, Maietti A, Supuran CT.: Flavones and
structurally related 4-chromenones inhibit carbonic anhydrases by a different mechanism of action compared
to coumarins. Bioorg Med Chem Lett. 2012 May 1;22(9):3063-3066.
 Salmon AJ, Williams ML, Wu QK, Morizzi J, Gregg D, Charman SA, Vullo D, Supuran CT, Poulsen SA.:
Metallocene-based inhibitors of cancer-associated carbonic anhydrase enzymes IX and XII. J Med Chem. 2012
Jun 14;55(11):5506-5517.
 Durdagi S, Vullo D, Pan P, Kähkönen N, Määttä JA, Hytönen VP, Scozzafava A, Parkkila S, Supuran CT.: Proteinprotein interactions: inhibition of mammalian carbonic anhydrases I-XV by the murine inhibitor of carbonic
anhydrase and other members of the transferrin family. J Med Chem. 2012 Jun 14;55(11):5529-5535.
 Alterio V, Di Fiore A, D'Ambrosio K, Supuran CT, De Simone G.: Multiple binding modes of inhibitors to carbonic
anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev. 2012 Aug 8;112(8):44214468.
 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. 2012 Jun 14;55(11):5591-5600.
 Carta F, Scozzafava A, Supuran CT.: Sulfonamides: A patent review (2008 - 2012). Expert Opin Ther Pat. 2012
Jul;22(7):747-758.
 Winum JY, Carta F, Ward C, Mullen P, Harrison D, Langdon SP, Cecchi A, Scozzafava A, Kunkler I, Supuran CT.:
Polypharmacology of sulfonamides: pazopanib, a multitargeted receptor tyrosine kinase inhibitor in clinical use,
potently inhibits several mammalian carbonic anhydrases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):46814685.
 D'Ambrosio K, Smaine FZ, Carta F, De Simone G, Winum JY, Supuran CT.: Development of potent carbonic
anhydrase inhibitors incorporating both sulfonamide and sulfamide groups. J Med Chem. 2012 Aug
9;55(15):6776-6783.
 Supuran CT.: Inhibition of carbonic anhydrase IX as a novel anticancer mechanism. World J Clin Oncol. 2012 Jul
10;3(7):98-103.
 De Luca V, Vullo D, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C.: Anion inhibition studies of an αcarbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1. Bioorg
Med Chem Lett. 2012 Sep 1;22(17):5630-5634.
 Di Fiore A, Maresca A, Supuran CT, De Simone G.: Hydroxamate represents a versatile zinc binding group for
the development of new carbonic anhydrase inhibitors. Chem Commun (Camb). 2012 Sep 11;48(70):8838-40.
doi: 10.1039/c2cc34275h. Epub 2012 Jul 27.
 Reich R, Hoffman A, Veerendhar A, Maresca A, Innocenti A, Supuran CT, Breuer E.: Carbamoylphosphonates
control tumor cell proliferation and dissemination by simultaneously inhibiting carbonic anhydrase IX and
matrix metalloproteinase-2. Toward nontoxic chemotherapy targeting tumor microenvironment. J Med Chem.
2012 Sep 13;55(17):7875-7882.
 Sechi M, Innocenti A, Pala N, Rogolino D, Carcelli M, Scozzafava A, Supuran CT.: Inhibition of α-class
cytosolic human carbonic anhydrases I, II, IX and XII, and β-class fungal enzymes by carboxylic acids and
their derivatives: new isoform-I selective nanomolar inhibitors. Bioorg Med Chem Lett. 2012 Sep 15;
22(18):5801-5806.
 Brzozowski Z, Sławiński J, Vullo D, Supuran CT.: Carbonic anhydrase inhibitors. Regioselective synthesis of novel
series 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic
isozymes I and II and transmembrane cancer-associated isozymes IX and XII. Eur J Med Chem. 2012 Oct;
56:282-291.
 Vullo D, De Luca V, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C.: The first activation study of
a bacterial carbonic anhydrase (CA). The thermostable α-CA from Sulfurihydrogenibium yellowstonense
YO3AOP1 is highly activated by amino acids and amines. Bioorg Med Chem Lett. 2012 Oct 15;22(20):63246327.
 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 Apr;39(2):171-179.
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Grant Agreement No. HEALTH-F2-2009-222741
 Marini AM, Maresca A, Aggarwal M, Orlandini E, Nencetti S, Da Settimo F, Salerno S, Simorini F, La Motta C,
Taliani S, Nuti E, Scozzafava A, McKenna R, Rossello A, Supuran CT.: Tricyclic sulfonamides incorporating
benzothiopyrano[4,3-c]pyrazole and pyridothiopyrano[4,3-c]pyrazole effectively inhibit α- and β-carbonic
anhydrase: X-ray crystallography and solution investigations on 15 isoforms. J Med Chem. 2012 Nov 26;
55(22):9619-9629.
 Vullo D, De Luca V, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C.: Anion inhibition studies of the
fastest carbonic anhydrase (CA) known, the extremo-CA from the bacterium Sulfurihydrogenibium azorense.
Bioorg Med Chem Lett. 2012 Dec 1; 22(23):7142-7145.
 Scozzafava A, Carta F, Supuran CT.: Secondary and tertiary sulfonamides: a patent review (2008 - 2012).
Expert Opin Ther Pat. 2013 Feb;23(2):203-213.
 Buanne P, Renzone G, Monteleone F, Vitale M, Monti SM, Sandomenico A, Garbi C, Montanaro D, Accardo M,
Troncone G, Zatovicova M, Csaderova L, Supuran CT, Pastorekova S, Scaloni A, De Simone G, Zambrano N.:
Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in
Hypoxic Cells. J Proteome Res. 2013 Jan 4; 12(1):282-292.
 Del Prete S, Isik S, Vullo D, De Luca V, Carginale V, Scozzafava A, Supuran CT, Capasso C.: DNA cloning,
characterization, and inhibition studies of an α-carbonic anhydrase from the pathogenic bacterium Vibrio
cholerae. J Med Chem. 2012 Dec 13; 55(23):10742-10748.
 Nishimori I, Vullo D, Minakuchi T, Scozzafava A, Capasso C, Supuran CT.: 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 Jan 1; 23(1):256-260.
 Tars K, Vullo D, Kazaks A, Leitans J, Lends A, Grandane A, Zalubovskis R, Scozzafava A, Supuran CT.:
Sulfocoumarins (1,2-Benzoxathiine-2,2-dioxides): A Class of Potent and Isoform-Selective Inhibitors of TumorAssociated Carbonic Anhydrases. J Med Chem. 2013 Jan 10; 56(1):293-300.
 Akdemir A, Vullo D, Luca VD, Scozzafava A, Carginale V, Rossi M, Supuran CT, Capasso C.: 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 Feb 15; 23(4):1087-1090.
10/KI:
 9th-13 Jan 2012, Croucher Advanced Study Institute 2012, Tumour Microenvironment – New Concepts and
Molecular Mechanisms, Hong Kong. Speaker Lorenz Poellinger: Mechanisms of Gene Regulation in Hypoxia –
Relevance for Regulation of Tumor Growth and the Cell Differentiation Status. Objective: To give an over-view
over the hypoxia-regulatory field. Target: International Scientists.
 12th-17th February 2012, Keystone Symposia, Banff, Alberta, Canada, “Advances in Hypoxic Signaling: From
Bench to Bedside”. Invited plenary speaker: Lorenz Poellinger: Epigenetic control of hypoxia gene expression
and metabolic stress. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: Lorenz Poellinger: Modulation of Notch signalling and/or HIF on tumour growth and metastasis
Also speakers: Lasse Jensen/Pegah Rouhi: On the role of hypoxia in promoting lymphangiogenesis and
lymphatic metastasis.
Objective: To discuss last year progress in 10/KI within METOXIA. Target: All partners of METOXIA.
 26th-29th June 2012, The 33rd NAITO conference, Sapporo, Japan, “Oxygen Biology: Hypoxia, Oxidative Stress and
Diseases”. Invited plenary speaker: Lorenz Poellinger: Epigenetic regulatory mechanisms underlying the cellular
response to hypoxia. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
 20th-23rd September 2012, Hypoxia-Net, EU-COST, Essen, Germany, “Sensing Hypoxia in the Cell and the
Organism”. Invited plenary speaker: Lorenz Poellinger: Epigenetic Mechanisms Regulating the Hypoxic
Response. Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
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Speaker: Lorenz Poellinger: Mechanisms of gene regulation under hypoxic conditions.
Target: Young PhD-students of partner organisations.
 5th-8th November 2012, “Frontiers in Cancer Science 2012”, Singapore, Singapore, Invited plenary speaker:
Lorenz Poellinger: Epigentic Mechanisms Regulating the Hypoxic Response in Cancer Disease. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
Scientific articles with acknowledgement for METOXIA-support:
 Stiehl, DP, Bordoli, MR, Abreu-Rodrıguez, I, Wollenick, K, Schraml, P Gradin, K, Poellinger, L, Kristiansen, G and
Wenger, RH: Non-canonical HIF-2a function drives autonomous breast cancer cell growth via an AREG–
EGFR/ErbB4 autocrine loop. Oncogene 31; (2012) 2283-2297.
 Zheng XF, Zheng XW, Wang X, Botusan I, Takeda T, Inoue M, Catrina, SB, Brismar K, Poellinger L, Pereira T
(2012) Acute hypoxia induces apoptosis by activation of the unfolded protein response and up-regulation
of CHOP. Cell Death Disease 3, e322. doi: 10.1038/cddis. (2012).66
 Cao R, Ji H, Feng N, Zhang Y, Yang X, Andersson P, Sun Y, Tritsaris K, Hansen AJ, Dissing S, Cao Y.:
Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc Natl
Acad Sci U S A. 2012 Sep 25;109(39):15894-9. Epub 2012 Sep 11.
 Chan KM, Wong HL, Jin G, Liu B, Cao R, Cao Y, Lehti K, Tryggvason K, Zhou Z.: MT1-MMP inactivates ADAM9
to regulate FGFR2 signaling and calvarial osteogenesis. Dev Cell. 2012 Jun 12;22(6):1176-90. doi:
10.1016/j.devcel.2012.04.014. Epub 2012 May 24.
 Jensen LD, Cao Z, Nakamura M, Yang Y, Bräutigam L, Andersson P, Zhang Y, Wahlberg E, Länne T, Hosaka K,
Cao Y.: Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent
angiogenesis in developing zebrafish. Cell Rep. 2012 Aug 30;2(2):231-41. doi: 10.1016/j.celrep.2012.07.005.
Epub 2012 Aug 9
 Lim S, Honek J, Xue Y, Seki T, Cao Z, Andersson P, Yang X, Hosaka K & Cao Y.: Cold-induced activation of brown
adipose tissue and adipose angiogenesis in mice. Nature Protocols, 2012 Mar 1;7(3):606-15. doi:
10.1038/nprot.2012.013.
 Jensen LD, Cao, Y.: Clock controls angiogenesis. Cell Cycle. 2013 Feb 1;12(3):405-8. doi: 10.4161/cc.23596. Epub
2013 Jan 16.
 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 Jan 8;110(2):654-9. doi: 10.1073/pnas.1209310110. Epub 2012 Dec 24.
 Cao Y.: Erythropoietin in cancer: A dilemma in risk therapy. Trends Endocrinol Metab. 2012 Dec 5. pii: S10432760(12)00186-5. doi: 10.1016/j.tem.2012.10.007. [Epub ahead of print]
11/MAD:
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speakers: Manuel Landazuri and María Calzada: Identification of new targets relevant to the EMT and
angiogenesis. Objective: To discuss last year progress in 11/MAD within METOXIA. Target: All partners of
METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
 Villar D, Ortiz-Barahona A, Gómez-Maldonado L, Pescador N, Sánchez-Cabo F, Hackl H, Rodriguez BA,
Trajanoski Z, Dopazo A, Huang TH, Yan PS, Del Peso L.: Cooperativity of stress-responsive transcription
factors in core hypoxia-inducible factor binding regions. PLoS One. 2012;7(9):e45708. doi:
10.1371/journal.pone.0045708. Epub 2012 Sep 24.
 Tiana M, Villar D, Pérez-Guijarro E, Gómez-Maldonado L, Moltó E, Fernández-Miñán A, Gómez-Skarmeta JL,
Montoliu L, Del Peso L.: A role for insulator elements in the regulation of gene expression response to hypoxia.
Nucleic Acids Res. 2012 Mar;40(5):1916-27. doi: 10.1093/nar/gkr842.
 Bienes-Martínez R, Ordóñez A, Feijoo-Cuaresma M, Corral-Escariz M, Mateo G, Stenina O, Jiménez B,
Calzada MJ.: Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via HIFindependent suppression of thrombospondin-1. Sci Rep. 2012; 2:788. doi: 10.1038/srep00788. Epub 2012
Nov 9.
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Grant Agreement No. HEALTH-F2-2009-222741
 Fernández-Sánchez R, Berzal S, Sánchez-Niño MD, Neria F, Gonçalves S, Calabia O, Tejedor A, Calzada MJ,
Caramelo C, Deudero JJ, Ortiz A.: AG490 promotes HIF-1α accumulation by inhibiting its hydroxylation. Curr
Med Chem. 2012;19(23):4014-23.
12/DHZM:
 9th -17th February 2012, Keystone Symosia; “Advances in Hypoxic Signaling: From Bench to Bedside (Q4)”,
Banff, Alberta, Canada. Chair Agnes Görlach: Transcriptional and Non-Transcriptional Regulation of Hypoxia
Responses. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Present and participating in
discussion: Agnes Görlach. 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-25th March 2012, Annual meeting of the German Society of Physiology, Dresden, Germany. Agnes Görlach
HIF-3alpha inhibits HIF-2 in vascular endothelial cells by dimerization with ARNT. Objective: To give an overview over the hypoxia-regulatory field. Target: German Scientists
 18th-20th April 2012, HypoxiaNet Workshop Learning from Hypoxia Signaling, Bilbao, Spain, Speaker Agnes
Görlach: The ancient fish peptide urotensin-II: A novel player in the hypoxia signaling network. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 3rd-8th June 2012, Gordon Research Conference on NOX Family NADPH oxidases, Waterville, NH, USA. Speaker
Agnes Görlach: NOX and the hypoxic stress response. Objective: To give an over-view over the hypoxiaregulatory field. Target: International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: Agnes Görlach: Biomarkers for tumour progression and/or metastatic risk and hypoxia/reoxygenation
in animal models. Objective: To discuss last year progress in 12/DHZM within METOXIA. Target: All partners of
METOXIA.
 25th July-16th August 2012, LehSymposium, The lung at high altitude, Leh, India and Global Hypoxia Summit,
Delhi, India. Speaker Agnes Görlach: Reactive oxygen species and hypoxia signaling pathways: Implications
for pulmonary vascular remodeling. Objective: To give an over-view over the hypoxia-regulatory field.
Target: International Scientists.
 19th-20th September 2012, HypoxiaNet Symposium, Essen, Germany. Speaker Agnes Görlach: Hypoxia and
NOX enzymes. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
 27th September 2012, GFMVB Meeting, Mannheim, Germany. Agnes Görlach organizer of session on
“Vascular Redox-Regulation: NO and Beyond”. Objective: To give an over-view over the hypoxia-regulatory
field. Target: International Scientists.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speaker: Agnes Görlach: The role of red-ox changes in cancer development.
Andreas Petry: The UPR response controls induction and activation of ADAM17/TACE by severe hypoxia and
ER-stress.
Target: Young PhD-students of partner organisations.
Scientific articles with acknowledgement for METOXIA-support:
 Görlach A: Reactive oxygen species and hypoxia signalling. In: “Tumour Hypoxia: Molecular Mechanisms and
Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN 978-3631-639917. pp 300-322.
 Flügel D, Görlach A, Kietzmann T. Glycogen synthase kinase-3β regulates cell growth, migration and
angiogenesis via Fbw7 and USP-28-dependent degradation of hypoxia-inducible factor-1α Blood. 119; (2012)
1292-301.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
 Kleikers PW, Wingler K, Hermans JJ, Diebold I, Altenhöfer S, Radermacher KA, Janssen B, Görlach A, Schmidt
HH. NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury. J Mol
Med (Berl). 90; (2012) 1391-406.
 Diebold I, Petry A, Sabrane K, Djordjevic T, Hess J, Görlach A. The HIF1 Target Gene NOX2 Promotes
Angiogenesis by Urotensin-II, J Cell Sci. 125; (2012) 956-64.
 Rzymski T, Petry A, Kracun D, Pike L, Harris AL, Görlach A: The unfolded protein response controls induction and
activation of ADAM17/TACE by severe hypoxia and ER-stress, Oncogene. 31; (2012) 3621-3634.
 Grunewald TG, Diebold I, Esposito I, Plehm S, Hauer K, Thiel U, da Silva-Buttkus P, Neff F, Unland R, MüllerTidow C, Zobywalski C, Lohrig K, Lewandrowski U, Sickmann A, da Costa OP, Görlach A, Cossarizza A, Butt E,
Richter GH, Burdach S: STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing
Tumors. Mol Cancer Res. 10; (2012) 52-65.
 Valcu CM, Reger K, Ebner J, Görlach A. Accounting for biological variation in differential display twodimensional electrophoresis experiments.J Proteomics. 75; (2012) 3585-91.
 Petry A, BelAiba RS, Weitnauer M, Görlach A. Inhibition of endothelial nitric oxide synthase increases capillary
formation via Rac1-dependent induction of hypoxia-inducible factor-1α and plasminogen activator inhibitor1.Thromb Haemost. 108; (2012) 849-62.
 Valcu CM , Reger K, Weitnauer M, Linne U, Görlach A.: Proteomic profiling of NOX1 depleted HepG2 cells,
submitted.
Book chapters:
 Görlach A, Reactive oxygen species and hypoxia signalling, in Pastorekova S., Kopacek J (eds). Tumor
hypoxia: Molecular mechanisms and clinical applications, Peter Lang GmbH, Frankfurt/M, 2012, p. 299-322
 Görlach A. Hypoxia and reactive oxygen species, in Melillo G (ed) Hypoxia and Cancer - Biological
Implications and Therapeutic Opportunities-Cancer Drug Discovery and Development, Springer, in press
13/CNRS:
 27th-28st Jan 2012, Plenary Lecture, Molecular Imaging & Biology in Oncology (MIBO) workshop, Nice Speaker:
Jacques Pouyssegur.
 8th February 2012, Meeting Contrat ARC Libre Chloe Feral, Pierre Fafournoux, Renaud LeFloch, Nice, France.
Speaker Jacques Pouyssegur.
 14th February 2012, Meeting Académie des Sciences, Prize committee, Paris. Speaker Jacques Pouyssegur.
 16th-17th February 2012, Rudbeck Life Science Symposium, 2nd Chiba-Uppsala Meeting, Uppsala, Sweden.
Invited speaker Jacques Pouyssegur: Tumor and metabolism. Objective: To give an over-view over the
hypoxia-regulatory field. Target: International Scientists.
 31st March-5th April 2012, American Association Cancer Research, Chicago, USA. Speaker Jacques
Pouyssegur.
 18th-21st April 2012, International Annual Porto Cancer meeting, Porto, Portugal. Invited speaker Jacques
Pouyssegur.
 23rd-26th April 2012, Two lectures 4th HKU - Pasteur Cell Biology Course, Hong Kong, China, Invited speaker
Jacques Pouyssegur.
 10th May 2012, Lecture invitation by Prof. jacques Haiech, University of Strasbourg. Invited speaker Jacques
Pouyssegur.
 2nd-5th June 2012, 17th International Vascular Biology Meeting, Wiesbaden, Germany. Speaker Jacques
Pouyssegur: Hypoxia, metabolism and cancer – novel anticancer approaches. Objective: To give an overview over the hypoxia-regulatory field. Target: International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia.
Speaker: Nathalie Mazure: Key role of Hypoxia-inducible MCT4 in pH regulation and Tumor Growth. Objective:
To discuss last year progress in 13/CNRS within METOXIA. Target: All partners of METOXIA.
 19th-20th June 2012, Journée Recherche fondamentale et clinique EUROCANCER, Paris, France. Speaker
Jacques Pouyssegur.
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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
 24th-26th June 2012, Lecture and Honor to Philip Cohen, 21 years of MRC, Dundee, Scotland. Invited speaker
Jacques Pouyssegur.
 4th-9th July, 22nd IUBMB & 37th FEBS Congress, Sevilla, Spain. Speaker Ibtissam Marchiq: Hypoxia signalling &
tumour metabolism. novel therapeutic approaches. Objective: To give an over-view over the hypoxiaregulatory field. Target: International Scientists.
 17th-19th September 2012, Annual Danish Cancer Symposium, “Cancer metabolism”, Copenhagen, Denmark.
Invited speaker Jacques Pouyssegur.
 22nd-25th September 2012, Annual EMBO Meeting, Nice, France. Chairman: Jacques Pouyssegur.
 1st-2nd October 2012, Lecture International Symposium Fondation RITC, Toulouse. Invited speaker Jacques
Pouyssegur.
 9th-10th October 2012, 2nd International Symposium INCa, Paris, France. Invited speaker Jacques Pouyssegur.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speaker: Jacques Pouyssegur: Metabolic reprogramming.
Joffry Pelletier: The asparaginal hydroxylase factor inhibiting HIF is essential for tumour growth through
supperession of the p53-p21 axis.
Ibtissam Marchiq: Genetic disruption of CD147/Basigin a subunit of lactate-H+ symporters (MCTs) sensitizes
glycolytic tumour cells to phenformin.
Target: Young PhD-students of partner organisations.
 28th October-9th November 2012, 2nd South American Symposium in Signal Transduction & Mol. Med.,
Bariloche, Argentina. Speaker: Jaques Pouyssegur: Hypoxia signaling and Cancer Metabolism - Novel
anticancer approaches. Objective: To give an over-view over the hypoxia-regulatory field. Target:
International Scientists.
 13th-17th November 2012, International Conference on Tumor Microenvironment, Suzhou Dushu, China.
Invited speaker Jacques Pouyssegur: Genetic disruption of CD147/ Basigin, a subunit of lactateH+/symporters (MCTs), Sensitizes Glycolytic Tumour cells to Phenformin. Objective: To give an over-view
over the hypoxia-regulatory field. Target: International Scientists.
 18th December 2012, Lecture : Annual Colloqium of LERMIT «therapeutic innovations», Paris, France. Invited
speaker Jacques Pouyssegur.
Scientific articles with acknowledgement for METOXIA-support:
 Parks SK, Mazure NM, Counillon L, Pouysségur J.: Hypoxia promotes tumor cell survival in acidic conditions
by preserving ATP levels. J Cell Physiol. 2013 Mar 4. doi: 10.1002/jcp.24346. [Epub ahead of print].
 Doyen J, Parks SK, Marcié S, Pouysségur J, Chiche J.: Knock-down of hypoxia-induced carbonic anhydrases IX
and XII radiosensitizes tumor cells by increasing intracellular acidosis. Front Oncol. 2012;2:199. doi:
10.3389/fonc.2012.00199. Epub 2013 Jan 7.
 Pelletier J, Bellot G, Gounon P, Lacas-Gervais S, Pouysségur J, Mazure NM.: Glycogen Synthesis is Induced in
Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival. Front Oncol. 2012;2:18. doi:
10.3389/fonc.2012.00018. Epub 2012 Feb 28.
 Brahimi-Horn MC, Ben-Hail D, Ilie M, Gounon P, Rouleau M, Hofman V, Doyen J, Mari B, Shoshan-Barmatz V,
Hofman P, Pouysségur J, Mazure NM.: Expression of a truncated active form of VDAC1 in lung cancer associates
with hypoxic cell survival and correlates with progression to chemotherapy resistance. Cancer Res. 2012 Apr
15;72(8):2140-50. doi: 10.1158/0008-5472.CAN-11-3940. Epub 2012 Mar 2.
 Ibtissam M, Le Floch R, Critchlow SE, Roux D, Pouysségur J.: Genetic targeting of MCT/CD147 complexes
ablate Lactic acid export and sensitizes Glycolytic tumour cells to Metformin. Manuscript in preparation.
 Chiche J, Fur YL, Vilmen C, Frassineti F, Daniel L, Halestrap AP, Cozzone PJ, Pouysségur J, Lutz NW: In vivo pH in
metabolic-defective Ras-transformed fibroblast tumors: Key role of the monocarboxylate transporter, MCT4,
for inducing an alkaline intracellular pH. Int J Cancer 130; (2012) 1511-1520.
 Pelletier J, Dayan F, Durivault J, Ilc K, Pécou E, Pouysségur J, Mazure NM: The asparaginyl hydroxylase factorinhibiting HIF is essential for tumor growth through suppression of the p53-p21 axis. Oncogene 31; (2012)
2989-3001.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
14/ALU-FR:
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Jochen Kieninger: An
over-view over approaches for ROS sensors and other micro-environmental controllers worked on at ALU-FR.
Objective: Follow-up of the sensor and 3D model sub-group discussions in Madrid 30th September 2011
Target: Participants of the CAIXi-sub-group of METOXIA.
 15th-18th May 2012, 22nd Anniversary World Congress on Biosensors, Cancun, Mexico. Speakers: Jochen
Kieninger: Cell culture monitoring with integrated biosensors for novel insights into metabolic pathways in
tumor cells. And Hubert Flamm: Enzyme less superoxide sensor for longtime monitoring in tumour cell culture.
Objective: To give an over-view over the micro-environmental sensor field on superoxide. Target:
International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers Jochen
Kieninger and Hubert Flamm: Optimization of the ROS sensors.
Objective: To discuss last year progress in 14/ALU-FR within METOXIA. Target: All partners of METOXIA.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speaker: Jochen Kieninger: Measuring of biological parameters of the tumor microenvironment advantages and limitations of micro-sensors.
Hubert Flamm: Global and local oxygen control in in vitro systems.
Kinga Slotwinsky: Monitoring platform with microfluidics for tumour cell culture screening.
Angelina Müller: From NO to HNO development of a novel sensor principle.
Target: Young PhD-students of partner organisations.
Scientific articles with acknowledgement for METOXIA-support:
15/Jobst:
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Gerhard Jobst: An
over-view of in vitro and in vivo approaches worked on at Jobst Technologies to monitor and control microenvironmental parameters. Objective: Follow-up of the sensor and 3D model sub-group discussions in Madrid
30th September 2011 Target: Participants of the CAIXi-sub-group of METOXIA.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers Gerhard
Jobst: Application development update of pericellular oxygen tension control.
Objective: To discuss last year progress in 15/Jobst within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
16/VX:
 9th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
of micro-environment sensors and Nova Matrix 3D models” in Munich, Germany. Speaker Jan Villadsen:
Wireless transmission of data from a micro-environmental glove-box. Objective: Follow-up of the sensor and
3D model sub-group discussions in Madrid 30th September 2011 Target: Participants of the CAIXi-sub-group of
METOXIA.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers Jan
Villadsen: Wireless data transfer in micro-environmental parameter recording.
Objective: To discuss last year progress in 16/VX within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
17/UCL:
 18th-20th April 2012, HypoxiaNet Workshop Learning from Hypoxia Signaling, Bilbao, Spain, Speaker Patrick
Maxwell: Translational medicine “hypoxia and related diseases”.
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
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speaker Patrick
Maxwell: Evaluation of arginine depletion with Arginine Deiminase as a therapeutic strategy
Objective: To discuss last year progress in 17/UCL within METOXIA. Target: All partners of METOXIA.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speaker: Patrick Maxwell: Hypoxia-inducible factor in cell biology.
Target: Young PhD-students of partner organisations.
Scientific articles with acknowledgement for METOXIA-support:
 Connor TMF, Maxwell P: VHL inactivation In: “Tumour Hypoxia: Molecular Mechanisms and Clinical
Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN 978-3631-63991-7. pp
66-105.
18/IVSAS:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker Silvia Pastorekova: Models,
possibility for toxicology studies and 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.
 11th-15th April 2012, 9th International Conference on Carbonic Anhydrase, Antalya, Turkey. Invited lectures:
I: Pastorekova S, Zatovicova M, Iuliano F, Barathova M, Csaderova L, Ditte P, Takacova M, Labudova M,
Sedlakova O, Svastova E, Kopacek J, Pastorek J. Acetazolamide – more than carbonic anhydrase inhibitor.
II: Pastorek J, Ditte P, Dequiedt F, Hulikova A, Svastova E, Zatovicova M, Kopacek J, Supuran CT, Pastorekova S.
Regulation of the CA IX function by phosphorylation in response to physiological stimuli.
III: Svastova E, Csaderova L, Witarski W, Hulikova A, Zatovicova M, Barathova M, Skvarkova L, Kopacek J,
Pastorek J, Pastorekova S. The role of CA IX in cell migration and invasion.
Posters:
I: Bartosova M, Skvarkova L, Zatovicova M, Vidlickova I, Csaderova L, Barathova M, Breza J, Jr, Bujdak P,
Pastorek J, Breza J, Sr, Pastorekova S, Takacova M. Comparative study of CA IX as a tumor tissue versus
circulating blood biomarker.
II: Csaderova L, Hulikova A, Zatovicova M, Barathova M, Skvarkova L, Kopacek J, Pastorek J, Pastorekova S,
Svastova E. CA IX-induced changes in migration-related cell parameters.
III: Ditte P, Dequiedt F, Hulikova A, Svastova E, Zatovicova M, Kopacek J, Supuran CT, Pastorekova S, Pastorek J.
Protein kinase A controls the capacity of CA IX to acidify extracellular pH in hypoxia.
IV: Radvak P, Repic M, Svastova E, Takacova M, Csaderova L, Pastorek J, Pastorekova S, Kopacek J. Signal
transduction pathways downstream of CA IX.
V: Zatovicova M, Vidlickova I, Supalova L, Dequiedt F, Ditte P, Pastorek J, Pastorekova S. Shedding of CA IX
ectodomain in response to cell death.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 18th-20 April 2012, Meeting of the COST action TD0901 HypoxiaNet, Bilbao, Spain, Invited lectures:
I: Pastorekova S, Svastova E, Ditte P, Zatovicova M, Hulikova A, Kosik I, Csaderova L, Kopacek J, Pastorek J.
Hypoxia-induced phosphorylation of carbonic anhydrase IX and its impact on pH regulation and cell migration.
II: Radvak P, Svastova E, Takacova M, Csaderova L, Pastorek J, Pastorekova S. Kopacek J. Expression profiling of
CA IX depleted fibrosarcoma cells.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. 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 in 18/IVSAS within METOXIA. 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
 26th-29th August 2012, XXIII. Biochemical meeting of the Czech and Slovak biochemical societies, Brno, Czech
Republic. Speaker Silvia Pastorekova: Pastorekova S, Zatovicova M, Iuliano F, Barathova M, Csaderova L,
Ditte P, Takacova M, Labudova M, Sedlakova O, Svastova E, Kopacek J, Pastorek J. Carbonic anhydrase
inhibitor acetazolamide modulates transcription and shedding of tumor hypoxia-related carbonic anhydrase
IX. Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 17th-19th September 2012, 18th Cancer Symposium: “Metabolism and Cancer”, Danish Cancer Society,
Copenhagen, Denmark, Invited lecture: Pastorekova S. Carbonic anhydrase IX: Regulation and role in cancer
development. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
Scientists.
 4th-9th October 2012, Aegean Conferences Series: Tumor Microenvironment and Cellular Stress: Signaling,
Metabolism, Imaging and Therapeutic Targets, Chania, Greece. Speaker: Pastorekova S: Pastorekova S,
Svastova E, Zatovicova M, Ditte P, Csaderova L, Takacova M, Kopacek J, Pastorek J. The role of HIF-inducible
carbonic anhydrase IX in tumor microenvironment and approaches to its therapeutic targeting. Objective: To
give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Silvia Pastorekova: The role of carbonic anhydrase IX in tumour acidosis and strategies for its
therapeutic targeting.
Peter Radvak: Signal transduction pathways downstream of CAIX.
Target: Young PhD-students of partner organisations.
Scientific articles with acknowledgement for METOXIA support:
 Svastova E, Pastorekova S. Hypoxia, regulation of pH and cell migration/invasion. In: “Tumour Hypoxia:
Molecular Mechanisms and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH
(2012) ISBN 978-3631-63991-7. pp 285-298.
 Takacova M, Goliasova T, Kopacek J. Hypoxia and oncogenic viruses. In: “Tumour Hypoxia: Molecular
Mechanisms and Clinical Implications” (Ed: Silvia Pastorekova and Juraj Kopacek) Peter Lang GmbH (2012) ISBN
978-3631-63991-7. pp 373-396.
 Svastova E, Pastorekova S. Carbonic anhydrase IX: A hypoxia-controlled "catalyst" of cell migration. Cell Adh
Migr. 2013 7(2). [Epub ahead of print].
 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. 29; (2013) 1147-53.
 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. Oncology Letters 5; (2013) 191-197.
 Svastova E, Witarski W, Csaderova L, Kosik I, Skvarkova L, Hulikova A, Zatovicova M, Barathova M, Kopacek
J, Pastorek J, Pastorekova S. Carbonic anhydrase IX interacts with bicarbonate transporters in lamellipodia
and increases cell migration via its catalytic domain. J Biol Chem 287; (2012) 3392-402.
19/IBT:
 12th -17th February 2012, Keystone Symosia; “Advances in Hypoxic Signaling: From Bench to Bedside (Q4)”,
Banff, Alberta, Canada. Speaker Arvydas kanopka:
I: E. Jakubauskienė, I. Pečiulienė, Y. Makino, L. Poellinger, A. Kanopka Role of 65 kDa protein in regulation of
HIF-3 pre-mRNA splicing.
II: S.Laurinavičius, L Vilys, I. Pečiulienė, E. Jakubauskienė, Y. Makino, A. Kanopka Role of JMJD6 on the
hypoxia-dependent pre-mRNA splicing.
Objective: To give an over-view over the hypoxia-regulatory field. Target: International Scientists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers Arvydas
Kanopka and E. Jakubauskiene: Summing up on the role of the splicing factor U2AF65 in the reprogramming of
cellular pre-mRNA splicing from normoxic to hypoxic activity.
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
Objective: To discuss last year progress in 1/UIO within METOXIA. Target: All partners of METOXIA.
Scientific articles with acknowledgement for METOXIA-support:
20/GROW-UM:
 8th March 2012 METOXIA sub-group meeting on the theme “Further development within the METOXIA-project
period as guided by the CR-UK proposed programme” in Munich, Germany. Speaker Brad Wouters: Tumour
models, possibility for toxicology studies and imaging. 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.
 9th-13th May 2012 ESTRO meeting Barcelona, Spain. Speakers Brad Wouters: Clinical relevance of tumour
micro-environment and metabolism. Brad Wouters: Novel mechanisms of oxygen sensing and adaptation to
hypoxic stress. Objective: To give an over-view over the hypoxia-regulatory field. Target: International
research scientists within radiation oncology.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Brad Wouters:
Pattern of UPR- and mTOR responsive genes as markers of hypoxia-mediated treatment resistance. Possible
new targets.
Also speaker: Brad Wouters and Ludwig Dubois: Possible in vivo pre-clinical models for testing of new drugs
(like CAIX-inhibitors and bioreductive compounds) in connection with CR-UK demands.
Objective: To discuss last year progress in 20/GROW-UM within METOXIA. Target: All partners of METOXIA.
 12th-16th November 2012: Transatlantic Science Week, Rice University and MD Anderson Cancer Center,
Houston, Texas, USA.
Speaker: Brad Wouters: Pattern of UPR- and mTOR responsive genes as markers of hypoxia-mediated
treatment resistance. Possible new targets for therapy. Objective: To give an over-view over the hypoxiaregulatory field. Target: International research scientists within radiation oncology.
Scientific articles with acknowledgement for METOXIA-support:
 Rouschop KM, 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 Mar 7. [Epub ahead of
print].
 Starmans MHW, Pintilie M, John T, Der SD, Shepherd FA, Jurisica I, Lambin P, Tsao MS, Boutros PC: Exploiting
the Noise: Exploiting the noice: improving biomarkers with ensembles of data analysis methodologies. Genome
Med, 2012, 4(11): 84.
 Starmans MHW, Chu KC, Haider S, Nguyen F, Seigneuric R, Magagnin MG, Koritzinsky M, Kasprzyk A,
Boutros PC, Wouters BG, Lambin P: The prognostic value of temporal in vitro and in vivo derived hypoxia
gene-expression signatures in breast cancer. Radiother Oncol, 102; (2012) 436-443.
21/OU:
 27th February-2nd March 2012, International Conference on Translational Research in Radiation Oncology –
Physics for Health in Europe, Geneva, Switzerland, Oral presentation by HB Ragnum: “Androgen Deprivation
Therapy Prior to Irradiation of Prostate Cancer: Expression of Hypoxia-Induced Proteins and Changes in
Diffusion Weighted MRI Parameters”. Objective: To give an over-view over the hypoxia-regulatory field.
Target: International research scientists within radiation oncology.
 9th-13th May 2012 ESTRO meeting Barcelona, Spain. Speakers E. Andersen: Impact of tumor delineation
errors on outcome prediction based on DCE-MRI of cervical cancer patients receiving RT. Target:
International research scientists within radiation oncology.
 14th-16th May 2012, Global Academic Programs 2012 Conference, Oslo Norway. Oral presentation by Anne
Hansen Ree: “Tumor Kinome Profiling in Recal Cancer – Identification of Functional Biomarkers of Signaling
Pathway Druggability”. Objective: To give an over-view over treatment of colorectal cancer. Target:
International oncology specialists.
 11th – 13th June 2012 The 4th General Assembly Meeting of METOXIA in Bratislava, Slovakia. Speakers:
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Metastatic tumours facilitated by hypoxic tumour micro-environment
EU 7th Research Framework Programme
Grant Agreement No. HEALTH-F2-2009-222741
Kjersti Flatmark: Chemoradiotherapy in locally advanced rectal cancer: CAIX inhibitors as radiosensitizers initial in vitro and in vivo experiments.
Mohammad Reza Mirlashari: New plans for the 21/OU-Kragh group: Cell proliferation of mesenchymal stem
cells under Normoxia versus Hypoxia.
Objective: To discuss last year progress in 20/OU within METOXIA. Target: All partners of METOXIA.
 15th June 2012, Current Topics in Cancer Biophysics Seminar Series, Oslo Norway. Oral presentation: HB
Ragnum: Repression of Hypoxia-Inducible Genes under Androgen Deprivation of Prostate Cancer. Objective:
To give an over-view over the hypoxia-regulatory field. Target: International research scientists within
radiation oncology.
 12th-15th September 2012, Annual Scientific Meeting of the Canadian Association of Radiation Oncology,
Ottawa Canada. Keynote address by Annr Hansen Ree: Design and Conduct of Trials Combining
Radiotherapy and Targeted Therapeutics. Objective: To give an over-view over the radiotherapy field.
Target: International radiation oncology specialists.
 10th-13th October 2012: METOXIA-course for PhD-students of METOXIA partner organisations at the NH Hotel
Maastricht, Address Forum 110, 6229GV Maastricht, the Netherlands: THEME: Tumour Hypoxia: From Biology
to Therapy III.
Speakers: Heidi Lyng: Tumour hypoxia detection and prognostic significance.
Harald Rognum: Reduced expression of hypoxia-inducible genes under androgen deprivation of prostate
cancer.
Target: Young PhD-students of partner organisations.
 26th October 2012, PamGene’s Triple T Conference – Tailoring Targeted Therapies, Den Bosch, The Netherlands.
Invited speaker: Anne Hansen Ree: Response Prediction in Locally Advanced Rectal Cancer. Target:
International oncology specialists.
 12th-16th November 2012: Transatlantic Science Week, Rice University and MD Anderson Cancer Center,
Houston, Texas, USA. Invited speaker: Heidi Lyng: Hypoxia Biomarkers for Personalized Radiotherapy.
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:
 Røe K, Mikalsen LT, van der Kogel AJ, Bussink J, Lyng H, Ree AH, Marignol L, Olsen DR.: Vascular responses
to radiotherapy and androgen-deprivation therapy in experimental prostate cancer. Radiat Oncol. 2012
May 23;7:75. doi: 10.1186/1748-717X-7-75.
 Ree AH, Kristensen AT, Saelen MG, de Wijn R, Edvardsen H, Jovanovic J, Abrahamsen TW, Dueland S,
Flatmark K.: Tumor phosphatidylinositol-3-kinase signaling and development of metastatic disease in locally
advanced rectal cancer.PLoS One. 2012;7(11):e50806. doi: 10.1371/journal.pone.0050806. Epub 2012 Nov
30.
 Saelen MG, Ree AH, Kristian A, Fleten KG, Furre T, Hektoen HH, Flatmark K.: Radiosensitization by the
histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal
carcinoma. Radiat Oncol. 2012 Sep 27;7:165. doi: 10.1186/1748-717X-7-165.
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