ANNUAL REPORT EDUCATION ACTIVITIES 336 STAFF 338

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3 PREFACE ANNUAL REPORT MARIO NEGRI INSTITUTE, MILAN DEPARTMENTS Department of Oncology.. 7 Department of Environmental Health Sciences Department of Neuroscience.. 69 Department of Cardiovascular Research Department of Molecular Biochemistry and Pharmacology Department of Epidemiology LABORATORIES AND CENTERS Laboratory of Regulatory Policies Laboratory for Mother and Child Health Centre of Computer Science Engineering. 226 Italian Cochrane Center The Catullo and Daniela Borgomainerio Center 236 Library NEGRI BERGAMO LABORATORIES DEPARTMENTS Department of Molecular Medicine Department of Biomedical Engineering. 264 Laboratory of Biology and Therapy of Metastasis ALDO and CELE DACCO CENTER DEPARTMENT Department of Renal Medicine. 282 LABORATORIES AND CENTERS Laboratory of Clinical Epidemiology. 306 Laboratory of Coordination of Diagnosis and Information on Rare Diseases A. and A. Valenti Health Economics Center, CESAV. 326 The Transplant Research Center. 334 EDUCATION ACTIVITIES 336 STAFF 338 All the staff of the Institute is listed on its website PUBLICATIONS A comprehensive list of the Institute s publications is available on the website Section Publications 1

4 Edited by Isabella Bordogna printed May

5 PREFACE This booklet provides a brief description of the research and training work done at the Mario Negri Institutes in Milan and Bergamo. It is divided by departments, and in some cases by single laboratories. Details of the results are provided in the text itself, so here we shall just draw a few general remarks. Compared to previous years, our research programs are increasingly spreading out to involve the collaboration among several laboratories within each department, and some are interdepartmental. We have slimmed down the number of research topics in order to focus more closely, to reach a critical mass of scientists and resources employed on each theme. The tendency nowadays is towards widespread use of molecular biology techniques, especially for studying the mechanism of action of drugs. In vitro studies are an essential basis for thorough investigations although a significant number of in vivo experiments are still needed as this is the only mean we have of validating in vitro findings and establishing models that resemble human diseases as closely as possible. This has led to a substantial increase in the use of transgenic animals. The Institute is still concentrating on its traditional research lines: oncology, neurosciences, cardiovascular and renal diseases, organ transplants with strong cell biology and molecular biochemistry connotations. Significant work has been carried out on the environment and health as a whole. Experimental, clinical and epidemiological research on rare diseases and orphan drugs is growing all the time. The Mario Negri Institute strives to develop a multifaceted approach to all these research themes, ranging from basic research, to pharmacokinetics, pharmacology, controlled clinical trials, epidemiological analysis and whenever possible the epidemiology of services. So far we have published more than articles on peer reviewed scientific journals. If research is to continue young scientists must be continually trained. Working in the laboratory not only gives them an outlet for their ideas, but enables them to obtain worthwhile qualifications by taking part in the Institute s training schemes, which are recognised by the Lombardy Region in Italy, or by working for a Ph.D. awarded by the Open University, UK. Training courses are also available on biomedical statistics, for general practitioners, family pediatricians, and clinical trial nurses. A vital part of the Institute s work involves providing information, at all levels. This is done, in particular, through the Rare Diseases Information Center, the Center for Information on Medicinal Drugs and the Website (www.marionegri.it). Scientific activities have been affected by the recent move to the new headquarters in via G. Masa 19 in Milan, where there is more space and new and modern technologies. These are difficult years for research in Italy, and the Institute is most grateful to all those public and private bodies, foundations and private citizens who generously support the work outlined here, with their steady flow of contributions. Our sincere thanks to all of them. Silvio Garattini Director 3

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7 Mario Negri INSTITUTE FOR PHARMACOLOGICAL RESEARCH Milan ANNUAL REPORT 2007 departments and laboratories 5

8 DEPARTMENT OF ONCOLOGY STAFF Chief Maurizio D INCALCI, M.D. Oncological Studies Office and Documentation Scientific Documentalist Stefania FILIPPESCHI, Chemist Laboratory of Cancer Pharmacology Head Biophysics Unit Head Flow Citometry Unit Head Cancer Clinical Pharmacology Unit Head Maurizio D INCALCI, M.D. Paolo UBEZIO, Phys.D. Eugenio ERBA, Biochem.D Massimo ZUCCHETTI, Chem.Pharm.D. Laboratory of Molecular Pharmacology Head DNA Repair Unit Head Massimo BROGGINI, Ph.D. Giovanna DAMIA, M.D. Laboratory of Biology and Therapy of Metastasis Head Tumor Angiogenesis Unit Head Molecular Cancer Therapeutics Unit Head Raffaella GIAVAZZI, Biol.Sci.D., Ph.D. Giulia TARABOLETTI, Biol.Sci.D. Maria Rosa BANI, Biol.Sci.D., Ph.D. 6

9 Laboratory for the development of new pharmacological strategies Head Valter TORRI, M.D. Laboratory of Clinical Trials Head Irene FLORIANI, Dr.Sci.Biol., Dr.Stat., Ph.D. Laboratory of Translational and Outcome Research in Oncology Head Gynecology Oncology Unit Head Giovanni APOLONE, M.D. Roldano FOSSATI, Dr.Med.Chir. CERP:Center for the Evaluation and Research on Pain Head Giovanni APOLONE, M.D. Laboratory of Medical Research and Consumer Involvement Head Paola MOSCONI, Biol.Sci.D. 7

10 CURRICULA VITAE Maurizio D'Incalci obtained his Medical Degree cum Laude from the University of Milan in After specializing in Pharmacology at the Mario Negri Institute of Milan and in Oncology at the University of Genoa, he worked in the Laboratory of Molecular Pharmacology of the National Cancer Institute in Bethesda, MD, USA. Since 1986 he has been chief of the Laboratory of Cancer Chemotherapy at the Mario Negri Institute and since 1996 he has become chief of the Department of Oncology at the Mario Negri Institute. He has been President of the Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer (EORTC). From 1994 to 1997 he was Chairman of the New Drug Development Coordinating Committee and from 1997 to 2000 he was chairman of the Research Division of the EORTC. He has been member of the Board of the EORTC from April 2000 to From 1997 he is the Preclinical Coordinator of the Southern Europe New Drug Organization (SENDO) and since 2006 the Chairman of the New Agents Committee (NAC). He is on the editorial board of many international cancer-related scientific journals and since September 2000 he is Editor for Experimental Oncology of the European Journal of Cancer. Dr D'Incalci is author of more than 440 papers on cancer chemotherapy published in peer reviewed international journals, and of several chapters in books on cancer chemotherapy. Selected publications Grosso F., Jones R.L. Demetri G.D., Judson I.R., Blay J.Y., Le Cesne A., Sanfilippo R., Casieri P., Collini P., Dileo P., Spreafico C., Stacchiotti S., Tamborini E., Tercero J.C., Jimeno J., D Incalci M., Gronchi A., Fletcher J.A., Pilotti S., Casali P.G. Efficacy of Trabectedin (ET-743) in advanced pre-treated myxoid liposarcomas. Lancet Oncology, 2007; 8: Salvati E., Leonetti C., Rizzo A., Scarsella M., Mottolese M., Galati R., Sperduti I., Stevens M., D Incalci M., Blasco M., Chiorino G., Horard B., Gilson E., Zupi G., Biroccio A. Telomere damage promotes antitumoral activity of the G- quadruplex ligand RHPS4. J. Clin. Invest., 2007; 117: Zongaro S., de Stanchina E., Colombo T., D Incalci M., Giulotto E., Mondello C. Stepwise neoplastic transformation of a telomerase immortalized fibroblast cell line. Cancer Research, 2005; 65:(24): Allavena P., Signorelli M., Chieppa M., Erba E., Bianchi G., Marchesi F., Garbi A., Lissoni A., de Braud F., Jimeno J. and D Incalci M. Anti-inflammatory properties of the novel antitumor agent Yondelis (Trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res., 2005; 65(7): Lupi M., Matera G., Branduardi D., D Incalci M., Ubezio P., Cytostatic and cytotoxic effects of topotecan decoded by a novel mathematical simulation approach, Cancer Research, 2004; 64: Gambacorti-Passerini C., Zucchetti M., Russo D., Frapolli R., Verga M., Bungaro S., Tornaghi L., Rossi F., Pioltelli P., Pogliani E., Corneo G., Alberti D., D Incalci M. Alpha 1 acid glycoprotein (AGP) binds to STI571 and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin. Cancer Res.,2005; 9: Tavecchio M., Natoli C., Ubezio P., Erba E., D Incalci M. Dynamics of cell cycle phase perturbations by Trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach. Cell proliferation, 2007; 40: Giovanni Apolone, got his Medical degree in 1982 (Pavia, Italy) and his post-doctoral specializations in Internal Medicine in 1987 (Pavia, Italy) and Pharmacological Research (1992). He is Head of the Laboratory of Translational and Outcome Research. He is also Vice-President of the Ethics Committee of the European Institute of Oncology in Milan (Italy) and listed as National Expert at the European Agency for the Evaluation of Medicinal products (EMEA) in London (UK). His main fields of interest are: Methodological, ethical and regulatory aspects of clinical research, with special emphasis on oncology and the cancer pain. Health care evaluation with special emphasis on oncology; Development and validation of case-mix and patient-reported outcome measures; Education and health promotion research and programs. He has authored or co-authored over 200 publications. 8

11 Selected publications Fossati R, Apolone G, Negri E., Compagnoni A, La Vecchia C, Mangano S, Clivio L, Garattini S, A double-blind, placebo controlled, randomized trial of bupropion for smoking cessation in primary care, Arch Intern Med 2007; 67: Bertele' V, Banzi R, Capasso F, Tafuri G, Trotta F, Apolone G, Garattini S Haematological anticancer drugs in Europe: any added value at the time of approval?, Eur J Clin Pharmacol 2007; 63: Apolone G, Mangano S, Compagnoni A, Negri Emanuele, Mosconi P, Mannino S, Villa M, Zuccaro P, A multidisciplinary project to improve the quality of cancer pain management in Italy. Background, methods and preliminary results J Ambul Care Manage 2006; 29: Apolone G, La Vecchia C, Garattini S. Targeted kinase inhibitors in lung cancer: from EGFR to patients Eur J of Cancer, 2006; 42: Apolone G, Joppi R, Bertelè V & Garattini S. Ten years of marketing approvals of anti-cancer drugs in Europe. Regulatory policy and guidance documents need to find a balance between different pressures BJC 2005; 93: Gallus S, Colombo P, Apolone G, Zuccaro P, La Vecchia C. A tax to prevent the epidemic of lung cancer. Lancet 2005; 366: 288 Massimo Broggini followed the faculty of Science of the University of Milan, got the specialization in Biochemistry at Mario Negri Institute, and the PhD degree at the Open University, London,UK. He worked for a period in the laboratory of Molecular Pharmacology of the National Cancer Institute of Bethesda, Md, in From 1991 is the head of the Molecular Pharmacology Unit of the Mario Negri Institute and from 1999 of the Laboratory of Molecular Pharmacology of the same Institute. His main fields of interest are the study of the mechanism of action of new anticancer agents, the search of proteins and genes altered in human cancer and the study of oncosuppressor genes. He is member of the "Pharmacology and Molecular Mechanisms Group" of the European Organisation for the Research and Treatment of Cancer (EORTC) and of the American Association for Cancer Research. He is in the Editorial board of the European Journal of Cancer. He is author of more than 100 articles published in international journals. Principali pubblicazioni Zangrossi S, Marabese M, Broggini M, Giordano R, D'Erasmo M, Montelatici E, Intini D, Neri A, Pesce M, Rebulla P, Lazzari L. Oct-4 expression in adult human differentiated cells challenges its role as a pure stem cell marker. Stem Cells. 2007;25(7): Marrazzo E, Marchini S, Previdi S, Broggini M. Questioning the oncogenic role of DeltaNp73alpha in different cell lines expressing p53 or not. Cancer Biol Ther. 2006;5(7): Polato F, Codegoni A, Fruscio R, Perego P, Mangioni C, Saha S, Bardelli A, Broggini M. PRL-3 phosphatase is implicated in ovarian cancer growth. Clin Cancer Res : Maffucci T, Piccolo E, Cumashi A, Iezzi M, Riley AM, Saiardi A, Godage HY,Rossi C, Broggini M, Iacobelli S, Potter BV, Innocenti P, Falasca M. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects. Cancer Res. 2005;65: Marabese M, Marchini S, Sabatino MA, Polato F, Vikhanskaya F, Marrazzo E, Riccardi E, Scanziani E, Broggini M. Effects of inducible overexpression of DNp73alpha on cancer cell growth and response to treatment in vitro and in vivo. Cell Death Differ. 2005;12: Sabatino MA, Colombo T, Geroni C, Marchini S, Broggini M. Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin. Clin Cancer Res. 2003;9: Irene Floriani got her degree in Biological Sciences at the University of Milan in 1988, her degree in Biostatistics and Experimental Statistics at the University of Milan in 2003 and her phd in Life Sciences at Open University of London (UK) in After ten-year experience in pharmaceutical industry, in 2002 she became Head of the Biometry and Data Management Unit of the Laboratory of Clinical Research in Oncology and since 2006 she is Head of Laboratory of Clinical Trials. She is also member as bio-statistician of three Italian Ethics Committees. Her main fields of interest are: statistical aspects of methodology of clinical research with focus on Controlled Clinical Trials in Oncology; Systematic Overview of the medical literature and Methodological aspects of diagnostic test evaluation. Selected publications Cascinu S, Labianca R, Barone C, Santoro A, Carnaghi C, Cassano A, Beretta GD, Catalano V, Bertetto O, Barni S, Frontini L, Aitini E, Rota S, Torri V, Floriani I. Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Institute (2007); 99: Ruzzo A, Graziano F, Loupakis F, Rulli E, Canestrari E, Santini D, Catalano V, Ficarelli R, Maltese P, Bisonni R, Masi G, Schiavon G, Giordano P, Giustini L, Falcone A, Tonini G, Silva R, Mattioli R, Floriani I, and Magnani M. 9

12 Phamacogeneic profiling in patients with advanced colorectal cancer treated first-line FOLFOX-4 chemotherapy Annals of Oncology (2007); 25: Cazzaniga M, Mustacchi G, Pronzato P, De Matteis A, Di Costanzo F, Floriani I on behalf of the NORA Study Group Adjuvant treatment of early breast cancer: do the St Gallen recommendations influence clinical practice? Results from the NORA study. Annals of Oncology (2007); 18: Mandalà M, Reni M, Cascinu S, Barni S, Floriani I, Cereda S, Berardi R, Mosconi S, Torri V, Labianca R. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Annals of Oncology (2007); 10: Mustacchi G, Cazzaniga ME, Pronzato P, De Matteis A, Di Costanzo F, Floriani I on Behalf of the NORA Study Group. Breast cancer in elderly women: a different reality? Results from the NORA study. Annals of Oncology (2007); 18: Gregorc V, Spreafico A, Floriani I, Colombo B, Ludovini V, Pistola L, Bellezza G, Vigano MG, Villa E, Corti A. Prognostic value of circulating chromogranin A and soluble tumor necrosis factor receptors in advanced nonsmall cell lung cancer. Cancer (2007); 110; Raffaella Giavazzi got her Biological Sciences degree (1979) at the University of Milan, and her Ph.D. in Pharmacology at the Mario Negri Institute of Milan (1984), followed by a specialization in pharmacology (1994) at the University of Milan. From 1981 to 1983 she was a Fellow in the Cancer Metastasis and Treatment Laboratory, NCI-FCRDC, Frederick, MD., and from 1983 to 1985 Assistant Professor at the Department of Cell Biology of M.D. Anderson Hospital and Tumour Institute, University of Texas System Cancer Centre in Houston (TX). Raffaella Giavazzi s research interests are in the field of tumour biology and pharmacology. Specifically, she is studying aspects related to the metastatic process and angiogenesis. She is involved in the preclinical evaluation of new therapeutic strategies against cancer focusing on the angiogenesis inhibitors and combination therapies. From 1986 to 1993 she was Head of the Cancer Metastasis Treatment Unit and since 1993 she has been the Head of the Laboratory of Biology and Treatment of Metastasis at Mario Negri Institute for Pharmacological Research. She is also adjutant Professor in Oncology, Medical School-University of Brescia, member of the Teaching Committee for the PhD course in Physiology-Pharmacology-Molecular and Cellular Tossicology-University of Siena, member of the Executive Committee at SENDO (South Europe New Drug Development Organization) and member of the Pezcoller Foundation Scientific Committee. She was consulting scientist for the NCI-Drug Therapeutics Program, USA ( ); She is a member of the American Association for Cancer Research (AACR), International Metastases Research Society, EORTC-Screening and Pharmacology Group, European Association for Cancer Research (EACR), Italian Cancer Society (SIC) of which she was President ( ). She is on the Editorial Board of the European Journal of Cancer, Journal of Clinical Experimental Metastasis, Journal Exp. Therapeutic & Oncology, The International Journal of Biological Markers, Current Cancer Therapy Reviews and Journal of Chemotherapy. She has published approximately 150 articles on peer reviewed journals and 34 book chapters. Selected publications Martinelli M., Bonezzi K., Riccardi E., Kuhn E., Frapolli R., Zucchetti M., Ryan A.J., Taraboletti G., Giavazzi R.: Sequence dependent antitumour efficacy of the vascular disrupting agent ZD6126 in combination with paclitaxel. British Journal of Cancer 97:888-94, Giavazzi R., Bani M.R.,Taraboletti G.: Tumor host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds. Cancer Metastasis Rev. 26:481 88, 2007 Naumova E., Ubezio P., Garofalo A., Borsotti P., Cassis L., Riccardi E., Scanziani E., Eccles S.A., Bani M.R., Giavazzi R.: The vascular targeting property of paclitaxel is enhanced by SU6668, a receptor tyrosine kinase inhibitor, causing apoptosis of endothelial cells and inhibition of angiogenesis. Clin. Cancer Research 12(6): , Bani M.R., Nicoletti M.I., Alkharouf N.W., Ghilardi C., Petersen D., Erba E., Sausville E.A., Liu E.T., Giavazzi R.: Gene expression correlating with response to paclitaxel in ovarian carcinoma xenografts. Molecular Cancer Therapeutics 3(2): , Belotti D., Paganoni P., Manenti L., Garofalo A., Marchini S., Taraboletti G., Giavazzi R.: Matrix Metalloproteinases (MMP9 and MMP2) Induce the Release of Vascular Endothelial Growth Factor (VEGF) by Ovarian Carcinoma Cells: Implications for Acites Formation. Cancer Res. 63: , Micheletti G., Poli M., Borsotti P., Martinelli M., Imberti B., Taraboletti G., Giavazzi R.: Vascular-targeting Activity of ZD6126, a Novel Tubulin-binding Agent. Cancer Res. 63: , Paola Mosconi got his Biological Science degree (Milan 1982) and the specialisation in Pharmacological Research (Milan 1984). Her main areas of interest are: development of strategies to involve patients- 10

13 consumer associations in health debate, and research projects; assessment of quality of life, translation and cultural adaptation of questionnaires for quality of life; studies to evaluate the type of information on diseases and treatments received by patients, mainly in cancer patients; set-up of websites targeted on consumers/patients studies to evaluate the consumers level of satisfaction with the health services and cure. Paola Mosconi has participated as a teacher, or coordinator, to the realization of training course on Methodological aspects of clinical research or Evaluation of quality of life for health care professionals and representatives of voluntary associations. Selected publications O Connel D, Mosconi P. An active role for patients in clinical research? Drug Development Research 67 (3): , Mosconi P, Colombo Cinzia, La Bianca R, Apolone G. Oncologists' opinions about research ethics committees in Italy: an update, Eur J Cancer Prev 2006; 15: Leone M A, Beghi E, Righini C, Apolone G, Mosconi P. Epilepsy and quality of life in adults: a review of instruments. Epilepsy Research 66: 23-44, Mosconi P, Poli P, Giolo A, Apolone G. How health consumers feel about clinical research: a questionnaire survey. European Journal of Public Health 15: , Mosconi P, Buchanan M, Kyriakides S, Fernandez-Marcos A, Horvatin J, O'Connell D, Zernik N, on behalf of EUROPA DONNA. EUROPA DONNA: has strength in its heterogeneity. European J Cancer 40: , Mosconi P, Apolone G. Fixed and dynamic health related quality of life measurements. J Headache Pain S31-S34, Domenighetti G, D Avanzo B, Egger M, Berrino F, Perneger T, Saracci R, Mosconi P. and M. Zwahlen.Women s perception of the benefits of mammography screening: population-based survey in four countries. Int J Epidem 32: , Valter Torri got his Medical degree in 1985 and the specialization in medical Oncology in 1989 at the University of Milano. Education: 1985: MD Degree with full honors cum Laude, University of Milano; 1988 Post-Doctoral Degree in Pharmacological Research, Mario Negri Institute, Milano; 1989 Post-Doctoral Degree in Medical Oncology, University of Milano; Research Fellow at the Biometric Research Branch of Cancer Treatment Evaluation Program, NCI, Bethesda, MD (USA) Areas of Interest: Statistical aspects of clinical research methodology with focus on Controlled Clinical Trials in Oncology; Systematic Overview of the medical literature; Methodological aspects of diagnostic test evaluation. Present Position: Head of Laboratory of Clinical Research In Oncology, Oncology Department, Mario Negri Institute, Milano. Chronology of Professional Appointments: : Clinical research Fellow in Internal Medicine at the University Hospital, University of Milan; : Research assistant at the Clinical Trial Unit of the Laboratory of Clinical Epidemiology, Mario Negri Institute for Pharmacological Research, Milano; : Research fellow at the Biometric Research Branch of Cancer Treatment Evaluation Program, NCI, Bethesda, MD (USA); 1994: Head of Biometric Unit of the Laboratory of Cancer Clinical Epidemiology, Oncology Department, Mario Negri Institute for Pharmacological Research, Milano, Italy; 1995 Vice Director of the Italian Cochrane Center; 2001: Head of Laboratory of Clinical Research In Oncology, Oncology Department, Mario Negri Institute, Milano. 2006: Head of Laboratory for the development of new pharmacological strategies, Oncology Department, Mario Negri Institute, Milano. Selected publications Mandalà M, Reni M, Cascinu S, Barni S, Floriani I, Cereda S, Berardi R, Mosconi S, Torri V, Labianca R. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Ann Oncol. 2007;18(10): Malesci A, Laghi L, Bianchi P, Delconte G, Randolph A, Torri V, Carnaghi C, Doci R, Rosati R, Montorsi MRoncalli M, Gennari L, Santoro A. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res. 2007;13(13): Garassino MC, Hollander L, Torri V. Bevacizumab for non-small-cell lung cancer. N Engl J Med. 2007;356(13):1373 Cascinu S, Labianca R, Barone C, Santoro A, Carnaghi C, Cassano A, Beretta GD, Catalano V, Bertetto O, Barni S, Frontini L, Aitini E, Rota S, Torri V, FlorianiI; Italian Group for the Study of Digestive Tract Cancer, Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomised controlled trial. J Natl Cancer Inst. 2007;99(8): Graziano F, Kawakami K, Ruzzo A, Watanabe G, Santini D, Pizzagalli F, Bisonni R, Mari D, Floriani I, Catalano V, Silva R, Tonini G, Torri V, Giustini L, Magnani M Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk Italian population. Int J Cancer : Torri V: Clinical trials and data management In: Oxford textbook of oncology, 2nd. ed. Vol. 1. Oxford Univ. Press, Oxford; 2002 :

14 Maria Rosa Bani got her Biological Sciences degree at the University of Milan in 1998 attaining the Italian Government Qualification to practice as Biologist in She obtained the specialization in Pharmacological Research from the Department of Education of the Regional Government of Lombardia in 1991 and the specialization in Biomedical Research from the Department of Education of the Regional Government of Abruzzo in In 2005 she was awarded the degree of Doctor of Philosophy (PhD), Discipline of Life Sciences of the Open University Research School (UK). From 1991 to 1995 she was a Post Doctoral Fellow in the Cancer Research Division, Sunnybrook Health Science Centre, University of Toronto (Canada); from 2000 to 2001 she was Guest Scientist at the Advance Technology Centre, National Cancer Institute, National Institute of Health (USA). At the MarioNegri Institute for Pharmacological Research she was a Fellow Research Scientist in the Laboratory of Biology and Treatment of Metastasis, Bergamo from 1996 to 2002 and she became a Staff Research Scientist in In April 2004 she became Head of the Molecular Cancer Therapeutics Unit. Since 2004 she is the Scientific Manager of STROMA, an integrated project within the 6 th Framework Program of the European Commission [FP6 LSHC-CT , STROMA]. She is a member of the American Association for Cancer Research (AACR), Italian Cancer Society (SIC) and European Association for Cancer Research (EACR). Maria Rosa Bani research interests are in the field of cancer biology and molecular therapeutics. She is co-author of 32 peer reviewed publications, 2 book chapters and 55 proceedings of which 15 selected for oral presentation at international meetings. Selected publications Giavazzi R., Bani M.R.,Taraboletti G.: Tumor host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds. Cancer Metastasis Rev. 26:481 88, Bani M.R., Nicoletti M.I., Alkharouf N.W., Ghilardi C., Petersen D., Erba E., Sausville E.A., Liu E.T. and Giavazzi R. Gene expression correlating with response to paclitaxel in ovarian carcinoma xenografts. Molecular Cancer Therapeutics 3: , Vikhanskaya F.*, Bani M.R.*., Borsotti P., Ghilardi C., Ceruti R., Ghisleni G., Marabese M., Giavazzi R., Broggini M. & Taraboletti G. p73 overexpression increases VEGF and reduces thrombospondin-1 production: implication for tumor angiogenesis. Oncogene 20 : , Taraboletti G., Sonzogni L., Vergani V., Hosseini G., Ceruti R., Ghilardi C., Bastone A., Toschi E., Borsotti P., Scanziani E., Giavazzi R., Pepper M.S., Stetler-Stevenson W.G. & Bani M.R. Post-transcriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells. Experimental Cell Research 258 : , Alessandri G., Chirivi R.G.S., Fiorentini S., Dossi R., Bonardelli S., Giulini S.M., Zanetta G., Landoni F., Graziotti P.P., Turano A., Caruso A., Zardi L. Giavazzi R. & Bani M.R., Phenotypic and functional characteristics of tumor-derived microvascular endothelial cells. Clinical & Experimental Metastasis 17 : , Bani M.R., Rak J., Adachi D., Wiltshire R., Trent J.M., Kerbel R.S. & Ben-David Y. Multiple features of advanced melanoma recapitulated in tumorigenic variants of early stage (radial growth phase) human melanoma cell lines: evidence for a dominant phenotype. Cancer Research 5 : , Giovanna Damia obtained her Medical Degree cum Laude from the University of Milan in After specializing in Pharmacology at the Mario Negri Institute of Milan and in Oncology at the University of Milan, she worked as a post-doctoral fellow in the Laboratory of Experimental Immunology of the National Cancer Institute, Frederick, USA. She worked as a research fellow in the Laboratory of Cancer Chemotherapy at the Mario Negri Institute and since April 2003 she has become chief of the DNA Repair Unit at the Mario Negri Institute. From 1992 to1995 she has been consultant of the General Secretariat of the Progetto Finalizzato CNR "Applicazioni Cliniche della Ricerca Oncologica". Since September 2005 she is Deputy Editor for Experimental Oncology of the European Journal of Cancer. Her main fields of interest are: mechanism of action of anticancer drugs, cell cycle checkpoints and natural compounds. Selected publications Simone M, Erba E, Damia G, Vikhanskaya F, Di Francesco A M, Riccardi R, Baldeyrou B, Bailly C, Cuevas C, Sousa- Faro J M F, D'Incalci M. Variolin B and its derivate deoxy-variolin B: New marine natural compounds with cyclindependent kinase inhibitor activity. Eur J Cancer 2005; 41: Carrassa L, Broggini M, Erba E, Damia G. Chk1, but not Chk2, is involved in the cellular response to DNA damaging agents. Differential activity in cells expressing or not p53. Cell Cycle 2004; 3: Damia G, Broggini M. Improving the selectivity of cancer treatment by interfering with cell response pathways. Eur J Cancer 2004; 40: Damia G, Broggini M. Cell cycle checkpoint proteins and cellular response to treatment by anticancer agents. Cell Cycle 2004; 3:

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