THE INVITED SPEAKERS BRIEF SCIENTIFIC PROFILE Cancer 2006

THE INVITED SPEAKERS – BRIEF SCIENTIFIC PROFILE “Cancer 2006: From molecular biology processes to tumor-tailored therapy” 20 -24, august, 2006 High Tatras, Slovakia

KEYNOTE LECTURE No. 1 Andy Futreal, Ph. D. Co-head of the Cancer Genome Project Wellcome Trust Sanger Institute Hinxton, United Kingdom Title of the lecture: The WTSI Cancer genome Project: understanding the targets

PUBLICATIONS: • Wooster R, Futreal AP, Stratton MR. Sequencing Analysis of BRAF Mutations in Human Cancers. Methods Enzymol. 2005 • Futreal PA, Wooster R, Stratton MR. Somatic mutations in human cancer: insights from resequencing the protein kinase gene family. Cold Spring Harb Symp Quant Biol. 2005 • Stratton MR, Wooster RW, Futreal PA. The BRAF gene is frequently mutated in malignant melanoma. J Drugs Dermatol. 2004 • Blow M, Futreal PA, Wooster R, Stratton MR. A survey of RNA editing in human brain. Genome Res. 2004 • Stratton MR, Futreal PA. Cancer: understanding the target. Nature. 2004 • Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR. A census of human cancer genes. Nat Rev Cancer. 2004

KEYNOTE LECTURE No. 2 Prof. Josef Jiricny Director, Institute of Molecular Cancer Research University of Zürich, Switzerland Title of the lecture: Towards therapy of tumors with microsatellite instability

PUBLICATIONS: • Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 2006 • Cejka P, Stojic L, Marra G, Jiricny J. Is mismatch repair really required for ionizing radiation-induced DNA damage signaling? Nat Genet 2004 • Jiricny J. An APE that proofreads. Nature 2002 • Palombo F, Gallinari P, Iaccarino I, Lettieri T, Hughes M, D'Arrigo A, Truong O, Hsuan JJ, Jiricny J. GTBP, a 160 -kilodalton protein essential for mismatch-binding activity in human cells. Science 1995 • Brown TC, Jiricny J. Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell. 1988

KEYNOTE LECTURE No. 3 Ivan Horak, MD. Vice - Director Enzon Pharmaceuticals, Inc. Research and Development New Jersey, USA Title of the lecture: Targeted therapy: from bench to bedside

PUBLICATIONS: • Karacay H, Brard PY, Sharkey RM, Chang CH, Rossi EA, Mc. Bride WJ, Ragland DR, Horak ID, Goldenberg DM. Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograft. Clin Cancer Res. 2005 • Sharkey RM, Cardillo TM, Rossi EA, Chang CH, Karacay H, Mc. Bride WJ, Hansen HJ, Horak ID, Goldenberg DM. Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody. Nat Med. 2005 • Govindan SV, Griffiths GL, Hansen HJ, Horak ID, Goldenberg DM. Cancer therapy with radiolabeled and drug/toxin-conjugated antibodies. Technol Cancer Res Treat. 2005 • Hartmann F, Horak EM, Cho C, Lupu R, Bolen JB, Stetler-Stevenson MA, Pfreundschuh M, Waldmann TA, Horak ID. Effects of the tyrosine-kinase inhibitor geldanamycin on ligand-induced Her-2/neu activation, receptor expression and proliferation of Her-2 -positive malignant cell lines. Int J Cancer. 1997 • Horak ID, Popovic M, Horak EM, Lucas PJ, Gress RE, June CH, Bolen JB. No T-cell tyrosine protein kinase signalling or calcium mobilization after CD 4 association with HIV-1 or HIV-1 gp 120. Nature. 1990

Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION Prof. Kathleen Boris-Lawrie Department of Veterinary Sciences The Ohio State University, USA Title of the lecture: New insight into translational regulation of growth control genes: lessons derived from study of retroviruses

PUBLICATIONS: • Younis I, Boris-Lawrie K, Green PL. Human T-cell leukemia virus open reading frame II encodes a posttranscriptional repressor that is recruited at the level of transcription. J Virol. 2006 • Altanerova V, Holicova D, Kucerova L, Altaner C, Lairmore MD, Boris-Lawrie K. Long-term infection with retroviral structural gene vector provides protection against bovine leukemia virus disease in rabbits. Virology. 2004 • Roberts TM, Boris-Lawrie K. Primary sequence and secondary structure motifs in spleen necrosis virus RU 5 confer translational utilization of unspliced human immunodeficiency virus type 1 reporter RNA. J Virol. 2003 • Butsch M, Boris-Lawrie K. Destiny of unspliced retroviral RNA: ribosome and/or virion? J Virol. 2002 • Butsch M, Hull S, Wang Y, Roberts TM, Boris-Lawrie K. The 5' RNA terminus of spleen necrosis virus contains a novel posttranscriptional control element that facilitates human immunodeficiency virus Rev/RRE-independent Gag production. J Virol. 1999

Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION Prof. Richard Kettmann Faculty of Agronomy, Gembloux, Belgium Title of the lecture: Metabolic pathways involved in transformational induced by oncoviral Tax proteins

PUBLICATIONS: • Debacq C, Heraud JM, Asquith B, Bangham C, Merien F, Moules V, Mortreux F, Wattel E, Burny A, Kettmann R, Kazanji M, Willems L. Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1. Oncogene. 2005 • Twizere JC, Lefebvre L, Collete D, Debacq C, Urbain P, Heremans H, Jauniaux JC, Burny A, Willems L, Kettmann R. The homeobox protein MSX 2 interacts with tax oncoproteins and represses their transactivation activity. J Biol Chem. 2005 • Dequiedt F, Van Lint J, Lecomte E, Van Duppen V, Seufferlein T, Vandenheede JR, Wattiez R, Kettmann R. Phosphorylation of histone deacetylase 7 by protein kinase D mediates T cell receptor - induced Nur 77 expression and apoptosis. J Exp Med. 2005 • Poturnajova M, Altanerov V, Kettmann R, Feikova S, Hlubinova K, Balazovjech I, Breza J, Fodo G, Knotek J, Matoska J, Podobov M, Altaner C. Germline mutation of the RET proto-oncogene in members of Slovak families with multiple endocrine neoplasia 2. Neoplasma 2001

Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION Prof. Jan Svoboda Professor of cellular and molecular biology CU Institute of Molecular Genetics Prague, Czech Republic Title of the lecture: Cell defense against retroviruses

PUBLICATIONS: • J. Svoboda: Presence of chicken tumour virus in the sarcoma of the adult rat inoculated after birth with Rous sarcoma tissue. Nature 1960 • J. Svoboda: Molecular biology of cell nonpermissiveness to retroviruses. Has the time come? Gene 1998 • J. Svoboda, J. Geryk, D. Elleder: Heterogeneous pathogenicity of retroviruses: Lessons from birds, primates, and rodents. Adv. Canc. Res. 2003 • Hejnar J, Hajkova P, Plachy J, Elleder D, Stepanets V, Svoboda J. Cp. G island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression. Proc Natl Acad Sci U S A. 2001

Session 2: MOLECULAR PATHOGENESIS OF CANCER Karl Heinimann, Ph. D. University of Basel Switzerland Title of the lecture: The mechanism of inactivation of the wild-type allele in hereditary cancers such as FAP and HNPCC

PUBLICATIONS: • Zhang J, Lindroos A, Ollila S, Russell A, Marra G, Mueller H, Peltomaki P, Plasilova M, Heinimann K. Gene conversion is a frequent mechanism of inactivation of the wild-type allele in cancers from MLH 1/MSH 2 deletion carriers. Cancer Res. 2006 • Westphalen AA, Russell AM, Buser M, Berthod CR, Hutter P, Plasilova M, Mueller H, Heinimann K. Evidence for genetic anticipation in hereditary non-polyposis colorectal cancer. Hum Genet. 2005 • Crabtree M, Sieber OM, Lipton L, Hodgson SV, Lamlum H, Thomas HJ, Neale K, Phillips RK, Heinimann K, Tomlinson IP. Refining the relation between 'first hits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients. Oncogene. 2003 • Sieber OM, Lamlum H, Crabtree MD, Rowan AJ, Barclay E, Lipton L, Hodgson S, Thomas HJ, Neale K, Phillips RK, Farrington SM, Dunlop MG, Mueller HJ, Bisgaard ML, Bulow S, Fidalgo P, Albuquerque C, Scarano MI, Bodmer W, Tomlinson IP, Heinimann K. Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. Proc Natl Acad Sci U S A. 2002

Session 2: MOLECULAR PATHOGENESIS OF CANCER Linda Wolff, Ph. D. Chief, Leukemogenesis Section Laboratory of Cellular Oncology, CCR National Cancer Institute, NIH Bethesda, USA Title of the lecture: Cyclin-dependent kinase inhibitor p 15 INK 4 B in leukemia and normal hematopoiesis

PUBLICATIONS: • Hu X, Bies J, Wolff L. Interferon beta increases c-Myc proteolysis in mouse monocyte/macrophage leukemia cells. Leuk Res. 2005 • Schmidt M, Bies J, Tamura T, Ozato K, Wolff L. The interferon regulatory factor ICSBP/IRF-8 in combination with PU. 1 up-regulates expression of tumor suppressor p 15(Ink 4 b) in murine myeloid cells. Blood. 2004 • Wolff L, Garin MT, Koller R, Bies J, Liao W, Malumbres M, Tessarollo L, Powell D, Perella C. Hypermethylation of the Ink 4 b locus in murine myeloid leukemia and increased susceptibility to leukemia in p 15(Ink 4 b)-deficient mice. Oncogene. 2003 • Haviernik P, Schmidt M, Hu X, Wolff L. Consistent inactivation of p 19(Arf) but not p 15(Ink 4 b) in murine myeloid cells transformed in vivo by deregulated c-Myc. Oncogene. 2003 • Schmidt M, Koller R, Haviernik P, Bies J, Maciag K, Wolff L. Deregulated c. Myb expression in murine myeloid leukemias prevents the up-regulation of p 15(INK 4 b) normally associated with differentiation. Oncogene. 2001

Session 2: MOLECULAR PATHOGENESIS OF CANCER Juraj Bies, Ph. D. National Cancer Institute, NIH Bethesda, USA Title of the lecture: Leukemogenesis and c-Myb: story of a tightly regulated transcriptional regulator

PUBLICATIONS: • Markus J, Feikova S, Sramko M, Wolff L, Bies J. Proliferation-linked expression of the novel murine gene m 4 mbt encoding a nuclear zinc finger protein with four mbt domains. Gene. 2003 • Bies J, Markus J, Wolff L. Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity. J Biol Chem. 2002 • Bies J, Feikova S, Markus J, Wolff L. Phosphorylation-dependent conformation and proteolytic stability of c-Myb. Blood Cells Mol Dis. 2001 • Bies J, Feikova S, Bottaro DP, Wolff L. Hyperphosphorylation and increased proteolytic breakdown of c-Myb induced by the inhibition of Ser/Thr protein phosphatases. Oncogene. 2000 • Hu X, Bies J, Wolff L. Interferon beta increases c-Myc proteolysis in mouse monocyte/macrophage leukemia cells. Leuk Res. 2005

Session 3: DNA DAMAGE AND REPAIR PROCESSES I. Bennett Van Houten, Ph. D. Chief, Program Analysis Branch & Investigator in the Laboratory of Molecular Genetics National Institutes of Environmental Health Sciences Research Triangle Park, NC, USA Title of the lecture: In search of damage: Structure-function studies of nucleotide excision repair

PUBLICATIONS: • Santos JH, Meyer JN, Van Houten B. Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis. Hum Mol Genet. 2006 • Truglio JJ, Karakas E, Rhau B, Wang H, Dellavecchia MJ, Van Houten B, Kisker C. Structural basis for DNA recognition and processing by Uvr. B. Nat Struct Mol Biol. 2006 • Truglio JJ, Rhau B, Croteau DL, Wang L, Skorvaga M, Karakas E, Della. Vecchia MJ, Wang H, Van Houten B, Kisker C. Structural insights into the first incision reaction during nucleotide excision repair. EMBO J. 2005 • Skorvaga M, Della. Vecchia MJ, Croteau DL, Theis K, Truglio JJ, Mandavilli BS, Kisker C, Van Houten B. Identification of residues within Uvr. B that are important for efficient DNA binding and damage processing. J Biol Chem. 2004 • Dubaele S, Proietti De Santis L, Bienstock RJ, Keriel A, Stefanini M, Van Houten B, Egly JM. Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients. Mol Cell. 2003

Session 3: DNA DAMAGE AND REPAIR PROCESSES I. Prof. Jiri Lukas Institute of Cancer Biology for Genotoxic Stress Resarch Danish Cancer Society, Copenhagen, Denmark Title of the lecture: Cellular response to DNA damage: Molecular mechanism and spatio-temporal organization in living mammalian cells

PUBLICATIONS: • Bartek J, Lukas J. Cell biology. The stress of finding NEMO. Science. 2006 • Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005 • Lukas J, Bartek J. Cell division: the heart of the cycle. Nature. 2004 • Lukas J, Bartek J. Watching the DNA repair ensemble dance. Cell. 2004 • Bartek J, Lukas J. Are all cancer genes equal? Nature. 2001 • Bartek J, Lukas J. Cell cycle. Order from destruction. Science. 2001.

Session 3: DNA DAMAGE AND REPAIR PROCESSES I. Mark O’Driscoll, Ph. D. Sussex Centre for Genome Damage and Stability University of Sussex Falmer, Brighton Title of the lecture: DNA double strands break repair and cancer predisposition: Lessons from human syndromes

PUBLICATIONS: • O'Driscoll M, Jeggo PA. The role of double-strand break repair - insights from human genetics. Nat Rev Genet. 2006 • Alderton GK, Joenje H, Varon R, Borglum AD, Jeggo PA, O'Driscoll M. Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet. 2004 • O'Driscoll M, Gennery AR, Seidel J, Concannon P, Jeggo PA. An overview of three new disorders associated with genetic instability: LIG 4 syndrome, RS-SCID and ATR-Seckel syndrome. DNA Repair (Amst). 2004 • Gennery AR, O'Driscoll M. Unravelling the web of DNA repair disorders. Clin Exp Immunol. 2003 • O'Driscoll M, Jeggo PA. Clinical impact of ATR checkpoint signalling failure in humans. Cell Cycle. 2003

Session 4: DNA DAMAGE AND REPAIR PROCESSES II. Miroslav Chovanec, Ph. D. Senior investigator Laboratory of Molecular Genetics Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: Cellular response to oxidative DNA damage in Saccharomyces cerevisiae

PUBLICATIONS: • Dudas A, Markova E, Vlasakova D, Kolman A, Bartosova Z, Brozmanova J, Chovanec M. The Escherichia coli Rec. A protein complements recombination defective phenotype of the Saccharomyces cerevisiae rad 52 mutant cells. Yeast. 2003 • Dudas A, Chovanec M. DNA double-strand break repair by homologous recombination. Mutat Res. 2004 • Dudasova Z, Dudas A, Chovanec M. Non-homologous end-joining factors of Saccharomyces cerevisiae. FEMS Microbiol Rev. 2004 • Brozmanova J, Vlckova V, Chovanec M. How heterologously expressed Escherichia coli genes contribute to understanding DNA repair processes in Saccharomyces cerevisiae. Curr Genet. 2004 • Kysela B, Chovanec M, Jeggo PA. Phosphorylation of linker histones by DNA-dependent protein kinase is required for DNA ligase IV-dependent ligation in the presence of histone H 1. Proc Natl Acad Sci U S A. 2005

Session 4: DNA DAMAGE AND REPAIR PROCESSES II. Miroslav Pirsel, Ph. D. Head of Laboratory of Molecular Genetics Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: Repair of oxidative DNA damage in the helicase mutants

PUBLICATIONS: • Wassermann K, Pirsel M, Bohr VA. Overexpression of metallothionein in Chinese hamster ovary cells and its effect on nitrogen mustard - induced cytotoxicity: role of gene-specific damage and repair. Cancer Res. 1992 • Pirsel M, Bohr VA. Methyl methanesulfonate adduct formation and repair in the DHFR gene and in mitochondrial DNA in hamster cells. Carcinogenesis. 1993 • Sedliakova M, Slezarikova V, Masek F, Vizvaryova M, Pirsel M. Role of DNA polymerase II in the tolerance of thymine dimers remaining unexcised in UV-irradiated Escherichia coli exposed to pre-UV nutritional stress. J Photochem Photobiol B. 2001 • Hall H, Gursky J, Nicodemou A, Rybanska I, Kimlickova E, Pirsel M. Characterization of ERCC 3 mutations in the Chinese hamster ovary 27 -1, UV 24 and MMC-2 cell lines. Mutat Res. 2006 • Pirsel M, Chovanec M, Dudas A, Kleibl K, Van Houten B. Fourth DNA repair workshop on DNA damage and repair: mechanisms and biological consequences Smolenice Castle, 2 -5 May 2004. DNA Repair (Amst). 2004

Session 5: CANCER GENETICS Minna Nystrom, Ph. D. Senior scientist & Research Manager Department of Biological and Environmental Sciences University of Helsinki, Finland Title of the lecture: Functional significance and clinical phenotype of non-truncating inherited mismatch repair gene variants

PUBLICATIONS: • Raevaara TE, Korhonen MK, Lohi H, Hampel H, Lynch E, Lonnqvist KE, Holinski-Feder E, Sutter C, Mc. Kinnon W, Duraisamy S, Gerdes AM, Peltomaki P, Kohonen-Ccorish M, Mangold E, Macrae F, Greenblatt M, de la Chapelle A, Nystrom M. Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH 1. Gastroenterology. 2005 • Kariola R, Abdel-Rahman WM, Ollikainen M, Butzow R, Peltomaki P, Nystrom M. APC and beta-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers. Fam Cancer. 2005 • Nystrom-Lahti M, Kristo P, Nicolaides NC, Chang SY, Aaltonen LA, Moisio AL, Jarvinen HJ, Mecklin JP, Kinzler KW, Vogelstein B, et al. Founding mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med. 1995 • Nystrom-Lahti M, Sistonen P, Mecklin JP, Pylkkanen L, Aaltonen LA, Jarvinen H, Weissenbach J, de la Chapelle A, Peltomaki P. Close linkage to chromosome 3 p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc Natl Acad Sci U S A. 1994 • Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M, et al. Mutations of a mut. S homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993

Session 5: CANCER GENETICS Vladimir Zajac, Ph. D. Head of Laboratory of Cancer Genetics Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: FAP and HBOC: two players in one playground

PUBLICATIONS: • Ciernikova S, Tomka M, Kovac M, Stevurkova V, Zajac V. Ashkenazi founder BRCA 1/BRCA 2 mutations in Slovak hereditary breast and/or ovarian cancer families. Neoplasma. 2006 • Kovac M, Tomka M, Ciernikova S, Stevurkova V, Valachova A, Zajac V. Multiple gynecologic tumors as rare associated phenotypes of FAP/Gardner syndrome in a family with the novel germline mutation in the APC gene. Clin Genet. 2006 • Mego M, Koncekova R, Mikuskova E, Drgona L, Ebringer L, Demitrovicova L, Nemova I, Trupl J, Mardiak J, Koza I, Zajac V. Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M 74. Phase II study. Support Care Cancer. 2006 • Anker P, Zajac V, Lyautey J, Lederrey C, Dunand C, Lefort F, Mulcahy H, Heinemann J, Stroun M. Transcession of DNA from bacteria to human cells in culture: a possible role in oncogenesis. Ann N Y Acad Sci. 2004 • Zajac V, Kirchhoff T, Levy ER, Horsley SW, Miller A, Steichen-Gersdorf E, Monaco AP. Characterisation of X; 17(q 12; p 13) translocation breakpoints in a female patient with hypomelanosis of Ito and choroid plexus papilloma. Eur J Hum Genet. 1997

Session 5: CANCER GENETICS Zdena Bartosova, Ph. D. Senior investigator Laboratory of Molecular Genetics Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: Advances in molecular diagnostics of hereditary non-polyposis colorectal cancer in Slovakia

PUBLICATIONS: • Venema J, Bartosova Z, Natarajan AT, van Zeeland AA, Mullenders LH. Transcription affects the rate but not the extent of repair of cyclobutane pyrimidine dimers in the human adenosine deaminase gene. J Biol Chem. 1992 • Bartosova Z, Pirsel M, Reinhold W, Stetler-Stevenson M, Zajac-Kaye M, May A, Horak ID, Bohr VA. Gene-specific repair in human CD 4+ lymphocytes reflects transcription and proliferation. Mutat Res. 1996 • Marra G, D'Atri S, Corti C, Bonmassar L, Cattaruzza MS, Schweizer P, Heinimann K, Bartosova Z, Nystrom-Lahti M, Jiricny J. Tolerance of human MSH 2+/- lymphoblastoid cells to the methylating agent temozolomide. Proc Natl Acad Sci U S A. 2001 • Bartosova Z, Fridrichova I, Bujalkova M, Wolf B, Ilencikova D, Krizan P, Hlavcak P, Palaj J, Lukac L, Lukacova M, Boor A, Haider R, Jiricny J, Nystrom-Lahti M, Marra G. Novel MLH 1 and MSH 2 germline mutations in the first HNPCC families identified in Slovakia. Hum Mutat. 2003 • Zavodna K, Bujalkova M, Krivulcik T, Alemayehu A, Skorvaga M, Marra G, Fridrichova I, Jiricny J, Bartosova Z. Novel and recurrent germline alterations in the MLH 1 and MSH 2 genes identified in hereditary nonpolyposis colorectal cancer patients in Slovakia. Neoplasma 2006

Session 6: TUMOR CELL SIGNALING AND CELL DEATH Prof. Gerhard Christofori Institute of Biochemistry and Genetics University of Basel, Switzerland Title of the lecture: Cell adhesion in tumor invasion and metastasis

PUBLICATIONS: • Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G. Tumor invasion in the absence of epithelial-mesenchymal transition: Podoplaninmediated remodeling of the actin cytoskeleton. Cancer Cell. 2006 • Kopfstein L, Christofori G. Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol Life Sci. 2006 • Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig. CAMs in cancer. Nat Rev Cancer. 2004 • Gannon G, Mandriota SJ, Cui L, Baetens D, Pepper MS, Christofori G. Overexpression of vascular endothelial growth factor-A 165 enhances tumor angiogenesis but not metastasis during beta-cell carcinogenesis. Cancer Res. 2002 • Cavallaro U, Niedermeyer J, Fuxa M, Christofori G. N-CAM modulates tumourcell adhesion to matrix by inducing FGF-receptor signalling. Nat Cell Biol. 2001

Session 6: TUMOR CELL SIGNALING AND CELL DEATH Jozef Bizik, Ph. D. , Ds. C. Senior investigator Laboratory of Molecular Oncology Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: Nemosis – prospective cell based cancer therapy

PUBLICATIONS: • Kankuri E, Cholujova D, Comajova M, Vaheri A, Bizik J. Induction of hepatocyte growth factor/scatter factor by fibroblast clustering directly promotes tumor cell invasiveness. Cancer Res. 2005 • Bizik J, Kankuri E, Ristimaki A, Taieb A, Vapaatalo H, Lubitz W, Vaheri A. Cell-cell contacts trigger programmed necrosis and induce cyclooxygenase 2 expression. Cell Death Differ. 2004 • Eleveld-Trancikova D, Kudela P, Majerciak V, Regendova M, Zelnik V, Pastorek J, Pastorekova S, Bizik J. Suppression subtractive hybridisation to isolate differentially expressed genes involved in invasiveness of melanoma cell line cultured under different conditions. Int J Oncol. 2002 • Vaheri A, Tapiovaara H, Myohanen H, Bizik J. Alpha 2 -macroglobulin in the regulation of pericellular plasminogen activation of human tumor cells. Ann N Y Acad Sci. 1994 • Bizik J, Lizonova A, Grofova M, Matoska J, Dore JF, Bertrand S, Blasko M, Vaheri A. Clonal variation in the production of tumor-associated alpha 2 macroglobulin in a malignant human melanoma and association with growth stimulation. Cancer Res. 1989

Session 7: CARCINOGENESIS / ANTICARCINOGENESIS I. Prof. Leonard Mullenders Department of Toxicogenetics Leiden University Medical Center Leiden, The Netherlands Title of the lecture: From initial DNA damage to cancer: Lessons from mouse models

PUBLICATIONS: • Alekseev S, Kool H, Rebel H, Fousteri M, Moser J, Backendorf C, de Gruijl FR, Vrieling H, Mullenders LH. Enhanced DDB 2 expression protects mice from carcinogenic effects of chronic UV-B irradiation. Cancer Res. 2005 • Fousteri M, van Hoffen A, Vargova H, Mullenders LH. Repair of DNA lesions in chromosomal DNA impact of chromatin structure and Cockayne syndrome proteins. DNA Repair (Amst). 2005 • Riou L, Eveno E, van Hoffen A, van Zeeland AA, Sarasin A, Mullenders LH. Differential repair of the two major UV-induced photolesions in trichothiodystrophy fibroblasts. Cancer Res. 2004 • Buterin T, Hess MT, Gunz D, Geacintov NE, Mullenders LH, Naegeli H. Trapping of DNA nucleotide excision repair factors by nonrepairable carcinogen adducts. Cancer Res. 2002 • Volker M, Mone MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell. 2001

Session 7: CARCINOGENESIS / ANTICARCINOGENESIS I. Prof. Andrew Collins Department of Nutrition, University of Oslo Blindern, Oslo, Norway Title of the lecture: Cancer prevention by fruits and vegetables; not just a question for antioxidants

PUBLICATIONS: • Dusinska M, Dzupinkova Z, Wsolova L, Harrington V, Collins AR. Possible involvement of XPA in repair of oxidative DNA damage deduced from analysis of damage, repair and genotype in a human population study. Mutagenesis. 2006 • Maitland NJ, Collins A. A tumour stem cell hypothesis for the origins of prostate cancer. BJU Int. 2005 • Collins AR. Antioxidant intervention as a route to cancer prevention. Eur J Cancer. 2005 • Gedik CM, Grant G, Morrice PC, Wood SG, Collins AR. Effects of age and dietary restriction on oxidative DNA damage, antioxidant protection and DNA repair in rats. Eur J Nutr. 2005 • Collins AR, Ferguson LR. Nutrition and carcinogenesis. Mutation Research. 2004

Session 8: CARCINOGENESIS / ANTICARCINOGENESIS II. Prof. Krzysztof Szyfter Institute of Human Genetics Polish Academy of Sciences Poznan, Poland Title of the lecture: Modulation of laryngeal cancer incidence and progression by gene polymorphism

PUBLICATIONS: • Rydzanicz M, Wierzbicka M, Gajecka M, Szyfter W, Szyfter K. The impact of genetic factors on the incidence of multiple primary tumors (MPT) of the head and neck. Cancer Lett. 2005 • Gajecka M, Rydzanicz M, Jaskula-Sztul R, Kujawski M, Szyfter W, Szyfter K. CYP 1 A 1, CYP 2 D 6, CYP 2 E 1, NAT 2, GSTM 1 and GSTT 1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma. Mutat Res. 2005 • Kujawski M, Jarmuz M, Rydzanicz M, Szukala K, Wierzbicka M, Grenman R, Golusinski W, Szyfter K. Frequent chromosome Y loss in primary, second primary and metastatic squamous cell carcinomas of the head and neck region. Cancer Lett. 2004 • lasiak J, Jaloszynski P, Trzeciak A, Szyfter K. In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues. Mutat Res. 1999

Session 9: TUMOR-TAILORED THERAPIES Geoffrey Margison, Ph. D Paterson Institute for Cancer Research senior investigator Manchester, United Kingdom Title of the lecture: DNA repair based strategies

PUBLICATIONS: • Ranson M, Middleton MR, Bridgewater J, Lee SM, Dawson M, Jowle D, Halbert G, Waller S, Mc. Grath H, Gumbrell L, Mc. Elhinney RS, Donnelly D, Mc. Murry TB, Margison GP. Lomeguatrib, a potent inhibitor of O 6 -alkylguanine-DNAalkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2006 • Margison GP, Heighway J, Pearson S, Mc. Gown G, Thorncroft MR, Watson AJ, Harrison KL, Lewis SJ, Rohde K, Barber PV, O'Donnell P, Povey AC, Santibanez-Koref MF. Quantitative trait locus analysis reveals two intragenic sites that influence O 6 -alkylguanine-DNA alkyltransferase activity in peripheral blood mononuclear cells. Carcinogenesis. 2005 • Barvaux VA, Ranson M, Brown R, Mc. Elhinney RS, Mc. Murry TB, Margison GP. Dual repair modulation reverses Temozolomide resistance in vitro. Mol Cancer Ther. 2004 • Middleton MR, Margison GP. Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway. Lancet Oncol. 2003

Session 9: TUMOR-TAILORED THERAPIES Jan Sedlak, Ph. D. Deputy director and Head of Laboratory of Tumor Immunology of Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: A possible role of dietary chemopreventive compounds in tumor therapy

PUBLICATIONS: • Bodo J, Jakubikova J, Chalupa I, Bartosova Z, Horakova K, Floch L, Sedlak J. Apoptotic effect of ethyl-4 -isothiocyanatobutanoate is associated with DNA damage, proteasomal activity and induction of p 53 and p 21(cip 1/waf 1). Apoptosis. 2006 • Slamenova D, Horvathova E, Robichova S, Hrusovska L, Gabelova A, Kleibl K, Jakubikova J, Sedlak J. Molecular and cellular influences of butylated hydroxyanisole on Chinese hamster V 79 cells treated with N-methyl-N'-nitro -N-nitrosoguanidine: antimutagenicity of butylated hydroxyanisole. Int J Oncol. 2005 • Jakubikova J, Sedlak J, Bacon J, Goldson A, Bao Y. Effects of MEK 1 and PI 3 K inhibitors on allyl-, benzyl- and phenylethyl-isothiocyanate-induced G 2/M arrest and cell death in Caco-2 cells. Environ Mol Mutagen. 2003 • Jakubikova J, Sedlak J, Bod'o J, Bao Y. Effect of isothiocyanates on nuclear accumulation of NF-kappa. B, Nrf 2, and thioredoxin in caco-2 cells. J Agric Food Chem. 2006 • Jakubikova J, Bao Y, Sedlak J. Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrugresistant cell lines. Anticancer Res. 2005

Session 9: TUMOR-TAILORED THERAPIES Prof. Martin Brendel Universidade Estadual de Santa Cruz, Bahia, Brasil Title of the lecture: Tumor regression by antisense therapy against Plk 1 and Bcl-2

PUBLICATIONS: • Viau C, Pungartnik C, Schmitt MC, Basso TS, Henriques JA, Brendel M. Sensitivity to Sn(2+) of the Yeast Saccharomyces cerevisiae Depends on General Energy Metabolism, Metal Transport, Anti-Oxidative Defences, and DNA Repair. Biometals. 2006 • Filho DF, Pungartnik C, Cascardo JC, Brendel M. Broken hyphae of the basidiomycete Crinipellis perniciosa allow quantitative assay of toxicity. Curr Microbiol. 2006 • Bonatto D, Brendel M, Henriques JA. In silico identification and analysis of new Artemis/Artemis-like sequences from fungal and metazoan species. Protein J. 2005 • Pungartnik C, Viau C, Picada J, Caldeira-de-Araujo A, Henriques JA, Brendel M. Genotoxicity of stannous chloride in yeast and bacteria. Mutat Res. 2005 • Brendel M, Bonatto D, Strauss M, Revers LF, Pungartnik C, Saffi J, Henriques JA. Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae. Mutat Res. 2003

Session 10: STEM CELLS AND CANCER STEM CELLS Cestmir Altaner Director of Cancer Research Institute of Slovak Academy of Sciences Bratislava Title of the lecture: Normal and cancer stem cells: potential implication for cancer therapy

PUBLICATIONS: • Soltysova A, Altanerova V, Altaner C. Cancer stem cells. Neoplasma. 2005 • Poturnajova M, Altanerova V, Kostalova L, Breza J, Altaner C. Novel germline mutation in the transmembrane region of RET gene close to Cys 634 Ser mutation associated with MEN 2 A syndrome. J Mol Med. 2005 • Altanerova V, Holicova D, Kucerova L, Altaner C, Lairmore MD, Boris. Lawrie K. Long-term infection with retroviral structural gene vector provides protection against bovine leukemia virus disease in rabbits. Virology. 2004 • Boris-Lawrie K, Altanerova V, Altaner C, Kucerova L, Temin HM. In vivo study of genetically simplified bovine leukemia virus derivatives that lack tax and rex. J Virol. 1997 • Hladka M, Altaner C. Suppression of the avian sarcoma virus genome in 8 azaquanine-resistant, transformed, hamster cells. J Natl Cancer Inst. 1976 • Altaner C, Temin HM. Carcinogenesis by RNA sarcoma viruses. XII. A quantitative study of infection of rat cells in vitro by avian sarcoma viruses. Virology. 1970