“Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006...

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“Cancer2006: From molecular biology processes to tumor- tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC PROFILE

Transcript of “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006...

Page 1: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

“Cancer2006: From molecular biology processes to tumor-tailored therapy”

20-24, august, 2006 High Tatras, Slovakia

THE INVITED SPEAKERS – BRIEF SCIENTIFIC PROFILE

Page 2: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

KEYNOTE LECTURE No.1

Andy Futreal, PhD.Co-head of the Cancer Genome Project Wellcome Trust Sanger InstituteHinxton, United Kingdom

Title of the lecture:The WTSI Cancer genome Project: understanding the targets

Page 3: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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

PUBLICATIONS:

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KEYNOTE LECTURE No. 2

Prof. Josef JiricnyDirector, Institute of Molecular Cancer ResearchUniversity of Zürich, Switzerland

Title of the lecture:

Towards the therapy of tumors with microsatellite instability

Page 5: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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

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KEYNOTE LECTURE No. 3

Ivan Horak, MD.Vice - Director Enzon Pharmaceuticals, Inc.Research and DevelopmentNew Jersey, USA

Title of the lecture:

Targeted therapy: from bench to bedside

Page 7: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Karacay H, Brard PY, Sharkey RM, Chang CH, Rossi EA, McBride 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, McBride 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 CD4 association with HIV-1 or HIV-1 gp120. Nature. 1990

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Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION

Prof. Kathleen Boris-LawrieDepartment of Veterinary SciencesThe Ohio State University, USA

Title of the lecture:

New insight into translational regulation of growth control genes: lessons derived from study of retroviruses

Page 9: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 RU5 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

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Page 10: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Prof. Richard KettmannFaculty of Agronomy, Gembloux, Belgium

Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION

Title of the lecture:

Metabolic pathways involved in transformational induced by oncoviral Tax proteins

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• 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 MSX2 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 Nur77 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

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Page 12: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 1: RETROVIRUSES IN MALIGNANT TRANSFORMATION

Prof. Jan SvobodaProfessor of cellular and molecular biology CU Institute of Molecular GeneticsPrague, Czech Republic

Title of the lecture:

Cell defense against retroviruses

Page 13: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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.

CpG 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

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Page 14: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 2: MOLECULAR PATHOGENESIS OF CANCER

Karl Heinimann, PhD.University of BaselSwitzerland

Title of the lecture:The mechanism of inactivation of the wild-type allele in hereditary cancers such as FAP and HNPCC

Page 15: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 MLH1/MSH2 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

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Session 2: MOLECULAR PATHOGENESIS OF CANCER

Linda Wolff, PhD.Chief, Leukemogenesis SectionLaboratory of Cellular Oncology, CCRNational Cancer Institute, NIHBethesda, USA

Title of the lecture:

Cyclin-dependent kinase inhibitor p15INK4B in leukemia and normal hematopoiesis

Page 17: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 p15(Ink4b) 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 Ink4b locus in murine myeloid leukemia and increased susceptibility

to leukemia in p15(Ink4b)-deficient mice. Oncogene. 2003

• Haviernik P, Schmidt M, Hu X, Wolff L. Consistent inactivation of p19(Arf) but not p15(Ink4b)

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 p15(INK4b) normally associated

with differentiation. Oncogene. 2001

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Page 18: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 2: MOLECULAR PATHOGENESIS OF CANCER

Juraj Bies, PhD.National Cancer Institute, NIHBethesda, USA

Title of the lecture:

Leukemogenesis and c-Myb: story of a tightly regulated transcriptional regulator

Page 19: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Markus J, Feikova S, Sramko M, Wolff L, Bies J. Proliferation-linked expression of the novel murine gene m4mbt 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

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Page 20: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 3: DNA DAMAGE AND REPAIR PROCESSES I.

Bennett Van Houten, PhD.Chief, Program Analysis Branch &Investigator in the Laboratory of Molecular GeneticsNational Institutes of Environmental Health SciencesResearch Triangle Park, NC, USA

Title of the lecture:

In search of damage: Structure-function studies of nucleotide excision repair

Page 21: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 UvrB. Nat Struct Mol Biol. 2006

• Truglio JJ, Rhau B, Croteau DL, Wang L, Skorvaga M, Karakas E, DellaVecchia MJ, Wang H, Van

Houten B, Kisker C. Structural insights into the first incision reaction during nucleotide excision

repair. EMBO J. 2005

• Skorvaga M, DellaVecchia MJ, Croteau DL, Theis K, Truglio JJ, Mandavilli BS, Kisker C, Van

Houten B. Identification of residues within UvrB 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

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Session 3: DNA DAMAGE AND REPAIR PROCESSES I.

Prof. Jiri LukasInstitute of Cancer Biology for Genotoxic Stress ResarchDanish Cancer Society, Copenhagen, Denmark

Title of the lecture:

Cellular response to DNA damage: Molecular mechanism and spatio-temporal organization in living mammalian cells

Page 23: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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.

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Session 3: DNA DAMAGE AND REPAIR PROCESSES I.

Mark O’Driscoll, PhD.Sussex Centre for Genome Damage and StabilityUniversity of SussexFalmer, Brighton

Title of the lecture:

DNA double strands break repair and cancer predisposition: Lessons from human syndromes

Page 25: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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: LIG4 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

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Session 4: DNA DAMAGE AND REPAIR PROCESSES II.

Miroslav Chovanec, PhD.Senior investigatorLaboratory of Molecular GeneticsCancer Research Institute of Slovak Academy of SciencesBratislava

Title of the lecture:

Cellular response to oxidative DNA damage in Saccharomyces cerevisiae

Page 27: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Dudas A, Markova E, Vlasakova D, Kolman A, Bartosova Z, Brozmanova J, Chovanec M. The Escherichia coli RecA protein complements recombination defective phenotype of the Saccharomyces cerevisiae rad52 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 H1. Proc Natl Acad Sci U S A. 2005

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Session 4: DNA DAMAGE AND REPAIR PROCESSES II.

Miroslav Pirsel, PhD.Head of Laboratory of Molecular GeneticsCancer Research Institute of Slovak Academy of SciencesBratislava

Title of the lecture:

Repair of oxidative DNA damage in the helicase mutants

Page 29: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 ERCC3 mutations in the Chinese hamster ovary 27-1, UV24 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

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Session 5: CANCER GENETICS

Minna Nystrom, PhD.Senior scientist & Research ManagerDepartment of Biological and Environmental SciencesUniversity of Helsinki, Finland

Title of the lecture:Functional significance and clinical phenotype of non-truncating inherited mismatch repair gene variants

Page 31: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Raevaara TE, Korhonen MK, Lohi H, Hampel H, Lynch E, Lonnqvist KE, Holinski-Feder E, Sutter C, McKinnon

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 MLH1. 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 3p 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 mutS homolog in hereditary nonpolyposis colorectal cancer. Cell.

1993

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Vladimir Zajac, PhD.Head of Laboratory of Cancer GeneticsCancer Research Institute of Slovak Academy of SciencesBratislava

Title of the lecture:

FAP and HBOC: two players in one playground

Session 5: CANCER GENETICS

Page 33: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Ciernikova S, Tomka M, Kovac M, Stevurkova V, Zajac V. Ashkenazi founder BRCA1/BRCA2 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(q12;p13) translocation breakpoints in a female patient with hypomelanosis of Ito and choroid plexus papilloma. Eur J Hum Genet. 1997

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Zdena Bartosova, PhD.Senior investigatorLaboratory of Molecular GeneticsCancer Research Institute of Slovak Academy of SciencesBratislava

Session 5: CANCER GENETICS

Title of the lecture:

Advances in molecular diagnostics of hereditary non-polyposis colorectal cancer in Slovakia

Page 35: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 CD4+ 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 MSH2+/- 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 MLH1 and MSH2 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 MLH1 and MSH2 genes identified in hereditary nonpolyposis colorectal cancer patients in Slovakia. Neoplasma 2006

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Page 36: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 6: TUMOR CELL SIGNALING AND CELL DEATH

Prof. Gerhard ChristoforiInstitute of Biochemistry and GeneticsUniversity of Basel, Switzerland

Title of the lecture:

Cell adhesion in tumor invasion and metastasis

Page 37: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G. Tumor

invasion in the absence of epithelial-mesenchymal transition: Podoplanin-

mediated 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-A165 enhances tumor

angiogenesis but not metastasis during beta-cell carcinogenesis. Cancer Res.

2002

• Cavallaro U, Niedermeyer J, Fuxa M, Christofori G. N-CAM modulates tumour-

cell adhesion to matrix by inducing FGF-receptor signalling. Nat Cell Biol. 2001

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Page 38: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Jozef Bizik, PhD., DsC.Senior investigatorLaboratory of Molecular OncologyCancer Research Institute of Slovak Academy of SciencesBratislava

Session 6: TUMOR CELL SIGNALING AND CELL DEATH

Title of the lecture:

Nemosis – prospective cell based cancer therapy

Page 39: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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

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Page 40: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 7: CARCINOGENESIS / ANTICARCINOGENESIS I.

Prof. Leonard MullendersDepartment of ToxicogeneticsLeiden University Medical CenterLeiden, The Netherlands

Title of the lecture:

From initial DNA damage to cancer: Lessons from mouse models

Page 41: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Alekseev S, Kool H, Rebel H, Fousteri M, Moser J, Backendorf C, de Gruijl FR,

Vrieling H, Mullenders LH. Enhanced DDB2 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

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Page 42: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 7: CARCINOGENESIS / ANTICARCINOGENESIS I.

Prof. Andrew CollinsDepartment of Nutrition, University of OsloBlindern, Oslo, Norway

Title of the lecture:

Cancer prevention by fruits and vegetables; not just a question for antioxidants

Page 43: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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

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Page 44: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 8: CARCINOGENESIS / ANTICARCINOGENESIS II.

Prof. Krzysztof SzyfterInstitute of Human Genetics Polish Academy of Sciences Poznan, Poland

Title of the lecture:

Modulation of laryngeal cancer incidence and progression by gene polymorphism

Page 45: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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. CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 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

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Page 46: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 9: TUMOR-TAILORED THERAPIES

Geoffrey Margison, PhDPaterson Institute for Cancer Researchsenior investigatorManchester, United Kingdom

Title of the lecture:

DNA repair based strategies

Page 47: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• Ranson M, Middleton MR, Bridgewater J, Lee SM, Dawson M, Jowle D, Halbert G, Waller S,

McGrath H, Gumbrell L, McElhinney RS, Donnelly D, McMurry TB, Margison GP.

Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: 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, McGown 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 O6-alkylguanine-

DNA alkyltransferase activity in peripheral blood mononuclear cells. Carcinogenesis. 2005

• Barvaux VA, Ranson M, Brown R, McElhinney RS, McMurry 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

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Page 48: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Jan Sedlak, PhD.Deputy director and Head of Laboratory of Tumor Immunology of Cancer Research Institute of Slovak Academy of SciencesBratislava

Session 9: TUMOR-TAILORED THERAPIES

Title of the lecture:

A possible role of dietary chemopreventive compounds in tumor therapy

Page 49: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 p53 and p21(cip1/waf1). 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 V79 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 MEK1 and PI3K inhibitors on allyl-, benzyl- and phenylethyl-isothiocyanate-induced G2/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-kappaB, Nrf2, 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 multidrug-resistant cell lines. Anticancer Res. 2005

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Page 50: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Session 9: TUMOR-TAILORED THERAPIES

Prof. Martin BrendelUniversidade Estadual de Santa Cruz, Bahia, Brasil

Title of the lecture:

Tumor regression by antisense therapy against Plk1 and Bcl-2

Page 51: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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

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Page 52: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

Cestmir Altaner Director of Cancer Research Institute of Slovak Academy of SciencesBratislava

Session 10: STEM CELLS AND CANCER STEM CELLS

Title of the lecture:

Normal and cancer stem cells: potential implication for cancer therapy

Page 53: “Cancer2006: From molecular biology processes to tumor-tailored therapy” 20-24, august, 2006 High Tatras, Slovakia THE INVITED SPEAKERS – BRIEF SCIENTIFIC.

• 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 Cys634Ser mutation associated with MEN 2A 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

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