30 Years’ German-Israeli Cooperation in Cancer Research 1976 - 2006 Deutsches Krebsforschungszentrum Ministry of Science and Technology German Cancer Research Center State of Israel Heidelberg Jerusalem March 2006 > WEBbildschirm6kkk.pdf 1 10.03.2006 16:01:55 recent trends in research, such as stem cell research and a focus on clinical topics. Several principal investigators contributed to this brochure with reports of their projects. Many thanks go to these individuals and to all the principal investigators and Ph.D. students who have been part of the program. Their achievements and the personal contacts with their project partners have shaped the structure of our cooperation program. This anniversary brochure also gives a brief look at the history of the cooperation program. All the projects, including ongoing work, are listed in the appendix. The present brochure represents a follow up to our brochure Cancer Research and Cooperation, which was compiled in 1999, Professor Dr. Dr. Nurit Topaz Dr. Shlomo Sarig and summarizes the history and the development of our program. Re- Wolfhard Semmler Director for Israeli coordinator German coordinator German-Israeli Cooperations cently, the literature appendix was also updated to include all publications and reports up to 2004. These documents are available on our homepage (www.dkfz.de/israel). 30 Years' German-Israeli Cooperation in Cancer Research The coordinators would like to thank the BMBF for funding and the management board of the German Cancer Research Center for their support. A 30-year anniversary is something to be proud of and offers the opportunity to look back to the beginnings of the German-Israeli cooperation, which started in 1976 initially with three projects. The following phases showed an increase to Heidelberg/Jerusalem, March 2006 10 projects. Since receiving supplemental financing in 1992, a constant number of Prof. Dr. Dr. Wolfhard Semmler Dr. Shlomo Sarig Nurit Topaz 14 projects have been ongoing. As of June 2005, a total of 105 projects had been successfully concluded. The cooperation program has developed very satisfactorily in the course of the past 30 years, as certified by the international review commission in 1997. Outstanding achievements have been made in day-to-day work at the bench and in joint publications: Every year the project partners have reported on the progress of the respective subprojects at the annual meeting of the program committee so as to expand and intensify the cooperation. Indeed, more young scientists are being encouraged to apply for new projects and the priority topics reflect the most > > > WEBbildschirm6kkk.pdf 2 10.03.2006 16:01:56 Foreword I. 26 Contributions to the Cooperation Between Israeli Research Institutes and the Deutsches Krebsforschungszentrum 1. The Initiation of Metamorphosisby E. Shaaya and C. Sekeris >> 9. Carcinogens and Retroviruses – A Dangerous Liaison Regulation of synthesis of HnRNA in epidermis cells of insects by M. Löchelt >> and its posttranscriptional modification Tumorigenic cooperation between human retroviruses, 2. Loss of MHC – A Trick to Escape Immune Attack by G. Hämmerling >> oncogenes, and other carcinogens The immunobiology of tumor metastases & Tumor-associated blood 10. Lipid Profiles Characterize Tumor Cells by W. D. Lehmann vessel endothelium as a barrier to infiltration of effector immunocytes and W. E. Hull >> 3. What Makes Cancer Cells Migrate? by M. Zöller >> Development of NMR and mass spectroscopic techniques Escape mechanisms of metastatic tumor variants and their application in the investigation of fatty acid and phospholipid metabolism and alterations involved 4. Elucidating the Cause of DNA Amplification by J. Schlehofer >> in cellular transduction and malignant growth The role of DNA-amplification in tumor initiation 11. A Shared Passion for Growth Factors by R. Schwartz- 5. Monitoring Interleukin Production in Single Cells by R. Zawatzky >> Albiez >> Agents controlling the growth and differentiation of primitive blood Growth factor regulated interaction between lymphomyeloid/erythroid stem cells leukemias/lymphomas and endothelium 6. The Potential of Tumor Necrosis Factor by D. N. Männel >> 12. A Pacemaker of Inflammation by G. Fürstenberger >> Mechanisms controlling the response to tumor necrosis factor Regulation of gene expression in tumor growth: 7. The Opposing Effects of Interleukin 1 by M. Zöller >> Overexpression of prostaglandin H synthase iso- Cytokine secretion of tumor cells: Influence on tumor initiation zymes as potential markers for epithelial tumors and interaction with the immune system & The impact 13. Breaking Complement Resistance of Tumor cells – of host and tumor derived IL-1 on tumor growth and host defense A Novel Approach in Cancer Immunotherapy? 8. How Do Parvoviruses Kill Tumor Cells? by J. Schlehofer >> by M. Kirschfink >> Involvement of the NS genes in the antitumor activity of parvo- Molecular basis of the resistance of tumor cells to viruses complement-mediated lysis & Sensitization of human tumor cells to complement-mediated lysis 30 Years’ German-Israeli Cooperation in Cancer Research . Content 1 > > > 14. The Secret Functions of HBV Protein Xby Y. Shaul and 22. Elucidating the Function of HNF4γ by G. Schütz >> C. Schröder >> A biochemical and molecular genetic approach to study the Functional interaction of px of HBV with the tumor role of hepatocyte nuclear factor 4 (HNF4) and suppression suppressor p53 of tumor development by fatty acids 15. Guided Missiles Against Cancer Cells by M. Little >> 23. Integrin Signalling in Men and Mice by T. Tennenbaum Redirecting effector lymphocytes to lymphomas using and D. Breitkreutz >> chimeric receptors with antibody specificity The functional relevance of alterations in integrin α6β4 16. Enhanced Kinase Activity – A General Feature in Viral Carcino- and protein kinase C regulation in human and mouse skin genesis? by F. Rösl >> carcinogenesis Characterization of the biological effects of EGF/IGF 24. Resensitizing Tumors to Programmed Cell Death kinase inhibitors on the transcriptional regulation of by P. Krammer >> human papilloma viruses in immortalized keratinocytes The CD95 (APO-1/Fas) death system in tumor progression and cervical carcinomas 25. Insulin’s Role Beyond Sugar Metabolism by E. Wertheimer 17. The Role of p53-Mutations in Chemoresistance and D. Breitkreutz >> by P. Krammer >> Functional significance of insulin signaling in skin and skin The guardian of the genome, p53, and death receptor CD95 tumorigenesis 18. The Cell’s Response to Carcinogensby P. Angel >> 26. Cancer – A Consequence of Fragile Chromosomes? Identification of cellular pathways mediating cell death by M. Schwab >> in response to radiation and genotoxic agents Chromosomal fragile sites and cancer 19. Bone Protein Expression – A Prerequisite for Skeletal Metastasis? by M. R. Berger >> Development and evaluation of non-viral antisense oligo- II. DKFZ/MOST Cooperation in Cancer Research nucleotide and gene-controlled delivery systems for the History >> treatment of mammary carcinoma and bone osteolysis 20. Heparanase – A Novel Cancer-Specific T-cell-target? III. Appendix by V. Schirrmacher >> Tumor-metastasis-associated heparanase: A newly dis- Facts and Figures >> covered target recognized by memory T-lymphocytes of Masterplan, diagrams to finances, scientific publications, breast-cancer patients Israeli establishments involved, and list of all workshops 21. Triggering NK-Cell Killing of Tumor Cells by F. Momburg >> List of all projects >> Identification of the NKp46 ligand: A ligand that is involved Ca001 – 120 with running period, joint title, and partners in the recognition of virus-infected and tumor cells 30 Years’ German-Israeli Cooperation in Cancer Research . Content 2 > > > The Initiation of Metamorphosis shortly after the appearance of the small peak of ecdysone, but DOPA decar- boxylase is induced only after a second peak of ecdysone, induction being a Eli Shaaya and Costas Sekeris left their Mediterranean home- two-step process dependent on both peaks. Our experiments further lands to enter the fascinating world of science in Munich, suggested that only after the second surge of ecdysone there was more where the secrets of steroid hormone action were being un- genetic information transferred to the cytoplasm.The fact that a-amanitin, veiled at Peter Karlson’s lab. After some years of fruitful colla- the specific inhibitor of RNA polymerase II, injected before pupariation, boration, they parted but met again, this time in Heidelberg, inhibits RNA synthesis and the induction of the enzyme leads to the conclu- where Costas was heading the Division of Molecular Biology of the Cell at sion that the appearance of DOPA decarboxylase mRNA after the second the German Cancer Research Center (DKFZ). Eli visited him – two good ecdysone peak is a result of the stimulation of giant HnNA containing the friends happy to plan their new research project. So did the German-Israeli DOPA decarboxylase mRNA sequence and not of reutilization of preexisting collaboration 007, (a symbolic number indeed) start (Costas, in his capacity HnRNA. Our results appeared in Gen. Compar. Endocrin. 34:110, 1978 of Division Head, scientifically nurtured in Germany, although a Greek and Z. Physiol. Chem. 360:445, 1979. Shortly before the project was national, in every right represented the German side). The project was based selected, Eli returned to Israel, to the Hebrew University, where most of on our common interest in the mode of action of ecdysone, the steroid this