The Ninth Annual Pezcoller Symposium entitled "The Biology of Tumors" was held in Rovereto, Italy, June 4-7, 1997. It focused on the genetic mechanisms underlying het erogeneity of tumor cell populations and tumor cell differentiation, on interactions be tween tumor cells and cells of host defenses, and the mechanisms of angiogenesis. With presentations at the cutting edge of progress and stimulating discussions, this symposium addressed issues related to phenomena concerned with cell regulation and cell interactions as determined by activated genes through the appropriate and timely media tion of gene products. Important methodologies that would allow scientists to measure dif ferentially genes and gene products and thus validate many of the mechanisms of control currently proposed were considered, as were the molecular basis of tumor recognition by the immune system, interactions between cells and molecular mechanisms of cell regula tion as they are affected by or implemented through these interactions. The molecular and cellular mechanisms of tumor vascularization were also discussed. It was recognized that angiogenesis provides a potential site of therapeutic intervention and this makes it even more important to understand the mechanisms underlying it. We wish to thank the participants in the symposium for their substantial contribu tions and their participation in the spirited discussions that followed. We would also like to thank Drs."

The Fourth Annual Pezcoller Symposium entitled Adhesion Molecules: Cellular Recognition Mechanisms was held in Rovereto, Italy, June 24-26, 1992 and was focussed on the detailed mechanisms whereby cells utilize certain integral membrane proteins to perceive their surrounding environment and interact with it. With timely presentations and stimulating discussions this Symposium addressed the genetics and biochemistry of adhesion molecules, the regulation of their functions and their role in cancer and the immune system. Emphasis was given to adhesion proteins in the integrin family because of the widespread distribution of this group of molecules and its important role in essentially all eukaryotic biological systems. The regulation of integrin genes and their expression are discussed in detail, as are specific aspects of the genetics of fibronectin. The molecular basis for the regulation of certain integrins, the function of these proteins in determining cell adhesion, and the consequences of this adhesion for the function of the cells involved are discussed. The role of certain integrins in stimulating signal transduction, the essential involvement of integrins in conditioning the function of T and NK cells function, the heterogeneity of integrins and its biological consequences, and the role of cell adhesion molecules in tumor cells invasion and metastases are all extensively analyzed. New information was presented on the role of CD44 and splice variants in normal differentiation and tumor progression.

The series of volumes entitled Biological Responses in Cancer: Progress toward Potential Applications provides information on approaches through which the interaction between neoplastic and normal cells may be modified. Each annual volume contains contributions in areas where significant prog ress has been made. Topics to be dealt with include immunologic and host defense systems, control mechanisms of cell and population growth, cell differentiation, and cell transformation. The regulatory mechanisms controlling the interactions between normal and tumor cells may be immunologic in nature or they may relate to diverse biological characteristics of tumor and normal cells and their response to micro environmental factors. While the central question of tumor immunol ogy addresses the nature and uniqueness of tumor-associated antigens in humans, the identification of the stages of differentiation and functions of the various cell types involved in immunity is advancing rapidly. The de velopment of monoclonal antibody methodologies, together with progress in the biochemical characterization of cell markers, cell separation, and measurement of cell functions, has significantly aided in the identification and quantitation of different cell types. Establishing the role of these cells in the regulation of human immune mechanisms offers a means for evalu ating the status of the immune responses in cancer patients and for assessing the effects that tumor and antitumor treatments may exert on their func tionality, which, in turn, may alter the effects of antitumor treatments."

The series of volumes entitled Biological Responses in Cancer provides information on approaches through which the interaction between neoplas tic and normal cells may be modified. Topics discussed in various volumes include immunological and host defense systems, control mechanisms of cell and population growth, cell differentiation, and cell transformation. This volume is specifically concerned with various aspects of cell interactions and regulation within heterogeneous tumor cell populations, and their role in tumor progression and metastasis. Knowledge in this area is likely to provide new leads toward the exploitation of novel cellular sites and mech anisms in the development of new types of therapies of cancer. Several topics are discussed within these general areas of consideration. The possibly unique characteristics and mechanisms of tumor vascularization and the potential sites of interference with angiogenesis that might have therapeutic impli cations are critically evaluated. Tumor cell-normal tissue interactions in volved in different phases of the growth and metastatic processes are dis cussed in two chapters dealing with mechanisms of tumor invasion and with the role of collagen in mammary tumor growth; here again potential leads are identified that may be exploited toward the development of new thera peutic approaches. The evolution of phenotypic diversity as a phenomenon complicating the biology of tumor metastasis and consequently affecting the opportunities offered by chemotherapy is also critically considered."

The series of volumes entitled Biological Responses in Cancer: Progress toward Potential Applications will provide information on approaches through which the interaction between neoplastic and normal cells may be modified. Each annual volume will contain contributions in areas where significant progress has been made. Topics to be dealt with include immunologic and host defense systems, control mechanisms of cell and population growth, cell differentiation, and cell transformation. The regulatory mech sms controlling the interactions between normal and tumor cells may be immunologic in nature or they may relate to diverse biological characteristics of tumor and normal cells and their response to micro environmental factors. While the central question of tumor immunol ogy addresses the nature and uniqueness of tumor-associated antigens in humans, the identification of the stages of differentiation and functions of the various cell types involved in immunity is advancing rapidly. The de velopment of monoclonal antibody methodologies together with progress in the biochemical characterization of cell markers, cell separation, and mea surement of cell functions has significantly aided in the identification and quantitation of different cell types. Establishing the role of these cells in the regulation of human immune mechanisms offers a means for evaluating the status of the immune responses in cancer patients and for assessing the effects tumor and antitumor treatments may exert on their functionality, which, in turn, may alter the effects of antitumor treatments."

The seventh Annual Pezcoller Symposium entitled, Cancer Genes: Functional As- pects, was held in Trento, Italy, June 14-16, 1995 and was focused on oncogenes func- tion, tumor suppressor gene function, transcription regulation, cell cycle progression regulation and apoptosis, and the clinical implications of oncogene function and regula- tion for prevention and therapy of cancer. With presentations at the cutting edge of pro- gress and stimulating discussions, this Symposium addressed issues related to the mechanisms of control of cell growth and death by certain genes such as c-myc, src, fyns, bcl2, the function of cdk inhibitors, the functions of p53 and WTI, the mechanisms of transcriptional activation of specific oncogenes, the genetic characterization of certain he- matological malignancies, the interference with specific sites along signal transduction and the genetic alterations of tumor immunity. We wish to thank the participants in the Symposium for their substantial contribu- tions and their participation in the spirited discussions which followed. We would also like to thank Drs. Jane Azizkhan, Paolo Comoglio, Giulio Draetta~ David M. Livingston and Alex Matter for their essential input as members of the Program Committee, and Ms. A. Toscani for her invaluable assistance. The aid of the Bank Cassa di Risparmio di Trento and Rovereto, and the Municipal, Provincial and Regional Administrations in sup- porting this Symposium through the Pezcoller Foundation are also acknowledged with deep appreciation. Finally, we wish to thank the staff of Plenum Publishing Corporation for their efficient cooperation in the production of these Proceedings.

The eighth Annual Pezcoller Symposium, entitled Genomic Instability and Immor- tality in Cancer, was held in Trento, Italy, June 17-19, 1996 and was focused on the clari- fication of the mechanisms of genetic instability, a characteristic of neoplastic cells which also determines tumor progression, and immortality consequent to the lack of susceptibil- ity to mechanisms of maturations, senescence and/or apoptosis. With presentations at the cutting edge of progress and stimulating discussions, this symposium addressed issues related to mutational lability, changes in DNA repair capa- bilities, gene recombination processes, cell cycle checkpoints and apoptosis, the signifi- cance of telomerases in cell immortalization and senescence, and the clinical relevance and exploitation of the phenomena considered. We wish to thank the participants in the symposium for their substantial contribu- tions and their participation in the spirited discussions that followed. We would also like to thank Drs. Carol Greider, Garth Anderson, Margherita Bignami, and David Livingston, for their essential input as members of the Program Committee, and Ms. A. Toscani for her invaluable assistance. The aid of the Savings Bank Cassa di Risparmio di Trento e Ro- vereto, and the Municipal, Provincial, and Regional Administrations in supporting this Symposium through the Pezcoller Foundation are also acknowledged with deep apprecia- tion. Finally, we wish to thank the staff of Plenum Publishing Corporation for their effi- cient cooperation in the production of these proceedings.

''An exciting glance at key issues in contemporary hematopoiesis.'' -The Quarterly Review of Biology

Provided here is a comprehensive examination of the basic and clinical condition of three innovative and promising approaches to cancer therapy, which may support or even substitute chemotherapy: differentiation, immunomodulation, and inhibition of angiogenesis. Differentiation shouldnormalize neoplastic cells and make them compatible with the host. Its feasibility with retinoids, interferons, chemotherapeutic and other agents is discussed. Modulation by biological agents, cytotoxic effector cells and drugs is considered in attempts to boost endogenous antitumour defenses and/or to render neoplastic cells more susceptible to the immune attack of the host. Finally, the important aspect of interfering with tumour blood vessel development and function is taken into account. Consideringthe importance that chemotherapy has in cancer treatment and in view of a more and more integrated strategy, the relationship between the aforementioned approaches and chemotherapeutic agents and chemoresistance is treated in detail.

The Ninth Annual Pezcoller Symposium entitled "The Biology of Tumors" was held in Rovereto, Italy, June 4-7, 1997. It focused on the genetic mechanisms underlying het erogeneity of tumor cell populations and tumor cell differentiation, on interactions be tween tumor cells and cells of host defenses, and the mechanisms of angiogenesis. With presentations at the cutting edge of progress and stimulating discussions, this symposium addressed issues related to phenomena concerned with cell regulation and cell interactions as determined by activated genes through the appropriate and timely media tion of gene products. Important methodologies that would allow scientists to measure dif ferentially genes and gene products and thus validate many of the mechanisms of control currently proposed were considered, as were the molecular basis of tumor recognition by the immune system, interactions between cells and molecular mechanisms of cell regula tion as they are affected by or implemented through these interactions. The molecular and cellular mechanisms of tumor vascularization were also discussed. It was recognized that angiogenesis provides a potential site of therapeutic intervention and this makes it even more important to understand the mechanisms underlying it. We wish to thank the participants in the symposium for their substantial contribu tions and their participation in the spirited discussions that followed. We would also like to thank Drs."

The fifth Annual Pezcoller Symposium entitled, Apoptosis, was held in Trento, Italy, June 9-1I, 1993 and was focused on the specific phenomena leading to Programmed Cell Death (PCD) or Apoptosis, and the mechanisms involved. With presentations at the cutting edge of progress and stimulating discussions, this Symposium addressed the genetics and molecular mechanisms determining PCD and the role of this suicidal process in cancer and the immune system. The functions of pS3, c myc and bel 2 in affecting apoptosis in different cell types and the role of ions and intracellular pH changes and that of intranuelear endonueleases are given particular emphasis as are the effects of anticancer agents, hormone imbalances and growth factors. The role of pS3, a tumor suppressor gene, in inducing PCD is discussed in detail as pertinent to hematological and non-hernatological tumors. The requirement of pS3 for the induction ofapoptosis by ionizing radiation or adenovirus oncoproteins is outlined. Decision points during the cell cyele affecting the cascade ofevents leading to PCD are discussed as is their role as "switches" under the control of c-myc and bel-2 proteins or the influence of cyele specific drugs. The concurrent requirement of multiple signals in determining apoptosis is emphasized. The examples of the role of PCD in the regulation of hematopoiesis, and in the generation of antigen-specific immune repertoire are illustrated.

The fifth Annual Pezcoller Symposium entitled, Apoptosis, was held in Trento, Italy, June 9-1I, 1993 and was focused on the specific phenomena leading to Programmed Cell Death (PCD) or Apoptosis, and the mechanisms involved. With presentations at the cutting edge of progress and stimulating discussions, this Symposium addressed the genetics and molecular mechanisms determining PCD and the role of this suicidal process in cancer and the immune system. The functions of pS3, c myc and bel 2 in affecting apoptosis in different cell types and the role of ions and intracellular pH changes and that of intranuelear endonueleases are given particular emphasis as are the effects of anticancer agents, hormone imbalances and growth factors. The role of pS3, a tumor suppressor gene, in inducing PCD is discussed in detail as pertinent to hematological and non-hernatological tumors. The requirement of pS3 for the induction ofapoptosis by ionizing radiation or adenovirus oncoproteins is outlined. Decision points during the cell cyele affecting the cascade ofevents leading to PCD are discussed as is their role as "switches" under the control of c-myc and bel-2 proteins or the influence of cyele specific drugs. The concurrent requirement of multiple signals in determining apoptosis is emphasized. The examples of the role of PCD in the regulation of hematopoiesis, and in the generation of antigen-specific immune repertoire are illustrated.

Telomeres and Cell Division in Drosophila melanogaster; G. Cenci, M. Gatti. A Molecular Cytogenetic View of Chromosomal Heterogeneity in Solid Tumors; J.W. Gray et al. Cell Cycle Control of Genetic Stability; G.M. Wahi et al. Aneupioidy and Heterogeneity Mechanisms in Human Colorectal Tumor Progression; W. Ciaretti. p53-Dependent Signaling in Response to DNA Damage or Arrest of DNA Synthesis and Its Role in Cell Cycle Control; M.L. Agarwal et al. Recombining DNA Damage Repair, Basal Transcription and Human Syndromes; J.H.J. Hoeijmakers et al. Telomere Length Regulation by the Pifl DNA Helicase; E.K. Monson et al. Consequences of Mutations that Alter Telomeres in the Yeast K . lactis; J. McEachern, E.H. Blackburn. Regulation of Telomere Length in Mammalian Cells; B.R. Grimes et al. The DNA Damage Checkpoint; L. Hartwell et al. A Eukaryotic Cell Cycle; K. Nasmyth. The Integration of Signaling Pathways in Mammalian Cells; G.I. Evan et al. Antitumor Drugs and Yeast Cell Cycle Checkpoints; M. Weinberger et al. Mechanisms of Neoplastic Progression in Barrett's Esophagus; M.T. Barrett et al. E2F-1 Degradation by the Ubiquitin Proteasome Pathway; F. Hofmann, D. Livingston. 2 Additional Articles. Index.

The Integrated Control of Cell Proliferation and Cell Viability; G.I. Evan, et al. Control of Invasive Cell Growth by the MET Family Oncogenes; F. Galimi, P.M. Comoglio. Src Family Kinases and the Cell Cycle; S.A. Courtneidge. p16 Family Inhibitors of Cyclin-Dependent Kinases; Y. Li, et al. p53-Mediated Apoptosis: Regulatory and Mechanistic Aspects; Y. Haupt, et al. The Molecular Genetics of Wilms Tumor; J. Pelletier, et al. HTLV-1 Tax: A Paradigm for How a Single Auxiliary Factor Can Regulate the Expression of Viral and Cellular Genes; G. Perini, M.R. Green. CREM: Transcriptional Pacemaker of the cAMP Response; J.S. Lee, et al. MADS-domain transcription Factor and Their Accessory Proteins (TCFs): Nuclear Targets for Growth Control Signals; M.A. Cahill, et al. Retinoblastoma Protein, Gene Expression, and Cell Cycle Control; J.C. Azizkhan, et al. Cyclin A-kinase Binding to and Regulation of the Function of a Growth-Promoting Transcription Factor; W. Krek, et al. Homeostatic Mechanisms Governing the Go hase as Defined by the Gas Genes; C. Schneider, et al. The TEL Gene and Human Leukemias; T.R. Golub, et al. Characterization of the TCLI Gene and Its Involvement in T-Cell Malignancies; L. Virgilio, et al. 3 Additional Articles. Index.

Regulation of Normal Hemopoiesis; D. Metcalf. Cytokine Regulation of Lymphohemopoietic Progenitors; M. Ogawa, F. Hirayama. Hematopoietic Stem Cells; I. Weissman. Transcriptional Control of Hematopoietic Development: Roles of GATA-Factors; S.H. Orkin, et al. Rearrangement of the ALL-1 Gene in Acute Myeloid Leukemia without Chromosomal Translocations; S.A. Schichman, C.M. Croce. Nonreceptor Protein Tyrosine Kinases: Pivotal Regulatory Molecules Controlling Lymphopoiesis; R.M. Perlmutter, et al. The Regulation and Function of p21Ras in T Cell Activation and Growth; D.A. Cantrell, et al. Irf-1 Functions as a Tumor Suppressor: Possible Involvement in Human Myelodysplasia and Leukemia; T. Taniguchi, et al. A Family of High Molecular Weight Proteins Active in Differentiation and Growth Control; R.E. Eckner, et al. Hematopoietic Signaling by the Cytokine Receptor Superfamily; J.N. Ihle. Positive and Negative Growth Effects of Abl Genes; C.L. Sawyers, et al. Advances in the Understanding of the Molecular Pathogenesis of Aggressive B Cell Lymphomas; K. Cechova, et al. Structure and Expression Pattern of the PML Gene; M. Fagioli, P.G. Pelicci. 5 additional articles. Index.