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Cancer Therapy: Differentiation, Immunomodulation and Angiogenesis PDF

287 Pages·1993·6.02 MB·English
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Cancer Therapy Differentiation, Immunomodulation and Angiogenesis NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The Series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics London and New York C Mathematical and Kluwer Academic Publishers Physical Sciences Dordrecht, Boston and London o Behavioural and Social Sciences E Applied Sciences F Computer and Springer-Verlag Systems Sciences Berlin Heidelberg New York G Ecological Sciences London Paris Tokyo Hong Kong H Cell Biology Barcelona Budapest I Global Environmental Change NATo-pea DATABASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to more than 30000 contributions from international scientists published in all sections of the NATO ASI Series. Access to the NATO-PCO DATABASE compiled by the NATO Publication Coordination Office is possible in two ways: - via online FILE 128 (NATO-PCO DATABASE) hosted by ESRIN, Via Galileo Galilei, 1-00044 Frascati, Italy. - via CD-ROM "NATO Science & Technology Disk" with user-friendly retrieval software in English, French and German (© WTV GmbH and DATAWARE Technologies Inc. 1992). The CD-ROM can be ordered through any member of the Board of Publishers or through NATO-PCO, Overijse, Belgium. Series H: Cell Biology, Vol. 75 Cancer Therapy Differentiation, Immunomodulation and Angiogenesis Edited by Natale D'Alessandro Institute of Pharmacology Piazza XX Settembre 4,98100 Messina, Italy Enrico Mihich Grace Cancer Drug Center Department of Experimental Therapeutics Roswell Park Center Institute Elm and Carlton Streets, Buffalo, NY 14263, USA Luciano Rausa Faculty of Medicine Policlinic of the University "P. Giaccone" Via del Vespro 129, 90127 Palermo, Italy Haim Tapiero Laboratoire de Pharmacologie Cellulaire & Moleculaire ICIG, Hopital Paul-Brousse 14 avo Paul-Vaillant-Couturier, 94800 Villejuif, France Thomas R. Tritton University of Vermont, School of Medicine Burlington, VT 05405, USA Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest Published in cooperation with NATO Scientific Affairs Division Proceedings of the NATO Advanced Study Institute on Specific Approaches in Cancer Therapy: Differentiation, Immunomodulation and Angiogenesis held at Erice, Italy, October 17-27, 1992 ISBN-13:978-3-642-84615-1 e-ISBN-13:978-3-642-84613-7 DOl: 10.1007/978-3-642-84613-7 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights oftranslation, reprinting, reuse of illustrations, recitation, broadcast- ing, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1993 Softcover reprint of the hardcover 1s t edition 1993 Typesetting: Camera ready by authors 31/3145 - 5 4 3 210 - Printed on acid-free paper FOREWORD The insufficient selectivity of antitumour drugs currently available and the frequent phenomenon of drug resistance represent a major obstacle to further advances in cancer treatment. With this in mind, the aim of the NATO ASI held from 17 to 27 october 1992 at the "Ettore Majorana Centre for Scientific Culture" in Erice, of which this book represents the proceedings, was to examine comprehensively the basic and clinical conditions of some innovative approaches, i.e. differentiation, immunomodulation and inhibition of angiogenesis, which may support or even substitute chemotherapy. A general consensus was that cancer cells are characterized by being arrested at an immature level of development while retaining their proliferative capacity; a rational approach thus involves the induction of tumour cell differentiation to a mature stage, where proliferation ceases. However, Alain Zweibaum (Villejuif, France) warned that, in colon cancer, a small proportion of cells capable of differentiating possess particular properties which allow them to escape stress conditions and to start again their growth. A deep insight into the mechanisms underlying the control of cell multiplication and differentiation was provided by various lectures. Eliezer Huberman (Argonne, Illinois) showed that the signal transduction pathway, which mediates phorbol 12-myristate 13- acetate-induced differentiation in the human promyelocytic HL-60 cells, requires specific protein kinase C isozymes (P, a "B-like") for the proper expression of the early response genes such as junB, c-jos and c-jun. Raymond Frade (paris, France) analyzed the signal transduction from the Epstein-Barr virus receptor (EBV/C3dR) in human B lymphocytes and demonstrated that, in the human B lymphoma cell line Raji, EBV/C3dR interacts specifically with the p53 cellular tumour suppressor gene- encoded phosphoprotein, which is not expressed in normal B cells; in normal B lymphocytes, EBV /C3dR interacts with p68, an intracellular calcium-binding protein belonging to the annexin VI family. Thomas R. Tritton (Burlington, Vermont) indicated that the ability of anticancer drugs like doxorubicin to kill susceptible cells involves a series of events initiated at the plasma membrane and proceeding through the protein kinase C signal transduction pathway to ultimate damage to the DNA in the nucleus. In the colon carcinoma cell lines described by Michael G. Brattain (Toledo, Ohio), a progressed, highly aggressive, phenotype is accompanied by a strong internal TGF-a. autocrine loop, which leads to independence from regulatory growth factors. Thus, the possibility raises of developing therapeutic approaches on the inhibition of TGF-a. transcription. Other firm experimental therapeutic options involving differentiation were outlined by Giovanni B. Rossi (Rome, Italy), who discussed the role of interferons in the differentiation of Friend erythroleukemia, and by Alexander Bloch (Buffalo, New York), VI who pointed out that DNA-specific antitumour agents, at concentrations that are minimally cytotoxic, are capable of increasing the responsiveness of cancer cells to differentiation signals. Finally, Laurent Degos (paris, France) showed how all- trans retinoic acid induces a very high rate of complete remissions in acute promyelocytic leukemia, which represents indeed the first model of differentiation therapy in human malignancies. Modulation by biological agents, cytotoxic effector cells and drugs was considered in attempts to boost endogenous antitumour defenses and/or to render neoplastic cells more susceptible to the host attack. Enrico Mihich (Buffalo, New York) presented the influence of doxorubicin on, both specific and natural, immune functions and the curative effects of this drug plus IL-2 or TNF in the EIA lymphoma in the C57B1I6 mouse, as a proper example of the useful interaction between an anticancer drug with immunomodulatory activity and certain cytokines with antitumour action. The interrelationship between anticancer drugs and immunity was again underscored by Jean-Luc Teillaud (Paris, France), who pinpointed the different ways doxorubicin, pirarubicin or aclacinomycin act on the B cell system. In addition, Paolo Puccetti (perugia, Italy) described how potent mutagenic compounds, such as triazene and nitrosoguanidine derivatives, generate highly immunogenic cell variants of murine lymphomas; Benjamin Bonavida (Los Angeles, California), suggested that the combination of TNF-a and either drugs (doxorubicin, CDDP) or diphteria toxin may overcome tumour resistance to either one or both agents. In the clinical context, Carlo Gambacorti Passerini (Milan, Italy) reviewed the use of IL-2 in advanced cancer, raising the question of whether, besides LAK cells, other subpopulations of lymphocytes could be responsible for the clinical effects of the treatment. Fiorella Guadagni (Rome, Italy) cited the possibility of improving the diagnostic and therapeutic efficacy of monoclonal antibodies by the use of interferons, which can upregulate human tumour antigens. In the last section, the importance of interfering with tumour blood vessel formation and function, and its potential in the treatment of metastasis, was taken into account. Claudio J. Conti (Smithville, Texas) made a complete report on the biology of angiogenesis, its factors and genetic regulation. Francesco Colotta (Milan, Italy) described the complex, ambiguous role of tumour associated macrophages in the regulation of primary tumour growth, angiogenesis and metastasis. Ralph J. Bernacki (Buffalo, New York) provided evidence of the role played by specific lectins of the extracellular matrix, such as galaptin, in tumour cell adhesion, suggesting the therapeutic exploitation of newly synthesized membrane sugar analogues as modulators of cell surface structure and adhesion. The Course was attended by about 90 selected participants from Albania, Bulgaria, Canada, Czechoslovakia, France, Germany, Greece, Italy, Moldavia, Poland, Portugal, Romania, Russia, Ukraine, USA and Turkey. The lectures were followed by intense and exhaustive discussions; among the many interesting interventions, there were those, VII presented as formal papers in this book, of Asterios S. Tsiftosoglou (Thessaloniki, Greece) on differentiation, Nicolo Borsellino (Palermo, Italy), Vasile F. Dima (Bucharest, Romania), Maurizio R. Soma (Milan, Italy) and Francesco Squadrito (Messina, Italy) on immunomodulation, and of Romano Danesi (Pisa, Italy) and Marina Ziche (Florence, Italy) on angiogenesis. To sum up, the participants in the Erice meeting were exposed to new concepts and/or models to be considered or applied in their laboratories or clinical practice. Indeed, they saw evidence indicating that the exploitation of discrete mechanisms in differentiation, immunomodulation or angiogenesis may be of therapeutic value, at least in selected human neoplasms. This situation could well improve in the next few years. Finally, the Course was a significant occasion for personal contact, especially between scientists from East Europe and those from the NATO area. We wish to express our appreciation to our main sponsoring Institutions, the NATO Scientific Affairs Division, the Ettore Majorana Centre for Scientific Culture, and the Sicilian Regional Government for their moral and financial support. Last, but not least, we gratefully acknowledge Dr. Carla Flandina for her patience, care and hard work in dealing with the organization of the course. The editors. TABLE OF CONTENTS Colon cancer cell differentiation as related to methotrexate and 5-fluorouracil resistance A. Zweibaum, T. LesujJleur, A. Barbat, E. Dussaulx, I. Chantret, L. Mahraoui, G. Chevalier, E. Brot-Laroche and M. Rousset The control of cell multiplication and differentiation 17 in human myelomonocytic cells E. Huberman, D.A. Tonetti, M. Horia, S. Murao and F. R. Collart Signal transduction through the Epstein-Barr virus 33 receptor in human B lymphocytes R. Fraae Signal transduction mechanisms as a target for cancer 39 chemotherapy T. R. Tritton Therapeutic approaches for colon cancer based on 51 transcriptional regulation of specific growth factors M. G. Brattain and K.M. Mulder Interferon regulation of differentiation and mechanisms 71 G.B. Rossi, G. Romeo, A. Battistini, E. AjJabris, E. Cocda and G. Fiorucd Induction of tumor cell differentiation as a mechanism 91 of action of DNA-specific antitumor agents A. Bloch ATRA therapy in acute promyelocytic leukemia. A model 99 for differentiation therapy L. Degas Hemin is transported in human leukemia K562 cells and 109 interacts with DNA sequences A.S. Tsijtosoglou, A.!, Tsamaaou, S.H. Robinson and W. Wong Immunomodulation by anticancer drugs in therapeutics 121 E. Mihich and M.J. Ehrke x Differential effects of low doses of structurally 135 different anthracyc1ines on immunoglobulin production by mouse hybridoma B cells 1.L. Teillaud and H. Tapiero Chemical xenogenization of experimental tumors by 147 antineoplastic drugs P. Puccetti, U. Grohmann, R. Bianchi, L. Binaglia, M.L. Belladonna, M. Allegrucci and M. C. Fioretti Reversal of drug resistance: synergistic anti-tumor 163 cytotoxic activity by combination treatment with drug and TNF or toxins B. Bonavida, 1. T. Safrit and H. Morimoto Immunomodulation in cancer patients treated with 179 interleukin-2. Induction of non-specific and specific immune responses C. Gambacorti-Passerini, G. Parmiani and P.A. Ruffini Potential role of tumor cell antigen modulation in 189 cancer immunotherapy F. Guadagni Effects of tumor necrosis factor-alpha on growth and 201 doxorubicin sensitivity of multidrug resistant tumor cell lines M. Crescimanno, N. Borsellino, V. Leonardi, L. Rausa and N. D 'Alessandro Activation of macrophages by treatment of rat 209 peritoneal cells with photofrin II and He-Ne laser V.F. Dima, M. ]onescu, V. Vasiliu and S. V. Dima Synergistic interaction between simvastatin and 217 antineoplastic drugs on glioma cell growth M.R. Soma, R. Baetta, C. Ferrari, M.R. de Renzis, R. Paoletti and R. Fumagalli CNS and cardiovascular effects of TNF-alpha 225 F. Squadrito and A. P. Caputi Angiogenesis and angiogenesis factors in stages of 231 carcinogenesis C.J. Conti XI Cytokine regulation of tumor-associated macrophages: 249 therapeutic implications A. Mantovani, B. Bottazzi, S. Sozzani, G. Peri, P. Allavena, C. Garlanda, A. Vecchi and F. Colotta The mechanism of lectin-mediated adhesion of human 259 ovarian carcinoma cells R.i. Bernacki Inhibitory effect of suramin and heparin-like drugs 269 on experimental angiogenesis R. Danesi, M. Costa, C. Agen, U. Renelli and M. Del Tacca Role of gangliosides in the modulation of the 275 angiogenic response M. Ziche, L. Morbidelli, A. Parenti, G. Alessandri, F. Ledda and P.M. Gullino Subject index 281

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