Bøger i Developments in Oncology serien

One.- 1 Characterization.- 2 Serum-Free Media.- 3 Differentiation Potential of Cancer Cells.- 4 Spheroids and Xenografts.- 5 Predictive Assays for Drug and Radiation Resistance.- Two.- 6 Colorectum.- 7 Testicular Germ Cell Tumours.- 8 Epidermis.- 9 Lung Cancer.- 10 Brain.- 11 Ovarian Tumours.- 12 Prostate.- 13 Breast Cancer.

Significant progress has been made in recent years in understanding the origins of cutaneous maligant melanoma. Knowledge of the relationship between solar radiation and melanoma has changed and it now appears that both the character and timing of exposure may be more important than total cumulative dose in accounting for risk. The melanoma-sunlight model may prove an instructive heuristic exercise for environmental epidemiology, as we currently tend to restrict ourselves to a search for uniform total dose--response relationships between cancers and suspected environmental carcinogens. The study of the relationship between acquired melanocytic nevi and melanoma has led to useful new information about predictors of melanoma risk, and in addition has opened new perspectives on the development of nevi in children. Definition of the factors for nevus development in children may lead to the possibility of primary prevention programs for melanoma in younger generations of children. Recent new evidence suggests that certain occupational groups may be at elevated risk of melanoma. A great deal of work is going into the study of ways of screening high risk populations in order to detect melanoma at its earliest stages when current treatment protocols are most effective. The visibility of lesions on the skin challenges classical definitions of early detection and screening in epidemiology.

With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

The methodology of drug development has been the subject of extensive dis­ cussion by a relatively small group of individuals in industry and government who have been intimately concerned with the identification and study of new anticancer drugs. The Chemotherapy Program of the National Cancer In­ stitute has represented the major focus of initial efforts in drug development, as summarized in the historical perspective presented in chapter 1 and its references. It is no coincidence that the Chemotherapy Program was the origin of the Division of Cancer Treatment, a government entity that has had a pivotal role in the growth of clinical oncology. In an analogous fashion this book presents the methodology employed in the clinical study of anticancer drugs within the broad context of cancer treatment. The research orientation promulgated in the study of new drugs is a central theme in most oncolo­ gists' approach to the clinical problem of cancer. Therefore, we hope that this book will introduce readers to treatment research in clinical oncology. For the oncologist, the clinical evaluation of antitumor therapy is both part of the day-to-day management of specific patients and the critical considera­ tion of developing therapeutic alternatives. For physicians in other fields of medicine it is important to acquaint themselves with the basic tools of the oncologist. For people without medical training, including patients who might be interested in treatment research, many of the chapters may be overly technical.

Despite the fact that the incidence of gastric cancer is declining in the Western world, it remains a significant problem with respect to accurate diagnosis and treatment since it has a high mortality rate. In June 1989 an International Conference was held at the University of Rome "La Sapienza" entitled "New Trends in Gastric Cancer: Background and videosurgery". During this meeting background information on the aetiopathogenesis of gastric cancer was presented together with talks and video presentations on the latest advances in the treatment of gastric carcinoma, both from the European and Japanese experience. Because of the poor prognosis of gastric carcinoma there is increasing pressure for early detection. Some of the problems in the early detection of gastric carcinoma are discussed together with methods of surveillance of high-risk subjects. It is generally accepted that the surgical approach to gastric carcinoma should take into account the site and extent of the lesion and there are chapters on new methods for pre and intraoperative staging of the disease which allow a more logical approach to surgery. A comparison between Japanese and Western rule and results was attempted and reasons for the differences were investigated. Since the field is still evolving not all aspects could be covered, and those angles not approached in this book will be addressed in a second International Conference to be held in Rome in June 1990.

The focus of this symposium was on the present and future capabilities of flow cytometry for both medical and biological applications in cancer. This technology began with quite modest instrumentation, with limited capabilities to answer biological questions. Today, both the clinical workhorses and the powerful multi-laser, multi-detector, sorting machinery, coupled with sophisticated computers and storage devices and the increasing storehouse of markers and dyes, are taking us to the limit and beyond in finding answers to the cause and cure of cancer. In the past, both normal hematopoietic tissue and leukemias have been the tissue samples of choice in the application of flow cytometry, and some of the most recent applications with these tissues are presented here. However, the book also discusses the increasingly sophisticated disaggregation techniques which allow investigators the possibility to train their lasers on solid tumors. Not only can we use flow cytometry with associated fluorescent markers to understand the biology of cancer, but also the wide array of existing and developing markers provides us with important diagnostic tools in the detection of cancer early in either the malignant or relapse process. And the field comes full circle, with the use of the technology for gene mapping and other genetic studies to unlock the basic malignant process.

Breast cancer is not only a burning public issue, but very soon we shall see genetic testing for a woman's predisposition to breast cancer. Many women will be demanding to know their degree of risk and will need counselling to cope with that information. This book is particularly aimed at primary health care professionals, including physicians, medical assistants, nurses and counsellors, who daily deal with questions from women concerned about their risk of developing breast cancer. To answer such questions, this book has combined a guide to identifying women at higher risk to breast cancer, with a balanced review of approaches which aim to reduce that risk. The book provides practical general measures which may reduce risk for women at average risk. For women at clearly increased risk various protective options with different levels of efficacy and acceptability are discussed. Central to the book is the patient-centered view. We need to face reality that it still will take many years before the current clinical trials of preventive measures provide meaningful results. Meanwhile, women who seek to diminish their risk of breast cancer need all the available information. They must be given full responsibility to make an informed decision on their own health care. Reducing Breast Cancer Risk in Women is a practical handbook, technicalities have been deliberately kept to a minimum, making it concise and easy to read.

The assessment of tumour response after treatment is one of the most important challenges in Oncology and the picture is so often complicated by the effects of therapy itself. Clinical assessment is still by far the most important method of assessment at our disposal but there is increasing dependence on investigations of all types as indices of response. This depen­ dence may be misplaced if inappropriate investigations are pursued and we have tried to emphasise in this book the importance of selectivity. Some indices of assessment (e. g. tumour markers, organ imaging) have a vital role to play; others (e. g. histopathology, genetics) are assuming greater impor­ tance as tumour behaviour becomes better understood. One subject, Immu­ nology, is still in its infancy as regards tumour follow-up, but shows much promise so that a full account of tumour immunology and trends in immu­ notherapy has been included. I am grateful to Dr. Brian Ross for his help with the chapter on Organ Imaging, to the Department of Medical Illustration for their ever-ready co-operation with illustrations and photographs and to Miss Shirley Francis for doing much of the typing. B. W. HANCOCK List of Contributors HANCOCK, B. W. , MD, DCH, MRCP, Senior Lecturer in Medicine, Hon­ orary Consultant Physician, Royal Hallamshire & Weston Park Hospitals, Sheffield, U. K. NEAL, F. E. , KSG, MBChB, FRCR, DMRT, Consultant Radiotherapist & Oncologist, Weston Park Hospital, Sheffield, u. K. POTTER, AM.

Molecular Genetics of Colorectal Neoplasia A Primer for the Clinician provides the latest information on the genetics of colorectal cancer within a context of basic genetics, describing the subject in understandable language and making it clinically relevant.

Although the anthracycline antibiotics represent much of the present and future of cancer treatment, their actual use c stretches back barely two decades to the pioneering efforts of Aurelio Di Marco, who characterized the antitumor properties of daunomycin and adriamycin.

In creating this book, we aimed to cover a broad "bench to bedside" research spectrum ranging from: genetic, molecular and cellular analyses to epidemiological studies, refinements in local treatment strategies and new biologically based non-hormonal treatments for systemic disease.

The development of monoclonal antibodies to human tumor associated antigens has greatly facilitated the application of immunohistochemical techniques to analyze surgically removed tissues. Phenotypes of tumor cells have been identified which correlate with the biology of tumor cells and with the clinical course of the disease.

Special thanks are also due to those who assisted in the preparation and organization of the Symposium: the UNESCO officers, the interpreters, the secretaries and hostesses, the BEBA Company with the help of Dr.Bernard Martin and Mrs.Jacqueline Bouchy, the WILD- LEITZ-France S.A.

The last 30 years have seen little improvement in the age-adjusted mortality rates for most common types of cancer, and until we develop more effective and less damaging treatment modalities for these tumours, selection of each patient's treatment must depend on prognostic pointers.

In this book basic principles of pharmacology, mechanisms of drug resis- tance, new methods of drug delivery, guidelines for studying new agents in children, new biological response modifiers and the pharmacology of the most commonly used chemotherapeutic agents in children are reviewed in depth.

Many of the discoveries from the biological studies have impacted on the pathologist in the form of disturbing evidence for a single stem cell origin for all the cell types of lung cancer and in the shape of new facilitation in diagnosis by appli- cation of immunoperoxidase techniques.

The International Meeting on Brain Oncology in Rennes was organised in honor of Jean Pecker, to pay tribute to his contribution to the development of neurological sciences and to take stock of the current state of knowledge on brain tumors, a domain in which the role of neurosurgery has been and will continue to be primordial.

The development of monoclonal antibodies to human tumor associated antigens has greatly facilitated the application of immunohistochemical techniques to analyze surgically removed tissues. Phenotypes of tumor cells have been identified which correlate with the biology of tumor cells and with the clinical course of the disease.

They include the production and ap plication of monoclonal antibodies against differentiation antigens on the cell sur face, the use of pulse cytophotometry - and cell sorter techniques, the employment of cytogenetics, the development of culture techniques for selective growth of precursor cells and several others.

Many of the discoveries from the biological studies have impacted on the pathologist in the form of disturbing evidence for a single stem cell origin for all the cell types of lung cancer and in the shape of new facilitation in diagnosis by appli cation of immunoperoxidase techniques.

Proceedings of a symposium presented at the University of Southern California, Department of Pathology and the Kenneth J. Norris Cancer Hospital and Research Institute, Los Angeles, U.S.A., November 16-17, 1984

In this book basic principles of pharmacology, mechanisms of drug resis tance, new methods of drug delivery, guidelines for studying new agents in children, new biological response modifiers and the pharmacology of the most commonly used chemotherapeutic agents in children are reviewed in depth.