There have been significant advances in the treatment of sarcomas in the past several years. Further, different clini cal treatment programs are being advocated in different areas including surgery alone, surgery with preoperative or post operative chemotherapy, surgery with different radiotherapy modalities, with each investigator espousing his own treat ment program. On the other side, there is the question of whether these treatment programs are offering better results or whether the natural history of sarcomas has changed. The International Symposium on Sarcomas was held at Innisbrook Resort, Tarpon Springs, Florida, October 8-10, 1987. This was the first international symposium to date involving all of the disciplines treating sarcomas including pathologists, orthopaedic surgeons, general surgeons, medical oncologists, pediatric oncologists, and radiation oncol ogists. The Symposium brought together a number of special ists working in the clinical field of sarcomas for a presen tation of their specific treatment programs and their results. The presentations were followed by panel discussions to stimulate educational debate as to the different forms of treatment for sarcomas and to formulate some conformity in control of disease, control of spread, and ultimate function for the patient. James R. Ryan, M.D."

The recent FDA approval of Provenger as the first therapeutic cancer vaccine together with the recent demonstration that Ipilimumabr, a monoclonal antibody that blocks the negative immune checkpoint cytotoxic T lymphocyte associated antigen-4, prolongs patient survival are major achievements that usher in a new era of cancer immunotherapy. These "first-in-class" treatments reflect the substantive progress that basic and translational scientists have made towards understanding the mechanisms underlying protective tumor immunity in cancer patients Immunotherapies were first explored at the turn of the twentieth century, but the crafting of potent treatments required more detailed knowledge of how the immune system responds to cancer. Advances in genetic, cellular, and biochemical technologies have begun to yield this critical information, focusing attention on immune recognition, regulation, and escape. Indeed, the dynamic interplay of these processes in the tumor microenvironment is now recognized to play a decisive role in determining disease outcome. This volume highlights the rapid progress and breadth of research in cancer immunology, and provides a framework for anticipating many more clinical successes in cancer immunotherapy.

This book overviews cancer immunity from broad scientific fields, based on the concept that cancer is a sort of by-product of infection, inflammation, and host immune response. The innate and acquired arms of the immune system mainly participate in tumor immune surveillance, and their activation is critically modulated by the situation of the tumor microenvironment. Many types of immune cells join the formation of the microenvironment. In particular, macrophages and dendritic cells enter the tumor mass to be main players in the inflammatory milieu of tumors. After introducing these topics, the book discusses immunotherapy for cancer patients as an outgrowth of this concept of infection and inflammation. With the contributions of leading scientists actively involved in the field of antitumor immunity study, this book encourages readers to understand the mechanism of general cancers based on inflammation and will facilitate prevention and the development of therapeutics for cancer.

Over one hundred contributions detail advances in the molecular and cellular biology of eicosanoid production, as well as their role in signal transduction. One of the most exciting developments explored within this collection of articles is the expression of the novel isoform of cyclooxygenase (cox-2), which may play a large role in the development of anti-inflammatory drugs.

Epigenetic modifications underlie all aspects of human physiology, including stem cell renewal, formation of cell types and tissues. They also underlie environmental impacts on human health, including aging and diseases like cancer. Consequently, cracking the epigenetic "code" is considered a key challenge in biomedical research. Chromatin structure and function are modified by protein complexes, causing genes to be turned "on" or "off" and controlling other aspects of DNA function. Yet while there has been explosive growth in the epigenetics field, human chromatin-modifying machines have only recently started to be characterized. To meet this challenge, our book explores complementary experimental tracks, pursued by expert international research groups, aimed at the physical and functional characterization of the diverse repertoire of chromatin protein machines - namely, the "readers, writers and erasers" of epigenomic marks. These studies include the identification of RNA molecules and drugs that interact selectively with components of the chromatin machinery. What makes this book distinctive is its emphasis on the systematic exploration of chromatin protein complexes in the context of human development and disease networks.

NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.

As in CANCER CHEMOTHERAPY 1, this volume brings to the reader highlights in three different areas of cancer therapeutics: new concepts and models; drug classes; and clinical settings. Topics were chosen because of their timeliness or probable current impact in cancer treatment. Authors were selected on the basis of their ability to provide a critical overview of specific subjects and their involvement in original work. I shall review the aims of this second volume, and then elaborate on the scope of its con tents. The principal aim of the volumes on cancer chemotherapy in the' Cancer Treatment and Research' series, as stated in the preface to the first volume, is to assemble in a concentrated form selected ingredients of chemothera peutic progress. These ingredients are to include concepts in therapeutic strategy, pre-clinical studies, development of major classes of compounds, identificatlon of new directions and of landmarks of clinical progress. Thus we do not foresee overlap with series which provide an yearly update of chemotherapy in an encyclopedic manner, or reviews of cancer chemother apy. Unlike those publications, our volumes are not intended to seek a place in shelves as a reference manual. It is this Editor's hope that persons repre senting various biomedical disciplines will seek the' Cancer Treatment and Research' chemotherapy volumes to survey advances in the field at regular intervals.

It is now becoming very clear that the development and progression of tumor towards the malignant (metastatic) phenotype depends tightly on the interaction between the tumor cells and the tumor microenvironment. Tumor cells respond to stimuli generated within the tumor microenvironment for their growth advantage while the tumor cell themselves reshape and remodel the architecture and function of their extracellular matrices. The term tumor microenvironment is a wide umbrella consisting of stromal cells such as fibroblasts and endothelial cells and infiltration immune cells including T and B cells, macrophages, and other inflammatory cells (PMNs). These different components of the tumor microenvironment could have stimulatory and inhibitory effects on tumor progression by regulating the gene expression repertoire within the tumor cells on one hand and the stroma cells on the other. In this volume we have seven contributors who will discuss several different aspects on the cross talk within the tumor microenvironment components leading to the acquisition of the metastatic phenotype. It is our hope that these state-of-the-art studies will shed further light on our understanding of these complicated processes.

We anticipate the book to be a definitive text on the subject that explores all aspects of the study of adrenal cancer and the treatment of patients with the disease. Chapters will cover epidemiology, pathogenesis, genetics, cancer stem cells, historic and emerging therapies, mouse models of adrenal cancer, new developments in tumor profiling, worldwide collaborative groups and tumor registries together with resources for the practitioner and community of adrenal cancer scientists.

We do not wish this book to compete with the other larger books in the Endocrine and Endocrine Surgery literature. In addition, it is not expected to cover benign adrenal diseases that have been covered in detail in other venues. We envision this book to be a very specialized and exhaustive text on basic, translational and clinical aspects of adrenal cancer.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfor tunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung can cer, genitourinary cancer, pediatric oncology, etc. Second, by asking emi nent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

In this volume, international experts discuss the following topics: molecular principles of the genesis of prostate cancer and the involvement of oncogenes and tumour suppressor genes; changes of cell-cell contacts; defects in androgen receptors and their effect on treatment with antiandrogens; drug resistance mechanisms and new therapeutic principles; and molecular diagnosis of prostate cancer.

During the last 10 years, the role of specific nutrients in cancer prevention and cancer treatment has been the subject of intense basic, preclinical, and clinical research. At present, the major focus of nutri tional oncology is on the mechanisms of carcinogenesis and their modification by nutrients and on cancer prevention studies in animals and humans. Some human epidemiological studies have confirmed the hypothesis, developed on animals, that there is an inverse relation ship between the intake and/or level of 3-carotene, vitamin A vita min E, or vitamin C and the risk of cancer, whereas others have shown no such relationship. This is not unexpected, since the protective effect of individual nutrients may be too small to be detected by epidemiological methodologies in which a single vitamin or mineral is considered as one variable. Conclusive evidence regarding the role of nutrients in human cancer prevention will come from a well designed human intervention study using one or more nutrients in a population that has a high risk of developing cancer. The involvement of specific nutrients in the regulation of protooncogene expression has just begun. Also, some of the results of human intervention trials are beginning to yield interesting results. A large number of interna tional scientists from various disciplines, including cell biology, mo lecular biology, nutritional oncology, epidemiology, and public health, reviewed and discussed their most recent findings. The following topics were emphasized: 1. Mechanisms of carcinogenesis; 2."

Leukemia continues to offer the scientist a unique opportunity to gain new knowledge about the malignant transformation. As a result, this multi-authored volume, devoted to advances which have occurred over the last seven years, provides the reader with an important new understanding of leukemia, but perhaps even more important, predicts analogous, new developments in the other malignant diagnoses. In this respect, this volume represents the cutting edge of cancer research. This text is unique in that it includes in a single volume the leading contributors to their respective fields covering what the editors feel are the major advances in our knowledge of the biology and therapy of leukemia over the last seven years.

Understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

This book presents a comprehensive collection of essential and up-to-date methods for studying both the biology of microtubules and the mechanisms of action of microtubule-interacting drugs. The book contains a straightforward presentation of readily reproducible protocols, tips for troubleshooting, and advice on avoiding common mistakes. Basic scientists and clinical researchers will benefit from this collection.

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.

Blood Stem Cell Transplantation conveys the excitement that accompanies the newest developments in hematopoietic stem cell transplantation. Some of the applications that stand to impact this field most significantly are based on recent advances in the biological sciences, as demonstrated by the chapters on gene therapy, on the detection of minimal residual disease using molecular techniques, and on the use of radioimmunoconjugates targeting lymphoma and leukemia-associated antigens. Others are the results of clinical observations - e.g., the association between graft-versus-host- disease (GVHD) and durable remissions that have led to creative clinical experiments such as donor leukocyte infusions (DLI). Attempts to unravel the biological events that underlie the responses seen in patients with relapsed chronic myelogenous leukemia treated with DLI are likely to provide the basis for future refinements in this clinical approach. Hopefully, improved response rates and reduced toxicity will result. The power of the immunologic response in controlling malignant disease is underscored in the chapter on post-transplant immunotherapy. The complex immunologic process that results in clinical GVHD may be dissected and engineered to provide clinical benefits that include, in addition to its antineoplastic effects, the amelioration of its clinical manifestations. Better control of GVHD with less global immunosuppression will facilitate the use of mismatched and unrelated donors. This area of investigation perfectly illustrates the continued interplay between the laboratory and the clinic. The continued cross-fertilization of ideas between immunologists, molecular biologists and clinical investigators is likely to yield important advances in this field for years to come. Possible applications of stem cell transplantation continue to grow with the identification of alternative sources of stem cells and the potential to engineer and/or expand the graft. Although the use of unrelated and mismatched donors continues to increase, the possibilities associated with umbilical cord blood transplantation are legion, especially if stem cells can be expanded ex vivo to provide grafts for full-sized adults. Using techniques in which contaminating malignant cells may be eliminated from autografts through positive selection, autologous transplantation may prove highly effective, especially when coupled with post-transplant immunotherapy. Some of these same methodologies have helped facilitate the use of autologous grafts for transplantation in patients with chronic myelogenous leukemia without allogeneic donors. Advances in the supportive care of transplant patients, including the pretransplant identification of those at risk from pulmonary complications and the use of cytokines to speed engraftment, have reduced morbidity and mortality to such a degree that it is appropriate to consider high-dose therapy and stem cell reconstitution in patients with nonmalignant diseases. The impressive advances that have occurred in transplantation for thalassemia are described by pioneers in their area of investigation. The burgeoning field of transplantation for autoimmune disorders, including its immunobiologic basis and soon-to- be-realized clinical potential, is also summarized. Continued progress in the use of high-dose therapy with stem cell rescue for the treatment of pediatric tumors, which derives in part from improved supportive care, is detailed. The sobering voice of the health care economists underscores the necessary limitations to our seemingly unbridled imagination. Cost- consciousness and financial know-how will need to be reflected in future study designs. Given the seemingly endless applications of our technology, strategies to insure its cost-effectiveness will be necessary. Continued financial support for laboratory investigation and for the clinical experiments they generate will be required if we are to go forward. Blood Stem Cell Transplantation lays the foundation for many of these future advances; it is incumbent upon us all to insure its realization.

Complex chemical mixtures impact our health every day. In the United States, and also in Central and Eastern Europe, there are a number of locations where complex chemical mixtures have been released to environmental media. Although exposure to mixtures is common, minimal information exists to quantify these exposures, or to determine their impact on human or ecological receptors. These proceedings present some of the most current research conducted to quantify complex mixtures in the environment and investigate their potential impact on human health. Many of the manuscripts reported in these proceedings represent the most up-to-date measurements of population exposures in Central and Eastern Europe. These studies are of value to health and environmental professionals around the world as they develop strategies for assessing exposures, remediating contaminated environments, and improving public health.

Developments in the understanding of the biology and treatment of Hodgkin's disease and non Hodgkin's lymphoma are moving at a rapid pace. New technologies, such as gene expression profiling in malignancy have been implemented using lymphoma to demonstrate their clinical utility. The objective of this volume is to review relevant aspects of the biology, diagnosis, and management with particular emphasis on emerging data available for this disease.

Timing, racing, combating, struggling and targeting are some actions through which cellular fate could be reflected and evaluated. Interaction between cell territory and environment occur during pre-embryonic, fetal development, and post-natal periods. What the researchers observe as the outcome of telomeres behavior is only the peak of an ice mountain within a stormy ocean. Cellular life depends on programmed behavior of telomeres, capable to surprise the cells. Telomeres provide an introduction to the history of our cells which govern the quality of life and status of health. Telomeres as the cooperative territory are capable of stabilizing the chromosomal territory. The status of telomeres reflects the key information, announcing the real age of individuals, and may be a valuable marker for prognosis and predicting cancer. Telomere territory is characterized with a multi-disciplinary manner. Therefore, this book is aimed to offer a wide range of chapters, hoping to be useful for diverse audiences, including hematologists-oncologists, radiotherapists, surgeons, cancer researchers, and all the sectors who affect the macro- and micro- environmental domains. Finally, telomeres are sensitive, cooperative, and trustable targets. It is worth to state that 'telomeres are messengers of NATURE', let's to know them as they are.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.

This edited volume describes cell-SELEX as the fundamental tool used to generate aptamer molecules for a wide range of applications in molecular medicine, bioanalysis and chemical biology. Easily integrated into the natural heterogeneous cell matrix, aptamers can be effectively used in theranostics, bioanalysis, environment detection and biomedical studies. The book gathers reviews that reflect the latest advances in the field of aptamers and consists in fourteen chapters demonstrating essential examples of these aptamers and aptamer-nanomaterial assemblies, depending on the types of applications and biological systems. It also includes a separate chapter on the utilization of aptamers in real clinics and what will be required to achieve this significant goal. The book will be both appealing and useful to a broad audience, including biologists, bioscientists, and clinicians whose interests range from chemistry and biomedical engineering to cell and molecular biology and biotechnology. Weihong Tan is a Distinguished Professor of Chemistry and Biomedical Engineering at Hunan University, China and also a University of Florida Distinguished Professor and V.T. and Louis Jackson Professor of Chemistry at the University of Florida, USA. Xiaohong Fang is a Professor at the Institute of Chemistry, Chinese Academy of Sciences, China.

In September 1998 experts from 19 countries came together for an interdisciplinary discussion of the function of animal peroxidases, a family of enzymes embracing myeloperoxidase, eosinophil peroxidase, thyroid peroxidase and lactoperoxidase. Their papers have been updated for publication, yielding a wide-ranging overview of the state of the art. The chapters cover a wide range of topics, including three-dimensional structure of representative family members, their biosynthesis and intracellular transport, mechanism of action as well as applications to clinical medicine. They are of clinical relevance in, for example, arteriosclerosis, multiple sclerosis, infections, tumorigenesis, rheumatic diseases and hypothyroidism. This book forms an excellent introduction for anyone interested in the peroxidase family of enzymes.