The fifth of the annual research conferences of the American Institute for Cancer Research was held September l-2, 1994, at the L'Enfant Plaza Hotel in Washington, DC. Appropriately, in view of current directions in research, the theme was "Diet and Cancer: Molecular Mechanisms of Interactions." This proceedings volume contains chapters from the platform presentations and abstracts from the poster session held on the end of the first day. The subtopics for the tl;rree sessions held were "Retinoids, Vitamins A and Din Cancer Prevention and Therapy," "Choline and Lipids: Signal Transduction, Gene Expression and Growth Regulation," and "Dietary Factors and Regulation of Oncogenes, Growth and Differentiation. " A general overview on vitamins A and D emphasized that A and D, in addition to their established roles in vision, reproduction, and bone mineral homeostasis, may play significant roles in regulating cell function. Vitamin A metabolites, trans-retinoic acid and 9-cis-retinoic acid, regulate growth and differentiation. Furthermore, vitamin A deprived animals were more susceptible to both spontaneous and carcinogen-induced tumors. Epidemiological studies showed a correlation between low A intake and higher incidences of certain types of human cancers. Conversely, all-trans retinoic acid is useful in treatment and control of certain types of cancer. Physiologically, Vitamin D is converted to the active form, l,25-dihydroxyvitamin D (VD). VD regulates hormone production and secretion, myocardial contractility, vascu 3 3 3 lar tone, and growth inhibition and differentiation."

This new work on oral complications of cancer chemotherapy is edited by two dentists who have made pioneering contributions in this previously neglected area. Their efforts have established the invaluable role of the dentist in oncologic research and cancer patient management. The editors have collected nine chapters that will be of interest to dentists and dental hygienists, oncology nurses, and all physicians treating cancer patients with chemo therapeutic agents. Background chapters on oral complications of cancer chemotherapy, the pharmacology of chemotherapeutic agents, and principles of infection management and prevention set the stage for more specific chapters focusing on prevention and treatment of chemotherapy induced oral and dental disorders. Valuable contributions to the supportive care of the cancer patient are contained in this book. A full comprehension of this book, coupled with an appreciation for advances in other areas of supportive care, such as antiemetic therapy and pain control, will allow all those involved in cancer treatment to be more successful. Peter H. Wiernik, M.D. Emil Frei, M.D."

The field of genito-urinary oncology is rapidly evolving at virtually every level. Significant advances have been made in our understanding of the molecular and cellular events which contribute to the generation of GU malignancies. At the same time, similar advances have been made in the clinical arena which have improved the diagnosis and treatment of urologic cancers. This volume attempts to summarize those advances which most impact us as clinicians, and has been divided into three sections. Section One, `Diagnostic advances: the use of molecular medicine in the diagnosis and prognosis of GU malignancies', details how epidemiologic studies and new molecular techniques are impacting our ability to diagnose and treat GU tumors. Section Two, `Surgical and radiation advances', details the recent major advances in the treatment of organ-confined cancers. Section Three, `Medical advances', addresses major issues in the treatment of metastatic disease. This volume will serve as a compendium of the advances, both at the basic science and clinical levels, which are currently impacting practicing oncologists and urologists.

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. Unfortunately, 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 cancer, genitour inary cancer, pediatric oncology, etc. Second, by asking eminent 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."

A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (Velcade (TM)) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

A comprehensive state-of-the-art summary of breast cancer research and treatment by leading authorities. The book's many distinguished contributors illuminate the biology and genetics of breast cancer, including what is known about the hereditary breast cancer genes, BRCA1 and 2, the cutting-edge cytogenic approaches, and the biology of breast cancer metastasis. In addition, the authors describe current and future methods of breast cancer treatment in depth, and discuss environment and diet as risk factors for the disease. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics constitutes an excellent reference and resource for all those clinical and experimental oncologists, as well as genetic counselors nurses, who need to understand the latest developments in breast cancer biology, risk, and treatment.

This book provides an up-to-date comprehensive overview of the exciting new developments shaping the current and future practice of radiation oncology. Advances in treatment planning and delivery, in biological targeted therapies combined with radiation and in functional and molecular imaging are all covered in a single volume. All of these advances are discussed by leading experts in the field and with a critical evaluation of their clinical relevance throughout.

In recent decades eicosanoids have been attracting an increasing amount of attention as a result of their important physiological roles in many areas of biology and medicine. The eicosanoids comprise the prostaglandins, thromboxanes and leukotrienes and are products of arachidonic acid, an essential polyunsaturated fatty acid stored in tissue phospholipids. Disturbances of eicosanoids and their metabolic products play a regulatory role in many types of cell injuries and diseases. One of the most exciting areas of eicosanoid research pinpoints their participation in the control of cell proliferation and differentiation. Eicosanoids form a link between different fields of research into such areas as cancer, inflammation and radiation-induced injury. This link provided the impetus for the development of the conference series of which the present volume represents the proceedings of the Second International Conference, held in Berlin in October 1991.

This thesis presents the development of theranostic gold nanostars (GNS) for multimodality cancer imaging and therapy. Furthermore, it demonstrates that a novel two-pronged treatment, combining immune-checkpoint inhibition and GNS-mediated photothermal nanotherapy, can not only eradicate primary treated tumors but also trigger immune responses to treat distant untreated tumors in a mouse animal model. Cancer has become a significant threat to human health with more than eight million deaths each year, and novel methods for cancer management to improve patients' overall survival are urgently needed. The developed multifunctional GNS nanoprobe with tip-enhanced plasmonics in the near-infrared region can be combined with (1) surface-enhanced Raman spectroscopy (SERS), (2) two-photon photoluminescence (TPL), (3) X-ray computed tomography (CT), (4) magnetic resonance imaging (MRI), (5) positron emission tomography (PET), and (6) photothermal therapy (PTT) for cancer imaging and treatment. The ability of the GNS nanoprobe to detect submillimeter intracranial brain tumors was demonstrated using PET scan - a superior non-invasive imaging modality - in a mouse animal model. In addition, delayed rechallenge with repeated cancer cell injection in cured mice did not lead to new tumor formation, indicating generation of a memorized immune response to cancer. The biocompatible gold nanostars with superior capabilities for cancer imaging and treatment have great potential for translational medicine applications.

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."

This book provides a comprehensive, highly readable overview of our current knowledge of the molecular pathology of basal cell and squamous cell carcinomas. The chapters present the newest findings in epidemiology, photocarcinogenesis, genetics, immunology and molecular pathology of these epithelial skin tumours. Topics include the importance of the hedgehog/patched/smoothened/GLI, p53, PDGF, or TGF-b signalling pathways as well as the relevance of papilloma virus infections, apoptosis, DNA-repair and telomerase.

A long time has passed since the war act on Cancer declared by former USA president Nixon, almost half a century ago. Today, after so many years of feverish research and uncountable efforts worldwide, the end of the war appears far as ever, whereas the fight is leading researchers to newer and newer battlefronts while frontiers in bioscience are continuously being surpassed. In this scenario, "The Selfish Cell" is a script record of the most important strategic points gathered during these years of war, with the goal to provide solid ground onto which to step ahead for future assaults against this terrible disease. At the same time, it is an attempt to shift the debate on cancer toward a more peaceful and possibly productive semantic terrain, where to reflect with the aid of superior wisdom to finally get out of that terrible chaos of fight and death dominating our days. In this perspective, "The selfish cell" becomes an occasion for reflecting the limits of our human selfishness and their consequences on both our social and natural environment.

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.

This volume provides insight into recent developments on experimental and clinical strategies for cancer gene therapy. Gene Therapy of Solid Cancers: Methods and Protocols guides readers through protocols on gene therapeutic strategies in combination with helpful technical notes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Gene Therapy of Solid Cancers: Methods and Protocols aims to ensure successful results in the further study of this vital field.

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.

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.

The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.

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.

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.

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.

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."

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.

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.

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.