Pancreatic cancer is the fourth leading cause of cancer death in the United States. Every year, about 33,700 people in the United States will be diagnosed with pancreatic cancer and over 32,000 patients will die from the disease. The median survival of patients with advanced pancreatic cancer is about 6-months. This dismal picture of pancreatic cancer is mainly due to the lack of early diagnosis and effective treatment for patients with advanced disease. To increase the survival rate of pancreatic cancer patients, better tumor markers for diagnosis and new molecular targets for drug development are desperately needed. A lot of effort has been made in searching for pancreatic cancer-causing genes or genes associated with progression of malignant behavior in pancreatic cancer. As a result, alterations in the expression of several cancer-related genes have been identified in pancreatic tumors. The identification and characterization of these cancer-related genes have significantly increased our understanding of pancreatic cancer development, but unfortunately the treatment of pancreatic cancer has not advanced as much in the past 20 years.

Over the past decade, tremendous advances have been made in the field of cancer drug discovery, particularly, in the area of molecular and genetic models and technologies. Many of those advanced models and technologies have been applied to the drug discovery processes for pancreatic cancer. In this book, a team of experts will describe the latest development in the application of these models and technologies in pancreatic cancer. The authors include basic researchers as well as clinicians who work in the front-line of the war against pancreatic cancer and have the first-hand experience on these cutting-edge tools and techniques. The book can be divided into two general areas: 1) model systems and 2) genomics and proteomics tools. In recent years there have been a lot of advances in the model systems for pancreatic cancer, including the further characterization of normal and cancerous pancreatic cell lines, the establishment of transgenic mouse models that recapitulate the initiation and progression of human pancreatic cancer, the development of a new xenograft model system for the evaluation of novel agents, and the establishment of a zebrafish pancreatic cancer model. The first four chapters of the book will be devoted to these models. The advances in genomics and proteomics research have made a major impact in cancer drug discovery. A number of these omics-based tools and techniques have been applied in the pancreatic cancer drug discovery. Chapters 5-9 of the book will discuss techniques for genome-wide examination of gene expression, copy number, methylation, function and regulation. Chapters 10-11 will discuss in situ techniques for studying chromosomal and gene copy number abnormalities as well protein expression changes in cancer samples. Chapters 12-14 will focus on techniques for global examination of protein expression levels in biospecimens obtained from pancreatic cancer patients. Cancer drug discovery has become more and more target-centric. "

Although pancreatic cancer is one of the most serious forms of cancers, the outlook for patients could be improved. The lack of clinical symptoms of early, surgically removable disease most often limits curative treatment options. The aggressive tumor cell biology, leading to a locally advanced nature of the disease and to early metastases, allows curative resection in only 20% of patients at the time of diagnosis. Patients are therefore often faced with a dreadful prognosis from a state of almost full physical health. Furthermore, because there is a high recurrence rate after curative resection, treatment of this tumor entity becomes a great challenge.

This book gives insight into the current understanding of the management of pancreatic cancer and considers recent findings in cancer research. It provides answers to questions of how to know when cancer is respectable, how to proceed when the diagnosis comes too late for a curative approach, and how to assess different study results. Moreover, it highlights new upcoming therapeutic options and experimental approaches, which might further improve the future prospects for patients with pancreatic adenocarcinoma.

Multivariate analysis is a mainstay of statistical tools in the analysis of biomedical data. It concerns with associating data matrices of n rows by p columns, with rows representing samples (or patients) and columns attributes of samples, to some response variables, e.g., patients outcome. Classically, the sample size n is much larger than p, the number of variables. The properties of statistical models have been mostly discussed under the assumption of fixed p and infinite n. The advance of biological sciences and technologies has revolutionized the process of investigations of cancer. The biomedical data collection has become more automatic and more extensive. We are in the era of p as a large fraction of n, and even much larger than n. Take proteomics as an example. Although proteomic techniques have been researched and developed for many decades to identify proteins or peptides uniquely associated with a given disease state, until recently this has been mostly a laborious process, carried out one protein at a time. The advent of high throughput proteome-wide technologies such as liquid chromatography-tandem mass spectroscopy make it possible to generate proteomic signatures that facilitate rapid development of new strategies for proteomics-based detection of disease. This poses new challenges and calls for scalable solutions to the analysis of such high dimensional data. In this volume, we will present the systematic and analytical approaches and strategies from both biostatistics and bioinformatics to the analysis of correlated and high-dimensional data.

Mesothelioma is a global problem, largely related to the previous use of asbestos products. Diagnosis is very difficult because of its diverse appearances and the potential for other diseases to mimic it. Written by experienced international experts to aid in pathological diagnosis, this book deals with clinical, radiological, epidemiological, molecular, and histopathological aspects of the disease. Tumors of the pleural, pericardial, peritoneal cavities as well as the ovary and tunica vaginalis are considered. Differential diagnoses of serosal-based lesions are discussed and the use of immunohistochemical stains is explained. Plentiful illustrations give further aid to diagnosis.An essential read for all diagnostic pathologists as well as general pathologists, who are sometimes required to diagnose the disease at biopsy or post mortem; also invaluable to medical and legal professions involved with various aspects of the disease.

Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases.This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events.

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the "DNA damage response". This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs). This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade. The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer's diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis and neuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

A cutting-edge review of how derangements in the hormonal and growth factor mechanisms controlling normal mammary development lead to breast cancer. Drawing on the multidisciplinary expertise of leading authorities, the book highlights the roles of oncogenes and tumor suppressor genes, spelling out the importance of autocrine/paracrine loops (e.g., stromal epithelial interactions) in supporting breast cancer cell proliferation and the progression to hormone independence. The book's many prominent contributors also illuminate significant recent advances in the biochemistry and physiology of hormone receptors and review the state-of -the-art in the endocrine therapy of breast cancer. Endocrinology of Breast Cancer provides a unique integrated overview of the most significant basic and clinical developments concerning the hormonal aspects of breast cancer.

This volume gives a general summary of the current understanding of lymphatic metastasis and the possibilities of more specific detection of lymph node metastasis. It describes in detail the procedure of sentinel lymph node detection in urogenital tumors, neck and thyroid tumors, malignant melanoma, gastric and colorectal cancer and tumors of the breast. The potential and limitations of this new method are discussed. This book provides comprehensive insight into a both clinically and scientifically important new field which is bringing about a marked improvement in the treatment of malignant tumors.

This book is about "Angiogenesis". A process in which new vasculature is formed from pre-existing capillaries. Angiogenesis process is associated with the proliferation and growth of both physiologically normal and neoplastic tissues, through the formation of vascular supply, essential for delivering growth requirements such as oxygen and nutrients. The book describes more than 100 genes and their key regulatory functions in the context of normal healthy condition, disease and malignancy, cancer proliferation and progression. New insights into the role of angiogenesis and the therapeutic inhibition of its regulators are investigated, due to the great potential for exploitation in the development of a novel treatment for cancer. New scientists, junior researchers and biomedical science students will find this book an invaluable introductory reference to their insight about angiogenesis and angiogenic role of more than 100 angiogenes and their role in healthy, disease and malignant conditions.

This book is about melanoma-its biology, immunology, and pathology, as well as the initial use of powerful genomic tools to study its fundamental mole- lar and genetic characteristics. The study of cancer will be profoundly impacted by the Human Genome Project. I would like to discuss some of these changes. The first draft of the human genome sequence was announced in June 2000, and we have just scratched the surface of the changes it will engender in medicine. A relevant question is what are the long-term effects of the Human Genome Project for medicine? I would argue that there are three, and each of these three point toward the view that systems biology will dominate biology and medicine of the 21st century. First, the Human Genome Project introduced a new type of s- ence-discovery science. Discovery science takes a biological system (e. g. , the genome) and defines all of its elements (e. g. , the sequences of the 24 human ch- mosomes). Thus, it creates a rich infrastructure from which the classical hypo- esis-driven science can be done more effectively. The effective integration of discovery- and hypothesis-driven science is a key for systems approaches to bi- ogy and medicine. Second, the Human Genome Project has provided a "periodic table of life.

Despite the major developments in the therapeutic armamentarium for the treatment of infection, the morbidity and mortality of this complication remains very high in patients with compromised defences. Cancer and its treatment represents a major predisposing condition to a variety of infections. These adverse events are still with us, in spite of much progress in the therapy of infectious disease, since cancer therapy is becoming more aggressive, yet further lowering the host's capacity to cope with infections. Moreover, the pathogens adapt effectively to drugs, and at a pace that might outrun industry's capability to produce new agents. Finally, new pathogens are appearing as a consequence of both selection and severe immunosuppression. Infection is so common among cancer patients that its diagnosis and management represent a daily challenge to all oncologists, who must continually strive to keep abreast of developments in the area. The present comprehensive review of the most crucial and challenging aspects of the infectious complications in cancer patients will help them to do just that.

In the late 1980s, a promising new treatment for breast cancer emerged: high-dose chemotherapy with autologous bone marrow transplantation or HDC/ABMT. By the 1990s, it had burst upon the oncology scene and disseminated rapidly before having been carefully evaluated. By the time published studies showed that the procedure was ineffective, more than 30,000 women had received the treatment, shortening their lives and adding to their suffering. This book tells of the rise and demise of HDC/ABMT for metastatic and early stage breast cancer, and fully explores the story's implications, which go well beyond the immediate procedure, and beyond breast cancer, to how we in the United States evaluate other medical procedures, especially life-saving ones.
It details how the factors that drove clinical use--patient demand, physician enthusiasm, media reporting, litigation, economic exploitation, and legislative and administrative mandates--converged to propel the procedure forward despite a lack of proven clinical effectiveness. It also analyzes the limited effect of technology assessments before randomized clinical trials evaluated decisively the procedure and the ramifications of this system on healthcare today.
Sections of the book consider the initial conditions surrounding the emergence of the new breast cancer treatment, the drivers of clinical use, and the struggle for evidence-based medicine. A concluding section considers the significance of the story for our healthcare system.

This volume contains a collection of writings from the leaders in the fields of Molecular Biology and Melanoma Research which will begin to tell the ever-expanding story of the most recent findings, discoveries, and potential of BRAF-directed targets in melanoma. Recent research has shown that BRAF inhibitors are effective for a short period of time, but there is little hope that this drugs as single agents will lead to durable benefit in a majority of patients. Among scientists and researchers who work in drug discovery, there is a lot of interest in the development of molecularly targeted cancer agents. Namely, the identification of a molecular target, the selection of molecules which effectively inhibit this target. What is starkly different about the development of this class of compounds, however, is that the mechanism of action of these agents are not as straightforward as was once previously assumed and the mechanisms of resistance that tumor cells employ to evade complete destruction are unlike any that have been described before. These discoveries in addition to utilization of modern molecular biology techniques have led to a series of hypotheses regarding which other types of molecules could be used in combination with BRAF-inhibitors in hopes of revolutionizing the potential of therapeutics in melanoma.

Pancreatic cancer is a formidable disease, and advances in early detection and improved therapeutics have been slow to come forth. With new advances in molecular genetics in the field of pancreatic tumorigenesis, it is an opportune time to use these recent discoveries to enhance our understanding of pancreatic cancer biology and to improve outcomes in patients. In this volume, leading experts in the field shed light on these findings describing the mutational landscape of pancreatic cancer, including new inroads into our understanding of familial pancreatic cancer, epidemiology, the biology of K-ras signaling, and the emerging contribution of epigenetic alterations to disease initiation and progression. The distinctive pancreatic cancer-stroma ecosystem as determined by the dynamic interplay of inflammation, hallmark mutations, EMT, and cancer stem cells is described, and implications of these interactions in the context of development of novel, personalized therapeutic options are explored.

Much of organic chemistry is based on the ability of suitably structured chemicals to bind together through the formation of covalent bonds. Biochemistry is replete with exam ples of enzymatically catalyzed reactions in which normal body constituents can be linked through covalent bonds during the process of intermediary metabolism. The finding that xenobiotic chemicals that enter the body from the environment, are metabolized to highly reactive species, and then covalently react with cellular macromolecules to induce toxic and carcinogenic effects was an observation that spawned the research featured in the Fifth International Symposium on Biological Reactive Intermediates (BRI V). The group of investigators that became fascinated with this process and its signifi cance in terms of human health began their discussions in Turku, Finland (J 975), and continued them at Guildford, England (1980), College Park, Maryland (1985), Tucson, Arizona (1990), and Munich, Germany (1995). Among the results were a series of reports listed below, as well as the book for which this serves as the Preface. * Jollow, DJ., Kocsis, J.J., Snyder, R. and Vainio, H. (eds), Biological Reactive Intermediates: Formation, Toxicity and Inactivation, Plenum Press, NY, 1975. * Snyder, R., Park, D.V., Kocsis, J.J., Jollow, D.V., Gibson, G.G. and Witmer, C.M. (eds), Biological Reactive Intermediates II: Chemical Mechanisms and Biological Effects, Plenum Press, N.Y., 1982.

Teddi Mervis lost her fight with cancer when she was 12 years old. Beginning with the diagnosis of her brain tumor, the story tells of her three-year battle for life--a struggle she eventually lost. Although Teddi passed away, her memory inspired those who had helped her to deal with her suffering to band together to aid other children who are facing cancer. These people and thousands of others inspired by Teddi's story--from construction workers to college students to bank presidents--helped form an organization whose primary purpose is to make the lives of children as happy and rewarding as possible. The organization, Camp Good Days and Special Times, Inc., has become one of the largest and most successful organizations of its kind in the world. It is credited with breaking down the barriers for children with cancer and creating pioneering new programs. The 2001 Edition carries the story forward from 1990 with new photographs and an afterword. This book serves to teach and guide those who must cope with the devastating ordeal of childhood cancer.

Biological inorganic chemistry is a field of research at the interface of inorganic and biological chemistry. The rapidly developing insights into the role of metals in biological systems has far-reaching implications not only for biological science but also for related disciplines, ranging from molecular medicine to the environment. In each volume the reader, whether engaged in chemistry, biochemistry, biology or molecular medicine, receives a comprehensive summary and critical overview of a topic of high current interest written by leading international experts.

Newly developed molecular target anticancer drugs have shown remarkable efficacy even in the treatment of intractable cancers such as hepatoma and renal cell carcinoma. As cancer research is becoming a multidisciplinary endeavor, close cooperation across the basic, translational, and clinical research fields holds the promise of further advances in cancer therapeutics. This book sets forth new strategies for development: cancer therapy targeting receptor tyrosine kinases with clinical utilization of new signaling regulations; interaction between cancer progression and extracellular environments such as inflammatory cytokines and the extracellular matrix; and investigation of biomarkers for personalized cancer therapy, with microarray analysis and pharmacogenomics technology. These and other findings from the latest investigations into cancer cell biology and therapeutics make this book an invaluable source for investigators in both the clinical and basic cancer research fields.

This book is based on presentations by some of the world 's leading experts at the Sixth International Conference on Clinical Cancer Prevention, held in St. Gallen, Switzerland, during March 2010. The main themes are the latest advances in the prevention of breast and prostate cancer and the role of infection in the development of liver and gastric cancer. Special emphasis is given to perspectives on the chemoprevention of breast cancer, as the conference included an international consensus meeting on this subject. New research findings are presented and potentially more effective cancer prevention strategies are discussed, with careful consideration of controversies. The expertise of the contributors encompasses genetics and microbiology, epidemiology, and health economics, as well as clinical cancer prevention. This book will be of interest to all who wish to learn about the most recent progress in combating the development of cancer.

The series, Hormones in Health and Disease, was launched in 1993 to provide a scientific platform for investigators engaged in research on the biological actions of hormones and to anticipate relevance for their findings in clinical applications. The first volume of the series was dedicated to the discussion and understanding of molecular mechanisms by which steroid hormones influence target cells in normal and pathological conditions. With the diversity of information and the vast amount of literature on steroid hormone physiology, a more thorough treatment of Hormones and Cancer was identified as a timely topic. In this second volume in the series, Dr. Wayne V. Vedeckis has success fully undertaken the monumental task of editing the findings of the leading investigators in hormone and cancer research. Dr. Vedeckis brings to this project two decades of research experience in hormone action; he is actively engaged in elucidating hormone and cancer interrelations. It is a pleasure to welcome him to the series as an editor and congratulate him and all contribu tors in presenting this comprehensive treatise. The 20 chapters include discussions on contemporary topics relating control of cell division and signal transduction to the basic mechanisms of carcinogenesis by cloning patient genes, and recognizing the importance of steroid receptors in treatment protocols of various endocrine abnormalities."

In 1890, just a few years after the discovery of the chromosomes, David Paul Hansemann, a pathologist-in-training with the famous Rudolph Virchow in Berlin, produced a theory of the pathogenesis of cancer involving the key current concept: that the first change which occurs in cancer is an alteration of the hereditary material of a normal cell at the site where the cancerous process begins.

In the process of linking cancer to chromosomal material, Hansemann coined the terms "anaplasia" and "dedifferentiation." These terms have remained the basis of descriptive terms concerning the microscopical appearances of tumours ever since. Nevertheless, despite the popularity of his terminology, Hansemann's ideas were attacked vigorously by almost all proponents of rival theories of the nature of cancer. Partly due to these disputes during his life-time, and partly due to other factors, interest in von Hansemann's ideas diminished during the twentieth century and his works are rarely mentioned today.

This book presents translations of all the relevant German texts, and analyses the background and context of Hansemann's theories as well as the reasons why he was almost completely forgotten. It shows that some of Hansemanna (TM)s ideas may still be relevant to cancer research today, and that he deserves to be remembered in relation to cancer as Vordenker unter den fA1/4hrenden Denkern seiner Zeit - The foremost of the leading thinkers of his time.

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.