Therapeutic options for late-stage liver cancer are very limited and the prognosis is often poor. A better understanding of the molecular mechanisms involved in the initiation, progression, and metastasis of hepatocellular carcinoma is critical for developing more rational diagnostic and therapeutic approaches. This e-book covers current developments on clinically relevant research on the molecular biology of hepatocellular carcinoma. It should be a valuable reference for professional gastroenterologists, hepatologists and oncologists as well as medical students and researchers.

The number of new discoveries related to diagnostics and therapeutics of hematological cancer is significant. These have resulted in continuous progress in fundamental knowledge about molecular and cellular mechanisms in hematological neoplasia. Physiopathogenesis of Hematological Cancer presents a concise overview of the cellular and molecular biology of myelo- and Lymphoproliferative disorders. The expert reviews presented within this e-book are also accompanied by bibliographic references for relevant scientific literature. This book should prove to be a valuable reference tool for both medical graduate and postgraduates in the field of oncology.

Cancer is one of the major causes of death worldwide. Despite hundreds of clinical trials currently in progress for cancer patients, the success rate is still very low. Understanding the molecular aspects of cancer development, the discovery of new molecular targets and rational drug design on this molecular basis should help in discovering early cancer biomarkers as well as novel therapeutic drugs. This book describes various cancer topics on a molecular level and integrates information on the relationship between causes of cancer, cancer cell biology, metastasis, cancer prevention and drug design. This book should prove to be an extraordinary reference text for students, physicians and oncologists.

Multiple Myeloma (MM), the second most common blood cancer in adults, is a clonal plasma cell malignancy within the bone marrow characterized by osteolytic bone lesions, renal disease, and immunodeficiency. It is now well established that MM cell- induced disruption of the bone marrow homeostasis between the highly organized cellular and extracellular compartments supports MM cell proliferation, survival, migration, and drug resistance via activation of various signaling pathways. Based on this knowledge, the prototypic drugs thalidomide, bortezomib, and lenalidomide, which target both MM cells and the bone marrow microenvironment, have already fundamentally changed treatment options of this disease. Indeed, their benefit is now not only shown in relapsed and refractory disease but they also improve overall response, duration of response, and progression-free and overall survival when used as part of first-line regimens. However, despite new insights into MM pathogenesis and exciting derived therapeutic advances, MM still remains incurable. Ongoing studies are therefore aiming to further delineate mechanisms of MM pathogenesis within the bone marrow to identify novel agents with enhanced cytotoxicity and decreased drug resistance to improve patient outcome. Multiple Myeloma - A New Era of Treatment Strategies is devoted to contributions from eminent scientists providing readers with comprehensive accounts of the most recent developments in the field of MM research. It addresses the interests of scientists and clinical investigators in MM research as well as other fields of oncology, in which the microenvironment is believed to play an important role.

The WHO report estimates that 12 million people will be diagnosed with some form of cancer this year. In addition, the report predicts that more than 7 million people will die early from the disease. Together, the number of cancer cases and deaths from cancer are expected to increase by one percent each year. Cancer research has seen remarkable advancements, including the multi-step carcinogenesis theory and the identification of a cancer stem cell. These advancements are being applied to clinical therapies targeting the oncogene. In addition, the function of the gene product is becoming clear through analysis of the intracellular signaling of the oncogene. As a result, it has become clear that the morphologies of the cancers depend on the kind of the abnormal gene. Of course, these differences would influence patient’s life and death and is summarized by specialists in this area. This theme includes the full range of human diseases regarding medical genetics, biochemistry, microbiology, immunology, anatomy, pathology, structural biology, molecular cell biology, neuroscience and developmental biology. The eBook contains articles written by specialists in this area. It should prove to be of great use to clinicians and scientists in all medical fields.

This e-book explains the essential role of angiogenesis in the progression and spread of the neoplasm, including the mechanics of initial carcinogenesis in promoting malignant transformation. The e-book deals with specific categories or subtypes of tumors with some emphasis on astrocytomas and glioblastoma multiforme. The process of carcinogenesis has been re-interpreted in terms of deranged physiologic principles and hence reference is made to what upsets homeostatic mechanisms. Readers of this e-book will have an opportunity to appreciate the essential role of angiogenesis not only in progression and spread of the neoplasm but especially also in the mechanics of initial carcinogenesis in promoting malignant transformation. This e-book should be a useful reference for scholars and clinicians interested in learning about cancer pathophysiology.

The book presents recent advances in the field of angiogenesis and antiangiogenesis. Starting with the hypothesis of Judah Folkman that tumor growth is angiogenesis dependent, this area of research now has a solid scientific foundation. Tumor growth, metastasis, progression, dormancy and apoptosis depend on angiogenesis: several clinical studies have shown a positive correlation between the number of vessels in the tumor, metastasis formation and disease prognosis. A number of approaches have been developed to inhibit tumor angiogenesis, and numerous compounds discovered that inhibit angiogenesis, but only a few of them proved effective in vivo and only a couple of agents were able to induce tumor regression. These and other related developments described in the book should prove to be of interest to a large number of readers wishing to keep abreast with the latest developments in the field.

Neuro-oncology is an embryonic field of cancer research with a number of clinical trials in progress. However, the prognosis on neuro-oncologic patients has remained poor. Moreover, several small scale phase I/II trials performed have proved to be inconclusive because of the limited number of patients involved. As a result, many controversies exist in neuro-oncology drug development for which a forum does not exist. This ebook presents a detailed account on the use of avastin in treating cancer patients. A discussion on clinical experiences and the controversial debate among researchers of avastin's role in restricting malignant gliomas is also included giving readers a diverse perspective on the rationale of treating CNS tumors.

This comprehensive ebook covers all the aspects of ADME/PK modeling including solubility, absorption, formulation, metabolic stability, drug-drug interaction potential and a special delivery tool of drug candidates. The book provides an integrated view of fundamental ADME issues and challenges in early drug development from the aspect of practicing drug researchers. It also provides valuable help for the medicinal chemist in the process of multiple optimization.

Thermodynamics and kinetics (i.e., chemical interactions) are extremely important concepts for pharmaceutical scientists to understand since the “drug selection process”, that is, the process used by pharmaceutical companies to discover and develop marketable drugs, is totally dependent upon these theories. While both theories are important, kinetic models describing complex chemical and biological processes provide a unifying theory for all phases of the discovery and development of drugs. Unfortunately, in most textbooks the mathematical descriptions necessary to develop a deeper understanding of kinetic models are omitted. This is primarily done such that the underlying chemistry and biochemistry principles are not obscured by the “mathematical maze” that is generated from these models. As a result many chemists and biologists veer rapidly away from thermodynamics and kinetics. For some scientists, this can lead to confusion on how to apply these models to real-life situations. For example, many enzyme kinetic models are formulated as rate equations. Since experimentally measurements typically determine concentrations and rarely determines rates directly, confusion arises on how to apply kinetic models. In this case, either the model is integrated to give a description of the concentration course of the enzyme reaction or the data is differentiated (i.e., the process of determining rates) by measuring tangents to the reaction curves at zero time. The level of mathematical skills required to solve kinetic models is minimal for anyone who has studied college level algebra and calculus. Thus, the objective of this book is to present a brief review of thermodynamics and kinetics followed by a detailed step-by-step approach in developing and solving kinetic models for complex chemical and biological processes. The book focuses on building a solid mathematical foundation of enzyme kinetic models by systematically evolving simple uni- and bi-molecular models to enzyme models. Applications for some of these kinetic models are generated from pharmaceutical examples and a selection of problems is presented at the end of each chapter. This elementary approach has been intentionally selected to keep the book at a self-explanatory level. It is anticipated that the reader will be able to follow the mathematical operations and in the process develop a deeper understanding of kinetic models and an improved ability to interpret kinetic parameters. The book is restricted to solution chemical kinetics and does not deal with the theories of chemical reactions, gas-phase reactions, experimental kinetic methods and so on. There are many excellent chemical kinetic textbooks available for those interested in these topics. The solution chemical kinetics materials for the book were obtained from literature papers and several books on physical chemistry and enzyme kinetics. The ideas from these sources have been hopefully reinterpreted in a style that is well matched to those pharmaceutical scientists that do not have a comprehensive knowledge of kinetic models and the mathematical skills to solve them. Chapter 1 presents a general overview to thermodynamic and kinetic principals and theory. In Section i, an overview to the scope of the book is presented. A brief review of mathematical fundamentals used in the book (Section ii) and kinetic and thermodynamic principals are present (Section iii and iv). A glossary of symbols and abbreviation used throughout the book is presented in Section v. Chapter 2 describes the basic theory of first-order kinetic models. These types of mathematical models are used for irreversible (Section I) and reversible (Section II) rearrangement reactions and some examples are presented to illustrate their applications to drug discovery. Chapter 3 describes second-order irreversible (Section III) and reversible (Section IV) dimerization reactions while Chapter 4 describes second-order irreversible (Section V) and reversible (Section VI) binding reactions. Chapter 5 describes partially and fully coupled reversible completive binding reactions (Section VII). Chapter 6 describes second-order kinetic models that are used to analyze consecutive irreversible (Section VIII) and reversible (Section IX) substrate suicide enzyme reactions. Chapter 7 describes kinetic models that are used to analyze consecutive irreversible (Section X) and reversible (Sections XI and XII) enzyme reactions. Chapter 8 describes kinetic models that are used to analyze consecutive reversible inhibition enzyme reactions (Section XIII - XVI). Chapter 9 describes kinetic models that are used to analyze substrate (Section XVII) and product inhibition (Section XVIII) enzyme reactions. The Appendix contains the answers to the problems.