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Cellular drug resistance is a major limitation to the success of chemotherapy of leu kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance.
The last ten years have seen the publication of a vast amount of data regarding cellular resistance to drugs in cancer cells. Recent studies have demonstrated that drug resistance assays appear to be predictive of clinical response and suggest that clinicians should now be considering the potential applications of these assays in the treatment of patients with hematological neoplasms. This collection of papers from the International Symposium on the Clinical Value of Drug Resistance Assays in Leukemia and Lymphoma, Amsterdam, 1992, provides a state-of-the-art discussion on drug resistance assays and their role in the design and individualization of treatment protocols.
This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.
Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .
This book provides with a comprehensive overview of the role of drug transporters in drug disposition and efficacy/toxicity, as well as drug-drug interactions and recent advances in the field. Transporters are known determinants of drug disposition and efficacy/toxicity. In general, they are divided into solute carrier (SLC) and ATP binding cassette (ABC) families, and are located along cell membranes, where they mediate drug uptake into cells and export out of cells. Drug transporters are essential in maintaining cell homeostasis, and their gene mutations may cause or contribute to severe human genetic disorders, such as cystic fibrosis, neurological disease, retinal degeneration, anemia, and cholesterol and bile transport defects. Conversely, some diseases may also alter transporter functions and expressions, in turn aggravating disease process. Further, since over-expression of some ABC transporters is a potential contributor to multidrug-resistance (MDR), the book presents a number of strategies to overcome MDR, including ABC transporter inhibitors and applying epigenetic methods to modulate transporter expressions and functions. This book is useful for graduate students and professionals who are looking to refresh or expand their knowledge of this exciting field.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.
Since the original publication of Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Allogeneic hematopoietic stem cell transplantation (HSC) has undergone several fast-paced changes. In this second edition, the editors have focused on topics relevant to evolving knowledge in the field in order to better guide clinicians in decision-making and management of their patients, as well as help lead laboratory investigators in new directions emanating from clinical observations. Some of the most respected clinicians and scientists in this discipline have responded to the recent advances in the field by providing state-of-the-art discussions addressing these topics in the second edition. The text covers the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. Comprehensive and up-to-date, Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Second Edition offers concise advice on today's best clinical practice and will be of significant benefit to all clinicians and researchers in allogeneic HSC transplantation.
This is the third volume in the new World Health Organization series on histological and genetic typing of tumours. Tumours of the haematopoietic and lymphoid tissues are covered. This was a collaborative project of the European Association for Haematolpathology and the Society for Haematopathology and others. The WHO classification is based on the principles defined in the Revised European-American Classification of Lymphoid Neoplasms (REAL) classification. Over 50 pathologists from around the world were involved in the project and proponents of all major lymphoma and leukaemia classifications have agreed to accept the WHO as the standard classification of haematological malignancies. So this classification represents the first true world wide concensus of haematologic malignancies. Colour photographs, magnetic resonance and ultrasound images and CT scans are included.