This volume provides detailed descriptions of prevailing and novel techniques used by experts in the study of PTEN function in disease and biology. The book begins with chapters exploring methods to detect expression levels of PTEN in normal and diseased human specimens; methods to evaluate specific PTEN function in brain cancer; methods that utilize a new biosensor to measure PTEN regulation; and techniques to measure post-transcriptional regulation of PTEN by micoRNAs and ceRNAs. Other chapters present methods describing novel techniques to detect PTEN localization and previously unstudied structural features of PTEN measured through X-Ray Crystallography and Hydrogen Deuterium Exchange Mass Spectrometry. The book concludes with methods to study PTEN function in model organisms including mice and C. elegans. 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 tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, PTEN: Methods and Protocols is a valuable collection of methodologies and protocols useful to researchers who are interested in the PTEN field.

Fluoropyrimidine Metabolism and Mechanism of Action.- 5-Fluoro-2?-Deoxyuridine: Role of Schedule in its Therapeutic Efficacy.- Comparison of Continuous Infusions and Bolus Injections of 5- Fluorouracil with or without Leucovorin: Implications for Inhibition of Thymidylate Synthase.- Critical Questions for the Future Direction of FU/LV.- Cellular Interactions Between the Natural and Unnatural Isomers of 5-Formyltetrahydrofolate.- Leucovorin as a Prodrug.- Clinical Use of Leucovorin: Intracellular Metabolism.- Some Considerations Concerning the Dose and Schedule of 5FU and Leucovorin: Toxicities of Two Dose Schedules from the Intergroup Colon Adjuvant Trial (INT-0089).- Effects of 5-Fluorouracil on mRNA.- Genetic Variation in Thymidylate Synthase Confers Resistance to 5-Fluorodeoxyuridine.- Experience with 5FU + L-Leucovorin.- 5-Fluorouracil Combined with the Pure [6S]-Stereoisomer of Folinic Acid in High Doses for Treatment of Patients with Advanced Colorectal Carcinoma: A Phase I-II Study of Two Consecutive Regimens.- 5-Fluorouracil Modulation in Colorectal Carcinoma: Experience of German Investigators.- An Overview of Adjuvant Treatment of Colon Cancer.- Dose-Dependent Inhibition of Aspartate Carbamoyltransferase in Peripheral Blood Mononuclear Cells in Patients Receiving N-Phosphonacetyl)-L-Aspartate.- Alternative Approaches to Modulation of Fluoropyrimidines.- Increasing the Efficacy of 5-Fluorouracil with Interferons: Preclinical, Clinical, and Pharmacokinetic Studies.- Enchanced Cytotoxicity of 5-Fluorouracil Combined with [6RS]-Leucovorin and Recombinant Human Interferon-?2a in Colon Carcinoma Cells.- Regulation of Thymidylate Synthase in Human Colon Cancer Cells Treated with 5-Fluorouracil and Interferon-Gamma.- Biochemical Modulation of 5-Fluorouracil by PALA: Mechanism of Action.- Implications of Chronobiology for 5-Fluorouracil (5-FU) Efficacy.- Update on Metabolic Modulation as a Therapeutic Approach for Adult Carcinomas.- Fluorouracil and Leucovorin in Advanced Breast Cancer.- Fluorouracil Modulation in Head and Neck Cancer.- Biomodulation in Head and Neck Carcinomas: Therapeutic Approaches in Europe.- Rationale for the Combination Therapy of 5FU and CDDP.- Biochemical Modulation of Fluoropyrimidines: The "Giscad" Studies.- New Drugs.- Clinical Experience with UFT in Japan.- Clinical Studies of the Modulation of Ftorafur.- The Role of the Reduced-Folate Carrier and Metabolism to Intracellular Polyglutamates for the Activity of ICI D1694.- The History of the Development and Clinical Use of CB 3717 and ICI D1694.- New Sites of Intervention in the Development of New Drugs in Solid Tumors.- P53: A Determinant of the Cell Cycle Response to DNA Damage.- Therapeutic Implications of Molecular Genetics.- Concluding Remarks.- Summary.- Abbreviations.- Author Index.

This book presents the theoretical foundations of Systems Biology, as well as its application in studies on human hosts, pathogens and associated diseases. This book presents several chapters written by renowned experts in the field. Some topics discussed in depth in this book include: computational modeling of multiresistant bacteria, systems biology of cancer, systems immunology, networks in systems biology.

Retinoids have received considerable attention in recent years and due cognizance has been given to their versatility as biological response modifiers, as evidenced by the virtually explosive growth of literature in this field in the past few years. This volume has been designed to give a current state-of-the-art picture of retinoids. The perceived potential of retinoids in the treatment of certain disease stated has initiated attempts at identifying and synthesizing new retinoid derivatives with definable and selective effects on aberrant biological phenomena. Appropriately, therefore, we begin with the chemistry of retinoids and their derivatives together with discussions of their biological activity. Major advances have been made in understanding the mechanisms by which retinoids modulate physiological and phenotypic traits of cells. The transduction of retinoid signaling by the mediation of nuclear receptors of the steroid/thyroid receptor superfamily has now been studied extensively and the cloning and defining the characteristics of these receptors has been a focus of discussion in this volume. Retinoids also markedly modulate the transduction of extracellular signals such as those imparted by growth factors and hormones, and thus actively influence and control cellular proliferative patterns. Retinoids can alter epidermal growth factor receptor expression (Kawaguchi et al., 1994), responsiveness to thyroid hormone (Esfandiari et al., 1994; Pallet et al., 1994), inhibit the proliferative responses of hematopoietic progenitor cells to granulocyte colony stimulating factor (Smeland et al., 1994), and modulate secretion on interleukins by leukaemic cells (Balitrand et al., 1994), among other things. This has obvious implications for pharmacological manipulation of deregulated growth (Dickens and Colletta, 1993; Mulshine et al., 1993). Apoptosis is another component in the regulation of growth control. Apoptotic cell death is influenced by several agents and retinoids may function by interfering with apoptotic pathways of regulation of growth control and quite legitimately, therefore, the importance of this aspect of retinoid function has been duly recognized here.

This issue of Radiologic Clinics of North America focuses on Extranodal Lymphoma from Head to Toe, and is edited by Dr. Mark Murphey. Articles will include: Pathology of Extranodal Lymphoma; Pulmonary and Mediastinal Extranodal Lymphoma; Gastrointestinal Extranodal Lymphoma; Extranodal Lymphoma Involving the CNS and Spine; Genitourinary Extranodal Lymphoma; Musculoskeletal Extranodal Lymphoma; Pediatric Extranodal Lymphoma; Extranodal Lymphoma of the Breast; Cardiac Extranodal Lymphoma, and more!

The study of the molecular events leading to cellular transformation and cancer has progressed significantly in the last decade, and it has become apparent that many genes subject to modification in cancer are, in fact, transcription factors that govern the execution of the genetic programme of the cell. Transcription factors can behave either as oncogenes or as tumour suppressor genes. To date only a limited number of transcription factors have been associated with cancer. This volume deals with several transcription factor families that were first identified in oncogenic retroviruses. Each chapter contains a description of the structure of the transcription factors, the nature of target genes, the regulation of their activities, and an explaination of how they can deregulate cell growth and differentiation. This text should be suitable for the specialist scientist and the advanced student

This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.

This issue of Surgical Clinics of North America, guest edited by Dr. Clifford Cho, is devoted to Technical Aspects of Oncological Hepatic Surgery. He has assembled expert authors to review the following topics: Determination of Resectability; Radiographic Characterization of Hepatic Tumors; Chemotherapy-associated Hepatotoxicity; Preoperative Assessment and Optimization of the Future Liver Remnant; Anatomy of Hepatic Resectional Surgery; Resection of Gallbladder Carcinoma; Resection of Hilar Cholangiocarcinoma; Technical Aspects of Orthotopic Liver Transplantation for Hepatocellular Carcinoma; Hemostasis and Hepatic Surgery; Minimally Invasive Hepatic Surgery; Hepatic Tumor Ablation; Hepatic Transarterial Therapies; Hepatic Perfusion Therapy; Hepatic Artery Infusional Chemotherapy; Ex vivo Hepatic Surgery, and more!

The tumor microenvironment has become a very important and hot topic in cancer research within the past few years. The tumor microenvironment is defined as the normal cells, molecules, and blood vessels that surround and feed a tumor cell. As many scientists have realized, studying the tumor microenvironment has become critical to moving the field forward, since there are many players in a tumor's localized and surrounding area, which can significantly change cancer cell behavior. There is a dual relationship wherein the tumor can change its microenvironment and the microenvironment can affect how a tumor grows and spreads. Tumor Microenvironment in Cancer Progression and Cancer Therapy aims to shed light on the mechanisms, factors, and mediators that are involved in the cancer cell environment. Recent studies have demonstrated that in addition to promoting tumor progression and protecting tumor cells from the spontaneous immune-mediated rejection and different forms of cancer therapeutics, tumor microenvironment can also be a target and mediator of both standard and newly-emerging forms of cancer therapeutics. Thus, the dual role of the tumor microenvironment is the integral focus of the volume. The volume highlights the bi-directional interactions between tumor cells and non-malignant tumor component during tumor progression and treatment. It also focuses on the three groups of the reactive tumor component: stromal cells, blood vessels and the infiltrating immune cells. These three groups are discussed under the lens of their role in promoting tumor growth, shielding the tumor from rejection and from standard forms of cancer therapies. They are emerging as targets and mediators of standard and new forms of potential therapy.

This book describes in detail current best practice in the diagnosis and treatment of malignant pediatric bone tumors and also discusses other important aspects of management. Clinical assessment, the role of different imaging modalities and choice of biopsy procedure are explained and an individual chapter is devoted to diagnostic pathology. The treatment-oriented chapters offer in-depth descriptions of chemotherapeutic regimens, radiation therapy, limb-salvage options and amputation-related issues and in addition consider the approach to lung nodules, the role of biomarkers, off-therapy monitoring and the treatment of relapse. Psychosocial impacts and needs are addressed and guidance provided on nursing during treatment and rehabilitation following orthopaedic surgery. Closing chapters evaluate emerging therapies and discuss disparate aspects of survivorship. The authors are acknowledged experts and include many contributors from the Nationwide Children's Hospital, a leading pediatric care facility in the United States.

This book gives insight into the functional role of non-coding RNAs in central pathways contributing to the development of obesity, type 2 diabetes, non-alcoholic fatty liver disease, atherosclerosis, myocardial infarction, cardiomyopathy, and heart failure. It also sheds light on the relationship of this cluster with cancer. Tumor cells, in contrast to cells in cardiometabolic tissues, can regulate this cluster of non-coding RNAs to escape from oxidative stress and anti-tumor immunity and maintain insulin sensitivity, facilitating cancer progression. The book presents a cluster of non-coding RNAs that may be prospectively analyzed in extensive cohort studies to determine their value in risk-predicting machine learning algorithms. In addition, it emphasizes the role of microvesicles in communication between tumor-adjacent tissue, inflammatory cells, and tumor cells, with a special focus on the role of miR-155. The book intends to promote interdisciplinary research. Due to the comprehensive background information provided in each chapter, it is suitable for researchers in academia and industry and for graduate students in biology, bioengineering, and medicine.

This issue of Surgical Oncology Clinics of North America, guest edited by Nipun Merchant, MD, is devoted to Pancreatic Neoplasms. Dr. Merchant has assembled expert authors to review the following topics: Molecular and Genetic Basis of Pancreatic Carcinogenesis: Which Concepts May Be Clinically Relevant?; Role Of EUS and ERCP In The Clinical Assessment Of Pancreatic Neoplasms; Optimal Imaging Modalities For The Diagnosis and Staging Of Periampullary Lesions; Advances in the Surgical Management of Resectable and Borderline Resectable Pancreatic Cancer; Minimally Invasive Approaches to Pancreatic Surgery; Adjuvant and Neoadjuvant Therapy for Pancreatic Cancer; Palliative Management of Unresectable Pancreatic Cancer; Spectrum and Classification of Cystic Lesions of the Pancreas; Therapeutic Approach to Cystic Neoplasms of the Pancreas; Clinical Presentation and Management of Pancreatic Neuroendocrine Tumors; State-of-the-Art Imaging of Pancreatic Neuroendocrine Tumors; Surgical Approaches to Pancreatic Neuroendocrine Tumors; and Medical Management of Pancreatic Neuroendocrine Tumors: Current and Future Therapy.

This book is a compilation of past and recent knowledge in the field of emerging drug resistance. The book covers major aspects of drug resistance in bacteria, fungi, malaria, and cancer.Human survival on earth is constantly threatened by disease and syndrome. From the early days, the aim of research in medicine was to find therapeutic agents that can improve the quality of human life. Although humans are dependent on natural compounds from early days their dependence of drugs increased excessively in last century. The advances in chemistry and biology have helped researchers to identify the drugs that have improved treatment of many diseases. The primary factor for treatment of these diseases is dependent on the efficacy of drugs available. The development of resistance to these drugs is one of the major hindrances. Although there are number of books available on this topic, "drug resistance" biology across kingdoms has never been discussed in a coherent way.

This issue focuses on meningiomas and includes articles on Incidental Meningiomas: Management Strategies in the Modern Neuroimaging Era, Advanced Neuroimaging for Intracranial Meningiomas, Endoscopic Endonasal and Keyhole Surgery for the Management of Skull Base Meningiomas, Preoperative Embolization for Intracranial Meningiomas, Management of Spinal Meningiomas, Medical Management of Meningiomas: Current Status, Failed Treatments and Promising Horizons, and many more!

This book discusses the efficacy of various naturally occurring chemopreventive agents in preventing or delaying cancer. It focuses on the holistic chemopreventive concept, demonstrating the relevant response is the combined effect of a series of compounds that alone have been shown to have some effect in different experimental models. Written by leading experts in the field, the contributions provide details of research on various chemopreventive agents. Offering insights into the unique molecular targets and mechanisms, safety issues, molecular efficacy, and occurrence in nature of these compounds, the book is a valuable resource for all scientists working in biomedicine, and specifically in cancer research.

This book is intended to serve as an authoritative reference source for a broad audience involved in the research, teaching, learning, and practice of nanotechnology in immunotherapy. The combination of nanotechnology and immunotherapy is recognized as a promising treatment modality. In particular, the use of nanoparticles in immunotherapy has attracted increased attention for their unique efficacy and specificity in cancer treatment. A wide variety of nanoparticles, such as polymeric and liposomal nanosystems, carbon nanotubes, and gold nanoparticles have provided important nanoplatforms for immunotherapeutic approaches. They have been shown to improve delivery and efficacy of immunotherapeutic agents such as vaccines or adjuvants. Nanoparticle-mediated thermal therapy has demonstrated the effectiveness for precise tumor cell ablation, radio-sensitization of hypoxic regions, enhancement of drug delivery, activation of thermosensitive agents, and enhancement of the immune system. Plasmonic nanoparticles are a special type of metallic nanoparticles that has received great interest due to their enhanced optical and electromagnetic properties and their superior capacity to convert photon energy into heat for selective photothermal therapy at the nanoscale level. Nanoparticle sizes can also be controlled such that they accumulate preferentially in tumors due to the enhanced permeability and retention effect of tumor vasculature. Various nanosystems such as gold nanoparticles have also been shown to stimulate the immune system. Immunotherapies could thus synergistically benefit from the combination with targeted nanoparticle-mediated photothermal therapies, especially when hyperthermia around immune-checkpoint inhibitors in the tumor bed is combined with precise thermal ablation of cancer cells. Of great importance is the possibility that such an approach can induce long-term immunological memory that can provide protection against tumor recurrence long after treatment of the initial tumors, like an 'anticancer vaccine'. Nanoparticle-mediated immunotherapy could lead to an entirely new treatment paradigm that challenges traditional surgical resection approaches for many cancers and metastases.

There are more than 63,000 new cases of uterine and endometrial cancer each year in the United States, up from approximately 41,000 when the first edition of Uterine Cancer was published in 2009. A book focusing on these cancers was timely, with emergent sophistication in diagnosis increasingly impacting clinical decision-making. However, five years later, the need for an updated book on this topic is even stronger as oncologists recognize opportunities to impact the outcome on women that are increasingly diagnosed with these malignancies. Uterine Cancer: Screening, Diagnosis, and Treatment, Second Edition, part of the Current Clinical Oncology series, enhances the awareness on this somewhat neglected area of therapeutics, helping to integrate targeted therapies into the management of women with uterine cancer. Written by experts in the field in a highly practical and comprehensive manner, it is a must-have for all gynecological residents and fellows, as well as gynecological oncologists, medical oncologists, radiation oncologists, and family practice doctors who wish to provide their patients with the best possible care.

Hsp90 in Cancer: Beyond the Usual Suspects, the latest volume in the Advances in Cancer Research series, focuses on the multifunctional molecular chaperone Hsp90 which regulates the post-translational stability and function of a broad repertoire of client proteins and discusses some of the lesser-known aspects of how Hsp90 and its related family members enable oncogenic transformation and malignant progression.

The Epidemiological Approach to the Study of Protease Inhibitors (Fontham, Correa). In vitro Studies of Anticarcinogenic Protease Inhibitors (Kennedy). Discovery and Background of the BowmanBirk Protease Inhibitors (Bowman). Antigenicity of Soybean Protease Inhibitors (Bandon et al.). Low Molecular Weight Protease Inhibitors of Microbial Origin (Umezawa et al.). Protease Inhibitor Synthesis by MCF7 Breast Cancer Cells (Finlay et al.). Analysis of StructurActivity Relationships of the BowmanBirk Inhibitor of Serine Proteases (Flecker). Prevention of Cancer by Vitamin B3 (Troll). Approaches to Studying the Target Enzymes of Anticarcinogenic Protease Inhibitors (Billings). Anticarcinogenic Activities of Naturally Occuring Cysteine Protease Inhibitors (Colella et al.). Cell Membrane Enzymes Containing ChymotrypsinLike Activity (Yavelow et al.). The Role of Active Oxygen Species in Biological Damage and the Effect of Some Chemopreventative Agents (Frenkel). 6 additional articles. Index.

This issue of Surgical Pathology Clinics is devoted to Soft Tissue Tumors, the first in this series was presented in 2011. This issue addresses the most difficult diagnostic challenges and focuses on differential diagnosis in soft tissue tumors. Each presentation is accompanied by abundant histologic slides to display the diagnostic differences. Additionally, authors selected two to five diagnoses they find can be particularly difficult, with an emphasis on how to approach such lesions on biopsy samples where relevant and the role of ancillary studies. Topics include coverage of diagnostically challenging: Vascular lesions; Retroperitoneal "Fatty" tumors of adults; Smooth muscle neoplasms; Chondro-osseous lesions of soft tissue; Pediatric tumors; Epithelioid tumors; Spindle cell neoplasms of the retroperitoneum; and Peripheral nerve sheath tumors. Also presented are: Non-mesenchymal mimics of benign and malignant soft tissue tumors; Soft tissue tumors with overlapping molecular findings; Recently characterized soft tissue tumors; Benign mimics of sarcoma; Advances in molecular methods in the analysis of soft tissue tumors and therapeutic implications; and Myoepithelial tumors: an update. Leona Doyle and Karen Fritchie lead this issue of experts in soft tissue pathology.

Cancer is a multifaceted and genomically complex disease and data obtained through high throughput technologies has provided near complete resolution of the landscape of how genomic, genetic and epigenetic mutations in cancerous cells effectively influence homeostasis of signaling networks within these cells, between cancerous cells, tumor microenvironment and at the organ level. Increasingly sophisticated information has helped us in developing a better understanding of the underlying mechanisms of cancer, and it is now known that intra-tumor genetic heterogeneity, cellular plasticity, dysregulation of spatio-temporally controlled signaling cascades, and loss of apoptosis are contributory in cancer development, progression and the development of resistance against different therapeutics. It is becoming progressively more understandable that earlier detection of pre-existing or emerging resistance against different therapeutics may prove to be helpful in personalizing the use of targeted cancer therapy. Despite the fact that there is a continuously increasing list of books, being guest edited by researchers, books on the subject are often composed of invited reviews without proper sequence and continuity and designed for a particular readership. This book progressively shifts and guides the readers from basic underlying mechanisms to translational approaches to treat cancer.