This second book of the three-volume collection "Ion Transport in Tumor Biology" helps readers gain comprehensive knowledge of the pathophysiology of cancer. The authors highlight that ion transport proteins, channels and transporters - collectively referred to as the transportome - are significantly involved in the development and progression of cancer. Nearly 90% of malignant tumor diseases originate from epithelial cells, the function of which, for the most part, is based on the transportome. This volume focuses on molecular principles by showing that dysregulated expression and/or function of ion transporters have been correlated with malignancy in the vast majority of tumor diseases. Within the story of the various chapters, the authors line out various malfunctions of the transportome and where they can be found at different stages of the metastatic cascade. The authors describe how the interactions between the tumor cells' transportome and the environment reinforce mesenchymal behaviour of cancer cells and contribute to their uncontrolled proliferation, migration, invasion, intra- and extravasation up to the formation of metastases. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.

This thesis documents the development of a multifunctional nanoparticle system to enhance the chemotherapeutic efficiency of anti-cancer drugs, and contributes to research that helps decrease the side-effects in cancer patients while simultaneously increasing their survival rates. The work begins with an introduction to nanomedicine and cancer therapy, and contains a literature review on magnetic, gold, and core-shell nanoparticles. It also covers synthesis techniques, properties, various surface modifications, and the importance of magnetic and gold nanoparticles. The author dedicates a chapter to characterization techniques, experimental setup, and cell cultivation techniques for in-vitro studies. Further chapters describe the background, characterizations, and applications of multifunctional magnetite coated gold core-shell nanoparticles, and the doping of cobalt to magnetite and manganese to magnetite nanoparticles. The important highlight of this research was the control of the size, shape, composition, and surface chemistry of nanoparticles.

The Physics of Three Dimensional Radiation Therapy presents a broad study of the use of three-dimensional techniques in radiation therapy. These techniques are used to specify the target volume precisely and deliver radiation with precision to minimize damage to surrounding healthy tissue. The book discusses multimodality computed tomography, complex treatment planning software, advanced collimation techniques, proton radiotherapy, megavoltage imaging, and stereotactic radiosurgery. A review of the literature, numerous questions, and many illustrations make this book suitable for teaching a course.
The themes covered in this book are developed and expanded in Webb's The Physics of Conformal Radiotherapy and the two may be used together or in successive semesters for teaching purposes.

This volume reviews advances in cancer chemotherapy research over the last 10 years. Chapters written by leading experts in their field reflect a range of current medicinal chemistry approaches to small molecule drugs. Each chapter covers the drug target and biological rationale, chemotypes, clinical status and future prospects in this rapidly developing area of drug research.

Sentinel lymph node (SLN) procedures have opened a window of opportunity for the study of micrometastasis. In eighty percent (80%) of metastasis there lies an orderly pattern of progression via the lymphatic network, while 20% of the time systemic metastasis occurs, bypassing the lymphatic system. During the past two decades, significant progress has been achieved in understanding the anatomical, functional, cellular and molecular aspects of the lymphovascular system and the metastasis process.

A- Molecular imaging advances help to localize early cancers more precisely.

A- Current status of the immune responses in the draining lymph nodes against cancer is summarized.

A- New paradigms of early cancer growth, proliferation, overcoming apoptosis are exploited in the development of anticancer treatment.

In this book, basic scientists and clinicians exchange ideas so that laboratory findings can be applied to clinical dilemmas, and clinical problems can be targeted for research in the laboratory.

Over the past 20 years, technological advances in molecular biology have proven invaluable to the understanding of the pathogenesis of human cancer. The application of molecular technology to the study of cancer has not only led to advances in tumor diagnosis, but has also provided markers for the assessment of prognosis and disease progression. The aim of Molecular Ana- sis of Cancer is to provide a comprehensive collection of the most up-to-date techniques for the detection of molecular changes in human cancer. Leading researchers in the field have contributed chapters detailing practical pro- dures for a wide range of state-of-the-art techniques. Molecular Analysis of Cancer includes chapters describing techniques for the identification of chromosomal abnormalities and comprising: fluor- cent in situ hybridization (FISH), spectral karyotyping (SKY), comparative genomic hybridization (CGH), and microsatellite analysis. FISH has a pro- nent role in the molecular analysis of cancer and can be used for the detection of numerical and structural chromosomal abnormalities. The recently described SKY, in which all human metaphase chromosomes are visualized in specific colors, allows for the definition of all chromosomal rearrangements and marker chromosomes in a tumor cell. Protocols for the detection of chromosomal re- rangements by PCR and RT-PCR are described, as well as the technique of DNA fingerprinting, a powerful tool for studying somatic genetic alterations in tumorigenesis.

Paul Sugarbaker and his colleagues have persevered in the study and treat ment of peritoneal carcinomatosis. The peritoneal cavity has many unique and incompletely appreciated properties. These properties, coupled with the biologic behavior of many cancers, results in the seeding and growth of these cancers on the peritoneum. Many of these cancers remain localized to the peritoneum only, never metastasizing to other sites. One possible reason for this may be the obstruction of the afferent lymphatics on the undersurface of the diaphragm. The mucopolysaccharides produced by many of these neoplasma are probably viscous enough to obstruct these lymphatics, leading to the syndrome of pseudomyxoma peritonei. Many of the neoplasms taking residence on the peritoneum have extremely long cell-cycle times and are resistant to radiotherapy and many chemotherapeutic agents. How ever, much can be done for these patients - resection of primary cancers, omentectomies to reduce ascites formation, management of recurrent ascites, management of intestinal obstruction, nutritional care, and, hopefully, intraperitoneal chemotherapy. We have reviewed many of these problems in the past [1-7]. Dr. Sugarbaker and his colleagues have organized the current state of knowledge and technology for continuing use. The book provides a basis for thoughtful, prospective research planning. John S. Spratt, M. D. , F. A. C. S. Professor of Surgery The James Graham Brown Cancer Center University of Louisville Louisville, Kentucky References 1. Long RTL, Spratt JS, Dowling E.

The focus of the 22nd Annual Detroit Cancer Symposium was the presentation and discussion of cytotoxic agents, with a significant portion of the symposium including the exciting frontiers of drug discovery being explored by the National Cooperative Drug Discovery Groups (NCDDG) Program. The symposium brought together a large number of investigators from government, universities and pharmaceutical companies involved in the discovery and development of new anticancer agents. Exciting new leads were presented and the status of others presently under development was discussed. Of particular significance has been the initiation of renewed efforts in the area of natural product drug discovery, where the discovery of new cytotoxics is very promising at the moment. A number of major changes have occurred during the last decade in research on drug discovery of cytotoxic agents. Critical reviews of a number of the models and concepts underlying drug discovery represented a continuous thread throughout the meeting, being constantly discussed in terms of their advantages, disadvantages and capabilities of discovering solid tumor active anticancer agents. A recent development which is to be much applauded and which portends to great discoveries is the new relationship formed between Government, University of Industry. The NCDDG mechanism which stimulates this interaction is an inexpensive manner to greatly magnify the drug discovery and development effort nationally. Cytotoxic Anticancer Drugs: Models and Concepts for Drug Discovery and Development represents a forum which will become the major mode for bringing together these three different components in the equation to regularly discuss new results and ideas.

In the post human-genome project era, cancer specific genomic maps are redesigning tumor taxonomy by evolving from histopathology to molecular pathology. The success of a cancer drug today is fundamentally based on the success in identifying target genes that control beneficial pathways. The overwhelming power of genomics and proteomics has enlightened researchers about the fact that the PI3K-mTOR pathway is the most commonly up-regulated signal transduction pathway in various cancers, either by virtue of its activation downstream of many cell surface growth factor receptors or by virtue of its collateral and compensatory circuitry with RAS-MAPK pathway. Oncogenic signaling in the majority of solid tumors is sustained via the PI3K-AKT-mTOR pathway. Because of its prominent role in many cancer types, the PI3K-mTOR pathway has become a major therapeutic target. The volume includes two complementary parts which address the problem of etiology and disease progression and is intended to portray the very basic mechanisms of the PI3K-AKT-mTOR signaling pathway's involvement in various facets of the cancer, including stem cell renewal, cell metabolism, angiogenesis, genetic instability, and drug resistance. Significant progress has been made in recent years elucidating the molecular mechanism of cancer cell proliferation, angiogenesis, and drug-resistance in relation to the PI3K-mTOR pathway and this volume provides an in-depth overview of recent developments made in this area.

With very few exceptions, eukaryotic cells possess two interdependent genomes, chromosomal and extra-chromosomal. Over the past several decades, cancer - search has focused primarily on deciphering the intricate alterations in the chro- somal genome, with until recently, very little attention to its cytoplasmic counterpart. In spite of the enormous complexity of the nuclear genome, which we now fully appreciate after completion of the human genome project, the efforts of cancer researchers are commendable in terms of the tremendous gains made in unraveling the numerous genetic changes in cancer. These changes include d- coveries of tumor suppressor genes, oncogenes, and caretaker genes that are often mutated in cancer. Recent studies of genomic pro?les are uncovering even more altered and mutated genes in cancer. Besides these ?ndings, several therapeutic targets for chemotherapy are currently made from studies of altered nuclear genetic pathways. Inspite of all these positive efforts, the war on cancer, declared in 1971 by Richard Nixon, is far from being worn. Indeed, the failure of chemotherapy is obvious to clinicians, oncologists, and their patients alike. Moreover, the global incidence and prevalence of cancer continue to rise. What are we missing? Which direction should we be taking? Of course, modern integrated nuclear genomics, proteomics, and metabolomics should provide important clues to carcinogenesis, but the contribution of cytoplasmic genetic alterations to carcinogenesis cannot be neglected.

This third and final volume in the "Ion Transport in Tumor Biology" collection presents novel diagnostic and therapeutic approaches in cancer based on the exploitation of ion transport proteins. The authors critically examine several transportome members, particularly Na+, K+, Ca2+, and Cl- channels, as well as organic solute carriers regarding their suitability as therapeutic targets. Synergistic effects resulting from the combined use of classical cytostatics with ion transport-inhibiting drugs are pointed out, and the capability of bispecific antibodies to function as anticancer drugs is discussed. As readers will also learn, the use of ion channel inhibitors could improve the outcome of radiotherapy because the development of radio-resistance during radiotherapeutic treatment often correlates with increases in the expression levels and conductance of ion channels. The translational topics of this volume form a bridge between biochemical research and therapeutic application. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians in the cancer field.

This book provides detailed information on the etiology, pathogenesis, diagnosis, prognosis, and treatment strategies for breast cancer. The first section of the book presents epidemiology, risk factors, histopathological, immunohistochemistry, and molecular subtypes of breast cancer based on the receptor status. It also discusses the association of breast cancer with other hormone-sensitive cancers. The second section of the book covers cover BRCA1 and BRCA2-associated breast carcinogenesis, early-stage progression of breast cancer, and noninvasive biomarkers for the early detection of breast cancer. It also discusses the role of epigenetic modifications and non-coding RNAs in breast cancer metastasis and explores these as the biomarkers and therapeutic targets for breast cancer therapy. Further, it discusses the role of fibrinolytic mechanisms and circulating tumor cells in breast cancer diagnosis, prognosis, and treatment. The book also provides an update on oral poly(ADP-ribose) polymerase (PARP) inhibitors to treat breast cancer. Finally, it offers potential new options for personalized therapies for breast cancer patients, including optimizing drug dosage and identifying genetic changes associated with cancer symptom occurrence and severity.

Peritoneal carcinomatosis dominates the clinical picture of many patients with gastrointestinal, gynecological and urological cancers. For many of them its dev astating effects contribute directly to their death. Most clinicians consider peritoneal carcinomatosis an incurable metastatic disease and give palliative treatment, re stricted to limited surgery and systemic chemotherapy. Contrary to this view, Paul Sugarbaker and his collegues base their approach on the concept that peritoneal carcinomatosis represents regional tumor spread, similar in its impact on treatment and prognosis to that of lymph node metastases in other malignancies. This concept emphasises the value of regional tumor control, as a potentially curative measure. In this book the combination of aggressive cytoreduction and intraperitoneal chemotherapy to control peritoneal carcinomatosis is extensively explored. Basic to this approach is the observation that most cancer cells show only relative resistence against commonly available drugs, which can be overcome by a sufficient increase of drug concentrations in tumor tissue. After intraperitoneal delivery, drugs will reach high tissue concentrations in the superficial few cell layers, while plasma concentrations will remain below toxic levels. Patients with only limited residual tumor at the peritoneal surface after cytoreduction may therefore benefit from intraperitoneal chemotherapy.

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 . . . . . . . . . . . . . . . . . . . . . . . . . .

The rationale for using intraoperative irradiation (IORT) is based on the realization that tolerable doses of external beam radiation are often insufficient to achieve control of locally advanced malignancies. In these instances, the IORT component of treatment becomes the optimal conformal technique of irradiation, since dose-limiting organs or structures can either be surgically displaced or protected by placement of lead shielding. This fully revised and expanded second edition is of interest to those with intraoperative electron (IOERT) capabilities, high-does-rate brachytherapy (HDR-IORT) capabilities, or both. Techniques, indications, and results are discussed by disease site. Each chapter is dual authored by a radiation oncologist and a surgeon, giving a balanced presentation of clinical scenarios. Issues of basic science and physics are also covered, and a notable chapter on normal tissue tolerance is included. Intraoperative Irradiation: Techniques and Results, Second Edition is a superb compilation, providing essential cutting-edge knowledge. It is a foundation for physicians as IORT develops and becomes more widely available.

This book encapsulates and occupies recent advances and state-of-the-art applications of nature-inspired computing (NIC) techniques in the field of bioinformatics and computational biology, which would aid medical sciences in various clinical applications. This edited volume covers fundamental applications, scope, and future perspectives of NIC techniques in bioinformatics including genomic profiling, gene expression data classification, DNA computation, systems and network biology, solving personalized therapy complications, antimicrobial resistance in bacterial pathogens, and computer-aided drug design, discovery, and therapeutics. It also covers the role of NIC techniques in various diseases and disorders, including cancer detection and diagnosis, breast cancer, lung disorder detection, disease biomarkers, and potential therapeutics identifications.

Latest generation sequencing revolutionizes the fields of cancer research and oncology. This follow-up volume focuses more extensively on single cell sequencing of cancer and trials in drug resistance. Another exciting feature is the bioinformatics tools given, that can be used on cancer genome studies. Scientists around the world are attempting to find the root cause of cancer. A reasonable cancer treatment plan and potential cure is more optimistic now with the unfolding of the cancer genome. The collective knowledge of how to leverage next generation sequencing in cancer research is paving the way. The important information provided in this volume will move the field forward in developing novel targeted cancer therapies.

- Controversial topic because many of the proposed solutions or policies may damage the economy in the short term in order to reap health benefits which will only become apparent several decades in the future

- Each chapter is written by experts in the field throughout the world

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 spo radically, 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, genitourina ry 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."

With tens of thousands of new CNS tumor cases each year in the US alone, this series of publications is a valuable aid to the diagnosis and treatment of these problematic neoplasms. Now, the eighth in the set returns to the topic of brain tumors, dealing with seven distinct types: astrocytoma, medulloblastoma, retinoblastoma, chordoma, craniopharyngioma, oligodendroglioma, and ependymoma. After updating the classification of medulloblastoma the volume provides an overview of ependymoma as well as describing the delineation of prognosis based on the genetic aberrations of the latter patients. The material offers key insights into the molecular pathways involved in tumor biology, such as the role of E-cadherin gene instability, carbonic anhydrase II, urokinase plasminogen activator, and Wnt signaling in meningioma. Contributors explain the genetic and clinical features associated with recurring meningioma, including the role played by erythropoietin receptor, and examine the way in which OTX2 transcription factor functions as an oncogene in medulloblastoma. With much more besides, including discussion of the molecular mechanisms that result in resistance to chemotherapy in medulloblastoma, this volume and its companions have a positive role to play in inspiring a new generation of researchers to design new drugs that are better targeted and thus more effective."

This volume highlights the molecular and cellular methods used in studying Chronic Myeloid Leukimia (CML) pathogenesis and stem cell biology. 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 cutting-edge, Chronic Myeloid Leukemia: Methods and Protocols aims to ensure successful results in the further study of this vital field.

The fact that tumors are composed of both tumor cells and host cells has long been known. These tumor-associated cells include vascular endothelial cells and pe- cytes, as well as inflammatory cells such as neutrophils, monocytes, macrophages, mast cells and eosinophils, and lymphocytes. The tumor cells also interact with stromal cells and with elements of the tissue extracellular matrix. What has been less appreciated is the role that these cells could have in modulating the growth, invasion, and metastasis of the tumor. Early on, the elements of what we now call the tumor microenvironment were considered to be more or less innocent bysta- ers to the role of the tumor cells as they grew and invaded local sites. Today, there is an increased understanding of the critical role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination. This volume represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment in cancer development and progression. Perhaps, the earliest recognition of the role of nonmalignant cells as cancer re- lators was the recognition that lymphocytes can participate in what was termed "immune surveillance" in the 1960s. Our understanding of tumor immunity has improved markedly since then, and there are now successful clinical studies sh- ing the potential use of immune-based therapies in cancer treatment.

Lesbian, Gay, Bisexual, and Transgender (LGBT) also known as sexual and gender minority (SGM) populations have been the focus of global attention. Most importantly, LGBT populations have been addressed in the context of human rights in multiple reports and other activities by the United Nations and other international organizations. There is great variation among countries in the recognition of LGBT individuals' human rights. A global focus on LGBT populations' health is still limited, with the notable exception of HIV research. This book on LGBT populations and cancer in the global context is, therefore, an important step in that it will broaden the focus on LGBT populations' health. Globally, cancer is the second leading cause of death. Cancer morbidity and mortality are increasing disproportionately among populations in lower-income countries. A review conducted by the World Health Organization (WHO) found that of the 82% of member states (158) countries, only 35% of the national cancer control plans addresses vulnerable population, including LGBT populations. These findings reflect an increasing awareness about equity when addressing cancer prevention and control, including LGBT populations. This book addresses LGBT populations' cancer burden across countries that range from high- to low-income countries to support efforts in diverse countries that are working towards reducing LGBT populations' cancer burden. It documents place-specific challenges that impede progress towards reducing the LGBT cancer burden as well as critically assesses the variation in cancer control efforts that target LGBT populations and cancer to support progress at a global scale. This book includes six sections that cover the six WHO regions, with each chapter written by an author from the specific region s/he is covering. Each chapter makes use of a template that contextualizes the region, local data collection/availability, risk factors, cancer prevention, detection, diagnosis, treatment, and survivorship.