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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 volume will be the first to provide a comprehensive description of tumor dormancy. It will define the clinical and biological aspects of this phenomenon, as well as the cellular and molecular mechanisms associated with tumor dormancy. Chapters will be authored by world-renewed experts who are conducting cutting-edge research in the field. A unique feature will be a conclusive paragraph detailing future development and foreseeable clinical applications at the end of each chapter. The volume will serve as a fundamental instrument for every researcher and clinician interested in the field of tumor dormancy as well as a means of disseminating stimulating concepts and prompting the development of innovative technological solutions.

This book would like to present the latest findings on different aspects of tumor matrix formation in connection with the tumor progression and metastasis and on alterations in the cellular components of tumor stroma during tumor demarcation and invasion.

In Vivo Models to Study Angiogenesis provides the latest information and an overview of the most common assays for studying angiogenesis in vivo. Under physiological conditions, angiogenesis is tightly controlled, whereas increased production of angiogenic stimuli and/or reduced production of angiogenic inhibitors leads to abnormal neovascularization, such as occurs in cancer, chronic inflammatory disease, diabetic retinopathy, macular degeneration and cardiovascular disorders. Several genetic and epigenetic mechanisms are involved in the early development of the vascular system. This book presents the latest information from the extensive literature and research available. Evidence is now emerging that blood vessels themselves have the ability to provide instructive regulatory signals to surrounding non-vascular target cells during organ development. Thus, endothelial cell signaling is currently believed to promote fundamental cues for cell fate specification, embryo patterning, organ differentiation and postnatal tissue remodeling. - Provides information on the most common assays to study angiogenesis in vivo - Presents an ideal reference for those interested in angiogenesis as a normal and vital process in growth and development - Covers wound healing, the formation of granulation tissue, and the transition of tumors from benign to malignant

This book reviews different aspects of the cancer microenvironment, and its regulation and importance for tumor progression. Methodological advancements and practical applications, in terms of how biomarkers are studied and increasingly included in clinical trials and therapy protocols, are described and discussed. Biomarkers of the Tumor Microenvironment is an educational resource for students and members of the cancer research community as a whole, especially for those using morphology analysis techniques and models focusing on the cross-talk between different cell types in tumors. The textbook provides a comprehensive overview of the microenvironment in various contexts from the perspectives of experienced and accomplished cancer researchers and clinicians.

Volume 542 of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This new volume covers research methods providing a theoretical overview on metabolic alterations of cancer cells and a series of protocols that can be employed to study oncometabolism, in vitro, ex vivo and in vivo. Malignant cells exhibit metabolic changes when compared to their normal counterparts, owing to both genetic and epigenetic alterations. Although such a metabolic rewiring has recently been indicated as'yet another'general hallmark of cancer, accumulating evidence suggests that the metabolic alterations of each neoplasm rather represent a molecular signature that intimately accompanies, and hence cannot be severed from, all facets of malignant transformation. - Continues the legacy of this premier serial with quality chapters authored by leaders in the field - Covers research methods in biomineralization science - Provides theoretical overview on metabolic alterations of cancer cells, and a series of protocols that can be employed to study oncometabolism, in vitro, ex vivo and in vivo

The last 15 years have brought an understanding of growth and differentiation at the molecular level, expanding our knowledge of the origin and progression of cancer. Early breakthroughs defining growth control pathways came via studies of oncogenes, mutated signaling molecules that have lost the capacity to tum off their proliferative signal. Oncogenes with diverse growth-promoting activities have been discovered, covering the gamut from cell surface to nuclear signaling. Sequencing of these oncogenes revealed that they were mutated forms of captured cellular genes and displayed tyrosine kinase activity. The epidermal growth factor (EGF) receptor was the first of 40-50 transmembrane tyrosine kinase receptors to be cloned and sequenced. Beyond cell proliferation, activation of EGF receptor by its specific ligands controls important physiological processes, such as cell differentiation, apoptosis, cell migration, and cell shape. Activation of autocrine growth loops, consisting in solid human tumors of upregulated expression of EGFR together with increased production of ligands suggested its crucial role in autonomous tumor growth.

This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers. Specific topics included the angiogenic switch, immune system interactions, cancer stem cells and signaling.

Tumor development and progression are multi-factorial processes, in which genomic alterations and modifications in gene expression in pre-malignant cells are joined by deleterious micro-environmental factors. The tumor microenvironment contains stroma cells and leukocytes, soluble factors and matrix components. The intensive interplay that exists between the host factors and the tumor cells plays a major role in dictating the final outcome of the malignant process. Inflammatory mediators are pivotal micro-environmental factors present in the tumor milieu. These inflammatory components support cell growth and invasion, induce mutagenesis, increase angiogenicity, and suppress potential anti-tumor immune functions. The inflammatory constituents that prevail in tumors include leukocytes and soluble mediators - cytokines and chemokines. This e-book describes the roles played by inflammatory cytokines /mediators and of other soluble regulatory factors in malignancy, and explains the basis for the consideration inflammatory constituents as therapeutic targets in cancer. The e-book is a timely overview of the roles played by inflammatory soluble mediators in neoplastic diseases. The topics addressed in this volume serve as a handy reference to investigators studying basic aspects of tumor growth, to clinicians who wish to better understand the processes involved in malignancy, and to pharmacological professionals seeking novel candidates for therapeutic intervention in cancer.

It is widely recognized that the host response to tumor munotherapy of experimental metastases in animal systems progression is an important determinant in cancer growth which are beginning to be developed for ultimate clinical and progression. Indeed, as indicated in Volume I of this trials of human cancer metastasis. series, the process of cancer growth and progression, leading This volume explores a variety of host properties that to tumor invasion and metastasis, is dependent upon the influence tumor development including dormancy, regress­ complex, dynamic interactions between the properties of the ion, and recurrence. In addition, current knowledge of the tumor as well as the properties of the host. While Volume III response of the central nervous system to cancer, cardiac of this series reviews in great detail the influence of tumor and pulmonary complications, dermatologic effects and development on the host, this volume emphasizes the in­ hematologic complications of malignancies is presented. fluence of the host on tumor development. These host re­ The endocrine and metabolic function of cancer patients, as sponses include host anti-tumor immune reactivity, tumor well as the production of hormones by tumors is also review­ dormancy, cachexia, multiple endocrine and paraneoplastic ed.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under­ with extracellular matrices, the basement membrane, attach­ scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate­ cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech­ a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

During the past 9 years, reports of'port-site'deposits following laparoscopic surgery for malignancy, especially laparoscopic resection of colonic cancer, have cast a shadow on the wisdom of the laparoscopic approach in the surgical man­ agement in patients with cancer. Those reports of port-site deposits, some 90 cases reported in the literature up to 1999, have opened a'can of worms'and highlighted the scarcity of our knowledge on cancer cell migration from solid tu­ mors and the factors that underlie their successful implantation in surgical wounds both in the presence and absence of a positive pressure pneumoperito­ neum. The jury is out even in relation to the effect of the healing surgical access wound - do the biochemical and cellular repair processes and the associated growth factors enhance or prevent implantation of exfoliated viable tumor cells? Whatever the answer to this question, it is clear that tumor cells do implant in healing surgical wounds and the key question is whether this is facilitated by lap­ aroscopic surgery with CO pneumoperitoneum compared to the traditional 2 surgical exposure. It is known that tumors shed malignant cells into the blood stream, the peritoneal cavity and in the case of hollow organs, intraluminally. Equally there is good evidence that surgical and instrumental manipulation of tumors induce exfoliation of viable tumor cells.

The book will detail the history, successes, and failures of targeted therapies for cancer, with a particular focus on IGF systems and cancer.

In recent years, a number of molecular pathways and cellular processes that are essential for normal vertebrate development have been implicated in cancer initiation and progression. In this volume, leaders in the field of cancer genetics and developmental biology share recent insights into the importance of developmental pathways for tumorigenesis. These discoveries provide important avenues for innovative new approaches to treating some of the most challenging developmental tumors. - Provides researchers an overview and synthesis of the latest research findings and contemporary thought in the area - There are now a large number of molecular targeted therapies for the treatment of cancer. Many of these therapies target pathways that are essential for normal development. Therefore, this volume provides an up-to-date and timely perspective on those pathways and biological processes that hold the greatest promise for targeted intervention.

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.

In this book, tumour growth is perceived as a deviation from the normal development of the human organism. The molecular, cellular, and tissue determinants of different tumours are discussed showing that each is a different disease, often corresponding to a particular developmental stage. The natural history of several cancers illustrates how clinical incidence can be just the visible part of the iceberg, while the first changes at the tissue level sometimes occur several years before tumour growth becomes manifest. Several mechanisms are proposed to explain the distribution of cancers during the human life span and the decline of the incidence of cancers during human senescence.

The enormity of the literature on growth factors, plus the breadth of the biological disciplines and technical expertise required prohibits a comprehensive review by even a multi-disciplinary panel of authors. To provide an alternative that is feasible for authors and digestible by readers, this review compendium consists of a collection of articles, each covering an aspect of teh ErbB/EGF field. This compilation features articles on growth factor ligands, neuregulins, and individual receptors. The second part of the book concentrates on the biological context of the ErbB receptors, particularly in mammary development and in cancer. It concludes with a discussion of the genetic systems that have enabled significant advances in research in this area.