Tumor Vascularization

Tumor Vascularization discusses the different types of growth of tumor blood vessels and their implications on research and healthcare. The book is divided into three parts: the first one, General Mechanisms, discusses different vessel growth mechanisms, such as sprouting angiogenesis, non-angiogenesis dependent growth, intussusceptive microvascular growth, vascular co-option and vasculogenic mimicry. The second and third parts, entitled Clinical Implications and Therapeutic Implications are dedicated to translating recent findings in this field to patient treatment and healthcare. This book is a valuable source for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in tumor progression and blood vessels. Explains new, non-orthodox concepts recently developed and related to the modality of growth of tumor blood vessels Provides information on the types of angiogenesis, non-angiogenesis dependent growth and vascular co-option, discussing both their similarities and differences Encompasses a discussion on clinical implications of tumor vascularization to translate research findings into treatment

The purpose of this book is to highlight novel advances in the field and to incentivize scientists from a variety of fields to pursue angiogenesis as a research avenue. Blood vessel formation and maturation to capillaries, arteries, or veins is a fascinating area which can appeal to multiple scientists, students, and professors alike. Angiogenesis is relevant to medicine, engineering, pharmacology, and pathology and to the many patients suffering from blood vessel diseases and cancer, among others. We are hoping that this book will become a source of inspiration and novel ideas for all.

To profoundly understand biology and harness its intricacies for human benefit and the mitigation of human harm requires cross-disciplinary approaches that incorporate sophisticated computational and mathematical modeling techniques. These integrative strategies are essential to achieve rapid and significant progress in issues, in health and disease, which span molecular, cellular and tissue levels. The use of mathematical models to describe various aspects of tumor growth has a very long history, dating back over six decades. Recently, however, experimental and computational advances have improved our in the understanding of how processes act at multiple scales to mediate the development of tumor vasculature and drive the advancement of cancer. This book will showcase the development and utilization of new computational and mathematical approaches to address multiscale challenges associated with tumor vascular development. In Part I: Cell Signaling and Molecular Aspects of Tumor Blood Vessel Formation, it will be come clear that mathematical modeling can help to biochemically and biomechanically phenotype one of the most important cell types involved in cancer progression: vascular endothelial cells. When subverted by the tumor modulated environment, vascular endothelial cells form a new vascular supply capable of nourishing and translocating cancer cells to other tissues. The models in Part I illustrate the importance of quantitative approaches for gaining a deeper understanding of how normal and abnormal aspects of signal integration culminate in the cell proliferation, migration, and survival decisions that result in pathological tumor angiogenesis. The focus of Part II is the angiogenesis cascade and all of its complexities. Successful angiogenesis is mediated by the intricate interplay between biochemical and biomechanical mechanisms, including cell-cell and cell-matrix interactions, cell surface receptor binding, and intracellular signal transduction. A major challenge facing the cancer research community is to integrate known information in a way that improves our understanding of the principal underpinnings driving tumor angiogenesis and that will advance efforts aimed at the development of new therapies for treating cancer. The chapters in Part II will highlight several mathematical and computational approaches for that can potentially address this challenge. While the first two thirds of the book’s chapters demonstrate how important insights can be gained by studying cell signaling and vascular morphology and function, the series of chapters in Part III: Whole Organ Modeling of Tumor Growth and Vasculature, will integrate vasculature development with tumor growth dynamics. These two processes strongly depend on one another in ways that can only be theoretically investigated by biophysical approaches that cut across several levels of biological organization and describe both the tumor and the developing vasculature as they co-evolve. The purpose of this edited volume is not to provide a comprehensive review of all modeling efforts that address tumor vascular modeling; instead, a variety of interesting and innovative mathematical modeling approaches for understanding the development and effects of tumor vasculature are highlighted in order to illustrate some of the emerging trends in the field.

Tumor angiogenesis is one of the most prominent mechanisms driving tumor development and progression. This book is written by internationally renowned experts. Part 1 describes the basic mechanisms. Tumor-angiogenic signaling pathways are presented as new potential targets for anti-angiogenic therapy. Part 2 reviews the efforts made to validate new targets and to show efficacy in animals. Part 3 is devoted to the clinical development of the novel anti-angiogenic drugs and their use in clinical practice.

Tumour Angiogenesis is the first comprehensive book to cover all areas of this rapidly expanding research area. Each chapter is written by world experts in the field and topics covered include in vivo models, mechanisms, inhibition, and the role of macrophages, cytokines, proteases,extracellular matrix components, nitric oxide, prostanoids and oncogenes/tumour suppressor genes in angiogenesis. Other chapters examine the role of specific growth factors in angiogenesis - these include vascular endothelial growth factor, the basic fibroblast growth factor family, transforminggrowth factor-beta, tumour necrosis factor-alpha, platelet-derived endothelial cell growth factor/thymidine phosphorylase and pleiotrophin and related molecules. Clinical issues are addressed in chapters that deal with the prognostic and predictive value of tumour microvessel density and thetherapeutic significance of microregional blood flow. The two final chapters examine the feasibility of targeting tumour vasculature using either antibodies or gene therapy.

Vascular-Targeted Therapies in Oncology provides an interesting insight to the current status and future potential of vascular-disrupting approaches in cancer management. Emphasis is placed on target development, preclinical assessment, and the use of such targeted approaches in combination with conventional treatment regimens and the current clinical status of these therapies.

This book is a comprehensive introduction to the expression of tumor markers in association with various neoplasms, the methods used in their detection and their clinical relevance to the diagnosis and treatment of cancer. It will be an invaluable guide for clinicians, pathologists and research workers requiring an in-depth introduction to this subject and, with sections devoted to the exploitation of new techniques in immunohistochemistry, flow cytomtry, cancer genetics and molecular biology for the identification of tumor markers, can also be used as a laboratory reference.

Is it advisable to go back from bedside to the bench? During the last decade, few topics encountered such a broad interest in bio- gy and medicine as angiogenesis. The amazing ability of the body to restore blood flow by induction of blood vessel growth as part of an adaptive process has alarmed physicians dealing with diseases in which angiogenesis is either exaggerated (as in tumors) or too slow (as in ischemic diseases of heart and brain). Not surprisingly, pro- and antiangiogenic strategies have found their way into clinical trials. For instance, for the USA, the NIH website in early 2004 displayed 38 clinical studies involving either pro- or antiangiogenic th- apies. Given the expected overwhelming wealth of clinical data, the question may be asked whether further exploration of biological mechanisms is required or whether results from the bedside are instructive enough to proceed. This question depends also on the progress of pro- and antiangiogenic clinical trials. In the following, I give a short overview about some of the progress that has been made in this field. Since Judah Folkman proposed antiangiogenic tumor therapy thirty years ago, it has become increasingly evident that agents which interfere with blood vessel formation also block tumor progression. Accordingly, antiangiogenic therapy has gained much attention as a potential adjunct to conventional c- cer therapy.