Development Of Angiogenesis Models And In Vivo Studies Of Angiogenesis Inhibitors

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential for physiological growth and over 18,000 research articles have been published describing the role of angiogenesis in over 70 different diseases, including cancer, diabetic retinopathy, rheumatoid arthritis and psoriasis. One of the most important technical challenges in such studies has been finding suitable methods for assessing the effects of regulators of eh angiogenic response. While increasing numbers of angiogenesis assays are being described both in vitro and in vivo, it is often still necessary to use a combination of assays to identify the cellular and molecular events in angiogenesis and the full range of effects of a given test protein. Although the endothelial cell - its migration, proliferation, differentiation and structural rearrangement - is central to the angiogenic process, it is not the only cell type involved. the supporting cells, the extracellular matrix and the circulating blood with its cellular and humoral components also contribute. In this book, experts in the use of a diverse range of assays outline key components of these and give a critical appraisal of their strengths and weaknesses. Examples include assays for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures, assessment of endothelial and mural cell interactions, and such in vivo assays as the chick chorioallantoic membrane, zebrafish, corneal, chamber and tumour angiogenesis models. These are followed by a critical analysis of the biological end-points currently being used in clinical trials to assess the clinical efficacy of anti-angiogenic drugs, which leads into a discussion of the direction future studies should take. This valuable book is of interest to research scientists currently working on angiogenesis in both the academic community and in the biotechnology and pharmaceutical industries. Relevant disciplines include cell and molecular biology, oncology, cardiovascular research, biotechnology, pharmacology, pathology and physiology.

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

Angiogenesis is attracting increased scientific and clinical interest. The identification of novel mediators and targeting molecules has led to significant progress in our understanding of tumor angiogenesis and tumor vessel targeting. Important advances in cancer treatment have already emerged, and in the future, blood vessel targeting will play a significant role within individualized therapeutic strategies. This volume provides a general overview of the latest developments in angiogenesis inhibition in cancer. All aspects from the bench to the bedside are considered, with detailed attention both to basic research and to its translation into clinical practice. Individual chapters are devoted to the roles of angiopoietins, HIF-1a, chemokines, PDGF and VEGF, and vascular integrins. The latest results of clinical trials are presented, and various advanced targeting strategies are discussed. This book will be invaluable to all who wish to learn of the most recent advances in this exciting field.

In 1971, J. Folkman published in the “New England Journal of Medicine” a hypothesis that tumor growth is angiogenesis-dependent. Folkman introduced the concept that tumors probably secrete diffusible molecules that could stimulate the growth of new blood vessels toward the tumor and that the resulting tumor neovascularization could conceivably be prevented or interrupted by angiogenesis inhibitors. Solid and haematological tumors consist of an avascular and a subsequent vascular phase. Assuming that this depends on the release of angiogenic factors, acquisition of angiogenic capability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis. Beginning in the 1980’s, the biopharmaceutical industry began exploiting the field of antiangiogenesis for creating new therapeutic compounds for modulating new blood vessels in tumor growth. In 2004, Avastin (Bevacizumab), a humanized anti-VEGF monoclonal antibody, was the first angiogenesis inhibitor approved by the Food and Drug Administration for the treatment of colorectal cancer. At present, it has been estimated that over 20,000 cancer patients worldwide have received experimental form of antiangiogenic therapy. This book offers a historical account of the relevant literature. It also emphasizes the crucial and paradigmatic role of angiogenesis as a biological process and the significance of antiangiogenic approach for the treatment of tumors.

Understanding how angiogenesis "works" and how to control it will have massive implications on the management, treatments, and ultimately the prevention of many common (and not so common) diseases. Angiogenesis is the growth of new blood vessels and is an important natural process in the body. A healthy body maintains a perfect balance of angiogenesis modulators. In many serious disease states, however, the body loses control over angiogenesis. Diseases that are angiogenesis-dependent result when blood vessels either grow excessively or insufficiently. Tried-and-tested techniques written by researchers that developed them, used them, and brought them to fruition Provides the "builder's manual" for essential techniques--a one-stop shop that eliminates needless searching among untested techniques Includes step-by-step methods for understanding the cell and molecular basis of wound healing, vascular integrin signaling, mechanical signaling in blood vessels, and vascular proteomics

Angiogenesis -- the growth of new blood vessels -- is an important natural process occurring in the body, both for health and as related to disease. Angiogenesis occurs in the healthy body to help heal wounds and to help to restore blood flow to tissues after injury or insult. In females, Angiogenesis also occurs during the monthly reproductive cycle (to rebuild the uterus lining, to mature the egg during ovulation) and during pregnancy (to build the placenta, the circulation between mother and foetus). The healthy body controls angiogenesis through a series of "on" and "off" switches. The main "on" switches are known as angiogenesis-stimulating growth factors. The main "off switches" are known as angiogenesis inhibitors. When angiogenic growth factors are produced in excess of angiogenesis inhibitors the balance is tipped in favour of blood vessel growth. When inhibitors are present in excess of stimulators, angiogenesis is stopped. The normal, healthy body maintains a perfect balance of angiogenesis modulators. In general, angiogenesis is "turned off" by the production of more inhibitors than stimulators. Tumour angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumour angiogenesis actually starts with cancerous tumour cells releasing molecules that send signals to surrounding normal host tissue. This signalling activates certain genes in the host tissue that, in turn, cause proteins to encourage growth of new blood vessels. This book examines its angiogenesis within the context of theory and its applications to cancer treatment.

This second edition provides new and updated methods and protocols for studying tumor angiogenesis in vitro and in vivo. Chapters detail morphological aspects of tumor angiogenesis, aortic ring, ex vivo tissue culture model for anti-angiogenic drug testing, transgenic zebrafish, orthotopic models of ovarian cancer, and uncovering metabolic effects of anti-angiogenic therapy in tumors by induced metabolic bioluminescence imaging.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. Cutting-edge and comprehensive, Tumor Angiogenesis Assays: Methods and Protocols, Second Edition is a valuable resource for all researchers interested in learning more about this important and developing field.

Dr. Judah Folkman is considered the "father of angiogenesis." Because of Folkman's discovery and research, the possibilities of angiogenic therapy have broadened beyond cancer to many noncancerous diseases. Angiogenesis: An Integrative Approach from Science to Medicine is a comprehensive, concise summary of tumor angiogenesis. It is an up-to-date and authoritative reference for the angiogenesis field as it relates to oncology. This book represents the first collection in a volume of which Folkman is co-editor. Folkman has authored nearly 400 original papers and more than 100 book chapters.

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