The present book is an attempt to provide a detailed review of studies that clarify our current understanding of the role of hypoxia in the progression of primary cancer to metastatic disease. It will enable researchers to discover the critical cellular changes that occur under hypoxic conditions and play a role in metastatic dissemination, from the activation of hypoxia-inducible factors, HIF-1 and HIF-2, to the transcriptional profile changes that occur in cancer cells and promote cancer cell survival under detrimental conditions. Readers will discover the methods and challenges involved in imaging and quantifying the degree of hypoxia in a primary tumor. We will provide an understanding of the hypoxia-induced phenotypes that influence heterogeneity, alter the secretome and tumor microenvironment, modify cellular metabolism, and promote immune suppression and resistance to chemotherapy. Finally, we will uncover the therapeutic strategies that are being devised to target the hypoxic microenvironment in the hopes of preventing metastasis and improving the efficacy of standard-of-care cancer treatments. This work is an up to date source of information on the challenges and complexity of the hypoxic tumor microenvironment. Basic and translational scientists, post-doctoral fellows, graduate students, and those interested in how tumors metastasize will find this book a reference that details how hypoxia influences metastatic disease.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

This book describes the methods of analysis and determination of oxidants and oxidative stress in biological systems. Reviews and protocols on select methods of analysis of ROS, RNS, oxygen, redox status, and oxidative stress in biological systems are described in detail. It is an essential resource for both novices and experts in the field of oxidant and oxidative stress biology.

This book reviews the central role of hypoxia in cancer initiation and progression. It discusses the mechanisms of hypoxia in chemoresistance, radioresistance, angiogenesis, vasculogenesis, metastasis, metabolic, and genomic instability. It also explores the potential of hypoxia in the diagnosis and treatment of cancer. The book provides an overview of hypoxia imaging, its biological relevance, and mechanism of action. It helps in understanding the molecular mechanisms of the regulation of senescence by hypoxia. It explores the contribution of hypoxia to immune resistance and immune suppression/tolerance and determines the hypoxia-responsive long non-coding RNAs in regulating hypoxic gene expression at chromatin, transcriptional, and post-transcriptional levels. Further, it presents the functional link between hypoxia and miRNA expressions and hypoxia-regulated miRNAs in cancer cell survival in a low oxygen environment. Lastly, it discusses the applications of tumor-on-a-chip technology for the understanding of hypoxia-tumor microenvironment. This book is a valuable source for oncologists and scientists working to understand the role of hypoxia in cancer and therapeutic approaches.

In this book current knowledge of the pathophysiology of shock, sepsis and multi organ failure is presented. The rapid progress which has been made and the results achieved in intensive care medicine are based on sound basic research, which is duly reflected in these chapters. Multiorgan failure is the foremost cause of postoperative and posttraumatic death and many complex mechanisms are involved. Only with a good foundation of basic research can abnormalities in the physiological, biochemical, and morphological course of shock be recognized and the necessary conclusions for treatment drawn. Therapy must proceed from profound knowledge of the multi variant physiological events in order to influence shock, sepsis and organ failure. Although numerous possibilities for therapy have arisen from pharmaceutical research in recent years, they are beyond the scope of this book and are not discussed here. To gain a better understanding of the pathophysiological events it was necessary to examine and to describe different models that simulate and reproduce these events. Here we describe the causative agents (shock) and the consequences (sepsis, organ failure) in two main sections, divided on the basis of their pathophysiology.