The Tumour Microenvironment: Causes and Consequences of Hypoxia and Acidity

In recent years, there has been great interest in exploiting the hypoxic tumour microenvironment for therapeutic gain. It has also become clear that this microenvironment is acidic and thus hostile to the growth and survival of viable normal cells. These observations lead to several fundamentally important questions that form the basis for this book. What are the relationships between tumour perfusion and tumour pH? What are the effects of tumour pH and hypoxia on carcinogenesis or tumorigenesis? What are the therapeutic consequences of tumour pH?
This exciting book brings together leading clinicians and researchers to address some of these key issues. It is hypothesized that low extracellular pH is not only an important consequence of tumour growth but may also promote further tumorigenic transformation. Furthermore, in vitro studies suggest that low pH strongly affects the efficacy of chemo– and radiotherapy. Therapeutic strategies taking into account the consequences of altered pH, or which seek to manipulate tumour pH, more be more effective than those currently employed.

Spis treści:
Introduction (Robert J Gillies).
Frontiers in the Measurement of Cell and Tissue pH (Robert J Gillies and Ronald M Lynch).
The Physiological Environment in Cancer Vascularization, Invasion and Metastasis (Zaver M Bhujwalla et al).
Why are Cancers Acidic? A Carrier–Mediated Diffusion Model for H+ Transport in the Interstitial Fluid (J R Griffiths et al).
pH and Therapy of Human Cancers (Jeffrey L Evelhoch).
Mathematical Models of Tumour Invasion Mediated by Transformation–Induced Alteration of Microenvironmental pH (Robert A Gatenby and Edward T Gawlinski).
pH Regulation of Renal Gene Expression (Norman P Curthoys et al)).
Genetic Determinants that influence Hypoxia–Induced Apoptosis (Rodolfo M Alarcon et al).
Genomic Instability in Cancer (Sara Rockwell et al).
pH, Hypoxia and Metastasis (R P Hill et al).< br>Modelling Tumour Acidity and Invasion (Steven D Webb et al).
pH, Aerobic Glycolysis and Vascular Endothelial Growth Factor in Tumour Growth (Jacques Pouyssé gur et al).
pH and Chemotherapy (Natarajan Raghunand).
The HIF Pathway: Implications for Patterns of Gene Expression in Cancer (Charles C Wykoff et al).
pH and Multidrug Resistance (Paul D Roepe).
′The Metabolism of Tumours′ 70 Years Later (Gregg L Semenza et al).
The Multiple Mechanisms of Multidrug Resistance and Cellular pH (Sanford Simon).
Summing Up (Robert J Gillies).
Index of Contributors.
Subject Index.

Okładka tylna:
In recent years, there has been great interest in exploiting the hypoxic tumour microenvironment for therapeutic gain. It has also become clear that this microenvironment is acidic and thus hostile to the growth and survival of viable normal cells. These observations lead to several fundamentally important questions that form the basis for this book. What are the relationships between tumour perfusion and tumour pH? What are the effects of tumour pH and hypoxia on carcinogenesis or tumorigenesis? What are the therapeutic consequences of tumour pH?
This exciting book brings together leading clinicians and researchers to address some of these key issues. It is hypothesized that low extracellular pH is not only an important consequence of tumour growth but may also promote further tumorigenic transformation. Furthermore, in vitro studies suggest that low pH strongly affects the efficacy of chemo– and radiotherapy. Therapeutic strategies taking into account the consequences of altered pH, or which seek to manipulate tumour pH, more be more effective than those currently employed.