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Redox and Cancer Part A
1st Edition, Volume 122 - June 24, 2014
Editors: Danyelle Townsend, Kenneth D. Tew
Language: English
Hardback ISBN:9780124201170
9 7 8 - 0 - 1 2 - 4 2 0 1 1 7 - 0
eBook ISBN:9780124201767
9 7 8 - 0 - 1 2 - 4 2 0 1 7 6 - 7
Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presen…Read more
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Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics — Volume 122 explores subjects related to redox, including: redox homeostasis in epithelial-derived cancers; reactive oxygen species in normal and tumor stem cells; and gamma-glutamyl transpeptidase and redox regulation.
Provides information on cancer research
Outstanding and original reviews
Suitable for researchers and students
Researchers and students in the basic and clinical sciences of cancer biology and oncology, plus related areas in genetics, immunology, pharmacology, cell biology, and molecular biology
Preface
Chapter One: Reactive Oxygen Species in Normal and Tumor Stem Cells
Abstract
1 Introduction
2 ROS
3 ROS and Normal Stem Cells
4 ROS and TSCS
5 Conclusion
Acknowledgments
Chapter Two: Emerging Regulatory Paradigms in Glutathione Metabolism
Abstract
1 Introduction
2 Glutathione Homeostasis
3 Glutathione Salvage
4 Precursor Availability
5 Remaining Questions and Emerging Pathways
6 Summary
Acknowledgment
Chapter Three: Gamma-Glutamyl Transpeptidase: Redox Regulation and Drug Resistance
Abstract
1 Introduction
2 Expression of GGT and Drug Resistance in Human Tumors
3 Structure of GGT
4 Biochemistry of GGT-Catalyzed Reactions
5 Function of GGT
6 GSH and Cysteine in Redox Regulation
7 The Role of GGT in Enhancing Cysteine Availability and Drug Resistance
8 Redox Regulation of GGT
9 Overcoming Resistance to Prooxidant Anticancer Therapy by Inhibiting GGT
10 Summary
Acknowledgments
Chapter Four: Pleiotropic Functions of Glutathione S-Transferase P
Abstract
1 Introduction
2 Subcellular Distribution of GSTP
3 GST Regulation of Kinase Signaling Pathways
4 GSTP in Redox Regulation and S-Glutathionylation
5 S-Glutathionylation Reactions
6 S-Glutathionylase Active Proteins
7 Deglutathionylase Active Proteins
8 GSTP, Nitric Oxide Synthases, and NO Homeostasis
9 GSTP Binding of Nitric Oxide Carriers
10 GSTP-Mediated Site-Specific Protein Nitrosylation/Glutathionylation
11 GSTP Polymorphisms and Pharmacogenetics
12 GSH Pathways and GSTP as Drug Platforms
13 Conclusions and Perspectives
Acknowledgments
Chapter Five: A Comparison of Reversible Versus Irreversible Protein Glutathionylation
Abstract
1 Introduction
2 Reversible Protein Glutathionylation Reactions
3 Irreversible Glutathionylation
4 2,3-Dehydroalanine and 2,3-Didehydrobutyrine Formation in Enzyme-Catalyzed Reactions
5 Historical Characterization of Dehydropeptides
6 Examples of Enzyme-Catalyzed Formation of Dehydroamino Acids in Peptide Linkage
7 Nonenzymatic Methods for the Introduction of DHA Residues into Glutathione and Proteins
8 Reducible Glutathionylation of Lens Proteins
9 Irreversible, Nonreducible Glutathionylation of Lens Proteins
Chapter Six: Glutathione Transferases in the Bioactivation of Azathioprine
Abstract
1 Preamble
2 Background
3 Polymorphisms
4 Azathioprine and Immunosuppression
5 Adverse Effects of Azathioprine
6 Polymorphisms in the Metabolic Pathways of Azathioprine
7 Structural Requirements for High GST Activity with Azathioprine
8 Rational Design of Chimeras
9 Saturation Mutagenesis of Two H-Site Residues in the C-Terminal Region
10 Redesign of GST A2-2 for Enhanced Azathioprine Activity
11 Concluding Remarks
Acknowledgments
Chapter Seven: Thioredoxin and Hematologic Malignancies
Abstract
1 Overview of Thioredoxin
2 Thioredoxin in Hematologic Malignancies and Other Cancers
3 Thioredoxin in Hematopoiesis
4 Closing Remarks
Acknowledgments
Chapter Eight: Role of the Keap1–Nrf2 Pathway in Cancer
Abstract
1 Introduction
2 The Keap1–Nrf2 Pathway
3 Dual Roles of Nrf2 in Cancer
4 Applications of the Keap1–Nrf2 System in Cancer Treatment
5 Concluding Remarks and Future Perspectives
Acknowledgments
Index
No. of pages: 338
Language: English
Edition: 1
Volume: 122
Published: June 24, 2014
Imprint: Academic Press
Hardback ISBN: 9780124201170
eBook ISBN: 9780124201767
DT
Danyelle Townsend
Affiliations and expertise
Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, USA
KT
Kenneth D. Tew
Professor & Chairman, Dept of Cell & Molecular Pharmacology John C. West Chair of Cancer Research, Medical University of South Carolina, USA
The Tew laboratory maintains an interest in using redox pathways as a platform to develop therapeutic strategies through drug discovery/development and biomarker identification. We interrogate how reactive oxygen and nitrogen species (ROS/RNS) impact cancer cells and develop novel drugs that impact on glutathione based pathways. Our research efforts have been integral to studies that have identified glutathione S-transferases (GST) as important in drug resistance, catalytic detoxification and as arbiters of kinase-mediated cell signaling events. In addition, we have been instrumental in defining how GSTP contributes to the process by which cells respond to ROS by selective addition of glutathione to specific protein clusters, so called S-glutathionylation. Each of these research areas has had broad impact on a number of cancer disciplines. Moreover, we have also been seminally involved in the Phase I to III clinical testing of three oncology drugs, Telcyta, Telintra and NOV-002. Other ongoing translational efforts have produced two ongoing clinical trials to measure the effectiveness of serum S-glutathionylated serine proteinase inhibitors as possible biomarkers for exposure to hydrogen peroxide mouthwashes and radiation.
Affiliations and expertise
Professor and Chairman, Department of Cell and Molecular Pharmacology John C. West Chair of Cancer Research, Medical University of South Carolina, USA