
Redox and Cancer Part A
- 1st Edition, Volume 122 - June 24, 2014
- Imprint: Academic Press
- Editors: Kenneth D. Tew, Danyelle Townsend
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 4 2 0 1 1 7 - 0
- eBook ISBN:9 7 8 - 0 - 1 2 - 4 2 0 1 7 6 - 7
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- 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
- 10 Nonreducible Glutathionylation Involving Covalent Tethering
- 11 Conclusions
- Acknowledgments
- 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
- Edition: 1
- Volume: 122
- Published: June 24, 2014
- No. of pages (Hardback): 338
- No. of pages (eBook): 338
- Imprint: Academic Press
- Language: English
- Hardback ISBN: 9780124201170
- eBook ISBN: 9780124201767
KT
Kenneth D. Tew
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.
DT