Download Drug Resistance in Cancer Cells PDF

TitleDrug Resistance in Cancer Cells
File Size10.8 MB
Total Pages372
Table of Contents
                            cover-large.tif
front-matter.pdf
	Foreword
	Contents
	Contributors
fulltext.pdf
	1  Multidrug Resistance Mediated by MDR-ABC Transporters
		Introduction
		Mechanistic Aspects of ABC Transporters
		MDR-ABC Transporters
			Transported Substrates
			Gene Regulation
		Significance of MDR-ABC Transporters in Cancer
			Association of MDR-ABC Transporters with Treatment Failure
			Overcoming MDR with Inhibitors
			Emerging Role of MDR-ABC Transporters in Resistance Against Targeted Agents
		Conclusion
		References
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	2  Metastasis and Drug Resistance
		Introduction
		The Pathogenesis of Metastasis
		Multidrug Resistance
		Reversal of Experimental MDR
			Calcium Channel Blockers
				Verapamil and Other Clinically Approved Agents
				Verapamil Derivatives and Other Experimental Calcium Channel Blockers
			Calmodulin Antagonists
			Antibiotics and Analogs
			Indole Alkaloids
			Cyclosporins and Analogs
			Hormones and Antihormones
			Pharmaceutical Emulsifying Surfactants
			Liposomal Encapsulation
			Other Molecules
		Clinical Reversal of MDR
		Overview of Experimental MDR-Reversal
		Metastasis and Drug Resistance
		Tumor Angiogenesis
		Antivascular Therapy of MDR Prostate Carcinoma
		References
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	3  The Role of Autophagy and Apoptosis in the Drug Resistance of Cancer
		Introduction
		Role of Autophagy in the Drug Resistance of Cancer
			Role of Autophagy in Cancer Treatment
			Role of Autophagy in Tumorigenesis
		Mechanism Regulating Autophagy and Apoptosis
			PI3K-AKT-mTOR Signaling Pathway
			BECN1
			BCL2 and Adenovirus E1B 19kDa Interaction Protein 3 (BNIP3)
			p53 Tumor Suppressor Pathway
			ER Stress
			Other Pathways
		Targeting Autophagy in Drug Resistance of Cancer
			Crosstalk Between Autophagy and Apoptosis
			Combination Treatment for Drug Resistance
		Conclusion
		References
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	4  Mechanisms of Resistance to Targeted Tyrosine Kinase Inhibitors
		Introduction
		Discovery of Viral and Cellular Oncogenes
		BCR-ABL Targeted Therapy
			The Philadelphia Chromosome
			BCR-ABL Signaling in CML
			Imatinib
			Imatinib Resistance in CML
				Nonmutation-Dependent Mechanisms
				Mutation of BCR-ABL
			Second-Generation BCR-ABL Inhibitors Aimed at Overcoming Imatinib Resistance
			Dasatinib
			Dasatinib Resistance
			Nilotinib
			Overcoming T315I Resistance
		EGFR-Targeted Therapy
			EGFR and Cancer
			Gefitinib and Erlotinib: EGFR-Targeted Therapies
			Response to Gefitinib Treatment
			Erlotinib
			Gefitinib and Erlotinib Resistance
				Secondary EGFR Mutations
				Non-EGFR Mutation-Dependent Mechanisms
			Overcoming T790M Resistance
		Concluding Remarks
		References
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	5  Targeting Transglutaminase-2 to Overcome Chemoresistance in Cancer Cells
		Introduction
		TG2The Protein with a Split Personality
		TG2, Drug Resistance, and Metastasis
		TG2-Mediated Cell Signaling
		TG2-Mediated NF-B Activation
		TG2 Promotes Cell Survival and Chemoresistance
		Therapeutic Significance of TG2
		Conclusions
		References
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	6  Extracellular Matrix-Mediated Drug Resistance
		Introduction
		ECM Proteins Promote Drug Resistance
		Mechanisms of ECM-Mediated Drug Resistance
			Altered Drug Penetration
			Reduced DNA Damage
			Effects on Cell Proliferation
			Interaction with Cell-Surface Integrins
		Integrin Signalling Pathways and Drug Resistance
			The Role of FAK as a Mediator of Drug Resistance
			The Role of ILK in Drug Resistance
			The Role of PI3-K Signalling in Integrin-Mediated Drug Resistance
		ECM-Mediated Drug Resistance in the Context of Metastatic Cancer
		Conclusions and Future Directions
		References
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	7  Oxidative Stress and Drug Resistance in Cancer
		Introduction
		Redox Alterations in Cancer
			The Findings
			Role of Oxidative Stress in Tumorigenesis
			Mechanisms of the Intrinsic ROS Stress in Cancer Cells
		Adaptive Response to Oxidative Stress
			Activation of Redox-Sensitive Transcription Factors
				NF-B
				Nrf2
				c-Jun
				HIF-1
			Alterations in Regulators of Redox Homeostasis
			Alterations in the Function of Proteins Involving in Cell Survival
		Mechanisms of Drug Resistance as the Consequence of Redox Adaptation
			Enhanced Cell Survival
			Increased Capacity to Maintain Redox Homeostasis
			Moderate Increase of Oxidative Stress Inhibits Apoptotic Execution
			Increased Repair and Tolerance of DNA Damage
		Altered Drug Metabolism
		Therapeutic Strategy to Overcome Drug Resistance
			Targeting Transcription Factors that Regulate Survival Pathways
			Targeting the Regulators of Redox Homeostasis
			Targeting Redox-Sensitive Factors Involving Cell Survival and Apoptosis
		Concluding Remarks
		References
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	8  Nuclear Factor-B and Chemoresistance: How Intertwined Are They?
		Introduction
		What Is NF-B?
		NF-B and Cancer
			NF-B Regulates the Expression of Cell Proliferative Gene Products
			NF-B Regulates the Expression of Anti-apoptotic Gene Products
			NF-B Regulates the Expression of Invasive Gene Products
			NF-B Regulates the Expression of Genes Involved in Angiogenesis
			NF-B Regulates the Expression of Genes Involved in Tumor Cell Metastasis
		Chemotherapeutic Agents Activate NF-B and Induce Drug Resistance
		NF-B-Mediated Drug Resistance Mechanisms
			Multidrug Resistance (MDR) Gene
			COX-2
			Survivin
			Bcl-2/Bcl-xL
			Inhibitor of Apoptosis Proteins
			cFLIP
			Cell Adhesion Molecules
			PI3K/Akt
			mTOR Pathway
			Protein Tyrosine Kinases
			5-LOX
			EGFR
			IL-6
			HER-2
			PKC/PKA
			Cyclin D1
			c-Myc
			Integrin
			TG-2
			STAT3
		NF-B Inhibitors and Chemosensitization
		Conclusion
		References
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	9  Drug Resistance and the Tumor Suppressor p53: The Paradox of Wild-Type Genotype in Chemorefractory Cancers
		Introduction
		Role of p53 in the Response of Sensitive Tumor Cells to Antitumor Agents
		Concept of Drug Resistance Caused by p53 Mutation
		Mutations in p53 Modulate Drug Response and Specificity
		Gene Status of p53 and Clinical Drug Resistance
		Relative Resistance Based on p53 Gene Status and the Role of the Antitumor Agent
		Resistance Mechanisms in Tumor Cells Harboring Wild-Type p53
			Downregulation of DNA Damage Recognition Proteins
			Downregulation of Upstream Pathways
				ATM/Chk2 and ATM/HIPK2 Pathways
				ATR/Chk1 Pathway
			Failure to Turn ''on'' the p53 Activation Switch
			Downregulation of Promoter Response to p53 in Target Genes
		Conclusion
		References
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	10  Resistance to Differentiation Therapy
		Introduction
		Acute Promelocytic Leukemia and Differentiation Therapy
		Retinoids and All-   trans   -Retinoic Acid
			The Biologic Effects of Retinoids Are Modulated Through Nuclear Receptors
		Pathogenesis of Acute Promyelocytic Leukemia
		Molecular Basis of ATRA Therapy in APL
		Resistance to Differentiation Therapy
			Accelerated ATRA Metabolism
			Increased Cellular RA-Binding Proteins (CRABPs)
			Mutations at the Ligand-Binding Domain of RAR
			Constitutive Degradation of PMLRAR
			P-Glycoprotein Expression
			Histone Deacetylase (HDAC) Activity
			The Role of PML/RAR       Isoforms in Resistance
			Telemerase Activity
			Tissue Transglutaminase Expression
			Topoisomerase II Activity
		Potential Treatment Strategies to Overcome ATRA Resistance in APL
			Liposomal ATRA
			Arsenic Trioxide (As      2         O         3      )
			Histone Deacetylase Inhibitors
			Others
			Conclusion
		References
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	11  MicroRNAs and Drug Resistance
		Introduction
		Biogenesis
		Cellular Function
		MiRNA and Cancer
		MiRNAs as Oncogenes and Tumor Suppressors
		MiRNA and Drug Resistance
		Conclusion
		References
fulltext_12.pdf
	12  Molecular Signatures of Drug Resistance
		Introduction
		Microarrays in the Heterogeneity of Cancer
		Observational vs. Experimental Studies in Drug Resistance
		Microarray Analysis: Supervised, Unsupervised, Significance, and Prediction
		Cancer Cell Lines and Signatures of Drug Resistance
		Linking Cell Line Data with Human Observational Data
		Animal Models and Signatures of Drug Resistance
		Linking Mouse Models with Human Cancer Biology
		Human Studies and Signatures of Drug Resistance
		Future Directions in Molecular Signatures of Drug Resistance
			Stem Cells
			Microenvironment
			Pathways or Modules vs. Individual Genes as Functional Units
		Conclusions
		References
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	13  Assessment of Drug Resistance in Anticancer Therapy by Nuclear Imaging
		Introduction
		Use of PET
		Imaging with PET
		Use of FDG to Identify Patients Resistant to Chemotherapy
			Imaging Pharmacokinetic Resistance
			Metabolic Resistance
		Metabolism of 5-FU and Resistance
		Imaging Physiological Causes of Resistance
			Blood Flow
			Angiogenesis
			Hypoxia
		Molecular Resistance
			Hormone Receptor-Mediated Resistance
			Apoptosis
			p53 Tumour Suppressor
		Imaging Signal Transduction Pathways
		Imaging Proliferation
			DNA Repair
			Integrin Signalling
			MDR
		Conclusions
		References
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	14  Overcoming Drug Resistance by Phytochemicals
		Introduction
			Cancer Drug Resistance
			Phytochemicals
		PhytochemicalChemotherapeutic Synergy
			Epigallocatechin-3-gallate
				Health Effects
				Cancer Drug Resistance
			Curcumin
				Health Effects
				Cancer Drug Resistance
			Resveratrol
				Health Effects
				Cancer Drug Resistance
			Other Phytochemicals
				Quercetin
				Genistein
				Indole-3-carbinol
				Phytochemicals from Medicinal Herbs
				Botanical Extracts
		Discussion
			Antagonistic Effects
			Combination Therapy
			Multiple Molecular Targets
		Safety
			Consumer Use of Phytochemicals
			Phytochemical Safety
		Bioavailability
			Bioefficacy
			Hormesis
		Conclusion and Perspective
		References
back-matter.pdf
	Index
                        

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