BOOK
Therapeutic Targets For Inflammation And Cancer: Novel Therapies For Digestive Diseases
(2017)
Additional Information
Book Details
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Contents | xix | ||
| Foreword | v | ||
| About the Editor | vii | ||
| List of Contributors | ix | ||
| Section I General Introduction to Inflammation and Cancer in the Digestive Tract | 1 | ||
| Reference | 3 | ||
| Section II Inflammation and Therapeutics in the Digestive Tract | 5 | ||
| Chapter 1. Brain–Gut Relationship on Mucosal Inflammation in the Gastrointestinal Tract\r | 7 | ||
| Abstract | 7 | ||
| Introduction | 8 | ||
| Overview of brain–gut relationship | 8 | ||
| Brain–Stomach Axis | 10 | ||
| Mental diseases, stress and gastric mucosal injury | 10 | ||
| Experimental evidence for the role of CNS in gastric mucosal homeostasis | 12 | ||
| Conveying the centrally initiated effect to the periphery | 13 | ||
| Stomach–Brain Axis | 15 | ||
| Brain–Gut Axis | 16 | ||
| Depression and IBD | 18 | ||
| Why can depression negatively influence the course of IBD? | 18 | ||
| Stress and IBD | 19 | ||
| Why does stress negatively influence the course of IBD? | 20 | ||
| Gut–Brain Axis | 21 | ||
| Mechanism of intestinal inflammation-induced brain alterations | 22 | ||
| Cytokines and prostaglandins | 22 | ||
| Gut–microbiota | 23 | ||
| Summary and Conclusion | 24 | ||
| References | 26 | ||
| Chapter 2. Nesfatin-1: The Novel Appetite Peptide with Therapeutic Efficacy to Prevent Acute Hemorrhagic Gastric Lesions and Accelerate Gastric Ulcer Healing\r | 33 | ||
| Abstract | 33 | ||
| Introduction | 34 | ||
| Expression of NUCB2/nesfatin-1 in peripheral tissues | 36 | ||
| The role of nesfatin-1 in the regulation of food intake | 38 | ||
| The emerging role of nesfatin-1 in the mechanism of gastric mucosal integrity and gastroprotection against damage induced by noxious agents | 40 | ||
| Involvement of nesfatin-1 and other appetite-controlling hormones the mechanism of gastric ulcer healing: A possible translation to the human peptic ulcer disease? | 49 | ||
| References | 51 | ||
| Chapter 3. Chemoprophylaxis in Inflammatory Bowel Disease | 57 | ||
| Abstract | 57 | ||
| Introduction | 58 | ||
| Potential Medical Therapies for Prevention of Colorectal Cancer in Inflammatory Bowel Disease | 60 | ||
| 5-Aminosalicylates (5-ASA) | 60 | ||
| Thiopurines | 62 | ||
| Anti-tumor necrosis factor-α (anti-TNF-α) therapy | 63 | ||
| Ursodeoxycolic acid (UDCA) | 64 | ||
| Folate | 65 | ||
| Aspirin and NSAIDs | 66 | ||
| Corticosteroids | 67 | ||
| Calcium and vitamin D | 67 | ||
| Statins | 68 | ||
| Limitations of Current Evidence | 69 | ||
| Conclusion | 69 | ||
| References | 70 | ||
| Chapter 4. Targeting the Nuclear Receptor HNF4a as a Potential Therapy for Gut Inflammation and Cancer\r | 77 | ||
| Abstract | 77 | ||
| Introduction | 78 | ||
| Nuclear Receptors as Subtypes of Transcriptional Regulators | 78 | ||
| The nuclear receptor HNF4a | 80 | ||
| Structural characteristics of HNF4a | 80 | ||
| HNF4a consists of several isoforms | 81 | ||
| Cellular functions of HNF4a | 84 | ||
| HNF4a’s involvement in cancer | 85 | ||
| HNF4a and liver cancer | 86 | ||
| HNF4a and gastric cancer | 86 | ||
| HNF4a and colorectal cancer | 87 | ||
| Regulation of HNF4a activity | 88 | ||
| Concluding Remarks | 89 | ||
| References | 90 | ||
| Chapter 5. Established Therapies and New Therapeutic Strategies in Alcoholic Liver Disease\r | 99 | ||
| Abstract | 99 | ||
| Introduction | 100 | ||
| Natural History of ALD | 101 | ||
| Established Therapy in ALD | 104 | ||
| Abstinence | 104 | ||
| Abstinence for alcoholic fatty liver | 104 | ||
| Abstinence for alcoholic hepatitis | 104 | ||
| Abstinence for alcoholic liver cirrhosis | 105 | ||
| How to achieve abstinence | 105 | ||
| Therapy of AH | 106 | ||
| General measures | 106 | ||
| Hyperalimentation | 107 | ||
| Corticosteroids | 108 | ||
| N-Acetylcysteine | 108 | ||
| Liver transplantation | 109 | ||
| Therapy of alcoholic cirrhosis of the liver | 110 | ||
| New Therapeutic Approaches in ALD | 110 | ||
| Endotoxins and cytokines as therapeutic targets: Anti-inflammatory and anti-fibrotic strategies | 111 | ||
| Counteracting oxidative stress and cytochrome P4502E1 induction | 114 | ||
| Homocysteine, endoplasmic reticulum stress, and apoptosis: The use of betaine and antiapoptotic strategies | 115 | ||
| Hepatic cell regeneration: Induction of proliferation of hepatic progenitor cells, mesenchymal stem cell transplantation, and bone marrow transplantation granulocyte colony stimulating factor | 117 | ||
| Liver progenitor cells in AH: Stem cell transplantation therapy | 118 | ||
| Bone marrow transplantation | 119 | ||
| Summary and Conclusion | 119 | ||
| Acknowledgments | 120 | ||
| References | 121 | ||
| Section III Carcinogenesis and Therapeutic Targets in the Gastrointestinal Tract\r | 129 | ||
| Chapter 6. Targets of Tumor Epigenetics and Its Microenvironment in Gastrointestinal Cancer\r | 131 | ||
| Abstract | 131 | ||
| Introduction | 132 | ||
| Histone Modifications and Inflammation in Gastrointestinal Cancer Epigenetics | 132 | ||
| Epigenetics in cancer | 133 | ||
| DNA methylation | 133 | ||
| Histone modification | 134 | ||
| Epigenetic events in inflammation | 134 | ||
| Regulation of microRNA Profiles by Cytokines and Chemokines in Gastrointestinal Cancer | 135 | ||
| microRNA in general | 135 | ||
| microRNAs in gastrointestinal cancer | 135 | ||
| microRNA regulation by cytokines and chemokines | 136 | ||
| Targeting Epithelial–Mesenchymal Transition Attenuates Gastrointestinal Tumor Invasion and Metastasis | 137 | ||
| What is epithelial–mesenchymal transition? | 137 | ||
| Regulation of epithelial–mesenchymal transition in cancer cells | 138 | ||
| Tumor stroma and its epithelial–mesenchymal transition induction | 138 | ||
| Microenvironmental regulators of epithelial–mesenchymal transition | 138 | ||
| Epithelial–mesenchymal transition regulates inflammation in cancer | 139 | ||
| Epithelial–mesenchymal transition confers a cancer stem cell phenotype | 139 | ||
| Targets of epithelial–mesenchymal transition as a therapeutic strategy | 140 | ||
| Targeting Endoplasmic Reticulum Stress on the Tumor Unfolding Protein, Causing Apoptosis | 141 | ||
| Endoplasmic reticulum stress | 141 | ||
| Unfolding protein response pathway | 141 | ||
| Endoplasmic reticulum stress and gastrointestinal cancer | 142 | ||
| Endoplasmic reticulum stress signaling as a therapeutic target in clinical cancer research | 142 | ||
| References | 144 | ||
| Chapter 7. Esophageal Cancer: From Bench to Bedside | 151 | ||
| Abstract | 151 | ||
| Introduction | 152 | ||
| Regulation of Esophageal Development and Homeostasis | 152 | ||
| Esophageal development and its regulation | 152 | ||
| Maintenance of homeostasis of esophageal epithelium | 155 | ||
| Esophageal Carcinoma | 156 | ||
| Epidemiology of esophageal cancer | 156 | ||
| Metastasis of esophageal cancer | 159 | ||
| Proteins regulating metastasis of ESCC | 160 | ||
| Non-coding RNAs and metastasis of ESCC | 161 | ||
| Microenvironmental regulation of metastasis in ESCC | 161 | ||
| Esophageal cancer stem cells | 163 | ||
| Therapeutics in Metastatic Esophageal Cancer | 164 | ||
| References | 167 | ||
| Chapter 8. Angiogenesis and Lymphangiogenesis in Gastric MALT Lymphoma: Relation of VEGF and VASH2\r | 177 | ||
| Abstract | 177 | ||
| Introduction | 177 | ||
| Gastric MALT Lymphoma Induced by Helicobacter heilmannii Infection | 178 | ||
| Hypoxia and Angiogenesis in Gastric MALT Lymphoma | 179 | ||
| Lymphangiogenesis of Gastric MALT Lymphoma | 181 | ||
| VEGF and VEGF-R in Gastric MALT Lymphoma | 181 | ||
| Significance of VASH2 | 183 | ||
| Effect of axitinib on VEGF and VASH2 | 185 | ||
| References | 186 | ||
| Chapter 9. NF-κB as a Potential Molecular Target for Therapy of Gastrointestinal Cancers\r | 189 | ||
| Abstract | 189 | ||
| Introduction | 189 | ||
| Structure and function of NF-kB | 190 | ||
| NF-kB regulation | 192 | ||
| The role of NF-kB in cancer and its regulated genes in gastrointestinal (GI) tract cancer | 194 | ||
| The influence of inflammation on NF-kB dysregulation and cancer risk | 195 | ||
| NF-kB signaling in cancers | 197 | ||
| Therapeutics targeting NF-kB in GI cancers | 199 | ||
| Inflammation | 200 | ||
| Upstream regulators, TNF-α, and Akt | 200 | ||
| IKK/proteasome inhibitors | 201 | ||
| Conclusions | 202 | ||
| References | 203 | ||
| Chapter 10. Hypoxia-Inducible Factor-1a Modulation in Colorectal Carcinogenesis\r | 213 | ||
| Abstract | 213 | ||
| Introduction | 214 | ||
| HIF-1α Activation in Colorectal Cancer\r | 214 | ||
| HIF-1α and the Wnt pathway \r | 216 | ||
| HIF-1α and the MMR system \r | 216 | ||
| HIF-1α and Modifications of Cellular Metabolism \r | 216 | ||
| HIF-1a regulation of glycolysis | 217 | ||
| HIF-1a and oxidative phosphorylation | 217 | ||
| HIF-1a as Modulator of Inflammation | 218 | ||
| HIF-1a and mucosal protection | 218 | ||
| HIF-1a and promotion of inflammation | 219 | ||
| HIF-1a and Tumor Growth | 220 | ||
| HIF-1a and regulation of angiogenesis and metastasis | 220 | ||
| HIF-1a and clinicopathological features | 221 | ||
| HIF-1a as a Therapeutic Target | 221 | ||
| Targeting HIF-1a pathways in colorectal carcinoma | 223 | ||
| New strategies for HIF-1a targeting | 223 | ||
| Conclusions | 224 | ||
| References | 225 | ||
| Chapter 11. Therapeutic Approaches Targeting the Serrated Pathway of Colorectal Cancer Characterized by Mutation in the BRAF Gene and Overexpression of GTPase Rac1b\r | 233 | ||
| Abstract | 233 | ||
| Introduction | 233 | ||
| The Serrated Pathway to CRC | 234 | ||
| Molecular and morphological characteristics | 234 | ||
| Role of BRAF in colon cancer | 236 | ||
| Inflammation and BRAF-driven tumorigenesis | 238 | ||
| Role of Rac1b overexpression in BRAF-driven tumorigenesis | 238 | ||
| Therapeutic Targets for the Serrated Pathway to CRC | 239 | ||
| Targeting BRAF with kinase inhibitors | 240 | ||
| Combined therapeutic targeting of BRAF and EGFR | 241 | ||
| Combined therapeutic targeting of BRAF and MEK1 | 241 | ||
| Other combination therapy strategies | 243 | ||
| Targeting CIMP | 244 | ||
| Targeting inflammation | 244 | ||
| Targeting Rac1b overexpression | 245 | ||
| Acknowledgments | 247 | ||
| References | 248 | ||
| Chapter 12. The “Yin” and “Yang” of Target-Oriented Anticancer \rPhytochemicals Derived from Herbal Medicines | 257 | ||
| Abstract | 257 | ||
| Introduction | 258 | ||
| Adverse Effects Resulting from the Use of Herbal Medicines or Phytochemical in Cancer Patients | 259 | ||
| Pharmacokinetic interaction involving CYP metabolizing enzymes | 259 | ||
| The herb–drug interaction via modulation of drug transporter expression | 260 | ||
| Approach to avoid potential risk of the herb–drug interaction | 261 | ||
| Quality control of herbal medicines | 261 | ||
| Awareness of the safety of herbal medicine | 263 | ||
| Beneficial Effects of Herbal Medicines or Phytochemicals in the Treatment of Cancer | 264 | ||
| Beneficial effects of TCM in cancer patients | 265 | ||
| Therapeutic effects of PHY906 in gastrointestinal cancers | 265 | ||
| Identification of potential anti-cancer herbal medicinal compounds: The experience in the past decade | 266 | ||
| Triptolide and pseudolaric acid B | 266 | ||
| Herbal isoprenoids | 267 | ||
| Licorice and isoliquiritigenin | 268 | ||
| Astragalus membranaceus and AST | 270 | ||
| Conclusion | 274 | ||
| References | 275 | ||
| Chapter 13. The Degradation System of Prostaglandin E2 in Gastrointestinal Cancer\r | 281 | ||
| Abstract | 281 | ||
| Introduction | 282 | ||
| Multidrug Resistance-Associated Protein 4 (MRP4) | 282 | ||
| Prostaglandin Transporter (PGT) | 283 | ||
| 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH) | 284 | ||
| Expression of 15-PGDH and PGT in Gastrointestinal Cancer and Its Significance | 285 | ||
| Biological Significance of Downregulation of 15-PGDH and PGT in Gastrointestinal Cancer | 285 | ||
| Regulation of PGT and 15-PGDH in Gastrointestinal Cancer | 286 | ||
| Epigenetic modulation | 286 | ||
| β-catenin \r | 287 | ||
| Epidermal growth factor receptor (EGFR) signaling | 288 | ||
| Transforming growth factor-β (TGF-β) signaling\r | 288 | ||
| Interleukin (IL)-1β\r | 288 | ||
| microRNAs | 288 | ||
| Perspectives | 289 | ||
| Acknowledgment | 289 | ||
| References | 289 | ||
| Chapter 14. Prostaglandin and Its Receptors: Potential Targets for Gastrointestinal Inflammation and Cancer\r | 295 | ||
| Abstract | 295 | ||
| Introduction | 296 | ||
| Cyclooxygenase (COX) metabolism | 297 | ||
| Roles of COX-2 in GI cancers | 298 | ||
| PGE2 signaling and its receptors | 299 | ||
| EP1 receptor | 299 | ||
| EP2 receptor | 300 | ||
| EP3 receptor | 301 | ||
| EP4 receptor | 302 | ||
| Conclusion and Future Direction | 303 | ||
| References | 304 | ||
| Section IV Autophagy and microRNAs as the Therapeutic Targets in Gastrointestinal Cancers\r | 309 | ||
| Chapter 15. Modulation of Autophagy as a Potential Therapeutic Target for Gastrointestinal Cancers: Promises and Uncertainties\r | 311 | ||
| Abstract | 311 | ||
| Introduction | 312 | ||
| Autophagy | 312 | ||
| Definition of autophagy | 312 | ||
| Molecular Basis of Autophagy | 314 | ||
| Functions of Autophagy | 316 | ||
| Autophagy and Cancer | 316 | ||
| Autophagy and tumorigenesis | 316 | ||
| Mechanisms of tumor suppression by autophagy | 317 | ||
| Autophagy and tumor progression | 318 | ||
| Mechanisms of tumor survival by autophagy | 319 | ||
| Autophagy and chemoresistance | 319 | ||
| Autophagy and cancer stem cells (CSCs) | 320 | ||
| Crosstalk between autophagy and apoptosis in cancer cells | 321 | ||
| Modes of crosstalk between autophagy and apoptosis in response to stress | 321 | ||
| Targeting Autophagy in GI Cancer | 325 | ||
| Preclinical studies | 325 | ||
| Cancer treatments that induce prosurvival autophagy | 325 | ||
| Cancer treatments that induce prodeath autophagy | 329 | ||
| Cancer treatments that inhibit autophagy | 329 | ||
| Clinical trials targeting autophagy in GI cancer | 329 | ||
| Limitations and Uncertainties of Autophagy Modulation in Cancer Therapy | 331 | ||
| Variation of autophagic response in different cancer context | 331 | ||
| Off-target effects of autophagy inhibition | 332 | ||
| Challenges of monitoring autophagic activity in vivo in patients | 333 | ||
| Uncertainty: The role of CQ in cancer treatment | 333 | ||
| Concluding Remarks | 334 | ||
| Acknowledgment | 335 | ||
| References | 335 | ||
| Chapter 16. microRNAs as Therapeutic Targets for Gastric Cancer | 343 | ||
| Abstract | 343 | ||
| Introduction | 343 | ||
| miRNAs Associated with Gastric Carcinogenesis | 344 | ||
| Helicobacter pylori | 345 | ||
| Epstein–Barr virus | 347 | ||
| miRNAs Associated with Refractory GC | 347 | ||
| miRNAs Involved in Metastatic Processes | 349 | ||
| Migration, invasion, and epithelial–mesenchymal transition | 349 | ||
| Tumor angiogenesis | 353 | ||
| Metastatic tumor formation using in vivo models | 354 | ||
| Future Perspectives | 355 | ||
| References | 356 | ||
| Chapter 17. microRNA-based Novel Therapeutic Development in Gastrointestinal Cancer\r | 365 | ||
| Abstract | 365 | ||
| Introduction | 366 | ||
| Significant Functions of miRNA in Gastrointestinal (GI) Cancers | 368 | ||
| OncomiRs | 368 | ||
| Tumor suppressor miRNAs | 370 | ||
| Therapeutic potential of miRNA: Therapeutics | 371 | ||
| Therapeutic potential of miRNA: Biomarkers | 377 | ||
| Conclusion | 380 | ||
| Acknowledgments | 380 | ||
| References | 380 | ||
| Chapter 18. Unraveling the Relationship between Autophagy and microRNA in Gastrointestinal Cancer\r | 387 | ||
| Abstract | 387 | ||
| Introduction | 388 | ||
| miRNAs Regulate Autophagy | 390 | ||
| The Relationship Between Autophagy and miRNAs in GC | 392 | ||
| miRNAs downregulate autophagy in GC cancer | 392 | ||
| miR-23b-3p: ATG12 and HMGB2 | 392 | ||
| miR-143: ATG8 | 398 | ||
| miR-181a: ATG5 | 398 | ||
| miR-19a/b, miR-21, miR-106a: PTEN/PI3K/Akt | 399 | ||
| miR-15b and miR-16: Bcl-2 | 399 | ||
| miR-30: BECN1 | 400 | ||
| The Relationship Between Autophagy and miRNAs in Colorectal Cancer | 400 | ||
| miRNAs upregulate autophagy in CRC | 400 | ||
| miR-210: Bcl-2 | 400 | ||
| miR-18a: ATM | 401 | ||
| miR-18a: hnRNP A1 E2 | 402 | ||
| miRNAs downregulate autophagy in CRC | 403 | ||
| miR-502: Rab1B | 403 | ||
| miR-22: PTEN | 403 | ||
| miR-22: BTG1 | 403 | ||
| miR-106b: ATG16L1 | 404 | ||
| miRNA profiling in CRC during 5-FU-induced autophagy | 404 | ||
| The Relationship Between Autophagy and miRNAs in Pancreatic Cancer | 405 | ||
| miRNAs downregulate autophagy in pancreatic cancer | 405 | ||
| miR-23b: ATG12 | 405 | ||
| miR-216a: BECN1 | 406 | ||
| The Relationship Between Autophagy and miRNAs in HCC | 406 | ||
| miRNAs upregulate autophagy in HCC | 406 | ||
| miR-100: IGF-1R, mTOR | 406 | ||
| miR-423-5p: ATG7 | 408 | ||
| miRNAs downregulate autophagy in HCC | 408 | ||
| miR-375: ATG7 | 408 | ||
| miR-199a-5p: ATG7 | 409 | ||
| miR-101: RAB5A, STMN1, ATG4D, and mTOR | 409 | ||
| miR-101: EZH2 | 410 | ||
| miR-17: ULK1, ATG7, and p62 | 411 | ||
| miR-20a: ULK1 and p62 | 411 | ||
| miR-30a: BECN1 | 411 | ||
| Autophagy downregulates miR-224 | 412 | ||
| miRNAs Regulate the Crosstalk Between Autophagy and Apoptosis in Gastrointestinal Cancer | 413 | ||
| Conclusion | 413 | ||
| References | 415 | ||
| Index | 421 |