MicroRNAs in Cancer Translational Research (eBook)
XIII, 557 Seiten
Springer Netherland (Verlag)
978-94-007-0298-1 (ISBN)
MicroRNA (miRNA) is a cutting-edge topic in the scientific and medical fields. This is a timely and specialized book focusing on the current understanding of miRNAs and the potential for their application in cancer diagnosis, prognosis, and therapeutic targets. It also provides discussion of the lessons learned from translational miRNA studies and exploration of the next steps required to advance this field.
The unique book comprises 22 in-depth chapters by gathering unparalleled topics of interest in miRNAs by international team of world-renowned experts in the field. The first fifteen chapters provide comprehensive and expert perspectives on the most common cancers from bench to bedside applications, there is no current book structured in this cancer-oriented way. The next seven chapters providing thorough overviews of miRNAs and cancer stem cells; miRNAs in cancer invasion and metastasis; miRNAs in predicting radiotherapy and chemotherapy response; as well as expounding the role of miRNA in anti-cancer drug resistance and as blood-based cancer biomarkers. Furthermore, this book explicates the interplay of miRNAs in cancer metabolism and an update on the pioneering RNAi-based treatment approaches is also presented.
This specialized book will contribute great to the scientific and medical community by providing the up-to-date discoveries of miRNAs and their important roles in cancer translational research.
MicroRNA (miRNA) is a cutting-edge topic in the scientific and medical fields. This is a timely and specialized book focusing on the current understanding of miRNAs and the potential for their application in cancer diagnosis, prognosis, and therapeutic targets. It also provides discussion of the lessons learned from translational miRNA studies and exploration of the next steps required to advance this field.The unique book comprises 22 in-depth chapters by gathering unparalleled topics of interest in miRNAs by international team of world-renowned experts in the field. The first fifteen chapters provide comprehensive and expert perspectives on the most common cancers from bench to bedside applications, there is no current book structured in this cancer-oriented way. The next seven chapters providing thorough overviews of miRNAs and cancer stem cells; miRNAs in cancer invasion and metastasis; miRNAs in predicting radiotherapy and chemotherapy response; as well as expounding the role of miRNA in anti-cancer drug resistance and as blood-based cancer biomarkers. Furthermore, this book explicates the interplay of miRNAs in cancer metabolism and an update on the pioneering RNAi-based treatment approaches is also presented.This specialized book will contribute great to the scientific and medical community by providing the up-to-date discoveries of miRNAs and their important roles in cancer translational research.
Preface 5
Contents 6
Contributors 8
1 MicroRNAs in Cancer (An Overview) 13
1.1 Introduction 13
1.2 Mechanisms of MiRNA Deregulation in Human Cancer 15
1.3 Numerous MiRNAs are Deregulated in Human Cancer 19
1.4 MiRNAs and Their Targets 21
1.5 MiRNA Expression Profiles as Cancer Classifiers 29
1.6 MiRNAs as Prognostic Predictors 59
1.7 MiRNAs as Drug Response Predictors/Modulators 61
1.8 MiRNAs as Cancer Biomarkers 62
1.9 Conclusions and Future Perspectives 63
References 64
2 The Role of MicroRNAs in Lung Cancer Development, Progression, and Metastasis 84
2.1 Introduction 84
2.2 MiRNA Profiling of Lung Cancer and Clinical Application 85
2.3 Pathogenesis 88
2.4 Regulation of Known Oncogenes in Lung Cancer 89
2.4.1 Let-7, RAS, c-Myc and HMGA2 89
2.4.2 EGFR 90
2.4.3 p53 and MiR-34 91
2.4.4 Fus-1 and the 3p21.3 Deletion 91
2.4.5 MiR-17-92 92
2.4.6 MiR-155 92
2.5 Invasion and Metastasis Progression 93
2.6 Therapeutics 94
2.7 Conclusions 96
References 96
3 MicroRNAs in Breast Cancer 101
3.1 Deregulated Expression of MiRNAs in Breast Cancer 101
3.2 Biological Functions and Targets of MiRNAs in Breast Cancer 103
3.2.1 Tumor Suppressive Functions of MiRNAs 103
3.2.2 Oncogenic MiRNAs 106
3.2.3 MiRNAs in Estrogen Receptor Signalling 108
3.3 MiRNAs in Breast Cancer Invasion and Metastasis 109
3.4 MiRNAs in Breast Cancer Therapeutics 112
3.5 Conclusions and Future Perspectives 113
References 113
4 MicroRNAs in Colorectal Cancer 117
4.1 Introduction 117
4.2 MiRNAs in Colorectal Cancer Signaling 119
4.2.1 Wnt/-Catenin Pathway 119
4.2.2 EGFR Signaling (KRAS and PI3K Pathways) 119
4.2.3 p53 Pathway 120
4.2.4 IGF Signaling 122
4.2.5 E2F Family and Cell Cycle Regulation 122
4.2.6 MET Signaling 122
4.2.7 Cyclooxygenase-2 123
4.2.8 DNA Reparation 123
4.2.9 Extracellular Matrix Breakdown and Epithelial-mesenchymal Transition 123
4.2.10 Alterations in MiRNA Processing Machinery 124
4.2.11 Others 125
4.3 Single Nucleotide Polymorphisms (SNPs) and MiRNAs: Risk Factors for CRC 126
4.4 Plasma and Serum MiRNAs: Diagnosis and Monitoring of CRC 127
4.5 MiRNA Expression Profiles of CRC Tissue 128
4.6 MiRNAs in CRC Prognosis and Prediction 134
4.7 MiRNAs as Potential Therapeutic Targets in CRC 137
4.8 Perspectives and Challenges 138
References 139
5 MicroRNAs in Gastric Cancer 144
5.1 MicroRNAs 144
5.2 Target Genes of MiRNAs 145
5.3 Regulatory Mechanisms of MiRNA Expression 145
5.4 Aberrant Expression of MiRNAs in Gastric Cancer 145
5.5 MiRNA Profile as a Diagnostic Tool and a Predictor of the Prognosis of Patients with Gastric Cancer 148
5.6 A Novel MiRNA-mediated Therapeutic Strategy for Gastric Cancer 149
5.7 Conclusion and Perspectives 150
References 150
6.1.1 Incidence and Screening 154
6.1.2 Diagnosis 154
6.1.3 Current Therapies 155
6.2 MiRNA Expression Studies in Prostate Cancer: Towards MiRNA-based Diagnostic and Prognostic Biomarkers 156
6.2.1 Diagnostic Value of MiRNAs in Prostate Cancer 156
6.2.2 MiRNAs and Prostate Cancer Progression 157
6.2.3 Prognostic Value of MiRNAs in Prostate Cancer 158
6.2.4 MiRNAs in Circulating Blood 159
6.2.5 Are We Still Far from MiRNA-based Biomarkers for Prostate Cancer? 159
6.3 Functional Investigation of MiRNAs in Prostate Cancer: Towards the Development of MiRNA-based Therapies 161
6.4 Future Implications for Personalized Prostate Cancer Care 165
References 167
7 MicroRNAs in Hepatocellular Carcinoma 171
7.1 Introduction 171
7.1.1 Hepatocellular Carcinoma 171
7.1.2 MicroRNAs 172
7.1.2.1 Biogenesis of MiRNAs 172
7.1.2.2 Detection of MiRNA Expression and Function 173
7.2 Expression and Function of MiRNAs in HCC 174
7.2.1 MiRNAs are Aberrantly Expressed in HCCs 174
7.2.2 The Mechanism of the MiRNAs Deregulation in HCCs 176
7.2.2.1 Genomic Level 176
7.2.2.2 Transcriptional Level 179
7.2.2.3 Epigenetic Level and Others 179
7.2.3 Function of Aberrant-expressed MiRNAs in HCC 180
7.2.3.1 Promote HCC Tumorigenesis 180
7.2.3.2 Promote Tumor Progression 181
7.2.3.3 Multiple Functions of MiR-122 and Let-7 185
7.3 Biomarkers for Diagnosis, Prognosis, and Therapy of HCC 186
7.3.1 Biomarkers for Diagnosis 186
7.3.1.1 HCC Biomarkers 186
7.3.1.2 HCC Subtype Biomarkers 188
7.3.2 Biomarker for Prognosis 188
7.3.2.1 Metastasis and Recurrence 188
7.3.2.2 Survival 189
7.3.3 Biomarker for Therapy 189
7.3.3.1 Block Tumor Initiation 189
7.3.3.2 Block Tumor Progression 190
7.3.3.3 Drug Sensitivity 190
7.4 Conclusion and Prospective 191
References 192
8 MicroRNAs in Cervical Carcinoma 197
8.1 Introduction 197
8.2 MiRNA Expression in Cervical Carcinoma Cell Lines and Tissues 199
8.3 MiRNAs Functioning as Potential Oncogenes or Tumor Suppressors in Cervical Cancer 200
8.4 Interactions of HPV Infection and MiRNA in Cervical Carcinogenesis 201
8.5 MiRNA Predicting Cervical Cancer Prognosis 203
8.6 MiRNAs as Potential Cancer Therapeutics 203
8.7 Conclusions 204
References 205
9 MicroRNAs in Esophageal Cancer 208
9.1 Introduction 208
9.2 MiRNAs in BE and EAC Development 211
9.3 MiRNAs in ESCC Development 215
9.4 MiRNA as Prognostic Factors 216
9.5 Genes and Molecular Pathways Regulated by MiRNAs in Esophageal Cancer 217
9.5.1 MiRNAs Acting as Oncogenes in Esophageal Cancer 217
9.5.1.1 MiR-21 217
9.5.1.2 MiR-106-25 Polycistron (miR-25, miR-93, and miR-106b) 217
9.5.1.3 MiR-10b 219
9.5.1.4 MiR-196a 219
9.5.1.5 MiR -373 220
9.5.1.6 MiR-194 220
9.5.2 MiRNAs Acting as Tumor Suppressors in Esophageal Cancer 220
9.5.2.1 MiR-145 220
9.5.2.2 MiR-205 221
9.5.2.3 MiR-375 222
9.5.2.4 MiR-133a and MiR-133b 222
9.6 Germline Genetic Variations in MiRNA Genes, MiRNA Processing Genes, and MiRNA Binding Sites and the Risk of Esophageal Cancer 222
9.7 Conclusions 223
References 224
10 MicroRNAs in Bladder Cancer 229
10.1 Introduction 229
10.2 Historical 230
10.2.1 Embryonic MiRNA Associations with Bladder Development 230
10.2.2 MiR-200 Family and Epithelial-mesenchymal Transition (EMT) 231
10.2.3 Other Identified MiRNAs 232
10.2.4 Genetic Variability in MiRNA Machinery 235
10.3 Prognostic Implications of MiRNAs 236
10.4 Perspective and Future Challenges 240
10.5 Conclusions 240
References 241
11 MicroRNAs in Lymphoma 244
11.1 MicroRNAs in the Normal Physiology of Lymphoid Cells 245
11.1.1 As Regulators of Lymphoid Cell Development in the Primary Lymphoid Organs 245
11.1.2 In B Cells 245
11.1.3 In T Cells 245
11.2 As Regulators of Immunologic Function of the Mature Lymphoid Cells 245
11.2.1 In B Cells 247
11.2.2 In T Cells 247
11.3 Oncomirs with Pathogenetic Implications in Lymphomas 247
11.3.1 Expression Deregulation as a Result of Genomic Instability 247
11.3.1.1 Involving Gains or Losses of MiRNA Chromosomal Loci 247
11.3.1.2 Involving Epigenetic Mechanisms Acting on MiRNA Genes 249
11.3.1.3 Involving Mutation of MiRNA Genes 249
11.3.2 Expression Deregulation as a Result of Virus Infection 249
11.4 As Regulators of Known Oncogenes and Tumor Suppressor Genes 250
11.4.1 Tumor Suppressor MiRNAs 250
11.4.2 Oncomirs 256
11.5 Oncomirs with Biomarker Implications in Lymphomas 259
11.5.1 Using MiRNA Expression for Lymphoma Diagnosis Improvement 259
11.5.1.1 In B/T Lymphomas 259
11.5.1.2 In Other Lymphomas 264
11.5.2 Using MiRNA Expression for Lymphoma Prognosis Stratification Improvement 264
11.5.2.1 In B/T Lymphomas 264
11.5.2.2 In Other Lymphomas 266
11.6 Oncomirs as Possible Candidates for Therapeutic Targeting: A Promise of More Specific Lymphoma Therapies 266
References 267
12 MicroRNAs in Leukemia 273
12.1 Introduction 273
12.2 Deregulated MiRNA Expression in AML 274
12.2.1 Profiling Deregulated MiRNA Expression in AML -- Association of MiRNA Profiles with Distinct AML Subtypes 275
12.2.2 Prognostic Impact of Altered MiRNA Expression in AML 276
12.2.3 MiRNAs of Pathogenic and Functional Relevance in AML 277
12.3 MiRNAs in CML 277
12.4 MiRNA in CLL 279
12.4.1 MiR-15a and MiR-16-1 280
12.4.2 MiRNA Microarray Screens Identifying Signatures and Subgroups for Prognostication 282
12.5 Summary 284
References 285
13 MicroRNAs in Pancreatic Cancer: Potential Interests as Biomarkers and Therapeutic Tools 290
13.1 Introduction 290
13.2 MiRNAs Differentially Expressed in PDAC 291
13.3 MiRNA Expression Profiles in PDAC Precursor Lesions 296
13.3.1 PanIN 296
13.3.2 Intraductal Papillary Mucinous Neoplasm (IPMN) 297
13.4 Molecular Mechanisms Responsible for Altered MiRNA Expression 297
13.4.1 Chromosomal Alterations 297
13.4.2 Transcription Factor Defects 298
13.4.3 Epigenetic Alterations 298
13.4.4 Exogenous Stimulation of MiRNA Expression 299
13.4.5 Hypoxia 299
13.4.6 Genetic Mutations in MiRNA Genes 300
13.5 Role of MiRNAs in Pancreatic Cancer Development and Metastasis 300
13.5.1 Cell Proliferation and Tumor Growth 300
13.5.2 Epithelial-mesenchymal Transition (EMT), Invasion, and Metastatic Behavior 301
13.5.2.1 Invasion 301
13.5.2.2 Metastatic Behavior 302
13.5.3 Apoptosis and Sensitivity to Anti-cancer Agents 303
13.6 Potential Interests in MiRNAs as Biomarkers for PDAC 303
13.6.1 MiRNAs as Diagnostic Marker 304
13.6.2 MiRNAs as Prognostic Markers 305
13.7 Potential Interests in MiRNAs as Therapeutic Tool for PDAC 306
13.8 Perspectives and Challenges 306
References 307
14 MicroRNAs in Epithelial Ovarian Cancer 311
14.1 Introduction 311
14.2 Overview of Epithelial Ovarian Cancer 312
14.2.1 Pathological Complexity of Ovarian Cancers 312
14.2.2 The Origin of EOC 312
14.2.3 Biomarkers of EOC 314
14.3 MiRNA Biology 315
14.3.1 MiRNA Biogenesis 315
14.3.2 MiRNA Directed Gene Silencing 316
14.3.3 Regulating MiRNA Function 316
14.4 MiRNA in Human Cancer 317
14.4.1 MiRNA as a Tumor Suppressor and Oncogene 318
14.4.2 Mechanism of MiRNA Deregulation in Cancer 319
14.4.3 MiRNA as Prognostic Marker and Therapeutic Agent in Cancer 320
14.5 MiRNA Deregulation in Epithelial Ovarian Cancer 321
14.5.1 Genomic Alteration of MiRNA in Ovarian Cancer 321
14.5.2 Epigenetic Alteration of MiRNA in Ovarian Cancer 322
14.5.3 Alteration of MiRNA Biogenesis in Ovarian Cancer 322
14.5.4 Subtype Specific MiRNA Deregulation 323
14.5.5 Factors Contributing to the Inter-study Conflicts 324
14.6 MiRNA Function in Epithelial Ovarian Cancer 324
14.6.1 Tumor Suppressive MiRNA in Ovarian Cancer 324
14.6.2 Oncogenic MiRNA in Ovarian Cancer 326
14.6.3 Epithelial-mesenchymal Transition (EMT) Associated MiRNA in Ovarian Cancer 326
14.7 MiRNAs as Biomarkers and Prognostic Tools in Ovarian Cancer 327
14.7.1 Serum MiRNA as Biomarker in Ovarian Cancer 327
14.7.2 MiRNA as Tools to Classify Ovarian Cancer Subtypes 327
14.7.3 MiRNA as Prognostic Marker 328
14.7.4 MiRNA as Predictor for Therapy Response 328
14.8 MiRNA as Therapeutic Agents in Ovarian Cancer 328
References 338
15 MicroRNAs in Brain Tumors 345
15.1 Introduction 346
15.1.1 MiRNAs in Normal and Neoplastic Brain Growth 347
15.2 Malignant Gliomas 349
15.2.1 Genetic and Molecular Features of Malignant Gliomas 349
15.2.2 MiRNAs in GBM Pathogenesis 349
15.2.2.1 Cell Cycle/Proliferative/Survival Defects 350
15.2.2.2 Cell Migration and Invasion 351
15.2.2.3 Angiogenesis and Tumor Metabolism 353
15.2.2.4 Differentiation and Self-renewal 354
15.3 Embryonal Brain Tumors 355
15.3.1 Medulloblastoma 355
15.3.2 MiRNAs in Medulloblastoma 357
15.3.2.1 MB MiRNAs, MYC, and SHH Signaling 357
15.3.2.2 MB MiRNAs and NOTCH Signaling 358
15.3.2.3 MB-associated MiRNAs and Neuronal Differentiation 358
15.3.3 CNS-PNETs 359
15.3.3.1 MiRNAs in CNS-PNET 360
15.4 Prospects for Translation into the Clinic 361
15.4.1 MiRNAs as Brain Tumor Diagnostic and Predictive Tools 361
15.4.2 MiRNAs as Biomarkers 362
15.4.3 MiRNAs as Targets for Brain Tumor Treatment 363
15.4.3.1 Antisense MiRNA Treatment 363
15.4.3.2 Selecting Candidate MiRNAs to Target for Treatment 364
15.4.3.3 Challenges to Brain Tumor Treatment Using Anti-miRNA Oligonucleotides 364
15.5 Conclusion 365
References 365
16 MicroRNAs and Cancer Stem Cells 374
16.1 Introduction 374
16.1.1 Definition of the Stem Cell and Cancer Stem Cell 374
16.1.2 Discovery of the Cancer Stem Cell 375
16.2 MicroRNA 376
16.2.1 MiRNA and the Stem Cell 376
16.2.2 MiRNA Expression Profile in ES Cells 377
16.2.3 MiRNA Expression in Cancer Stem Cells 377
16.3 Individual MiRNAs 378
16.3.1 MiR-302 378
16.3.2 MiR-17 Cluster 378
16.3.3 MiR-181 379
16.3.4 Let-7 379
16.3.5 MiR-145 380
16.3.6 MiR-203 381
16.3.7 MiR-34 382
16.3.8 MiR-199b 382
16.3.9 MiR-128 383
16.3.10 MiR-200 383
16.4 MiRNA, Cancer Stem Cell, EMT, and Cancer Metastasis 383
16.5 MiRNA, Cancer Stem Cell, and Cancer Therapy 384
16.6 MiRNA-mediated Heterotypic Signals in Tumorigenesis 384
16.7 The Challenges of MiRNA-based Therapeutic 385
16.7.1 How to Alter the MiRNA Level in Tumors? 385
16.7.2 How to Deliver MiRNA to Patients? 385
16.7.3 How to Locate MiRNA to the Tumor Tissue? 386
References 386
17 MicroRNAs in Cancer Invasion and Metastasis 390
17.1 Introduction 391
17.2 The Role of MiRNAs in the Regulation of Tumor Cell Invasion 394
17.2.1 Cell Invasion as the 1st Step of Cancer Progression 394
17.2.2 The Role of MiR-1 Down-regulation in Lung Cancer 395
17.2.3 The Role of MiR-21: A Major MiRNA in Tumor Cell Invasion 395
17.2.4 The Role of MiR-29 Family in Cancer 396
17.2.5 Down-regulation of MiR-205 in Several Cancers 396
17.3 The Functional Role of MiRNA in the Regulation of Cancer Cell Migration, Invasion, and Metastasis 397
17.3.1 Epithelial-mesenchymal Transition (EMT) as a Prerequisite for Cancer Metastasis 400
17.3.2 Role of MiR-101 in Modulating E-cadherin Expression 400
17.3.3 Role of MiR-520h in EMT 401
17.3.4 Elevation of MiR-155 Correlates with Invasive Breast Cancer 401
17.3.5 The Role of MiR-200, MiR-205, and Modulation of ZEB Expression 401
17.4 Metastatic MiRNAs 402
17.4.1 Over-expression of MiR-10b in Metastatic Tumors 402
17.4.2 The Role of MiR-9 and MiR-10a in Pancreatic and Other Cancers 403
17.4.3 The Role of MiR-211 in Oral Carcinoma 404
17.4.4 The Role of MiR-373 and MiR-520c Expressions in Promoting Metastasis Through Suppression of CD44 404
17.5 Anti-metastatic MiRNA 404
17.5.1 The Emerging Role of Let-7 Family Members in Malignancies 404
17.5.2 The Role of MiR-17/20 Cluster in Human Malignancies 405
17.5.3 The Role of MiR-31 as an Anti-metastatic Human MiRNA 406
17.5.4 The Regulatory Role of MiR-34a Expression 406
17.5.5 The Role of MiR-122 in Liver Cancer 406
17.5.6 The Role of MiR-138 in Head and Neck Squamous Cell Carcinoma 407
17.5.7 The Role of MiR-145 and MiR-146a/146b 407
17.5.8 Over-expression of MiR-335, MiR-206, and MiR-126 Inhibits Metastasis 408
17.6 The Role of MiRNAs in Angiogenesis 408
17.7 Conclusions and Perspectives 408
17.7.1 Critical Role of MiRNA in Tumor Cell Invasion, Migration, and Metastases 409
17.7.2 The Role of MiRNAs as Diagnostic/Prognostic Markers 409
17.7.3 Development of MiRNA Targeted Therapies for Cancers 409
References 410
18 MicroRNAs in Predicting Radiotherapy andINTtie Chemotherapy Response415
18.1 Introduction 415
18.1.1 Current Classification of Malignancies 415
18.1.2 Biomarkers in Sensitization and Resistance to Radiotherapy (RT) and Chemotherapy (CT) 416
18.1.2.1 RT 416
18.1.2.2 CT 417
18.2 MiRNAs in Cancer: Tumor Suppressors and Oncogenes 418
18.2.1 Tumor Suppressive MiRNAs 418
18.2.2 Oncogenic MiRNAs 419
18.2.3 MiRNAs Involved in Cell Cycle and Apoptosis 420
18.2.4 MiRNAs in Metastasis and EMT 420
18.3 MiRNAs as Biomarkers of Cancer 421
18.3.1 MiRNAs in Determining Cancer Prognosis 422
18.3.2 Circulating MiRNAs 422
18.3.3 MiRNA Biomarkers in Clinical Trials 423
18.4 MiRNAs in Altering Sensitivity to RT and CT 423
18.4.1 MiRNAs in Predicting Response to RT 424
18.4.1.1 Radiosensitivity 424
18.4.1.2 Radioresistance 424
18.4.2 MiRNAs in Predicting Response to CT 428
18.4.2.1 Breast Cancer 428
18.4.2.2 Lung Cancer 429
18.4.2.3 Hematological Malignancies 430
18.4.2.4 Pancreatic Cancer 431
18.4.2.5 Ovarian Cancer 432
18.4.2.6 Other Cancers 432
18.4.2.7 MiRNA Predictors in Clinical Trials 434
18.4.3 Targeting MiRNAs for More Effective Treatment 435
18.4.4 MiRNA Diagnostics 435
18.5 Conclusions 436
References 436
19 Role of MicroRNAs in Anti-cancer Drug Resistance 448
19.1 Drug Resistance 448
19.2 MicroRNAs: Biogenesis, Targets, and Function 450
19.3 MiRNAs and Cancer 450
19.4 Anti-cancer Drugs Affect MiRNA Expression 451
19.5 MiRNAs Capable of Modulating Sensitivity to Anti-cancer Drugs 452
19.5.1 MiR-21 471
19.5.2 MiR-214 471
19.5.3 MiR-200 Family 472
19.5.4 MiR-221 and 222 473
19.6 Future Prospects 474
References 475
20 MicroRNAs and Cancer Metabolism 483
20.1 Introduction 483
20.2 Aerobic Glycolysis, or Warburg Effect, Is the Central Hallmark of Cancer Metabolism 484
20.3 Genetic Alteration of Oncogenes and Tumor Suppressors and Its Interplay with MiRNAs in Cancer Metabolism 485
20.3.1 c-Myc 485
20.3.2 HIF-1 487
20.3.3 LKB1/AMPK 489
20.3.4 P53 490
20.4 Conclusion and Future Outlook 492
References 493
21 MicroRNAs as Blood-based Biomarkers of Cancer 496
21.1 Introduction 496
21.2 Detection and Characterization of Circulating MiRNAs in Serum and Plasma 499
21.2.1 MiRNAs and Human Cancer 499
21.2.2 Existence of MiRNAs in Serum and Plasma 499
21.2.3 Circulating MiRNAs as a Biomarker for Cancer Diagnosis 506
21.2.4 Circulating MiRNAs as a Biomarker for Tumor Classification and Prognostication 507
21.2.5 Circulating MiRNAs as an Indicator to Reflect Other Diseases 508
21.3 Detection and Characterization of Circulating MiRNAs in Other Body Fluids 513
21.4 Experimental Techniques and Issues in Analysis of Circulating MiRNAs 516
21.5 Circulating MiRNAs Serving as Novel Potential Biomarkers for Early Tumor Detection, Diagnosis, and Prognosis 517
21.5.1 A Panel of Circulating MiRNAs Instead of Individual Circulating MiRNA as a Biomarker for Tumor Detection 517
21.5.2 A Working Model for Identifying Circulating MiRNA-based Biomarkers for Diseases 518
21.6 Some Key Issues Regarding the Sources and Biological Functions of Circulating MiRNAs 520
21.6.1 Sources of Circulating MiRNAs 520
21.6.2 Molecular Basis of the High Stability of Circulating MiRNAs 521
21.6.3 Correlation Between Tissue MiRNAs and Circulating MiRNAs 523
21.6.4 Potential Biological Functions of Circulating MiRNAs 524
21.7 Concluding Remarks and Future Directions 524
References 525
22 RNAi-based Approaches to the Treatment of Brain Tumors 530
22.1 Introduction 531
22.1.1 RNA Interference (RNAi) 531
22.1.2 Non-coding RNAs that Impart RNAi 532
22.1.3 MiRNA 533
22.2 Mechanisms of Interference 533
22.3 Rational Design of siRNA for Pre-clinical and Clinical Studies 534
22.4 Pre-clinical Experimental Strategies 535
22.5 siRNA Targets in Glioma Pre-clinical Studies 536
22.5.1 Targeting Cell Surface Receptors 537
22.5.2 Targeting Invasive Nature of Glioma 538
22.5.3 Induction of Glioma Apoptosis 538
22.5.4 Targeting Hypoxia-induced Glioma Angiogenesis Cascades via RNAi 539
22.5.5 Modulation of Immuno-activity Against Glioma 539
22.6 MiRNA Targets in Glioma 539
22.7 Systemic Delivery of RNAi to Brain Tumors 540
22.8 RNAi-mediated Glioma Therapy Clinical Trials 541
22.9 Conclusions 542
References 542
Index 547
| Erscheint lt. Verlag | 25.1.2011 |
|---|---|
| Zusatzinfo | XIII, 557 p. |
| Verlagsort | Dordrecht |
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik | |
| Schlagworte | Cancer • MicroRNAs • Oncology • small non-coding RNAs • Translational research |
| ISBN-10 | 94-007-0298-1 / 9400702981 |
| ISBN-13 | 978-94-007-0298-1 / 9789400702981 |
| Haben Sie eine Frage zum Produkt? |
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