癌症研究及其治疗的最新进展 英文PDF电子书下载

1 Cancer Biotherapy:Progress in China&Zhen-Yu Ding and Yu-Quan Wei 1

1.1 Introduction 1

1.2 Immunotherapy 2

1.2.1 Cancer Vaccine 2

1.2.2 Cell Therapy 3

1.2.3 Antibody Therapy 8

1.3 Gene Therapy 11

1.4 Antiangiogenesis Therapy 19

1.5 Targeted Therapy 21

2 Cancer Targeting Gene-Viro-Therapy and Its Promising Future&Xin-Yuan Liu,Wen-Lin Huang,Qi-Jun Qian,Wei-Guo Zou,Zi-Lai Zhang,Liang Chu,Kang-Jian Zhang,Li-Li Zhao,Yan-Hong Zhang,Song-Bo Qiu,Zhen-Wei Zhang,Tian Xiao,Jun-Kai Fan,Na Wei,Xin-Ran Liu,Xin Cao,Jin-Fa Gu,Rui-Cheng Wei,Miao Ding,and Shuai Wu 33

2.1 Gene Therapy of Cancer 34

2.1.1 Introduction 34

2.2 Replicating Oncolytic Virus on Cancer Therapy 45

2.3 Cancer Targeting Gene-Viro-Therapy(CTGVT) 47

2.3.1 General Description of CTGVT 47

2.4 Modification of CTGVT 55

2.4.1 Cancer Targeting Dual Gene-Viro-Therapy 55

2.4.2 CTGVT with RNAi 63

2.4.3 CTGVT by Killing CSC 64

2.4.4 CTGVT for Tissue-Specific Cancer 67

2.4.5 CTGVT with Cytokine Armed Antibodies 68

2.5 Questions 71

2.6 Conclusion 73

3 Relationship Between Antiproliferative Activities and Class I MHC Surface Expression of Mouse Interferon Proteins on B16-F10 Melanoma Cells&Ronald G.Jubin,Doranelly H.Koltchev,Diane Vy,and Sidney Pestka 85

3.1 Introduction 85

3.2 Materials and Methods 87

3.2.1 AP Assay 87

3.2.2 MHC I Up-Regulation 87

3.3 Results 88

3.3.1 AP Activity 88

3.3.2 MHC I Surface Expression 90

3.4 Discussion 91

4 Mitotic Regulator Hec1 as a Potential Target for Cancer Therapy&Erin M.Goldblatt,Eva Lee and Wen-Hwa Lee 97

4.1 Cell Growth and Cancer 98

4.2 Mitotic Regulators as Cancer Therapy Targets 101

4.3 Discovery of Hec1,a Novel Protein in Mitotic Regulation 103

4.4 Development of Hec1 Inhibitors for Cancer Therapeutics 106

4.5 Conclusion 109

5 Advances in Liposome-Based Targeted Gene Therapy of Cancer&Jennifer L.Hsu,Chi-Hong Chao,Xiaoming Xie,and Mien-Chie Hung 113

5.1 Introduction 113

5.2 Cationic Liposome-Mediated Nonviral Gene Delivery 114

5.3 Improvement of Therapeutic Efficiency of Liposome-Mediated Gene Therapy 115

5.3.1 Modifications of Liposome Composition 115

5.3.2 Combinational Strategy for Liposome-Mediated Gene Therapy 116

5.4 Improvement of Nonviral Gene Expression System 117

5.4.1 Cancer/Tissue-Specific Promoters 117

5.4.2 Two-Step Transcription Amplifier Module 120

5.4.3 VISA Expression Platform 120

5.5 Therapeutic Genes for Cancer Gene Therapy 121

5.5.1 p53 121

5.5.2 E1A 122

5.5.3 Bik 123

5.5.4 HSV-TK 124

5.6 Conclusion 124

6 Rewiring the Intracellular Signaling Network in Cancer&Jing Liu and Anning Lin 135

6.1 Introduction 135

6.2 The JNK Signaling Pathway 136

6.3 The NF-κB Signaling Pathway 136

6.4 The Negative Crosstalk Between NF-κB and JNK1 Wires the TNF-α Signaling Circuitry for Cell Survival 137

6.4.1 The TNF-α Signaling Circuitry and Cell Death 137

6.4.2 The Crosstalk Between NF-κB and JNK Determines TNF-α Cytotoxicity 138

6.4.3 Multiple Mechanisms Are Involved in NF-κB-Mediated Inhibition of TNF-α-Induced Prolonged JNK Activation 139

6.4.4 Prolonged JNK1 Activation Contributes to TNF-α-Induced Cell Death Through Elimination of Caspase Inhibitor(S) 141

6.5 The Positive Crosstalk Between NF-κB and JNK1 Wires the UV Signaling Circuitry for Cell Death 142

6.5.1 The UV Signaling Circuitry and Cell Death 142

6.5.2 Augmentation of UV-Induced Rapid and Robust JNK Activation by NF-κB Promotes UV-Induced Cell Death 142

6.5.3 The"Priming"Model in Which the Preexisting Nuclear RelA/NF-κB via Induction of PKCδ to Promote UV-Induced Cell Death 143

6.5.4 The RelA-PKCδ Axis May Be Involved in the Assembly of UV-Induced JNK1 Signalsome 143

6.5.5 JNK1 Contributes to UV-Induced Cell Death Through Promotion of both Cytoplasmic and Nuclear Death Events 144

6.6 Toward Cell Signaling-Based Cancer Therapy 145

7 Research and Development of Highly Potent Antibody-Based Drug Conjugates and Fusion Proteins for Cancer Therapy&Rong-guang Shao and Yong-su Zhen 153

7.1 Introduction 153

7.2 Intact AbDCs 154

7.2.1 mAb-Maytansinoid Drugs 155

7.2.2 mAb-Auristatin Drugs 159

7.2.3 mAb-Enediyne Drugs 161

7.3 Downsizing ADCs 163

7.3.1 Fragment mAb-Drug Conjugates 164

7.3.2 Engineered Antibody-Based Fusion Proteins 165

7.4 Conclusion 167

8 Cancer Stem Cell&Qiang Liu,Feng-Yan Yu,Wei Tang,Shi-Cheng Su,and Er-Wei Song 173

8.1 Introduction 173

8.2 History of CSC 175

8.3 Controversy Over CSC 177

8.4 Origin of CSC 178

8.5 Pivotal Signaling Pathways in CSCs 180

8.5.1 Wnt Pathway 181

8.5.2 Hedgehog Pathway 181

8.5.3 Notch Pathway 182

8.5.4 Pathways Related with Cancer Therapy 182

8.5.5 Other Pathways 183

8.6 CSCs and Metastasis 184

8.6.1 Phenotype of CSCs Related to Metastasis 184

8.6.2 Mechanism of Cancer Metastasis Regulated by Niche 184

8.6.3 CSC and EMT 185

8.6.4 CSC and Angiogenesis 185

8.6.5 Anoikis and Circulating Tumor Cells 186

8.7 Cancer Therapies Targeting CSCs 186

8.7.1 Targeting the Self-Renewal Ability 187

8.7.2 Targeting Survival Pathways 187

8.7.3 Targeting ABC Transporters 188

8.7.4 Targeting Cell Surface Marker and the Interaction with Niche 188

8.8 Future Directions of CSC 188

9 p53:A Target and a Biomarker of Cancer Therapy?&Xin Lu 197

9.1 Introduction 197

9.2 Can p53 Act as a Biomarker in Cancer Management and Therapy? 200

9.2.1 p53 Mutation Status and Cancer Management 200

9.2.2 Clinical Implications of Serological Analysis of Auto-Anti-p53 Antibodies 202

9.3 p53-Based Cancer Therapy 203

9.3.1 Increasing Wild-Type p53-Mediated Killing 203

9.3.2 Utilizing Mutant p53 to Induce Cancer Cell Death 204

9.4 What Can We Do to Accelerate p53-Based Cancer Management and Therapy? 207

10 Recombinant Adenoviral-p53 Agent(Gendicine？):Quality Control,Mechanism of Action,and Its Use for Treatment of Malignant Tumors&Shu-Yuan Zhang,You-Yong Lu,and Zhao-Hui Peng 215

10.1 Introduction 215

10.2 Recombinant Adenoviral-p53 Agent(Trademarked Gendicine) 218

10.2.1 Product Description 218

10.2.2 Quality Control 219

10.3 Mechanisms of Actions 220

10.4 Safety of Gendicine in Clinics 223

10.5 Efficacy of Gendicine in Clinics 224

10.5.1 Gendicine in Combination with Radiation Therapy for Treatment of Nasopharyngeal Carcinoma and HNSCC 224

10.5.2 Gendicine in Combination with Chemotherapy for Treatment of Advanced Cancers 226

10.5.3 Gendicine in Combination with Hyperthermia for Treatment of Advanced Cancers 232

10.6 Overview of Intellectual Property Rights of Recombinant Ad-p53,Methods of Manufacture,and Clinical Applications 233

10.6.1 Four Core Patents Covering Recombinant Ad-p53 Compositions 233

10.6.2 Two Patents for Methods of Recombinant Ad-p53 Manufacture 235

10.6.3 Two Patented Cell Lines for Production of Recombinant Adenoviral Vectors 235

10.6.4 Patents Covering Clinical Use of Recombinant Ad-p53 236

10.7 Summary and Prospective 237

11 Three-Dimensional Tumor Model and T-Lymphocytes Immunotherapy for Cancer&Hua Liu 245

11.1 Introduction 245

11.2 Three-Dimensional Tumor Models 246

11.2.1 Anticancer Drug Discovery 250

11.2.2 In Vitro Drug Resistance Test 251

11.2.3 Metastasis Tumor 252

11.2.4 Cancer Stem Cells 252

11.3 3D Tumor Model and T-Lymphocytes Immune Therapy for Cancer 253

11.3.1 New Dimension of Immune Therapy 253

11.3.2 Activation of Immune Cells(Initial Stage) 255

11.3.3 Proliferation of the Effectors(Induced Stage) 256

11.3.4 Biologic Effects Against Tumor(Effective Stage) 256

11.3.5 Clinical Observation 258

11.4 Recent Advances in Cancer Immune Therapy 258

11.4.1 The Tumor Antigens 258

11.4.2 The Immune Effectors 259

11.4.3 The Host Environment 263

11.5 New Strategies for Cancer Therapy Based on Immune Intervention 266

11.5.1 Synergy and Individualized Cancer Treatments 266

11.5.2 Combinatorial Immunotherapy for Cancer 276

11.6 Conclusion 281

12 Advances in Cancer Chemotherapeutic Drug Research in China&Bin Xu,Jian Ding,Kai-Xian Chen,Ze-Hong Miao,He Huang,Hong Liu,and Xiao-Min Luo 287

12.1 Introduction of Background of Anticancer Drug Research in China 287

12.2 Natural-Derived Anticancer Agents Developed in China 290

12.2.1 Gengshengmeisu(Actinomycin K,D) 290

12.2.2 Hydroxycamptothecin 292

12.2.3 Homoharringtonine 292

12.2.4 Polysaccharide Preparations 293

12.2.5 Some Meaningful Anticancer Substances from Traditional Chinese Medicine(TCM) 293

12.3 Synthetic Anticancer Drugs 294

12.3.1 Alkylating Agents 294

12.3.2 Metal Anticancer Agents,Antimony-71(Sb-71),Sb-57,and so forth 298

12.3.3 Other Effective Compounds and Preparations 299

12.4 New Inhibitors of Topoisomerases and Molecular-Targeted Anticancer Agents 300

12.4.1 New Inhibitors of Topoisomerases 300

12.4.2 Molecular-Targeted Anticancer Agents 311

12.5 Recent Work on Design,Synthesis,and Antitumor Evaluation of Several Series of Derivatives 317

12.5.1 N-Substituted-Thiourea Derivatives 317

12.5.2 3,5-Substituted Indolin-2-One Derivatives 321

12.5.3 3-Nitroquinolines 325

12.5.4 Quercetin-3-O-Amino Acid-Esters 328

12.5.5 Triaminotriazine Derivatives 332

12.6 Discussion and Perspectives 338

13 Doxorubicin Cardiotoxicity Revisited:ROS Versus Top2&Yi Lisa Lyu and Leroy F.Liu 351

13.1 Doxorubicin Kills Tumor Cells Through Top2 Poisoning 351

13.2 Doxorubicin Causes Unique Tissue Toxicities 355

13.3 Doxorubicin Cardiotoxicity,an ROS Theory 355

13.4 Doxorubicin Cardiotoxicity,a Top2 Twist 356

13.5 Prevention of Doxorubicin Cardiotoxicity by ICRF-187 357

13.5.1 Antagonizing the Formation of Doxorubicin-Induced Top2-DNA Covalent Adducts 359

13.5.2 Top2β Depletion Through Proteasome-Mediated Degradation 360

13.6 Conclusion 360

14 Biochemistry and Pharmacology of Human ABCC1/MRP1 and Its Role in Detoxification and in Multidrug Resistance of Cancer Chemotherapy&Wei Mo,Jing-Yuan Liu,and Jian-Ting Zhang 371

14.1 Introduction 371

14.2 Structure of ABCC1 372

14.3 Monomer Versus Dimer 376

14.4 Regulations of ABCC1 Expression 377

14.5 Biogenesis and Trafficking 378

14.6 Mechanism of Action 380

14.7 Substrates of ABCC1 384

14.8 Inhibitors of ABCC1 386

14.9 Physiologic Functions of ABCC1 389

14.10 ABCC1 in Clinical Drug Resistance 390

14.11 Conclusion and Perspectives 391

15 The Role of Traditional Chinese Medicine in Clinical Oncology&Yan Sun and Jing-Yu Huang 405

15.1 Historical Note on the Understanding of Cancer:West and East 405

15.2 Search for Anticancer Agents from Medicinal Plants 407

15.3 Traditional Medicinal Herbs as BRMs 409

15.3.1 Results of Clinical Trials 409

15.3.2 Experimental Studies 412

15.3.3 Long-Term Follow-Up 415

15.4 TCM as Angiogenesis Inhibitors 416

15.4.1 Studies in Esophageal Cancer 416

15.4.2 In Nonsmall Cell Lung Cancer 423

15.4.3 Other TCM Herbs 424

15.5 Future Perspective-Integration of TCM with Modern Medicine Both in Experimental and in Clinical Study 425

16 Effect of Arsenic Trioxide on Acute Promyelocytic Leukemia and Glioma:Experimental Studies,Clinical Applications,and Perspectives&Shi-Guang Zhao,Jin Zhou,Yao-Hua Liu,Li-Gang Wang,and Bao-Feng Yang 431

16.1 Historical Perspectives of Arsenic Derivatives in Medicine 431

16.2 Effect of Arsenic Trioxide in APL 432

16.2.1 What Is the Role of Arsenic in Newly Diagnosed APL? 432

16.2.2 Conclusion and Perspectives:Can We Induce a 100R Rate in Newly Diagnosed APL? 434

16.3 The Application of Arsenic Trioxide in Glioma 434

16.3.1 Characteristics of Glioma 434

16.3.2 Experimental Studies 437

16.3.3 Clinical Application 441

16.3.4 Perspectives 445

16.4 Experimental Studies and Clinical Applications of As2O3 in Harbin Medical University 447

16.5 Conclusions 447

17 Recent Advances in Nasopharyngeal Carcinoma Research and Its Pathogenesis&Yi-Xin Zeng,Wenlin Huang,and Kai-tai Yao 453

17.1 Introduction 453

17.2 Molecular Pathogenesis of NPC 454

17.2.1 Genetic Factor and NPC Susceptibility 454

17.2.2 EBV and NPC 457

17.3 Molecular Diagnosis of NPC 462

17.3.1 Discovery of Molecular Biomarker of NPC 462

17.3.2 Application of Molecular Diagnosis in NPC 466

17.4 Advances in the Treatment of NPC 469

17.4.1 Clinical Application of Cytotoxic Therapeutics 469

17.4.2 Targeted Therapy 470

17.4.3 Immunotherapy 472

17.4.4 Gene Therapy 474

17.5 Summary 479

18 Esophageal Carcinoma&Qi-min Zhan,Lu-hua Wang,Yong-mei Song,Yun-wei Ou,Jing Jiang,Jing Fan,Jing-bo Wang,and Jie Shen 493

18.1 An Overview of Esophageal Carcinoma 493

18.1.1 Epidemiology 494

18.2 The Pathogenesis of Esophageal Carcinoma 496

18.2.1 The Pathogenesis of Barrett's Esophagus 496

18.2.2 The Pathogenesis of Esophageal Carcinoma 497

18.3 The Etiopathogenesis of Esophageal Carcinoma 503

18.3.1 Diet,Smoking,and Intemperance 503

18.3.2 Genetics and Genes 503

18.3.3 Virus and Inflammation 504

18.4 The Treatment of Esophageal Carcinoma 504

18.4.1 Anatomy 504

18.4.2 Histology 504

18.4.3 Clinical Presentation 505

18.4.4 Diagnostic Work-Up 505

18.4.5 Stage 506

18.4.6 Treatment 507

18.5 The Prevention of Esophageal Carcinomas 521

18.5.1 Protecting the Esophagus by Changing Poor Diet and Living Habits 521

18.5.2 Reducing the Intake of Nitrosamines 522

18.5.3 The Significance of Balanced Nutrition 523

18.5.4 The Active Treatment of Esophageal Epithelial Hyperplasia and Severe Esophagitis 524

18.5.5 The Identification of the Genetic Susceptibility to Esophageal Cancer Among Groups or Individuals 524

19 Research on Colorectal Cancer in China&Shu Zheng,Su-Zhan Zhang,Kun Chen,Yong-Liang Zhu,and Qi Dong 535

19.1 The Progress of Epidemiological Study on CRC 535

19.1.1 Introduction 535

19.1.2 Distribution of CRC 536

19.1.3 Environmental Influencing Factors 539

19.1.4 Physical Activity and Obesity 541

19.1.5 Medical History 541

19.1.6 Family History of Cancer 542

19.1.7 Biomarkers 542

19.1.8 Genome Wide Association Study 545

19.1.9 Conclusions 546

19.2 CRC Screening and Early Detection in China 547

19.2.1 Introduction 547

19.2.2 The First Population-Based CRC Screening and Prospective Cohort Study in Haining County 547

19.2.3 Cluster Randomization Trial of Sequence Mass Screening for CRC in Jiashan County 551

19.2.4 Validity of Immunochemical Fecal Occult Blood Test and High-Risk Questionnaire in a Population-Based CRC Screening in Hangzhou 554

19.2.5 Conclusion 555

19.3 The Clue of Microbe Pathogens and CRC—Study on the Carcinogenesis of Microcystin and H.pylori 556

19.3.1 Introduction 556

19.3.2 Epidemiology Survey of Microcystin and H.pylori Prevalence 557

19.3.3 Experimental Study of Molecular Carcinogenesis of Microcystin and H.pylori Molecular Carcinogenesis of Microcystin 558

19.3.4 Molecular Carcinogenesis of H.pylori 561

19.3.5 Activation of Erk1/2 Pathway Was Involved in Carcinogenesis 563

19.3.6 Conclusion 566

19.4 CRC-Related Gene(SNC6/ST13,SNC19/ST14,SNC73) 567

19.4.1 Introduction 567

19.4.2 SNC6/ST13 569

19.4.3 SNC19/ST14 573

19.4.4 SNC73 582

20 Molecular and Cellular Characteristics of Small Cell Lung Cancer:Implications for Molecular-Targeted Cancer Therapy&Yu-Juan Jin,Chao Zheng,and Hong-Bin Ji 597

20.1 Introduction 597

20.2 Clinical Diagnosis and Staging of SCLC 598

20.3 The Clinical Management of SCLC 599

20.4 Genetic Alteration of SCLC 600

20.4.1 Oncogenes 600

20.4.2 Allelic Loss of Chromosome in SCLC 601

20.4.3 Dys-regulation of Signaling Pathways in SCLC 603

20.5 Transition from SCLC to Its Variants and/or NSCLC 606

20.6 SCLC Metastasis 607

20.7 Drug Resistance of SCLC 608

20.8 Perspective 609

21 Possibility to Partly Win the War Against Cancer&Xin-Yuan Liu,Guang-Wen Wei,Dong-Qin Yang,Lun-Xu Liu,Lin Ma,Xiao Li,Jian OuYang,Cui-Ping Li,Kang-Jian Zhang,Jian Wang,Liang Chu,Jin-Fa Gu,Huang-Guang Li,Jian Ding,Na Wei,Ying Cai,Xin-Ran Liu,Xin Cao,Yi Chen,Zhi-Jiang Wu,Miao Ding,and Ming Zuo 617

21.1 Cancer Targeting Gene-Viro-Therapy with Excellent Antitumor Effects 618

21.1.1 The CTGVT with Potent Antitumor Effect 618

21.1.2 Modification of CTGVT by the Use of Two Genes,CTGVT-DG 618

21.1.3 Other Modification of CTGVT 621

21.2 Super Interferon(sIFN-I)with Super Antitumor Effects on Solid Tumor in Animals and in Patients 622

21.2.1 sINF-I with Super Antitumor Effect on Solid Tumor in Animal Models 624

21.2.2 sIFN-I with Super Antitumor Effects on Solid Tumor in Patients 630

21.2.3 Mechanism of sIFN-I Action 641

21.2.4 Discussion concerning the action of IFN or sIFN-I Briefly 643

21.2.5 Summary of sIFN-I 647

21.3 Cytokine-Induced Killer Cell Therapy and its Important Modification 647

21.3.1 Background 647

21.3.2 Characteristics of CIK Cells 648

21.3.3 Clinical Studies of CIK 648

21.3.4 Modification and Future Prospective of CIK 651

21.3.5 Summary of CIK Therapy 652

21.4 Antibody Protein Therapy and Antibody Gene Therapy or Armed Antibody Gene Therapy 652

21.4.1 Antitumor Protein(mAb)Therapy 652

21.4.2 Immune Therapy Steps Up the Attack 653

21.4.3 Antibody Gene Therapy and Armed Antibody Gene Therapy 653

21.5 Cancer Crusade at 40 654

21.5.1 Introduction:Celebrating an Anniversary(by Paula Kiberstis and Eliot Marshall) 654

21.5.2 Cancer Research and the 90 Billion USD Metaphor(by Eliot Marshall) 655

21.5.3 Combining Target Drug to Stop Resistant Tumors(by Jocelyn Kaiser) 656

21.5.4 Exploring the Genomes of Cancer Cells:Progress and Promise(by M.R.Stratton) 657

21.5.5 A Perspective on Cancer Cell Metastasis(by Christine Chaffer and Robert A.Weinberg) 658

21.5.6 Cancer Immunoediting:Integrating Immunity's Roles in Cancer Suppression and Promotion(by R.D.Schreiber,L.J.Old,and M.J.Smyth) 661

21.6 Conclusion 663

About the Editors 673