癌症研究及其治疗的最新进展 英文PDF|Epub|txt|kindle电子书版本网盘下载

癌症研究及其治疗的最新进展 英文PDF格式电子书版下载

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1 Cancer Biotherapy:Progress in China&Zhen-Yu Ding and Yu-Quan Wei1

1.1 Introduction1

1.2 Immunotherapy2

1.2.1 Cancer Vaccine2

1.2.2 Cell Therapy3

1.2.3 Antibody Therapy8

1.3 Gene Therapy11

1.4 Antiangiogenesis Therapy19

1.5 Targeted Therapy21

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 Wu33

2.1 Gene Therapy of Cancer34

2.1.1 Introduction34

2.2 Replicating Oncolytic Virus on Cancer Therapy45

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

2.3.1 General Description of CTGVT47

2.4 Modification of CTGVT55

2.4.1 Cancer Targeting Dual Gene-Viro-Therapy55

2.4.2 CTGVT with RNAi63

2.4.3 CTGVT by Killing CSC64

2.4.4 CTGVT for Tissue-Specific Cancer67

2.4.5 CTGVT with Cytokine Armed Antibodies68

2.5 Questions71

2.6 Conclusion73

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 Pestka85

3.1 Introduction85

3.2 Materials and Methods87

3.2.1 AP Assay87

3.2.2 MHC I Up-Regulation87

3.3 Results88

3.3.1 AP Activity88

3.3.2 MHC I Surface Expression90

3.4 Discussion91

4 Mitotic Regulator Hec1 as a Potential Target for Cancer Therapy&Erin M.Goldblatt,Eva Lee and Wen-Hwa Lee97

4.1 Cell Growth and Cancer98

4.2 Mitotic Regulators as Cancer Therapy Targets101

4.3 Discovery of Hec1,a Novel Protein in Mitotic Regulation103

4.4 Development of Hec1 Inhibitors for Cancer Therapeutics106

4.5 Conclusion109

5 Advances in Liposome-Based Targeted Gene Therapy of Cancer&Jennifer L.Hsu,Chi-Hong Chao,Xiaoming Xie,and Mien-Chie Hung113

5.1 Introduction113

5.2 Cationic Liposome-Mediated Nonviral Gene Delivery114

5.3 Improvement of Therapeutic Efficiency of Liposome-Mediated Gene Therapy115

5.3.1 Modifications of Liposome Composition115

5.3.2 Combinational Strategy for Liposome-Mediated Gene Therapy116

5.4 Improvement of Nonviral Gene Expression System117

5.4.1 Cancer/Tissue-Specific Promoters117

5.4.2 Two-Step Transcription Amplifier Module120

5.4.3 VISA Expression Platform120

5.5 Therapeutic Genes for Cancer Gene Therapy121

5.5.1 p53121

5.5.2 E1A122

5.5.3 Bik123

5.5.4 HSV-TK124

5.6 Conclusion124

6 Rewiring the Intracellular Signaling Network in Cancer&Jing Liu and Anning Lin135

6.1 Introduction135

6.2 The JNK Signaling Pathway136

6.3 The NF-κB Signaling Pathway136

6.4 The Negative Crosstalk Between NF-κB and JNK1 Wires the TNF-α Signaling Circuitry for Cell Survival137

6.4.1 The TNF-α Signaling Circuitry and Cell Death137

6.4.2 The Crosstalk Between NF-κB and JNK Determines TNF-α Cytotoxicity138

6.4.3 Multiple Mechanisms Are Involved in NF-κB-Mediated Inhibition of TNF-α-Induced Prolonged JNK Activation139

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 Death142

6.5.1 The UV Signaling Circuitry and Cell Death142

6.5.2 Augmentation of UV-Induced Rapid and Robust JNK Activation by NF-κB Promotes UV-Induced Cell Death142

6.5.3 The"Priming"Model in Which the Preexisting Nuclear RelA/NF-κB via Induction of PKCδ to Promote UV-Induced Cell Death143

6.5.4 The RelA-PKCδ Axis May Be Involved in the Assembly of UV-Induced JNK1 Signalsome143

6.5.5 JNK1 Contributes to UV-Induced Cell Death Through Promotion of both Cytoplasmic and Nuclear Death Events144

6.6 Toward Cell Signaling-Based Cancer Therapy145

7 Research and Development of Highly Potent Antibody-Based Drug Conjugates and Fusion Proteins for Cancer Therapy&Rong-guang Shao and Yong-su Zhen153

7.1 Introduction153

7.2 Intact AbDCs154

7.2.1 mAb-Maytansinoid Drugs155

7.2.2 mAb-Auristatin Drugs159

7.2.3 mAb-Enediyne Drugs161

7.3 Downsizing ADCs163

7.3.1 Fragment mAb-Drug Conjugates164

7.3.2 Engineered Antibody-Based Fusion Proteins165

7.4 Conclusion167

8 Cancer Stem Cell&Qiang Liu,Feng-Yan Yu,Wei Tang,Shi-Cheng Su,and Er-Wei Song173

8.1 Introduction173

8.2 History of CSC175

8.3 Controversy Over CSC177

8.4 Origin of CSC178

8.5 Pivotal Signaling Pathways in CSCs180

8.5.1 Wnt Pathway181

8.5.2 Hedgehog Pathway181

8.5.3 Notch Pathway182

8.5.4 Pathways Related with Cancer Therapy182

8.5.5 Other Pathways183

8.6 CSCs and Metastasis184

8.6.1 Phenotype of CSCs Related to Metastasis184

8.6.2 Mechanism of Cancer Metastasis Regulated by Niche184

8.6.3 CSC and EMT185

8.6.4 CSC and Angiogenesis185

8.6.5 Anoikis and Circulating Tumor Cells186

8.7 Cancer Therapies Targeting CSCs186

8.7.1 Targeting the Self-Renewal Ability187

8.7.2 Targeting Survival Pathways187

8.7.3 Targeting ABC Transporters188

8.7.4 Targeting Cell Surface Marker and the Interaction with Niche188

8.8 Future Directions of CSC188

9 p53:A Target and a Biomarker of Cancer Therapy?&Xin Lu197

9.1 Introduction197

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

9.2.1 p53 Mutation Status and Cancer Management200

9.2.2 Clinical Implications of Serological Analysis of Auto-Anti-p53 Antibodies202

9.3 p53-Based Cancer Therapy203

9.3.1 Increasing Wild-Type p53-Mediated Killing203

9.3.2 Utilizing Mutant p53 to Induce Cancer Cell Death204

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 Peng215

10.1 Introduction215

10.2 Recombinant Adenoviral-p53 Agent(Trademarked Gendicine)218

10.2.1 Product Description218

10.2.2 Quality Control219

10.3 Mechanisms of Actions220

10.4 Safety of Gendicine in Clinics223

10.5 Efficacy of Gendicine in Clinics224

10.5.1 Gendicine in Combination with Radiation Therapy for Treatment of Nasopharyngeal Carcinoma and HNSCC224

10.5.2 Gendicine in Combination with Chemotherapy for Treatment of Advanced Cancers226

10.5.3 Gendicine in Combination with Hyperthermia for Treatment of Advanced Cancers232

10.6 Overview of Intellectual Property Rights of Recombinant Ad-p53,Methods of Manufacture,and Clinical Applications233

10.6.1 Four Core Patents Covering Recombinant Ad-p53 Compositions233

10.6.2 Two Patents for Methods of Recombinant Ad-p53 Manufacture235

10.6.3 Two Patented Cell Lines for Production of Recombinant Adenoviral Vectors235

10.6.4 Patents Covering Clinical Use of Recombinant Ad-p53236

10.7 Summary and Prospective237

11 Three-Dimensional Tumor Model and T-Lymphocytes Immunotherapy for Cancer&Hua Liu245

11.1 Introduction245

11.2 Three-Dimensional Tumor Models246

11.2.1 Anticancer Drug Discovery250

11.2.2 In Vitro Drug Resistance Test251

11.2.3 Metastasis Tumor252

11.2.4 Cancer Stem Cells252

11.3 3D Tumor Model and T-Lymphocytes Immune Therapy for Cancer253

11.3.1 New Dimension of Immune Therapy253

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 Observation258

11.4 Recent Advances in Cancer Immune Therapy258

11.4.1 The Tumor Antigens258

11.4.2 The Immune Effectors259

11.4.3 The Host Environment263

11.5 New Strategies for Cancer Therapy Based on Immune Intervention266

11.5.1 Synergy and Individualized Cancer Treatments266

11.5.2 Combinatorial Immunotherapy for Cancer276

11.6 Conclusion281

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 Luo287

12.1 Introduction of Background of Anticancer Drug Research in China287

12.2 Natural-Derived Anticancer Agents Developed in China290

12.2.1 Gengshengmeisu(Actinomycin K,D)290

12.2.2 Hydroxycamptothecin292

12.2.3 Homoharringtonine292

12.2.4 Polysaccharide Preparations293

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

12.3 Synthetic Anticancer Drugs294

12.3.1 Alkylating Agents294

12.3.2 Metal Anticancer Agents,Antimony-71(Sb-71),Sb-57,and so forth298

12.3.3 Other Effective Compounds and Preparations299

12.4 New Inhibitors of Topoisomerases and Molecular-Targeted Anticancer Agents300

12.4.1 New Inhibitors of Topoisomerases300

12.4.2 Molecular-Targeted Anticancer Agents311

12.5 Recent Work on Design,Synthesis,and Antitumor Evaluation of Several Series of Derivatives317

12.5.1 N-Substituted-Thiourea Derivatives317

12.5.2 3,5-Substituted Indolin-2-One Derivatives321

12.5.3 3-Nitroquinolines325

12.5.4 Quercetin-3-O-Amino Acid-Esters328

12.5.5 Triaminotriazine Derivatives332

12.6 Discussion and Perspectives338

13 Doxorubicin Cardiotoxicity Revisited:ROS Versus Top2&Yi Lisa Lyu and Leroy F.Liu351

13.1 Doxorubicin Kills Tumor Cells Through Top2 Poisoning351

13.2 Doxorubicin Causes Unique Tissue Toxicities355

13.3 Doxorubicin Cardiotoxicity,an ROS Theory355

13.4 Doxorubicin Cardiotoxicity,a Top2 Twist356

13.5 Prevention of Doxorubicin Cardiotoxicity by ICRF-187357

13.5.1 Antagonizing the Formation of Doxorubicin-Induced Top2-DNA Covalent Adducts359

13.5.2 Top2β Depletion Through Proteasome-Mediated Degradation360

13.6 Conclusion360

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 Zhang371

14.1 Introduction371

14.2 Structure of ABCC1372

14.3 Monomer Versus Dimer376

14.4 Regulations of ABCC1 Expression377

14.5 Biogenesis and Trafficking378

14.6 Mechanism of Action380

14.7 Substrates of ABCC1384

14.8 Inhibitors of ABCC1386

14.9 Physiologic Functions of ABCC1389

14.10 ABCC1 in Clinical Drug Resistance390

14.11 Conclusion and Perspectives391

15 The Role of Traditional Chinese Medicine in Clinical Oncology&Yan Sun and Jing-Yu Huang405

15.1 Historical Note on the Understanding of Cancer:West and East405

15.2 Search for Anticancer Agents from Medicinal Plants407

15.3 Traditional Medicinal Herbs as BRMs409

15.3.1 Results of Clinical Trials409

15.3.2 Experimental Studies412

15.3.3 Long-Term Follow-Up415

15.4 TCM as Angiogenesis Inhibitors416

15.4.1 Studies in Esophageal Cancer416

15.4.2 In Nonsmall Cell Lung Cancer423

15.4.3 Other TCM Herbs424

15.5 Future Perspective-Integration of TCM with Modern Medicine Both in Experimental and in Clinical Study425

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 Yang431

16.1 Historical Perspectives of Arsenic Derivatives in Medicine431

16.2 Effect of Arsenic Trioxide in APL432

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 Glioma434

16.3.1 Characteristics of Glioma434

16.3.2 Experimental Studies437

16.3.3 Clinical Application441

16.3.4 Perspectives445

16.4 Experimental Studies and Clinical Applications of As2O3 in Harbin Medical University447

16.5 Conclusions447

17 Recent Advances in Nasopharyngeal Carcinoma Research and Its Pathogenesis&Yi-Xin Zeng,Wenlin Huang,and Kai-tai Yao453

17.1 Introduction453

17.2 Molecular Pathogenesis of NPC454

17.2.1 Genetic Factor and NPC Susceptibility454

17.2.2 EBV and NPC457

17.3 Molecular Diagnosis of NPC462

17.3.1 Discovery of Molecular Biomarker of NPC462

17.3.2 Application of Molecular Diagnosis in NPC466

17.4 Advances in the Treatment of NPC469

17.4.1 Clinical Application of Cytotoxic Therapeutics469

17.4.2 Targeted Therapy470

17.4.3 Immunotherapy472

17.4.4 Gene Therapy474

17.5 Summary479

18 Esophageal Carcinoma&Qi-min Zhan,Lu-hua Wang,Yong-mei Song,Yun-wei Ou,Jing Jiang,Jing Fan,Jing-bo Wang,and Jie Shen493

18.1 An Overview of Esophageal Carcinoma493

18.1.1 Epidemiology494

18.2 The Pathogenesis of Esophageal Carcinoma496

18.2.1 The Pathogenesis of Barrett's Esophagus496

18.2.2 The Pathogenesis of Esophageal Carcinoma497

18.3 The Etiopathogenesis of Esophageal Carcinoma503

18.3.1 Diet,Smoking,and Intemperance503

18.3.2 Genetics and Genes503

18.3.3 Virus and Inflammation504

18.4 The Treatment of Esophageal Carcinoma504

18.4.1 Anatomy504

18.4.2 Histology504

18.4.3 Clinical Presentation505

18.4.4 Diagnostic Work-Up505

18.4.5 Stage506

18.4.6 Treatment507

18.5 The Prevention of Esophageal Carcinomas521

18.5.1 Protecting the Esophagus by Changing Poor Diet and Living Habits521

18.5.2 Reducing the Intake of Nitrosamines522

18.5.3 The Significance of Balanced Nutrition523

18.5.4 The Active Treatment of Esophageal Epithelial Hyperplasia and Severe Esophagitis524

18.5.5 The Identification of the Genetic Susceptibility to Esophageal Cancer Among Groups or Individuals524

19 Research on Colorectal Cancer in China&Shu Zheng,Su-Zhan Zhang,Kun Chen,Yong-Liang Zhu,and Qi Dong535

19.1 The Progress of Epidemiological Study on CRC535

19.1.1 Introduction535

19.1.2 Distribution of CRC536

19.1.3 Environmental Influencing Factors539

19.1.4 Physical Activity and Obesity541

19.1.5 Medical History541

19.1.6 Family History of Cancer542

19.1.7 Biomarkers542

19.1.8 Genome Wide Association Study545

19.1.9 Conclusions546

19.2 CRC Screening and Early Detection in China547

19.2.1 Introduction547

19.2.2 The First Population-Based CRC Screening and Prospective Cohort Study in Haining County547

19.2.3 Cluster Randomization Trial of Sequence Mass Screening for CRC in Jiashan County551

19.2.4 Validity of Immunochemical Fecal Occult Blood Test and High-Risk Questionnaire in a Population-Based CRC Screening in Hangzhou554

19.2.5 Conclusion555

19.3 The Clue of Microbe Pathogens and CRC—Study on the Carcinogenesis of Microcystin and H.pylori556

19.3.1 Introduction556

19.3.2 Epidemiology Survey of Microcystin and H.pylori Prevalence557

19.3.3 Experimental Study of Molecular Carcinogenesis of Microcystin and H.pylori Molecular Carcinogenesis of Microcystin558

19.3.4 Molecular Carcinogenesis of H.pylori561

19.3.5 Activation of Erk1/2 Pathway Was Involved in Carcinogenesis563

19.3.6 Conclusion566

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

19.4.1 Introduction567

19.4.2 SNC6/ST13569

19.4.3 SNC19/ST14573

19.4.4 SNC73582

20 Molecular and Cellular Characteristics of Small Cell Lung Cancer:Implications for Molecular-Targeted Cancer Therapy&Yu-Juan Jin,Chao Zheng,and Hong-Bin Ji597

20.1 Introduction597

20.2 Clinical Diagnosis and Staging of SCLC598

20.3 The Clinical Management of SCLC599

20.4 Genetic Alteration of SCLC600

20.4.1 Oncogenes600

20.4.2 Allelic Loss of Chromosome in SCLC601

20.4.3 Dys-regulation of Signaling Pathways in SCLC603

20.5 Transition from SCLC to Its Variants and/or NSCLC606

20.6 SCLC Metastasis607

20.7 Drug Resistance of SCLC608

20.8 Perspective609

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 Zuo617

21.1 Cancer Targeting Gene-Viro-Therapy with Excellent Antitumor Effects618

21.1.1 The CTGVT with Potent Antitumor Effect618

21.1.2 Modification of CTGVT by the Use of Two Genes,CTGVT-DG618

21.1.3 Other Modification of CTGVT621

21.2 Super Interferon(sIFN-I)with Super Antitumor Effects on Solid Tumor in Animals and in Patients622

21.2.1 sINF-I with Super Antitumor Effect on Solid Tumor in Animal Models624

21.2.2 sIFN-I with Super Antitumor Effects on Solid Tumor in Patients630

21.2.3 Mechanism of sIFN-I Action641

21.2.4 Discussion concerning the action of IFN or sIFN-I Briefly643

21.2.5 Summary of sIFN-I647

21.3 Cytokine-Induced Killer Cell Therapy and its Important Modification647

21.3.1 Background647

21.3.2 Characteristics of CIK Cells648

21.3.3 Clinical Studies of CIK648

21.3.4 Modification and Future Prospective of CIK651

21.3.5 Summary of CIK Therapy652

21.4 Antibody Protein Therapy and Antibody Gene Therapy or Armed Antibody Gene Therapy652

21.4.1 Antitumor Protein(mAb)Therapy652

21.4.2 Immune Therapy Steps Up the Attack653

21.4.3 Antibody Gene Therapy and Armed Antibody Gene Therapy653

21.5 Cancer Crusade at 40654

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 Conclusion663

About the Editors673