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

1.1 Introduction

1.2 Immunotherapy

1.2.1 Cancer Vaccine

1.2.2 Cell Therapy

1.2.3 Antibody Therapy

1.3 Gene Therapy

1.4 Antiangiogenesis Therapy

1.5 Targeted Therapy

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

2.1 Gene Therapy of Cancer

2.1.1 Introduction

2.2 Replicating Oncolytic Virus on Cancer Therapy

2.3 Cancer Targeting Gene-Viro-Therapy(CTGVT)

2.3.1 General Description of CTGVT

2.4 Modification of CTGVT

2.4.1 Cancer Targeting Dual Gene-Viro-Therapy

2.4.2 CTGVT with RNAi

2.4.3 CTGVT by Killing CSC

2.4.4 CTGVT for Tissue-Specific Cancer

2.4.5 CTGVT with Cytokine Armed Antibodies

2.5 Questions

2.6 Conclusion

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

3.1 Introduction

3.2 Materials and Methods

3.2.1 AP Assay

3.2.2 MHC I Up-Regulation

3.3 Results

3.3.1 AP Activity

3.3.2 MHC I Surface Expression

3.4 Discussion

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

4.1 Cell Growth and Cancer

4.2 Mitotic Regulators as Cancer Therapy Targets

4.3 Discovery of Hec1,a Novel Protein in Mitotic Regulation

4.4 Development of Hec1 Inhibitors for Cancer Therapeutics

4.5 Conclusion

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

5.1 Introduction

5.2 Cationic Liposome-Mediated Nonviral Gene Delivery

5.3 Improvement of Therapeutic Efficiency of Liposome-Mediated Gene Therapy

5.3.1 Modifications of Liposome Composition

5.3.2 Combinational Strategy for Liposome-Mediated Gene Therapy

5.4 Improvement of Nonviral Gene Expression System

5.4.1 Cancer/Tissue-Specific Promoters

5.4.2 Two-Step Transcription Amplifier Module

5.4.3 VISA Expression Platform

5.5 Therapeutic Genes for Cancer Gene Therapy

5.5.1 p53

5.5.2 E1A

5.5.3 Bik

5.5.4 HSV-TK

5.6 Conclusion

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

6.1 Introduction

6.2 The JNK Signaling Pathway

6.3 The NF-κB Signaling Pathway

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

6.4.1 The TNF-α Signaling Circuitry and Cell Death

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

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

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

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

6.5.1 The UV Signaling Circuitry and Cell Death

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

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

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

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

6.6 Toward Cell Signaling-Based Cancer Therapy

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

7.1 Introduction

7.2 Intact AbDCs

7.2.1 mAb-Maytansinoid Drugs

7.2.2 mAb-Auristatin Drugs

7.2.3 mAb-Enediyne Drugs

7.3 Downsizing ADCs

7.3.1 Fragment mAb-Drug Conjugates

7.3.2 Engineered Antibody-Based Fusion Proteins

7.4 Conclusion

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

8.1 Introduction

8.2 History of CSC

8.3 Controversy Over CSC

8.4 Origin of CSC

8.5 Pivotal Signaling Pathways in CSCs

8.5.1 Wnt Pathway

8.5.2 Hedgehog Pathway

8.5.3 Notch Pathway

8.5.4 Pathways Related with Cancer Therapy

8.5.5 Other Pathways

8.6 CSCs and Metastasis

8.6.1 Phenotype of CSCs Related to Metastasis

8.6.2 Mechanism of Cancer Metastasis Regulated by Niche

8.6.3 CSC and EMT

8.6.4 CSC and Angiogenesis

8.6.5 Anoikis and Circulating Tumor Cells

8.7 Cancer Therapies Targeting CSCs

8.7.1 Targeting the Self-Renewal Ability

8.7.2 Targeting Survival Pathways

8.7.3 Targeting ABC Transporters

8.7.4 Targeting Cell Surface Marker and the Interaction with Niche

8.8 Future Directions of CSC

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

9.1 Introduction

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

9.2.1 p53 Mutation Status and Cancer Management

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

9.3 p53-Based Cancer Therapy

9.3.1 Increasing Wild-Type p53-Mediated Killing

9.3.2 Utilizing Mutant p53 to Induce Cancer Cell Death

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

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

10.1 Introduction

10.2 Recombinant Adenoviral-p53 Agent(Trademarked Gendicine)

10.2.1 Product Description

10.2.2 Quality Control

10.3 Mechanisms of Actions

10.4 Safety of Gendicine in Clinics

10.5 Efficacy of Gendicine in Clinics

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

10.5.2 Gendicine in Combination with Chemotherapy for Treatment of Advanced Cancers

10.5.3 Gendicine in Combination with Hyperthermia for Treatment of Advanced Cancers

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

10.6.1 Four Core Patents Covering Recombinant Ad-p53 Compositions

10.6.2 Two Patents for Methods of Recombinant Ad-p53 Manufacture

10.6.3 Two Patented Cell Lines for Production of Recombinant Adenoviral Vectors

10.6.4 Patents Covering Clinical Use of Recombinant Ad-p53

10.7 Summary and Prospective

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

11.1 Introduction

11.2 Three-Dimensional Tumor Models

11.2.1 Anticancer Drug Discovery

11.2.2 In Vitro Drug Resistance Test

11.2.3 Metastasis Tumor

11.2.4 Cancer Stem Cells

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

11.3.1 New Dimension of Immune Therapy

11.3.2 Activation of Immune Cells(Initial Stage)

11.3.3 Proliferation of the Effectors(Induced Stage)

11.3.4 Biologic Effects Against Tumor(Effective Stage)

11.3.5 Clinical Observation

11.4 Recent Advances in Cancer Immune Therapy

11.4.1 The Tumor Antigens

11.4.2 The Immune Effectors

11.4.3 The Host Environment

11.5 New Strategies for Cancer Therapy Based on Immune Intervention

11.5.1 Synergy and Individualized Cancer Treatments

11.5.2 Combinatorial Immunotherapy for Cancer

11.6 Conclusion

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

12.1 Introduction of Background of Anticancer Drug Research in China

12.2 Natural-Derived Anticancer Agents Developed in China

12.2.1 Gengshengmeisu(Actinomycin K,D)

12.2.2 Hydroxycamptothecin

12.2.3 Homoharringtonine

12.2.4 Polysaccharide Preparations

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

12.3 Synthetic Anticancer Drugs

12.3.1 Alkylating Agents

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

12.3.3 Other Effective Compounds and Preparations

12.4 New Inhibitors of Topoisomerases and Molecular-Targeted Anticancer Agents

12.4.1 New Inhibitors of Topoisomerases

12.4.2 Molecular-Targeted Anticancer Agents

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

12.5.1 N-Substituted-Thiourea Derivatives

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

12.5.3 3-Nitroquinolines

12.5.4 Quercetin-3-O-Amino Acid-Esters

12.5.5 Triaminotriazine Derivatives

12.6 Discussion and Perspectives

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

13.1 Doxorubicin Kills Tumor Cells Through Top2 Poisoning

13.2 Doxorubicin Causes Unique Tissue Toxicities

13.3 Doxorubicin Cardiotoxicity,an ROS Theory

13.4 Doxorubicin Cardiotoxicity,a Top2 Twist

13.5 Prevention of Doxorubicin Cardiotoxicity by ICRF-187

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

13.5.2 Top2β Depletion Through Proteasome-Mediated Degradation

13.6 Conclusion

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

14.1 Introduction

14.2 Structure of ABCC1

14.3 Monomer Versus Dimer

14.4 Regulations of ABCC1 Expression

14.5 Biogenesis and Trafficking

14.6 Mechanism of Action

14.7 Substrates of ABCC1

14.8 Inhibitors of ABCC1

14.9 Physiologic Functions of ABCC1

14.10 ABCC1 in Clinical Drug Resistance

14.11 Conclusion and Perspectives

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

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

15.2 Search for Anticancer Agents from Medicinal Plants

15.3 Traditional Medicinal Herbs as BRMs

15.3.1 Results of Clinical Trials

15.3.2 Experimental Studies

15.3.3 Long-Term Follow-Up

15.4 TCM as Angiogenesis Inhibitors

15.4.1 Studies in Esophageal Cancer

15.4.2 In Nonsmall Cell Lung Cancer

15.4.3 Other TCM Herbs

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

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

16.1 Historical Perspectives of Arsenic Derivatives in Medicine

16.2 Effect of Arsenic Trioxide in APL

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

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

16.3 The Application of Arsenic Trioxide in Glioma

16.3.1 Characteristics of Glioma

16.3.2 Experimental Studies

16.3.3 Clinical Application

16.3.4 Perspectives

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

16.5 Conclusions

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

17.1 Introduction

17.2 Molecular Pathogenesis of NPC

17.2.1 Genetic Factor and NPC Susceptibility

17.2.2 EBV and NPC

17.3 Molecular Diagnosis of NPC

17.3.1 Discovery of Molecular Biomarker of NPC

17.3.2 Application of Molecular Diagnosis in NPC

17.4 Advances in the Treatment of NPC

17.4.1 Clinical Application of Cytotoxic Therapeutics

17.4.2 Targeted Therapy

17.4.3 Immunotherapy

17.4.4 Gene Therapy

17.5 Summary

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

18.1 An Overview of Esophageal Carcinoma

18.1.1 Epidemiology

18.2 The Pathogenesis of Esophageal Carcinoma

18.2.1 The Pathogenesis of Barrett's Esophagus

18.2.2 The Pathogenesis of Esophageal Carcinoma

18.3 The Etiopathogenesis of Esophageal Carcinoma

18.3.1 Diet,Smoking,and Intemperance

18.3.2 Genetics and Genes

18.3.3 Virus and Inflammation

18.4 The Treatment of Esophageal Carcinoma

18.4.1 Anatomy

18.4.2 Histology

18.4.3 Clinical Presentation

18.4.4 Diagnostic Work-Up

18.4.5 Stage

18.4.6 Treatment

18.5 The Prevention of Esophageal Carcinomas

18.5.1 Protecting the Esophagus by Changing Poor Diet and Living Habits

18.5.2 Reducing the Intake of Nitrosamines

18.5.3 The Significance of Balanced Nutrition

18.5.4 The Active Treatment of Esophageal Epithelial Hyperplasia and Severe Esophagitis

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

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

19.1 The Progress of Epidemiological Study on CRC

19.1.1 Introduction

19.1.2 Distribution of CRC

19.1.3 Environmental Influencing Factors

19.1.4 Physical Activity and Obesity

19.1.5 Medical History

19.1.6 Family History of Cancer

19.1.7 Biomarkers

19.1.8 Genome Wide Association Study

19.1.9 Conclusions

19.2 CRC Screening and Early Detection in China

19.2.1 Introduction

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

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

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

19.2.5 Conclusion

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

19.3.1 Introduction

19.3.2 Epidemiology Survey of Microcystin and H.pylori Prevalence

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

19.3.4 Molecular Carcinogenesis of H.pylori

19.3.5 Activation of Erk1/2 Pathway Was Involved in Carcinogenesis

19.3.6 Conclusion

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

19.4.1 Introduction

19.4.2 SNC6/ST13

19.4.3 SNC19/ST14

19.4.4 SNC73

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

20.1 Introduction

20.2 Clinical Diagnosis and Staging of SCLC

20.3 The Clinical Management of SCLC

20.4 Genetic Alteration of SCLC

20.4.1 Oncogenes

20.4.2 Allelic Loss of Chromosome in SCLC

20.4.3 Dys-regulation of Signaling Pathways in SCLC

20.5 Transition from SCLC to Its Variants and/or NSCLC

20.6 SCLC Metastasis

20.7 Drug Resistance of SCLC

20.8 Perspective

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

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

21.1.1 The CTGVT with Potent Antitumor Effect

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

21.1.3 Other Modification of CTGVT

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

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

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

21.2.3 Mechanism of sIFN-I Action

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

21.2.5 Summary of sIFN-I

21.3 Cytokine-Induced Killer Cell Therapy and its Important Modification

21.3.1 Background

21.3.2 Characteristics of CIK Cells

21.3.3 Clinical Studies of CIK

21.3.4 Modification and Future Prospective of CIK

21.3.5 Summary of CIK Therapy

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

21.4.1 Antitumor Protein(mAb)Therapy

21.4.2 Immune Therapy Steps Up the Attack

21.4.3 Antibody Gene Therapy and Armed Antibody Gene Therapy

21.5 Cancer Crusade at 40

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

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

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

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

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

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)

21.6 Conclusion

About the Editors