Basic Mechanisms and Clinical Treatment of Tumor Metastasis

Basic Mechanisms and Clinical Treatment of Tumor Metastasis provides information pertinent to the basic mechanism of tumor metastasis and the clinical results with immunochemotherapy of cancer. This book explores the extensive studies of clinical trials of cancer immunotherapy by Japanese investigators who played a significant role in the clinical assessment of different immunomodulating drugs. Organized into five parts encompassing 36 chapters, this book begins with an overview of both the in vivo and in vitro behavior of metastatic tumor cells. This text then examines the pathogenesis of cancer metastasis and its possible modulation by immune cells per se of by those treated with immunopotentiators in experimental animals. Other chapters consider the effects of different soluble immune mediators on tumor cell growth and metastasis. This book discusses as well the immunobiology and immunopathology of human tumor cell metastasis. The final chapter deals with successful and unsuccessful trials with cancer immunotherapy using various biological and chemical compounds. This book is a valuable resource for biologists, oncologists, and clinical researchers.

Contributors and Participants

Preface

Acknowledgments

Part I Cellular Behavior of Metastatic Tumors

1. Role of Cellular Heterogeneity in Tumor Behavior

I. Tumor Cell Heterogeneity of Mammary Tumors

II. Host Cell Heterogeneity of Mammary Tumors

References

Discussion

2. The Quantitation of Some Aspects of Invasion in Vivo and in Vitro

I. Introduction

II. Invasion—Assessment of the Contribution of Active Movement in Vivo

III. Invasion and Metastasis

IV. Invasion and Host Tissue "Barriers"

References

Discussion

3. Spontaneous Regression of Xenogenized Tumor Metastasis in Rats

I. Introduction

II. Xenogenization of Tumor Cells

III. Regression of Metastasis of Xenogenized Tumors

IV. Specific Immunotherapy to Tumor Metastasis by Xenogenized Tumor Cells

References

Discussion

4. Experimental Studies of Operative Stress on Tumor Growth in Rats

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

V. Summary

References

Discussion

Part IIA Regulations of Metastatic Tumor Cells

5. Tumor Cell Heterogeneity and the Pathogenesis of Cancer Metastasis

I. Introduction

II. The Cellular Diversity of Malignant Tumors

III. Evolution of Tumor Cell Heterogeneity in Malignant Tumors and Regulation of Metastatic Tumor Cell Subpopulations

IV. Conclusions

References

Discussion

6. Molecular Mechanism of Adhesiveness and Dissociation of Cancer Cells

I. Introduction

II. Adhesiveness of Cancer Cells

III. Dissociation of Cancer Cells

IV. Concluding Remarks

References

Discussion

7. Systemic and Local Regulation of Human Natural Killer Cytotoxicity

I. Introduction

II. Systemic Regulation of NK

III. Local and Regional Regulation of NK

IV. Conclusions

References

Discussion

8. Significance of Local T Cell Response to Human Cancer

I. Introduction

II. Patients and Methods Used in This Study

III. Distribution of the Antigens Defined with Monoclonal Antibodies in the Hematopoietic Cell Lines and Normal Lymphoid Tissues

IV. T and B Cells in Cancer Tissues

V. Functional Role of Infiltrating T Cells

VI. Carcinogenic Process and T Cell Response

VII. Clinical Significance of T Cell Infiltration in Cancer Tissue

VIII. Conclusions

References

Discussion

9. Natural and Induced Resistance to Metastasis from Mouse Mammary Carcinomas

I. Introduction

II. Resistance to Metastasis at the Primary Tumor

III. Resistance to Tumor Cell Dissemination

IV. Resistance to Secondary Tumor Growth

V. Concluding Remarks

References

Discussion

Part IIB

10. The Cell Surface Markers of Tumoricidal Macrophages

I. Introduction

II. A New Biochemical Marker of Tumoricidal Macrophages in Mice

III. New Serological Markers for Tumoricidal Macrophages

IV. Concluding Remarks

References

Discussion

11. Human Amnion as a New Quantitative Model for Tumor Invasion in Vitro

I. Introduction

II. Amnion Invasion Assay

III. Migration of Polymorphonuclear Leukocytes (PMN) through the Amnion

IV. Migration of Tumor Cells through the Amnion

V. The Effect of a Chemoattractant (FMLP) and Natural Protease Inhibitors on Timor Cell Invasion of the Amnion

VI. The Effect of Inhibitors to Protein and DNA Synthesis on Tumor Cell Invasion of the Amnion

VII. Conclusions

References

Discussion

12. Effect of Regional Administration of Nonspecific Immunostimulators on the Lymph Node Metastasis

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

V. Summary

References

Discussion

13. Effects of Surgical Intervention and Immunopotentiators on Metastatic Tumor Proliferation and Its Cell-Mediated Immunity

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

V. Conclusions

References

Discussion

14. Increased Immunogenicity of Tumor Cells by Induction of Complement Activating Capacity of Cell Membrane

I. Introduction

II. Methods to Detect Complement-Activating Capacity (CAC)

III. Induction of CAC on Tumor Cells by Sendai Virus Infection

IV. Suppression of Tumor Growth by Sendai Virus-Treated Cells

V. Possible Mechanism Involved in the Induction of CAC

References

Discussion

Part III The Effects of Soluble Mediators on Tumor Cell Metastasis

15. Noncytotoxic Effects of Lymphokines on Tumor Cells

I. Introduction

II. Properties of Lymphokines

III. Tumor Migration Inhibition Factor (TMIF)

IV. Endothelial Cell Migration

V. Attachment of Tumor Cells to Endothelium

VI. Summary and Conclusions

References

Discussion

16. In Vivo Effects of Lymphokines on Tumor Cells

I. Introduction

II. Migration Inhibition of the Cells Obtained from Human Solid Tumors

III. Detection of TMIF in Vivo

IV. Characterization of Serum TMIF

V. Serum TMIF in Tumor-Bearing Mice

VI. Serum Lymphokine Activities in Cancer Patients

VII. Effects of TMIF on Tumor Cells in Vivo

VIII. In Vivo Effects of Lymphokines on Tumors

IX. Conclusions

References

Discussion

17. Induction of Human Specific Killer T Cell against Autologous Cancer Cells and Its Propagation by T Cell Growth Factor

I. Introduction

II. Induction of Cytotoxic Lymphoid Cells against Squamous Cell Carcinoma Cell Line

III. Induction of Cytotoxic Lymphoid Cells against Autologous Fresh Osteosarcoma Cells

IV. Effect of Cytotoxic Lymphoid Cells Induced by Autologous Tumor Cells and Propagated by T Cell Growth Factor (TCGF) (or Interleukin 2, IL-2) on Allogeneic Tumor Cells

References

Discussion

18. Prostaglandins in Tumor Cell Metastasis

I. Arachidonic Acid (20.4) Metabolism to Cyclooxygenase and Lipoxygenase Products

II. Platelet-Tumor Cell Interactions and Metastasis

III. Prostacyclin, Thromboxanes, and Tumor Cell Metastasis

IV. Role of Tumor Cell Cathepsin B-like Proteinase in TCIPA and Metastasis

V. Sumary

References

Discussion

Part IV Immunological Aspects of Metastatic Tumors

19. Clinicopathological and Immunological Aspects of Metastatic Malignant Melanoma in Man

I. Introduction

II. Prognostic Factors in Patients with (Lymph Node Located) Regional Spread of Malignant Melanoma

III. Results

IV. An Investigation of the Accuracy of Conventional Lymph Node Assessment for Tumor Presence

V. Assessment of the Role of Host Defense Mechanisms in Determining the Survival of Melanoma Patients after Lymphadenectomy for Malignant Melanoma Spread to the Regional Lymph Nodes

References

Discussion

20. The Primary Immunoregulatory Role of Regional Lymph Nodes on the Development of Local Tumor and Lymphatic Metastasis

I. Introduction

II. Properties of MM48 Cells Metastasized in the Regional Lymph Node

III. Routes of Lymph Flow and Lymphatic Metastases

IV. The Growth of the Primary Tumor and Metastasizing Tumor in Vivo

V. In Vitro Analysis of the Immune Response of the Regional Lymph Node to Tumor Cells

VI. Relationship between Regulatory Activities and Metastasis in the Lymph Node

VII. Conclusion

References

Discussion

21. Antibodies To Tumor-Associated Gangliosides (GM2 and GD2): Potential for Suppression of Melanoma Recurrence

I. Introduction

II. Effects of Anti-OFA-I Titer on Survival of Melanoma Patients

III. In Vitro Production of Human Monoclonal Antibody to OFA-I

IV. Identification of the OFA-I-1 and OFA-I-2 Antigens as Gangliosides GM2 and GD2

V. Prospects

References

Discussion

22. A Study of Immune Complex of Glomeruli in Cancer Patients, Associated with IgG-Rheumatoid Factor and Antinuclear Antibody

I. Introduction

II. Circulating Immune Complexes in Cancer Patients

III. Nature of Circulating Immune Complexes in Cancer Patients

IV. Nephropathy in Cancer Patients

V. Nature of Immune Complexes in Glomeruli in Cancer Patients

VI. Significance of IgG Rheumatoid Factor (RF) and IgG Antinuclear Antibody (ANA) in Cancer Patients

VII. Summary

References

Discussion

23. Antibody Therapy of Metastatic Proliferation of Human Neoplastic Cells Heterotransplanted into Immunodeficient Mice

I. Introduction

II. Experimental Models of Metastases

III. Specific Immunotherapy

IV. Summary

References

Discussion

Part VA Clinical and Experimental New Approaches to Cancer Treatment

24. Effect of Intrapleural Instillation of Nocardia Rubra Cell Wall Skeleton on Lung Cancer

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

References

Discussion

25. Nonspecific Immunotherapy on Gastric Cancer

I. Introduction

II. The First Protocol: Randomized Clinical Trial with BCG-CWS

III. The Second Protocol: Randomized Clinical Trial with N-CWS

IV. Association of HLA DR4 with Long-term Survivors of Gastric Cancer

V. Discussion

References

26. Superiority of AVCF (Adriamycin, Vincristine, Cyclophosphamide, and 5-Fluorouracil) over CMF (Cyclophosphamide, Methotrexate, and 5-Fluorouracil) as Adjuvant Chemotherapy for Breast Cancer: A Phase III Trial of Association Oncofrance

I. Introduction

II. Patients and Methods

III. Results

IV. Discussion

References

Discussion

27. Monoclonal Antibodies for Tumor Detection and Targeting of Antitumor Agents

I. Introduction

II. Monoclonal Antibodies to Human Osteogenic Sarcoma

III. Localization of Anti-Osteogenic Sarcoma Monoclonal Antibody

IV. Drug-Targeting Studies

V. Conclusions

References

Discussion

Part VB

28. Experimental Immunotherapy of Human Melanoma with Human Monoclonal Antibody to a Tumor Antigen (OFA-I-2) Using Athymic Nude Mice

I. Introduction

II. Characterization of Anti-OFA-I-2

III. Experimental Immunotherapy Using Nude Mice Inoculated with Human Melanomas

IV. Summary

References

29. Postoperative Long-Term Immunostimulatory Protein-Bound Poysaccharide Kureha (PSK) Therapy for Advanced Gastric Cancer

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion

V. Summary

References

30. The Antitumor and Tumor Metastasis-Inhibitory Activities of Lentinan in Preclinical Animal Models and Its Possible Immune Mechanisms

I. Introduction

II. Antitumor and Metastasis-Inhibitory Activites of Lentinan in Animal Models

III. Possible Immune Mechanisms

IV. Toxicology

V. Conclusion

References

31. Lentinan: Biological Activity and Clinical Trial

I. Characteristics of Lentinan in Animal Experiments

II. Clinical Studies of Lentinan on Neoplastic Diseases in Humans

III. Conclusion of Phase III Study on Patients with Gastrointestinal Cancer

References

Part VC

32. New Horizons in Surgical Oncology: Malignant Melanoma

I. Introduction

II. Prospective Randomized Clinical Trial of BCG Adjuvant Immunotherapy

III. Investigation of Reasons for Differences in Trial Results

IV. Identification of Patients Who Can Benefit from Adjuvant Therapy

V. Conclusions

References

33. In Vivo and in Vitro Experiments Using OK-432 as an Immunobiological Response Modifier

I. Introduction

II. Clinical Studies of OK-432 Treatment

III. Immunological Studies on OK-432

IV. Conclusion

References

Discussion

34. Successful Treatment of Malignant Ascites: Clinical Evaluation and Role of Host's Inflammatory Cells in Tumor Cell Destruction in Ascites

I. Introduction

II. Clinical Trial for Management of Malignant Ascites

III. Interaction between Host's Inflammatory Cells and Tumor Cells

IV. Conclusions

References

Discussion

35. Immunotherapy versus Chemoimmunotherapy as Adjuvant Treatment of Malignant Melanoma

I. Introduction

II. Patients and Methods

III. Results

IV. Discussion

References

36. Evaluation of an Anticancer Activity of a Protein-Bound Polysaccharide PS-K (Krestin)

I. Introduction

II. PS-K

III. Antitumor Effect

IV. Application of PS-K to Aged Immune-Deficient Subjects

V. Clinical Application of PS-K to Stage III Gastric Cancer Patients

VI. Side Effects

VII. Conclusions

References

Discussion

Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Basic Mechanisms and Clinical Treatment of Tumor Metastasis

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