Leukolysins and Cancer

Generation.- 3. Lytic Activity of MCF.- 3.1. Kinetics of Lysis.- 3.2. Augmentation of MCF-Mediated Lysis by Actinomycin D.- 3.3. Enhancement of MCF Activity by IFN.- 4. Biochemical and Biophysical Characteristics of MCF.- 4.1. Temperature Stability of MCF.- 4.2. Sensitivity of MCF to Proteolytic Enzyme.- 4.3. Effect of Protease Inhibitors on MCF Activity.- 4.4. Other Physicochemical Characteristics of MCF.- 5. Biological Significance of MCF.- 5.1. Target Cell Specificity of MCF.- 5.2. Biological Role of MCF in Human Neoplasia.- 6. Conclusion.- References.- Antiproliferative Effects of Interferon.- 1. Introduction.- 2. Structure of Interferon.- 2.1. Gene Structure.- 2.2. Protein Structure.- 3. Interferon Receptors.- 3.1. Types and Affinities of Receptors.- 3.2. Receptor Interactions with the Cytoskeleton.- 4. Mechanisms of Action.- 4.1. Intracellular Messengers.- 4.2. Alterations in Gene Expression.- 4.3. Cell Cycle Progression.- 5. In Vitro Antiproliferative Effects.- 5.1. Assays for Interferon Activity.- 5.2. Cells Inhibited by Interferon.- 5.3. Differentiation Affected by Interferon.- 5.4. Interferon Synergisms.- 6. Structure-Function Relationships.- 7. In Vivo Tumor Biology.- 7.1. Antibodies to Interferon.- 7.2. Interferon-Resistant Tumors.- 7.3. Xenografts in Nude Mice.- 7.4. Direct vs. Indirect Effects.- 8. Conclusion.- References.- Natural Killer Cell Cytotoxic Factor.- Human and Rodent Natural Killer Cytotoxic Factors (NKCF): Characterization and Their Role in the NK Lytic Mechanism.- 1. Introduction.- 2. Materials and Methods.- 2.1. Production of NKCF.- 2.2. Assay of NKCF.- 3. Results and Discussion.- 3.1. NK Cells Produce NKCF.- 3.2. Mechanism of NKCF Release and Its Regulation.- 3.3. Mechanism of Action of NKCF.- 3.4. Properties That Determine NK Sensitivity in a Tumor Cell Line.- 3.5. Biochemical Characterization of NKCF.- 3.6. Relationship of NKCF to Other Cytotoxins.- 4. Concluding Remarks.- References.- Human Natural Killer Cytotoxic Factor (NKCF): Relevance, Mode of Action, and Relationship to Other Cytotoxic Factors.- 1. Introduction.- 2. Results.- 2.1. Production of NKCF by Human LGL.- 2.2. Biochemical Characterization of Purified NKCF.- 2.3. Relationship of NKCF to Other Cytotoxic or Cytostatic Effectors.- 3. Discussion.- References.- Natural Killer Cell Cytotoxic Factor.- 1. Introduction.- 2. Biology of NKCF.- 2.1. Generation of NKCF.- 2.2. NKCF Receptor.- 2.3. NKCF as an Immunoregulatory Factor.- 3. Biochemistry of NKCF.- 3.1. Molecular Weights.- 3.2. Susceptibility to Chemical Attack and pH.- 3.3. Temperature Stability.- 3.4. Susceptibility to Enzymatic Attack.- 4. Mechanism of Action of NKCF.- 4.1. Kinetic Model for NKCF-Mediated Lysis.- 4.2. Effects of Chemical Crosslinking Agents.- 4.3. Effects of Agents That Break Disulfide Bonds.- 4.4. Effects of Inhibitors of Serine Proteases.- 4.5. Effects of Membrane Active Agents.- 4.6. Effects of Inhibitors of Receptor-Mediated Endocytosis.- 5. Future Studies.- References.- Leukoregulin.- Leukoregulin: Biology, Biochemistry, and Mode of Action.- 1. Introduction.- 2. Biology of Leukoregulin.- 2.1. Cell Source of Leukoregulin.- 2.2. Bioassays.- 2.3. Target Cell Sensitivities.- 2.4. Relationship of Leukoregulin to Other Cytotoxic Lymphokines.- 2.5. Leukoregulin Species Specificity.- 2.6. Mechanism of Action.- 3. Physicochemical Characteristics of Leukoregulin.- 3.1. Leukoregulin Sensitivity to pH and Enzymatic Digestion.- 3.2. Molecular Weight.- 3.3. Isoelectric pH.- 3.4. Stability.- 4. Conclusions.- References.- Leukoregulin Mechanisms of Anticancer Action.- 1. Discovery of Leukoregulin.- 2. Assays Defining Leukoregulin Activity.- 2.1. Cytostasis-Inhibition of Cell Proliferation.- 2.2. Cytolysis-Target Cell Dissolution.- 2.3. Inhibition of Target Cell Transformation and Tumor Cell Outgrowth.- 2.4. Augmentation of Target Cell Sensitivity to Natural Killer Lymphocyte Cytotoxicity.- 2.5. Destabilization of the Target Cell Membrane.- 3. Preparation of Leukoregulin.- 3.1. Cell Sources and Stimuli for Induction.- 3.2. Isolation Procedures and Retention of Biological Activity.- 4. Pathways of Leukoregulin Action.- 5. Role of Leukoregulin in Homeostasis and Pathophysiology.- 6. Therapeutic Implications and Research Directions.- References.- Lymphotoxins: Mediators of Cellular Activation, Inflammation, and Cell Lysis That Are Immunologically Related to Macrophage Toxins and Tumor Necrosis Factors.- 1. Introduction.- 2. Studies of Lymphotoxin from Normal Lymphocytes.- 2.1. Human B-Cell Lymphotoxin.- 2.2. Human T-Cell Lymphotoxin.- 3. Immunological Relationships of LT-1, LT-2, LT-3, MCT, and TNF.- 4. Effects of Lymphotoxins on Cells In Vitro.- 5. Antitumor Effects of Lymphotoxins In Vivo.- 6. Lymphotoxins as Inducers of Inflammation.- 7. Conclusion.- References.- Tumor Necrosis Factors Alpha and Beta: A Family of Biochemically Related Cytokines.- 1. History of Tumor Necrosis Factors.- 2. Nomenclature: In Vivo Necrosis Activities.- 3. HuTNF-? and HuTNF-?: Biochemistry and Molecular Biology.- 3.1. Bioassays.- 3.2. HuTNF-? and HuTNF-? Induction Schemes.- 3.3. HuTNF-?.- 3.4. HuTNF-?.- 3.5. Amino Acid Homologies.- 4. Summary.- References.- 2. Clinical Applications Interferons.- Clinical Aspects of Interferon Therapy in Human Cancer.- 1. Introduction.- 2. Human Trials.- 3. Solid Malignancies.- 3.1. Osteosarcoma and Soft Tissue Sarcoma.- 3.2. Melanoma.- 3.3. Breast Cancer.- 3.4. Renal Cell Carcinoma.- 3.5. Kaposi's Sarcoma.- 3.6. Colorectal Adenocarcinoma.- 3.7. Carcinoid.- 3.8. Lung Cancer.- 3.9. Ovarian Carcinoma.- 3.10. Bladder Carcinoma.- 3.11. Head and Neck Carcinoma.- 3.12. Cervical Cancer.- 4. Hematologic Malignancies.- 4.1. Hairy Cell Leukemia.- 4.2. Non-Hodgkin's Lymphoma and Hodgkin's Disease.- 4.3. Cutaneous T-Cell Lymphoma.- 4.4. Chronic Lymphocytic Leukemia.- 4.5. Multiple Myeloma.- 4.6. Chronic Myelogenous Leukemia.- 4.7. Essential Thrombocythemia.- 4.8. Acute Leukemia.- 5. Mode of Action.- 5.1. Oncogene Expression.- 6. Immunomodulatory Activity.- 7. Conclusion.- References.- Antiproliferative and Clinical Antitumor Effects of Interferons.- 1. Introduction.- 2. Direct Antiproliferative Activity of Interferons.- 3. Clinical Antitumor Activity.- 3.1. Solid Tumors.- 3.2. Hematological Malignancies.- 4. Toxicities.- 5. Perspective.- 5.1. IFN and Other Lymphokines.- 5.2. IFN and Hyperthermia.- 5.3. IFN and Cytotoxic Agents.- 6. Conclusion.- References.- Biologic Effects of Tumor Necrosis Factors Alpha and Beta.- 1. Introduction.- 2. In Vivo Production of TNF.- 3. Effects of TNF on Tumors In Vivo.- 4. Metabolic Effects of TNF In Vivo.- 5. Tumor Necrosis Factor: Additional Biological Effects.- 5.1. Endotoxin Shock.- 5.2. Inflammation.- 5.3. Autoimmune Disease.- 5.4. Infection.- 6. Summary.- References.- Leukoregulin: Potential as a Clinical Cancer Therapeutic Agent.- 1. Introduction.- 2. In Vitro Preclinical Tests.- 3. In Vivo Preclinical Tests.- 4. Conclusions.- References.