Small Molecular Immunomodifiers of Microbial Origin

Small Molecular Immunomodifiers of Microbial Origin

Fundamental and Clinical Studies of Bestatin

1st Edition - January 1, 1981

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  • Editor: Hamao Umezawa
  • eBook ISBN: 9781483190334

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Description

Small Molecular Immunomodifiers of Microbial Origin: Fundamental and Clinical Studies of Bestatin focuses on the results of experimental and clinical studies suggesting that bestatin and small molecular weight immunity-enhancing agents can contribute to the treatment of cancer and resistant infections. The selection first offers information on the screening, discoveries, and genetics of microbial secondary metabolites and activity of bestatin. Topics include the effect of bestatin on colony formation of murine bone marrow progenitor cells in vitro; antitumor effect of bestatin on murine transplantable tumors; and structures and properties of bestatin, amastatin, forphenicine, and esterastin. The text then examines the effects of bestatin on DNA and RNA metabolism in T-cells and levamisole and bestatin in immunodefficient aged mice. The text examines the influence of bestatin on the lymphoid system in humans, natural killer activity, and bone marrow. The preliminary phase I study of bestatin in lung cancer cases and malignant skin tumors are discussed. Topics include dosage schedule, clinical findings, and changes in immunological parameters. The selection is a vital reference for readers interested in the applications of bestatin in the treatment of cancer and resistant infections.

Table of Contents


  • Preface

    Small Molecular Weight Immunomodifiers Produced by Microorganisms: Their Screening and Discoveries, and the Genetics of Microbial Secondary Metabolites

    Genetics of Microbial Secondary Metabolites

    A Biochemical Screening Method for Small Molecular Weight Immunomodifiers

    Structures and Properties of Bestatin, Amastatin, Forphenicine, and Esterastin

    1. Bestatin

    2. Amastatin

    3. Forphenicine

    4. Esterastin

    Conclusion with Future Prospect

    Summary

    Activity of Bestatin: Enhancement of Immune Responses and Antitumor Effect

    Effect of Bestatin on Immune Responses

    1. Effect of Bestatin on Delayed-Type Hypersensitivity (DTH) to Sheep Red Blood Cells (SRBC)

    2. Effect of Bestatin on Delayed-Cutaneous Hypersensitivity (DCH) to Oxazolone

    Mitogenicity of Bestatin on Murine Splenic Lymphocytes

    Antitumor Effect of Bestatin on Murine Transplantable Tumors

    1. Effect of Bestatin on Syngeneic Tumors, IMC Carcinoma, and Gardner's Lymphosarcoma

    2. Antitumor Effect of Bestatin in Combination with Antitumor Antibiotics Against Fast-Growing Tumors

    3. Effect of Bestatin on Induction of Skin Cancer by Painting 20-Methylcholanthrene (20-MC) on Mouse Skin

    The Effect of Bestatin on Colony Formation of Murine Bone Marrow Progenitor Cells in Vitro

    Discussion and Conclusion

    Summary

    Effect of Bestatin on DNA and RNA Metabolism in T-Cells

    Studies in the Animal System

    1. Effect of Bestatin Pretreatment on the Incorporation Rate of [3H]-Thymidine (dThd) in Lymphoid and Non-Lymphoid Tissues

    2. Influence of Bestatin Pretreatment on the Incorporation Rate of [3H]-dThd into Fractionated Lymphocytes

    3. in Vivo Activation of DNA Polymerase α in Lymphocytes by Bestatin

    4. Distribution of Terminal Deoxynucleotidyl Transferase Activity in Lymphoid Tissue

    5. Conclusion

    Studies with Cells in Culture

    1. Activation of DNA Polymerase α

    2. Effect on Polysome Assembly

    3. Conclusion

    Remarks

    Summary

    Levamisole and Bestatin in Immunoefficient Aged Mice

    Materials and Methods

    1. Modalities of Drug Administration

    2. Assay for Macrophage-Mediated Cytostasis

    3. Spleen Cell Responses to Mitogens

    4. Antibody Response

    5. Delayed-Type Hypersensitivity Reaction

    6. Antibody-Dependent Cell-Mediated Cytotoxicity

    Results

    1. Effect on Macrophage Activation

    2. Effect on Lymphocyte Responsiveness to Mitogens

    3. Effect on Suppressor Cell Activity

    4. Effect on Antibody Response to Various Antigens

    5. Effect on Delayed-Type Hypersensitivity

    6. Effect on Antibody-Dependent Cell Cytotoxicity

    7. Effect of the Repeated Administration of Levamisole and Bestatin on the Lifespan and the Spontaneous Tumor Incidence

    Discussion

    Summary

    The Influence of Bestatin on the Lymphoid System in the Human

    Materials and Methods

    1. Patients

    2. Preparation of Cell Suspensions

    3. Rosette Tests

    4. Natural Killer (NK)-Cell Activity of Lymphocytes

    5. Antibody-Dependent Cellular Cytotoxicity (ADCC) of Lymphocytes

    6. Lectin-Dependent Cellular Cytotoxicity (LDCC) of Lymphocytes

    7. Mitogenic Substances

    8. Lymphocyte Cultures

    9. Blood Sampling and Experimental Design

    10. Statistical Methods

    Results

    1. in Vitro Incubation of Lymphoid Cells from Healthy Donors with Bestatin

    2. Bestatin Therapy in Advanced Cancer

    3. Immunological Follow-Up in Individual Patients

    Discussion

    Summary

    Effect of Bestatin on Natural Killer Activity

    Materials and Methods

    Results

    Discussion

    Summary

    Effects of An Aminopeptidase Inhibitor (Bestatin) on Human Lymphocytes I. Effect on Pokeweed Mitogen-Induced in Vitro Immunoglobulin Production

    Materials and Methods

    1. Bestatin

    2. Lymphocytes

    3. Separation of T- and B-Lymphocytes

    4. Sera for Lymphocyte Treatment

    5. Serum Treatment of Lymphocytes

    6. Incubation of Lymphocytes

    7. Quantitation of Ig in the Supernatant

    8. Statistical Analysis

    Results

    1. Effects of Bestatin on Ig Production by the Lymphocytes from Healthy Individuals

    2. Effects of Bestatin on Ig Production by Lymphocytes Stimulated by Various Concentrations of PWM

    3. Effects of Bestatin on Ig Production by Lymphocytes Treated with Sera from Stomach Cancer Patients

    4. Effects of Bestatin on the Helper Activity of T-Cells Treated with Cancer Sera

    5. Ability of Bestatin to Block the Suppressive Effect of Cancer Sera on Ig Production by Lymphocytes

    Dicussion

    Summary

    Effect of Bestatin on Bone Marrow

    Materials and Methods

    Results

    Discussion

    Summary

    Preliminary Phase I Study of Bestatin in Lung Cancer Cases

    Clinical Findings

    Changes in Immunological Parameters

    1. Rosette Tests in Microtest Plate (2)

    2. Responses to Mitogens

    Summary

    Phase I Study of Bestatin: (I) A Clinical Study for Determination of the Optimal Dose of Bestatin

    Methods

    1. Subjects

    2. Medication Schedule and Collection of Specimens

    3. Parameters Examined and Examination Schedule

    Results

    1. Changes in Immunological Parameters in the Low Dosage, Low Pretreatment Value Group

    2. Changes in Immunological Parameters in the Low Dosage, High Pretreatment Value Group

    3. Changes in Immunological Parameters in the High Dosage, Low Pretreatment Value Group

    4. Changes in Immunological Parameters in the High Dosage, High Pretreatment Value Group

    5. Changes in Immunological Parameters in the Group at 90 mg Only Once

    6. Adverse Effects of Bestatin

    Discussion

    Summary

    Phase I Study of Bestatin: (II) Clinical Trial of Bestatin in Malignant Skin Tumors

    Materials

    Dosage Schedule

    Results

    1. Malignant Melanoma

    2. Squamous Cell Carcinoma

    3. Basal Cell Carcinoma

    4. Adenocarcinoma

    5. Malignant Lymphoma and Allied Diseases

    6. Soft Tissue Sarcoma

    Discussion

    Summary

    Phase I and Preliminary Phase II Clinical Trials of Bestain

    Materials and Methods

    Results

    Discussion

    Summary

    Clinical Experiences in the Use of Bestatin in the Treatment of Locally Advanced Cancers: Case Report

    Summary

    Clinical Experience with Bestatin in Head and Neck Cancer

    The Mode of Administration, Cases and the Results

    Summary

    Clinical and Experimental Study of Bestatin for Esophageal Cancer

    Clinical Investigation

    1. Materials and Methods

    2. Results

    Animal Experiment

    1. Materials and Methods

    2. Results

    Discussion

    Summary

    Clinical Effect of Bestatin on Malignant Tumors of Female Genital Organs

    Methods

    Results

    1. Carcinoma of the Cervix

    2. Malignant Tumors of the Ovary

    Conclusion

    Summary

    Pharmacokinetics and Metabolism of Bestatin in Humans and Rats by Gas Chromatography-Mass Spectrometry

    Materials and Methods

    1. Samples

    2. Extraction and Clean-Up Procedure from Human Serum

    3. Isolation of Metabolites in Rat Urine

    4. Preparation of Derivatives

    Results and Discussion

    1. Identification of Rat Urinary Metabolites by Radiochromatography

    2. Identification of Rat Urinary Metabolites by Use of GC-MS

    3. Quantitation of Metabolites after Bestatin Administration

    Summary

    Appendix Methods of Testing Human Immune Responses

    Ontogeny of the Lymphatic System

    Determination of the Cellular Composition of Lymphocyte Populations

    Determinations of the Proliferative Responses of Lymphocytes to Specific and Nonspecific Mitogenic Stimuli in Vitro

    Studies on the Functional Activity of B-Lymphocytes

    Migration Inhibition Assay for the Detection of Specifically-Sensitized Lymphocytes

    Cytotoxic Functions of Lymphocytes

    Detection of Antitumor Immunity

    Summary

Product details

  • No. of pages: 268
  • Language: English
  • Copyright: © Pergamon 1981
  • Published: January 1, 1981
  • Imprint: Pergamon
  • eBook ISBN: 9781483190334

About the Editor

Hamao Umezawa

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