Small Molecular Immunomodifiers of Microbial Origin
Fundamental and Clinical Studies of Bestatin
- 1st Edition - September 29, 2014
- Latest edition
- Editor: Hamao Umezawa
- Language: English
- Paperback ISBN:9 7 8 - 1 - 4 8 3 1 - 7 4 5 2 - 5
- eBook ISBN:9 7 8 - 1 - 4 8 3 1 - 9 0 3 3 - 4
Small Molecular Immunomodifiers of Microbial Origin: Fundamental and Clinical Studies of Bestatin focuses on the results of experimental and clinical studies suggesting that… Read more
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.
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
- Edition: 1
- Latest edition
- Published: September 29, 2014
- Language: English
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