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  • TITLE
  • DECLARATION
  • CERTIFICATE
  • ACKNOWLEDGEMENT
  • CONTENTS
  • I. INTRODUCTION & REVIEW OF LITERATURE
  • INTRODUCTIOIY
  • Immune defects in Cancer- patients
  • Immune defects in Carcinogenesis
  • Immune defects in chemo: ~nd radiotherapy
  • Tumour Immunology
  • lmmunotherapy in Cancer
  • Immunomodulators of plant origin
  • Withania somnifera
  • Objectives of the study in general
  • REVIEW OF LITERATURE
  • Different treatment modalities of cancer
  • Surgery
  • Chemotherapy
  • Table 1 Chemotherapeutic agents
  • Side effects of chemotherapy
  • Carcinogenicity of Chemotherapy
  • Radiotherapy
  • Principles of Radiation therapy
  • Radiation techniques
  • Adverse effects of Radiation
  • Photodynamic therapy (PDT)
  • Endocrine therapy
  • Toxicities associated with endocrine therapy
  • Thermotherapy
  • Immunotherapy in Cancer
  • A Cytokines as therapeutic agents
  • 1. Interleukin - 1 (IL-1)
  • 2. lnterleukin - 2 (IL-2)
  • 3. lnterleultin -3 (IL-3)
  • 4. Interleukin - 4 (IL-4)
  • 5. Interleukin-6 (EL-6)
  • 6. Interleukin-l l jlL-l I)
  • 7. Interleukin -12 (IL-12)
  • 8. Interferon (IFN)
  • 9. Interferon - y
  • 10. Turnour necrosis factor
  • B. Haematopoietic growth factors in cancer therapy
  • 1. Erythropoietin
  • 2. Granulocyte colony-stimulating factor (G-CSF)
  • 3. Granulocyte - M: ~crophage colony stimulating factor (GM-CSF)
  • 4. Macrophage colony stimuling factor (M-CXF)
  • 5. Transforming growth factors
  • 6. Thrornbopoietin
  • Toxicity of biologic therapy
  • C. Monoclonal antibodies (MAbs)
  • 1. Murine monoclon; ll: intibodies
  • 2. Chimeric, human and humanized monoclonal antibodies
  • Imaging studies with Radiolabelled: intibodies.
  • D. Targeted therapy
  • 1. Immunotoxins
  • 2. Chimeric toxins
  • E. Adoptive cellular therapy, gene therapy and cancer vaccines
  • TUMOUR IMMUNOLOGY
  • Tumour antigens
  • Tumour Escape mechar~isms
  • 1. Sneaking through
  • 2. Antigenic modulation
  • 3. Masking of surface antigens
  • 4. Induction of lmmune tolerance
  • 5. Production of blockirlg antibodies
  • Effector mechanisms resulting in tumour cell destruction
  • a. Antibodies
  • b. Cytotoxic T lymphocytes (CTL)
  • c. Natural killer cells (NI<)
  • d. Macrophages
  • Immunomodulators
  • Immumodulators of plant origin
  • Combination therapy
  • 1. Radioirnrnunotherapy
  • 2. Chemoimmunotherapy
  • 3. Chemotherapy - endocrine therapy combin a t ~ o n
  • 4. Surgery and chemotherapy
  • 5. Surgery and radiation
  • 6. Radiation and chemotherapy
  • 7. Combination of chemotherapy and hyperthermia
  • 8. Thermoradiotheraphy
  • Anticancer activity of plant extracts and derived compounds
  • Fig. Withania somnifera
  • II. MATERIALS AND METHODS
  • I Chemicals
  • II. Test Compounds
  • III. Instruments & Devices
  • IV. Reagents and Buffers
  • V. Stains
  • VI. Tissue culture methods
  • VII. Maintenance of cell lines in tissue culture
  • VIII. Assessment of cell viability using trypan blue
  • IX Animals
  • X. Cell lines
  • XI Sheep Red blood cells (SRBC)
  • XII. Maintenance of tumour cells in mice.
  • XIII. Antitumour studies.
  • XIV Immunological Parameters
  • Determination of total leukocyte count
  • Differential count of leukocytes
  • Preparation of peritoneal macrophages (44)
  • Preparation of bonemarrow cells (43)
  • Determination of circulating antibody titre
  • Determination of antibody forming cells
  • Assay of lymphocyte 1 bonernarrowlthyrnus cell proliferation
  • Cr - release assays.
  • Determination of Natural killer cell mediated cytotoxicity.
  • Determination of antibody - dependent cellular cytotoxicity
  • Determination of antibody - dependent complement mediated cytotoxicity
  • Determination of macrophage mediated cytotoxicity
  • XV. Histopathological techniques
  • XVI. Biochemical Parameters
  • Estimation of protein
  • Determination of hemoglobin
  • Determination of serum / tissue alkaline phosphatase
  • Serum/ tissue glutamate pyruvate transaminase
  • Determination of Total Protein and urea
  • Determination of serum lipid peroxides
  • Deterniination of tissue lipid peroxides
  • XVII. Determination of effect of Witlzania somnifera onantioxidant Enzymes
  • Estimation of Reducetl C; lutathione (GSH)
  • Estimation of cytosolic glutathione - S - transferase (GST) activity
  • Estimation of tissue catalase activity.
  • Estimation of tissue glutathione peroxidases (Gpx) activity
  • XVIII. Anti carcinogeriicity testing
  • XIX. Determination offt-equency of micronuclei induced byRadiation
  • XX Statistical Analysis
  • III. IMMUNOMODULATORY ACTIVITY OF WITHANIA SOMNIFERA
  • I. Introduction
  • II. Materials and rncthods
  • 11.1. Chemicals
  • 11.2 Animals
  • 11.3 Drug treatment
  • 11. 4. Determination of the efTect of Wtlzu~ziuso nirziferrr on the l~aematologicalparameters.
  • 11. 5. Determination of the effect Withaniu somnij5eru on organ weight of mice.
  • 11. 6. Determination of the effect of Witlzuniu sonzngeru on circulating antibodytitre.
  • 11. 7. Determination of the effect of Witltuniu sontniferu on various lmn~unoglobulinlevel.
  • 11. 8. Determination of the effect of J, Vi/irlrurrio su112nifer.cl on t i ~ ca ntibodyproducing cells.
  • 11.9. Determination of the effect of Willruniu sonzniferr~ on the bonen~al-rowcellularity as well as tx-esterasc positive cells.
  • 11. 10. Determination of the effect of Withania extract on delayed typehypersensitivity reaction (DTH)
  • 11.11. Determination of effect of Mithania on the phagocytic activity ofmacrophages.
  • III. Results
  • III.1. Effect of Withuniu snnznifera on the haematological parameters.
  • III.2. Effect of Withaniu somnijeru an relative organ weights.
  • III.3. Effect of Withania somngera on circulating antibody titre.
  • III.4. Effect of Witl~uniaso nznifera on In~munoglobulinl evel.
  • III.5. Effect of Withunia sonznifera on antibody producing cells.
  • III. 6. Effect of Withunia.somrzifcru on the bone~narrowc ellularity and a-esterasepositive cells.
  • III.7 Effect of Witlruniusor~zni/~orun delayed type hypersensitivity (DTH) reaction.
  • III.8 Effect of Withuniu.son?niferu on phagocytic activity of peritonealmacrophages.
  • IV. Discussion
  • IV. EFFECT OF WITHANIA SOMNIFERA ON CELL MEDIATED IMMUNITY
  • I. Introduction
  • II. R4aterials and Methods
  • III. Results
  • III.1 Effect of Withuniu somnifL.ra on lymphocytes blastogenesis.
  • III.2 Effect of Withania somnifera on thymocyte proliferation.
  • III.3 Effect of Withunia.omnijera on bonemarrow blastogenesis.
  • III.4 Effect of Withunia somngera on Natural killer cell activity (NIC)
  • III.5 Effect of Witlzuniu.sontn (feru on ADCC activity.
  • III.6 Effect of Withunia somniferu on ACC activity.
  • IV. Discussion
  • V. EFFECT OF WITHANIA SOMNIFERA ON CYTOSINE AND CTL PRODUCTION
  • I. Introduction
  • II. Materials and methods
  • III. Results
  • IV. Discussion
  • VI. EFFECT OF WITHANIA SOMNIFERA ON RADIATION INDUCED TOXICITY
  • I. Introduction
  • II. Materials and IClethods
  • III. Results
  • IV. Discussion
  • VII. EFFECT OF WITHANIA SOMNIFRA ON CYCLOPHOSPHAMIDE INDUCED TOXICITY
  • I. Introduction
  • II. Materials and Methods
  • III. Results
  • IV. Discussion
  • Fig. 1 HISTOPATHOLOGY OF C.S. OF INTESTINE
  • Fig. (a) NORMAL
  • Fig. (b) CTX - I 1TH DAY
  • Fig. (c) CTX + WITHANIA - 11TH DAY
  • Fig. (d) CTX - 15TH DAY
  • Fig. (e) CTX + WITHANIA - 15TH DAY
  • Fig. 2 HISTOPATHOLOGY OF URINARY BLADDER
  • Fig. (a) NORMAL
  • Fig. (b) CTX ALONE 4h
  • Fig. (c) CTX + WITHANIA 4h
  • Fig. 3 HISTOPATHOLOGY OF URINARY BLADDER
  • Fig. (d) CTX AI, ONE 24h
  • Fig (e) LTX + WITHANIA 24h.
  • Fig. (0 CTX ALONE 48 h.
  • Fig. (g) CTX + WITHANIA 48h
  • VIII. EFFECT OF WITHANIA SOMNIFERA ON CHEMICALLY INDUCED SKIN CARCINOGENESIS
  • I. Introduction
  • II. Materials and Methods.
  • III. Results
  • IV. Discussion
  • IX. EFFECTOF WITHANIA SOMNIFERA ALONG WITH CHEMO, RADIO AND THERMOTHERAPY ON SOLID TUMOUR REDUCTION
  • I. Introduction
  • II. Materials and Methods
  • III Results
  • IV. Discussion
  • X. SUMMARY AND CONCLUSION
  • BIBLIOGRAPHY
  • PAPERS PUBLISHED