Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 3 uppsatser.

by Suen Yick-keung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Bibliography: leaves 163-170. / Abstract --- p.i / Acknowledgements --- p.v / Abbreviations --- p.vi / Objective of the study --- p.vii / Contents --- p.viii / Chapter Section 1 --- Introduction / Chapter 1. --- Roles of macrophges in immune system --- p.3 / Chapter 2. --- Special features of macrophages --- p.6 / Chapter 3. --- Transmembrane signalling in mammalian cells --- p.9 / Chapter 4. --- Transmembrane signalling in macrophages --- p.32 / Chapter 5. --- Choice of the macrophages for the study --- p.40 / Chapter Section 2 --- Materials and Methods / Materials / Chapter 1. --- Animals --- p.44 / Chapter 2. --- Chemicals --- p.44 / Chapter 3. --- Reagents --- p.45 / Methods / Chapter 1. --- pell culture --- p.47 / Chapter 2. --- 3H-thymidine incorporation --- p.48 / Chapter 3. --- Cytosolic free calcium determination --- p.48 / Chapter 4. --- Intracellular pH mesurement --- p.50 / Chapter 5. --- Determination of membrane potential --- p.50 / Chapter 6. --- Determination of phagocytic activity --- p.51 / Chapter 7. --- Cell adhesion assay --- p.52 / Chapter 8. --- Statistical analysis --- p.52 / Chapter Section 3 --- Results / Chapter 1. --- Effect of membrane potential on cell proliferation in PU5-1.8 cells and bone marrow-derived macrophages / Evidence for induction of cell proliferation mediated by membrane depolarization in PU5-1.8 cells --- p.53 / Evidence of an array of agonists on cell proliferation and membrane potential in PU5-1.8 cells --- p.57 / Interrelationship between membrane potential and FCS-mediated proliferation in PU5-1.8 cells --- p.61 / Cytosolic alkalinization induces membrane depolarization in PU5-1.8 cells --- p.64 / Suppression of membrane depolarization and cell proliferation by protein kinase C activation --- p.66 / Effect of membrane potentials on cell proliferation in bone marrow-derived macrophages --- p.68 / Chapter 2. --- Intracellular signals for the regulation of phagocytosis in PU5-1.8 cells / Phagocytosis of unopsonized yeast in PU5-1.8 cells --- p.71 / Effect of membrane potential on phagocytosis in PU5-1.8 cells --- p.73 / Changes in phagocytic activities in PU5-1.8 cells by activation of protein kinase C --- p.82 / Effects of protein kinase C on membrane potential- induced enhancement of phagocytosis in PU5-1.8 cells --- p.84 / Phagocytosis in PU5-1.8 cells requires assembly of microtubule --- p.90 / Effects of intracellular calcium and cAMP on phagocytosis in PU5-1.8 cells --- p.93 / Acidic intracellular pH enhances phagocytosis in PU5-1.8 cells --- p.98 / Chapter 3. --- Effects of various agonists on phagocytosis of yeast in PU5-1.8 cells / Effect of chemotactic peptide N-formyl- methionyl-leucyl-phenylalanine (FMLP) on phagocytosis in PU5-1.8 cells --- p.100 / Effects of lipopolysaccharide (LPS) on phagocytosis in PU5-1.8 cells --- p.105 / Effects of concanavalin A (Con A) on phagocytosis in PU5-1.8 cells --- p.109 / Effect of complement components on phagocytosis in PU5-1.8 cells --- p.113 / Chapter 4. --- Signal pathways for the regulation of cell adhesion on plastic surface in PU5-1.8 cells / Adhesion of PU5-1.8 cells on plastic surface --- p.119 / Effects of membrane potential on cell adhesion on plastic surface in PU5-1.8 cells --- p.121 / Effects of activation of protein kinase C on cell adhesion on plastic surface in PU5-1.8 cells --- p.125 / Effects of intracellular calcium and cAMP on adhesion on plastic surface in PU5-1.8 cells --- p.129 / In vivo cell adhesion of PU5-1.8 cells in Balb/c mice --- p.133 / Chapter 5. --- Effects of various agonists on the cell adhesion on plastic surface in PU5-1.8 cells / Dose dependent of various agonists against the cell adhesion ability of PU5-1.8 cells --- p.141 / Chapter 6. --- Cell adhesion to plastic surface in bone marrow-derived macrophages / Membrane potentials control the adhesiveness of bone marrow-derived macrophages (BMDM0) to plastic surface --- p.143 / Effects of phorbol ester PMA on cell adhesion to plastic surface in bone marrow-derived macrophages --- p.143 / "Effects of cAMP, [Ca2+ ]i and microtubule assembly on cell adhesion to plastic surfacein bone marrow-derived macrophages" --- p.146 / Chapter Section 4 --- Discussion / Chapter 1. --- Effects of membrane potential on cell proliferation in PU5-1.8 cells and bone marrow-derived macrophages --- p.148 / Chapter 2. --- Intracellular signals for the regulation of phagocytosis in PU5-1.8 cells --- p.151 / Chapter 3. --- Signal pathways for the regulation of cell adhesion on plastic surface in PU5-1.8 cells and bone marrow-derived macrophages --- p.158 / Chapter 4. --- General discussion --- p.161 / Chapter Section 5. --- Bibliography / References --- p.163

by Kong Siu-Kai. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 313-340.

Poon Yin-tat. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 101-111). / ACKNOWLEDGEMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.IV / TABLE OF CONTENTS --- p.V / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter CHAPTER 2: --- PURIFICATION OF α- AND β-MOMORCHARINS --- p.26 / Chapter CHAPTER 3: --- N-GLYCOSIDASE ACTIVITY OF α- AND β-MOMORCHARINS --- p.45 / REFERENCES --- p.101

Xie Tong. / "May 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 113-126). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The progressive growth of tumors in human cancer patients and experimental animals has frequently been associated with a generalized depression of immunological responsiveness. Suppressor cells have been implicated as mediators of tumor-associated immunosuppression, but the identities of the cells causing suppression and the mechanisms by which they act have been unclear. The object of this thesis was thus to determine: if suppressor cells capable of non specifically suppressing immune responses were present in anergic mice bearing methylcholanthrene-induced sarcomas; the cell types responsible for suppression; and the mechanisms by which suppression occurs. The spleens of mice with large tumors were found to contain two distinct populations of non specific suppressor cells. One population inhibited the proliferative responses of normal lymphocytes to the T cell mitogen, Concanavalin A (Con A) and the B cell mitogen, lipopolysaccharide (LPS). These cells also inhibited the generation of antibody forming cells by normal lymphoid cells stimulated in vitro with the T cell dependent antigen, sheep red blood cells (SRBC) and the T cell independent antigen, dinitrophenylated-lipopolysaccharide (DNP-LPS). These suppressor cells appeared to be from the macrophage/monocyte line since they adhered to plastic and nylon wool, were removed by carbonyl iron and magnet, and were inactivated by carragheenan treatment, but were not removed by anti-Thy-1 or anti-mouse immunoglobulin sera plus complement. They were among the less dense spleen cells since they were retained in the light fraction after centrifugation on hypaque-ficoll of specific gravity 1.08 and did not appear to require cell division in order to suppress- since mitomycin C treatment did not inactivate them. Cell-cell contact appeared to be essential for suppression. The second population of suppressor cells, which pelleted to the bottom of a hypaque-ficoll gradient, inhibited only the generation of plaque forming cells to the T cell dependent antigen, SRBC. These cells appeared to be T cells since they were non adherent to plastic or nylon wool, were not removed by carbonyl iron and magnet, but were removed by anti-Thy-1 serum plus complement. Cell division was necessary since suppressive activity was totally removed by mitomycin C treatment. Suppression by this cell type appeared to be mediated by a soluble factor with a molecular weight of about 3,500 to 12,000. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

by Kok Dick Shun, Louis. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references. / Acknowledgements --- p.I / Table of Contents --- p.II / Abbreviations --- p.V / Aim and Scope of This Dissertation --- p.IX / Abstract --- p.X / Chapter Chapter One： --- General Introduction --- p.1 / Chapter 1.1 --- An Overview of the Immune System --- p.2 / Chapter 1.1.1 --- Innate Immunity --- p.2 / Chapter 1.1.2 --- Adaptive Immunity --- p.3 / Chapter 1.1.2.1 --- Humoral antibody immune response --- p.4 / Chapter 1.1.2.2 --- Cell- mediated immune response --- p.5 / Chapter 1.2 --- Immunomodulation --- p.6 / Chapter 1.3 --- An overview of the Host-mediated response against tumours --- p.9 / Chapter 1.3.1 --- T and B lymphocytes --- p.9 / Chapter 1.3.2 --- M acrophages --- p.14 / Chapter 1.3.3 --- Natural killer cells --- p.17 / Chapter 1.3.4 --- Lymphokines-activated killer cells --- p.20 / Chapter 1.3.5 --- Tumour infiltrating lymphocytes --- p.22 / Chapter 1.3.6 --- Cytokines --- p.23 / Chapter 1.4 --- Carbohydrates as Potential Immunostimulating agents --- p.33 / Chapter 1.5 --- General Properties of Bupleuri radix (B.R.) --- p.35 / Chapter Chapter Two： --- Materials and Methods --- p.36 / Chapter 2.1 --- Materials --- p.37 / Chapter 2.1.1 --- Animals --- p.37 / Chapter 2.1.2 --- Bupleuri radix --- p.37 / Chapter 2.1.3 --- "Buffers, culture media and chemicals" --- p.37 / Chapter 2.1.4 --- Cell lines --- p.48 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- Extraction and fractionation of Bupleuri radix --- p.49 / Chapter 2.2.2 --- Purification of Bupleuri radix --- p.54 / Chapter 2.2.3 --- Characterization of Bupleuri radix --- p.55 / Chapter 2.2.4 --- In vivo Drug Treatment --- p.59 / Chapter 2.2.5 --- Isolation and preparation of cells --- p.59 / Chapter 2.2.6 --- Assays for the immunomodulatory activities of Bupleuri radix --- p.62 / Chapter 2.2.7 --- Assays for the immunorestorative properties of Bupleuri radix --- p.74 / Chapter 2.2.8 --- Assays for the anti-tumour activities of Bupleuri radix --- p.75 / Chapter 2.2.9 --- Statistical analysis --- p.83 / Chapter Chapter Three： --- "Fractionation, Purification and Characterization of Bioactive Compounds from Bupleuri radix" --- p.84 / Chapter 3.1 --- Results / Chapter 3.1.1 --- Extraction and Fractionation of Bupleuri radix --- p.85 / Chapter 3.1.2 --- Purification of Bupleuri radix --- p.85 / Chapter 3.1.3 --- Carbohydrate and Protein Contents of B.R. Fractions --- p.87 / Chapter 3.1.4 --- Lack of cytotoxicity of Bupleuri radix to Mouse Splenocytes --- p.91 / Chapter 3.1.5 --- LC50 of B.R. Fractions determined by Brine Shrimp Bioassay --- p.91 / Chapter 3.1.6 --- Heat stability of B.R. Fractions --- p.93 / Chapter 3.1.7 --- "Uronic Acid Content of BRIai, BRIaii, BRIbi and BRIbii" --- p.93 / Chapter 3.2 --- Discussion --- p.93 / Chapter Chapter Four： --- The Immunomodulatory Activities of Bupleuri radix --- p.96 / Chapter 4.1 --- Results / Chapter 4.1.1 --- Effect of Bupleuri radix on the Specific and Nonspecific Immunity --- p.97 / Chapter 4.1.1.1 --- Mitogenic effect of B.R. Fractions on Murine Splenocytes in vitro --- p.97 / Chapter 4.1.1.2 --- Mitogenic effect of B.R. Fractions on Murine Splenocytes ex vivo --- p.97 / Chapter 4.1.1.3 --- In vitro Mitogenic effect of B.R. Fractions treated with Periodate --- p.103 / Chapter 4.1.1.4 --- In vitro Mitogenic effect of B.R. Fractions treated with Acetic Acid --- p.103 / Chapter 4.1.1.5 --- In vitro Co -mitogenic effect of B.R. Fractions with Polymyxin B Sulphate --- p.107 / Chapter 4.1.1.6 --- Effect of B.R. Fractions on Lymphocyte sub-populations --- p.107 / Chapter 4.1.1.7 --- Primary Humoral Immune Response to SRBC in B.R.-treated mice --- p.107 / Chapter 4.1.1.8 --- Activity of cytotoxic T cells in B.R-treated mice --- p.111 / Chapter 4.1.1.9 --- Effect of B.R. Fractions on Interleukin-1 - like Factors Production --- p.111 / Chapter 4.1.1.10 --- Effect of B.R. Fractions on Interleukin-2 Production --- p.116 / Chapter 4.1.1.11 --- Effect of B.R. Fractions on Interleukin-2 Receptor Expression on Murine Splenocytes --- p.116 / Chapter 4.1.1.12 --- Effect of B.R. Fractions on GM-CSF Production --- p.119 / Chapter 4.1.1.13 --- Immunopotentiating effects of B.R. Fractions on Macrophages: --- p.119 / Chapter 4.1.1.13.1 --- In vivo Migration of Macrophages in B.R.-treated mice --- p.119 / Chapter 4.1.1.13.2 --- Effect of B.R. Fractions on the Fc Receptor Expression on Murine Resident Peritoneal Exudate Cells --- p.123 / Chapter 4.1.2 --- Immunorestorative Properties of Bupleuri radix --- p.123 / Chapter 4.1.2.1 --- Effect of B.R. Fractions on Lymphocyte Blastogenesis in Aged Mice --- p.123 / Chapter 4.1.2.2 --- Effect of B.R. Fractions on Lymphocyte Blastogenesis in Tumour-bearing Mice --- p.125 / Chapter 4.2 --- Discussion --- p.125 / Chapter Chapter Five： --- The Anti-tumour Activities of Bupleuri radix --- p.132 / Chapter 5.1 --- Results / Chapter 5.1.1 --- Cytostatic Effect of B.R. Fractions on Murine Tumour Cell Lines in vitro --- p.133 / Chapter 5.1.2 --- Effect of B.R. Fractions on the Growth of Tumour Ceils in vivo --- p.133 / Chapter 5.1.3 --- Effect of B.R. Fractions on the Survival of EAT-bearing mice --- p.140 / Chapter 5.1.4 --- Ex vivo Induction of Natural Killer Cell Activity by B.R. Fractions --- p.146 / Chapter 5.1.5 --- In vitro Induction of Lymphokine-activated Killer Cell Activity by B.R Fractions --- p.149 / Chapter 5.1.6 --- In vivo Induction of Tumour Infiltrating Lymphocytes by B.R. Fractions --- p.149 / Chapter 5.1.7 --- In vitro Induction of Macrophage-mediated Cytostatic Effect on Tumour Cells by B.R. Fractions --- p.151 / Chapter 5.1.8 --- In vitro Induction of Macrophage-mediated Cytostatic Eifect on Tumour Cells by B.R. Fractions --- p.153 / Chapter 5.1.9 --- Effect of B.R. Fractions on γ-interferon Production in vitro --- p.156 / Chapter 5.2 --- Discussion --- p.156 / Chapter Chapter Six： --- "General Discussion, Conclusion and Future Prospects" --- p.164 / Bibliography --- p.i

Leung Yiu Kwong, Michael. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 155-161). / Acknowledgements --- p.i / Abbreviations --- p.ii / Aim and scope of this dissertation --- p.v / Abstract --- p.vi / Table of contents --- p.viii / Introduction --- p.1 / Chapter 1.1 --- Introduction --- p.2 / Chapter 1.2 --- Tumor Biology --- p.3 / Chapter 1.3 --- The Defence Mechanisms --- p.4 / Chapter 1.3.1 --- Non-specific defence mechanisms --- p.5 / Chapter 1.3.2 --- Specific defence mechanisms --- p.6 / Chapter 1.4 --- Effector Mechanisms in Anti-tumor Immunity --- p.7 / Chapter 1.4.1 --- B-cell --- p.8 / Chapter 1.4.2 --- "Natural killer (NK) cells (Non-T, Non-B)" --- p.8 / Chapter 1.4.3 --- Macrophages --- p.9 / Chapter 1.4.4 --- Cytolytic T-lymphocytes (CTLs) --- p.10 / Chapter 1.5 --- Cancer Treatment --- p.10 / Chapter 1.5.1 --- Surgery --- p.10 / Chapter 1.5.2 --- Radiotherapy --- p.12 / Chapter 1.5.3 --- Drug therapy --- p.12 / Chapter 1.5.4 --- Gene therapy --- p.13 / Chapter 1.5.5 --- lmmunotherapy --- p.13 / Chapter 1.6 --- Non-cytotoxic Antitumor Polysaccharides of Fungi --- p.14 / Chapter 1.6.1 --- Yeast polysaccharides --- p.14 / Chapter 1.6.2 --- Lichen polysaccharides --- p.15 / Chapter 1.6.3 --- Fungal polysaccharides --- p.18 / Chapter 1.7 --- Fungi and their Polysaccharides --- p.20 / Chapter 1.7.1 --- Reserve carbohydrates --- p.20 / Chapter 1.7.2 --- Structural polysaccharides --- p.21 / Chapter 1.8 --- The Architecture of the Fungal Cell Wall --- p.22 / Materials and Methods --- p.26 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- Animals --- p.27 / Chapter 2.1.2 --- Mushrooms --- p.27 / Chapter 2.1.3 --- "Buffers, culture media and chemicals" --- p.27 / Chapter 2.1.4 --- Cell lines --- p.34 / Chapter 2.2 --- Methods --- p.35 / Chapter 2.2.1 --- Screening of β-(l→3)-D-glucan --- p.35 / Chapter 2.2.2 --- Extraction and Fractionation of Flammulina velutipes --- p.35 / Chapter 2.2.3 --- Characterisation of Flammulina velutipes --- p.38 / Chapter 2.2.3.1 --- The determination of carbohydrate content of F.V fractions --- p.38 / Chapter 2.2.3.2 --- The determination of protein content of F.V. fractions --- p.39 / Chapter 2.2.3.3 --- The determination of uronic acid content of F.V fractions --- p.39 / Chapter 2.2.3.4 --- The determination of component sugar units of F.V fractions --- p.39 / Chapter 2.2.3.5 --- Periodate uptake of F.V. fractions --- p.40 / Chapter 2.2.3.6 --- Limulus amebocyte lysate (LAL) coagulation assay --- p.40 / Chapter 2.2.3.7 --- The digestion of F.V. fractions with laminarinase --- p.41 / Chapter 2.2.3.8 --- The Secondary and tertiary structure determination of FH and SFA1 --- p.42 / Chapter 2.2.3.9 --- Molecular weight estimation of FH and SFA1 --- p.43 / Chapter 2.2.3.10 --- Vascular dilation and hemorrhage (VDH) activity of F.V. fractions / Chapter 2.2.4 --- Isolation and preparation of cells --- p.43 / Chapter 2.2.4.1 --- Bone marrow cell --- p.43 / Chapter 2.2.4.2 --- Peritoneal exudate cell (PEC) --- p.44 / Chapter 2.2.4.3 --- Splenocytes --- p.44 / Chapter 2.2.4.4 --- Depleting mouse T-cells by anti-mouse T-cell antigen antibody plus complement treatment --- p.45 / Chapter 2.2.4.5 --- Depleting mouse B-cells by Cedarlane column kit --- p.45 / Chapter 2.2.5 --- Assays for the cytotoxicity of Flammulina velutipes --- p.45 / Chapter 2.2.5.1 --- Brine shrimp assay --- p.45 / Chapter 2.2.5.2 --- In vitro cytotoxicity of FH and SFA1 on bone marrow cells of female BALB/c mice --- p.46 / Chapter 2.2.5.3 --- In vivo cytotoxicity of FH and SFA1 on female BALB/c mice --- p.47 / Chapter 2.2.6 --- "Assays for the immunomodulatory activities of Flamm""lina velutipes" --- p.47 / Chapter 2.2.6.1 --- In vitro mitogenic activities of FH and SFA1 on murine lymphocytes --- p.47 / Chapter 2.2.6.2 --- In vitro mitogenic activities of FH and SFA1 with PMB on murine lymphocytes --- p.48 / Chapter 2.2.6.3 --- In vitro mitogenic activities of FH and on T-cell depleted murine lymphocytes --- p.48 / Chapter 2.2.6.4 --- In vitro mitogenic activities of FH on B-cell depleted murine lymphocytes --- p.49 / Chapter 2.2.6.5 --- In vitro co-mitogenic activitiy of FH and SFA1 on murine lymphocytes --- p.49 / Chapter 2.2.6.6 --- In vitro mitogenic activities of FH and SFA1 on murine bone marrow cells --- p.50 / Chapter 2.2.6.7 --- In vivo mitogenic activities of FH and SFA1 on murine lymphocytes --- p.50 / Chapter 2.2.6.8 --- Effect of FH and SFA1 on the enhancement of first antibody production of SRBC immunised mice --- p.51 / Chapter 2.2.6.9 --- Effect of FM and SFA1 on the in vitro phagocytic activity of murine macrophage --- p.51 / Chapter 2.2.6.10 --- Effect of FM and SFA1 on the in vivo phagocytic activity of murine macrophage --- p.51 / Chapter 2.2.6.11 --- In vivo migration of macrophage in FH- and SFAl-treated mice --- p.53 / Chapter 2.2.6.12 --- Effect of FH and SFA1 on the enhancement of murine PEC cytostatic activity --- p.53 / Chapter 2.2.6.13 --- Effect of FH and SFA1 on the Fc receptor expression of peritoneal exudate cells --- p.54 / Chapter 2.2.6.14 --- Effect of FH and SFA1 on murine serum cytokine level --- p.55 / Chapter 2.2.6.15 --- Effect of FH and SFA1 on murine serum TNF level --- p.55 / Chapter 2.2.6.16 --- Effect of FH and SFA1 on the augmentation of SRBC lysing ability of murine serum --- p.56 / Chapter 2.2.7 --- Assays for the anti-tumor activities of Flammulina velutipes --- p.57 / Chapter 2.2.7.1 --- In vitro anti-tumor activity of FH and SFA1 --- p.57 / Chapter 2.2.7.2 --- Effect of FH and SFA1 on the growth of murine transplantable tumor invivo --- p.58 / Chapter 2.2.8 --- Statistical analysis --- p.59 / "Screening, Purification, Fractionation and Characterisation of β-(l→3)-D-glucan(s) from Flammulina velutipes" --- p.60 / Introduction --- p.61 / Results --- p.62 / Chapter 3.1 --- Screening of β-(l→3)-D-Glucan --- p.62 / Chapter 3.2 --- Extraction and Fractionation of Flammulina velutipes --- p.62 / Chapter 3.3 --- The Determination of Carbohydrate Content of F.V. Fractions --- p.65 / Chapter 3.4 --- The Determination of Protein Content of F.V. Fractions --- p.65 / Chapter 3.5 --- The Determination of Uronic Acid Content of F.V. Fractions --- p.69 / Chapter 3.6 --- The Determination of Component Sugar Units of F.V. Fractions --- p.69 / Chapter 3.7 --- Periodate Uptake of F.V. Fractions --- p.69 / Chapter 3.8 --- Limulus Amebocyte Lysate (LAL) Coagulation Assay --- p.73 / Chapter 3.9 --- The Digestion of F.V. Fractions with Laminarinase --- p.73 / Chapter 3.10 --- The Secondary and tertiary Structure Determination of FH and SFA1 --- p.80 / Chapter 3.11 --- Molecular Weight Estimation of FH and SFA1 --- p.82 / Chapter 3.12 --- "Vascular Dilation and Hemorrhage (VDH) Activity of FH, SFA1 and lFA1" --- p.82 / Discussion --- p.90 / The Toxicity of Flammulina velutipes --- p.96 / Introduction --- p.97 / Results --- p.97 / Chapter 4.1 --- Lack of Cytotoxicity of Flammulina velutipes to Brine Shrimp --- p.97 / Chapter 4.2 --- Lack of Cytotoxicity of Flammulina velutipes to Murine Bone Marrow Cells --- p.99 / Chapter 4.3 --- Lack of Cytotoxicity of Flammulina velutipes to Mouse --- p.99 / Discussion --- p.102 / The Immunomodulatory Activities of Flammulina velutipes --- p.103 / Introduction --- p.104 / Results --- p.105 / Chapter 5.1 --- Effect of Flammulina velutipes on Murine Lymphocytes --- p.105 / Chapter 5.2 --- Effect of Flammulina velutipes on Murine Macrophage --- p.115 / Chapter 5.3 --- Effect of Flammulina velutipes on Murine Serum Cytokine and Complement Level --- p.125 / Discussion --- p.133 / The Anti-tumor Activities of Flammulina velutipes --- p.136 / Introduction --- p.137 / Results --- p.137 / Chapter 6.1 --- In Vitro Anti-Tumor Activity of FH and SFA1 --- p.137 / Chapter 6.2 --- Effect of FH and SFAI on the Growth of Murine TransplantableTumors --- p.138 / Discussion --- p.145 / General Discussion --- p.146 / General Discussion and Future Perspectives --- p.147 / References --- p.154

by Poon Yam Kau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 174-183). / Abstract --- p.1 / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- Discovery of melatonin --- p.4 / Chapter 1.2 --- Biosynthesis of melatonin --- p.4 / Chapter 1.3 --- Physiology of melatonin and other pineal indoles --- p.5 / Chapter 1.4 --- Relationship between pineal indoles and cancers --- p.6 / Chapter 1.5 --- Macrophages --- p.9 / Chapter 1.6 --- Lymphocytes --- p.11 / Chapter Chapter 2 --- Effects of different light/dark cycles on serum melatonin level in mice and effect of melatonin-feeding on serum glutamate-oxaloacetate transaminase (GOT) activity in mice / Chapter 2.1 --- Introduction --- p.14 / Chapter 2.2 --- Materials and methods --- p.15 / Chapter 2.3 --- Results --- p.22 / Chapter 2.4 --- Discussion --- p.23 / Chapter Chapter 3 --- Actions of endogenous and exogenous melatonin on murine peritoneal macrophages / Chapter 3.1 --- Introduction --- p.27 / Chapter 3.2 --- Materials and methods --- p.28 / Chapter 3.3 --- Results --- p.33 / Chapter 3.4 --- Discussion --- p.36 / Chapter Chapter 4 --- Actions of endogenous and exogenous melatonin on murine splenic lymphocytes / Chapter 4.1 --- Introduction --- p.55 / Chapter 4.2 --- Materials and methods --- p.56 / Chapter 4.3 --- Results --- p.62 / Chapter 4.4 --- Discussion --- p.69 / Chapter Chapter 5 --- In vitro effects of melatonin on murine peritoneal macrophages and splenic lymphocytes / Chapter 5.1 --- Introduction --- p.105 / Chapter 5.2 --- Materials and methods --- p.106 / Chapter 5.3 --- Results --- p.109 / Chapter 5.4 --- Discussion --- p.113 / Chapter Chapter 6 --- Effects of methoxytryptamine on murine peritoneal macrophages and splenic lymphocytes / Chapter 6.1 --- Introduction --- p.125 / Chapter 6.2 --- Materials and methods --- p.126 / Chapter 6.3 --- Results --- p.129 / Chapter 6.4 --- Discussion --- p.132 / Chapter Chapter 7 --- In vitro effects of pineal indoles on cultured tumor cell lines / Chapter 7.1 --- Introduction --- p.145 / Chapter 7.2 --- Materials and methods --- p.146 / Chapter 7.3 --- Results --- p.148 / Chapter 7.4 --- Discussion --- p.152 / Chapter Chapter 8 --- General Discussion --- p.170 / References --- p.174

Orientador: Laura Sterian Ward, José Vassallo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T19:34:22Z (GMT). No. of bitstreams: 1 Cunha_LucasLeite_D.pdf: 3273726 bytes, checksum: 85653bdcc1b0fa91465a6ac9ed73359a (MD5) Previous issue date: 2015 / Resumo: O câncer de tiroide é a neoplasia maligna endócrina mais frequente. Muito embora a maioria destes pacientes apresente boa evolução clínica com as ferramentas terapêuticas atuais, 10-30% evoluirão com doença recorrente e contribuirão para as 1.890 mortes que são estimadas para 2014 nos Estados Unidos . As ciclooxigenases (COX) são um grupo de enzimas que catalisam a formação de prostaglandinas a partir do ácido aracdônico e a atividade de COX2 tem sido implicada na carcinogênese. Nosso grupo demonstrou anteriormente que diferentes células do sistema imunológico infiltram tecidos de cânceres de tiroide. O presente trabalho investigou a presença de marcadores de células do sistema imunológico, bem como marcadores tumorais de perfil inflamatório, procurando marcadores de prognóstico em pacientes com carcinoma diferenciado de tiroide. Foram investigados retrospectivamente 437 pacientes com carcinoma diferenciado da tiroide, cujas amostras de tecido previamente fixadas em formalina e incluidas em blocos de parafina eram mantidas no Banco de Tecidos do A.C.Camargo Cancer Center. Câncer bem diferenciado de tiroide foi diagnosticado em 305 pacientes: 252 com carcinoma papilífero e 53 com carcinoma folicular. Informações clínicas foram obtidas dos prontuários. Obtivemos tecidos de metástases linfonodais ao diagnóstico de 25 pacientes. Para estes casos, fizemos análise pareada entre tecido metastático e tumor primário. Foram investigados marcadores de células imunológicas em áreas intratumorais, incluindo macrófagos associados a tumores (CD68) e subpopulações de linfócitos infiltrantes de tumor, como CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZIMA B, CD69 e CD25. Também foi investigada a expressão de COX2, IL-17A, IL-1'beta', IL-10, IL-6, CD134 e IL-23 nas células tumorais. Entre todos os parâmetros imunológicos avaliados, apenas o enriquecimento de linfócitos CD8+ e expressão de COX2 foram associados à recorrência. A análise multivariada, utilizando o modelo de riscos proporcionais de Cox ajustado para a presença de tiroidite crônica concomitante, identificou CD8+/COX2 como marcador independente de recidiva. Outros marcadores imunoistoquímicos não conseguiram prever o prognóstico dos pacientes. Notamos um aumento da densidade de linfócitos GRANZIMA B+ nas metástases linfonodais se comparado com os respectivos tumores primários. Metástases linfonodais apresentam menor expressão de COX2 e de IL-10. Isto sugere que mecanismos de evasão tumoral estejam diminuídos nos tecidos metastáticos, explicando, pelo menos em parte, por que a presença de metástases linfonodais não seria um excelente marcador de prognóstico nos pacientes com câncer diferenciado de tiroide. Nosso estudo mostrou que o câncer diferenciado de tiroide é infiltrado por múltiplas células do sistema imunológico e que o padrão de infiltração celular parece se associar a características clínicas e anatomopatológicas distintas. Este misto celular infiltrativo, juntamente com a produção de citocinas inflamatórias, cria um perfil de microambiente que é importante na determinação da agressividade tumoral. De fato, a presença de linfócitos T citotóxicos e a expressão de COX2 puderam prever o pior prognóstico dos pacientes estudados. Ainda, observamos que a metástase linfonodal é o sítio onde ocorreria uma resposta imunológica mais efetora e menos evasiva, de forma a determinar de forma mais assertiva um ataque imunológico efetivo coerente com a pouca força da metástase linfonodal como um preditor de prognóstico / Abstract: Thyroid cancer is the most common endocrine malignancy. Although most of these patients experience clinical improvement with current therapeutic tools, 10-30% will develop recurrent disease and contribute to the 1,890 deaths that are estimated for 2014 in the United States. The cyclooxygenase (COX) are a group of enzymes that catalyze the formation of prostaglandins from arachidonic acid and COX2 activity has been implicated in carcinogenesis. Our group previously demonstrated that mixture of immune cells infiltrates tissue of thyroid cancers. The present study investigated the presence of immune cells markers and tumor markers of inflammatory profile, looking for prognostic markers in patients with differentiated thyroid carcinoma. We retrospectively investigated 437 patients with differentiated thyroid carcinoma, whose tissue samples previously fixed in formalin and included in paraffin blocks were kept in the Tissue Bank of the AC Camargo Cancer Center. Well-differentiated thyroid cancer was diagnosed in 305 patients: 252 with papillary carcinoma and 53 with follicular carcinoma. Clinical information was obtained from medical records. We obtained tissue of lymph node metastases at diagnosis of 25 patients. For these cases, we performed a paired analysis of metastatic tissue and primary tumor. Immunological cell markers were investigated in intratumoral areas, including tumor-associated macrophages (CD68) and subpopulations of tumor infiltrating lymphocytes, such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of COX2, IL-17A, IL-1'beta', IL-10, IL-6, IL-23 and CD134 in the tumor cells. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes and expression of COX2 were associated with recurrence. Multivariate analysis using the Cox model of proportional hazards adjusted for the presence of concurrent chronic lymphocytic thyroiditis, identified CD8+/COX2 as an independent marker for recurrence. Other immunohistochemical markers failed to predict the prognosis of patients. We notice an increase in the density of GRANZYME B + lymphocytes in lymph node metastases when compared with their primary tumors. Lymph node metastases have lower expression of COX2 and IL-10. This suggests that tumor evasion mechanisms are impaired in metastatic tissues, explaining, at least in part, why the presence of lymph node metastases would not be an excellent prognostic marker in patients with differentiated thyroid cancer. Our study showed that the differentiated thyroid cancer is infiltrated by multiple immune cells and that the pattern of cellular infiltration appears to be associated with distinct clinical and pathological characteristics. This infiltrative mixed cell along with the production of inflammatory cytokines, creates a microenvironment profile that is important in determining the tumor aggressiveness. In fact, the presence of cytotoxic T lymphocytes and COX2 expression could predict the worst prognosis of the patients. Still, we found that lymph node metastasis is the place where there would be a more productive immune response and less evasive, favoring and effective immune response. It is fairly coherent with the little strength of lymph node metastasis as a prognostic predictor / Doutorado / Clinica Medica / Doutor em Ciências