Poon Shuk-ching. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 113-125). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese Version) --- p.iv / Table of Contents --- p.vi / List of Tables --- p.x / List of Figures --- p.xi / List of Abbreviations --- p.xiii / Chapter Chapterl 1 --- ntroduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.5 / Chapter 2.1 --- Mushroom Polysaccharides From Basidiomycetes --- p.5 / Chapter 2.1.1 --- Antitumor and Immunomodulatory Activity --- p.6 / Chapter 2.1.2 --- Antiviral Activity --- p.9 / Chapter 2.1.3 --- Hypoglycermic Activity --- p.11 / Chapter 2.1.4 --- Free Radical Scavenging Activity --- p.11 / Chapter 2.2 --- Mushroom Dictyophora indusiata --- p.13 / Chapter 2.2.1 --- Nutritional Value --- p.13 / Chapter 2.2.2 --- Structural Characteristic of Dictyophora indusiata Polysaccharides --- p.14 / Chapter 2.2.3 --- Biological Activity --- p.16 / Chapter 2.3 --- In vivo Antitumor Study --- p.19 / Chapter 2.4 --- Induction of Cytokines Production in Immune System --- p.21 / Chapter 2.5 --- In vitro Antitumor Study --- p.25 / Chapter 2.6 --- Cell Cycle Regulation --- p.28 / Chapter Chapter 3 --- Materials & Methods --- p.34 / Chapter 3.1 --- Extraction --- p.34 / Chapter 3.1.1 --- Extraction of Dictyophora indusiata Polysaccharides --- p.34 / Chapter 3.1.2 --- Purification of Dictyophora indusiata Polysaccharides --- p.35 / Chapter 3.1.2.1 --- Preparation of DEAE-cellulose Ion Exchanger --- p.35 / Chapter 3.1.2.2 --- Fractionation --- p.35 / Chapter 3.2. --- Characterization of Dictyophora indusiata Polysaccharides --- p.39 / Chapter 3.2.1 --- Polysaccharide Content Determination --- p.39 / Chapter 3.2.2 --- Protein Content Determination --- p.39 / Chapter 3.2.3 --- Gas Chromatography (GC) --- p.40 / Chapter 3.2.4 --- Uronic Acid Content Determination --- p.42 / Chapter 3.2.5 --- High Performance Liquid Chromatography (HPLC) --- p.43 / Chapter 3.3 --- In vivo Studies --- p.44 / Chapter 3.3.1 --- Animals --- p.44 / Chapter 3.3.2 --- Maintenance of Sarcoma 180 Cell Line --- p.44 / Chapter 3.3.3 --- Effect of DI3 Fraction on Sarcoma 180 Solid Tumor --- p.45 / Chapter 3.3.4 --- Effect of DI3c Fraction on Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin 2 (IL-2) Production --- p.47 / Chapter 3.3.4.1 --- Treatment of Mice --- p.47 / Chapter 3.3.4.2 --- Preparation of Mouse Serum --- p.47 / Chapter 3.3.4.3 --- Enzyme-linked Immunosorbent Assay (ELISA) for TNF-α Production --- p.48 / Chapter 3.3.4.4 --- Enzyme-linked Immunosorbent Assay (ELISA) for IL-2 Production --- p.49 / Chapter 3.4 --- In vitro Studies --- p.51 / Chapter 3.4.1 --- Maintenance of Cell Lines --- p.51 / Chapter 3.4.2 --- Effect on Cancer Cell Lines --- p.52 / Chapter 3.4.3 --- Cytotoxicity on Normal Cell Line --- p.52 / Chapter 3.4.4 --- Trypan Blue Exclusion Method --- p.53 / Chapter 3.4.5 --- MTT Assay --- p.54 / Chapter 3.4.6 --- BrdU Incorporation --- p.55 / Chapter 3.5 --- Statistical Analysis --- p.56 / Chapter Chapter 4 --- Results --- p.57 / Chapter 4.1 --- Extraction and Fractionation of Polysaccharides from Dictyophora indusiata --- p.57 / Chapter 4.1.1 --- Percentage Yield of Crude DI Polysaccharides --- p.57 / Chapter 4.1.2 --- Percentage Yield of DI3 Fractions --- p.57 / Chapter 4.2 --- Characterization of DI3 Fractions --- p.62 / Chapter 4.2.1 --- Polysaccharide and Protein Contents of DI3 Fractions --- p.62 / Chapter 4.2.2 --- Relative Monosaccharide and Uronic Acid Content in Different DI3 Fractions --- p.62 / Chapter 4.2.3 --- Estimated Molecular Weight of DI3 Fractions --- p.65 / Chapter 4.3 --- Antitumor Effect of Dictyophora indusiata Polysaccharides In vivo --- p.70 / Chapter 4.3.1 --- In vivo Antitumor Effect of Crude DI Polysaccharides --- p.70 / Chapter 4.3.2 --- In vivo Antitumor Effect of Various Fractions of DI3 --- p.70 / Chapter 4.3.3 --- Effect of DI3c on TNP-α and IL-2 Production in Mice --- p.78 / Chapter 4.4 --- In vitro Effects of DI3 Fractions on Cell Density and Viability on Normal and Cancer Cell Lines --- p.86 / Chapter 4.4.1 --- Effects of DI3 Fractions on Cell Density and Viability of Human Leukemic HL-60 and K-562 and Mouse Sarcoma 180 Cells --- p.86 / Chapter 4.4.2 --- Effects of DI3 Fractions on the Growth of Human Liver Cancer HepG2 and Normal Monkey Kidney Vero Cells --- p.86 / Chapter 4.4.3 --- Effect of DI3b Fraction on Proliferation of HL-60 Cells Determined by BrdU Incorporation --- p.94 / Chapter Chapter 5 --- Discussions --- p.96 / Chapter 5.1 --- Extraction and Characterization of DI3 Fractions --- p.96 / Chapter 5.2 --- Antitumor Effects of Dictyophora indusiata Polysaccharides --- p.101 / Chapter 5.3 --- Further Studies --- p.109 / Chapter Chapter 6 --- Conclusion --- p.111 / References --- p.113

Vitamin D3 must be metabolically activated by the liver to 25-hydroxyvitamin D3 (25OHD3) and then by the kidney 1alphahydroxylase (1alphaOHase) to become 1,25dihydroxyvitamin D 3 (1,25(OH)2D3). 1,25(OH)2 D3 is a potent inhibitor of tumor growth in vitro and in vivo. Recent studies indicate that metabolic activation of 1,25(OH) 2D3 also occurs in cancer cells such as breast cancer. Consequently, the major objective of this project was to determine if tumoral 25OHD 3-1alphahydroxylase modulates any or all of the stages of breast tumor progression without inducing the hypercalcemic side effects of 1,25(OH) 2D3. For this purpose we used the PyVMT breast cancer mouse model in which the oncoprotein, polyomamiddle T antigen (PyMT) is under the control of mouse mammary tumor virus LTR (MMTV LTR). Mice exhibited tumors restricted to the mammary epithelium progressing to the various stages of breast cancer. Animals were treated with either vehicle, 25OHD3 (2000 pM/24h) or 1,25(OH)2D3 (12pM/24h). Mice treated with the vitamin D precursor, 25OHD3, exhibited a marked reduction in tumor onset and growth comparable to the 1,25(OH)2D3 treated group. Furthermore, biomarkers of tumor progression were markedly reduced in 25OHD3 and 1,25(OH)2D3 animals as compared to vehicle-treated animals. However, mean circulating calcium concentrations remained unchanged in 25OHD3 treated animals but increased significantly in 1,25(OH)2D3 treated animals as compared to controls. Tumoral levels of 1,25(OH)2D3 in mice treated with 25OHD3 were increased 79% in comparison to vehicle control mice. Additionally, 25OHD3 and 1,25(OH)2D 3 treated animals had a significant decrease in the mean number of lung metastases per animal as compared to vehicle treated control animals. This study therefore suggests an important autocrine role of 1alphaOHase expression in breast tumor cells. Furthermore, accumulation of intra-tumoral 1,25(OH) 2D3 in response to 25OHD3 administration strongly suggests that locally produced 1,25(OH)2D3 plays a significant role in restraining tumor growth without inducing the hypercalcemic side effects associated with 1,25(OH)2D3.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 155-161.

No description available.

Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2007. / Typescript. Non-Latin script record Includes bibliographical references (leaves 112-128). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;