by Ng Ping-chung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 161-179). / List of Abbreviation / Abstract / Acknowledgements / Table of contents / Chapter 1. --- Introduction / Chapter 1.1 --- Hormone and carcinogenesis --- p.1 / Chapter 1.2 --- Estrogen and carcinogenesis --- p.3 / Chapter 1.2.1 --- Carcinogenesis and endogenous sex hormone status --- p.3 / Chapter 1.2.2 --- Etiology of breast cancer --- p.3 / Chapter 1.2.2.1 --- Epidemiology --- p.3 / Chapter 1.2.2.2 --- Hormonal factors --- p.5 / Chapter 1.2.2.3 --- Genetic predisposition --- p.8 / Chapter 1.2.2.4 --- Influence of diet --- p.8 / Chapter 1.2.3 --- Hormonal therapy --- p.18 / Chapter 1.2.3.1 --- Anti-estrogen --- p.18 / Chapter 1.2.3.2 --- Progestins --- p.21 / Chapter 1.2.3.3 --- Aromatase inhibitor --- p.22 / Chapter 1.2.3.4 --- GnRH analogue therapy --- p.26 / Chapter 1.3 --- Estrogen pool --- p.26 / Chapter 1.4 --- Estrogen receptor --- p.30 / Chapter 1.4.1 --- General features of estrogen receptor and action mechanism --- p.30 / Chapter 1.4.2 --- Anti-estrogen binding site (AEBS) --- p.31 / Chapter 1.4.3 --- Physiological consideration --- p.32 / Chapter 1.4.3.1 --- Uterus: uterotrophic responses --- p.32 / Chapter 1.4.3.2 --- "Progesterone, the physiological estrogen antagonist" --- p.34 / Chapter 1.5 --- The role of growth factors and steroid hormones in breast cancer cell --- p.35 / Chapter 1.6 --- Alternate cytotoxic action of TAM --- p.37 / Chapter 1.7 --- In vitro models utilised in breast cancer study --- p.38 / Chapter 1.8 --- Current development of anti-estrogen --- p.39 / Chapter 1.9 --- Background about yuehchukene (YCK) --- p.41 / Chapter 2. --- Materials and methods / Chapter 2.1 --- Studies using whole animals --- p.47 / Chapter 2.1.1 --- Uterotrophic assay in rats --- p.47 / Chapter 2.1.2 --- Anti-implantation assay in rats --- p.48 / Chapter 2.1.3 --- Vaginal smear in mice --- p.49 / Chapter 2.2 --- Studies using breast cancer cells --- p.49 / Chapter 2.2.1 --- MCF-7 cell culture --- p.49 / Chapter 2.2.1.1 --- Measurement of cell number --- p.50 / Chapter 2.2.1.1.1 --- Cell count with haemocytometer --- p.50 / Chapter 2.2.1.1.2 --- Cell number estimated by DNA content in culture using Hoechst33258 --- p.51 / Chapter 2.2.1.1.3 --- Cell number estimated by [3H]-thymidine incorporation --- p.52 / Chapter 2.2.1.1.4 --- Preparation of dextran coated charcoal stripped serum --- p.52 / Chapter 2.2.2 --- MDA-MB-231 cell culture --- p.53 / Chapter 2.3 --- Studies using steroid receptors --- p.54 / Chapter 2.3.1 --- Rat uterine estrogen receptor --- p.54 / Chapter 2.3.2 --- Mice uterus and vaginal estrogen receptor --- p.55 / Chapter 2.3.3 --- MCF-7 cell estrogen receptor --- p.55 / Chapter 2.3.3.1 --- MCF-7 whole cell estrogen receptor binding --- p.55 / Chapter 2.3.3.2 --- Cytosolic estrogen receptor preparation from MCF-7 cell --- p.57 / Chapter 2.3.4 --- Progesterone receptor binding in MCF-7 cell --- p.57 / Chapter 2.3.5 --- Rat hepatic anti-estrogen binding site (AEBS) --- p.58 / Chapter 2.3.6 --- Estrogen receptor content estimation by enzyme immunoassay --- p.58 / Chapter 2.4 --- Enzyme studies related to estrogen metabolism --- p.60 / Chapter 2.4.1 --- Rat uterine ornithine decarboxylase (ODC) --- p.60 / Chapter 2.4.2 --- Rat hepatic ethoxyresorufin O-deethylase (EROD) --- p.60 / Chapter 2.4.3 --- Rat hepatic estradiol-2-hydroxylase --- p.62 / Chapter 2.4.4 --- MCF-7 cell estradiol-2-hydroxylase --- p.62 / Chapter 2.4.5 --- Human placental microsomal aromatase activity --- p.63 / Chapter 2.5 --- Enzymatic studies related to signal transduction --- p.64 / Chapter 2.5.1 --- Inhibition of Protein Kinase C activity of MCF-7 cell and protein phosphorylation --- p.64 / Chapter 2.5.2 --- Inhibition of calmodulin activation of cyclic nuleotide phosphodiesterase --- p.66 / Chapter 2.6 --- "Preparation of Pre-YCK, crude-YCK and post-YCK fractions" --- p.67 / Chapter 2.7 --- Preparation of Indole-3-carbinol acid condensation product (I3Ca) --- p.71 / Chapter 2.8 --- Studies on TCP series of YCK analogues --- p.71 / Chapter 2.9 --- List of test compounds --- p.75 / Chapter 2. 10 --- List of radio-ligands --- p.77 / Chapter 2.11 --- Miscellaneous reagents related to cell culture --- p.78 / Chapter 2.11.1 --- Culture medium --- p.78 / Chapter 2.11.2 --- Fetal calf serum --- p.78 / Chapter 2.11.3 --- Penicillin-streptomycin powder --- p.78 / Chapter 2.11.4 --- Phosphate buffer saline --- p.78 / Chapter 2.12 --- "Solvents, chemical and scintillants" --- p.78 / Chapter 3. --- Result / Chapter 3.1 --- Rat uterotrophic response with EE2 and YCK --- p.80 / Chapter 3.2 --- Mice vaginal cornification with estradiol (E2) and YCK --- p.83 / Chapter 3.3 --- Human breast cancer cell culture --- p.86 / Chapter 3.3.1 --- MCF-7 cell growth with YCK --- p.86 / Chapter 3.3.2 --- MCF-7 cell growth with YCK analogues and other related compounds --- p.91 / Chapter 3.3.3 --- MDA-MB-231 cell culture --- p.100 / Chapter 3.4 --- Receptor Binding --- p.100 / Chapter 3.4.1 --- Rat uterine estrogen receptor --- p.100 / Chapter 3.4.2 --- Mice uterine and vaginal estrogen receptor --- p.103 / Chapter 3.4.3 --- MCF-7 whole cell and cytosolic estrogen receptor --- p.103 / Chapter 3.4.4 --- MCF-7 cell progesterone receptor --- p.107 / Chapter 3.4.5 --- Rat hepatic anti-estrogen binding sites (AEBS) --- p.111 / Chapter 3.5 --- Enzyme activities related to estrogen metabolism --- p.111 / Chapter 3.5.1 --- Rat uterine ornithine decarboxylase (ODC) --- p.111 / Chapter 3.5.2 --- Rat hepatic estradiol-2-hydroxylase and ethoxyresorufin O-deethylase --- p.114 / Chapter 3.5.3 --- MCF-7 cell estradiol-2-hydroxylase --- p.121 / Chapter 3.5.4 --- Human placenta and MCF-7 cell aromatase --- p.126 / Chapter 3.6 --- Enzyme activities related to signal transduction --- p.126 / Chapter 3.6.1 --- Protein kinase C inhibition in vitro --- p.126 / Chapter 3.6.2 --- Calmodulin-dependent phosphodiesterase inhibitory actions in vitro --- p.131 / Chapter 3.7 --- Studies on TCP series of YCK analogues --- p.131 / Chapter 4. --- Discussion / Chapter 4.1 --- Estrogenicity of YCK --- p.140 / Chapter 4.2 --- Estrogenicity of YCK correlates with estrogen receptor (ER) binding --- p.141 / Chapter 4.3 --- Attenuation by YCK --- p.142 / Chapter 4.3.1 --- Attenuation by YCK on estrogen induced uterotrophic activity --- p.142 / Chapter 4.3.2 --- Attenuation by YCK on mice vaginal cornification with estradiol and YCK --- p.142 / Chapter 4.3.3 --- Attenuation by YCK on MCF-7 cell growth --- p.143 / Chapter 4.3.4 --- Attenuation of YCK on ornithine decarboxylase (ODC) induced by estrogen --- p.144 / Chapter 4.4 --- Deviation between YCK potency and RBA --- p.145 / Chapter 4.5 --- Estrogen inhibition action of YCK via non receptor binding mechanism --- p.148 / Chapter 4.6 --- Protein kinase C/ calmodulin-dependent phosphodiesterase inhibitor --- p.152 / Chapter 4.7 --- Progesterone receptor --- p.154 / Chapter 4.8 --- Aromatase inhibitor? --- p.155 / Chapter 4.9 --- Posssible mechanism for the attenuation of estrogenic action by YCK --- p.157 / Chapter 4.10 --- TCP series of YCK analogues --- p.158 / Chapter 4.11 --- Future works --- p.159 / Chapter 5. --- Reference --- p.161 / Appendix / Appendix 1 YCK analogues / Appendix 2 Structure of compounds mentioned in this thesis
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_318193 |
| Date | January 1994 |
| Contributors | Ng, Ping-chung., Chinese University of Hong Kong Graduate School. Division of Biochemistry. |
| Publisher | Chinese University of Hong Kong |
| Source Sets | The Chinese University of Hong Kong |
| Language | English |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, 179, [5] leaves : ill. (some mounted col.) ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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