Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Wang Ya-Ping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 152-161). / 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.

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

Yau, Ka Long. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 97-113). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

"July, 2003" / "Amendments of the thesis" and "abbreviations (additional)" inside back cover. / Includes bibliographical references (leaves 195-231) / x, 231, [20] leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2003

Breast cancer is a heterogeneous disease comprised of distinct biological entities that correlate with diverse clinical outcomes. Gene expression profiling has divided this heterogeneity into luminal, ERBB2+ and basal molecular subtypes. Basal breast cancers are difficult to treat as they lack expression of candidates suitable for targeted therapies and are associated with poor outcome. / Elevated protein level of the hepatocyte growth factor receptor, MET, is observed in 20% of human breast cancers and correlates with poor prognosis. However, the role of MET in mammary tumorigenesis is poorly understood. To address this, we generated a murine model that expresses weakly oncogenic mutants of Met (Metmt) in the mammary epithelium under the transcriptional control of the mouse mammary tumor virus promoter. We demonstrate that Metmt induces mammary carcinomas with diverse phenotypes and used gene expression microarrays to elucidate gene expression changes induced by Met. Since mammary tumors contained variable contents of epithelium and stroma, we used laser capture microdissection to procure epithelial cells for microarray analysis. Based on immunohistochemistry and expression profiling, we show that Metmt produces tumors with luminal or basal characteristics. From hierarchical clustering, Metmt-induced basal tumors clustered with murine models that share features of epithelial to mesenchymal transition and human basal breast cancers. Moreover, Metmt basal tumors clustered with human basal breast cancer. The status of MET among the human breast cancer subtypes has not previously been addressed. We demonstrate that MET levels are variable across molecular subtypes but show elevation in the basal subtype and correlates with poor outcome. We used a candidate gene approach derived from microarray data to gain an understanding of signals required for Met-dependent tumorigenesis. We investigated Nck adaptor proteins and demonstrate a role for Nck in cell motility and actin dynamics of Met-dependent breast carcinoma cells and show elevated expression in human basal breast cancers. By generating a unique mouse model in which Met is expressed in mammary epithelia, with the examination of MET levels in human breast cancer, we have established a novel link between MET and basal breast cancer. This work identifies poor outcome basal breast cancers that may benefit from anti-MET therapies.

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