Thesis (Ph. D.)--University of Chicago, Dept. of Biochemistry and Molecular Biology, August 1999. / Includes bibliographical references. Also available on the Internet.

One in 8 women will be diagnosed with breast cancer in the United States and estrogen receptor (ER) status largely influences the type and subsequent success of treatment employed. Although ER-positive breast cancer can be treated with endocrine therapy, the more invasive ER-negative breast cancer is non-responsive to this therapy and cytotoxic agents are often utilized which are associated with many adverse side effects. Consequently, there is a genuine need to develop more effective, less toxic treatments for invasive breast cancer. Indole-3-carbinol is a phytochemical found in cruciferous vegetables and one of its major metabolites, 3,3’-diindolylmethane (DIM), exhibits a broad range of anticancer and antitumorigenic activities. ER-negative MDA-MB-231 and MDA-MB-453 breast cancer cell growth was inhibited after treatment with a novel series of methylenesubstituted DIMs (C-DIMs), namely 1,1-bis(3’-indolyl)-1-(p-substitutedphenyl) methanes containing trifluoromethyl (DIM-C-pPhCF3), t-butyl (DIM-C-pPhtBu) and phenyl (DIM-C-pPhC6H5) groups. In addition, DIM-C-pPhC6H5 (40 mg/kg/d) inhibited tumor growth in nude mice bearing MDA-MB-231 cells as xenografts. Treatment of breast cancer cells with C-DIMs lead to downregulation of cyclin D1 and induction of non-steroidal anti-inflammatory drug-activated gene 1. Detection of necrosis, caspasedependent or caspase-independent apoptosis were not observed in breast cancer cells treated with C-DIMs, however autophagic cell death was induced by C-DIMs. DIM and ring-substituted DIMs have exhibited antitumorigenic activity in tumor murine mammary models. An investigation into the mechanism of cell death induced by DIM and 5,5’-dibromoDIM (5,5’-diBrDIM) in both ER-positive (MCF-7) and ERnegative (MDA-MB-231) breast cancer cells revealed modulation of several key signaling pathways involved in growth control. Both DIM and 5,5’-diBrDIM downregulated cyclin D1, although only 5,5’-diBrDIM induced a depolarization of the mitochondrial membrane. In addition, apoptosis was observed in MCF-7 cells treated with 5,5’-diBrDIM but not MDA-MB-231 cells. In summary, C-DIMs may represent new mechanism-based agents for treatment of breast cancer through induction of autophagic cell death. The ring-substituted DIMs correspond to a novel class of uncharged mitochondrial poisons that are also highly effective in inhibiting breast cancer cell growth. Results of this research provide evidence for the potential role of two new series of DIM analogs for the treatment of highly aggressive breast cancer.

Thesis (M.Med.Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 53-65).

Thesis--PlanB (M.S.)--University of Wisconsin--Stout, 2002. / Includes bibliographical references.

Report (Ed. D.)--Teachers College. / Issued also on microfilm. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 165-186).

Thesis (Ph. D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 176-200).

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 150-190). Available also in a digital version from Dissertation Abstracts.

Background: breast cancer patients were found to experience multiple concurrent symptoms. These concurrent symptoms (termed symptom cluster) could have synergistic effects on patient functional status and quality of life. Understanding symptom cluster provided us new insight in symptom assessment and symptom management. Previous studies on symptom cluster among breast cancer patients focused on Caucasian. The current study attempt to identify symptom cluster and the factors associated with it among Chinese breast cancer patients. Methods: this study was a secondary analysis on a sample of 348 breast cancer patients. Data on symptom distress (assessed by Memorial symptom Assessment scale Short Form) was retrieved. Symptom clusters were identified through factor analysis using principal components method and Varimax rotation. Demographics and medical characteristics were proposed to be associated with symptom cluster. Uni-variate analysis and linear regression performed on these variables. Results: four symptom clusters (namely gastrointestinal cluster, general malaise cluster, self image cluster, and cutaneous cluster) were identified. Recurrence of breast cancer and chemotherapy were associated with either gastrointestinal cluster or general malaise cluster. Age, cancer status and occupation were associated with self image cluster while no variable was associated with cutaneous cluster. Conclusion: The current study provided empirical evidence that Chinese breast cancer patients experienced similar symptom clusters as Caucasian. Future study could be done to verify these four symptom clusters and identify underlying mechanism. Recommendations: health care providers could pay more attention to those suffer from breast cancer recurrence or currently receiving chemotherapy. These patients tend to experience gastrointestinal cluster and general malaise cluster. Clinical setting and evaluation tools could be adjusted to fit these high risk groups. / published_or_final_version / Public Health / Master / Master of Public Health

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