京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第21689号 / 医科博第93号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 斎藤 通紀, 教授 中川 一路, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第21694号 / 医科博第98号 / 新制||医科||7(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 竹内 理, 教授 Shohab YOUSSEFIAN, 教授 藤渕 航 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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As we face an expanding elderly population and increased age-related chronic diseases, we must seek solutions that address interconnected problems. Dasatinib plus quercetin (D+Q), a novel combination drug, is a proposed solution to improve the health and longevity of aged individuals with minimal side effects, exceptional efficacy, and maximum convenience. In this experiment, intermittent D+Q treatment was completed on young and old mice. RNA was extracted from perigonadal adipose tissue and cDNA libraries of mRNA and miRNA were made. Real-time quantitative polymerase chain reaction was used to assess relative gene expression for mRNA and miRNA pertaining to cell senescence, inflammation, and insulin resistance. miR-146a was found to have a significant difference (p < 0.05) in relative expression based on the interaction between age and treatment, while other genes showed no difference in relative expression. Furthermore, miR-149 was found to show near significance in interaction (p=0.0552) and had significant difference between old control and old D+Q treated mice. The miR-149 presents an avenue for future research in senescence markers and shows potential as a novel senolytic target.

The current standard treatment of prostate cancer by androgen deprivation therapy involves using drugs such as bicalutamide (Casodex) to antagonistically block androgen receptors that are normally present within prostate cells. Usually, the therapy is successful in the short run at limiting the growth of prostate cancer. However, in virtually all cases tumors begin to grow aggressively again after several months of treatment and new therapies must be started. The mechanism by which these prostate cells transform from androgen sensitive to androgen independent and anti-androgen resistant is unclear. In this study, we investigated the role of microRNAs, small 15 to 18 nucleotide regulatory RNAs, in regulating the desensitization of prostate cancer cells to the androgen receptor antagonist drug bicalutamide. In order to identify significant microRNAs, quantitative PCR was used to obtain genome-wide microRNA expression levels of 885 human microRNAs at different timepoints for androgen sensitive LNCaP cancer cells treated with bicalutamide and for untreated control cells in tissue culture. Analysis of microRNA expression by clustering analysis and by statistical comparisons of treatment groups resulted in identification of 28 microRNAs that have altered expression in the progression process. In silico target prediction analysis was performed with the microRNAs shown to have altered expression, and a group of genes predicted to be under microRNA regulatory control during cancer progression to resistance was identified. A microRNA expression profile can be useful in developing more effective prognostic and therapeutic tools for prostate cancer.

The Dawdle (DDL) gene in Arabidopsis encodes a protein with a Fork Head-Associated domain. A mutation in the DDL gene causes pleiotropic phenotypes and reduced the levels of several microRNAs. However, it is not completely known whether the FHA domain of the DDL is necessary for its function. Furthermore, the interactors involved in the same signaling pathway as DDL have not been identified yet. To determine the role of FHA domain in DDL function, four Tiller mutant lines were isolated and characterized. Results from phenotypic characterization suggest that the FHA domain may require for DDL function. For interactors, the interactions between DDL and At1G68010, At2G28200, At3G68010 and At4G18372 were identified by Yeast Two Hybrid, and then confirmed by the Split Luciferase assays. In addition, T-DNA mutants for each interactor were isolated and analyzed phenotypically suggesting that the genes carrying those T-DNAs should function in the same signaling pathway as DDL.

No description available.

No description available.

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No description available.