No description available.

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

No description available.

Thesis (Ph. D. in Cancer Biology)--Vanderbilt University, Dec. 2007. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 249-259).

Thesis (M.S.)--Ball State University, 2009. / Title from PDF t.p. (viewed on June 08, 2010). Includes bibliographical references (p. 75-80).

No description available.

Hepatocellular carcinoma (HCC) accounts for 70-85% of liver cancer, which is the sixth most common cancer in the world. Prognosis of HCC is dismal with little chance of complete recovery after diagnosis. It is of essence to discover the key molecules involved in the tumor progression. This could help earlier detection of HCC and establish targeted molecular therapies. Cyclin E1 (CCNE1) is a cyclin molecule responsible for the transition from G1 to S phase of the cell cycle and is often dysregulated in human cancers. CCNE1 is reported with overexpression in about 30-70% of HCC cases. It expresses in tumor cells as a ladder of proteins and as low molecular weight CCNE1. The study is aimed to investigate the role of CCNE1 in HCC. From the local cohort of HCC patients, 6 out of 13 patients (46.2%) of HCC tumor tissues were found with CCNE1 overexpression compared with the non-tumor tissues by western blotting. The presence of three CCNE1 isoforms in HCC was detected. The expression of total CCNE1 and each isoform varied independently among the studied HCC cell lines, with HepG2 having the highest expression and 97L the lowest. To extend our study on the regulation of CCNE1 expression, the expression of selected four genes associating with the CCNE1 expression and functions was studied by quantitative PCR (qPCR). F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) and cullin 3 (CUL3), the two genes responsible for CCNE1 degradation, had increased expression in the HCC cell lines with higher CCNE1 expression. Cyclin A (CCNA2), the downstream cyclin molecule of CCNE1, also had higher expression in these cell lines. In contrast, the expression of cyclin dependent kinase 2 (CDK2), the catalytic partner of CCNE1, had the least difference among the six HCC cell lines compared to other three genes. To characterize the role of CCNE1 isoforms in HCC, CCNE1 isoform 1, 2, and 3 were overexpressed in PLC cells and such overexpression remained even after 8 passages in culture. In flow cytometric analysis, GFP signal in cell culture population was viewed to observe the transduction efficiency. The vector control showed the strongest GFP signal, followed by CCNE1 isoform 3 showing dim signal. CCNE1 isoform 1 and 2 almost showed no signal. In the functional studies, the overexpression of CCNE1 isoform 3 could increase proliferation and migration of HCC cells. In summary, CCNE1 could promote proliferation and migration of HCC cells through elevated expression of CCNE1 isoform 3. / published_or_final_version / Surgery / Master / Master of Philosophy

Cell-cycle progression in mammalian cells is coordinated by a series of control points. The D-type cyclins are a family of key cell cycle regulators that are controlled largely by mitogens and their association with and activation of cdk 4 and 6 at the G1 phase of the cell cycle. This study seeks to first analyze cyclins D1, D2, and D3 expression patterns in preimplantation mouse embryos using in vivo studies and then analyze the effects of Dilantin on the cyclin D1 expression pattern in cultured embryos. Antibody staining against cyclin D1, D2, and D3 via indirect immunofluorescence using a Zeiss Confocal Microscope and analysis of individual embryo staining intensities using Zeiss computer software were employed to evaluate expression patterns throughout the first three cell cycles. The data showed that all three D cyclins were present throughout the first three cell cycles. Cyclin D1 had peak average fluorescence intensity at the G2 phase of the second cell cycle with a decrease at the G1 in the third cell cycle. Cyclin D2 had a consistent increase of fluorescence intensity throughout all three cell cycles. Cyclin D3 had peak average fluorescence intensity at the G2 phase of the second cell cycle with an immediate decrease at the Gl phase in the third cell cycle. Cyclin D1 was localized to the nucleus in G1 phases of the cell cycle. In contrast, cyclin D2 was found in the nucleus during G2 phases of the cell cycle rather than in G1. Cyclin D3 was not localized to the nucleus in either cell cycle phase throughout the first three cell cycles. These unique nuclear staining patterns seen by D1, D2, and D3 may reflect a function in the cell cycle. Embryos cultured in the presence of l0gg/ml of Dilantin were found to be slowed in development indicated by the absence of transition from the one-cell to the two-cell stage when compared to the controls. Since the Dilantin cultured embryos never reached G1 of the second cell cycle the increase in fluorescence intensity seen was still considered to be a representation of the G2 phase of the first cell cycle. Cyclin Dl's fluorescence intensity was affected by Dilantin and accompanied with unstained nuclei during the G2 phase of the first cell cycle. The peak average fluorescence intensity occurred during the G1 phase of the second cell cycle for cyclin D1 stained CZB control, while the vehicle control, 0.001N NaOH, remained constant. Both CZB and 0.001N NaOH had similar expression patterns seen previously in the cyclin D1 in vivo data. The information gained from the in vivo and in vitro experiments will help to better understand what causes the problems associated with exposure to Dilantin, and also the effects Dilantin has on the cell cycle. / Department of Biology

Thesis (Ph. D.)--University of Chicago, Committee on Virology, June 2001. / Includes bibliographical references. Also available on the Internet.