Ovarian cancer is regarded as the most lethal gynecological malignancy around the world. Despite the advancing medical improvements in both surgery and chemotherapy, the mortality rate did not appear to be reduced. This could be account for the late diagnosis of ovarian cancer until advanced stage. Recently, p-21 activated kinase 4 (PAK4), as a potential significant prognostic marker of ovarian cancer, has been widely studied on its contribution in oncogenesis properties. It was suggested that PAK4 proteins were activated and confer chemoresistance in ovarian cancers. In this study, we hypothesized that the up-regulation of PAK4 in ovarian cancers maybe resulted from mutations and amplification in genomic DNA level. Investigations on PAK4 genetic alterations were carried out. Recurrent mutations were found in the kinase domain of PAK4 in three ovarian cancer cell lines and two clinical samples. Single mutation was found in the exon 3 of PAK4 coding for GTPase binding domain (GTB). Amplifications of PAK4 genomic DNA were also found in four ovarian cancer cell lines. On top of that, dysregulated PAK4 level in chemosensitivity ovarian cancer cell line, A2780s showed PAK4 contribution in protection against apoptosis. Meanwhile PAK4 transfected chemoresistance cell line A2780cp also showed similar effect to PAK4 transfected A2780s. Kinase-dead and constitutively active PAK4 did not show any significance contribution to the apoptosis property. This may suggest that PAK4 do not operate all kinase domains towards apoptotic function. Immortalized normal ovarian epithelial cell line, HOSE6-3 was also upregulated with PAK4 transfection. However it did not induce the oncogenesis property of cell survival. / published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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Akt activation mediates increases in glycogen synthesis in response to insulin in humans, while extracellular signal-regulated kinase (ERK) activation increases gene transcription and protein translation in response to endurance and resistance exercise. Akt activation increases only in response to intense muscle contractions and during hypertrophy in rats. No study has examined Akt and ERK activation with increasing numbers of intense muscle contractions in humans. Therefore, the primary objectives of this investigation were to determine if Akt activation increases in response to resistance exercise in humans, and to compare the changes in Akt and ERK activation in response to increasing numbers of muscle contractions.Akt and ERK activation were compared in muscle biopsy samples from 7 men before (Pre) and after (Post) knee extension and control protocols using enzyme linkedimmunosorbent assays. Baseline information was obtained including body composition and maximal strength (1-RM). Subjects were familiarized with knee extensions performed at 70% of 1-RM and a specified repetition cadence (2sec up, 2sec down). Once/wk, subjects performed one protocol in random order: 1 repetition (rep), 10reps, 3 sets of l0reps (3x10), or 6min of sitting. Akt activation decreased 42%, while ERK activation increased 108% in response to 3x10 (p<0.05). Akt and ERK activation did not change with 1 and 10reps, and thus their responses were not dose-dependent with resistance exercise in humans. The findings from this study represent the first indication that Akt activation is reduced in response to resistance exercise in human skeletal muscle, possibly to help mediate reductions in glycogen synthesis. / Human Performance Laboratory

Thesis (Ph. D.)--School of Biological Sciences. University of Missouri--Kansas City, 2006. / "A dissertation in molecular biology and biochemistry and cell biology and biophysics." Advisor: Gerald M. Carlson. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Nov. 9, 2007. Includes bibliographical references (leaves 103-113). Online version of the print edition.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1994. / Vita. Abstract. Includes bibliographical references (leaves 110-123). Also available via the Internet.