published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Master / Master of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Physiology / Master / Master of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Par-4 is a leucine zipper domain protein that induces apoptosis on its own in certain cancer cells and in Ras-transformed cells, but not in normal or immortalized cells. Par-4 induces apoptosis by activation of the Fas death receptor pathway and co-parallel inhibition of NF-B transcription activity. Cells that are resistant to apoptosis by Par-4 alone, however, are greatly sensitized by Par-4 to the action of other pro-apoptotic insults such as growth factor withdrawal, TNF, ionizing radiation, intracellular calcium elevation, or those involved in neuronal degeneration such as Alzheimer's, Parkinson's, Huntington's and Stroke. Previous studies have suggested that the apoptosis-sensitization potential of Par-4 is dependent upon inhibition of PKC or WT1 cell survival function by direct interaction between the leucine zipper domain at the carboxy-terminus of Par-4 and the zinc finger domains of PKC or WT1. In this study, I performed structure-function analysis using GFP-fusion proteins and deletion mutants to identify the functional localization and domains of Par-4 that are essential for apoptosis induction. My findings suggest that apoptosis by Par-4 is dependent on its translocation to the nucleus for induction of apoptosis. A bipartite nuclear localization signal sequence corresponding to amino acids 137-155 was necessary for nuclear translocation of Par-4. Importantly, the core residues 137-204 in the center part of Par-4 were necessary and sufficient to induce Fas pathway activation, inhibition of nuclear NF-B transcription activity and apoptosis. These findings imply that binding of Par-4 via its leucine zipper domain to other proteins is dispensable for apoptosis by Par-4.

No description available.

It is estimated that more than 218,000 men will be diagnosed with prostate cancer in the year 2007. With a mean age at diagnosis of 72, and extended long-term survival, prostate cancer represents a significant health problem among older men. Despite the fact that the treatment for prostate cancer has significant effects upon one's physical appearance and functional ability, there exists a gap in the literature regarding body image in men with prostate cancer. Additionally, there is a large gap in our knowledge of the relationship of body image and QOL in men with prostate cancer.The purpose of this study was to describe changes in body image and quality of life among men with prostate cancer, to describe the relationship between the two, and to explore the differences in body image and quality of life related to treatment, age, duration of therapy and body mass index.The sample consisted of one hundred and thirty-two older men (> age 60) with prostate cancer, recruited from the oncology and urology out-patient departments at an urban Veterans Affairs Medical Center. The participants completed 2 established questionnaires, the Body Image Scale and the Quality of Life Index Cancer Version. Descriptive and inferential statistics were used in the analysis.For purposes of analysis, the sample was grouped according to treatment with ADT as part of therapy for prostate cancer. The ADT-naive group composed 34.1% of the sample (n = 45); the ADT group composed 65.9% of the sample (n = 87). Whether or not one received ADT was correlated with body image change: those men who received ADT had a greater perception of negative change. There was, however, no difference in quality of life between men who received ADT and men who did not. Neither age nor duration of therapy had any relationship with the perceptions of change in body image or quality of life. A significant negative correlation was demonstrated between body image change and quality of life overall, and with each of the domains.

No description available.