2009 MU dissertations - Freely available online
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Item Targeting estrogen- and hedgehog-signaling pathways in prostate cancer(University of Missouri--Columbia, 2009) Ślusarz, Anna; Slusarz, Anna; Lubahn, Dennis B.Prostate cancer is the second most frequent cause of cancer deaths in men, and the risk to develop cancer increases with age. Since the lifespan of the society is progressively increasing, the importance of preventing the development of this common disease is becoming more urgent. The prevention and therapy options for non-metastatic prostate cancer are available but limited. For the androgen-insensitive, metastatic form of prostate cancer there still is no effective therapy. Our laboratory has an estrogen receptor based perspective on prostate cancer. We are using a transgenic mouse as an animal model to study the development and treatment of prostate cancer. We are also investigating a selection of botanical compounds that have been implicated as cancer protective either by traditional medicine or in modern cancer research. The TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) model enables us to study the specific roles of estrogen receptors in prostate cancer progression. The expression of the two estrogen receptors alpha (ERα) and beta (ERβ) in TRAMP mouse prostates switches upon progression from non-metastatic to metastatic tumor phenotype. During earlier stages of cancer, ERβ is the main estrogen receptor present, as the phenotype of the cancer changes to the more neuro-endocrine like, the expression of ERβ decreases and ERα seems to remain the only active receptor. Initial studies in the Lubahn lab and elsewhere led us to hypothesize a protective role for ERβ in prostate cancer tumorigenesis. The presence of ERβ only seems to prevent or slow down the incidence of (PDC) poorly differentiated carcinoma in contrast to ERα, which promotes the metastatic, neuro-endocrine like phenotype. We have found though a study in double transgenic mice, that were WT and KO for estrogen receptors alpha or beta on a TRAMP background, that ERαKO mice did not develop poorly differentiated carcinoma (75% reduction compared to control animals), however ERβKO mice had significantly increased PDC incidence and had double the PDC compared to animals WT for both receptors. We were also interested in cancer protective properties of a variety of botanical compounds, reported in the literature to be potentially beneficial for prostate health, and widely bought through health food stores around the country. We specifically investigated apigenin, baicalein, curcumin, EGCG, genistein, quercetin, and resveratrol, both in vitro and in vivo. All seven compounds were able to delay prostate cancer cell growth of both human (LNCaP, PC3, and PC3M) and mouse (TRAMP-C2) prostate cancer cell lines. All seven compounds combinations were also able to inhibit or delay prostate cancer incidence by up to 80%, specifically at the well differentiated carcinoma stage, when fed to TRAMP mice. The protective effects were only present in ERWT mice, indicating a need for both receptors for these compounds to act on the prostate cancer incidence. I introduced a new pathway to the lab, the hedgehog signaling pathway, which has been recently found to play a role in prostate cancer, specifically in metastatic cancer. Several botanicals used in the lab were able to inhibit the hedgehog pathway as indicated by decreasing Gli1 levels. With IC[subscript 50] values ranging from <1μM to 25μM these compounds demonstrated hedgehog pathway inhibition by deceasing Gli1 mRNA concentration by up to 95% and down regulating Gli-reporter activity by 80%. Also, both estrogen and ICI inhibit Gli1 mRNA in TRAMP-C2 cells, and Gli-reporter activity in Shh Light II cells. My research sheds light on an additional mechanism by which phytoestrogens are potentially protecting against cancer. My work suggests a potential new treatment target for addressing both slow and fast growing prostate cancers. Based on data presented here, we propose that a combination of ERα antagonists, ERβ agonists and selected botanicals should present a comprehensive prostate cancer remedy.Item An exploration of chemical agents detection using the quantum fingerprint [superscript TM] technology(University of Missouri--Columbia, 2009) Tipton, Annie YuNing Hsu, 1979-; Tompson, R. V. (Robert Vaughn), 1958-; Prelas, Mark Antonio, 1953-The detection of chemical agents using a novel, gas-phase, sensor technology has been examined experimentally in this work. The goal of the work was to determine the feasibility of using solid-state materials as gas-phase Quantum Fingerprint TM(QFTM) sensors. The energy levels created by various targeted species adhered on the semiconductor substrate surface, acted as charge traps which can be excited and the transient signals associated with their relaxation examined. A Charge-based Deep Level Transient Spectroscopy (Q-DLTS) system has been used to characterize the deep level states created by surface impurities. In this research, critical components have been examined for the development of such sensor technology. These include selection of appropriate semiconductor substrates and metal contacts for ohmic contacts, fabrication protocols and metallic pattern designs for optimal signals, development of sensor technology measurement protocols, and testing of sensor chips under a controlled environment. The substrate materials tested in this work include silicon, silicon carbide, and sapphire. Fabrication of each sensor chip followed stringent material cleaning procedures to prevent contamination that would affect performance and integrity of the metallization. A few chemical agents were selected for testing, which included: water, 1-propanol, isopropanol, methanol, butanol, ethanol, nitrogen gas, argon gas, and methane gas. The testing of the sensor chips was performed in a controlled, high vacuum environment, isolated from the presence of other species. The experimental measurements made in this work have shown some dependency of targeted species concentrations and pressures with electrical charge collected from trap centers.Item Explicating journalism-as-a-conversation : two experimental tests of online news(University of Missouri--Columbia, 2009) Marchionni, Doreen Marie; Thorson, EstherThe concept of journalism as a conversation has been richly explored in descriptive studies for decades. Largely missing from the literature, though, are clear operationalizations that allow theory building for purposes of explanation and prediction. Using Steven Chaffee's articulation of concept-explication as a guide, this dissertation conducted a pair of online news experiments to measure the concept, tracing it in literatures as varied as political communication and computer-network analysis, often as an embedded concept. The first experiment tested whether readers perceive conversational stories as different from traditional stories and as more credible and expert. The second tested types of journalistic conversation on these outcomes. Findings suggest the conversational features coorientation/homophily and interactivity are key, not only in distinguishing this type of news but in predicting its perceived credibility and expertise.Item Athletes' experiences of sport psychology consultation : exploring a multi-season, cross gender intervention(University of Missouri--Columbia, 2009) Mapes, Renee; Bergin, David AllenApplied sport psychology consultations can provide beneficial services to athletes and coaches, particularly regarding performance enhancement. This study examined the experiences of ten wrestlers involved in a long-term sport psychology program through the use of in-depth interviews. Grounded Theory methodology guided the analysis of the data which led to the creation of five main themes: Athlete Characteristics; Intervention Characteristics; Outcomes; Social Processes; and Sport Psychologist. Participants acknowledged their initial resistance to working with a female sport psychologist, based on gender stereotypes and fears of being negatively perceived by other members of the team. Issues around physical attraction, the degree to which a female could be seen as knowledgeable in the sport and social hierarchies helped the team redefine what actions were considered acceptable. Participants developed an understanding of how sport psychology could help them achieve their athletic goals and talked about the establishment of trust. They also discussed many ways in which they felt that sport psychology had unexpectedly contributed to their lives within and beyond sport; for example, many felt more connected with their teammates after attending team talks. Finally, most participants believed that the most significant outcome of working with a sport psychologist was that of gaining a friend and positive support.Item Social cognitive predictors of Mexican American college students' academic and life satisfaction(University of Missouri--Columbia, 2009) Ojeda, Lizette, 1981-; Flores, Lisa Y. (Lisa Yvonne), 1969-This study used Lent's (2004) social cognitive model of well-being to examine the academic and life satisfaction of 460 Mexican American college students. A model demonstrated that positive affect, acculturation, college self-efficacy, college outcome expectations, and academic goals predicted academic satisfaction and life satisfaction. Specifically, positive affect had a significant positive relation to all variables measured in the model. Further, acculturation predicted college self-efficacy, college outcome expectations, and academic goals but not academic satisfaction. In addition, college self-efficacy predicted college outcome expectations, academic goals, academic satisfaction, and life satisfaction. College outcome expectations predicted academic satisfaction but not academic goals. Academic goals predicated academic satisfaction and life satisfaction while academic satisfaction predicted life satisfaction. Implications of the study and suggestions for future research are discussed.
