Sex-Related Alcohol Expectancies, Alcohol Consumption, and Risky Sexual Behavior Among African American College Women

African American college women are experiencing sex-related negative consequences (e.g., contracting sexually transmitted diseases or human immunodeficiency virus, having an unplanned pregnancy) at disproportionate rates in comparison to Caucasian college women. Furthermore, African American college women are likely engaging in risky sexual behaviors (e.g., unprotected anal, vaginal, oral sex) that may be placing them at a greater risk for experiencing sex-related negative consequences. Research suggests that increased alcohol consumption is predictive of more risky sexual behavior among college women. Additionally, sex-related alcohol expectancies, or beliefs about the effects of alcohol on sexual behavior, are positively associated with increased alcohol consumption and risky sexual behavior and therefore, may attenuate the association alcohol use has with risky sexual behaviors among African American college women. Because of the underrepresentation of African American college women in research examining the aforementioned factors, the purpose of the present study was to examine the link between sex-related alcohol expectancies (i.e., enhancement, sexual risk taking, disinhibition), alcohol consumption, and risky sexual behaviors exclusively among a sample of African American college women at a mid-sized Southern university. Multiple and hierarchical linear regression analyses yielded the following results: (a) enhancement sex-related alcohol expectancies predicted increased risky sexual behavior, (b) sex-related alcohol expectancies did not predict increased alcohol consumption and (c) did not moderate the relationship between alcohol consumption and risky sexual behaviors. Clinical and research implications will be discussed

Gendered Racism and Risky Sexual Behavior Among African American College Women: A Moderated Mediation Study of Psychological Distress, Alcohol Use, Safe Sex Practices, and Alcohol Protective Behavioral Strategies

Investigation of the effects of gender racism (i.e., discrimination based on race and gender) among African American college women is limited, which is concerning considering the impact this specific type of discrimination may have on mental health and coping behaviors among African American college women. African American students who have experienced racial discrimination and college women who have experienced sexual discrimination experience increased levels of psychological distress (i.e., symptoms of depression and anxiety). Further, harmful alcohol use is a common coping strategy for psychological distress among college students and has been linked to increased risky sexual behavior among African American college women. The present study explored the relationship between experiences of gendered racism, psychological distress, harmful alcohol use, and risky sexual behavior among African American college women at a mid-sized, Southern, and predominantly White institution. Additionally, the present study investigated factors associated with less harmful alcohol use and risky sexual behavior among AACW, specifically the moderating effects of alcohol protective behavioral strategies (PBS-A) and safe sex practices. Psychological distress and harmful alcohol use did not sequentially mediate the relationship between gendered racism and risky sexual behavior; however, symptoms of anxiety and harmful alcohol use uniquely mediated the relationship between gendered racism and risky sexual behavior. PBS-A and safe sex practices did not moderate the predicted sequential relationship. Clinical and research implications will be discussed

The Role of miR-21 and miR-31 in Cellular Responses Mediated by TGF-β: A Dissertation

The function of transforming growth factor β (TGF-β) in cancer is notoriously complex. Initially TGF-β limits tumorigenesis, but at later stages in tumor progression TGF-β promotes the malignant spread of tumor cells. Past studies to understand the pro-metastasis utility of TGF-β centered upon its ability to regulate protein-coding genes. Recently, a small class of non-coding RNAs known as microRNAs (miRNAs) emerged as novel posttranscriptional regulators of gene expression. The significance of miRNA function in cellular processes from embryonic development to the maintenance of homeostasis in adult tissues is becoming increasingly clear. Also apparent is the strong association between aberrant miRNA expression and human diseases, such as cancer. The contribution of miRNAs to TGF-β-mediated cellular responses remains an open question. Thus, I became interested if miRNAs offered an additional layer of regulation in TGF-β signaling through which this cytokine exerts its pro-metastasis function. To address this inquiry, in the first part of this dissertation I investigated whether miRNAs influenced the ability of TGF-β to induce cellular responses directly involved with carcinoma metastasis, such as epithelial-mesenchymal transition (EMT). Here, I identified two miRNAs, miR-21 and miR-31, that are upregulated during EMT in LIM 1863 organoids, a colon carcinoma model of EMT driven by TGF-β. We performed in vitro studies to characterize the function of miR-21 and miR-31 and found that these two miRNAs positively impact the induction of EMT, migration and invasion by TGF-β. Furthermore, we uncovered TIAM1 (T lymphoma and metastasis gene 1) as a novel target of both miR-21 and miR-31 and show that downregulation of TIAM1 is critical for the pro-migration and pro-invasion activities of miR-21 and miR-31. Together these findings reveal miR-21 and miR-31 as downstream effectors of TGF-β signaling by facilitating EMT, migration and invasion of colon carcinoma cells. How TGF-β regulates miR-21 and miR-31 became important questions and thus the focus of the second part of this thesis. Interestingly, I found that TGF-β and TNF-α synergize to increase miR-21 and miR-31 levels in LIM 1863 organoids and that the synthesis of new factors induced by TGF-β/TNF-α are required for this upregulation. Moreover, I report that regulation of miR-21 by TGF-β/TNF-α occurs at multiple levels of biogenesis. More specifically data provided here show that Smad4 binds to the promoter of miR-21 to upregulate its expression thereby specifying miR-21 as a typical TGF-β target gene. This mechanism is different from one recently observed in smooth muscle cells in which TGF-β did not stimulate miR-21 transcription, but interestingly, Smad4 enhanced the Drosha-mediated processing of the miR-21 precursor. These two mechanisms suggest that TGF-β regulation of miR-21 is contextual and highlight the complexity of TGF-β signaling. As a whole, my findings establish important roles for miR-21 and miR-31 in TGF-β-mediated cellular responses that facilitate the pro-metastasis utility of TGF-β in colon cancer. Also, I describe a novel mechanism by which TGF-β/TNF-α signaling elevates the level of miR-21 and miR-31. Future studies that identify additional targets of miR-21 and miR-31 may offer further insight into the molecular mechanisms underlying cellular regulation by TGF-β. This information will be vital for the design of therapeutic interventions for colon cancer patients

MicroRNA profiles discriminate among colon cancer metastasis

MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor

Harmful Alcohol Use and Alcohol-Related Sex Expectancies as Predictors of Risky Sex Among African American Female College Drinkers

African American college women are experiencing sex-related negative consequences at alarming rates. Alcohol use and alcohol-related sex expectancies are predictors of risky sexual behavior among college women; however, African American college women are often underrepresented in empirical studies. The purpose of the present study was to examine the link between alcohol-related sex expectancies (i.e., enhancement, sexual risk taking, and disinhibition expectancies), alcohol use, and risky sexual behavior among a sample of 222 sexually active African American female college drinkers. Participants completed measures assessing alcohol-related sex expectancies, typical weekly drinking, harmful alcohol use, and risky sexual behavior. Results indicated that combined sexual risk taking and disinhibition alcohol-related sex expectancies predicted both typical weekly drinking and harmful alcohol use. In addition, enhancement alcohol-related sex expectancies and harmful alcohol use predicted risky sexual behavior; however, typical weekly drinking did not. Clinical and research implications are discussed

MicroRNAs in colorectal cancer metastasis

Contains fulltext : 97112.pdf (publisher's version ) (Closed access)Metastatic disease is the major cause of death in colorectal cancer (CRC) patients. The metastatic process is highly inefficient and comprises multiple sequential steps. While many genetic factors relevant in this process have already been identified, the epigenetic factors underlying each step still remain obscure. MicroRNAs (miRNAs) are key regulators in tumourigenesis, but their role in the development of cancer metastasis is poorly investigated. The majority of miRNAs involved in the metastatic process have been identified in breast cancer cell lines, and in CRC less data are available. We review the role of miRNAs in the metastatic pathway of CRC, including escape of apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis, and invasion. Better understanding of the complex role of miRNAs in the development of CRC metastases may provide new insights that could be of therapeutic consequence