Current approaches to the treatment of ovarian cancer are limited because of the development of resistance to chemotherapy. Prohibitin (Phb1) is a possible candidate protein that contributes to development of drug resistance, which could be targeted in neoplastic cells. Phb1 is a highly conserved protein that is associated with a block in the G0/G1 phase of the cell cycle and also with cell survival. Our study was designed to determine the role of Phb1 in regulating cellular growth and apoptosis in ovarian cancer cells. Our results showed that Phb1 content is differentially overexpressed in papillary serous ovarian carcinoma and endometrioid ovarian adenocarcinoma when compared to normal ovarian epithelium and was inversely related to Ki67 expression. Immunofluorescence microscopy and Western analyses revealed that Phb1 is primarily associated with the mitochondria in ovarian cancer cells. Overexpression of Phb1 by adenoviral Phb1 infection resulted in an increase in the percentage of ovarian cancer cells accumulating at G0/G1 phase of the cell cycle. Treatment of ovarian cancer cells with staurosporine (STS) induced apoptosis in a time-dependent manner. Phb1 over-expression induced cellular resistance to STS via the intrinsic apoptotic pathway. In contrast, silencing of Phb1 expression by adenoviral small interfering RNA (siRNA) sensitized ovarian cancer cells to STS-induce apoptosis. Taken together, these results suggest that Phb1 induces block at G0/G1 phase of the cell cycle and promotes survival of cancer cells. Furthermore, silencing of the Phb1 gene expression may prove to be a valuable therapeutic approach for chemoresistant ovarian cancer by increasing sensitivity of cancer cells to apoptosis. ' 2008 Wiley-Liss, Inc.Key words: prohibitin; mitochondria; adenovirus; ovarian cancer; gene silencing Epithelial cancer of the ovary is the leading cause of death from gynecological malignancy worldwide and the sixth most common cancer in women with an incidence of~1 in 70 women in the developed world. A key feature of ovarian and other cancer is the uncontrolled proliferation, invasion and metastasis of cancer cells that overrides naturally occurring programmed cell death or apoptosis. Therefore, studies on the mechanisms that mediate or regulate apoptosis in cancer cells are likely to provide innovative strategies for developing novel chemotherapeutic or immunotherapeutic agents. Although significant improvements have been achieved in the treatment of ovarian carcinoma over the past decade, these successes have been limited because of the development of resistance to chemotherapy. Consequently, most women will ultimately die of the disease. Novel approaches that effectively target the mechanisms leading to the development of chemoresistance in these tumors will limit the toxicity to normal cells and reduce the dosage and duration of therapy.Prohibitin (Phb1) is a possible therapeutic target for drug resistant neoplastic cells. In humans, the prohibitin gene PHB1 is located on chromosome 17q21 close to the ovar...
Pain severity and pain interference only partially mediated SWB. Gender and race were associated with lower vocational SWB. Future research should assess potential explanations for this disparity.
In 2015, data released by the Association of American Medical Colleges (AAMC) showed that there were more Black men applying and matriculating to medical school in 1978 than 2014. The representation of Black men in medicine is a troubling workforce issue that was identified by the National Academies of Sciences, Engineering, and Medicine as a national crisis. While premedical pathway programs have contributed to increased workforce diversity, alone they are insufficient to accelerate change. In response, the AAMC and the National Medical Association launched a new initiative in August 2020, the Action Collaborative for Black Men in Medicine, to address the systems factors that influence the trajectory to medicine for Black men. The authors provide a brief overview of the educational experiences of Black boys and men in the United States and, as members of the Action Collaborative, describe their early work. Using research, data, and collective lived experiences, the Action Collaborative members identified premedical and academic medicine systems factors that represented opportunities for change. The premedical factors include financing and funding, information access, pre-health advisors, the Medical College Admission Test, support systems, foundational academics, and alternative career paths. The academic medicine factors include early identification, medical school recruitment and admissions, and leadership accountability. The authors offer several points of intervention along the medical education continuum, starting as early as elementary school through medical school matriculation, for institutional leaders to address these factors as part of their diversity strategy. The authors also present the Action Collaborative’s process for leveraging collective impact to build an equity-minded action agenda focused on Black men. They describe their initial focus on pre-health advising and leadership accountability and next steps to develop an action agenda. Collective impact and coalition building will facilitate active, broad engagement of partners across sectors to advance long-term systems change.
OBJECTIVE: The purpose of this study is to identify whether protective and risk health behaviors are more common among African Americans with spinal cord injury (SCI) compared with African Americans in the general population. METHODS: Mail-in surveys were collected from 252 adult participants with SCI. Behavioral Risk Factor Surveillance System data from 2009 was downloaded. RESULTS: Participants with SCI were more likely to report currently smoking. Among those who reported currently smoking, persons with SCI were less likely to report ever trying to quit. Those with SCI were also more likely to report consuming alcohol and binge drinking in the past month. Participants with SCI were more likely to receive a flu shot/spray in the past year and to have ever received a pneumonia vaccine. Conversely, those with SCI were less likely to report ever having their blood cholesterol checked. CONCLUSIONS: Results of this study suggest that, consistent with previous research, individuals with SCI focused their preventive health behaviors on conditions consistent with SCI prophylactic standard of care (e.g., flu shots and pneumonia vaccines), as compared to behaviors intended to prevent chronic diseases consistent with the overall population.
Background: Ovarian cancer and ovarian related diseases affect reproductive health. Therapeutic molecules are needed to improve treatment outcomes and overcome drug resistance. The benzimidazole-based sulphonamide LLW-3-6 has both anti-apoptotic and anti-proliferative effects when used to treat prostate, breast, and brain cancer cells. Objective: The study described herein evaluates the anti-proliferative and anti-migratory effects of LLW-3-6 SKOV-3 ovarian cystadenocarcinoma cell line. Methods: Studies were conducted using SKOV-3 cells treated with LLW-3-6. The cell line was propagated and proliferative activity was evaluated by hemocytometric and MTT colorimetric assays. Cellular apoptosis was assessed using Caspase-3 spectrophotometric analysis. Lastly, a scratch wound assay was conducted in a dose and time-dependent manner to assess the effect of LLW-3-6 on migration. Results & Conclusion: Proliferative studies suggest, SKOV-3 cells exposed to LLW-3-6 in culture resulted in decreased growth and proliferation of cells in a time and dose-dependent manner. The apoptotic effect of this agent was noted with the confirmed presence of Caspase-3 in a dose and time-dependent manner as well. Preliminary studies also suggest an anti-migratory effect of LLW-3-6, confirmed by scratch wound analysis. LLW-3-6 is potentially a chemotherapeutic option for decreasing proliferation and inducing apoptosis in ovarian carcinomas. Additional biological analysis are ongoing to further assess the utility of the molecule and its mechanism of action.
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