Although p16 is seldom mutated in ovarian tumors, the overexpression of p16 in most ovarian tumor cases indicates a dysfunction in the regulatory complex for G1 arrest. Therefore, overexpression of p16 may be an important early event in the neoplastic transformation of the ovarian epithelium.
SinaryWe have investigated the effects on breast cancer cell growth of 4-hydroxytamoxifen (4OHT), a conventional antioestrogen with agonist activity, and 7m- [9-(4,4,5,5,5-pentafluoropentyhlulphinyl)
p53 is an important tumor suppressor gene which is activated in response to DNA damage. The induced expression of p53 causes either cell cycle G1 arrest or apoptosis. The recently cloned p21 gene (WAF1/CIP1/SDI1) is known to be directly activated by wild‐type but not mutant p53 and can suppress the growth of human cells in G1 by inhibiting the activity of cyclin‐dependent kinases (CDKs). As p21 is activated by p53 and is a negative regulator of the cell cycle, it is possible that p21 could be a sensitive marker to monitor p53 function. To investigate the mRNA expression level and mutation status of p53 and p21 genes, quantitative polymerase chain reaction (PCR) and direct cDNA sequence analysis were performed. mRNA expression levels of p53 and p21 genes relative to the β‐tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potentials (LMPs), two benigns) and six normal ovaries. Of 13 ovarian tumors with p21 underexpression, nine p53 mutated cases (69%) and one polymorphism case were found. Among nine p53 mutated cases, three cases showed p53 overexpression, another three cases showed p53 underexpression and a further three cases showed normal expression of p53. These findings suggest that mRNA underexpression of p21 may be a more useful indicator of p53 dysfunction than mRNA expression of p53.
Objective: To report on the sentiments of the Australian health and medical research (HMR) workforce on issues related to employment and funding opportunities.
Design, setting and participants: In August 2006, the Australian Society for Medical Research (ASMR) invited all of its members to participate in an online survey. The survey took the form of a structured questionnaire that focused on career aspirations, career development and training opportunities, attitudes toward moving overseas to work, and employment conditions for medical researchers.
Main outcome measures: Researchers’ views on career opportunities, funding opportunities, salary and quality of the working environment; impact of these views on retaining a skilled medical research workforce in Australia.
Results: Of the 1258 ASMR members, 379 responded (30% response rate). Ninety‐six per cent of respondents were currently based in Australia; 70% had a PhD or equivalent; and 58% were women. Most respondents worked at hospital research centres (37%), independent research institutes (28%) or university departments (24%). Sixty‐nine per cent had funding from the National Health and Medical Research Council, with the remainder funded by other sources. Over the previous 5 years, 6% of respondents had left active research and 73% had considered leaving. Factors influencing decisions about whether to leave HMR included shortage of funding (91%), lack of career development opportunities (78%) and poor financial rewards (72%). Fifty‐seven per cent of respondents were directly supported by grants or fellowships, with only 16% not reliant on grants for their continuing employment; 62% believed that funding had increased over the previous 5 years, yet only 30% perceived an increase in employment opportunities in HMR. Among the respondents, twice as many men as women held postgraduate qualifications and earned ≥ $100 000 a year.
Conclusions: Employment insecurity and lack of funding are a cause of considerable anxiety among Australian health and medical researchers. This may have important implications for the recruitment and retention of researchers.
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