MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases

background: Tamoxifen has anti-oestrogenic and anti-tumour activity in the breast, but is oestrogenic and carcinogenic in the endometrium. It can induce experimental tumours by both hormonal and DNA-damaging mechanisms, but its carcinogenic mode of action in human endometrium remains unclear. methods: We investigated whether an epigenetic mechanism, involving promoter hypermethylation of the gene for the DNA repair enzyme MGMT (O6-methylguanine DNA methyltransferase), was associated with K-RAS, TP53 and PTEN mutations in endometrial tumours from women treated with tamoxifen (TAM, n=30) or unexposed to the drug (EC, n=38). results: There were significant (PA, occurred in small numbers in both groups. TP53 mutations were of mainly A>G, C>T and indel modifications in both groups, but more frequent in TAM cases. PTEN mutations dominated in EC tumours and were of the type that has large impact on protein function, such as indel or nonsense mutations. These observations alongside the mutational spectrum in PTEN suggest that the malignancies arise from different backgrounds, hence pointing to an effect of tamoxifen. Both groups displayed MGMT promoter hypermethylation. This coincided with mutations more frequently in the TAM (78%) than in the EC (50%) group, even though there were significantly (P<0.05) fewer mutations and methylations in TAM cases. conclusions: Although the difference in coincidence did not reach significance with the current sample size, the findings suggest that epigenetic processes may play a role in the way tamoxifen induces endometrial cancer

Development of a computer assisted instruction program for use in teaching basic mathematics to graduate students

The mathematical knowledge needed for the successful completion of the Navy Management program at the Postgraduate School is greater than that initially possessed by many of the officers assigned. Due primarily to a lack of time, the lecture-type review course currently offered to correct this situation has been only partially successful. More individualized instruction would be beneficial to all students involved; this could be realized in the given time period by the use of programmed instruction in general and computer-assisted in particular. It was directed toward an attempt to determine the feasibility of utilizing computer assisted instruction at this school. Specifically, the study developed a programmed instruction course in arithmetic and geometric progressions to be used with the IBM Computer Assisted Instruction System currently installed at the school. The course is designed to be used, after extensive testing and revising, in a feasibility study to determine if this method of instruction is superior to the lecture method of teaching basic mathematics to graduate students in the Navy Management Program. This paper is an extensive report of the research conducted, the techniques adopted and the procedures followed in developing the programmed instruction course in progressions. It is intended to be beneficial both to an academic administrator and program authors interested in computer assisted instruction.http://www.archive.org/details/developmentofcom00bainLieutenant, United States Navy .Commander, United States Navy .Lieutenant, United States NavyLieutenant, United States Coast GuardApproved for public release; distribution is unlimited