Evaluation of endometrial changes and p53 expression in tamoxifen treated women: Comparision of various methods.

Objective: To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial aspiration (EA) and p53 expression in assessing endometrial abnormalities in women on tamoxifen. Methods: In a cross sectional study of 50 pre- and post-menopausal women receiving tamoxifen for > 2 years, all participants underwent TVS and EA. Those with endometrial thickness > 4 mm on TVS underwent hysteroscopy and SHG. Serum p53 antibody and p53 immunohistochemistry were tested in all women. Results: The sensitivity and specificity when compared with histopathology as the reference standard were as follows: TVS 100% and 33.3%, SHG 85.7% and 50%, hysteroscopy 92.8% and 80.8%, serum p53 50% and 83.3%, and p53 immunohistochemistry 57.1% and 61.1%. Prevalence of endometrial abnormalities was not significantly different in asymptomatic and symptomatic women. Conclusion: Tamoxifen-users require routine testing for endometrial evaluation. TVS followed by hysteroscopy and biopsy is an effective option. p53 expression correlates with histological abnormalities. Key words: Tamoxifen, Sonography, Sonohysterography, Hysteroscopy, Endometrium, p53.     

Synthesis and cytotoxic studies of hydroximino derivatives of some 16E-arylidenosteroids

Oxime and dioxime derivatives of various 16E-arylidenosteroids in the androstene series have been prepared and evaluated at the National Cancer Institute (NCI), Bethesda (USA) for their antineoplastic activity against various tumor cell lines in order to determine the structural requirements for cytotoxic activity. Aldol condensation of dehydroepiandrosterone (DHA) and DHA acetate with various aldehydes followed by treatment with hydroxylamine hydrochloride resulted in the formation of 16E-arylidenosteroid-oxime system. Oximes 15, 16 and compound 20 with a higher degree of oxidation in ring A have been found active in a 60 cell line antitumor prescreen by virtue of their cytotoxic effect against one or more tumor cell line and were further referred for in vivo hollow fiber bioassay. These compounds showed interesting intraperitoneal and subcutaneous scores in the in vivo hollow fiber bioassay and have been referred to the Biological Evaluation Committee for Cancer Drugs for further detailed in vivo testing.     

Synthesis and evaluation of a dimer of 2-(4-pyridylmethyl)-1-indanone as a novel nonsteroidal aromatase inhibitor

A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.