Sunthesis of ovarian steroids in vivo in women with mammary cancer.
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Biomedical subjects
Publications and source records attributed to N Deshpande.
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Tissues from human benign prostatic hyperplasia [BPH] were collected from twelve patients undergoing routine transurethral resection of the prostate to relieve urine out-flow obstruction. Viable epithelial organoids were obtained after enzymatic digestion of the tissue. Primary cultures of epithelium were successfully maintained on collagen gel for up to 21 days. Immunocytochemical staining revealed that there was no expression of either desmin or vimentin in these cells; however, the anticytokeratin antibodies LP-34 (cytokeratins 4, 5, 6, 10, 13, 16, 17 and 18), LE-61 (cytokeratin 18) and CAM 5.2 (cytokeratins 7 and 8) all showed positive responses, indicating the epithelial nature of the cells. Cell growth was significantly increased in the presence of 3 x 10(-10) M testosterone propionate [TP] in the culture medium. The presence of the non-steroidal anti-androgens, Flutamide and Hydroxy-Flutamide [Flu-OH], in the concentration range 1.0-0.001 micrograms per ml of medium inhibited the growth in the presence of androgens in a dose-dependent manner. The anti-androgens failed to affect cell growth in the absence of TP. In view of these preliminary findings, it is postulated that the antiandrogens might be acting either by displacing the androgen from its receptor or alternately by inhibiting the activity of prostatic 5 alpha-reductase.
The efficacy of the addition of prednisolone to tamoxifen as adjuvants to mastectomy in patients with primary breast cancer who were at a high risk of recurrence was investigated in a randomized trial. Primary carcinomas were collected from a series of 169 patients with loco-regional disease, undergoing mastectomy. The activities of alpha-glycerolphosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the carcinomas were estimated biochemically and the ratio of the two enzymes was used to as the parameter to determine the risk of recurrence. 116 patients with a high risk of recurrence within five years of mastectomy were then randomized to either tamoxifen (2x20 mg/day) or tamoxifen+prednisolone (3x2.5 mg/per day) until recurrence. The patients are currently followed quarterly. The data were analysed at a median follow-up of 26 months (range 7-62 months). The probabilities of both disease-free and overall survival were not significantly different in either arm of the trial, indicating that there is no advantage in combining prednisolone with the antioestrogen. Recently, similar findings in terms of response have been reported for patients with metastatic disease treated with the same combination, raising doubts over the role of prednisolone in the management of patients with endocrine treatments.