Search PubMed⌕ Search

Biomedical subjects

N Kadohama

Publications and source records attributed to N Kadohama.

32 records · Page 2Linked to original sources

5alpha-Reductase as a target enzyme for anti-prostatic drugs in organ culture.

Short-term organ culture of rat and human prostatic tissues has been utilized as a means of testing drlgs potentially useful in cancer of the prostate. Optimal conditions, particularly the concentration of T, have been established for organ culture of such tissues and the effects of various drugs on 5alpha-reductase activity (5alpha-RA) have been utilized as a means of ascertaining antiprostatic actions of the various compounds and drugs tested. Thus, it was shown that estracyt, estradiol-17beta, progesterone, and novel steroids and steroid-conjugates have definite effects on 5alpha-RA in this system.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Some new approaches to potential test systems for drugs against prostatic cancer.

We have previously reported on test systems, based on 5alpha-reductase (5alpha-RA) and arginase activities and steroid deposition in animal prostates, potentially useful in screening drugs possibly effective in cancer of the prostate. Recently, we have concentrated on the development of other in vivo and in vitro systems which may prove of further value in testing such drugs. These systems include the following: (a) The effects of drugs on 5alpha-RA activity in human and animal non-malignant and human cancerous prostatic tissues in organ culture. The parameters necessary for the maintenance of optimal 5alpha-RA in such explants have been determined, and it has been shown that certain agents (estramustine phosphate, progesterone, estradiol-17beta) can inhibit 5alpha-RA under in vitro conditions, pointing to the potential use of such an approach in screening various cytostatic agents. In addition, 65Zn deposition, the histology, and the androgen metabolism in such tissues in organ culture are being determined as additional parameters. (b) The deposition of 65Zn in the rat dorsolateral gland, particularly as affected by prolactin and testosterone, and the effects of chemotherapeutic agents on such deposition. Methotrexate and CCNU have been shown to be potent inhibitors of 65Zn deposition in the dorsolateral gland. The parameters related to zinc metabolism in the prostate are being further investigated. (c) The demonstration of receptors for estrogens (estradiol-17beta, diethylstilbestrol) in the prostate of the baboon. The various parameters related to the specificity of such receptors have been established. The development and standardization of these approaches, some facets of which are reported in the present publication, may prove them to be more sensitive, specific, and optimal than other systems and should afford an opportunity to test various combinations of drugs potentially useful in cancer of the prostate with relative speed, efficacy, and ease of manipulation.

Adrenalectomy↗