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At least 235 records · Page 13Linked to original sources
PubMed1980

Effects of diethylstilbestrol and estramustine phosphate on serum sex hormone binding globulin and testosterone levels in prostate cancer patients.

Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (less than 50 and more than 65 years old) and in 7 groups of prostatic cancer patients treated with various endocrine manipulation procedures, including orchiectomy, and estramustine phosphate and diethylstibestrol therapy. There were 133 individuals studied. Total serum testosterone levels were significantly higher in the younger versus the older control group and testosterone-estradiol binding globulin levels were significantly higher in the older men. Whereas orchiectomy reduced serum testosterone to low concentrations (72 plus or minus 11 ng. per 100 ml.) testosterone-estradiol binding globulin levels were not altered. In contrast, estramustine phosphate and diethylstilbestrol therapy, when administered to intact or castrated patients, resulted in depressed testosterone and markedly elevated testosterone-estradiol binding globulin serum levels, particularly in those patients receiving estramustine phosphate (less than 35 ng. per 100 ml. and more than 6 micrograms per 100 ml., respectively). These studies led to the conclusion that diethylstilbestrol or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting a concomitant elevation of testosterone-estradiol binding globulin and a depression of total testosterone. Even though free serum testosterone was not measured in the present study the law of mass action would indicate that in those patients with high testosterone-estradiol binding globulin (more than 5 microgram. per 100 ml.) and low total testosterone levels (less than 80 ng. per 100 ml.) the availability of biologically active (unbound steroid) testosterone would be negligible.

Adult↗
PubMed1982

Toxicity, interstrand cross-links and DNA fragmentation induced by 'activated' cyclophosphamide in yeast: comparative studies on 4-hydroperoxy-cyclophosphamide, its monofunctional analogon, acrolein, phosphoramide mustard, and nor-nitrogen mustard.

Activated cyclophosphamide (CP) is known to achieve its cytotoxic and alkylating capacity upon spontaneous hydrolytic breakdown of the oxazaphosphorine ring structure. Treatment of yeast cells with the chemically activated form of CP (4-hydroperoxy-CP, 4-OOH-CP) and with several potentially toxic cleavage products revealed that cytotoxicity is closely linked to the formation of DNA interstrand cross-links and to DNA fragmentation. While this holds true for 4-OOH-CP and its bifunctional alkylating breakdown products, phosphoramide mustard (PM) and nor-nitrogen mustard (NNM), equimolar concentrations of acrolein and the monofunctional analogon of activated CP were inactive. NNM, the ultimate cleavage product within the successive degradation of the oxazaphosphorine structure was five times more toxic than 4-OOH-CP, whereas the cytotoxic action of PM was only slightly enhanced. The high cytotoxicity of NNM was matched by its ability to induce DNA interstrand cross-links: at concentrations and treatment times producing equal cell killing, 4-OOH-CP and NNM produced the same extent of cross-linking and DNA fragmentation. Biochemical potency of NNM is in contrast to data found with the NBP colorimetric assay which suggest that NNM loses its alkylating activity at neutral pH. 4-OOH-CP and PM are much more stable than predicted from half-life measurements performed via the NBP colorimetric assay: they retain a considerable fraction of their cytotoxic and cross-linking activity in spite of a 12-h preincubation at pH 7 and 36 degrees C.

Acrolein↗