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At least 109 records · Page 6Linked 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↗
PubMed2003

A new approach for evaluating in vivo anti-leukemic activity using the SCE assay. An application on three newly synthesised anti-tumour steroidal esters.

Three newly synthesised steroidal esteric derivatives of nitrogen mustard (compounds 1-3) were comparatively studied on a molar basis regarding their ability to induce sister chromatid exchanges (SCEs) in normal human lymphocytes in vitro and therapeutic effects on leukemia P388 bearing mice. Compounds 1 and 3 are modified steroidal esters of p-methyl-m-N,N-bis(2-chloroethyl)amino benzoic acid, and compound 2 is a modified steroidal ester of chlorambucil. All compounds induced statistically significant increases in SCEs and decreases in proliferation rate indices (PRIs) of cultured human lymphocytes and significantly increased the life span of P388 bearing mice. In this study, the doses applied for therapeutic purposes upon leukemia P388 bearing mice in vivo were derived from cytogenetic observations in normal human lymphocytes in vitro. A substantially better therapeutic effect was obtained compared to the effect achieved after the use of quite higher doses related with LD(10) values. We have demonstrated that the order of anti-tumour effectiveness of the treatment schedules of the three newly synthesised compounds tested (at doses derived from cytogenetic observations) coincides with the order of the cytogenetic effects they induce. The SCE assay appears to have an application in the clinical prediction of tumour sensitivity to potential chemotherapeutics.

Animals↗
PubMed2000

Role of DNA minor groove alkylation and DNA cross-linking in the cytotoxicity of polybenzamide mustards.

Interstrand DNA cross-links have been considered essential to the activity of current clinical DNA-alkylating antitumour drugs, which generally alkylate in the major groove. However, the relationship between cross-linking adducts located in the minor groove of DNA with cytotoxicity and antitumour activity has not been extensively investigated. Previous studies have shown that cross-linking ability is not correlated with cytotoxicity in a novel series of polybenzamide-linked nitrogen mustard compounds which alkylate DNA at adenines in the minor groove. In the present study the nature of these cross-linking adducts was explored for a related pair of compounds which are both highly effective cross-linkers but which differ in antitumour potential. Both of these drugs effectively interact with adenines in the minor groove, although their sequence specificity differs. However, the cross-linking event was not inhibited by pre-treatment with Hoechst 33258, although this pre-treatment effectively prevented adenine alkylation. The primary cross-links detected may thus represent guanine N7 alkylations in the major groove. Whether minor groove cross-linking adducts can be formed is uncertain, since the effect of background guanine N7 alkylation may complicate analysis. The cytotoxicity of the polybenzamides may therefore be related to other factors such as their interaction with cellular repair systems.

Adenine↗
PubMed1976

[The influence of the N-mustard derivative "cytostasan" on pregnancy and fetal development in the rat].

This presentation describes the action of Cytostasan, a nitrogen mustard compound of benzimidazole, on reproduction and embryonic development of Wistar rats. Single doses from 20 through 100 mg/kg body weight were given intraperitoneally on the 4th, 7th, 9th, 11th or 13th day post coitum. All test animals were sacrificed on the 20th day of pregnancy. The following parameters served as a base for evaluation: the means of implantation rates, resorption rates, fetal body weights and the number of dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by means of the razor blade technique for malformations of organs and by alizarin preparations for detecting anomalies of the osseuos skeleton. All results were compared with those of an untreated control group and evaluated by statistical means. Cytostasan exerts embryotoxic and teratogenic effects in appropriate dosage. Notwithstanding the fact of giving high doses (1/2 LD 50) there is no loss of blastocysts before implantation: the number of implantation sites equals that of the control group. The resorption rate increases at all examined days of development after application of 40 mg/kg, but 20 mg/kg exert effects only on days 4, 7, and 11 p. c. There is no action on the number of living fetuses after injection of 20 mg Cytostasan/kg body weight. After application of 40 mg/kg the number of living fetuses decreases especially on the 7th, 9th, and 13th day p. c. There is a dose-dependent stunting: the fetal body weight is not reduced after a dosage of 20 mg/kg, but 40 mg/kg cause a considerable loss of weight during embryogenesis (days 9, 11, 13). It is impossible to induce stunting during blastogenesis (days 4 and 7). The observed patterns of malformation are relatively uniform: kinked tails, omphaloceles, hydronephroses, hydrocephali. Skeletal defects are absent. The results received are compared with other findings on aklylating antitumour drugs.

Abnormalities, Drug-Induced↗