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Biomedical subjects

B R Rao

Publications and source records attributed to B R Rao.

At least 73 records · Page 4Linked to original sources
PubMed1988

Efficacy and advantages in the use of low doses of Anandron and estrogen combination in the treatment of prostate cancer.

Treatment effects of RU 23908 antiandrogen (Anandron) and estrogen in low doses on hormone-dependent rat prostatic adenocarcinoma (R3327-H) were investigated. Tumor-bearing Copenhagen rats were treated for 6 weeks with 8 micrograms Anandron and 1 microgram estradiol-17 beta every two days. Reduction and counteraction of androgen synthesis and action was established by an observed decline in serum testosterone level and by changes in both histology and weight of androgen target organs. Prostate tumor growth rate was significantly retarded in rats treated with Anandron/Estradiol combination compared to untreated intact control and was equal to the slow growth rate in castrate tumor-bearing animals. Tumor histology changes during treatment correlated with the observed growth rate retardation. Areas of necrosis, metaplasia, and acellularity were more frequently observed in tumors of Anandron/Estradiol-treated compared to castrated rats. These results suggest that low doses of Anandron and estrogen can effectively be combined as a complete androgen counteracting therapy for hormone-dependent prostatic carcinoma with minimal undesired side effects.

Animals↗
PubMed1988

Merits and considerations in the use of anti-androgen.

Anandron administration (300 mg/daily) to 16 human normal genetic male volunteers (who opted for male to female gender transformation) induced clinical signs of feminisation during 8 weeks of treatment. More than 2-fold increase in blood luteinising hormone and testosterone was measured while follicle stimulating hormone remained without any change in the levels. Prolactin showed a slight but significant increase at 8 weeks of treatment. The prostate size measured in 6 subjects using transrectal ultrasonography before and at 8 weeks of anandron treatment showed no change. The prostate size measured in 6 subjects who received androcur (100 mg/daily) in combination with ethinyl estradiol (100 micrograms/daily) for longer than 18 months did not differ compared to pre-treatment size. However, the prostate histology showed a clear predominance of stromal components with a significant reduction in the number of acini. The epithelial cells appeared atrophic. Histology of the testes showed a readily observable reduction in tubular and interstitial cells. The monodispersed cells prepared from the testes consisted of Leydig and non-Leydig cells. These cells responded to stimuli (hCG and Pregnenolone) in terms of an increase in testosterone synthesis in vitro. Anandron treatment of intact mature male rats increased the blood testosterone level. Estrogen administration dramatically reduced the anandron induced increase in testosterone to castration level. The benefits of a combination of low doses of anandron and estrogen for achieving an effective anti-androgenic action are presented.

Animals↗
PubMed1988

Doisynolic-type acids--uterotropically potent estrogens which compete poorly with estradiol for cytosolic estradiol receptors.

Doisynolic acids, a class of seco-steroid acids some of which exhibit greater uterotropic estrogenicity than estradiol-17 beta, are D-ring cleavage products of steroidal estrogens formed by fusion with KOH above 200 degrees C. We have found that electron-transfer reactions between estrone or estradiol and CCl4 or CBrCl3 in KOH-t-BuOH at 25 degrees C rapidly provide 16,16-dichloro- or -dibromodoisynolic acid, respectively, the former approaching estradiol in uterotropic potency. Simple esters from these highly hindered tertiary carboxylic acids, easily prepared via phase-transfer-catalyzed alkylations, also rival estradiol in uterotropic activity. Unlike natural steroidal estrogens or their commonly used artificial equivalents (DES, hexoestrol, ethynylestradiol, etc.) whose uterotropic activity is accompanied by substantial binding affinity for cytosolic estradiol receptors, these highly uterotropic doisynolic-type acids and esters exhibit binding affinities for this receptor of only about 1% that of estradiol-17 beta as determined by the usual competitive binding-inhibition studies with [3H]estradiol. Other highly uterotropic carboxylic acids may exhibit similar characteristics. These unusual results leave open the possibilities that uterotropic seco-steroid and related carboxylic acids undergo some unknown metabolic activation, are exceptionally persistent estrogens, bind to a cytosolic receptor site other than the conventional (type I) estradiol site, or bind directly to type I or type II nuclear receptor sites. At dosages of 1000 times those required for a uterotropic effect, the doisynolic-type acids (24 doses over an 8-week period) were neither toxic nor carcinogenic.

Animals↗
PubMed1987

Pregnancy-related primary brain and spinal tumors.

We reviewed the literature concerning primary brain and spinal tumors with first manifestation or acceleration of symptoms during pregnancy or within the first postpartum week and encountered four new cases in our center. The incidence of brain tumors that become symptomatic during pregnancy appears to be decreased compared with that in age-matched women. The relative frequency of the different primary brain tumor types is not changed by pregnancy. The number of meningiomas gradually tends to increase during pregnancy, with gliomas and spinal vascular tumors accumulating in the first and third trimesters, respectively. Postpartum amelioration of symptoms has especially been described for meningiomas and spinal vascular tumors. We conclude that different types of tumors are influenced at different stages of pregnancy. Although progesterone receptors predominate compared with estrogen receptors, no definite causal relationship with progesterone has been established.

Adult↗
PubMed1987

Renewal timing of long-acting depot luteinizing hormone-releasing hormone agonist (Zoladex) is critical in the treatment of hormone-dependent rat prostatic carcinoma (R3327-H).

The effects of luteinizing hormone-releasing hormone (LHRH) agonist (Zoladex) treatment on hormone-dependent rat prostate adenocarcinoma (R3327-H) were investigated based on changes in tumor volume and histology. Tumor-bearing rats were treated for 10 weeks with Zoladex in depot preparation by implantation every 2, 4, or 6 weeks. Tumor growth rate was similar in the castrated group and in the rats treated every 2 weeks with Zoladex. This growth rate was significantly slower than in animals treated with Zoladex every 6 weeks and the nontreated group. The growth rate in rats treated every 4 weeks appeared to be faster than that in the castrated animals (not significant). Changes in testosterone levels measured during Zoladex treatment correlated with tumor growth kinetics. Zoladex implantation yields effective and complete androgen deprivation only in the rats with two weekly depot renewal regimen. Tumor histology indicated that the stromal as well as the glandular epithelial cells responded to both castration and to Zoladex treatment. However, in tumors from rats treated with Zoladex every 4 and 6 weeks progressive increasing signs of restoration of normal elements, comparable to non-treated tumors were observed. These results strongly suggest that careful attention has to be paid to the timing of LHRH depot renewal in prostate cancer treatment.

Androgens↗
PubMed1987

Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate.

The effect of androgen blockade on the normal human prostate was studied in 16 healthy volunteers opting for male-to-female gender reassignment. Their ages ranged from 19 to 27 years. After 8 weeks of treatment with Anandron, serum hormone levels indicated anti-androgenic action and physical signs of feminization appeared. Prostate volumes (measured by ultrasound) before and following Anandron treatment remained the same. After 18 months of treatment with cyproterone-acetate and ethinyl estradiol, prostate volumes again were not changed. However, histology revealed glandular atrophy and an increase in stromal tissue. The significance of these findings is discussed.

Adult↗
PubMed1987

Development of an in vivo clonogenic cell assay for rat prostate metastatic tumor--R3327-MatLyLu.

The effects of intravenous (iv) inoculation of rat prostate R3327-MatLyLu tumor cells in syngeneic Copenhagen rats have been investigated both qualitatively and quantitatively in order to establish an in vivo clonogenic cell assay. Intravenous injection of tumor cells resulted in formation of tumor nodules only in the lungs. A linear relationship existed between the number of tumor cells injected and the number of measured lung nodules. The distribution patterns of iv injected radiolabelled tumor cells and of non-labelled tumor cells injected in both arterial and venous blood vessels confirmed the major role of the lungs as recipient organ for injected tumor cells. Although a similar distribution pattern was observed after iv injection with radiolabelled fibroblasts, no lung nodules were observed even one year after injection. The sensitivity for measuring drug treatment effects by this in vivo clonogenic cell assay has been compared with that of the in vitro clonogenic cell assay. Information obtained using both in vitro and in vivo clonogenic cell assay will provide a better understanding of efficacy of treatment modalities.

Animals↗
PubMed1987

Androgen receptor predominance in human ovarian carcinoma.

Cytosols of 94 untreated common epithelial ovarian cancer tissues were analysed for the presence of estrogen-, progesterone- and androgen receptors. Androgen receptors clearly predominated (90%) over and above estrogen- (55%) and progesterone receptors (52%). Further characterisation particularly of the androgen receptor revealed steroid-receptor complex with the sedimentation coefficient similar to ovalbumin (3,6 S). Only androgens, natural and synthetic, were able to alter the sedimentation profile. Estrogen appeared to slightly lower the peak, while progesterone and cortisol did not alter the profile at all. No difference in receptor concentrations between tumor tissues from pre-, peri- and postmenopausal women was found. The serum hormone levels (estradiol-17 beta, testosterone, FSH, LH) measured preoperatively in 20 postmenopausal patients did not correlate with the receptor status. Majority of the ovarian carcinomas studied contained androgen receptors. We therefore suggest consideration of the addition of anti-androgens to the therapeutic strategies applicable to ovarian cancer.

Adolescent↗
PubMed1987

Estrogen synthesizing rare malignant Brenner tumor of the ovary with the presence of progesterone and androgen receptors in the absence of estrogen receptors.

A case of a malignant Brenner tumor of a postmenopausal woman presenting with vaginal bleedings is described. Clinical and laboratory findings demonstrated estrogenic secretory function and action. The presence of aromatase activity based on in vitro tumor microsomal metabolism of androgen to estrogen is described. Tumor cytosol contained progestin and androgen binding components in the absence of estrogen binding activity. Estrogen binding activity was undetectable both by biochemical as well as histochemical assays.

Aged↗
PubMed1987

Correlation of multiple steroid receptors with histological type and grade in human ovarian cancer.

One hundred eight human ovarian cancers were analyzed for estrogen (ER), progestin (PgR), and androgen (AR) receptors. The receptor levels were related to histological type and grade of the tumor. There were 103 common epithelial carcinomas subdivided into serous (36), endometrioid (36), mucinous (18), clear cell (5), malignant Brenner (3), mixed epithelial (2), and undifferentiated (3) types. Of the remaining five, four were sex cord-stromal tumors and there was a single case of germ cell tumor. ER was detected in 52%, PgR in 52%, and AR in 91% of the cases. There was no correlation between the presence of ER and AR and the tumor histology. The presence of PgR correlated with the grade of endometrioid carcinoma, while no clear correlation existed for the other tumor types. PgR was absent in the three undifferentiated carcinomas. Interestingly, high PgR levels were detected in the three granulosa cell tumors.

Adenocarcinoma↗
PubMed1987

Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen.

This study evaluated the effects of estrogens and androgens on LH pulse frequency and amplitude in male subjects. To assess the role of estrogens we compared the serum LH pulse frequency and amplitude between 3 groups: 8 agonadal subjects receiving no steroid treatment; 6 agonadal subjects continuously treated with 50 micrograms ethinylestradiol/day; and 17 eugonadal men. Mean serum LH levels and LH pulse amplitude were significantly lower in the agonadal subjects receiving estrogens (14.8 +/- 5.4 (SD) U/L and 4.1 +/- 1.5 U/L, respectively) than in the group of agonadal subjects not receiving sex steroid treatment (35.7 +/- 8.4 U/L and 7.3 +/- 2.0 U/L, respectively). The mean LH pulse frequency was 7.1 +/- 1.5/7 h in the group not receiving sex steroid treatment and 6.0 +/- 1.4/7 h in the group receiving estrogens (P NS). The LH pulse frequency in the eugonadal men (3.8 +/- 1.3/7 h) was significantly lower than the frequency in both groups of agonadal subjects. The LH pulse amplitude was of the same magnitude in the estrogen-treated agonadal subjects and in eugonadal men (4.1 +/- 1.5 U/L and 3.5 +/- 1.2 U/L, respectively). The role of androgens was studied in 15 eugonadal male subjects (who presented for female role reassignment) by determining the effects of a novel nonsteroidal androgen receptor blocker, Anandron, on basal and LH-releasing hormone (LHRH)-stimulated serum LH/FSH levels; LH pulse frequency and amplitude; sex steroid and sex hormone-binding globulin levels; and serum PRL levels during an 8-week period. Basal and LHRH-stimulated LH levels and testosterone rose progressively during the first 6 weeks and reached a plateau thereafter, while estradiol levels continued to increase somewhat. The LH pulse amplitude and frequency had increased after 6 weeks (3.1 +/- 0.6 vs. 4.5 +/- 1.2 U/L and 4.4 +/- 2.4 vs. 6.6 +/- 1.1 pulses/7 h, respectively). Basal FSH levels were not affected while LHRH-stimulated FSH levels progressively decreased from 2 to 6 weeks, after which they did not change. Along with the rise of estradiol levels an increase of sex hormone-binding globulin and PRL levels occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Malignant Brenner tumor. A histologic, morphometrical, immunohistochemical, and ultrastructural study.

The histologic, morphometric, immunohistochemical, and ultrastructural study of a malignant Brenner tumor in a postmenopausal women presenting with vaginal bleeding is described. A comparison with transitional cell carcinomas is made, and the use of morphometry in grading the urothelial-like epithelium in malignant Brenner tumors is suggested. High preoperative urinary estrogen, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and histologically confirmed atypical endometrial hyperplasia suggested a hyperestrogenism. The reduction in urinary estrogen and the increase in serum LH and FSH after tumor removal and the presence of aromatase activity detected in tumor microsomes confirmed that the tumor was synthesizing estrogen. Estrogen receptors were undetectable both by biochemical and histochemical analysis in the tumor.

Adnexa Uteri↗
PubMed1986

Sex hormone receptors in localized and advanced transitional cell carcinoma of urinary tract in humans.

Sex hormone receptors were identified in patients with localized and advanced transitional cell carcinoma of the bladder and kidney. Dihydrotestosterone and testosterone receptors were found most consistently in the specimens analyzed. Estrogen receptors were found less frequently. Androgen receptors in transitional cell carcinoma may prove to be a useful biologic marker in this disease.

Carcinoma, Transitional Cell↗
PubMed1985

Increased dihydrotestosterone receptor levels in high-stage renal adenocarcinoma.

Primary renal adenocarcinoma tissue, metastatic deposits, and normal kidney parenchyma from 16 patients were assayed for sex hormone receptors by dextran-coated charcoal adsorption and sucrose gradient centrifugation techniques. Dihydrotestosterone receptors (DHTR) were found in all renal carcinomatous tissue (20/20) and in 93% (13/14) autologous normal kidneys analyzed. Testosterone receptors were found in 84% (16/19) of tumors and 93% (14/15) or normal kidneys analyzed. Estrogen receptors in small amounts (ER) were detected in only 5% (1/19) of tumors and in 7% (1/15) of normal kidneys. Progesterone receptors (PR) in low quantities were detected in 30% (6/20) of renal tumors and in 40% (6/15) of normal kidneys. DHTR levels in high-stage tumors (T3, T4) were significantly elevated over levels in autologous normal kidney, whereas in low-stage tumors localized to the kidney (T1 and T2 tumors) DHTR levels were not significantly different from autologous normal kidney. The mean levels of DHTR in high-stage kidney tumors were significantly elevated over levels in low-stage tumors (P less than 0.001). DHTR estimation in renal neoplasms may help in biologic staging of renal adenocarcinoma and could define a group of patients in whom anti-androgen therapy may be worth a trial.

Adenocarcinoma↗