Biomedical subjects

R R Mehta

Publications and source records attributed to R R Mehta.

33 records · Page 2Linked to original sources

PubMed1992

Endocrine profile in breast cancer patients receiving chemotherapy.

Cyclophosphamide and other alkylating agents suppress ovarian function in pre-menopausal women. However, endocrine details remain unknown regarding the influence of patients' age and obesity on CMF-induced hormonal changes. We studied changes in endocrine profile due to chemotherapy (CMF) in 70 pre-menopausal patients with axillary node positive, stage II and/or III breast carcinoma. Plasma levels of estrone (E1), estradiol (E2), androstenedione (A2), luteinizing hormone (LH), and prolactin (PRL) were determined on day 1 and 8 of each chemocycle for 12 cycles. After receiving therapy, 23% of the women continued to have regular menstrual cycles (non-amenorrheic group). In the remaining 77%, ovarian function was suppressed, as evidenced by the onset of amenorrhea within 0-11 months (amenorrheic group). The mean time to amenorrhea was 2.83 +/- 0.33 months (SE). The time required to develop amenorrhea inversely correlated to the patient's age. Both incidence of amenorrhea and time to amenorrhea remained unaffected by either patient's obesity or the timing of chemotherapy initiation in relation to menstrual cycle phase (progestational, follicular). Plasma hormone levels fluctuated widely in both groups during the first three chemocycles. During chemocycle months 4 to 10, in the amenorrheic group, plasma E1, E2, and P declined to their baseline levels with a concomitant rise in LH levels. At this time, E1, E2, and P levels were significantly lower in amenorrheics, despite menstrual cycle associated fluctuations in the non-amenorrheic group. Estrogens (E1 and E2) gradually declined further following the onset of amenorrhea in subsequent months. Further data analysis suggests that host age or obesity did not influence CMF-induced changes in the plasma endocrine profile.

Adult↗

PubMed1991

Antiovulatory action of anordrin in the cynomolgus monkey (Macaca fascicularis).

Anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol dipropionate) was studied for its antiovulatory potency in the cynomolgus monkey. Anordrin, administered daily on days 9-13 of the menstrual cycle in doses of 4.0 and 8.0 mg/kg body weight, did not inhibit luteal activity in the cycle in which it was given, but delayed the development of ovarian follicles for 5 to 6 months. When a single low dose (0.1 or 0.2 mg/kg b.w.) was administered during the first 3 days of the menstrual cycle, follicular maturation was delayed such that luteal activity was not observed for an average of 26 and 39 days, respectively, and pregnanediol in the ensuing luteal phases was significantly decreased. Anordrin appears to inhibit follicular development when given during the stage of follicular recruitment.

Animals↗

PubMed1990

Cellular retinol binding protein and breast carcinoma.

Cellular retinol binding protein (C-RBP) levels were measured in 87 malignant and 18 non-malignant breast cancer tissues. C-RBP, sedimenting in the '2S' region on 5-20% sucrose density gradients, was detectable in 70% of malignant tissues examined. None of the non-malignant tissues contained detectable C-RBP. No significant association between tumour steroid receptors status, patients' obesity or menopausal status and C-RBP contents was observed. However, patients with stage IV disease had higher C-RBP levels than patients at stages II and III (P less than 0.0001), which suggested altered intracellular mobilization of retinol in the tumour, probably as an indirect consequence of inadequate nutrient intake.

Breast Neoplasms↗

PubMed1987

Subcellular concentrations of estrone, estradiol, androstenedione and 17 beta-hydroxysteroid dehydrogenase (17-beta-OH-SDH) activity in malignant and non-malignant human breast tissues.

Total and subcellular (cytosol and nuclear) concentrations of estrone (E1), estradiol (E2), and androstenedione were determined in non-malignant (n = 61) and malignant (n = 65) human breast tissues obtained from post-menopausal women. The 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH) activity was determined in 800g supernatant fraction. Total estrogens, E1 and E2 levels and 17 beta-OH-SDH activity were significantly (p less than 0.005, 0.0005, 0.001, respectively) higher in malignant than in non-malignant breast tissues. We failed to observe significant changes in subcellular steroid concentrations or enzyme activity associated with patients' obesity or tumor estrogen receptor status. When the steroid levels were analyzed in relation to clinical staging of the disease, nuclear contents of estradiol were significantly higher (p less than 0.005) in Stage-IV patients than in those with less advanced disease (Stages I to III). 17 beta-OH-SDH activity was significantly (p less than 0.001) lower in patients with advanced disease than in those with relatively less advanced (Stages I to III) disease and was positively correlated with tissue concentration of androstenedione. Our present data indicate that differential intracellular metabolism of steroid hormones may have some influence on availability of estradiol at nuclear sites. In postmenopausal women, local interconversion of estrogens may provide sufficient estrogenic stimulus to enhance the growth and progression of breast tumors.

17-Hydroxysteroid Dehydrogenases↗

PubMed1987

Antiestrogen binding sites in microsomal fractions of malignant and nonmalignant human breast tissues.

Antiestrogen binding sites (AEBS) were measured in microsomal fractions of 102 malignant breast tumors and 24 nonmalignant breast tissues. The number of AEBS was determined by Scatchard analysis. The cytosol contents of estrogen and progesterone receptors were also analyzed in these tissues. Overall, 50% of the malignant tumors and 33% of the nonmalignant normal breast tissues had detectable contents of AEBS. No correlation was observed between cytosol estrogen receptor (ER) content and microsomal AEBS in the tumors. Detailed data analysis in patients at Stage IV disease revealed that 60% of estrogen receptor positive tumors had no detectable microsomal AEBS contents whereas in the remaining 40% tumors, high affinity AEBS were observed. On the other hand, AEBS were also detected in 35% of ER-poor tumors. Anti-estrogen binding sites were higher in tumors obtained from premenopausal women than in those of postmenopausal women. The incidence of AEBS-positive tumors or AEBS concentration was not influenced by either the patients' obesity or their disease stage.

Breast↗

PubMed1987

Significance of plasma retinol binding protein levels in recurrence of breast tumors in women.

Plasma retinol-binding protein (RBP), prealbumin, vitamin A (total) and beta-carotene levels were studied in premenopausal women with node-positive breast carcinoma receiving adjuvant chemotherapy. Plasma levels were measured prior to chemotherapy and at monthly intervals during the chemotherapy course. The results showed that significantly lower RBP levels during the course of the study were associated with early tumor recurrence. Patients who maintained a disease-free status for 24 months or longer had significantly higher plasma RBP levels than those who had tumor metastasis at distant sites within 24 months after beginning chemotherapy. RBP levels were not associated with adjuvant chemotherapy (CMF)-induced hormonal changes (amenorrhea vs. no amenorrhea), or family history of breast cancer. In contrast, breast cancer patients with a prior history of benign breast disease had significantly lower RBP levels than did healthy, premenopausal women. Reduced RBP levels in these patients are due to neither an inadequate dietary intake of beta-carotene, nor to severe protein malnutrition.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

Estrogen and antiestrogen binding sites in desmoid tumors.

Clinical and experimental evidence suggests a role for estrogen in the natural history of desmoid tumors (DT). Antiestrogen (tamoxifen) has been used empirically in some patients with significant tumor regression. To further investigate the mechanism of hormonal influence on desmoid tumors we initially characterized the cytosol estrogen receptor (ER) and antiestrogen binding sites (AEBS) in microsomal fractions of 15 cases of DT. Biopsy specimens were obtained from nine female and six male patients. ER assay was determined in cytosol (105,000 g) and the AEBS was detected in the microsomal fraction (7000 g for 20 min) by a DCC assay technique. ER was present in 33% of DT assayed (5/15), with equal incidence in males and females. Receptor content in female patients was higher than in male patients (26.52 +/- 16 vs 10.82 +/- 8.32 fmol/mg protein). Dissociation constant (Kd) range (0.44-3.97 nM) was well within the values seen in other estrogen target tissues. The AEBS were detected in 79% of the cases. The mean binding value was 236.7 +/- 170.2 fmol/mg protein. Kd values were between 0.39 and 5.97 nM. ER settled predominantly in the 4S region and AEBS settled in the 5-5.5S region in a 5-20% sucrose gradient. AEBS was detected in seven patients with negative ER. No correlation between ER and AEBS contents was observed. Competition studies revealed minimal binding with either DEX, DHT, R5020, and R1881, but partial binding with tamoxifen in cytosol and estradiol in microsomal fractions. ER and AEBS assays may be of prognostic significance in the natural history of these tumors.

Adult↗

PubMed1986

Relationships between ovarian morphology, vaginal cytology, serum progesterone, and urinary immunoreactive pregnanediol during the menstrual cycle of the cynomolgus monkey.

Three different indices of ovulation and luteal activity were studied in eight regularly cycling cynomolgus monkeys. A significant relation between changes in serum progesterone and immunoreactive pregnanediol (I-PD) in urine was obtained. The occurrence of ovulation could be determined reliably from a change in the ratio of cornified to basal epithelial cells in vaginal smears, and luteal activity could be assessed reliably from daily measurements of urinary pregnanediol. The time of ovulation could be defined more precisely by daily I-PD radioimmunoassays than by the vaginal smear pattern. Measurements of I-PD also have the advantage of ease and noninvasiveness over serum progesterone determinations. More detailed information about changes in hormonal activities could not be obtained reproducibly from thorough examination of cell types in vaginal smears.

Animals↗

PubMed1982

Antagonism of the actions of estrogens, androgens and progesterone by anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol dipropionate).

Anordrin, an antifertility agent that is an antiestrogen with weak estrogenic activity, has been studied to further characterize its hormonal activities. A dose of 2.0 micrograms/mouse X day for 7 days did not increase the uterine content of protein, but it did inhibit to a small extent the effect of administered estradiol-17 beta on uterine protein content and more significantly the effect of estradiol-17 beta on the uterine content of progesterone receptors. Anordrin also decreased serum corticosteroid-binding globulin levels. Administration of an average daily dose of 160 micrograms/day of anordrin to intact male mice had no effect on weights of kidney, testis, or seminal vesicle after 10 days, but seminal vesicle weight was significantly decreased after 30 days at a slightly lower dose. Similarly, anordrin inhibited the increase in seminal vesicle weight induced by testosterone propionate treatment of castrated mice. In female mice anordrin failed to maintain deciduomata and blocked the ability of progesterone (2.0 mg/mouse X day) to do so. However, anordrin did not compete with the androgen [3H]R1881 for binding in kidney cytosol or with the progestin [3H]R5020 for uterine receptor sites. Anordrin also did not compete with [3H]corticosterone for binding to serum proteins.

Anabolic Agents↗

PubMed1982

Ability of implants of polymer-entrapped antiprogesterone antiserum to absorb and deplete progesterone from serum of the pregnant rat.

A highly specific antiprogesterone antiserum (APA) produced by immunization of sheep with an 11 alpha-hydroxyprogesterone hemisuccinate-thyroglobulin conjugate was purified, and the IgG fraction was entrapped within a polysiloxane matrix. The matrix immobilized APA but allowed penetration and binding of progesterone (P) to the APA. In this entrapped form APA implanted intraperitoneally in rats on the tenth day of pregnancy resulted in a decline in serum P from 50 to 12 ng/ml within 12 hours and to less than 2 ng/ml within 36 hours. Free serum P measured by equilibrium dialysis fell to less than 0.2 ng/ml at 36 hours. Concomitant with the decline in serum P was a rise in both serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and eventual fetal resorption.

Animals↗

PubMed1981

Antiestrogenic and antifertility actions of Anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol 2,17-dipropionate).

Anordrin, administered in a single s.c. dose of 62.5 micrograms in sesame oil, stimulated sustained uterine growth (wet weight) when measured at 24 and 72 hr, but total soluble protein and total DNA per uterus was not increased. By comparison, 3 micrograms of estradiol-17 beta under the same conditions significantly increased all three parameters of uterine growth. Both of the above steroid treatments significantly increased nuclear estrogen receptor content of the uterus, but only the estradiol-17 beta treatment resulted in significantly elevated cytosol receptor content per uterus. Anordrin binds to the 8S estrogen receptor with an affinity of about 2 x 10(5) M-1 as determined by competition with [3H]estradiol-17 beta. The abortifacient activity of Anordrin when given orally (8 mg/kg b.w.) to mice on the 7th day of pregnancy was almost completely blocked by simultaneous oral administration of estradiol-17 beta (0.8 mg/kg b.w.). It is concluded that the actions of Anordrin on the uterus can be attributed to its antiestrogenic activities.

Abortifacient Agents↗

PubMedDate not supplied

Human breast carcinoma cell lines: ultrastructural, genotypic, and immunocytochemical characterization.

Two new breast carcinoma cell lines, designated as UISO-BCA-1 and UISO-BCA-2, have been established from pleural effusions of postmenopausal women. Both cell lines show properties of mammary epithelial cells, such as positive immunoreactivity to cytokeratins and human milk fat globulin, presence of desmosomal junctions, numerous microvilli, intracytoplasmic duct-like vacuoles and tonofilaments. UISO-BCA-1 and UISO-BCA-2 cells differ from each other with respect to cellular morphology, ultramicroscopic details, immunoreactivity to Her-neu oncogene protein, chromosomal mode and in vivo and in vitro growth rates. UISO-BCA-1 cells are well-differentiated (as evident from their morphology and ultrastructural details) and hyperploid (42-114 chromosomes). In vitro, UISO-BCA-1 cells are fast growing, with a population doubling time of 31.2 +/- 9.6 hrs (n = 4), and are tumorigenic (100%) in athymic nude mice. In contrast, UISO-BCA-2 cells are poorly differentiated, but are also hyperploid, with 54-64 chromosomes. UISO-BCA-2 cells are slow growing in vitro (population doubling time: 56.0 +/- 5.0 hrs [n = 4]) and have limited tumorigenic potency (20-40%). Both these cell lines are estrogen and progesterone receptor (less than 10 fmol/mg protein) negative.

Aged↗

PubMedDate not supplied

Steroid receptors in breast cancer patients. Influence of obesity and age at diagnosis.

The influence of host age on estrogen (ER) and progesterone (PR) receptor status was studied in 603 tumors obtained from women with confirmed diagnosis of breast carcinoma. Both ER and PR analysis were performed in our own laboratory using standard techniques. Tumors were classified as positive if minimum receptor contents were greater than 10 fmol/mg cytosol protein and if dissociation constants were 1-9 x 10(-10) M or lower. Data from our study indicate that the incidence of receptor negative (ER-PR-) tumors was higher in women from 21 to 40 years of age than in women from 41 to 60 years of age. In women over 60 years of age, the incidence of ER+PR+ tumors was higher than in women under 40 years of age. Interestingly, women from 51 to 60 years of age had a significantly lower incidence (P less than 0.06, 0.0001) of ER+PR+ but higher incidence (P less than 0.01) of ER-PR- tumors than women 41-50 or greater than 60 years of age. Analysis of steroid receptor distribution in relation to host age and obesity showed a definite tendency: in obese women over 60 years of age, frequency of ER+PR+ was significantly greater than in non-obese women of similar age groups. This altered ER and PR distribution in tumors is probably a result of difference in the hormonal milieu associated with host menopausal status and obesity.

Adult↗

PubMedDate not supplied

Effects of vitamin C deficiency on physiology of male reproductive organs of guinea pigs.

Vitamin C dietary deficiency in guinea pigs markedly affected the androgen-sensitive parameters of the reproductive tissues--testis, epididymis, vas deferens, and accessory sex glands--and caused an "androgen-deprived effect" in these target organs. This in turn altered their internal milieu and caused changes in their metal ion profile and the morphology, motility, and density of spermatozoa in the cauda epididymis and vas deferens. The sensitivity of the vas deferens to adrenaline was also reduced in scorbutic guinea pigs, thus decreasing their fertility rate. The primary action seems to be at the level of the testis, and androgen deprivation and partial antifertility effects are probably secondary manifestations consequent to the primary effect. The present study demonstrated that ascorbic acid is essential for maintaining the physiological integrity of the androgen target reproductive organs in guinea pigs.

Animals↗

PubMedDate not supplied

A cell line derived from a clinically benign phyllodes tumor: characterization and implications.

Phyllodes are uncommon tumors of the breast. Improved understanding of their behavior is hampered by the paucity of good laboratory models. We have developed two cell lines, by both xenograft and direct cell culture, derived from a histologically benign phyllodes tumor. Both cell lines have the same characteristics and growth kinetics. They grow as monolayers of spindle-shaped cells, with surface markers consistent with a mesenchymal origin. They do not express either estrogen or progesterone receptors. The cells have a relatively short doubling time of just over 1.5 days, and show a stimulatory effect with the addition of insulin. Karyotype analysis reveals the absence of one X chromosome.

Animals↗