Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To treat ovarian cancer of stage III-IV the authors have used an antimetabolite-fluorafur. A total dosage of 17-23 g. "marked improvement" was noted in 15 patients, "insignificant improvement" - in 9, there was no improvement in one case. It was found that the level of FSH excretion was reduced twice under the influence of fluorafur, the greater decrease corresponding to a better clinical effect. The drug used in doses applied by the authors, proved to be nontoxic.
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PMID:[Use of ftorafur for the treatment of 3d-4th stage]. 109 24

During the last two decades, considerable experimental evidence has been collected indicating that epithelial ovarian cancer might be gonadotropin dependent. LH and FSH receptors have been described in some of these tumors. The proliferation of ovarian cancer cells could be stimulated in vitro by gonadotropins. Suppression of endogenous LH and FSH secretion by GnRH-agonist treatment inhibited the growth of experimental or heterotransplanted ovarian cancers in various animal models. A number of recent phase II clinical trials have shown that the application of GnRH-agonists can lead to remission or stable disease in patients with relapsed advanced ovarian cancer. At present, prospective controlled clinical studies are being performed to assess the efficacy of GnRH-agonist treatment in addition to conventional surgical and cytostatic therapy in ovarian cancer in FIGO stages III and IV. Also, direct effects of GnRH analogues on ovarian cancer seem possible: a GnRH-like protein has been found in the human ovary. Our group discovered and partially characterized a specific GnRH-binding site (mol. wt 63.2 kDa) in ovarian cancer which is very similar to other human extrapituitary GnRH-binding sites of the low affinity, high capacity type, e.g. in breast cancer or the placenta. Recently, other groups have described also high affinity GnRH-agonist binding sites in ovarian cancer as well as in other extrapituitary tissues. First results from our laboratory indicate that the proliferation of certain ovarian cancer cell lines in vitro is reduced by both agonistic and antagonistic analogues of GnRH. Other authors were able to inhibit gonadotropin-induced in vitro proliferation of ovarian cancer cell lines by co-incubation with a GnRH-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular actions of gonadotropic and peptide hormones and the therapeutic value of GnRH-agonists in ovarian cancer. 138 55

Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment.
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PMID:Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. 190 82

Considerable evidence exists that ovarian cancer might be gonadotrophin-dependent. Receptors for LH and FSH have been discovered in these tumors. Proliferation of ovarian cancer cells in vitro could be stimulated by gonadotrophins. Withdrawal of LH and FSH in animal models of ovarian cancer inhibited growth of these tumors. Phase-II clinical studies have shown that suppression of endogenous gonadotrophins by LHRH-agonists can be beneficial in women with advanced ovarian cancer. Respective controlled clinical trials are performed at present. Also direct effects of LHRH analogues on ovarian tumors have been reported. An LHRH like protein was found in human ovarian tissue. We discovered a specific LHRH binding site (mol. wt 63.2 kDa) in ovarian cancer tissue which is very similar to other human extrapituitary LHRH binding sites, of the low-affinity, high-capacity type, e.g. in breast cancer and the placenta. In the latter tissues, LHRH or a related substance has been proposed as an autocrine regulator of cellular function. If this was also the case in ovarian cancer, direct effects of LHRH analogs on the tumor cells could be used as additional therapeutical points of attack.
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PMID:LHRH-receptors and LHRH-agonist treatment in ovarian cancer: an overview. 217 60

Observations in healthy women led us to suppose that the increase of the tumor marker CA 125 observed during progression of ovarian cancer could be dependent on pituitary gonadotropins. Therefore we administered the GnRH-analog, DTrp 6-LH-RH, to 19 patients with progressive ovarian cancer and increasing CA 125 serum levels. When compared to 11 untreated patients, CA 125 levels increased at a considerably slower rate in 9 of 11 patients who were treated with the substance for more than 3 months. This was associated with stable disease, ranging from 4 to 20 months so far. The further analysis of 2 patients who developed an increase in CA 125 serum levels and a progression of disease during treatment demonstrated that FSH and LH levels had escaped suppression. The results support our assumption, that gonadotropins may be involved in the mechanisms leading to increasing CA 125 concentrations in ovarian cancer. The reduced increase of CA 125 and the observed stabilisation of disease during pituitary blockade offers a rationale for GnRH analogues in the therapeutic approach to this disease.
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PMID:Some observations on the effect of a GnRH analog in ovarian cancer. 252 88

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.
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PMID:Androgen receptor predominance in human ovarian carcinoma. 349 2

Peripheral serum concentrations of estrone (E1), estradiol (E2), testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), cortisol, prolactin, LH, and FSH were measured in 28 postmenopausal women with epithelial ovarian tumors (12 ovarian cancer, 5 borderline malignant, 11 benign neoplasms) and in 15 controls before bilateral salpingo-oophorectomy and 1 and 8 weeks postoperatively. The levels of these hormones were also measured in ovarian venous blood of 15 patients with ovarian tumors. E2 was significantly higher in the tumor group than in controls preoperatively and the levels of E1 and E2 decreased after radical operation. Hormone levels were similar in the benign and malignant tumor groups. Only DHEAS levels in peripheral serum were significantly lower in ovarian cancer patients than in the group with benign neoplasm. This was not the case in testosterone and androstenedione measurements. The measured levels of the hormones in ovarian venous blood were highest in mucinous ovarian tumors. E2 and testosterone levels were higher in mucinous ovarian tumors than in others. LH(hCG)-receptor levels were measured in 24 specimens and none of these showed detectable concentrations of LH(hCG) receptor. The results indicate that of all epithelial tumors mucinous ovarian tumors had hormonal activity most often, and malignancy had no effect on hormonal activity.
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PMID:Peripheral and ovarian venous concentrations of steroid and gonadotropin hormones in postmenopausal women with epithelial ovarian tumors. 373 8

The (basal) level of FSH measured during early menses is emerging as a predictor of ovarian competence. In this study, correlates of basal FSH were examined in 222 premenopausal women who were not using oral contraceptives and selected from either the general population or a clinic for women with family histories of ovarian cancer. Using analysis of variance, the effect on FSH by age, smoking history, and reproductive variables was examined. Dietary galactose (as a potential oocyte toxin) was estimated, and red cell activity of galactose-1-phosphate uridyl transferase (GALT) was measured. Qualitative features of GALT were described by its electrophoretic or molecular genetic patterns. Possession of GALT polymorphisms previously linked with low GALT activity, including the Q188R mutation of classic galactosemia or N314D mutation of the Duarte galactosemia variant, was associated with significantly higher FSH, even in the heterozygous state. Other factors significantly influencing FSH included age, smoking history, cycle length, and cycle regularity. No effect of current galactose consumption was found, and GALT activity was only weakly correlated (inversely) with FSH. Applying multiple linear regression, variables independently predictive of high FSH were age of 40 yr or more, current smoking, and possession of a GALT polymorphism.
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PMID:Determinants of basal follicle-stimulating hormone levels in premenopausal women. 796 82

Inhibin is a peptide hormone normally produced by the ovary. We have previously reported that serum inhibin concentrations are elevated in patients with granulosa cell tumours of the ovary. The aim of this study was to measure serum inhibin in a prospective, consecutive series of 200 patients admitted for suspected ovarian cancer. The serum inhibin radioimmunoassay had a sensitivity of 77 mu/l. The median effective dose was 640 mu/l, while within- and between-assay coefficients of variation in the region of maximal assay precision were 4.3% and 4.3%, respectively. The average effective doses (10 and 90%) in 35 consecutive assays were 211 and 1908 mu/l, respectively. We designated a serum inhibin concentration of > or = 130 mu/l as pathological in castrate or functionally agonadal women. Serum inhibin concentrations were elevated in 12 of 13 post-menopausal patients with mucinous cystadenocarcinoma of the ovary. By contrast, elevated serum inhibin values were found in only nine of 65 women with non-mucinous epithelial ovarian cancers. All patients showed a fall in serum inhibin levels to below 130 mu/l by 1 week after surgery. In post-menopausal women (n = 54) with proven ovarian cancer, serum inhibin concentrations correlated negatively with serum FSH and the clinical stage of their disease (P < 0.05). By contrast, serum inhibin correlated positively with serum oestradiol and progesterone (P < 0.001) but there was no correlation between serum inhibition and serum CA-125 values. We conclude that serum inhibin concentrations are typically elevated in patients proven to have mucinous cystadenocarcinoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and pathophysiological aspects of inhibin. 827 48

The follistatin/activin/inhibin system increasingly appears to have important growth and differentiating effects in a variety of cell types, including cancer. We have developed a two-site immunoradiometric assay for measurement of human follistatin using two monoclonal antibodies against recombinant human follistatin. This cloned protein donor assay is sensitive (0.5 ng/mL), specific for free human follistatin, and precise (<5% within assay coefficient of variation). Using this assay, native human follistatin could be measured in human pituitary extracts, follicular fluid, and granulosa-luteal cell-conditioned medium. To identify and characterize human follistatin secreted by ovarian cancer cells, we screened five human ovarian carcinoma cell lines currently available from the American Type Culture Collection (Rockville, MD). One of these, a cell line derived from a teratocarcinoma (designated PA-1, American Type Culture Collection, CRL1572), secreted large (3 microg/10(6) cells per 24 h) quantities of immunoreactive follistatin constituitively. Increasing volumes of conditioned medium from these cultured cells generated response curves parallel to those of recombinant human follistatin 288 reference protein, human follicular fluid, or culture medium from human granulosa-luteal cells. Secretion of follistatin by PA-1 cells was time and cell-number dependent with 297.9 +/- 15.2, 654 +/- 29.8, and 940 +/- 49.1 ng follistatin secreted over 24 h by 1 x 10(5), 2 x 10(5), and 3 x 10(5) cells, respectively. Western and ligand blot analysis revealed that the immunoreactive follistatin secreted by PA-1 cells and isolated by sulfate-cellufine chromatography was identical to the molecular weight variants (32,000 and 35,000 Mr) of recombinant human follistatin 288. PA-1 cell-conditioned medium suppressed basal secretion of FSH by cultured rat anterior pituitary cells in a dose-dependent fashion. This follistatin bioactivity was completely removed by adsorption with either solid-phase monoclonal antifollistatin or a dextran-sulfate chromatography gel. Because activin suppressed the proliferation of PA-1 cells, secretion of bioactive follistatin may represent an autocrine mechanism opposing activin to maintain the rapid growth rate of PA-1 cells. These observations demonstrate that the ovarian teratocarcinoma cell line, PA-1, secretes considerable amounts of human follistatin that is biologically active, capable of binding human activin, and antigenically similar to recombinant human follistatin 288. The monoclonal antibodies and two-site assay reported herein should be useful in assessing the regulation of follistatin secretion and as a diagnostic tool, especially if follistatin measurements prove to be a marker for some ovarian cancers.
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PMID:A two-site monoclonal antibody immunoradiometric assay for human follistatin: secretion by a human ovarian teratocarcinoma-derived cell line (PA-1). 863 47


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