Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid sulfatase desulfates a number of 3 beta-hydroxysteroid sulfates, converting inactive steroid hormone to the active form. I have developed an enzyme-linked immunosorbent assay (ELISA) using polyclonal antibody against the sulfatase which was purified from human placenta to measure an amount of the enzyme protein in sera of gynecologic cancer patients. By this method, it was found that the serum steroid sulfatase level is significantly elevated in patients with endometrial carcinoma (p less than 0.05) and ovarian carcinoma (p less than 0.01) as compared to that of normal women. Steroid sulfatase deficiency, X-linked ichthyosis (XLI) is an inherited skin disorder. The sulfatase gene and the enzyme protein were examined in patients with XLI. When the first and last (exon 10) exons of the sulfatase gene were amplified by PCR using patients' genomic DNA as templates, no product was detected in all six cases examined. In addition, neither mRNA of the sulfatase nor the enzyme protein was detected in a patient with XLI. These observations suggest that most Japanese XLI patients are caused by an extensive deletion of the steroid sulfatase gene.
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PMID:[Biochemical study on steroid sulfatase and its clinical application to the obstetrics and gynecology]. 142 99

Plasma ethinylestradiol increases 47.6% when taken with ascorbic acid because of competition in producing sulfate conjugation. Thus the role of sulfates may be important. Serum and urinary estrone sulfate (E1-S) in pregnancy and non-pregnancy were analyzed. Its serum peak during the menstrual cycle was 2.67 +/- 0.37 ng/ml (mean +/- SE) and about ten times that of estradiol-17 beta. E1-S showed lower levels in malignant tissues of breast cancer and endometrial cancer. Increased sulfatase activity in the malignant tissue hydrolyzes E1-S to E1, which may develop the tumors. Serum estradiol 17-sulfate (E2-17-S) in pregnancy was first measured. As E2-17-S decreased, lipid peroxides increased. E2-17-S is converted to 2-OH or 4-OH E2-17-S, which act as lipid peroxide scavengers. Pregnancy-induced hypertension showed lower levels of E2-17-S. In vitro study using the human endothelial cell of the aorta, E2-17-S and 2-OH E2-17-S strongly suppressed lipid peroxidation, which precedes atherosclerotic change.
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PMID:[Endogenous levels and dynamics of estrogen sulfates--physiological and pathological roles of estrone sulfate and estradiol 17-sulfate]. 146 92

Arylsulfatase A was radioimmunoassayed in serum specimens of 96 healthy volunteers and 368 patients with histopathologically confirmed cancer of gastrointestinal tract, breast, lung, central nervous system, kidney and woman genital tract. Sensitivity, specificity and predictive value of the test were 43%, 82% and 90%, respectively, which means that a positive test is significant for diagnosis of cancer regardless of its localization. More detailed statistical analysis of the results indicates that determination of the serum concentration of arylsulfatase A might be helpful in the diagnosis of lung (59% sensitivity, 82% specificity) and central nervous system cancer (60% sensitivity, 82% specificity). Further studies should also be continued in respect to renal and women genital tract cancers for which the results of the test, although promising, are at present not conclusive due to the small numbers of examined cases. Particularly, determination of serum arylsulfatase A in case of endometrial cancer seems to be of diagnostic value. Arylsulfatase A concentration in serum with a lower than 40% sensitivity of the test cannot be considered as a valuable tumor indicator in the case of cancer of breast and gastrointestinal tract, although 80% predictive value of the test for the latter group of tumors is quite high and perhaps merits additional consideration.
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PMID:Arylsulfatase A in serum from patients with cancer of various organs. 168 88

Estrone sulfatase activity was measured in normal and neoplastic endometrial tissues of human uterus. The tissue homogenates were incubated in air with [3H] estrone sulfate (E1-S, 20 microM) at 37 degrees C for 30 min. After the enzyme reaction was terminated with ethyl ether, the ethyl ether extract was purified by thin-layer chromatography. The apparent Km of sulfatase was 3.0 microM, and the maximum velocity was 14.7 nmol/h/mg protein. Estrone sulfatase activity in endometrial tissues was detected throughout the menstrual cycle with no significant change. Moreover, estrone sulfatase activity in endometrial cells was not stimulated by the addition of progestogen. The enzyme activity in cancer tissue was significantly higher than in normal tissue. Thus we concluded that this enzyme may play a role in regulating the estrogen action by sifting the intracellular equilibrium between free estrogens and estrogen sulfates. We also concluded that in the endometrial cancer tissue, sulfatase appears to act on local production of estrone.
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PMID:Estrone sulfatase activity in normal and neoplastic endometrial tissues of human uterus. 252 75

Estrone sulfate (E1-S) in the serum and tissues of patients with breast cancer or endometrial cancer was measured by a direct radioimmunoassay without hydrolysis. The concentration of E1-S in breast cancer tissue was 1.64 +/- 0.28 ng/g wet wt (+/- SE), lower than in surrounding normal breast tissue (4.46 +/- 1.23). Estradiol-17 beta(E2)/E1-S was higher in endometrial cancer tissue than normal endometrial tissue. Estrone sulfatase activity in breast cancer tissue was 0.81 +/- 0.23 nmol/h/mg protein, higher than in surrounding normal breast tissue (0.35 +/- 0.11). These results suggest that E1-S, which is abundant in the peripheral circulation, is hydrolyzed by sulfatase in breast cancer tissue or endometrial cancer tissue and liberates free estrogens, which may stimulate the growth of these malignant tumors.
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PMID:Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer. 255 48

Estrogen metabolism was studied in a newly established cell line (RL95-2) derived from a human endometrial carcinoma. Estradiol and estrone were metabolized to water-soluble derivatives by cells under in vitro culture conditions. Between 80-90% of the added steroids were metabolized, with nearly quantitative recovery of the products from the incubation medium. Arylsulfatase treatment converted the metabolites to ether-soluble forms, whereas beta-glucuronidase had no effect on the aqueous solubility of these compounds. Butanol extracts of the water-soluble estradiol metabolites cochromatographed on high performance liquid chromatography with 17 beta-estradiol-3-sulfate (93.6%) or estrone-3-sulfate (3.5%). No more than 6% of the estradiol added to the incubation medium was recovered in the form of estrone, either as estrone or estrone sulfate. After arylsulfatase treatment of the estradiol conjugates, 92% of the ether-soluble radioactivity cochromatographed with estradiol, and 3.8% cochromatographed with estrone. Estrogen-sulfurylating activity was localized in the cytosol of subcellular fractions of RL95-2 cells. The sulfoconjugation of estrogens by RL95-2 cells may prove useful as a model for the investigation of estrogen metabolism in endometrial carcinoma cells.
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PMID:Estrogen sulfoconjugation by human endometrial cancer cells (RL95-2) in culture. 669 41

Steroid sulfatase (STS) desulfates a number of 3 beta-hydroxysteroid sulfates, converting inactive steroid hormone to the active form. We have established an enzyme-linked immunosorbent assay (ELISA) of STS by using polyclonal antibody against STS purified from human placenta to measure the amount of the enzyme protein in sera. ELISA was performed by a 'Sandwich' method using a peroxidase conjugated anti-STS IgG Fab' fragment. A range of STS of 10-1,500 ng/ml in serum was assayed by this method. When the serum STS from the patients with gynecologic carcinomas was assayed by the ELISA, the level was significantly elevated in endometrial carcinoma (P < 0.05) and ovarian carcinoma (P < 0.01), respectively, as compared with that of normal healthy women.
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PMID:Serum levels of steroid sulfatase protein in gynecologic carcinomas. 807 Jan 31

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.
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PMID:Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. 847 61

Estrogen-dependent endometrial cancer is related to unopposed and prolonged estrogen stimulation. We examined the expression of estrogen-metabolizing enzymes in correlation with the ERalpha and ERbeta estrogen receptors in human endometrial Ishikawa adenocarcinoma cells and in endometrial cancer specimens and adjacent normal endometrium from the same patients. Real-time PCR analysis revealed that both estrogen receptors and selected estrogen-metabolizing enzymes were expressed in the Ishikawa cells and in endometrial tissue. We detected higher expression of ERalpha than ERbeta, higher expression of sulfatase than sulfotransferase and low expression of aromatase in the Ishikawa cells and the tissue, as well as higher levels of type 2 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in normal and diseased tissue than in the Ishikawa cells. When we compared the expression in endometrial cancer samples and in the adjacent normal endometrium, ERalpha and ERbeta, sulfatase and sulfotransferase were seen to be downregulated in the majority of the cancerous tissue specimens.
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PMID:Expression analysis of estrogen-metabolizing enzymes in human endometrial cancer. 1633 31

The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice.
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PMID:The use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer. 1845 Sep 55


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