Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
 ...
PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

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.
 ...
PMID:Arylsulfatase A in serum from patients with cancer of various organs. 168 88

Arylsulfatase A was isolated from urine and human liver. The enzyme was homogeneous with respect to charge and had high specific activity--64 U/mg and 34 U/mg for arylsulfatase A from urine and liver respectively. The enzyme from urine as well as the liver one contained two nonidentical subunits with molecular weights varying about 5 kDa. Treatment of the enzyme from urine, liver and from placenta with endo-beta-N-acetylglucosaminidase F did not remove all carbohydrate from any subunit even in denaturing conditions. Deglycosylation of the enzyme with this one and other glycosidases under various conditions resulted in a decrease in the apparent molecular weights of subunits only by 1-2 kDa. The difference between molecular weights of subunits did not change upon deglycosylation of arylsulfatase A. The results suggest that the presence of two nonidentical subunits is due to presence of different polypeptides rather than various glycosylation of a single polypeptide chain. Arylsulfatase A from urine was inactivated following reaction with diethyl pyrocarbonate at pH 5.5 or at pH 7.0. This confirmed the presence of histidine essential for its catalytic activity. It was also shown that the enzyme was inactivated with ferrate ion, structural analogue of orthophosphate and strong oxidizing agent. The conditions of inhibition of arylsulfatase A carried out with the use of ferrate as well as catalytic and immunochemical properties of the modified enzyme suggest that ferrate reacted with the active site of arylsulfatase A. The results allow to expect that a reactive histidine is present in enzyme's active site and that this aminoacid is modified with ferrate. A simple, sensitive and specific radioimmunoassay was developed for the determination of arylsulfatase A in human serum and urine. The method allows to measure less than nanogram amounts of the enzyme in human body fluids. The test was used to determine arylsulfatase A in serum specimens of 368 patients with histopathologically confirmed cancer of gastrointestinal tract, breast, lung, central nervous system, kidney and woman genital tract. The highest mean concentration of arylsulfatase A in serum and significantly higher than that in the control group of 96 healthy blood donors was found in the case of groups of lung, kidney and central nervous system cancer. The results indicate that the radioimmunoassay determination of serum level of arylsulfatase A might be helpful in diagnosis of lung and central nervous system cancer. Arylsulfatase A serum level cannot be treated as a valuable indicator in the case of cancer of breast and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Arylsulfatase A--physico-chemical properties and the use of enzyme radioimmunoassay in medical diagnosis]. 168 65

Testis cancer and ichthyosis are both relatively rare diseases. Hence the finding of six individuals with both these conditions in a small population with testicular cancer is highly conspicuous and indicates some kind of connection among such persons. Despite the identical clinical appearances of their ichthyoses, three of the ichthyotic subjects had no measurable activity of the enzyme, steroid sulfatase (STS) in leucocytes, a distinct characteristic of recessive X-linked ichthyosis (RXLI). However, the remaining three subjects had normal STS activity, a strong indicator of autosomal dominant ichthyosis (ADI). The STS activity in patients with testicular cancer who do not have ichthyosis (N = 30) was also within the normal range. The patients with testicular cancer with no skin disease had elevated serum levels of 4-androstenedione (4-AD), follicle stimulating hormone (FSH), and luteinizing hormone (LH) but had reduced levels of estrone and estrone sulfate. The other serum parameters measured did not significantly differ from normal levels. In essence, the hormone levels obtained for the patients with ichthyotic testicular cancer followed the same pattern, although their dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate levels tended to be slightly higher than normal. However, no conspicuous aberrations in any of the parameters examined were observed, and why men with ichthyosis are at high risk for testicular cancer remains an unresolved issue.
Cancer 1991 Feb 01
PMID:Testis cancer. Ichthyosis constitutes a significant risk factor. 189 10

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]-Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.
 ...
PMID:Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens. 237

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.
 ...
PMID:Estrone sulfatase activity in normal and neoplastic endometrial tissues of human uterus. 252 75

We previously demonstrated that an acidic variant form of lysosomal arylsulfatase B accumulated in chronic myelogenous leukemia (CML) cells was highly phosphorylated at its carbohydrate moiety (Uehara Y, et al, Cancer Res 43:5618, 1983). Since lysosomal hydrolases including the sulfatase underwent the posttranslational phosphorylation processing at the carbohydrate moiety, we investigated two enzymes acting on the processing in peripheral leukocytes from leukemia patients. The activity level of the first enzyme in the processing, an N-acetylglucosamine-1-phosphotransferase to form phosphodiester at the carbohydrates, was significantly higher in CML cells than in normal control. The transferase level in CML cells was also higher compared with that in normal bone marrow cells, which include myeloid progenitor cells. However, the activity of the second processing enzyme, a phosphodiester glycosidase that converts a phosphodiester to a phosphomonoester, showed no consistent change in CML cells. Thus, increment of the sulfatase variant containing phosphomonoesters and diesters in CML cells is most probably associated with elevated activities of the phosphotransferase. In two cases of CML in blastic crisis and a case of acute myelogenous leukemia (AML), activity of the processing enzyme was considerably decreased concomitant with reduction of peripheral blastic cells by chemotherapy.
 ...
PMID:Processing enzymes acting on carbohydrate moiety of lysosomal hydrolases in leukemic cells: elevated activity of N-acetylglucosamine-1-phosphotransferase. 254 Aug 59

Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells. It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17 beta-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormone-dependent mammary cancer.
 ...
PMID:Importance of estrogen sulfates in breast cancer. 256 May 11

Lactosylceramide sulfate and galactosylceramide sulfate were found to increase markedly in human renal cell carcinoma (adenocarcinoma) as compared to uninvolved tissue. Activities of two sulfotransferases toward galactosylceramide and lactosylceramide as substrates were significantly elevated in the carcinoma compared to the uninvolved tissue resulting in enhanced synthesis of the two sulfatides in the carcinoma. The elevation of the two sulfotransferases was parallel in most tumors, suggesting that the same enzyme is responsible for the enhanced synthesis of two sulfatides. No consistent difference in the activity of arylsulfatase A, which desulfates the two sulfatides, was observed between the carcinoma and uninvolved tissue. Both the present and previous results show that the increased synthesis of the sulfatide(s) due to elevated sulfotransferase activity could be a biochemical characteristic common to adenocarcinomas derived from different tissues.
Cancer Res 1989 Jan 15
PMID:Association of elevated sulfatides and sulfotransferase activities with human renal cell carcinoma. 256 26

Purified arylsulfatase A (EC 3.1.6.1) from human urine was radioiodinated under conditions that caused no significant loss of antigenic activity. We used this labeled arylsulfatase A (specific radioactivity 4-7.5 Ci/g) together with nonlabeled enzyme and rabbit antiserum produced against homogeneous enzyme to develop a radioimmunoassay for arylsulfatase A in urine. A solid-phase, second-antibody technique (Immunobead Second Antibody; Bio-Rad Laboratories) was used to separate free enzyme from antigen-antibody complexes. The working range of the assay was 0.1-4.0 ng of enzyme; within- and between-assay CVs were around 10%, and the analytical recovery was 105.5% (SD 7.7%). The lower limit of detection was 0.08 ng of arysulfatase A per assay, substantially less than that of typical activity-based assays. Over a wide range of urinary arylsulfatase A activities, results by this method agreed well (r = 0.99) with those obtained by activity assays. We measured the enzyme in urines of 59 healthy volunteers and 92 patients with different diseases, including a group of colorectal cancer cases, to determine whether this could serve as a reliable marker for cancer of the colon; however, urinary excretion of arylsulfatase A by most patients with colon cancer was within normal limits.
 ...
PMID:Radioimmunoassay for arylsulfatase A in urine. 285


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>