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)

Tamoxifen is a synthetic nonsteroidal drug with antiestrogenic properties. This report describes the response of patients with metastatic breast cancer to tamoxifen and correlates clinical responses with tumor tissue content of cytoplasmic estrogen binding proteins (EBPs) and other biochemical parameters. Ages of patients ranged from 27 to 82 years. 7 patients were premenopausal, 63 postmenopausal, and 2 had recent endocrine ablaetion. Prior hormone therapy, radiotherapy, or chemotherapy ahd been given to all patients. Tamoxifen was given at a dose of 20 mg orally for a minimum of 4 weeks and continued if an objective remission was shown. Before therapy a biopsy specimen was taken for determination of EBP and for specific enzyme activities. Another biopsy specimen was taken for at least 8 weeks after therapy. A total of 72 patients were treated for at least 4 weeks. The overall response rate was 38%. Most frequent responses were in the over-70 age group. The median duration of response has been 9.5 months. Bony involvement responded to therapy in 21 of 28 patients. No responses were shown in 6 patients with liver metastases. Only 1 of 18 patients who had previous chemotherapy responded. Of 31 who had no prior chemotherapy, 73% achieved a remission. There was a 44% correlation between patients with a positive EBP assay and response to therapy, but none in EBP-negative patients. In this study 20 of 28 patients had normal arylsulfatase B/DNA ratios in their tumor tissue and 11 of the 20 responded to tamoxifen therapy. Patients who responded most favorably to therapy had normal G-6-PD activities. It is concluded that tamoxifen therapy may cancel the need for ablative surgery in postmenopausal patients with positive EBPs and who have had a prior response to additive hormonal treatment.
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PMID:Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. 19 Nov 85

More than two-thirds of breast cancers occur in post-menopausal women, and depend on the estrogens for their proliferation and survival. For the treatment of estrogen-dependent breast cancers, two major treatment options are now available. One is selective estrogen receptor modulator (SERM) such as Tamoxifen and another is aromatase inhibitor such as Anastrozole, Letrozole and Exemestane, which reduce local in situ formation of estrogens. Although these therapies are clinically active for advanced and early breast cancers, de novo and/or acquired resistance to SERM and/or aromatase inhibitors are also clinical problem. Recent studies suggest that local formation of estrogens in the breast tumors is more important than circulating estrogen in plasma for the growth and survival of estrogen-dependent breast cancer in post-menopausal women. The rationale for the importance of local formation of estrogens is based on the following evidences. Estradiol (E2) levels in breast tumors are equivalent to those of pre-menopausal patients, although plasma E2 levels are 50-fold lower after menopause. E2 concentrations in breast tumors of post-menopausal women are 10-40 times higher than serum level. Biosynthesis of estrogens in breast tumors tissues occurs via two major different routes, one is aromatase pathway and another is steroid-sulfatase (STS) pathway. Whereas many studies has been reported about aromatase inhibitor and its clinical trial results in breast cancer patients, limited information are available regarding to other estrogen regulating enzymes including STS, its role in breast tumors and STS inhibitors. STS is the enzyme that hydrolyses estrone 3-sulfate (E1S) and dehydroepiandrosterone-sulfate (DHEA-S) to their active un-sulfoconjugated forms, thereby stimulating the growth and survival of estrogen-dependent breast tumors. It has been well known that E1S level are much higher than E2 level both in plasma and tumor of post-menopausal patients. Recent reports show that more than 80% of breast tumors are stained with anti-STS antibody and the expression of STS is an independent prognostic factor in breast cancer. Taking these findings into consideration, local formation of estrogens could be partially synthesized from large amount of E1S by STS, which exist in breast cancer. On the other hand, aromatase localizes in stroma and adipocyte surrounding breast cancer. Furthermore, since estrogen formation from E1S and DHEA-S (STS pathway) cannot be blocked by aromatase inhibitors, STS is thought to be a new molecular target for the treatment of estrogen-dependent tumor post-SERM and/or aromatase inhibitors. In this symposium, these recent rationale for the importance of STS in post-menopausal breast cancer patients is reviewed as well as STS inhibitor.
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PMID:Role of steroid sulfatase in local formation of estrogen in post-menopausal breast cancer patients. 1462 44

Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer. Keeping this in view, the present review focuses on selective estrogen receptor modulators and estrogen antagonists such as sulfatase and aromatase inhibitors involved in breast cancer therapy. A succinct and critical overview of the structure of estrogen receptors, their signaling and involvement in breast carcinogenesis are herein described.
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PMID:Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review. 2827 82