Human prostatic dehydroepiandrosterone sulfate sulfatase

Farnsworth, Wells E.

doi:10.1016/0039-128x(73)90134-7

Cited by 44 publications

(23 citation statements)

References 13 publications

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“…Digitonin, a powerful activator of CHS-ase [33,34], had no effect on the purified DHEAS-ase activity. The data concerning the influence of steroids on DHEAS-ase, presented here are different from those obtained by Payne and Jaffe [16], Farnworth [57] and Townsly [58] for the non-purified of dehydroepiandrosterone sulphate sulphohydrolase from human testes and prostate.…”

Section: Resultscontrasting

confidence: 59%

Dehydroepiandrosterone sulphate sulphoydrolase from human placenta microsomes—Properties of the purified enzyme

Gniot-Szulzycka

2006

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Resultscontrasting

confidence: 59%

Dehydroepiandrosterone sulphate sulphoydrolase from human placenta microsomes—Properties of the purified enzyme

Gniot-Szulzycka

2006

The Journal of Steroid Biochemistry and Molecular Biology

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“…STS has been shown to be active in the prostate gland, an important site for the peripheral formation of biologically active androgens from circulating precursors such as DHEAS (Farnsworth 1973). Research by Labrie et al (2004) suggests that the intracrine production of biologically active androgens within the prostate may make a similar contribution to levels obtained from the uptake of circulatory testosterone.…”

Section: Androgen Metabolismmentioning

confidence: 87%

Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers

Purohit¹,

Foster²

2011

Journal of Endocrinology

116

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Estrogens and androgens are instrumental in the maturation of many hormone-dependent cancers. Consequently, the enzymes involved in their synthesis are cancer therapy targets. One such enzyme, steroid sulfatase (STS), hydrolyses estrone sulfate, and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone respectively. These are the precursors to the formation of biologically active estradiol and androstenediol. This review focuses on three aspects of STS inhibitors: 1) chemical development, 2) biological activity, and 3) clinical trials. The aim is to discuss the importance of estrogens and androgens in many cancers, the developmental history of STS inhibitor synthesis, the potency of these compounds in vitro and in vivo and where we currently stand in regards to clinical trials for these drugs. STS inhibitors are likely to play an important future role in the treatment of hormone-dependent cancers. Novel in vivo models have been developed that allow pre-clinical testing of inhibitors and the identification of lead clinical candidates. Phase I/II clinical trials in postmenopausal women with breast cancer have been completed and other trials in patients with hormone-dependent prostate and endometrial cancer are currently active. Potent STS inhibitors should become therapeutically valuable in hormone-dependent cancers and other non-oncological conditions.

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“…STS activity is present in prostatic tissue and in LNCaP cells, which were derived from prostatic cancer tissue [18,19]. In men with prostate cancer, castration results in only a 50% reduction in prostatic tissue concentrations of dihydrotestosterone [20].…”

Section: Sts Inhibitors In Prostate and Endometrial Cancersmentioning

confidence: 99%

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

et al. 2007

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Key Words. Breast cancer • Estrogen • Estrone sulfate • Steroid sulfatase • Sulfatase inhibitor LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the role of steroid sulfatase in regulating estrogen production in postmenopausal women.2. Describe the potential of steroid sulfatase inhibition in cancer therapy.3. Discuss a potential new endocrine therapy for patients progressing on aromatase.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTInhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to estrone and DHEA, which can be converted to steroids with potent estrogenic properties, that is, estradiol and androstenediol, respectively. Several potent irreversible STS inhibitors have now been identified, including STX64 (BN83495), a tricyclic sulfamate ester. This drug recently completed the first-ever trial of this new type of therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. STX64, tested at 5-mg and 20-mg doses, was able to almost completely block STS activity in peripheral blood lymphocytes and tumor tissues. Inhibition of STS activity was associated with significant reductions in serum concentrations of androstenediol and estrogens. Unexpectedly, serum androstenedione concentrations also decreased by up to 86%, showing that this steroid, which is the main substrate for the aromatase in postmenopausal women, is derived mainly from the peripheral conversion of DHEAS. Of eight patients who completed therapy, five showed evidence of stable disease for up to 7.0 months. This new endocrine therapy offers considerable potential for the treatment of hormone-dependent breast cancer in postmenopausal women.

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Human prostatic dehydroepiandrosterone sulfate sulfatase

Cited by 44 publications

References 13 publications

Dehydroepiandrosterone sulphate sulphoydrolase from human placenta microsomes—Properties of the purified enzyme

Dehydroepiandrosterone sulphate sulphoydrolase from human placenta microsomes—Properties of the purified enzyme

Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

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