Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction

Imaoka, Shingi; Yoneda, Yukio; Sugimoto, Toshikado; Ikemoto, Shinichi; Hiroi, Toyoko; Yamamoto, Keisuke; Nakatani, Tatsuya; Funae, Yoshihiko

doi:10.1016/s0304-3835(00)00572-3

Cited by 36 publications

(20 citation statements)

References 16 publications

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“…ABP can be activated by the P450 CYP4B1 isozyme present in the urothelium, and hence is able to transform HUC-PC cells to become tumorigenic (Imaoka et al, 1997(Imaoka et al, , 2001 and induce tumors in nude mice (Bookland et al, 1992). ABP exposure in vitro results in alterations in the proteomic profile (Kanitz et al, 2004) and F/G ratio (Rao et al, 1990), formation of DNA adducts (Swaminathan et al, 1996), and genomic instability (Kao et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack

Yuen

Gohel

2008

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack

Yuen

Gohel

2008

Journal of Ethnopharmacology

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“…Additionally, Ugt levels were higher in mouse bladders from wild-type females than those from wild-type males, those from castrated males than those from intact males and in those from ARKO males than those from wildtype littermates. The findings from these two studies (55,62) suggest that androgen-mediated AR signals promote bladder carcinogenesis by up-regulating CYP4B1 and downregulating UGTs in the bladder. (31 -33,63,64).…”

Section: Other Animal Modelsmentioning

confidence: 98%

“…In monkey models, orteronel administered orally successfully reduced serum levels of DHEA and testosterone [62]. An initial phase I/II trial established the safety of orteronel and showed its efficacy in patients with metastatic CRPC comparable to that of abiraterone [63].…”

Section: Orteronel (Tak-700)mentioning

confidence: 99%

“…Orteronel is a non-steroidal inhibitor of 17,20-lyase activity of CYP17A1 [62]. In monkey models, orteronel administered orally successfully reduced serum levels of DHEA and testosterone [62].…”

Section: Orteronel (Tak-700)mentioning

confidence: 99%

“…Castration down-regulated cytochrome P450 CYP4B1, which activates amines to more genotoxic substances, in male rat bladders, and testosterone supplement restored CYP4B1 levels (62). We have recently shown that AR signals reduce the levels of UDP-glucuronosyltransferase [UGT (for human)/Ugt (for mouse)], which is known to play an important role in detoxifying bladder carcinogens, such as BBN and NNAL (55).…”

Section: Other Animal Modelsmentioning

confidence: 99%

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Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

Miyata¹

2015

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE May 2015 REPORT TYPEFinal Annual Summary PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERJohn s Hopkins Uni versity 600 N. Wolfe Street Baltimore, Maryland 21287 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTWe hypothesized that dehydroepiandrosterone metabolites or their synthetic derivatives are able to bind to the androgen receptor with low, if any, agonist activity and thus function as better antiandrogens than currently available ones. We preliminarily identified three potential dehydroepiandrosterone derivatives with marginal androgenic activity. In this project, we assessed the effects of these compounds, in comparison with classic antiandrogens clinically used, on cell proliferation/apoptosis, cell migration/invasion, and prostate-specific antigen expression in prostate cancer lines in vitro as well as on tumor growth in animal models for prostate cancer and found their inhibitory effects on androgen-mediated tumor outgrowth. We further dissected molecular mechanisms of how such compounds suppress the progression of prostate cancer and found that they could alter androgen-mediated androgen receptor functions in prostate cancer cells. Importantly, these dehydroepiandrosterone derivatives were found to possess marginal agonist effects on the activity of androgen receptor. SUBJECT TERMS IntroductionAlthough antiandrogens that can block androgen action through the androgen receptor (AR) have been widely used for the treatment of prostate cancer, the majority of available agents possess agonist activity, resulting in increases in serum prostate-specific antigen (PSA) levels, known as the antiandrogen withdrawal syndrome [1,2]. In addition, we previously demonstrated that androstenediol, a physiological metabolite from dehydroepiandrosterone (DHEA) and a precursor of testosterone, has an ...

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Hormonale en reproductieve factoren in de ontwikkeling van blaaskanker

Egbers¹,

Vermeulen²,

Kiemeney³

et al. 2014

Tijdschrift voor Urologie

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Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction

Cited by 36 publications

References 16 publications

The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack

The dual roles of Ganoderma antioxidants on urothelial cell DNA under carcinogenic attack

Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

Hormonale en reproductieve factoren in de ontwikkeling van blaaskanker

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