			Home About us Contact

Androgen-independent Prostate Carcinoma (androgen-independent + prostate_carcinoma)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells: Location, hydrolysis and 12-lipoxygenase metabolism

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2007
Michael P. Endsley
Abstract Endogenous 2-arachidonoylglycerol (2-AG) is antiinvasive in androgen-independent prostate carcinoma (PC-3) cells. Invasion of PC-3 cells is also inhibited by exogenously added noladin ether, a non-hydrolyzable analog of 2-AG. In contrast, exogenous 2-AG has the opposite effect. Cell invasion significantly increased with high concentrations of exogenous 2-AG. In PC-3 cells, arachidonic acid (AA) and 12-hydroxyeicosatetraenoic acid (12-HETE) concentrations increased along with exogenously added 2-AG, and 12-HETE concentrations increased with exogenously added AA. Invasion of PC-3 cells also increased with exogenously added AA and 12(S)-HETE but not 12(R)-HETE. The exogenous 2-AG-induced invasion of PC-3 cells was inhibited by 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP, an inhibitor of 2-AG hydrolysis) and baicalein (a 12-LO inhibitor). Western blot and RT-PCR analyses indicated expression of 12-HETE producing lipoxygenases (LOs), platelet-type 12-LO (P-12-LO) and leukocyte-type 12-LO (L-12-LO), in PC-3 cells. These results suggest that exogenous 2-AG induced, rather inhibited, cell invasion because of its rapid hydrolysis to free AA, and further metabolism by 12-LO of AA to 12(S)-HETE, a promoter of PC cell invasion. The results also suggest that PC-3 cells and human prostate stromal (WPMY-1) cells released free AA, 2-AG, and 12-HETE. In the microenvironment of the PC cells, this may contribute to the cell invasion. The 2-AG hydrolysis and concentration of 2-AG in microenvironment are critical for PC cell's fate. Therefore, inhibitors of 2-AG hydrolysis could potentially serve as therapeutic agents for the treatment of prostate cancer. © 2007 Wiley-Liss, Inc. [source]

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma

CANCER, Issue 4 2004
David J. Vaughn M.D.
Abstract BACKGROUND The current study determined the efficacy and toxicity of weekly paclitaxel in combination with estramustine phosphate (EMP) in patients with androgen-independent prostate carcinoma (AIPC). METHODS Patients with progressive AIPC received 90 mg/m2 paclitaxel by 1-hour intravenous infusion weekly for 3 weeks, followed by a 1-week treatment rest. Patients received 140 mg EMP orally 3 times daily on the day before, the day of, and the day after paclitaxel administration. Patients received 1 mg warfarin daily to prevent thromboembolism. RESULTS Sixty-six patients with progressive AIPC received treatment at 29 centers. Forty-two percent of patients had a 50% decline in prostate-specific antigen (PSA; 95% confidence interval [CI], 30,54%). For 26 patients with bidimensionally measurable disease, the objective response rate was 15% (95% CI, 1,30%). The median time to disease progression was 6.3 months, and the median time to PSA progression was 11.4 months. The median survival period was 15.6 months. Grade 3,4 toxicities were uncommon and included thromboembolism (8%), anemia (3%), neutropenia (3%), and peripheral neuropathy (2%). There was one treatment-related death. CONCLUSIONS This regimen of EMP plus weekly paclitaxel was an active and well tolerated treatment for patients with AIPC. Cancer 2004;100:746,50. © 2004 American Cancer Society. [source]

Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinoma

CANCER, Issue 3 2002
Report of four cases
Abstract BACKGROUND PC-SPES is an herbal supplement whose mechanisms of action are poorly understood, but may be estrogenic. The objective of the current report is to describe the effects of discontinuing PC-SPES treatment in four patients with androgen-independent prostate carcinoma. METHODS Patient charts were retrospectively reviewed. A MEDLINE search was performed to investigate whether these effects of PC-SPES had been previously reported. RESULTS Four men whose metastatic prostate carcinoma progressed despite androgen ablation and subsequent PC-SPES treatment are described. All four patients developed a rapid increase in serum prostate specific antigen (PSA) within one month of stopping PC-SPES, ranging from 345% to 880%. Two patients increased their PSA levels to 1300% and 1400% after 7 weeks. Compared to the rate of rise of PSA levels prior to and during PC-SPES therapy, the rise after stopping this treatment was much higher than expected. Clinical symptoms remained relatively stable despite the serologic changes. CONCLUSIONS Discontinuing PC-SPES therapy can be associated with a rapid rise in PSA. To the authors' knowledge, this effect has not been reported previously. This effect should be considered in the design of clinical trials as well as in the standard management of androgen-independent prostate carcinoma patients. Cancer 2002;94:686,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10269 [source]