Fwd: Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer.
To: mesothelioma77@gmail.com


[1]Prostate. 2008 Jul 30;
Singh P, Hallur G, Anchoori RK, Bakare O, Kageyama Y, Khan SR, Isaacs JT

BACKGROUND: The standard hormonal therapy with currently available antiandrogens and the leutinizing hormone releasing hormone (LHRH) analogs is not effective in the hormone-refractory stage of prostate cancer due to changes in androgen receptor (AR) signaling axis. In this refractory stage, AR continues to play a significant role in the growth of cancer cells even though the cancer cells are no longer dependent on the level of circulating androgens. METHODS: A series of 11beta-Delta(9)-19 nortestosterone compounds were designed through structure-based rationale and tested for their binding affinity against AR and glucocorticoid receptor (GR) using fluorescence polarization assays, their agonistic ability to induce AR dependent transcription using PSA-driven report gene assays, and their growth inhibitory affects against a series of AR positive (LAPC4, LNCap, and CWR22R) and negative human prostate cancer cell lines (PC3) using MTT cell proliferation assays. RESULTS: This study proposes the design of novel bifunctional antiandrogens based on the conjugation of 11beta and/or 7alpha-Delta(9)-19 nortestosterone class of steroidal compounds to the synthetic ligand for FK506-binding proteins. As a critical step towards the development of bifunctional antiandrogens, highly potent and AR-specific lead compounds were identified using in vitro data. The lead compounds identified in this study possessed low binding affinity for GR, indicating the absence of undesirable antiglucocorticoid activity. CONCLUSIONS: The results of this study validate our drug discovery rationale based on the structural biology of AR and pave the pay for future development of bifunctional compounds in order to block AR function in hormone refractory stage of prostate cancer. Prostate (c) 2008 Wiley-Liss, Inc.



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Source: http://www.hubmed.org/display.cgi?uids=18668523
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Fwd: Is pleomorphic lobular carcinoma really a distinct clinical entity?

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Fri, Aug 1, 2008 at 4:32 PM
Subject: Is pleomorphic lobular carcinoma really a distinct clinical entity?
To: mesothelioma77@gmail.com


[1]J Surg Oncol. 2008 Jul 30;
Buchanan CL, Flynn LW, Murray MP, Darvishian F, Cranor ML, Fey JV, King TA, Tan LK, Sclafani LM

BACKGROUND: Attempts to define the clinical behavior of pleomorphic lobular carcinoma (PLC) have been limited to small series, and clinical management strategies have yet to be established. We describe our experience with PLC as compared to classic ILC and invasive ductal carcinoma (IDC). METHODS: From 9/1996 to 5/2003, clinical and histopathologic data for 5,635 patients undergoing primary surgical treatment and sentinel lymph node biopsy for breast cancer were collected. Four hundred eighty one (8.5%) patients were diagnosed with ILC; 3,978 (70.6%) with IDC. Of those with ILC, 356 (74%) patients had material available for pathologic re-review and comprise our study population: 52 were classified as PLC; 298 were classified as classic ILC; and 6 cases were reclassified as IDC. We compared clinical, pathologic, and treatment factors for patients with PLC, ILC, and IDC using the Wilcoxon rank sum and Fisher's exact tests. RESULTS: PLC were larger than ILC and IDC (20 vs. 15 vs. 13, P

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Source: http://www.hubmed.org/display.cgi?uids=18668643
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