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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Fwd: [The attendance of the second screening period (2004-2005) of the Hungarian organized breast cancer screening program.]

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: [The attendance of the second screening period (2004-2005) of the Hungarian organized breast cancer screening program.]
To: mesothelioma77@gmail.com


[1]Orv Hetil. 2008 Aug 10; 149(32): 1491-8
Boncz I, Sebestyén A, Döbrossy L, Péntek Z, Kovács A, Budai A, Kövi R, Ember I

Aim: Organised, nationwide screening for breast cancer with mammography in the age group of 45-65 years with a 2-year screening interval started in Hungary in January 2002. The aim of this study is to analyze the attendance rate of breast screening programme, including the analysis of the ratio of screening and diagnostic mammography examinations. Data and methods: The data derive from the financial database of the National Health Insurance Fund Administration (NHIFA) covering the 6-year period between 2000-2006. The ratio of women in the age group of 45-65 years was calculated having either a screening mammography or a diagnostic mammography. The analysis was carried out for the years 2000-2001 before and 2002-2003, 2004-2005 after the implementation of nationwide organised programme. Results: In the years 2000-2001 7.26% of the women aged 45-65 had an opportunistic screening mammography, while in 2002-2003 34% and in 2004-2005 29.5% of the target population had screening mammography within the organised programme. During the same periods 19.8% (2000-2001), 22.1% (2002-2003) and 23.2% (2004-2005) of women aged 45-65 had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 26.2% (2000-2001) to 53.5% (2002-2003) and 50.8% (2004-2005). Conclusions: The attendance of the Hungarian organised breast cancer screening programme slightly declined in 2004-2005, and to achieve the expected results in mortality decrease a further improvement of the uptake is necessary.



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Source: http://www.hubmed.org/display.cgi?uids=18672438
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Fwd: [Epidemiological data on radiation-induced breast cancer.]

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: [Epidemiological data on radiation-induced breast cancer.]
To: mesothelioma77@gmail.com


[1]Rev Epidemiol Sante Publique. 2008 Jul 29;
Telle-Lamberton M

BACKGROUND: Female breast cancer is the most frequent cancer, both in incidence and mortality. It is well known that exposure to ionizing radiation increases the risk, but some questions remain concerning low dose and low-dose rate effects and cofactors. These potential effects have to be taken into account to carry out adequate risk assessment on medically exposed populations. A literature review is proposed on this issue. METHODS: A Medline research was undertaken. Keywords used were ionizing radiation, breast cancer and epidemiology. More studies were added through references included in the first list of articles. The focus was placed on studies including quantitative dose-effect relationship analyses. RESULTS: A latency of five to 10 to 13 years is observed in the appearance of risk. The risk diminishes with age at exposure. A diminution with age at risk is also suspected. The excess relative risk per gray varies between 0.3 and 1.5 for an age at first exposure of 25 years. The study of Hiroshima and Nagasaki survivors shows that risk is increased even if doses are restricted to below 0.5Gy. Above high doses (20Gy), the risk no longer increases. This can be interpreted as a cell-killing effect. The excess subsists if doses are fractionated, but a diminution of the effect is suspected. CONCLUSION: The effects of exposure to levels of doses used for medical diagnostic are very difficult to study in the general population by epidemiological methods. Only studies conducted on very young children could achieve enough power, because of their high radiosensitivity. Available information on the effects of doses above 0.5Gy allows extrapolation on maximal effects. Models deduced from existing cohorts can be used to assess risk, with their limits due to associated uncertainties. Preston et al. proposed an excess absolute-risk model, which makes estimates from the more comprehensive cohorts compatible. This model has been retained by the 2006 committee "Biological effects of ionizing radiation" (report VII).



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Source: http://www.hubmed.org/display.cgi?uids=18672338
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Fwd: Perspectives on hormone replacement therapy: the Women's Health Initiative and new observational studies sampling the overall population.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: Perspectives on hormone replacement therapy: the Women's Health Initiative and new observational studies sampling the overall population.
To: mesothelioma77@gmail.com


[1]Fertil Steril. 2008 Aug; 90(2): 258-64
Tannen RL, Weiner MG, Xie D, Barnhart K

This commentary integrates the most recent information on coronary heart disease from the Women's Health Initiative (WHI) trial and our new large observational studies, which complement and expand the WHI results to the overall population. Breast and colon cancer findings are also considered.



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Source: http://www.hubmed.org/display.cgi?uids=18672122
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Fwd: Breast cancer stem cells: implications for therapy of breast cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Aug 3, 2008 at 8:08 AM
Subject: Breast cancer stem cells: implications for therapy of breast cancer.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res. 2008 Jul 22; 10(4): 210
Morrison BJ, Schmidt CW, Lakhani SR, Reynolds BA, Lopez JA

ABSTRACT: The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to more meaningful clinical remissions. Here, we review the role of stem cells in the healthy breast, the role of breast cancer stem cells in disease, and the potential to target these cells.



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Source: http://www.hubmed.org/display.cgi?uids=18671830
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