Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells

BACKGROUND: Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer. METHODS: The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data. RESULTS: Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents. CONCLUSIONS: Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer

Evaluating the Validity of Quality Indicators for Colorectal Cancer Care

BackgroundQuality indicators (QI) have been developed to measure quality of colorectal cancer care in the Netherlands. The aim of this study is to evaluate if these QI consistently assess the quality of colorectal cancer care in a hospital (internal consistency) and if these QI correlate with each other (construct validity). MethodsThe performance of 85 hospitals participating in the Dutch Surgical Colorectal Audit between the 1st of January 2010 and 31st of December 2010, were evaluated on nine QI: three process indicators for colon cancer, three process indicators for rectal cancer and three outcome indicators. Consistency between all process indicators was assessed, and correlations between all process and outcome indicators were evaluated for colon and rectal cancer care separately. ResultsHospital performance on the nine QI ranged widely. There was little consistency between the process indicators in assessing hospital performance. Most evaluated process indicators for colorectal cancer care did not correlate with each other, but were associated with better hospital specific patient outcomes. ConclusionQI on colorectal cancer care do provide complementary information. Individual QI are not suitable as a surrogate measure for the quality of colorectal cancer care. More comprehensive measures are needed for true assessment of hospital performance. J. Surg. Oncol. 2013; 108:465-471. (c) 2013 Wiley Periodicals, Inc