Breast Cancer Research 2013, 15:R29?doi:10.1186/bcr3409
Published: 8 April 2013Abstract (provisional)
Introduction
Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic breast cancer models, over-expression of COX-2 leads to tumour formation while COX-2 inhibition exerts anti-tumour effects in breast cancer cell lines. To further determine the effect of COX-2 inhibition in primary breast cancer, here we aimed at identifying transcriptional changes in breast cancer tissues of patients treated with the selective COX-2 inhibitor celecoxib.
Methods
In a single-centre double-blinded phase II study, thirty-seven breast cancer patients were randomised to receive either pre-operative celecoxib (400 mg) twice daily for two to three weeks (n = 22) or a placebo likewise (n = 15). Gene expression in fresh-frozen pre-surgical biopsies (before treatment) and surgical excision specimens (after treatment) was profiled by using Affymetrix arrays. Differentially expressed genes and altered pathways were bioinformatically identified. Expression of selected genes was validated by quantitative PCR (qPCR). Immunohistochemical protein expression analyses of the proliferation marker Ki-67, the apoptosis marker cleaved caspase-3, and the neo-angiogenesis marker CD34 served to evaluate biological response.
Results
We identified 972 and 586 significantly up- and down-regulated genes, respectively, in celecoxib-treated specimens. Significant expression changes in six out of eight genes could be validated by qPCR. Pathway analyses revealed over-representation of deregulated genes in the networks of proliferation, cell cycle, extracellular matrix biology, and inflammatory immune response. The Ki-67 mean change relative to baseline was -29.1% (P = 0.019) and -8.2% (P = 0.384) in the treatment and control arm, respectively. Between treatment groups, the change in Ki-67 was statistically significant (P = 0.029). Cleaved caspase-3 and CD34 expression were not significantly different between the celecoxib-treated and placebo-treated group.
Conclusions
Short-term COX-2 inhibition by celecoxib induces transcriptional programs supporting an anti-tumour activity in primary breast cancer tissue. The impact on proliferation-associated genes is reflected by a reduction of Ki-67 positive cells. Therefore, COX-2 inhibition should be considered as treatment strategy for further clinical testing in primary breast cancer. Trial registration: ClinicalTrials.gov NCT01695226.
Source: http://breast-cancer-research.com/content/15/2/R29
12 12 12 Concert miley cyrus miley cyrus amazing race Cam Cameron Ada Lovelace 12/12/12
Also advertised are several sprays for smelly rubbish tins! Has anyone considered emptying the bin instead of spraying a toxic chemical to mask the smell? There must be big business when you take into account the cost of producing ads for TV and magazines to make us feel insecure about our natural world.
উত্তরমুছুনobagi rosacea