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PubMed · 12230642

Stroke management.

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Gord Gubitz, Peter Sandercock. 2002. Stroke management.. https://pubmed.ncbi.nlm.nih.gov/12230642/

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Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin.

The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/).

Aspirin↗

Why are eligible patients not prescribed aspirin in primary care? A qualitative study indicating measures for improvement.

BACKGROUND: Despite evidence-based guidelines, aspirin prescribing for the secondary prevention of stroke is sub-optimal. Little is known about why general practitioners do not prescribe aspirin to indicated patients. We sought to identify and describe factors that lead general practitioners (GPs) not to prescribe aspirin to eligible stroke patients. This was the first stage of a study exploring the need for and means of improving levels of appropriate aspirin prescribing. METHOD: Qualitative interviews with 15 GPs in the West Midlands. RESULTS: Initially, many GPs did not regard their prescribing as difficult or sub-optimal. However on reflection, they gave several reasons that lead to them not prescribing aspirin for eligible patients or being uncertain. These include: difficulties in applying generic guidelines to individuals presenting in consultations, patient resistance to taking aspirin, the prioritisation of other issues in a time constrained consultation and problems in reviewing the medication of existing stroke patients. CONCLUSION: In order to improve levels of appropriate aspirin prescribing, the nature and presentation risk information available to GPs and patients must be improved. GPs need support in assessing the risks and benefits of prescribing for patients with combinations of complicating risk factors, while means of facilitating improved GP-patient dialogue are required to help address patient uncertainty. A decision analysis based support system is one option. Decision analysis could synthesise current evidence and identify risk data for a range of patient profiles commonly presenting in primary care. These data could then be incorporated into a user-friendly computerised decision support system to help facilitate improved GP-patient communication. Measures of optimum prescribing based upon aggregated prescribing data must be interpreted with caution. It is not possible to assess whether low levels of prescribing reflect appropriate or inappropriate use of aspirin in specific patients where concordance between the GP and the patient is practised.

Aspirin↗