Loss of beta-catenin expression in metastatic gastric cancer.

PURPOSE: Beta-catenin (beta-catenin) participates in intercellular adhesion and is an integral part of the Wnt signaling pathway. The role of beta-catenin in the pathogenesis of gastric cancer and its metastasis is largely unknown. PATIENTS AND METHODS: Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines. The beta-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations. Furthermore, methylation of the beta-catenin promoter in cell lines was assessed by treatment with 5'-azadeoxycytidine and sodium bisulfite genomic sequencing. RESULTS: beta-Catenin expression was present at either the cell membrane or the cytoplasm in 34 of 75 primary gastric cancers. Expression of beta-catenin was significantly more frequent in intestinal-type (P =.0049) and well-differentiated gastric cancers (P <.001). There were no quantitative differences between gastric cancers and the nonmalignant gastric tissues, as determined by Western blot analysis. One of 18 metastatic cancer lesions and four of five gastric cancer cell lines expressed beta-catenin protein. N87 cells, derived from the liver metastasis of a gastric cancer, did not express beta-catenin. Treatment with 5'-azadeoxycytidine restored beta-catenin protein levels in this cell line, which exhibited significantly more 5-methylcytosines in the beta-catenin promoter compared with the other cell lines. CONCLUSION: beta-Catenin expression is lost in a subgroup of primary gastric cancers, is frequently absent in metastases, and exhibits nuclear localization in cancers with either beta-catenin or APC gene mutations. Interestingly, the loss of beta-catenin expression in metastatic gastric cancers may result from hypermethylation of the beta-catenin promoter.     

Influence of heparin coating of coronary stents and ex vivo efficacy of different doses of acetylsalicylic acid and ticlopidine in a pulsed floating model of recirculating human plasma

Acute occlusion of stented coronary vessels still occurs in up to 3%. Acitvated platelets have been found to play a major role in the pathogenesis of these complications. We therefore analyzed the efficacy of a heparin coating of coronary stents and investigated the ex vivo efficacy of different antiplatelet drugs. Each of seven healthy volunteers was treated with each of the following medications for 7 days: ASA 100 mg/day, ASA 300 mg/day, ticlopidine 250 mg/day, and ticlopidine 500 mg/day. Three standardized in vitro silicon tubing models, one of them containing an uncoated stent, one a heparin-coated stent, and one without a stent (control) were filled with PRP and circulation was started. TOS in systems with heparin-coated stents was 2.4-times longer compared to systems with uncoated stents ( P <0.001), and 1.5-times longer compared to the control ( P <0.01). The increase of CD62p expression within the first 5 min was 2.5-times higher in systems with uncoated stents and 1.7-times higher in the control than in systems with heparin-coated stents ( P <0.05). Aggregometry revealed significant medication- and dose-dependent inhibition of platelet aggregability for all medications. Heparin-coating of coronary stents reduces their thrombogenicity significantly. ASA and ticlopidine effectively reduce platelet activation ex vivo . The used in vitro system facilitates a reproducible method to estimate the thrombogenicity of coronary stents prior to in vivo trials.     

Criteria for Emergency Brain MRI During Stroke-Alert

ObjectivesIntravenous (IV) tissue plasminogen activator (tPA) should be given to patients with acute ischemic stroke (AIS) and avoided in stroke mimics (SM). Select use of emergency brain magnetic resonance imaging (eMRI-brain) in stroke-alerts aids diagnosis, but accepted utilization criteria for eMRI-brain do not currently exist. We developed criteria for eMRI-brain and report the yield of eMRI-brain in stroke-alert patients.Materials and MethodsWe developed three history-based criteria for performing eMRI-brain during stroke-alerts: (1) history of previous similar deficits, (2) change in consciousness at onset of symptoms, (3) symptom presentation consistent with migraine aura. We then performed a retrospective chart review of patients who presented as a stroke-alert over a 5-year period and determined how these criteria affected administration of IV tPA to AIS and SM patients.ResultsAmong 3,512 stroke-alerts, 230 (8.1%) patients met our criteria for eMRI-brain exams: 217 (92.6%) had SM and 17 (7.4%) had AIS. Our IV tPA decision-making analysis showed that based on eMRI-brain IV tPA was less frequently administered to SM patients (PCC-0.841, p=0.036) with less failures to administer IV tPA to patients with AIS (PCC -0.907, p-value=0.013, Pearson correlation coefficient). No patients became ineligible for IV tPA due to MRI-related time delays.ConclusionsOur history based criteria for performing eMRI-brain during stroke-alerts show a high yield of stroke mimics. Selective eMRI-brain improves decision-making accuracy regarding IV tPA administration.     

Gesundheit und Frühe Hilfen: Die intersektorale Kooperation im Blick der Forschung

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