993 resultados para 221


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Background: CD56 expression has been associated with a poor prognosis in lymphoid neoplasms, including T-cell acute lymphoblastic leukemia (T-ALL). MicroRNAs (miRNAs) play an important role in lymphoid differentiation, and aberrant miRNA expression has been associated with treatment outcome in lymphoid malignancies. Here, we evaluated miRNA expression profiles in normal thymocytes, mature T-cells, and T-ALL samples with and without CD56 expression and correlated microRNA expression with treatment outcome. Methods: The gene expression profile of 164 miRNAs were compared for T-ALL/CD56+ (n=12) and T-ALL/CD56- (n=36) patients by Real-Time Quantitative PCR. Based on this analysis, we decided to evaluate miR-221 and miR-374 expression in individual leukemic and normal samples. Results: miR-221 and miR-374 were expressed at significantly higher levels in T-ALL/CD56+ than in T-ALL/CD56- cells and in leukemic blasts compared with normal thymocytes and peripheral blood (PB) T-cells. Age at diagnosis (15 or less vs grater than 15 years; HR: 2.19, 95% CI: 0.98-4.85; P=0.05), miR-221 expression level (median value as cut off in leukemic samples; HR: 3.17, 95% CI: 1.45-6.92; P=0.004), and the expression of CD56 (CD56- vs CD56+; HR: 2.99, 95% CI: 1.37-6.51; P=0.006) were predictive factors for shorter overall survival; whereas, only CD56 expression (HR: 2.73, 95% CI: 1.03-7.18; P=0.041) was associated with a shorter disease-free survival rate. Conclusions: miR-221 is highly expressed in T-ALL and its expression level may be associated with a poorer prognosis.

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Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.

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A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high-risk prostate cancer, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway. miR-221 expression sensitized prostate cancer cells for IFN-γ-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer.

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Beilage 2 fehlt

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Welsch (Projektbearbeiter): Stellungnahme Sethes zum Konflikt von Krone und Nationalversammlung: Der Protest der Volksvertreter gegen das Ministerium Brandenburg stellt einen Eingriff in die Rechte des Königs dar. Da eine Verfassung jedoch bislang nicht geschaffen wurde, sind nach wie vor die alten Gesetze gültig, und danach ist a) der König berechtigt, die Nationalversammlung an einen beliebigen Ort zu berufen und zu verlegen, b) die Regierung berechtigt, den Belagerungszustand zu verhängen und c) gibt es keinerlei rechtliche Grundlage für eine Anklage gegen das Staatsministerium. Eine Anklage jedoch, die das Staatsministeriums des Hochverrats bezichtigt (§ 92, Tit. 20, Tl. II Allg. Landrecht) ist rechtlich unhaltbar. Vonnöten ist folglich die alsbaldige Ausarbeitung einer Verfassung

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Tod eines Bekannten, Dank für ein Gedicht, Königstein, Frankfurter Latern, Kladderadatsch

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130 Briefe zwischen Max Horkheimer und Leo Löwenthal, September 1946 - April 1947; 4 Briefe zwischen Samuel H. Flowerman und Max Horkheimer, 1946; 1 Brief von Walter Hallstein an Leo Löwenthal, 03.03.1947; 1 Brief von Herman L. Filene an Frederick Wild, 18.09.1946; 1 Brief von Leo Löwenthal an Frederick Pollock, 16.09.1946; 2 Briefe (Auszüge) von William M. Bennett an Leo Löwenthal, September 1946; 1 Brief von Jim Farrell an Leo Löwenthal, 06.09.1946; 1 Brief von Leo Löwenthal an Edward N. Barnhart, 21.04.1947; 1 Brief von John Slawson an Max Horkheimer, 20.03.1947; 1 Brief von Max Horkheimer an Marjorie Fiske, 12.03.1947;

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Vorbesitzer: P. Henckel

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Vorbesitzer: P. Henckel;

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Fil: Poquet, Adriana.