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1تقرير
المؤلفون: Melling, Nathaniel, Muth, Johanna, Simon, Ronald, Bokemeyer, Carsten, Terracciano, Luigi, Sauter, Guido, Izbicki, Jakob, Marx, Andreas
مصطلحات موضوعية: Biological markers, Cell cycle checkpoints, Colorectal neoplasms, Immunohistochemistry, Prognosis
الوصف: Background Cdc7 is a widely expressed protein kinase implicated in cell division, cell cycle checkpoint mechanisms and cancer progression. Recently, it has been suggested as a target for anti-cancer therapy. Methods To determine the relationship of Cdc7 protein expression with tumor phenotype, molecular features and prognosis, 1800 colorectal carcinomas were analyzed by immunohistochemistry on a tissue microarray. Results Cdc7 expression was considered negative in 33.6 %, weak in 57.2 % and strong in 9.2 % of 1711 interpretable CRCs. Loss of Cdc7 expression was significantly associated with high tumor stage ( p < 0.0001) and high tumor grade ( p = 0.0077), but was unrelated to the nodal status ( p = 0.5957). Moreover, a link between Cdc7 expression and the tubular histological tumor type was seen ( p < 0.0001). p53 and Cdc7 expression were significantly linked to each other ( p = 0.0013). In a multivariate survival analysis, strong Cdc7 expression of CRC was an independent marker of improved patient survival ( p = 0.0031). Conclusion Our data show that Cdc7 is highly expressed in CRC and a potential therapeutic target in a subset of cancers with high p53 expression. Moreover, our findings strongly argue for a clinical utility of Cdc7 immunostaining as an independent prognostic biomarker in colorectal cancer enabling to select patients for adjuvant treatment.
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2مراجعة
المؤلفون: Tyson, John, Novák, Béla
مصطلحات موضوعية: Mathematical models, Mitosis-promoting factor, Cell cycle checkpoints, Regulated kinases, Regulated phosphatases, Regulated proteolysis
الوصف: In this essay we illustrate some general principles of mathematical modeling in biology by our experiences in studying the molecular regulatory network underlying eukaryotic cell division. We discuss how and why the models moved from simple, parsimonious cartoons to more complex, detailed mechanisms with many kinetic parameters. We describe how the mature models made surprising and informative predictions about the control system that were later confirmed experimentally. Along the way, we comment on the ‘parameter estimation problem’ and conclude with an appeal for a greater role for mathematical models in molecular cell biology.
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3مراجعة
المؤلفون: Bertwistle, David, Ashworth, Alan
مصطلحات موضوعية: BRCA1, BRCA2, breast cancer, cell cycle checkpoints, DNA repair, gene expression
الوصف: Women with mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2 , have an increased risk of developing breast cancer. Both BRCA1 and BRCA2 are thought to be tumour suppressor genes since the wild type alleles of these genes are lost in tumours from heterozygous carriers. Several functions have been proposed for the proteins encoded by these genes which could explain their roles in tumour suppression. Both BRCA1 and BRCA2 have been suggested to have a role in transcriptional regulation and several potential BRCA1 target genes have been identified. The nature of these genes suggests that loss of BRCA1 could lead to inappropriate proliferation, consistent with the high mitotic grade of BRCA1 -associated tumours. BRCA1 and BRCA2 have also been implicated in DNA repair and regulation of centrosome number. Loss of either of these functions would be expected to lead to chromosomal instability, which is observed in BRCA1 and BRCA2 -associated tumours. Taken together, these studies give an insight into the pathogenesis of BRCA -associated tumours and will inform future therapeutic strategies.
