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  Hydroxyurea DNA synthesis requires production of deoxyribonucleotides and ribon

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wangqian
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Počet príspevkov : 115
Registration date : 28.11.2013

 Hydroxyurea DNA synthesis requires production of deoxyribonucleotides and ribon Empty
OdoslaťPredmet: Hydroxyurea DNA synthesis requires production of deoxyribonucleotides and ribon    Hydroxyurea DNA synthesis requires production of deoxyribonucleotides and ribon Icon_minitimePo február 10, 2014 7:54 am

revealed a gradual decrease in cell membrane B catenin immunoreactivity from normal to atypical hyperplasia and to grade 3 carcinomas. Disruption in both B catenin and E cadherin expression is associated with reduced cell to cell adhesion, Amuvatinib 臨床試験 the advancement of the clinical stage of the disease and the increased risk of metastasis, The Wnt signaling pathway is a multi protein complex consisting of axins, B catenin, APC, kinase CKI and GSK3B, In the absence of Wnt ligands, the APC GSK3B Axin complex is activated which results in phos phorylation of B catenin and its ubiquitination and proteasomal inactivation. Once the Wnt pathway is activated, APC GSK3B Axin does not form a complex with B catenin and phosphorylation of this protein is inhibited.<br><br> Stabilized B catenin is translocated to the nucleus and is assembled AT-406 代理店 into a complex with tran scription factors LEF and TCF, promoting expression of many genes involving in cell proliferation, angio genesis, adhesion and apoptosis, Activation of B catenin Wnt pathway is a physiological phenomenon during the menstrual cycle, but it differs among cycle phases. Nei et al. showed the presence of nuclear B catenin in the proliferative phase, whereas during the secretory phase the protein was found mainly in the cytoplasm and the cell membrane. Estradiol can change the expression of the Wnt ligands including Wnt 4 and 7A, Furthermore, it is also linked to Wnt and PI3k Akt signaling pathways. It was found that after estrogen stimulation, ER alpha induced PI3K and subsequently activated Akt.<br><br> This in turn re sulted in phosphorylation and inhibition of GSK3, Consequently, B catenin cannot be phosphorylated and degraded in proteasomes. A number of studies indicate disruptions in B catenin expression in EC, most frequently in the endometrioid AG-490 臨床試験 type. Mutations in CTNNB1, but also in other genes encoding proteins taking part in Wnt pathway, result in stabilization of B catenin, its excessive nuclear accumulation and promotion of many genes which lead to neoplastic transformation, Konopka et al. found mutations in the CTNNB1 region in 16. 1% of ECs. The mutations detected at the atypical hyperplastic endometrium and the early stages of EC suggest their significant role in early carcinogenesis, Limited literature concerning B catenin expression in diabetic EC patients makes it impossible to compare our findings to other studies.<br><br> In our material concerning EC, B catenin nuclear staining was found in 13. 9% of cases which corresponds accordingly to the Nout et al. research of 14%. In our findings the majority of cases con cerned non diabetic patients with EC, Due to a small number of diabetic patients with a positive nuclear reaction, it is difficult to assess the influence of anti diabetic treatment on nuclear accumulation of B catenin. However, if met formin reduces the expression of ER, which was dem onstrated in our study, it is presumed that it may also decrease the activation of PI3K Akt signaling, increasing the unphosphorylated fraction of GSK3 and reducing the amount of B catenin. Further studies are necessary to examine the correlation between B catenin expression, Wnt pathway activation and diabetes in women with EC.
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