59,095 research outputs found

    RT-PCR Analysis of TOPBP1 Gene Expression in Hereditary Breast Cancer

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    Hereditary predisposition to breast cancer determined in large part by loss of function mutations in one of two genes BRCA1 and BRCA2. Besides BRCA1 and BRCA2 other genes are also likely to be involved in hereditary predisposition to breast cancer. TopBP1 protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Expression of TopBP1 gene at the mRNA level was analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 94 samples of hereditary breast cancer. Analysis of TopBP1 mRNA level showed that expression of TopBP1 is significantly downregulated in poorly differentiated breast cancer (grade III according Bloom-Richardson system (P<0.05)

    Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats.

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    BackgroundEstrogen deficiency is thought to be responsible for the higher frequency of aneurysmal subarachnoid hemorrhage in post- than premenopausal women. Estrogen replacement therapy appears to reduce this risk but is associated with significant side effects. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor (ER) modulator with fewer estrogenic side effects, reduces cerebral aneurysm rupture in a new model of ovariectomized rats.MethodsTen-week-old female Sprague-Dawley rats were subjected to ovariectomy, hemodynamic changes, and hypertension to induce aneurysms (ovariectomized aneurysm rats) and treated with vehicle or with 0.3 or 1.0 mg/kg/day bazedoxifene. They were compared with sham-ovariectomized rats subjected to hypertension and hemodynamic changes (HT rats). The vasoprotective effects of bazedoxifene and the mechanisms underlying its efficacy were analyzed.ResultsDuring 12 weeks of observation, the incidence of aneurysm rupture was 52% in ovariectomized rats. With no effect on the blood pressure, treatment with 0.3 or 1.0 mg/kg/day bazedoxifene lowered this rate to 11 and 17%, almost the same as in HT rats (17%). In ovariectomized rats, the mRNA level of ERα, ERβ, and the tissue inhibitor of metalloproteinase-2 was downregulated in the cerebral artery prone to rupture at 5 weeks after aneurysm induction; the mRNA level of interleukin-1β and the matrix metalloproteinase-9 was upregulated. In HT rats, bazedoxifene restored the mRNA level of ERα and ERβ and decreased the level of interleukin-1β and matrix metalloproteinase-9. These findings suggest that bazedoxifene was protective against aneurysmal rupture by alleviating the vascular inflammation and degradation exacerbated by the decrease in ERα and ERβ.ConclusionsOur observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans

    Estradiol, Progesterone, and Transforming Growth Factor α Regulate Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Expression in Mouse Endometrial Cells

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    Insulin-like growth factor 1 (IGF1) Is Involved in the proliferation of mouse and rat endometrial cells in a paracrine or autocrine manner. Insulin-like growth factor binding protein-3 (IGFBP3) modulates actions of IGFs directly or indirectly. The present study aimed to determine whether IGFBP3 is Involved In the regulation of proliferation of mouse endometrial cells. Mouse endometrial epithelial cells and stromal cells were isolated, and cultured In a serum free medium. IGF1 stimulated DNA synthesis by endometrial epithelial and stromal cells, and IGFBP3 Inhibited IGF1-induced DNA synthesis. Estradiol-17 beta (E2) decreased the Igfbp3 mRNA level in endometrial stromal cells, whereas It Increased the Igf1 mRNA level. Transforming growth factor alpha (TGF alpha) significantly decreased IGFBP3 expression at both the mRNA and secreted protein levels in endometrial stromal cells. Progesterone (134) did not affect the E2-induced down-regulation of Igfbp3 mRNA expression in endometrial stromal cells, although P4 alone increased Igfbp3 mRNA levels. The present findings suggest that in mouse endometrial stromal cells E2 enhances IGF1 action through enhancement of IGF1 synthesis and reduction of IGFBP3 synthesis, and that TGF alpha affects IGF1 actions through modulation of IGFBP3 levels

    The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: MiR-21 and promoter methylation

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    Background: PTEN is a tumor suppressor gene which is involved in cellular proliferation, differentiation, and apoptosis. Loss or down-regulation of PTEN plays an important role in human cancers development. In this study, we investigated the effect of miR-21 and promoter methylation on the PTEN expression status in CRC tissues and analyzed association of the PTEN expression status with clinicopathological features in patients with CRC. Results: The PTEN expression was positively detected in 67.2 CRC tissues and all adjacent non-cancerous samples. PTEN mRNA level was negatively correlated with miR-21 level (r = -0.595, P < 0.001). PTEN expression was also correlated directly with the PTEN mRNA level (r = 0.583, P < 0.001) and conversely with miR-21 level (r = -0.632, P < 0.001). PTEN Promoter methylation was significantly associated with PTEN expression status (p = 0.013). PTEN expression was negatively associated with tumor size (p = 0.007) and advanced tumor stage (P = 0.011). Multivariate analysis indicated that tumor stage, tumor differentiation and PTEN expression status were independent prognostic factors for overall carcinoma in CRC patients (P < 0.05). The Kaplan-Meier curve indicated a negative correlation between PTEN expression levels and survival of CRC patients (P = 0.013). Conclusions: This study suggests a high frequency of miR-21 overexpression and aberrant promoter methylation in down-regulation of PTEN expression in colorectal carcinoma. Loss of PTEN may be a prognostic factor for patients with CRC. © 2016 Yazdani et al

    Assessing the impact of non-additive noise on modelling transcriptional regulation with Gaussian processes

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    In transcriptional regulation, transcription factors (TFs) are often unobservable at mRNA level or may be controlled outside of the system being modelled. Gaussian processes are a promising approach for dealing with these difficulties as a prior distribution can be defined over the latent TF activity profiles and the posterior distribution inferred from the observed expression levels of potential target genes. However previous approaches have been based on the assumption of additive Gaussian noise to maintain analytical tractability. We investigate the influence of a more realistic form of noise on a biologically accurate system based on Michaelis-Menten kinetics

    H3 mRNA level as a new proliferative marker in astrocytomas

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    AbstractReplication-dependent H3.1 and H3.2 histones are encoded by 11 genes. The H3 mRNA levels in brain astrocytomas using real-time RT-PCR assay was examined. The sequence of primers and probe used in amplification was designed basing on the reference sequence GenBank accession no. Z83737. The H3 mRNA levels correlated with tumor grade (R=0.56, P=0.0012), Ki-67 proliferative antigen labeling index (R=0.58, P=0.0008) and patient survival time (R=−0.50, P=0.005), discriminating low-grade and high-grade tumors. Quantification of H3 mRNA with real-time RT-PCR using the proposed pair of primers may supplement classic proliferative tests and predictive factors in brain astrocytomas

    Stochastic Simulations of the Repressilator Circuit

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    The genetic repressilator circuit consists of three transcription factors, or repressors, which negatively regulate each other in a cyclic manner. This circuit was synthetically constructed on plasmids in {\it Escherichia coli} and was found to exhibit oscillations in the concentrations of the three repressors. Since the repressors and their binding sites often appear in low copy numbers, the oscillations are noisy and irregular. Therefore, the repressilator circuit cannot be fully analyzed using deterministic methods such as rate-equations. Here we perform stochastic analysis of the repressilator circuit using the master equation and Monte Carlo simulations. It is found that fluctuations modify the range of conditions in which oscillations appear as well as their amplitude and period, compared to the deterministic equations. The deterministic and stochastic approaches coincide only in the limit in which all the relevant components, including free proteins, plasmids and bound proteins, appear in high copy numbers. We also find that subtle features such as cooperative binding and bound-repressor degradation strongly affect the existence and properties of the oscillations.Comment: Accepted to PR

    Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice

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    The study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days were also studied. Snca mRNA levels were increased in the raphe nuclei in the losers and in the VTA of the winners. After fighting deprivation Snca mRNA levels were decreased to the control level in both groups. Snca mRNA levels were similar to the control level in the VTA of the losers and in the raphe nuclei of the winners. However Snca gene expression was increased in these areas after no-fight period in the winners and losers in comparison with respective mRNA levels in the undeprived animals. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei. It was concluded, that social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice