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71.
Kristen A. Mitchell 《Biochemical pharmacology》2009,77(6):947-135
The aryl hydrocarbon receptor (AhR) was implicated as a mediator of xenobiotic toxicity over three decades ago. Although a complete picture continues to elude us, investigations by many laboratories during the ensuing period have revealed much about AhR biology in normal physiological processes, as well as the toxicities induced by the dioxins and related polychlorinated aromatic hydrocarbons. The findings are captured in numerous excellent reviews. This commentary attempts to inject a new perspective on some new as well as frequently overlooked observations in the context of established receptor properties. Specifically, we examine the impact of transient versus sustained receptor activation on AhR biology, and explore the potential role for cytochrome P450 expression in regulating AhR activity amongst various tissues. The growing recognition that AhR action functions through multiple mechanisms serves to further highlight the importance of limiting prolonged receptor activation. 相似文献
72.
目的:探讨CDK4蛋白在膀胱移行细胞癌(BTCC)中的表达及其临床意义。方法:采用免疫组化方法,测定10例正常膀胱黏膜及40例BTCC标本中的CDK4蛋白的表达。结果:CDK4蛋白在正常膀胱黏膜和BTCC中的阳性表达率分别为0.00%、52.50%(P<0.05)。CDK4蛋白在G1、G2、G3中的阳性表达率依次为36.84%、61.54%、75.00%,差异无显著性(P>0.05);在Tis~T1中CDK4阳性表达率为40.00%,明显低于T2~T4中的73.33%(P<0.05)。结论:CDK4的过度表达可能在BTCC的进展中发挥了重要作用,CDK4可成为一种新的预后判断的参考指标。 相似文献
73.
Tang Liu Jacson K. Shen Edwin Choy Yu Zhang Henry J. Mankin Francis J. Hornicek Zhenfeng Duan 《Journal of orthopaedic research》2018,36(6):1581-1589
74.
Rafael Benito Rosario Gil‐Benso Vicente Quilis Miguel Perez Mariela Gregori‐Romero Pedro Roldan Jose Gonzalez‐Darder Miguel Cerdá‐Nicolas Concha Lopez‐Gines 《Neuropathology》2010,30(4):392-400
Glioblastomas express a notable heterogeneity in both the histological and cell patterns with glial astrocytic differentiation. Primary glioblastoma, which is the most frequent presentation (90–95%), occurs mainly in older patients and arises de novo, without any clinical or histological evidence of a less malignant precursor lesion. EGFR amplification has been identified as a genetic hallmark of primary glioblastomas and occurs in 40–60% of cases. However, there exist primary glioblastomas without EGFR amplification/overexpression. The purpose of this study was to stabilize the association between cases with and without EGFR gene amplification with clinical and genetic parameters in 45 cases of primary glioblastomas. EGFR amplification was observed in 24 cases (53%), while in the remaining 21 cases (47%) this alteration was not displayed. And whereas EGFR was overexpressed in 79% of cases with EGFR amplification, only 33% of the cases without EGFR amplification showed overexpression. The amplification of EGFR was associated with amplifications in MDM2 and CDK4 and a higher percentage of cases with promoter methylation of INK4a. Only one case of glioblastoma with EGFR amplification presented TP53 mutation simultaneously. Seven remaining cases with TP53 mutations were glioblastomas without EGFR amplification. The INK4a, INK4b and ARF deletions were similar in the two groups. Primary glioblastomas with and without EGFR amplification did not show any significant differences in average survival. The genetic studies suggest the existence of molecular subtypes within primary glioblastoma that may, when fully defined, contribute toward the development of drugs that specifically target tumors with divergent genetic profiles. 相似文献
75.
76.
CDK2、CDK4基因与自体移植静脉内膜增殖的关系 总被引:1,自引:0,他引:1
[目的]了解CDK2、CDK4在大鼠移植血管的表达及对平滑肌细胞增殖的影响。[方法]Wistar大鼠50只,随机分为5组,建立自体静脉移植模型,分别于术后1、2、3、7及14 d取组织形态学观察,并用免疫组织化学和RT-PCR方法检测血管移植后不同时期CDK2、CDK4的表达情况,取正常静脉为对照组。[结果]移植后7 d,内膜厚度与管壁厚度接近高峰,与对照组及移植后1、2、3 d比较,差异有显著性意义(P<0.05)。免疫组织化学显示,移植静脉CDK2、CDK4阳性细胞在移植后2 d明显增加,7 d达到高峰,与移植后1 d比较,差异有显著性意义(P<0.05)。RT-PCR检测结果显示,CDK2、CDK4基因mRNA表达产量7~14 d达到高峰,与移植后1、2、3 d比较,差异有显著性意义(P<0.05)。[结论]CDK2、CDK4蛋白和mRNA表达在移植静脉早期开始增加,在7~14 d达到高峰。在移植静脉内膜增生过程中CDK2、CDK4表达可能起着一定的作用。 相似文献
77.
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79.
Benjamin G. Hale Catherine H. Botting Bernard L. Precious Richard M. Elliott Richard E. Randall 《Virology》2009,383(1):6-11
Posttranslational modification of viral proteins by cellular enzymes is a feature of many virus replication strategies. Here, we report that during infection the multifunctional human influenza A virus NS1 protein is phosphorylated at threonine-215. Substitution of alanine for threonine at this position reduced early viral propagation, an effect apparently unrelated to NS1 antagonizing host interferon responses or activating phosphoinositide 3-kinase signaling. In vitro, a subset of cellular proline-directed kinases, including cyclin dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs), potently phosphorylated NS1 protein at threonine-215. Our data suggest that CDK/ERK-mediated phosphorylation of NS1 at threonine-215 is important for efficient virus replication. 相似文献
80.
Thomas HD Wang LZ Roche C Bentley J Cheng Y Hardcastle IR Golding BT Griffin RJ Curtin NJ Newell DR 《European journal of cancer (Oxford, England : 1990)》2011,47(13):2052-2059
To facilitate the evaluation of CDK2 (cyclin-dependent kinase 2) as a cancer target, the in vitro and in vivo properties of NU6102 (O6-cyclohexylmethyl-2-(4′-sulphamoylanilino)purine) and a water soluble prodrug (NU6301) were investigated. NU6102 selectively inhibited the growth of CDK2 WT (wild type) versus KO MEFs (knockout mouse embryo fibroblasts) (GI50 (concentration required to inhibit cell growth by 50%) 14 μM versus >30 μM), and was more growth-inhibitory in p53 mutant or null versus p53 WT cells (p = 0.02), and in Rb (retinoblastoma protein) WT SKUT-1B versus SKUT 1 Rb deficient cells (p = 0.01). In SKUT-1B cells NU6102 induced a G2 arrest, inhibition of Rb phosphorylation and cytotoxicity (LC50 2.6 μM for a 24 h exposure). The prodrug NU6301 rapidly generated NU6102 in vitro in mouse plasma, and tumour NU6102 levels in vivo consistent with activity in vitro. Eight or 12 hourly dosing of 120 mg/kg NU6301 for 10 days was well tolerated in SKUT-1B tumour-bearing mice and inhibited Rb phosphorylation in tumour tissue. Two (8 hourly dosing) and 3 (12 hourly dosing) day tumour growth delay was observed (p = 0.04 and p = 0.007, respectively) following NU6301 administration. NU6102 and its prodrug NU6301 have pharmacological properties consistent with CDK2 inhibition, and represent useful tool molecules for the evaluation of CDK2 as a target in cancer. 相似文献