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51.
52.
Guo-Qiang Zhang Chuan He Li Tao Feng Liu 《International journal of clinical and experimental pathology》2015,8(6):6944-6951
Breast cancer which has a high incidence rate is the 2nd lethal diseases only followed by lung cancer in women. How to improve the recovery rate is the principal problem should be solved in clinical. Previous studies demonstrated the importance of DJ-1 in the existence of breast cancer for the secreted of protein into serum by breast cancer cells both in vitro and in vivo. So the DJ-1 probably could be selected as the target in breast cancer treatment. Adriamycin resistance breast cancer cells MCF-7 and DJ-1 siRNA plasmid were employed to explore the potential clinical application of DJ-1 in this study. Our results showed that the sensitivity of cancer cells to chemotherapeutics was significantly improved with the transfection of DJ-1 siRNA. Further mechanism studies indicated the role of PI3K/AKT/MTOR pathway in the improvement of apoptosis after treatment with adriamycin in DJ-1 silence group. 相似文献
53.
Fan-Dong Meng Yan Li Xin Tian Ping Ma Cheng-Guang Sui Li-Ye Fu You-Hong Jiang 《International journal of clinical and experimental pathology》2015,8(6):6157-6168
Renal cell carcinoma has become the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Because of lack of knowledge in events that correlated with tumor cell migration and invasion, few therapeutic options are available. Therefore, in current study, we explore the anti-tumoral effect of a potential chemopreventive natural product, quercetin, combined with anti-sense oligo gene therapy (inhibiting Snail gene). We found that either one of them had the remarkable effects in suppressing cell proliferation and migration, inducing cell cycle arrest and apoptosis in a ccRCC cell line, Caki-2 cells. The combination of both means provides even strong suppressive effects toward these ccRCC cells. Our study, for the first time, provides the possibility of using a novel treatment for renal cancer, by combining natural product and gene therapy. 相似文献
54.
Shuai Li Yulian Ma Xinfang Hou Ying Liu Ke Li Shuning Xu Jufeng Wang 《International journal of clinical and experimental pathology》2015,8(9):11854-11862
Increasing evidence has shown that microRNAs play critical roles in the initiation and progression of non-small cell lung cancer (NSCLC). miR-185 is deregulated in various cancers, whereas its functional mechanism in NSCLC is still unclear. Here, we confirmed that the expression of miR-185 was significantly down-regulated in NSCLC tissues and cell lines. miR-185 over-expression caused significant suppression of in vitro cell proliferation, migration and invasion, and in vivo tumor growth. We subsequently identified that AKT1 was a target gene of miR-185. Re-expression of AKT1 could partially rescue the inhibitory effects of miR-185 on the capacity of NSCLC cell proliferation and motility. Collectively, we conclude that miR-185 has a critical function by blocking AKT1 in NSCLC cells, and it may be a novel therapeutic agent for miRNA based NSCLC therapy. 相似文献
55.
目的:观察白藜芦醇(RES)对大鼠肾脏缺血-再灌注(I/ R)保护作用并初步探讨其相关机制。方法 SD 大鼠随机分为4组:空白对照组、I/ R 模型组、白藜芦醇(RES)处理组、RES + IR 模型组;检测各组大鼠血清肌酐(Cr)、尿素氮(BUN)及肾脏病理学改变,使用超氧化物歧化酶(SOD)活力、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-PX)试剂盒检测肾脏组织 SOD、MDA、GSH-PX 产生;Western blot 法检测肾脏组织 p-AKT 蛋白水平。结果与空白对照组相比,I/ R模型组 Cr、BUN 含量均有升高,与 I/ R 模型组相比,RES + I/R 模型组 Cr、BUN 含量均有明显下降;病理学检测显示 RES+ I/ R 模型组肾脏损伤较 I/ R 模型组明显减轻,肾小球结构基本正常,细胞间质有少量炎性细胞浸润,基底膜稍有增厚;与空白对照组相比,I/ R 模型组 SOD、MDA、GSH-PX 含量均有升高,与 I/ R 模型组相比,RES + I/ R 模型组 SOD、GSH-PX含量均有明显下降; Western blot 检测显示,与空白对照组相比,I/ R 模型组 p-AKT 表达水平有所降低,但 RES 可提高 p-AKT 表达水平,差异有统计学意义。结论 RES 通过氧化应激保护 I/ R 肾脏损伤,其作用机制可能与 PI3K/ AKT 信号通路活化有关。 相似文献
56.
《现代诊断与治疗》2015,(15):3371-3373
目的通过研究胃黏膜活检组织标本中PTEN,PI3K,Akt的m RNA及蛋白水平的变化,从而证实PTEN/PI3K/AKT通路可能是诱发并参与胃癌发生的重要信号传导通路,使之成为重要的肿瘤治疗新靶点。方法通过研究胃黏膜活检的组织标本,(1)A组:胃炎组(黏膜慢性炎),(2)B组:癌前病变组(萎缩性胃炎、肠上皮化生、异型增生),(3)C组:胃癌组(各种病理类型的胃癌),研究各项指标的变化1用RT-PCR检测各组PTEN的m RNA水平的变化;2用免疫组织化学方法检测各组PTEN,PI3K,p-AKT蛋白水平的变化。结果 (1)胃黏膜活检的组织标本B组较A组PTEN m RNA及蛋白有下调趋势,但无显著性差异(P>0.05)。C组较A组PTEN m RNA及蛋白均显著下调(P<0.01)。C组较B组PTEN m RNA及蛋白均显著下调(P<0.05)。(2)胃黏膜活检的组织标本B组较A组PI3K蛋白有上调趋势,但无显著性差异(P>0.05)。C组较A组PI3K蛋白均显著上调(P<0.05)。C组较B组PI3K蛋白均显著上调(P<0.05)。(3)胃黏膜活检的组织标本B组较A组p-AKT蛋白有上调趋势,但无显著性差异(P>0.05)。C组较A组p-AKT蛋白均显著上调(P<0.05)。C组较B组p-AKT均有显著上调(P<0.05)。结论 (1)胃黏膜组织内癌前病变组及胃癌组PTEN的表达均低于胃炎组,而PI3K及Akt磷酸化的表达均高于胃炎组,提示在慢性胃炎一萎缩性胃炎一肠上皮化生一异型增生一胃癌这一过程中,可以激活胃黏膜组织PTEN/PI3K/Akt的促增殖信号途径,这可能是胃癌发生的的致病机制之一。(2)PTEN/PI3K/AKT细胞信号网络在慢性胃炎-萎缩性胃炎-肠上皮化生-异型增生-胃癌这一过程中的变化和作用,并参与胃癌的发生,从癌前病变提前干预,从而可减少胃癌的发病率,寻找胃癌分子治疗的可能靶标,从而延长胃癌病人的生存期,减轻患者痛苦,减轻患者经济负担。 相似文献
57.
目的 探讨乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBX)调节miR-199a的表达在HBV相关性肝癌发生中的分子机制.方法 重组HBX腺病毒(Ad-HBX)感染人肝癌HepG2细胞,HBX的siRNA转染稳定表达HBV基因的人肝癌HepG2.2.15细胞,荧光定量PCR方法检测HBV相关性肝癌组织标本和肝癌细胞中HBX、miR-199a、AKT的mRNA表达水平及运用Western blot检测肝癌组织标本和肝癌细胞中HBX、AKT的蛋白表达水平;分别用miR-199a mimics和miR-199a inhibitor的转染肝癌细胞后,荧光定量PCR方法检测肝癌细胞中AKT的mRNA表达水平及运用Westem blot检测肝癌细胞中AKT的蛋白表达水平.结果 miR-199a在HepG2.2.15细胞中表达水平显著低于HepG2细胞,并且证实其表达下调受到了HBX的调控(P<0.05),HepG2.2.15细胞中AKT表达水平显著高于HepG2细胞(P<0.05),在HepG2.2.15细胞中过表达miR-199a能明显下调AKT表达水平以及在HepG2细胞中抑制miR-199a能明显上调的AKT表达水平(P<0.05),此外,miR-199a的表达量在HBV相关性肝癌组织比相应的癌旁组织表达降低.结论 HBX可以通过miR-199a调节AKT导致HBV相关性肝癌发生. 相似文献
58.
Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells 下载免费PDF全文
Ya‐Fang Wang Ting Li Zheng‐Hai Tang Lin‐Lin Chang Hong Zhu Xiu‐Ping Chen Yi‐Tao Wang Jin‐Jian Lu 《Phytotherapy research : PTR》2015,29(5):674-679
Baicalein (BA), isolated from the Chinese medicinal herb Scutellariae radix (Huangqin in Chinese), is a flavonoid with various pharmacological effects. Herein, we found that BA only slightly reduced the cell viability on HepG2 cells after 24‐h treatment as determined by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay. However, BA (50 μM) effectively blocked the colony formation. Meanwhile, BA remarkably induced the formation of autophagosomes after 24‐h treatment as determined by immunofluorescence with monodansylcadaverine staining as well as transmission electron microscopy, respectively. Moreover, BA obviously up‐regulated the expression of microtubule‐associated protein 1A/1B‐light chain 3‐II in concentration‐dependent and time‐dependent manners in HepG2 cells. When combined with the autophagy inhibitor chloroquine and BA, the cell viability and colony formation were significantly decreased, indicating that BA triggered protective autophagy, which prevented cell death. Further study showed that BA concentration‐dependently and time‐dependently decreased the expression of p‐AKT (S473), p‐ULK1 (S757) and p‐4EBP1 (T37 and S65), suggesting the involvement of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) in BA‐triggered autophagy. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
59.
Shannon N. Westin Zhenlin Ju Russell R. Broaddus Camilla Krakstad Jane Li Navdeep Pal Karen H. Lu Robert L. Coleman Bryan T. Hennessy Samuel J. Klempner Henrica M.J. Werner Helga B. Salvesen Lewis C. Cantley Gordon B. Mills Andrea P. Myers 《Molecular oncology》2015,9(8):1694-1703
Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3‐kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathway alterations on progression free survival in a cohort of endometrioid endometrial cancers. Prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss by immunohistochemistry, was explored in the context of patient body mass index. Reverse‐phase protein arrays were utilized to assess protein expression based on PTEN status. Among 187 endometrioid endometrial cancers, there were no statistically significant associations between PFS and PIK3CA, PIK3R1, PTEN mutation or loss. When stratified by body mass index, PTEN loss was associated with improved progression free survival (P < 0.006) in obese (body mass index ≥ 30) patients. PTEN loss resulted in distinct protein changes: Canonical PI3K pathway activation was observed only in the non‐obese population while decreased expression of β‐CATENIN and phosphorylated FOXO3A was observed in obese patients. These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of body mass index, and provide a potential explanation for discrepant reports on the effect of PTEN status and obesity on prognosis in endometrial cancer. This reveals a clinically important interaction between metabolic state and tumor genetics that may unveil the biologic underpinning of obesity‐related cancers and impact ongoing clinical trials with PI3K pathway inhibitors. 相似文献
60.
EZH2 expression is a prognostic factor in childhood intracranial ependymoma: A Canadian Pediatric Brain Tumor Consortium study 下载免费PDF全文
Amanda M. Li MD MSc Christopher Dunham MD Uri Tabori MD Anne‐Sophie Carret MD P. Daniel McNeely MD Donna Johnston MD Lucie Lafay‐Cousin MD Beverly Wilson MD David D. Eisenstat MD MA Nada Jabado MD PhD Shayna Zelcer MD Mariana Silva MD Katrin Scheinemann MD MSc Christopher Fryer MD Glenda Hendson MB BCh Abbas Fotovati PhD Cynthia Hawkins MD PhD Stephen Yip MD PhD Sandra E. Dunn PhD Juliette Hukin MBBS 《Cancer》2015,121(9):1499-1507