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131.
Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma
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Georgia Levidou Dimitrios Theodorou Nikolaos V. Michalopoulos Efstratios Patsouris Angelica A. Saetta 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(8):639-647
Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings. 相似文献
132.
目的 探讨NRP-1单克隆抗体(NRP-1 MAb)的特异性,以及不同剂量的NRP-1 MAb治疗乳腺癌裸鼠移植瘤的疗效。方法 Western blot和共聚焦免疫荧光法检测NRP-1 MAb是否识别MCF7细胞上NRP-1蛋白。将MCF7细胞接种于BALB/c裸鼠皮下建立乳腺癌细胞移植瘤模型,并进行瘤组织传代。传代的肿瘤体积生长至300~500 mm3时,随机分为对照组、NRP-1 MAb低剂量组、中剂量组和高剂量组,每组6只,给药7次。观察荷瘤裸鼠一般状况,测量瘤体大小及裸鼠体重。实验结束时剥离瘤体称重,提取组织蛋白,Western blot检测组织中VEGF蛋白和NRP-1蛋白的表达量。结果 NRP-1MAb成功识别MCF7细胞上的NRP-1蛋白;NRP-1 MAb能够有效抑制MCF7细胞裸鼠移植瘤的生长,低剂量组(1 mg/kg)抑瘤率为47.01%,中剂量组(5 mg/kg)抑瘤率为65.70%,高剂量组(10 mg/kg)抑瘤率为69.19%。。结论 NRP-1 MAb能够识别并有效结合MCF7细胞膜上的NRP-1蛋白,且可抑制MCF7细胞移植瘤的生长,NRP-1 MAb抑制移植瘤的增长可能与下调NRP-1和VEGF表达有关。 相似文献
133.
目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。 相似文献
134.
135.
近年来,抗程序性细胞死亡蛋白1(PD-1)药物在转移性结直肠癌患者错配修复缺陷治疗中的成功使得该疾病的免疫治疗得以重视。然而,失配修复缺陷的结直肠癌患者仅占结肠癌患者的一部分。目前的研究重点是将免疫治疗应用到疾病的早期阶段,包括辅助一线治疗,以及检测免疫检查点抑制剂治疗的敏感性。然而,哪些患者能够从该免疫治疗中获益仍是值得商榷的问题,因为这类药物具有自身免疫毒性。PD-1的配体之一程序性细胞死亡蛋白配体1(PD-L1)作为一种检测生物标记物,其检测可以通过免疫组化来实现。但其免疫组化的检测存在一些混杂因素,包括应用不同的检测抗体、不同的免疫组化临界值、肿瘤组织的采集准备方式不同、处理过程的不同、原发与继发的活检标本、肿瘤源性或诱导的PD-L1表达,以及肿瘤与免疫细胞的染色等。目前的结果表明,免疫组化检测肿瘤过表达PD-L1的患者在接受抗PD-L1治疗时临床效果更理想,而有些低表达的肿瘤也对该治疗有所缓解,这使PD-L1的分析中存在复杂性。阐明宿主免疫系统与肿瘤微环境的机制则能够更好地解释针对PD-L1药物是否让患者受益。 相似文献
136.
WT1基因位于人类染色体11p13,在80%的急性髓系白血病(acute myeloid leukemia,AML)患者中高表达,是AML预后不良的分子标志,可作为AML预后评估和微小残留病变(minimal residual disease,MRD)监测的有效指标。由于WT1在AML中均有异常高表达,故认为是一种AML抗原,可作为特异性免疫治疗的新靶点。一些小规模的临床试验证实以WT1为靶点的免疫治疗是有效的、安全的,这些免疫治疗可作为那些有高危复发风险及初始标准化疗失败的AML患者的辅助治疗。本文就近几年WT1与AML的预后及有关以WT1为靶点的主动特异性免疫治疗的研究进展予以综述。 相似文献
137.
138.
Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献139.
140.
C. Knipfer F. Wagner K. Knipfer G. Millesi J. Acero J.A. Hueto E. Nkenke 《International journal of oral and maxillofacial surgery》2019,48(6):841-846
The aim of this study was to evaluate learners’ acceptance of a webinar for continuing medical education that was instigated by the International Association of Oral and Maxillofacial Surgeons (IAOMS). A live, interactive webinar on orthognathic surgery was broadcast via the Internet. The learners’ acceptance of the webinar was evaluated using a standardized, validated questionnaire (Student Evaluation of Educational Quality, SEEQ). One hundred and fifty-three participants attended the webinar; 55 participants (46 male, nine female) completed the questionnaire. The mean age of the respondents was 41.6 ± 10.0 years. The age of male and female respondents did not differ significantly. The respondents were spread over five continents, with the highest number from Brazil. The SEEQ showed a high level of acceptance for almost all subscales. There was no statistically significant difference between male and female respondents concerning acceptance of the webinar (P = 0.614). The wide distribution of participants shows the potential for webinars as facilitators of barrier-free distribution of knowledge. The webinar was well accepted by the attendees independent of sex, specialty, and work experience. However, the sex ratio reflects the underrepresentation of women in oral and maxillofacial surgery. 相似文献