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原发性纤毛数量增加,并在人类癌症中表现出结构异常。

Primary cilia are increased in number and demonstrate structural abnormalities in human cancer.

作者信息

Yasar Binnaz, Linton Kim, Slater Christian, Byers Richard

机构信息

Division of Medical Education, Faculty of Biology, Medicine and Health, School of Medical Sciences, The University of Manchester, Manchester, UK.

Department of Medical Oncology, The Christie Foundation NHS Trust, Manchester, UK.

出版信息

J Clin Pathol. 2017 Jul;70(7):571-574. doi: 10.1136/jclinpath-2016-204103. Epub 2016 Nov 21.

Abstract

AIMS

Primary cilia play an important role in the regulation of cell signalling pathways and are thought to have a role in cancer but have seldom been studied in human cancer samples.

METHODS

Primary cilia were visualised by dual immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin in a range of human cancers (including carcinomas of stomach, pancreas, prostate, lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in matched normal tissue (stomach, pancreas, lung, large and small intestines, breast and reactive lymph nodes) samples using a tissue microarray; their frequency, association with proliferation, was measured by Ki-67 staining and their structure was analysed.

RESULTS

Compared with normal tissues, primary cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75% vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively, p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant difference compared with normal control tissue for gastric and prostatic adenocarcinomas or for lobular and ductal breast cancers. Additionally, structural abnormalities of primary cilia were identified in cancer tissues, including elongation of the axoneme, multiple basal bodies and branching of the axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically significant correlation with primary cilia frequency across all tissues (p=0.1501).

CONCLUSIONS

The results show upregulation of primary cilia and the presence of structural defects in a wide range of human cancer tissue samples demonstrating association of dysregulation of primary cilia with human cancer.

摘要

目的

初级纤毛在细胞信号通路调节中发挥重要作用,被认为与癌症有关,但在人类癌症样本中很少被研究。

方法

使用组织微阵列,通过抗CROCC(纤毛小根卷曲螺旋)和抗微管蛋白的双重免疫荧光法,在一系列人类癌症(包括胃癌、胰腺癌、前列腺癌、肺癌和结肠癌、小叶和导管乳腺癌以及滤泡性淋巴瘤)和匹配的正常组织(胃、胰腺、肺、大肠和小肠、乳腺和反应性淋巴结)样本中观察初级纤毛;通过Ki-67染色测量其频率、与增殖的相关性,并分析其结构。

结果

与正常组织相比,肺癌腺癌(2.75%对1.85%,p = 0.016)、结肠癌腺癌(分别为3.80%对2.43%,p = 0.017)、滤泡性淋巴瘤(1.18%对0.83%,p = 0.003)和胰腺腺癌(7.00%对5.26%,p = 0.002)中初级纤毛频率显著升高;胃癌和前列腺癌腺癌或小叶和导管乳腺癌与正常对照组织相比无统计学显著差异。此外,在癌组织中发现了初级纤毛的结构异常,包括轴丝伸长、多个基体和轴丝分支。Ki-67评分范围为0.7%至78.4%,在所有组织中与初级纤毛频率均无统计学显著相关性(p = 0.1501)。

结论

结果显示在多种人类癌症组织样本中初级纤毛上调且存在结构缺陷,表明初级纤毛失调与人类癌症有关。

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