兰州大学机构库 >学院待认领
重离子辐射经VEGF-DLL4/Notch通道对肾癌肿瘤血管形成的影响
Alternative TitleHeavy iron radiation impacted on Tumor angiogenesis in renal cell carcinoma by the VEGF-DLL4/Notch signaling pathway
王伟
Thesis Advisor岳中瑾
2014-12-08
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword肾透明细胞癌 Delta 样分子4 血管内皮生长因子受体2 预后 重离子 辐照
Abstract第一部分 目的:研究DLL4的表达与肾癌患者手术后的预后关系。方法:用Western blot检测样标本中DLL4、VEGFR-2的表达水平。研究DLL4在肾癌组织中的表达量与肾癌术后生存时间的相关性。结果: DLL4的表达水平与肿瘤组织中VEGFR-2的表达、TNM分期、肿瘤的分化、肿瘤的转移有相关性,是患者预后的独立预测因子。结论:DLL4高表达是肾癌术后预后不良的独立预测因子。 第二部分 目的:研究肾癌细胞在重离子辐照后VEGF-DLL4/Notch通路中VEGF和DLL4蛋白的关系,探讨重离子辐照对肾癌肿瘤血管形成的影响。 方法:用Western blot 方法检测重离子辐照后肾癌细胞中VEGF和DLL4的表达情况;免疫组化检测辐照后肾癌组织中VEGF、DLL4和CD31的表达情况。结果:重离子辐照后VEGF 和DLL4表达上调,辐射剂量 1 Gy、2 Gy、3 Gy肾癌细胞中 VEGF 和 DLL4 的表达水平都高于空白对照组,且 DLL4 的升高与 VEGF 相对应;重离子辐照组移植瘤体积增大缓慢,对照组生长速度加快。两组裸鼠在重离子辐照后体重未见明显差异。免疫组化结果显示重离子辐照后 VEGF 和 DLL4 均高表达 结论:重离子辐照能促进人肾癌细胞中 VEGF 和 DLL4 的表达,且 DLL4 的表达受 VEGF 的诱导;重离子辐照能抑制人肾癌 786-O 移植瘤的生长速度,可能的机制是辐照后使 DLL4 表达上调,负反馈于 VEGF,抑制了肾癌肿瘤血管VEGF 信号通路中 DLL4/Notch 作用,抑制肿瘤的生长。
Other AbstractSection 1 Objective: To study whether high DLL4 expression is correlated with poor prognosis after curative resection for clear cell renal cell carcinoma (ccRCC) and determine the relationship between DLL4 expression and VEGF receptor 2 (VEGFR-2) expression for patients with ccRCC. Methods:the consecutive patients with a confirmed surgical specimens obtained from 121 patients with ccRCC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) levels. Prognostic significance of DLL4 expression was evaluated by Kaplan–Meier method and Cox proportional hazards models with backward step wise selection. Results: both OS and PFS were associated with DLL4 expression, VEGFR-2 expression, tumor stage, tumor differentiation status. patients with low DLL4 expression had a significantly better survival than those with high DLL4 expressionIn multivariate survival analyses Conclusions:High DLL4 expression is an independent poor predictor for ccRCC. Section 2 Objective: To clarify the relationship between DLL4 and VEGF in the prosess of tumor development, and to explore the role of VEGF-DLL4/Notch signaling pathway during tumor angiogenesis in renal cell carcinoma. Methods: DLL4 and VEGF in 786-O cells were assayed by Western blot after heavy ions irradiation; nude mouse model of renal cell carcinoma was established and the volume of tumor and weight of nude mouse were measured; after heavy ions irradiation, renal tissues were immunohistochemically assessed for DLL4, VEGF together with CD31。Results: After heavy ion irradiation 12h, 24h, 48h, VEGF and DLL4 were upregulated significantly; In the study of 1Gy、2Gy、3Gy heavy ions irradiation, DLL4 and VEGF expression were higher than that in control group. Similarly, DLL4 increased with the rise of VEGF; Tumor growth is slower in heavy ion irradiation group than that in the control group. The tumor volume increased slowly in the experimental group. However, the tumors’ weight shows no significant differences between the two groups. Immunohistochemistry showed both VEGF and DLL4 were overexpressed after heavy ion irradiation. Conclusions: Heavy ion irradiation can promote the expression of VEGF and DLL4 in renal cancer cells. The expression of DLL4 was regulated by VEGF; Heavy ion irradiation can inhibit growth speed of transplanted kidney tumors, the potential mechanism may be that the increasing DLL4 expression functions as a negative regulator of ...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/222188
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
王伟. 重离子辐射经VEGF-DLL4/Notch通道对肾癌肿瘤血管形成的影响[D]. 兰州. 兰州大学,2014.
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