【佳学基因检测】DNA依赖性蛋白激酶在介导常染色体显性多囊肾病囊肿生长中的作用

肿瘤基因检测需要多长时间香港

根据认识到《Int J Mol Sci》在 2021 Sep 29;22(19):10512发表了一篇题目为《DNA依赖性蛋白激酶在介导常染色体显性多囊肾病囊肿生长中的作用》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Ashley N Chandra , Sayanthooran Saravanabavan , Gopala K Rangan  等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

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肿瘤靶向治疗基因检测临床应用结果

DNA 依赖性蛋白激酶 (DNA-PK) 是一种参与 DNA 损伤反应 (DDR) 信号传导的丝氨酸/苏氨酸蛋白，由于其对增殖和存活的多效性作用，可能介导常染色体显性多囊肾病 (ADPKD) 中的肾囊肿生长。为了验证这一假设，评估了人 ADPKD 中 DNA-PK 的表达以及在 Madin-Darby 犬肾 (MDCK) 囊肿生长和人 ADPKD 细胞的三维模型中 DNA-PK 抑制的体外效果。在人类 ADPKD 中，DNA-PK 复合物的所有三个亚基的 mRNA 表达增加，并且使用免疫组织化学，在人类 ADPKD 的囊肿衬里上皮细胞中以局灶方式检测到催化亚基 (DNA-PKcs)。在体外，经过 6-12 天的长期治疗，NU7441（一种 DNA-PK 激酶抑制剂）可将 MDCK 囊肿的生长减少多达 52%。尽管与正常人肾细胞 (HK-2) 相比，人 ADPKD 细胞系 (WT9-7/WT9-12) 对 DNA-PK 激酶抑制的反应没有表现出合成杀伤力，但低剂量 NU7441 的组合增强了抗西罗莫司对 WT9-7 和 WT9-12 细胞的增殖作用分别为 17 ± 10% 和 11 ± 7%。总之，这些初步数据表明，DNA-PK 在没有综合致死相互作用的情况下介导体内肾囊肿生长，从而在人类 ADPKD 细胞中赋予细胞特异性。 NU7441 增强了雷帕霉素复合物 1 抑制剂的抗增殖作用，但作用不大。

肿瘤发生与复发转移国际数据库描述：

DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein involved in DNA damage response (DDR) signaling that may mediate kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD) due to its pleiotropic effects on proliferation and survival. To test this hypothesis, the expression of DNA-PK in human ADPKD and the in vitro effects of DNA-PK inhibition in a three-dimensional model of Madin-Darby Canine Kidney (MDCK) cyst growth and human ADPKD cells were assessed. In human ADPKD, the mRNA expression for all three subunits of the DNA-PK complex was increased, and using immunohistochemistry, the catalytic subunit (DNA-PKcs) was detected in the cyst lining epithelia of human ADPKD, in a focal manner. In vitro, NU7441 (a DNA-PK kinase inhibitor) reduced MDCK cyst growth by up to 52% after long-term treatment over 6-12 days. Although human ADPKD cell lines (WT9-7/WT9-12) did not exhibit synthetic lethality in response to DNA-PK kinase inhibition compared to normal human kidney cells (HK-2), the combination of low-dose NU7441 enhanced the anti-proliferative effects of sirolimus in WT9-7 and WT9-12 cells by 17 ± 10% and 11 ± 7%, respectively. In conclusion, these preliminary data suggest that DNA-PK mediates kidney cyst growth in vivo without a synthetically lethal interaction, conferring cell-specificity in human ADPKD cells. NU7441 enhanced the anti-proliferative effects of rapamycin complex 1 inhibitors, but the effect was modest.