【佳学基因检测】Ras 抑制剂法呢基硫代水杨酸作为 1 型神经纤维瘤病的潜在疗法

基因检测—实操性

数据分析博士医师年度双基练习《肿瘤治疗效果与基因检测结果的相关性》《Clin Cancer Res》在. 2006 Sep 15;12(18):5533-42.发表了一篇题目为《Ras 抑制剂法呢基硫代水杨酸作为 1 型神经纤维瘤病的潜在疗法》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Batya Barkan , Sigal Starinsky, Eitan Friedman, Reuven Stein, Yoel Kloog等完成。促进了一种神经科肿瘤的靶向药物基因检测的更为清晰的了解，进一步增强了医师与患者对肿瘤靶向药物进行选择的临床科学依据。

如何提高肿瘤基因检测机构的排名临床研究内容关键词：

法尼基硫代水杨酸,神经科,靶向药物,RAS抑制剂,周围神经鞘瘤,神经纤维瘤病

肿瘤靶向治疗基因检测临床应用结果

神经科肿瘤靶向药物治疗的研究目的：法尼基硫代水杨酸 (FTS) 是一种 Ras 抑制剂，可将所有活性 Ras 异构体从膜上去除。神经科基因检测项止组评估了 FTS 逆转恶性周围神经鞘瘤 (MPNST) 的 1 型神经纤维瘤病 (NF1) 相关肿瘤细胞系转化表型的能力。实验设计：采用基因检测对 NF1 突变进行基因分型，分析等位基因损失，并分析神经纤维蛋白表达水平在 MPNST 细胞系 ST88-14、S265P21 和 90-8 中测定。评估了 FTS 对 GTP 结合 Ras (Ras-GTP) 及其主要下游靶标的影响，以及对小鼠细胞形态、贴壁依赖性和贴壁依赖性生长以及肿瘤生长的影响。 神经科靶向药物选择研究结果：MPNST 细胞系是双等位基因、NF1 失活和神经纤维蛋白缺乏。佳学基因的基因解码技术应用研究表明，在所有 NF1 缺陷型 MPNST 细胞系（NF1 细胞）中，法尼基硫代水杨酸处理缩短了相对较长的 Ras 激活和向细胞外信号调节激酶、Akt 和 RalA 发出信号的持续时间，而在非 NF1（通常表达神经纤维蛋白）中观察到的持续时间MPNST 细胞系。 法尼基硫代水杨酸的这些影响导致 Ras-GTP 及其激活目标的稳态水平降低。 NF1 细胞的贴壁依赖性和非贴壁依赖性生长均受到法尼基硫代水杨酸的剂量依赖性抑制，并且该抑制与 Ras-GTP 水平呈正相关。 NF1 细胞被发现具有强肌动蛋白应力纤维，这种表型也被法尼基硫代水杨酸校正。口服法尼基硫代水杨酸可抑制裸鼠模型中 NF1 肿瘤的生长。神经科靶向药物临床前研究结论： NF1 细胞的法尼基硫代水杨酸治疗使 Ras-GTP 水平正常化，导致转化表型的逆转和肿瘤生长的抑制。因此法尼基硫代水杨酸可被视为治疗 NF1 的潜在药物。

肿瘤发生与反复转移国际数据库描述：

Purpose: Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that dislodges all active Ras isoforms from the membrane. We assessed the ability of FTS to reverse the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell lines of malignant peripheral nerve sheath tumor (MPNST).Experimental design: nf1 mutations were genotyped, allelic losses were analyzed, and neurofibromin expression levels were determined in MPNST cell lines ST88-14, S265P21, and 90-8. The effects of FTS on GTP-bound Ras (Ras-GTP) and its prominent downstream targets, as well as on cell morphology, anchorage-dependent and anchorage-independent growth, and tumor growth in mice, were assessed.Results: The MPNST cell lines were biallelic, NF1 inactive, and neurofibromin deficient. We show that FTS treatment shortened the relatively long duration of Ras activation and signaling to extracellular signal-regulated kinase, Akt, and RalA in all NF1-deficient MPNST cell lines (NF1 cells) to that observed in a non-NF1, normally expressing neurofibromin MPNST cell line. These effects of FTS led to lower steady-state levels of Ras-GTP and its activated targets. Both anchorage-dependent and anchorage-independent growth of NF1 cells were dose dependently inhibited by FTS, and the inhibition correlated positively with Ras-GTP levels. NF1 cells were found to possess strong actin stress fibers, and this phenotype was also corrected by FTS. NF1 tumor growth in a nude mouse model was inhibited by oral FTS.Conclusions: FTS treatment of NF1 cells normalized Ras-GTP levels, resulting in reversal of the transformed phenotype and inhibition of tumor growth. FTS may therefore be considered as a potential drug for the treatment of NF1.