【佳学基因检测】依维莫司在啮齿动物多囊肝病模型中停止肝囊发生

肿瘤基因检测需要多长时间香港

根据如何选择有效的靶向药物治疗认识到《World J Gastroenterol》在. 2017 Aug 14;23(30):5499-5507.发表了一篇题目为《依维莫司在啮齿动物多囊肝病模型中停止肝囊发生》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Frederik Temmerman, Feng Chen, Louis Libbrecht, Ingrid Vander Elst, Petra Windmolders, Yuanbo Feng, Yicheng Ni, Humbert De Smedt, Frederik Nevens, Jos van Pelt等完成。促进了肿瘤的正确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。

肿瘤靶向药物及正确治疗临床研究内容关键词：

肿瘤靶向治疗基因检测临床应用结果

基因解码基因检测的研究目的：开发一种基于 MRI 的肝体积（LV）正确测定基因解码基因检测的研究方法，并探讨长期依维莫司（EVR）治疗对肝肿大 PCK 大鼠 LV 的影响。基因解码基因检测的研究方法：31 只雌性 PCK 大鼠（模型对于多囊性肝病：PCLD）被随机分为 3 组，并在 16 周开始治疗，此时广泛肝肿大（与人类疾病中所做的相当）。接受的动物：对照（n = 14）、兰瑞肽（LAN：每 2 周 3 mg/kg）（n = 10）或依维莫司（EVR：每天 1 mg/kg）（n = 7）。在第 16、24、28 周测量 LV。在第 28 周，处死所有大鼠并收获肝组织。使用定量图像分析评估纤维化。此外，还研究了 PI3K/AkT/mTOR 信号通路的基因（定量 RT-PCR）和蛋白质表达（通过蛋白质印迹）。基因解码基因检测的研究结果：通过 MRI 确定的 LV 与离体测量基因解码基因检测的研究结果具有极好的相关性（r = 0.99，P < 0.001)。治疗结束时 LV 的相对变化为：（对照组）+31.8%； (LAN) +5.1% 和 (EVR) +8.8%，表明与对照组相比，LV 进展显着停止（分别为 P = 0.01 和 P = 0.04）。此外，EVR 显着减少了肝纤维化的数量（P = 0.004），因此也可能预防门静脉高压症的发展。在 LAN 处理的 PCK 大鼠和对照 PCK 大鼠之间，Akt（苏氨酸 308）的磷酸化没有差异，而 LAN 组中 S6 的磷酸化程度明显更高。 Akt 的磷酸化在对照组和 EVR 处理的大鼠之间没有差异，然而，对于 S6，在 EVR 处理的大鼠中磷酸化显着减少。因此，这两种药物都与 PI3K/AkT/mTOR 信号级联相互作用，但作用于不同的分子水平。基因解码基因检测的研究结论：依维莫司与兰瑞肽相比可阻止囊肿生长并减少纤维化的发展。应在 PCLD 患者中进一步探索 mTOR 抑制作用，尤其是那些需要免疫抑制的患者。肝体积测量；磁共振成像；生长抑素类似物； mTOR 抑制剂。

肿瘤发生与反复转移国际数据库描述：

Aim: To develop a MRI-based method for accurate determination of liver volume (LV) and to explore the effect of long-term everolimus (EVR) treatment on LV in PCK rats with hepatomegaly.Methods: Thirty-one female PCK rats (model for polycystic-liver-disease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly (comparable to what is done in the human disease). Animals received: controls (n = 14), lanreotide (LAN: 3 mg/kg per 2 wk) (n = 10) or everolimus (EVR: 1 mg/kg per day) (n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene (quantitative RT-PCR) and protein expression (by Western blot) of the PI3K/AkT/mTOR signaling pathway was investigated.Results: LV determination by MRI correlated excellent with the ex vivo measurements (r = 0.99, P < 0.001). The relative changes in LV at the end of treatment were: (controls) +31.8%; (LAN) +5.1% and (EVR) +8.8%, indicating a significantly halt of LV progression compared with controls (respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis (P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt (Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/AkT/mTOR signaling cascade but acting at different molecular levels.Conclusion: Everolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. mTOR-inhibition should be further explored in PCLD patients especially those that need immunosuppression.Keywords: Fibrocystic liver disease; Liver volume measurement; Magnetic resonance imaging; Somatostatin analogue; mTOR inhibitor.