【佳學基因檢測】依維莫司在嚙齒動物多囊肝病模型中停止肝囊發(fā)生

腫瘤基因檢測需要多長時間香港

根據(jù)如何選擇有效的靶向藥物治療認識到《World J Gastroenterol》在.?2017 Aug 14;23(30):5499-5507.發(fā)表了一篇題目為《依維莫司在嚙齒動物多囊肝病模型中停止肝囊發(fā)生》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由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。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

基因解碼基因檢測的研究目的：開發(fā)一種基于 MRI 的肝體積（LV）正確測定基因解碼基因檢測的研究方法，并探討長期依維莫司（EVR）治療對肝腫大 PCK 大鼠 LV 的影響。基因解碼基因檢測的研究方法：31 只雌性 PCK 大鼠（模型對于多囊性肝?。篜CLD）被隨機分為 3 組，并在 16 周開始治療，此時廣泛肝腫大（與人類疾病中所做的相當）。接受的動物：對照（n = 14）、蘭瑞肽（LAN：每 2 周 3 mg/kg）（n = 10）或依維莫司（EVR：每天 1 mg/kg）（n = 7）。在第 16、24、28 周測量 LV。在第 28 周，處死所有大鼠并收獲肝組織。使用定量圖像分析評估纖維化。此外，還研究了 PI3K/AkT/mTOR 信號通路的基因（定量 RT-PCR）和蛋白質(zhì)表達（通過蛋白質(zhì)印跡）?；蚪獯a基因檢測的研究結(jié)果：通過 MRI 確定的 LV 與離體測量基因解碼基因檢測的研究結(jié)果具有極好的相關(guān)性（r = 0.99，P < 0.001)。治療結(jié)束時 LV 的相對變化為：（對照組）+31.8%； (LAN) +5.1% 和 (EVR) +8.8%，表明與對照組相比，LV 進展顯著停止（分別為 P = 0.01 和 P = 0.04）。此外，EVR 顯著減少了肝纖維化的數(shù)量（P = 0.004），因此也可能預(yù)防門靜脈高壓癥的發(fā)展。在 LAN 處理的 PCK 大鼠和對照 PCK 大鼠之間，Akt（蘇氨酸 308）的磷酸化沒有差異，而 LAN 組中 S6 的磷酸化程度明顯更高。 Akt 的磷酸化在對照組和 EVR 處理的大鼠之間沒有差異，然而，對于 S6，在 EVR 處理的大鼠中磷酸化顯著減少。因此，這兩種藥物都與 PI3K/AkT/mTOR 信號級聯(lián)相互作用，但作用于不同的分子水平?；蚪獯a基因檢測的研究結(jié)論：依維莫司與蘭瑞肽相比可阻止囊腫生長并減少纖維化的發(fā)展。應(yīng)在 PCLD 患者中進一步探索 mTOR 抑制作用，尤其是那些需要免疫抑制的患者。肝體積測量；磁共振成像；生長抑素類似物； mTOR 抑制劑。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.