發(fā)布時間：2018-06-05 03:39

  本文選題：結(jié)直腸癌 + 復發(fā)轉(zhuǎn)移　； 參考：《中國癌癥雜志》2017年07期

【摘要】：背景與目的:結(jié)直腸癌患者中BRAF基因突變的概率為5%~15%,臨床預后明顯差于無突變者。該研究將BRAF與表皮生長因子受體(epidermal growth factor receptor,EGFR)抑制劑聯(lián)合用于BRAF V600E突變型復發(fā)轉(zhuǎn)移性結(jié)直腸癌的患者來源異種移植(patient-derived xenografts,PDXs)模型,觀察其安全性、可行性及療效。方法:2016年1月—2016年12月,復旦大學附屬腫瘤醫(yī)院34例疑似結(jié)直腸癌術(shù)后復發(fā)或轉(zhuǎn)移的患者利用CT引導下的穿刺活檢方法獲取組織標本,建立復發(fā)轉(zhuǎn)移性結(jié)直腸癌的PDXs模型,篩選BRAF突變者傳代培養(yǎng)至F2代進行藥物實驗,實驗組分為BRAF抑制劑組(A組)、EGFR抑制劑組(B組)、BRAF和EGFR抑制劑聯(lián)合組(C組)及安慰劑對照組(D組)。給藥3周后處死實驗動物,統(tǒng)計建模成功率及抑瘤率。結(jié)果:34例患者中共23例病理證實為結(jié)直腸癌復發(fā)或轉(zhuǎn)移,成功建立16個PDX模型,建模成功率為69.6%(16/23)。共篩選出4例BRAF V600E基因突變者,成功建立4個BRAF突變型復發(fā)轉(zhuǎn)移性結(jié)直腸癌的PDXs模型。實驗組無明顯藥物毒性相關(guān)性死亡,實驗組抑瘤率分別為21.57%、21.61%和66.81%,差異有統(tǒng)計學意義(P0.05)。結(jié)論:CT引導下的穿刺活檢建立復發(fā)轉(zhuǎn)移性結(jié)直腸癌的PDXs模型成功率高,針對EGFR和BRAF的雙重打擊治療安全、可行,能夠明顯提高BRAF突變型結(jié)直腸癌的療效。
[Abstract]:Background & objective: the probability of BRAF gene mutation in patients with colorectal cancer is 50.15%, and the clinical prognosis is significantly worse than that without mutation. In this study, BRAF was combined with epidermal growth factor receptor (EGFR) inhibitor in patients with BRAF V600E mutant recurrent and metastatic colorectal cancer. The model of patient-derived xenografts-PDXs was used to observe its safety, feasibility and efficacy. Methods: from January 2016 to December 2016, 34 patients suspected of recurrence or metastasis of colorectal cancer were obtained by CT-guided biopsy in Fudan University Cancer Hospital. The PDXs model of recurrence and metastasis of colorectal cancer was established. The experimental group was divided into BRAF inhibitor group (group A) and EGFR inhibitor group (group C) and placebo control group (group D). After 3 weeks of administration, the experimental animals were killed, and the success rate of modeling and tumor inhibition rate were statistically analyzed. Results Sixteen PDX models were successfully established in 23 patients with recurrence or metastasis of colorectal cancer confirmed by pathology in 34 patients. The success rate of modeling was 69.6% / 23%. Four patients with BRAF V600E gene mutation were selected and 4 PDXs models of BRAF mutation were successfully established. There was no obvious drug-toxicity related death in the experimental group. The tumor inhibition rate in the experimental group was 21.57% and 66.81%, respectively. The difference was statistically significant (P 0.05). Conclusion the success rate of PDXs model of recurrent and metastatic colorectal cancer established by puncture biopsy guided by 10% CT is high. It is safe and feasible to treat EGFR and BRAF with double blows, and can obviously improve the curative effect of BRAF mutant colorectal cancer.
【作者單位】： 復旦大學附屬腫瘤醫(yī)院介入治療科 復旦大學上海醫(yī)學院腫瘤學系;
【基金】：國家重點研發(fā)計劃(2016YFC0106203)
【分類號】：R735.34

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本文編號：1980328