Guided chemotherapy based on patient-derived mini-xenograft models improves survival of gallbladder carcinoma patients.

Guided chemotherapy based on patient-derived mini-xenograft models improves survival of gallbladder carcinoma patients.
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基于患者来源的微型异种移植模型的引导化疗可提高胆囊癌患者的生存率

DOI:
10.1186/s40880-018-0318-8
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发表时间:
2018-07-17
期刊:
Cancer communications (London, England)
影响因子:
--
通讯作者:
Wang J
Wang J
中科院分区:
其他
文献类型:
--
作者:
Zhan M;Yang RM;Wang H;He M;Chen W;Xu SW;Yang LH;Liu Q;Long MM;Wang J

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背景胆囊癌具有高度侵袭性,对化疗耐药,目前尚无一致的一线化疗策略。然而,患者来源的异种移植物(PDX)模型已越来越多地被用作一个有效的模型,在临床前研究chemosensitivity.MethodsMini-PDX模型建立使用新鲜切除的原发性病变从12例胆囊检查的敏感性与五个最常用的化疗药物,即吉西他滨,奥沙利铂,5-氟尿嘧啶,纳米粒白蛋白结合(NAB)-紫杉醇,和伊立替康。结果用于指导术后持续治疗的化疗药物选择。Kaplan-Meier法比较45例接受吉西他滨和奥沙利铂常规化疗的患者的总生存期(OS)和无病生存期(DFS)。Kaplan-Meier分析显示,PDX引导化疗组患者的中位OS(18.6个月; 95%CI 15.9-21.3个月)显著长于常规化疗组患者(13.9个月; 95%CI 11.7-16.2个月)(P= 0.030; HR 3.18; 95%CI 1.47-6.91)。PDX引导化疗组患者的中位DFS也显著延长(17.6个月; 95% CI 14.5-20.6个月)(12.0个月; 95% CI 9.7-14.4个月)(P= 0.014; HR 3.37;结论应用mini-PDX模型指导胆囊癌化疗方案的选择,可提高胆囊癌患者的预后。
BackgroundGallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity.MethodsMini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan. The results were used to guide the selection of chemotherapeutic agents for adjunctive treatment after the surgery. Kaplan–Meier method was used to compare overall survival (OS) and disease free survival (DFS) with 45 patients who received conventional chemotherapy with gemcitabine and oxaliplatin.ResultsCell viability assays based on mini-PDX model revealed significant heterogeneities in drug responsiveness. Kaplan–Meier analysis showed that patients in the PDX-guided chemotherapy group had significantly longer median OS (18.6 months; 95% CI 15.9–21.3 months) than patients in the conventional chemotherapy group (13.9 months; 95% CI 11.7–16.2 months) (P= 0.030; HR 3.18; 95% CI 1.47–6.91). Patients in the PDX-guided chemotherapy group also had significantly longer median DFS (17.6 months; 95% CI 14.5–20.6 months) than patients in the conventional chemotherapy group (12.0 months; 95% CI 9.7–14.4 months) (P= 0.014; HR 3.37; 95% CI 1.67–6.79).ConclusionThe use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.
DOI: 10.1038/cddis.2017.530
发表时间: 2017-10-19
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