Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid.

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid.
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肝内胆管癌的转化治疗与改善预后相关,并已通过患者来源的类器官病例得到验证

DOI:
10.3390/cancers13051179
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发表时间:
2021-03-09
期刊:
影响因子:
5.2
通讯作者:
Li J
Li J
中科院分区:
医学2区
文献类型:
--
作者:
Wang Z;Jin Y;Guo Y;Tan Z;Zhang X;Ye D;Yu Y;Peng S;Zheng L;Li J

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简单总结本研究的第一个核心提示是,我们总结了单中心肝内胆管细胞癌(IHCC)的转归治疗经验,发现转归治疗可以显着改善IHCC患者的总体生存。以往的研究主要集中在病例报告和病例系列上,我们的研究为转化治疗在IHCC中的疗效提供了更多的证据。二是我们建立了用于药物筛选的IHCC有机化合物,并首次验证了癌症有机化合物药物筛选试验的结果与在患者身上观察到的疗效水平一致。根据我们的研究,癌症有机化合物是一种很有前途的转化治疗技术,但仍需要更多的有机化合物。摘要本研究旨在探讨转化性治疗对肝内胆管细胞癌的疗效,并探讨癌组织类物质指导转化性治疗的可行性。在这项研究中,我们回顾了患者的资料,并利用从两名患者身上获取的组织建立了癌症类器官。42例肝细胞癌患者接受了中转治疗,其中9例成功降期,另有157例患者初步可切除。卡普兰-迈耶曲线显示,与降级不成功的患者相比,成功降级的患者的总存活率显著提高(p=0.017),与最初可切除的患者的总存活率相似(p=0.965)。从获得的两个组织中的一个组织中成功地建立了IHC有机类化合物。常规苏木精-伊红染色和免疫组织学染色发现,类器官保留了原始组织的组织病理学特征。整个外显子组测序结果表明,IHCC有机类物质在原始组织中保留了87%的变体。通过药物筛选试验确定,吉西他滨和紫杉醇对癌症有机物的抑制作用最强,这与在其来源的患者身上观察到的疗效水平一致。这项研究表明,尽管转化疗法的成功率较低,但仍能提高IHCC患者的存活率,而且可能是由癌症有机物质指导的,尽管这只是可行性的证明。
Simple Summary The first core tip of this study is that we summarized the experience of conversion therapy of intrahepatic cholangiocarcinoma (IHCC) in a single center and found conversion therapy could provide a significant improvement in the overall survival of patients with IHCC. Previous studies mainly focused on case reports and case series, and our research provided more evidence for the efficacy of conversion therapy in IHCC. The second is that we established the organoid of IHCC for drug screening and firstly verified the results of drug screening tests in cancer organoid were consistent with the levels of efficacy observed in the patient from whom it was derived. Cancer organoid is a promising technology for conversion therapy according to our study but more organoids are still needed. Abstract This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.
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发表时间: 2018-12-13
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影响因子: 64.5
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