A patient-derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
A patient-derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
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患者来源的异种移植物和源自其的细胞系形成了有用的小肠腺癌临床前模型
DOI：
10.1002/cam4.2986
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发表时间：
2020
期刊：
影响因子：
4
通讯作者：
Naohiro Tomita
中科院分区：
文献类型：
--
作者：
Tomoki Yamano;Shuji Kubo;Naohiro Tomita
由于小肠腺癌（SBA）的罕见性，其基础和临床研究有限。我们利用患有肝和腹膜转移的晚期 SBA 患者的肿瘤组织以及来自 PDX 的细胞系建立了患者来源的异种移植物 (PDX) 模型。在PDX模型中，与对照组相比，5-氟尿嘧啶（5-FU）治疗产生了统计学上显着的肿瘤生长抑制（TGI），而奥沙利铂（OHP）和伊立替康没有显着的抑制作用。 OHP 与 5-FU 联合使用时，TGI 发生率最高。与结肠癌细胞系 HT29 相比，PDX 衍生细胞系中 OHP 的 IC50 显着低于紫杉醇、吉西他滨和三氟胸苷。对患者肿瘤、PDX 肿瘤和细胞系的遗传分析表明，TP53、APC、HRAS、CSF1R、FGFR3、FLT3、PDGFRA 和 RET 基因的微卫星状态和突变具有一致性。然而，单独的 PDX 肿瘤有额外的突变，表明 PDX 衍生细胞系可能支持 PDX 不稳定的遗传状态。我们的研究结果证实了 OHP 和 5-FU 联合治疗的有效性，这是晚期 SBA 和晚期结直肠癌的常见治疗方法，在临床前模型中。这种 SBA 的临床前模型有助于进一步了解 SBA 的生物学。
Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient‐derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX model, compared to the control group, 5‐fluorouracil (5‐FU) treatment resulted in statistically significant tumor growth inhibition (TGI), while oxaliplatin (OHP) and irinotecan had no significant inhibitory effects. In combination with 5‐FU, OHP showed the highest rate of TGI. The IC50for OHP was significantly lower than those for paclitaxel, gemcitabine, and trifluorothymidine in the PDX‐derived cell line when compared to in HT29, a colon cancer cell line. Genetic analysis of the patient tumor, PDX tumor, and the cell line demonstrated consistency in the microsatellite status and mutations inTP53,APC,HRAS,CSF1R,FGFR3,FLT3,PDGFRA, andRETgenes. However, the PDX tumor alone had additional mutations, indicating that the PDX‐derived cell line may support the unstable genetic status of the PDX. Our findings confirmed the effectiveness of the combination of OHP and 5‐FU, which is a common treatment for advanced SBA and advanced colorectal cancer, in a preclinical model. This preclinical model of SBA can help in further understanding the biology of SBA.