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源自同一患有无功能胰腺神经内分泌肿瘤患者的不同临床前模型之间的比较。

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.

作者信息

Wang Yan, Ye Zeng, Lou Xin, Xu Junfeng, Jing Desheng, Zhou Chenjie, Qin Yi, Chen Jie, Xu Xiaowu, Yu Xianjun, Ji Shunrong

机构信息

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

出版信息

Hum Cell. 2024 Sep;37(5):1522-1534. doi: 10.1007/s13577-024-01107-5. Epub 2024 Jul 30.

Abstract

Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.

摘要

胰腺神经内分泌肿瘤是胰腺第二常见的肿瘤,约一半患者被诊断为肝转移。目前,相关治疗方法疗效的改善仍然有限。因此,迫切需要对胰腺神经内分泌肿瘤的分子生物学机制进行深入研究。然而,由于其生物学特性相对惰性,临床前模型极其稀缺。在此,成功构建了患者来源的类器官和患者来源的异种移植模型。这两种模型以及先前构建的名为SPNE1的细胞系均来自同一例3级无功能性胰腺神经内分泌肿瘤患者,提供了新的肿瘤建模平台,并通过免疫组织化学、全外显子组测序和单细胞转录组测序进行了表征。结合免疫缺陷小鼠中的肿瘤形成实验,我们选择了与亲本肿瘤最相似的模型。总体而言,患者来源的异种移植模型与人类肿瘤组织最为相似。

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