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建立患者来源的异种移植模型并将其作为胃癌临床前模型进行表征。

Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer.

作者信息

Choi Yoon Young, Lee Jae Eun, Kim Hyunki, Sim Moon Hee, Kim Ka-Kyung, Lee Gunho, Kim Hyoung-Il, An Ji Yeong, Hyung Woo Jin, Kim Choong-Bai, Noh Sung Hoon, Kim Sangwoo, Cheong Jae-Ho

机构信息

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2016 Mar 1;6:22172. doi: 10.1038/srep22172.

Abstract

The patient-derived xenograft (PDX) model is emerging as a promising translational platform to duplicate the characteristics of tumours. However, few studies have reported detailed histological and genomic analyses for model fidelity and for factors affecting successful model establishment of gastric cancer. Here, we generated PDX tumours surgically-derived from 62 gastric cancer patients. Fifteen PDX models were successfully established (24.2%, 15/62) and passaged to maintain tumours in immune-compromised mice. Diffuse type and low tumour cell percentage were negatively correlated with success rates (p = 0.005 and p = 0.025, respectively), while reducing ex vivo and overall procedure times were positively correlated with success rates (p = 0.003 and p = 0.01, respectively). The histology and genetic characteristics of PDX tumour models were stable over subsequent passages. Lymphoma transformation occurred in five cases (33.3%, 5/15), and all were in the NOG mouse, with none in the nude mouse. Together, the present study identified Lauren classification, tumour cell percentages, and ex vivo times along with overall procedure times, as key determinants for successful PDX engraftment. Furthermore, genetic and histological characteristics were highly consistent between primary and PDX tumours, which provide realistic paraclinical models, enabling personalised development of treatment options for gastric cancer.

摘要

患者来源的异种移植(PDX)模型正成为一种很有前景的转化平台,用于复制肿瘤的特征。然而,很少有研究报告针对模型保真度以及影响胃癌模型成功建立的因素进行详细的组织学和基因组分析。在此,我们从62例胃癌患者手术切除的肿瘤中构建了PDX肿瘤。成功建立了15个PDX模型(24.2%,15/62),并进行传代以在免疫缺陷小鼠体内维持肿瘤生长。弥漫型和低肿瘤细胞百分比与成功率呈负相关(分别为p = 0.005和p = 0.025),而缩短体外操作时间和总操作时间与成功率呈正相关(分别为p = 0.003和p = 0.01)。PDX肿瘤模型的组织学和遗传特征在后续传代过程中保持稳定。5例(33.3%,5/15)发生淋巴瘤转化,均发生在NOG小鼠中,裸鼠中未发生。本研究共同确定了劳伦分类、肿瘤细胞百分比、体外操作时间以及总操作时间是PDX移植成功的关键决定因素。此外,原发性肿瘤和PDX肿瘤之间的遗传和组织学特征高度一致,这提供了现实的临床前模型,能够实现胃癌治疗方案的个性化制定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/165c/4772087/d1e0a935ecd5/srep22172-f1.jpg

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