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个体化条件重编程系统在指导胃癌治疗中的应用研究

Application Research of Individualized Conditional Reprogramming System to Guide Treatment of Gastric Cancer.

作者信息

Zhao Weizhu, Liu Kai, Sun Zhikun, Wang Longgang, Liu Bing, Liu Luguang, Qu Xianlin, Cao Zhixiang, Sun Jujie, Chai Jie

机构信息

Department of Radiology, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, Jinan, China.

Department of Oncology, Binzhou People's Hospital, Binzhou, China.

出版信息

Front Oncol. 2021 Jul 16;11:709511. doi: 10.3389/fonc.2021.709511. eCollection 2021.

DOI:10.3389/fonc.2021.709511
PMID:34336697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8322696/
Abstract

BACKGROUND

Gastric cancer (GC) is one of the most common causes of malignant tumors in the world. Due to the high heterogeneity of GC and lack of specificity of available chemotherapy regimens, these tumors are prone to resistance, recurrence, and metastasis. Here, we formulated an individualized chemotherapy regimen for GC using a modified individual conditional reprogramming (i-CR) system. We established a primary tumor cell bank of GC cells and completed drug screening in order to realize individualized and accurate GC treatment.

METHODS

We collected specimens from 93 surgical or gastroscopy GC cases and established a primary tumor cell bank using the i-CR system and PDX models. We also completed culture and drug sensitivity screening of the GC cells using the i-CR system. Whole-exome sequencing (WES) of the i-CR cells was performed using P0 and P5. We then chose targeted chemotherapy drugs based on the i-CR system results.

RESULTS

Of the 72 cases that were collected from surgical specimens, 26 cases were successfully cultured with i-CR system, and of the 21 cases collected from gastroscopy specimens, seven were successfully cultured. Among these, 20 cases of the PDX model were established. SRC ± G3 had the highest culture success rate. The i-CR cells of P0 and P5 appeared to be highly conserved. According to drug sensitivity screening, we examined the predictive value of responses of GC patients to chemotherapeutic agents, especially in neoadjuvant patients.

CONCLUSION

The i-CR system does not only represent the growth characteristics of tumors , but also provides support for clinical drug use. Drug susceptibility results were relatively consistent with clinical efficacy.

摘要

背景

胃癌(GC)是全球最常见的恶性肿瘤病因之一。由于胃癌的高度异质性以及现有化疗方案缺乏特异性,这些肿瘤易于产生耐药性、复发和转移。在此,我们使用改良的个体条件重编程(i-CR)系统为胃癌制定了个体化化疗方案。我们建立了胃癌细胞的原代肿瘤细胞库并完成药物筛选,以实现个体化且精准的胃癌治疗。

方法

我们收集了93例手术或胃镜检查的胃癌病例标本,使用i-CR系统和PDX模型建立了原代肿瘤细胞库。我们还使用i-CR系统完成了胃癌细胞的培养和药敏筛选。使用P0和P5对i-CR细胞进行全外显子测序(WES)。然后根据i-CR系统的结果选择靶向化疗药物。

结果

从手术标本中收集的72例病例中,26例通过i-CR系统成功培养,从胃镜标本中收集的21例病例中,7例成功培养。其中,建立了20例PDX模型。SRC±G3的培养成功率最高。P0和P5的i-CR细胞似乎高度保守。根据药敏筛选,我们检测了胃癌患者对化疗药物反应的预测价值,尤其是在新辅助治疗患者中。

结论

i-CR系统不仅代表肿瘤的生长特征,还为临床用药提供支持。药敏结果与临床疗效相对一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/650c591670d3/fonc-11-709511-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/ea9fefb1881d/fonc-11-709511-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/7f42ad6c7782/fonc-11-709511-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/3158d82833f1/fonc-11-709511-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/f1cafe0c20bf/fonc-11-709511-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/b06b99d327de/fonc-11-709511-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/650c591670d3/fonc-11-709511-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/ea9fefb1881d/fonc-11-709511-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/7f42ad6c7782/fonc-11-709511-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/3158d82833f1/fonc-11-709511-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/f1cafe0c20bf/fonc-11-709511-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/b06b99d327de/fonc-11-709511-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c5/8322696/650c591670d3/fonc-11-709511-g006.jpg

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