基础医学与临床 ›› 2023, Vol. 43 ›› Issue (4): 596-602.doi: 10.16352/j.issn.1001-6325.2023.04.0596

• 研究论文 • 上一篇    下一篇

结直肠癌PDX模型成瘤率的影响因素及临床意义

张燕萍1#, 姚刘旭2#, 丁倩男2, 黄则勇1, 李玉红3*, 黄素琴3*   

  1. 1.树兰(杭州)医院 麻醉科,浙江 杭州 310004;
    2.绍兴市人民医院 医学研究中心,浙江 绍兴 312000;
    3.浙江树人学院树兰国际医学院附属树兰(杭州)医院 麻醉科,浙江 杭州 310004
  • 收稿日期:2022-05-11 修回日期:2022-10-11 出版日期:2023-04-05 发布日期:2023-04-03
  • 通讯作者: *yuh_li@zju.edu.cn; suqin.huang@shulan.com
  • 作者简介:#对本文有相同贡献
  • 基金资助:
    浙江省科学技术厅公益项目(LY21H150001);浙江省医药卫生科技计划项目(2020KY329);绍兴市科技项目(2020A13014);杭州市科技项目(B20210683)

Influencing factors and the clinical significance of tumorigenesis rate in PDX model of colorectal cancer

ZHANG Yanping1#, YAO Liuxu2#, DING Qiannan2, HUANG Zeyong1, LI Yuhong3*, HUANG Suqin3*   

  1. 1. Department of Anesthesiology, Shulan (Hangzhou) Hospital, Hangzhou 310004;
    2. Clinical Research Center, Shaoxing People's Hospital, Shaoxing 312000;
    3. Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren College, Hangzhou 310004, China
  • Received:2022-05-11 Revised:2022-10-11 Online:2023-04-05 Published:2023-04-03
  • Contact: *yuh_li@zju.edu.cn; suqin.huang@shulan.com

摘要: 目的 建立结直肠癌(CRC)患者来源的肿瘤组织异种移植(PDX)模型,评估PDX模型成瘤率的影响因素,并初步进行化学治疗实验。方法 选取2019年11月至2020年10月绍兴市人民医院择期手术CRC患者。将手术获取的肿瘤组织接种于NSG小鼠右侧腰背部,建立PDX模型,并传至F3代,分析PDX模型成瘤率的影响因素;化学治疗药物选择5-氟尿嘧啶、奥沙利铂以及丙泊酚。结果 本研究共纳入60例CRC患者,PDX模型成瘤为37例,成瘤率62%;平均成瘤时间为(34±12)d;原发瘤恶性程度(CRC分期和细胞分化程度)、术前癌胚抗原(CEA)水平以及肿瘤位置等因素影响PDX模型成瘤率(P<0.01)。CRC-PDX移植瘤组织与患者肿瘤组织生物学特征高度一致。4种化学治疗方案均能抑制肿瘤生长,致肿瘤组织破坏,丙泊酚可以抑制小鼠腹泻,对肠黏膜具有保护作用。结论 本研究建立的CRC-PDX模型,较好地保持原发肿瘤的生物学特性,可作为CRC患者个体化治疗的参考模型。原发肿瘤恶性程度是PDX 模型成瘤率的主要影响因素。

关键词: 结直肠癌, 患者来源异种移植, 影响因素, 成瘤率, 个体化治疗

Abstract: Objective To establish a patient derived xenograft (PDX) model of tumor tissue from patients with colorectal cancer (CRC) and to identify the factors affecting the tumorigenesis rate of PDX model, as well as to conduct a preliminary chemotherapy. Methods From November 2019 to October 2020, CRC patients undergoing elective surgery in Shaoxing People's Hospital were selected. The tumor tissue obtained from surgical operation was inoculated to the right lumbar back of NSG mice to establish a PDX model, which was subcultured to F3 generation, and the influencing factors of the tumor formation rate of PDX model were analyzed. Chemotherapy drugs include 5-fluorouracil, oxaliplatin and anesthetic propofol. Results A total of 60 patients with CRC were included in this study and 37 samples from patients had PDX tumor formation in mice with a tumorigenesis rate of 62%; The average tumorigenesis time was (34±12)d; Primary tumor malignant degree (tumor stage and degree of cell differentiation), preoperative carcinoembryonic antigen (CEA) level and tumor location of CRC patients affected the tumorigenesis rate of PDX model (P<0.01). The biology of CRC-PDX transplanted tumor tissue was highly consistent with that of the patient's tumor tissue. All four chemotherapy regimens could inhibit tumor growth and cause tumor tissue damage. Propofol could inhibit diarrhea in mice and protect intestinal mucosa. Conclusions The CRC-PDX model established in this study may better keep biological characteristics of primary tumors and be used as a reference model for individualized treatment of CRC patients. The malignant degree of the primary tumor is the main factor affecting the tumorigenesis rate of PDX model.

Key words: colorectal cancer, patient derived xenograft, influencing factors, tumorigenesis rate, individualized treatment

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