Jung Joohee, Kim Jisup, Lim Hyun Kyung, Kim Kyoung Mee, Lee Yun Sun, Park Joon Seong, Yoon Dong Sup
College of Pharmacy, Duksung Women's University, Seoul, Korea.
Innovative Drug Center, Duksung Women's University, Seoul, Korea.
Ann Surg Treat Res. 2017 Oct;93(4):173-180. doi: 10.4174/astr.2017.93.4.173. Epub 2017 Sep 28.
In order to suggest optimal anticancer drugs for patient-tailored chemotherapy, we developed a colorectal cancer (CRC)-liver metastasis patient-derived tumor xenograft (PDTX) model.
Tissue obtained from a patient with CRC-liver metastasis (F0) was transplanted in a nonobese female mouse with diabetic/severe combined immune deficiency (F1) and the tumor tissue was retransplanted into nude mice (F2). When tumor volumes reached ~500 mm, the F2 mice were randomly divided into 4 groups (n = 4/group) of doxorubicin, cisplatin, docetaxel, and nontreated control groups. The tumor tissues were investigated using H&E staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunohistochemistry. To determine where the mutant allele frequencies varied across the different passages, we isolated genomic DNA from the primary tumor, liver metastasis, and PDTX models (F1/F2).
The physiological properties of the tumor were in accord with those of the patient's tumors. Anticancer drugs delayed tumor growth, inhibited proliferation, and caused apoptosis. Histological assessments revealed no observable heterogeneity among the intragenerational PDTX models. Target exon sequencing analysis without high-quality filter conditions revealed some genetic variations in the 83 cancer-related genes across the generations. However, when mutations were defined as a total count of zero in F0 and ≥5 in F2, exactly prognostic impact of clone cancer profiling (EGFR, KRAS, BRAF, PIK3CA, NRAS, APC and TP53) were detected in the paired.
A CRC liver metastasis PDTX model was established for the evaluation of chemotherapeutic efficacy. This model retained the physiological characters of the patient tumors and potentially provides a powerful means of assessing chemotherapeutic efficacy.
为了推荐适合患者个体化化疗的最佳抗癌药物，我们建立了一种结直肠癌（CRC）肝转移患者来源的肿瘤异种移植（PDTX）模型。
从一名患有CRC肝转移的患者（F0）获取的组织移植到一只患有糖尿病/重度联合免疫缺陷的非肥胖雌性小鼠（F1）体内，然后将肿瘤组织再次移植到裸鼠（F2）体内。当肿瘤体积达到约500立方毫米时，将F2小鼠随机分为4组（每组n = 4），分别为多柔比星组、顺铂组、多西他赛组和未治疗的对照组。使用苏木精-伊红染色、末端脱氧核苷酸转移酶dUTP缺口末端标记测定法和免疫组织化学对肿瘤组织进行研究。为了确定不同传代中突变等位基因频率的变化情况，我们从原发性肿瘤、肝转移灶和PDTX模型（F1/F2）中分离基因组DNA。
肿瘤的生理特性与患者肿瘤的特性一致。抗癌药物延缓了肿瘤生长，抑制了增殖并导致细胞凋亡。组织学评估显示代内PDTX模型之间没有可观察到的异质性。在没有高质量过滤条件的情况下进行的目标外显子测序分析显示，各代中83个癌症相关基因存在一些基因变异。然而，当将F0中突变总数定义为零且F2中≥5时，在配对中检测到克隆癌谱分析（EGFR、KRAS、BRAF、PIK3CA、NRAS、APC和TP53）的准确预后影响。
建立了一种用于评估化疗疗效的CRC肝转移PDTX模型。该模型保留了患者肿瘤的生理特征，并可能提供一种评估化疗疗效的有力手段。
