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Establishing a colorectal cancer liver metastasis patient-derived tumor xenograft model for the evaluation of personalized chemotherapy

Authors
 Joohee Jung  ;  Jisup Kim  ;  Hyun Kyung Lim  ;  Kyoung Mee Kim  ;  Yun Sun Lee  ;  Joon Seong Park  ;  Dong Sup Yoon 
Citation
 ANNALS OF SURGICAL TREATMENT AND RESEARCH, Vol.93(4) : 173-180, 2017 
Journal Title
 ANNALS OF SURGICAL TREATMENT AND RESEARCH 
ISSN
 2288-6575 
Issue Date
2017
Keywords
Colorectal neoplasms ; Metastasis ; Sequence analysis ; Xenograft model antitumor assays
Abstract
Purpose: 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. Methods: 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 mm3, 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). Results: 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 de novo 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. Conclusion: 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.
Files in This Item:
T201704042.pdf Download
DOI
10.4174/astr.2017.93.4.173
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Jisup(김지섭) ORCID logo https://orcid.org/0000-0002-0742-5517
Park, Joon Seong(박준성) ORCID logo https://orcid.org/0000-0001-8048-9990
Yoon, Dong Sup(윤동섭) ORCID logo https://orcid.org/0000-0001-6444-9606
Lee, Yun Sun(이윤선)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161079
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