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A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma

Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient‐derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX mod...

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Autores principales: Yamano, Tomoki, Kubo, Shuji, Tomita, Naohiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221307/
https://www.ncbi.nlm.nih.gov/pubmed/32168428
http://dx.doi.org/10.1002/cam4.2986
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author Yamano, Tomoki
Kubo, Shuji
Tomita, Naohiro
author_facet Yamano, Tomoki
Kubo, Shuji
Tomita, Naohiro
author_sort Yamano, Tomoki
collection PubMed
description Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient‐derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX model, compared to the control group, 5‐fluorouracil (5‐FU) treatment resulted in statistically significant tumor growth inhibition (TGI), while oxaliplatin (OHP) and irinotecan had no significant inhibitory effects. In combination with 5‐FU, OHP showed the highest rate of TGI. The IC(50) for OHP was significantly lower than those for paclitaxel, gemcitabine, and trifluorothymidine in the PDX‐derived cell line when compared to in HT29, a colon cancer cell line. Genetic analysis of the patient tumor, PDX tumor, and the cell line demonstrated consistency in the microsatellite status and mutations in TP53, APC, HRAS, CSF1R, FGFR3, FLT3, PDGFRA, and RET genes. However, the PDX tumor alone had additional mutations, indicating that the PDX‐derived cell line may support the unstable genetic status of the PDX. Our findings confirmed the effectiveness of the combination of OHP and 5‐FU, which is a common treatment for advanced SBA and advanced colorectal cancer, in a preclinical model. This preclinical model of SBA can help in further understanding the biology of SBA.
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spelling pubmed-72213072020-05-15 A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma Yamano, Tomoki Kubo, Shuji Tomita, Naohiro Cancer Med Clinical Cancer Research Basic and clinical studies on small bowel adenocarcinoma (SBA) are limited due to the rare nature of this cancer. We established a patient‐derived xenograft (PDX) model from the tumor tissue of an advanced SBA patient with liver and peritoneal metastasis, and a cell line from the PDX. In the PDX model, compared to the control group, 5‐fluorouracil (5‐FU) treatment resulted in statistically significant tumor growth inhibition (TGI), while oxaliplatin (OHP) and irinotecan had no significant inhibitory effects. In combination with 5‐FU, OHP showed the highest rate of TGI. The IC(50) for OHP was significantly lower than those for paclitaxel, gemcitabine, and trifluorothymidine in the PDX‐derived cell line when compared to in HT29, a colon cancer cell line. Genetic analysis of the patient tumor, PDX tumor, and the cell line demonstrated consistency in the microsatellite status and mutations in TP53, APC, HRAS, CSF1R, FGFR3, FLT3, PDGFRA, and RET genes. However, the PDX tumor alone had additional mutations, indicating that the PDX‐derived cell line may support the unstable genetic status of the PDX. Our findings confirmed the effectiveness of the combination of OHP and 5‐FU, which is a common treatment for advanced SBA and advanced colorectal cancer, in a preclinical model. This preclinical model of SBA can help in further understanding the biology of SBA. John Wiley and Sons Inc. 2020-03-13 /pmc/articles/PMC7221307/ /pubmed/32168428 http://dx.doi.org/10.1002/cam4.2986 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Yamano, Tomoki
Kubo, Shuji
Tomita, Naohiro
A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title_full A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title_fullStr A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title_full_unstemmed A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title_short A patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
title_sort patient‐derived xenograft and a cell line derived from it form a useful preclinical model for small bowel adenocarcinoma
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221307/
https://www.ncbi.nlm.nih.gov/pubmed/32168428
http://dx.doi.org/10.1002/cam4.2986
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