Establishment of a Patient-Derived Xenograft Tumor From Hepatitis C-Associated Liver Cancer and Evaluation of Imatinib Treatment Efficacy.
Animals
Antineoplastic Agents
/ therapeutic use
Carcinoma, Hepatocellular
/ drug therapy
Disease Models, Animal
Hepatitis C, Chronic
/ complications
Heterografts
Humans
Imatinib Mesylate
/ therapeutic use
Liver Neoplasms
/ drug therapy
Mice
Neoplasm Transplantation
Treatment Outcome
Xenograft Model Antitumor Assays
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
24
02
2020
revised:
25
03
2020
accepted:
04
04
2020
pubmed:
2
5
2020
medline:
30
4
2021
entrez:
2
5
2020
Statut:
ppublish
Résumé
Chronic hepatitis C virus (HCV) infection is one of the major causal factors for hepatocellular carcinoma (HCC). The treatment options for HCC are limited for lack of a convenient animal model for study in HCV infection and liver pathogenesis. This study aimed to develop a patient-derived xenograft (PDX) tumor in mice by using a tumor from a patient with HCV-associated HCC and evaluating this model's therapeutic potential. After resection of the primary tumor from the patient liver, excess viable tumor was implanted into highly immunodeficient mice. A mouse xenograft tumor line was developed, and the tumor was successfully passaged for at least three rounds in immunodeficient mice. The patient's primary tumor and the mouse xenografts were histologically similar. Genetic profiling by short-tandem-repeat analysis verified that the HCC-PDX model was derived from the HCC clinical specimen. HCV RNA present in the patient liver specimen was undetectable after passage as xenograft tumors in mice. Human albumin, α Our results demonstrated establishment of an HCV-associated HCC-PDX model as a powerful tool for evaluating candidate drugs. Information on molecular changes in cancer-specific gene expression facilitates efficient targeted therapies and treatment strategies.
Sections du résumé
BACKGROUND AND AIMS
Chronic hepatitis C virus (HCV) infection is one of the major causal factors for hepatocellular carcinoma (HCC). The treatment options for HCC are limited for lack of a convenient animal model for study in HCV infection and liver pathogenesis. This study aimed to develop a patient-derived xenograft (PDX) tumor in mice by using a tumor from a patient with HCV-associated HCC and evaluating this model's therapeutic potential.
APPROACH AND RESULTS
After resection of the primary tumor from the patient liver, excess viable tumor was implanted into highly immunodeficient mice. A mouse xenograft tumor line was developed, and the tumor was successfully passaged for at least three rounds in immunodeficient mice. The patient's primary tumor and the mouse xenografts were histologically similar. Genetic profiling by short-tandem-repeat analysis verified that the HCC-PDX model was derived from the HCC clinical specimen. HCV RNA present in the patient liver specimen was undetectable after passage as xenograft tumors in mice. Human albumin, α
CONCLUSIONS
Our results demonstrated establishment of an HCV-associated HCC-PDX model as a powerful tool for evaluating candidate drugs. Information on molecular changes in cancer-specific gene expression facilitates efficient targeted therapies and treatment strategies.
Identifiants
pubmed: 32356575
doi: 10.1002/hep.31298
pmc: PMC7483967
mid: NIHMS1599759
doi:
Substances chimiques
Antineoplastic Agents
0
Imatinib Mesylate
8A1O1M485B
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
379-388Subventions
Organisme : NCI NIH HHS
ID : R21 CA188472
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113645
Pays : United States
Organisme : NIH HHS
ID : R01 DK081817
Pays : United States
Organisme : NIH HHS
ID : R21CA188472
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK081817
Pays : United States
Informations de copyright
© 2020 by the American Association for the Study of Liver Diseases.
Références
Science. 1998 Jan 23;279(5350):577-80
pubmed: 9438854
Transl Cancer Res. 2015 Jun;4(3):256-269
pubmed: 26213686
J Virol. 2010 Jun;84(12):5936-46
pubmed: 20357092
Cancer Res. 2001 Nov 15;61(22):8118-21
pubmed: 11719439
Clin Infect Dis. 2013 Jul;57(2):230-6
pubmed: 23616492
Clin Cancer Res. 2018 Feb 15;24(4):972-984
pubmed: 29246941
J Exp Clin Cancer Res. 2019 Nov 4;38(1):447
pubmed: 31684985
J Virol. 2012 Dec;86(24):13621-8
pubmed: 23035229
Hum Pathol. 2020 Feb;96:48-55
pubmed: 31931021
Cancer Lett. 2005 Jan 20;217(2):231-6
pubmed: 15617841
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
J Hepatol. 2016 Oct;65(1 Suppl):S95-S108
pubmed: 27641991
World J Gastroenterol. 2018 Sep 28;24(36):4152-4163
pubmed: 30271080
Blood. 1997 Aug 15;90(4):1345-64
pubmed: 9269751
J Hepatol. 2014 Nov;61(1 Suppl):S79-90
pubmed: 25443348
Annu Rev Med. 2012;63:247-58
pubmed: 22017446
JAMA. 2012 Dec 26;308(24):2584-93
pubmed: 23268517
Hepatology. 2017 Dec;66(6):1766-1778
pubmed: 28664988
N Engl J Med. 2019 Apr 11;380(15):1450-1462
pubmed: 30970190
J Hepatol. 2016 Oct;65(4):727-733
pubmed: 27349488
Am J Clin Oncol. 2008 Feb;31(1):84-8
pubmed: 18376233
Gastroenterology. 2019 Jun;156(8):2313-2329.e7
pubmed: 30836093
Cancer Lett. 2014 Apr 10;345(2):210-5
pubmed: 23871966
Hepatology. 2020 Mar;71(3):780-793
pubmed: 31400158
J Virol. 2015 Nov;89(22):11549-56
pubmed: 26355082
Nat Rev Cancer. 2013 Feb;13(2):123-35
pubmed: 23344543
J Hepatol. 2016 Oct;65(4):719-726
pubmed: 27084592
J Carcinog. 2017 May 29;16:1
pubmed: 28694740