Mouse models in liver cancer research: A review of current literature

Leenders, M.W.H.; Nijkamp, Maarten W.; Rinkes, Inne H.M. Borel

doi:10.3748/wjg.14.6915

Cited by 67 publications

(71 citation statements)

References 74 publications

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“…Rodent models such as mice, have been commonly used to study the mechanisms underlying hepatocarcinogenesis, due to similarities between murine and human hepatic lesions at the histological and molecular levels (Klaunig and Kamendulis, 2004;Leenders, 2008;Santos et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

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Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to expo-sure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks.2 Samples were taken 18 h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection. DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p < 0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

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“…The epigenetic carcinogens stimulate the pre-neoplastic state to evolve into a malignant neoplasm by controlling cell proliferation, apoptosis and cell differentiation without DNA modification (12)(13)(14). Common hepatocarcinogens include diethylnitrosamine and phenobarbital (4,15). These chemicals are either administered to newborn mice in order to determine genotoxicity, or for longer periods to induce epigenetic carcinogenesis (11,16).…”

Section: Discussionmentioning

confidence: 99%

“…Animal models are widely used to improve our understanding of HCC, in particular mouse models (4). These mouse models include the carcinogen-induced model, the implantation model, the genetically engineered mouse, and the viral hepatocarcinogenesis model, which are distinguished by etiological aspects (4).…”

Section: Discussionmentioning

confidence: 99%

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Generation of liver-specific TGF-α and c-Myc-overexpressing fibroblasts for future creation of a liver cancer porcine model

Kim

Ahn

Woo

et al. 2014

Molecular Medicine Reports

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Abstract. Liver cancer is one of the most serious life-threatening diseases in the world. Although the rodent model of hepatocellar carcinoma (HCC) is commonly used, it is limited when considering preclinical applications, including transarterial chemoembolization. The pig is a more appropriate model for applying preclinical procedures as it has similar anatomical and physiological characteristics to humans. In the current study, transgenic fibroblasts were generated that overexpressed two proto-oncogenes specifically in hepatocytes. Porcine TGF-α and c-myc genes were isolated and these were linked with the porcine albumin promoter, which has exhibited selective activity in liver cells. Targeting vectors were introduced into the porcine fibroblasts using a liposome-mediated delivery system and the transgenic cell line was screened with 3 weeks of G-418 treatment. Selected vector-positive colonies were further confirmed with polymerase chain reaction-based genotyping. Thus, the transgenic cell lines created in the current study should induce liver cancer in pig models following somatic cell nuclear transfer.

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“…In addition, nude mice are expensive, difficult to rear and uncommonly used (Cai et al, 2005). As a result, using orthotopic nude models to validate targeting agents is rarely reported (Leenders et al, 2008). Nude mice models are typically divided into subcutaneous transplantation model and orthotopic transplantation model.…”

Section: Xenograft Models Of Human Hepatomamentioning

confidence: 99%

The application of antitumor drug-targeting models on liver cancer

Yan¹,

Chen²,

Wang³

et al. 2015

Drug Delivery

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Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

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Mouse models in liver cancer research: A review of current literature

Cited by 67 publications

References 74 publications

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Generation of liver-specific TGF-α and c-Myc-overexpressing fibroblasts for future creation of a liver cancer porcine model

The application of antitumor drug-targeting models on liver cancer

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