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Animal Models of Hepatocellular Carcinoma Prevention.

ABSTRACT: Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant modulation of tumor microenvironment and incomplete understanding of HCC tumorigenesis. To this end, animal models of HCC are valuable tools to evaluate biology of tumor initiation and progression with specific insight into molecular and genetic mechanisms involved. In this review, we describe various animal models of HCC that facilitate effective ways to study therapeutic prevention strategies that have translational potential to be evaluated in a clinical context.

SUBMITTER: Shankaraiah RC

PROVIDER: S-EPMC6895981 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Animal Models of Hepatocellular Carcinoma Prevention.

Shankaraiah Ram C RC Gramantieri Laura L Fornari Francesca F Sabbioni Silvia S Callegari Elisa E Negrini Massimo M

Cancers 20191114 11

Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant mo ...[more]

PMID: 31739536

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Project description:Several studies have reported that metformin can reduce the risk of hepatocellular carcinoma (HCC) in diabetes patients. However, the direct anti-HCC effects of metformin have hardly been studied in patients, but have been extensively investigated in animal models of HCC. We therefore performed a systematic review and meta-analysis of animal studies evaluating the effects of metformin on HCC.We collected the relevant studies by searching EMBASE, Medline (OvidSP), Web of Science, Scopus, PubMed Publisher, and Google Scholar. Studies were included according to the following inclusion criteria: HCC, animal study, and metformin intervention. Study quality was assessed using SYRCLE's risk of bias tool. A meta-analysis was performed for the outcome measures: tumor growth (tumor volume, weight and size), tumor number and incidence.The search resulted in 573 references, of which 13 could be included in the review and 12 included in the meta-analysis. The study characteristics of the included studies varied considerably. Two studies used rats, while the others used mice. Only one study used female animals, nine used male, and three studies didn't mention the gender of animals in their experiments. The quality of the included studies was low to moderate based on the assessment of their risk of bias. The meta-analysis showed that metformin significantly inhibited the growth of HCC tumour (SMD -2.20[-2.96,-1.43]; n=16), but no significant effect on the number of tumors (SMD-1.05[-2.13,0.03]; n=5) or the incidence of HCC was observed (RR 0.62[0.33,1.16]; n=6). To investigate the potential sources of significant heterogeneities found in outcome of tumor growth (I2=81%), subgroup analyses of scales of growth measures and of types of animal models used were performed.Metformin appears to have a direct anti-HCC effect in animal models. Although the intrinsic limitations of animal studies, this systematic review could provide an important reference for future preclinical animal trials of good quality and clinical development.

Project description:IntroductionGlobally, hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer and the third important cause of cancer-related death. As there are only two targeted drugs for the treatment of advanced HCC-that merely extend survival by a few months-the need for alternative treatments is inevitable. Lycopene, a carotenoid that is known to be most abundant in red tomatoes and tomato-based products, has been investigated for its anticancer activity in various types of cancers including HCC. This review was conducted to evaluate the effects of lycopene on HCC from animal models to pave the way for further clinical studies.MethodsElectronic databases and search engines including PubMed, EMBASE, and Google Scholar were searched for original records addressing the anticancer effect of lycopene in animal models of HCC. Data were extracted using a format prepared in Microsoft Excel and exported to Stata 15.0 for analyses. A meta-analysis was performed using a random-effects model at a 95% confidence level for the outcome measures: tumor incidence, number, and growth (tumor volume and size). The presence of publication bias between studies was evaluated using Egger's test and funnel plot. The study protocol was registered in the PROSPERO database with reference number: CRD42019159312.ResultsThe initial database search yields 286 articles, of which 15 studies met the inclusion criteria. The characteristics of the included studies were a bit diversified. The studies involved a total of 644 animals (312 treatment and 332 control groups) and mice shared the majority (488) followed by rats (117) and ferrets (39). The meta-analysis showed that lycopene significantly reduced the incidence [RR 0.8; 95% CI 0.69, 0.92 (p=0.00); I2 = 30.4%, p=0.16; n=11], number [SMD-1.83; 95% CI -3.10, -0.57 (p=0.01); I2 = 95.9%, p=0.00; n=9], and growth [SMD -2.13; 95% CI -4.20, -0.04 (p=0.04); I2 = 94.6%, p=0.00; n=4] of HCC.ConclusionsAdministration of lycopene appears to inhibit the initiation and progression of cancer in animal models of HCC. However, more controlled and thorough preclinical studies are needed to further evaluate its anti-HCC effects and associated molecular mechanisms.

Dataset Information

Animal Models of Hepatocellular Carcinoma Prevention.

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Animal Models of Hepatocellular Carcinoma Prevention.

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