Experimental Models to Define the Genetic Predisposition to Liver Cancer

Pascale, Rosa M.; Simile, Maria M.; Peitta, Graziella; Seddaiu, Maria A.; Feo, Francesco; Calvisi, Diego F.

doi:10.3390/cancers11101450

Cited by 16 publications

(13 citation statements)

References 134 publications

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“…Previous study of the genetic mechanisms of the inherited predisposition to HCC, based on the comparative evaluation of the molecular pathways involved in HCC developing in rat strains differently predisposed to HCC, have shown that the genes responsible for the susceptibility to HCC control the amplification and/or overexpression of c- Myc , the expression of cell cycle regulatory genes, the activity of Ras/Erk and Akt/mTor , the methionine cycle, and DNA repair pathways [ 84 ]. The activation of oncogenes or the mutation of oncosuppressor genes, including p53, may be responsible of different deregulations leading to glycolytic metabolism and to the inhibition of the respiratory enzymes including cytochrome c oxidase.…”

Section: The Genetic Susceptibility To Cancermentioning

confidence: 99%

The Warburg Effect 97 Years after Its Discovery

Pascale

Calvisi

Simile

et al. 2020

Cancers

Self Cite

195

128

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The deregulation of the oxidative metabolism in cancer, as shown by the increased aerobic glycolysis and impaired oxidative phosphorylation (Warburg effect), is coordinated by genetic changes leading to the activation of oncogenes and the loss of oncosuppressor genes. The understanding of the metabolic deregulation of cancer cells is necessary to prevent and cure cancer. In this review, we illustrate and comment the principal metabolic and molecular variations of cancer cells, involved in their anomalous behavior, that include modifications of oxidative metabolism, the activation of oncogenes that promote glycolysis and a decrease of oxygen consumption in cancer cells, the genetic susceptibility to cancer, the molecular correlations involved in the metabolic deregulation in cancer, the defective cancer mitochondria, the relationships between the Warburg effect and tumor therapy, and recent studies that reevaluate the Warburg effect. Taken together, these observations indicate that the Warburg effect is an epiphenomenon of the transformation process essential for the development of malignancy.

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Section: The Genetic Susceptibility To Cancermentioning

confidence: 99%

The Warburg Effect 97 Years after Its Discovery

Pascale

Calvisi

Simile

et al. 2020

Cancers

Self Cite

195

128

View full text Add to dashboard Cite

show abstract

“…Transgenic species-The use of transgenic species or even mice with a humanized liver [99] could aid in mechanistic studies or down-stream analysis of (specific) chronic liver disease in a more human-like setting. Although several genetically modified species are available, e.g., for NAFLD [100] or liver cancer [101], only a few PCLS research papers make use of transgenic species. We recommend the use of transgenic species for PCLS research, as this would improve the progression in chronic liver disease research.…”

Section: Liver Diseasementioning

confidence: 99%

Best Practices and Progress in Precision-Cut Liver Slice Cultures

Dewyse

Reynaert

Grunsven

2021

IJMS

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Thirty-five years ago, precision-cut liver slices (PCLS) were described as a promising tool and were expected to become the standard in vitro model to study liver disease as they tick off all characteristics of a good in vitro model. In contrast to most in vitro models, PCLS retain the complex 3D liver structures found in vivo, including cell–cell and cell–matrix interactions, and therefore should constitute the most reliable tool to model and to investigate pathways underlying chronic liver disease in vitro. Nevertheless, the biggest disadvantage of the model is the initiation of a procedure-induced fibrotic response. In this review, we describe the parameters and potential of PCLS cultures and discuss whether the initially described limitations and pitfalls have been overcome. We summarize the latest advances in PCLS research and critically evaluate PCLS use and progress since its invention in 1985.

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“…Genetically engineered mouse models (GEMMs), cell line-derived xenograft (CDX) or patient-derived xenograft (PDX) models, and humanized mouse models (HMMs) have their own benefits and are commonly employed in cancer research [19,20,21,22,23,24,25,26,27,28,29,30]. Nevertheless, several issues in the development of animal models for cancer research have been encountered, such as different susceptibility of various mouse and rat strains to cancers, genetic diversions and technical variations in the animals, and polygenic predisposition in different strains controlled by multiple genetic loci [31,32,33,34,35,36,37,38]. Based on these and other limitations, currently used animal models might result in an inaccurate recapitulation of tumor development, leading to discrepancies between the outputs of preclinical research and clinical trials for development of cancer treatment [39,40,41].…”

Section: Discussionmentioning

confidence: 99%

Development of a MEL Cell-Derived Allograft Mouse Model for Cancer Research

Kim

Choi

Lee

et al. 2019

Cancers

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Murine erythroleukemia (MEL) cells are often employed as a model to dissect mechanisms of erythropoiesis and erythroleukemia in vitro. Here, an allograft model using MEL cells resulting in splenomegaly was established to develop a diagnostic model for isolation/quantification of metastatic cells, anti-cancer drug screening, and evaluation of the tumorigenic or metastatic potentials of molecules in vivo. In this animal model, circulating MEL cells from the blood stream were successfully isolated and quantified with an additional in vitro cultivation step. In terms of the molecular-pathological analysis, we were able to successfully evaluate the functional discrimination between methyl-CpG-binding domain 2 (Mbd2) and p66α in erythroid differentiation, and tumorigenic potential in spleen and blood stream of allograft model mice. In addition, we found that the number of circulating MEL cells in anti-cancer drug-treated mice was dose-dependently decreased. Our data demonstrate that the newly established allograft model is useful to dissect erythroleukemia pathologies and non-invasively provides valuable means for isolation of metastatic cells, screening of anti-cancer drugs, and evaluation of the tumorigenic potentials.

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Experimental Models to Define the Genetic Predisposition to Liver Cancer

Cited by 16 publications

References 134 publications

The Warburg Effect 97 Years after Its Discovery

The Warburg Effect 97 Years after Its Discovery

Best Practices and Progress in Precision-Cut Liver Slice Cultures

Development of a MEL Cell-Derived Allograft Mouse Model for Cancer Research

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