In vitro transformation of primary human hepatocytes: Epigenetic changes and stemness properties

Pez, Floriane; Gifu, Patricia; Esposti, Davide Degli; Farés, Nadim; Lopez, Anaïs; Lefrançois, Lydie; Michelet, Maud; Rivoire, Michel; Bancel, Brigitte; Sylla, Bakary S.; Herceg, Zdenko; Merle, Philippe; Fromentel, Claude Caron de

doi:10.1016/j.yexcr.2019.111643

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Besides, it has been reported that heterogeneous vascularization within the tumor is associated with poorly differentiated HCC cells [34]. After repetitive TACE treatment, these poorly differentiated tumor cells are probably empowered with stemness properties and chemoresistance under hypoxia microenvironment induced by TACE [35,36]. Hence, with the introduction of this important radiological feature, the p-TACE model was able to predict TACE refractoriness risk accurately before on-demand TACE.…”

Section: Discussionmentioning

confidence: 96%

A Novel Pre-treatment Model Predicting Risk of Developing Refractoriness to Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

Hu¹,

Lu²,

Li³

et al. 2020

J. Cancer

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Background and aim: Refractoriness to transarterial chemoembolization is common during the therapeutic process of hepatocellular carcinoma, which is an intractable issue and may compromise the prognosis. We aim to establish a pre-treatment model to identify patients with high risks of refractoriness. Methods: From 2010 to 2016, 824 treatment-naive patients who had initially underwent at least two sessions of transarterial chemoembolization in Zhongshan Hospital, Fudan University were retrospectively enrolled. These patients were randomly allocated into a training cohort and a validation cohort. The pre-treatment scoring model was established based on the clinical and radiological variables using logistic regression and nomogram. The discrimination and calibration of the model were also evaluated. Results: Logistic regression identified vascularization pattern, ALBI grade, serum alpha-fetoprotein level, serum γ-glutamyl transpeptidase level and major tumor size as the key parameters related to refractoriness. The p-TACE model was established using these variables (risk score range: 0-19.5). Patients were divided into six risk subgroups based on their scores (<4, ≥4, ≥7, ≥10, ≥13, ≥16). The discriminative ability, as determined by the area under receiver operating characteristic curve was 0.784 (95% confidence interval: 0.741-0.827) in the training cohort and 0.743 (95% confidence interval: 0.696-0.789) in the validation cohort. Moreover, satisfactory calibration was confirmed by Hosmer-Lemeshow test with P values of 0.767 and 0.913 in the training cohort and validation cohort. Conclusions: This study presents a pre-treatment model to identify patients with high risks of refractoriness after transarterial chemoembolization and shed light on clinical decision making.

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Section: Discussionmentioning

confidence: 96%

A Novel Pre-treatment Model Predicting Risk of Developing Refractoriness to Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

Hu¹,

Lu²,

Li³

et al. 2020

J. Cancer

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“…PHH isolated from liver tissue have been principally used to elucidate the physiological liver function but are also a valid model for studying HCC initiation. 85 , 86 Further applications of PHH consist of (i) 3D culture approach as spheroidal aggregates able to retain the main hepatocyte functions for a longer time 87 and (ii) studies of biotransformation and toxicity, including those used to evaluate drug-induced liver injury. 88 , 89 , 90 , 91 Unfortunately, studies on sex differences have been rarely performed with these models due to the poor characterization of the male and female donors.…”

Section: Sex-based In Vitro Models Of Hepatocellul...mentioning

confidence: 99%

Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

Smiriglia,

Lorito,

Serra

et al. 2023

iScience

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“…More recently, PHH have been used to elucidate the molecular pathways or genomic effects in response to carcinogens [ 246 , 258 , 259 , 260 , 261 , 262 ]. In addition, PHH have been addressed to evaluate the molecular and cellular events of HCC initiation through in vitro transformation based on lentiviral-transduction of oncogenic Harvey-RAS, simian virus 40 (SV40) small T antigen, and SV40 large T antigen [ 263 ]. The major drawbacks of PHH are the high donor-to-donor variability [ 253 ] and their progressive dedifferentiation, which makes them less suitable for long-term culture [ 264 ].…”

Section: In Vitro Models Of Hccmentioning

confidence: 99%

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

Romualdo

Leroy

Costa

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks.

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In vitro transformation of primary human hepatocytes: Epigenetic changes and stemness properties

Cited by 4 publications

References 36 publications

A Novel Pre-treatment Model Predicting Risk of Developing Refractoriness to Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

A Novel Pre-treatment Model Predicting Risk of Developing Refractoriness to Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

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