Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidișel, Alexandru; Marcovici, Iasmina; Coricovac, Dorina; Hut, Florin; Dehelean, Cristina; Creţu, Octavian

doi:10.3390/cancers13153651

Cited by 38 publications

(44 citation statements)

References 184 publications

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“…Thereafter, the cells employed for this study were cultured at low passages to avoid any lack of reliability. HepaRG is an immortalized human hepatic progenitor cell line recently emerging as a useful in vitro model for toxicological evaluations, representing one of the most employed cell lines for the study of drug-induced toxicity [28][29][30]. Compared to primary hepatocytes, HepaRG cells are more advantageous in terms of availability and reproducibility [28].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells

et al. 2022

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Background and Objectives: The consumption of dietary supplements has increased over the last decades among pregnant women, becoming an efficient resource of micronutrients able to satisfy their nutritional needs during pregnancy. Furthermore, gestational drug administration might be necessary to treat several pregnancy complications such as hypertension. Folic acid (FA) and folate (FT) supplementation is highly recommended by clinicians during pregnancy, especially for preventing neural tube birth defects, while labetalol (LB) is a β-blocker commonly administered as a safe option for the treatment of pregnancy-related hypertension. Currently, the possible toxicity resulting from the co-administration of FA/FT and LB has not been fully evaluated. In light of these considerations, the current study was aimed at investigating the possible in vitro cardio- and hepato-toxicity of LB-FA and LB-FT associations. Materials and Methods: Five different concentrations of LB, FA, FT, and their combination were used in myoblasts and hepatocytes in order to assess cell viability, cell morphology, and wound regeneration. Results: The results indicate no significant alterations in terms of cell viability and morphology in myoblasts (H9c2(2-1)) and hepatocytes (HepaRG) following a 72-h treatment, apart from a decrease in the percentage of viable H9c2(2-1) cells (~67%) treated with LB 150 nM–FT 50 nM. Additionally, LB (50 and 150 nM)–FA (0.2 nM) exerted an efficient wound regenerating potential in H9c2(2-1) myoblasts (wound healing rates were >80%, compared to the control at 66%), while LB-FT (at all tested concentrations) induced no significant impairment to their migration. Conclusions: Overall, our findings indicate that LB-FA and LB-FT combinations lack cytotoxicity in vitro. Moreover, beneficial effects were noticed on H9c2(2-1) cell viability and migration from LB-FA/FT administration, which should be further explored.

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Section: Discussionmentioning

confidence: 99%

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells

et al. 2022

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“…To date, several mouse models for the study of hepatocarcinogenesis exist; however, available rodent models can be very diverse in terms of tumor development and histological subtypes heavily depending on their strain and biological background [ 28 , 42 ]. Often genetically engineered mice develop cancer without premalignant lesions or early tumors are not detected in the endpoint studies [ 28 , 43 ]. GEMM or chemically induced mouse models are widely used to study specific genes of interest or drug interactions but only few authors specifically address the role of the tumor vasculature [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Vascular Remodeling Is a Crucial Event in the Early Phase of Hepatocarcinogenesis in Rodent Models for Liver Tumorigenesis

Tulessin

Sarker²,

Griger³

et al. 2022

Cells

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The investigation of hepatocarcinogenesis is a major field of interest in oncology research and rodent models are commonly used to unravel the pathophysiology of onset and progression of hepatocellular carcinoma. HCC is a highly vascularized tumor and vascular remodeling is one of the hallmarks of tumor progression. To date, only a few detailed data exist about the vasculature and vascular remodeling in rodent models used for hepatocarcinogenesis. In this study, the vasculature of HCC and the preneoplastic foci of alteration (FCA) of different mouse models with varying genetic backgrounds were comprehensively characterized by using immunohistochemistry (CD31, Collagen IV, αSMA, Desmin and LYVE1) and RNA in situ hybridization (VEGF-A). Computational image analysis was performed to evaluate selected parameters including microvessel density, pericyte coverage, vessel size, intratumoral vessel distribution and architecture using the Aperio ImageScope and Definiens software programs. HCC presented with a significantly lower number of vessels, but larger vessel size and increased coverage, leading to a higher degree of maturation, whereas FCA lesions presented with a higher microvessel density and a higher amount of smaller but more immature vessels. Our results clearly demonstrate that vascular remodeling is present and crucial in early stages of experimental hepatocarcinogenesis. In addition, our detailed characterization provides a strong basis for further angiogenesis studies in these experimental models.

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“…Signs of chronic damage, like severe cell infiltration and necrosis of the centrilobular tissue, were discovered in the 4 th week (Fig 12b). 44 Lobular collapse and severe fibrosis were discovered in the 8 th week (Fig 12c)…”

Section: And Fig 5 -Fig 10)mentioning

confidence: 98%

“…In the 2 nd week (Table 2), histopathological studies showed non-specific damages like cellular infiltration and cellular swelling. [43][44] Cellular infiltration was primarily discovered in 2 nd week (Fig 12a). Signs of chronic damage, like severe cell infiltration and necrosis of the centrilobular tissue, were discovered in the 4 th week (Fig 12b).…”

Section: And Fig 5 -Fig 10)mentioning

confidence: 99%

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Histomorphological Progression of Diethylnitrosamine (DEN) Induced Hepatocellular Carcinoma Model in Rat

Mukherjee¹,

Biswas²,

Roy

et al. 2022

Int J Life Sci Pharm Res

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Hepatocellular carcinoma (HCC) commonly known as hepatoma is a frequently occurring liver cancer that occupies 75% of all types of liver cancers. It affects the hepatocellular cells which is the major cell of the liver. Some models can be developed for HCC in rats but it is time-consuming. Nitrosodiethylamine is a very popular carcinogenic drug, very useful to develop experimental animal models. The present study focuses on the establishment of an animal model through a simple approach of experimental protocol along with the duration of the experiment that leads to creating a scope for future studies associated with metastasis as well as anti-metastasis studies. For the present study 2 groups were formed where each group containing 16 rats. Phenobarbital was given for 7 days to each group after diluting with water at a concentration of 0.3g/L before administering the first DEN. The control group received the same number of vehicles for 8 weeks. 50mg/kg of DEN was received intraperitoneally by the animal of the 2nd group twice a week for eight weeks. Bodyweight, the weight of the liver, and all the blood parameters were analysed like alpha-fetoprotein, SGPT, SGOT, and ALP, and a comparison was made with the control group. After evaluating all biological and histological data it can be concluded that the outcome of the present study signifies a simple experimental protocol along with an appropriate experimental duration animal model which leads to help in the study of the mechanism of metastasis and anti-metastasis agent in near future. The current work also represents a straightforward experimental methodology that aids in the investigation of metastatic mechanisms and anti-metastasis agents, with phenobarbital serving as a good promoting agent.

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Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cited by 38 publications

References 184 publications

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells

In Vitro Toxicological Profile of Labetalol-Folic Acid/Folate Co-Administration in H9c2(2-1) and HepaRG Cells

Vascular Remodeling Is a Crucial Event in the Early Phase of Hepatocarcinogenesis in Rodent Models for Liver Tumorigenesis

Histomorphological Progression of Diethylnitrosamine (DEN) Induced Hepatocellular Carcinoma Model in Rat

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