Past, present, and future of chemically induced hepatocarcinogenesis rodent models: Perspectives concerning classic and new cancer hallmarks

Romualdo, Guilherme Ribeiro; Heidor, Renato; Bacil, Gabriel Prata; Moreno, Fernando Salvador; Barbisan, Luı́s Fernando

doi:10.1016/j.lfs.2023.121994

Cited by 3 publications

(2 citation statements)

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“…Hepatocellular carcinoma (HCC) is a neoplasm whose development, beyond microbiological factors (HBV, HCV infections), depends on lifestyle choices, including dietary choices [ 1 ]. HCC develops as a consequence of chronic liver diseases characterized by inflammation and cirrhosis [ 2 ]. It is estimated that this type of cancer constitutes over 80% of diagnosed primary liver tumors.…”

Section: Introductionmentioning

confidence: 99%

“…The non-metabolic causes of liver cell carcinogenesis relate to the intake of substances with mutagenic effects through diet, adversely affecting gene expression, and to engagement in a diet characterized by insufficient antioxidant potential [ 2 , 7 , 8 ]. As a result of these abnormalities, a diet lacking essential substances for detoxification and repair processes may promote the development of the cancer process [ 2 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

Janota,

Szymanek

2024

Cancers

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Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized by a low intake of antioxidants, such as vitamins E and C, selenium, and polyphenols, as well as an excessive consumption of energy and harmful substances. Repeated bad dietary choices that contribute to an unbalanced lifestyle lead to the accumulation of fatty substances in the liver and to it entering an inflammatory state, which, without intervention, results in cirrhosis, the main cause of HCC. This review of the English language literature aims to present the food components that, when included in the daily diet, reduce the risk of developing HCC, as well as identifying foods that may have a carcinogenic effect on liver cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

Janota,

Szymanek

2024

Cancers

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Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities

Kafle,

Suttiprapa,

Muhammad

et al. 2024

PLoS Negl Trop Dis

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Background Epigenetic modifications, such as DNA methylation and histone modifications, are pivotal in regulating gene expression pathways related to inflammation and cancer. While there is substantial research on epigenetic markers in cholangiocarcinoma (CCA), Opisthorchis viverrini-induced cholangiocarcinoma (Ov-CCA) is overlooked as a neglected tropical disease (NTD) with limited representation in the literature. Considering the distinct etiological agent, pathogenic mechanisms, and pathological manifestations, epigenetic research plays a pivotal role in uncovering markers and potential targets related to the cancer-promoting and morbidity-inducing liver fluke parasite prevalent in the Great Mekong Subregion (GMS). Emerging studies highlight a predominant hypermethylation phenotype in Opisthorchis viverrini (O. viverrini) tumor tissues, underscoring the significance of abnormal DNA methylation and histone modifications in genes and their promoters as reliable targets for Ov-CCA. Principal findings Relevant published literature was identified by searching major electronic databases using targeted search queries. This process retrieved a total of 81 peer-reviewed research articles deemed eligible for inclusion, as they partially or fully met the pre-defined selection criteria. These eligible articles underwent a qualitative synthesis and were included in the scoping review. Within these, 11 studies specifically explored Ov-CCA tissues to investigate potential epigenetic biomarkers and therapeutic targets. This subset of 11 articles provided a foundation for exploring the applications of epigenetics-based therapies and biomarkers for Ov-CCA. These articles delved into various epigenetic modifications, including DNA methylation and histone modifications, and examined genes with aberrant epigenetic changes linked to deregulated signalling pathways in Ov-CCA progression. Conclusions This review identified epigenetic changes and Wnt/β-catenin pathway deregulation as key drivers in Ov-CCA pathogenesis. Promoter hypermethylation of specific genes suggests potential diagnostic biomarkers and dysregulation of Wnt/β-catenin-modulating genes contributes to pathway activation in Ov-CCA progression. Reversible epigenetic changes offer opportunities for dynamic disease monitoring and targeted interventions. Therefore, this study underscores the importance of these epigenetic modifications in Ov-CCA development, suggesting novel therapeutic targets within disrupted signalling networks. However, additional validation is crucial for translating these novel insights into clinically applicable strategies, enhancing personalised Ov-CCA management approaches.

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Insights on epithelial cells at the single-cell level in hepatocellular carcinoma prognosis and response to chemotherapy

Qi,

Zhang

2023

Front. Pharmacol.

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Background: Hepatocellular carcinoma (HCC) originates from Epithelial cells, and epithelial lineage plasticity has become a promising research direction for advancing HCC treatment. This study aims to focus on Epithelial cells to provide target insights for detecting HCC prognosis and response to drug therapy.Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE149614 were clustered using Seurat, and the differentiation and evolution of epithelial cells were analyzed by Monocle 2. Scissor+ and Scissor− Epithelial cells associated with the prognostic phenotypes of bulk RNA-seq of HCC were screened using the Scissor algorithm for differential analysis to screen candidate genes. Candidate genes were overlapped with prognostic related genes screened by univariate Cox regression, and the Least Absolute Shrinkage and Selection Operator (LASSO) sparse penalty was imposed on the intersection genes to construct a risk assessment system.Results: Eight major cell subpopulations of HCC were identified, among which the proportion of epithelial cells in non-tumor liver tissues and HCC tissues was significantly different, and its proportion increased with advanced clinical stage. During the progression of HCC, the whole direction of epithelial cells differentiation trajectory was towards enhanced cell proliferation. Differential analysis between Scissor+ and Scissor− epithelial cells screened 1,265 upregulated and 191 downregulated prognostic candidate genes. Wherein, the upregulated genes were enriched in Cell processes, Genetic information processing, Metabolism and Human disease with Infection. Nevertheless, immune system related pathways took the main proportions in downregulated genes enriched pathways. There were 17 common genes between upregulated candidate genes and prognostic risk genes, of which CDC20, G6PD and PLOD2 were selected as components for constructing the risk assessment system. Risk score showed a significant correlation with tumor stage, epithelial-mesenchymal transition (EMT) related pathways and 22 therapeutic drugs, and was an independent prognostic factor for HCC.Conclusion: This study revealed the cellular composition of HCC, the differentiation evolution and functional landscape of epithelial cells in the further deterioration of HCC, and established a 3-gene risk model, which was closely related to clinical features, EMT, and drug sensitivity prediction. These findings provided insights in patient prognosis and drug therapy detection for HCC.

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Past, present, and future of chemically induced hepatocarcinogenesis rodent models: Perspectives concerning classic and new cancer hallmarks

Cited by 3 publications

References 151 publications

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities

Insights on epithelial cells at the single-cell level in hepatocellular carcinoma prognosis and response to chemotherapy

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