Exercise retards hepatocarcinogenesis in obese mice independently of weight control

Arfianti, Arfianti; Pok, Sharon; Barn, Vanessa; Haigh, W. Geoffrey; Yeh, Matthew M.; Ioannou, George N.; Teoh, Narci C.; Farrell, Geoffrey C.

doi:10.1016/j.jhep.2020.02.006

Cited by 31 publications

(20 citation statements)

References 50 publications

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“…Moreover, resistance training appeared to improve NAFLD with less energy consumption. A recent study conducted in mice with diethyl nitrosamine-induced hepatocellular carcinoma has shown that in early stages, voluntary exercise decreases the proliferation rate of dysplastic hepatocytes [66].…”

Section: Discussionmentioning

confidence: 99%

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial

et al. 2020

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Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease worldwide, and lifestyle modification is the current standard treatment. The aim of the study was to estimate the effect of two different physical activity (PA) programs, a Low Glycemic Index Mediterranean Diet (LGIMD), and their combined effect on the NAFLD score as measured by FibroScan®. Methods: Moderate or severe NAFLD subjects (n = 144) were randomly assigned to six intervention arms during three months. Interventions arms were a control diet, LGIMD, aerobic activity program (PA1), combined activity program (PA2), and LGIMD plus PA1 or LGIMD plus PA2. The data were compared at baseline, at 45 days, and at 90 days. Analysis of variance was performed under the intention-to-treat principle. Results: There was a statistically significant reduction in the NAFLD score after 45 days of treatment in every working arm except for Arm 1 (control diet). After 90 days, the best results were shown by the intervention arms in which LGIMD was associated with PA: LGIMD plus PA1 (−61.56 95% CI −89.61, −33.50) and LGIMD plus PA2 (−38.15 95% CI −64.53, −11.77). Conclusion: All treatments were effective to reduce NAFLD scores, but LGIMD plus PA1 was the most efficient.

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Section: Discussionmentioning

confidence: 99%

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial

et al. 2020

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“…In addition, several mouse studies have now also found a beneficial role of exercise in reducing HCC incidence. [405][406][407] Using a genetic model of NASH-HCC (PTEN-deficient mice), Dufour and colleagues found that regular exercise reduces the number and size of genetically determined liver tumors without affecting steatosis or other NAFLD parameters. 405 Importantly, exercise mediated these benefits by upregulating AMPK and consequently downregulating mTOR activity.…”

Section: Lifestyle Interventions: the Role Of Exercise And Caffeine In Hcc Developmentmentioning

confidence: 99%

“…406 Furthermore, a recent study demonstrated using the Alms1 mutant (foz/foz) obese/diabetic mice that voluntary exercise reduces DEN-induced HCC development through p53-mediated induction of p27 and JNK suppression. 407 All in all, there is mounting evidence pointing to exercise being beneficial against hepatocarcinogenesis in mice and men, but further studies are required in humans to conclusively prove this is indeed the case.…”

Section: Lifestyle Interventions: the Role Of Exercise And Caffeine In Hcc Developmentmentioning

confidence: 99%

The therapeutic landscape of hepatocellular carcinoma

Gallage

García‐Beccaria

Szydlowska

et al. 2021

Med

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The liver is endowed with an amazing regenerative capacity that allows it to withstand an enormous amount of damage. Nevertheless, it is precisely this highly regenerative capacity that renders it susceptible to dysplasia and liver cancer. Liver cancer is not only one of the most common cancers but also one of the deadliest. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 70%-90% of all cases, but treatment options for advanced stages remain scarce. Therefore, a great deal of effort has gone into identifying early diagnostic markers as well as novel therapies, both local and systemic, for the treatment of this deadly disease. In this review, we aim to shed light into the current therapeutic landscape of HCC with an emphasis on the available treatments, ranging from surgical and local-ablative therapy for early and intermediate stages of the disease to systemic therapies for advanced cancer treatments. We will also address the molecular mechanisms and limitations of currently available systemic therapies and the causes of treatment resistance and finally summarize the emerging future avenues and novel concepts that are promising.

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“…APP, the amyloid beta precursor protein, is central to the pathogenesis of Alzheimer disease (30). It has been reported that accumulation of APP in mitochondria can impair mitochondrial function and lead to obesity (31), a potential driver of various cancers (32)(33)(34)(35). ESR1 is an effective therapeutic target in breast cancer (36).…”

Section: Regulation Of Angiogenesis In Hccmentioning

confidence: 99%

Integrated bioinformatics analysis revealed the regulation of angiogenesis by tumor cells in hepatocellular carcinoma

Huo

Zheng

et al. 2021

Bioscience Reports

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, metastasis accounts for most of the cases. Angiogenesis plays an important role in cancer metastasis, but how tumor cells affect the function of endothelial cells by dictating their miRNA expression remains largely unknown.Differentially expressed miRNAs (DEMs) were identified through dataset downloaded from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R. We then use online tools to obtain potential targets of candidate microRNAs(miRNAs) and functional enrichment analysis，as well as the protein-protein interaction (PPI). Finally, the function of miR-302c-3p was validated through in vitro assay.In the current study, we found that HCC cells altered miRNAs expression profiles of human umbilical vein endothelial cells (HUVECs) and miR-302c-3p was the most downregulated miRNA in HUVECs when they were co-cultured with HCC-LM3 cells. Functional enrichment analysis of the candidate targets revealed that these genes were involved in epigenetic regulation of gene expression, in particular, histone methylation. In addition, PPI network demonstrated distinct roles of genes targeted by miR-302c-3p. Importantly, inhibition of angiogenesis, migration and permeability by the most downregulated miR-302c-3p in HUVECs was confirmed in vitro. These findings brought us novel insight into the regulation of angiogenesis by HCC cells and provided potential targets for the development of therapeutic strategies.

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Exercise retards hepatocarcinogenesis in obese mice independently of weight control

Cited by 31 publications

References 50 publications

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial

Physical Activity and Low Glycemic Index Mediterranean Diet: Main and Modification Effects on NAFLD Score. Results from a Randomized Clinical Trial

The therapeutic landscape of hepatocellular carcinoma

Integrated bioinformatics analysis revealed the regulation of angiogenesis by tumor cells in hepatocellular carcinoma

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