Involvement of TLR4/ CXCL9/ PREX-2 pathway in the development of hepatocellular carcinoma (HCC) and the promising role of early administration of lactobacillus plantarum in Wistar rats

Elshaer, Asmaa M; El-Kharashi, Omnyah A.; Hamam, Ghada Galal; Nabih, Enas Samir; Magdy, Yosra; Samad, Abeer A. Abd El

doi:10.1016/j.tice.2019.07.010

Cited by 16 publications

(7 citation statements)

References 33 publications

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“…Moreover, supplementation with probiotics attenuates HCC pathogenesis by downregulating the expression of TLRinduced inflammation. In Wistar rats with thioacetamide-induced liver cirrhosis, early administration of L. plantarum significantly decreased the expression of TLR4, CXCL9, and PREX-2 together with improvement in liver function [46].…”

Section: Probioticsmentioning

confidence: 92%

Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

Temraz

Nassar

Kreidieh

et al. 2021

IJMS

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Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

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Section: Probioticsmentioning

confidence: 92%

Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

Temraz

Nassar

Kreidieh

et al. 2021

IJMS

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“…Studies in a nude mouse model showed that blocking NF-κB could significantly inhibit the expression of the transcription factor Snail, thus inhibiting the occurrence of EMT ( Jing et al, 2014 ). TLR4/CXCL9/PREX-2 (phosphatidylinositol-3, 4, 5-trisphosphate RAC exchanger 2) is an important pathway in the pathogenesis of liver cirrhosis and can be activated by thioacetamide ( Elshaer et al, 2019 ). However, this pathway can be significantly inhibited upon the addition of Lactobacillus plantarum in rats ( Elshaer et al, 2019 ).…”

Section: Mechanisms By Which the Gut Microbiota Mediates The Developm...mentioning

confidence: 99%

“…TLR4/CXCL9/PREX-2 (phosphatidylinositol-3, 4, 5-trisphosphate RAC exchanger 2) is an important pathway in the pathogenesis of liver cirrhosis and can be activated by thioacetamide ( Elshaer et al, 2019 ). However, this pathway can be significantly inhibited upon the addition of Lactobacillus plantarum in rats ( Elshaer et al, 2019 ). The transcription factor STAT3 (which can be activated by IL-6) can regulate a series of genes, including cyclin D1, Bcl-2, c-myc and IL-10, that promote cell growth and angiogenesis ( Lin et al, 2016 ).…”

Section: Mechanisms By Which the Gut Microbiota Mediates The Developm...mentioning

confidence: 99%

Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy

et al. 2022

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The gut microbiota is gaining increasing attention, and the concept of the “gut-liver axis” is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.

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“…Studies have shown that these biomarkers are involved in the immune and inflammatory responses in the development and progression of liver cancer, among which, the level of α-AFP is associated with the diversity of intestinal microorganisms ( Zhang et al, 2019a ). Elshaer et al reported that in thioacetame-induced liver cirrhosis rats, the TLR4-CXCL9 pathway was activated and the serum α-AFP level increased, which could be prevented by administration of Lactobacillus Plantarum ( Elshaer et al, 2019 ). Another study reported that the levels of serum zonulin, a marker of intestinal permeability, increased significantly in patients with liver cirrhosis and HCC.…”

Section: Role Of Gut Microbiota and Their Metabolites On The Immune Mechanisms Of The Progression Of Liver Cancermentioning

confidence: 99%

Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer

Xiao

Liu

et al. 2021

Front. Cell Dev. Biol.

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Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson’s disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.

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Involvement of TLR4/ CXCL9/ PREX-2 pathway in the development of hepatocellular carcinoma (HCC) and the promising role of early administration of lactobacillus plantarum in Wistar rats

Cited by 16 publications

References 33 publications

Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy

Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer

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