Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy DOI Creative Commons
Wenyu Luo, Shiqi Guo, Yang Zhou

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: April 27, 2022

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

Language: Английский

MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma DOI Open Access
Hyuk Moon, Simon Weonsang Ro

Cancers, Journal Year: 2021, Volume and Issue: 13(12), P. 3026 - 3026

Published: June 17, 2021

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic clinical researchers. The activated more than 50% of human cases; however, activating mutations RAS RAF genes are rarely found HCC, which genetic events leading to activation other cancers. This suggests that there an alternative mechanism behind HCC. Here, we will review recent advances understanding cellular molecular mechanisms involved discuss potential therapeutic strategies targeting context

Language: Английский

Citations

203
Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options DOI Open Access
Zuzanna Sas, Ewa Cendrowicz, Isabel Weinhäuser

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3778 - 3778

Published: March 29, 2022

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe the USA recent decades. Among different subtypes cancers, hepatocellular carcinoma (HCC) most commonly diagnosed cancer. Besides advances diagnosis promising results pre-clinical studies, HCC remains a highly lethal disease. In many cases, an effect chronic inflammation, which leads to formation complex tumor microenvironment (TME) composed immune stromal cells. TME patients challenge for therapies, as it involved metastasis development resistance. However, given that intricate system cells interacting cells, new immune-based therapies are being developed target HCC. Therefore, understanding complexity will provide possibilities design novel more effective immunotherapeutics combinatorial overcome resistance treatment. this review, we describe role inflammation during progression by focusing on TME. We also therapeutic possible treatment options.

Language: Английский

Citations

118
Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers DOI Open Access
Martha Dillon, Antonio R. Lopez,

Edward H. Lin

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(20), P. 5059 - 5059

Published: Oct. 10, 2021

The mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates genes that control cellular development, differentiation, proliferation, and apoptosis. Within multiple isoforms Ras Raf each display differences in functionality, efficiency, and, critically, oncogenic potential. According to NCI, over 30% all human cancers are driven by genes. This dysfunctional is implicated a wide variety leukemias solid tumors, both with without viral etiology. Due strong evidence Ras-Raf involvement tumorigenesis, many have attempted target cascade treat these malignancies. Decades unsuccessful experimentation had deemed undruggable, but recently, approval Sotorasib as first ever KRas inhibitor represents monumental breakthrough. advancement not novel challenges. As G12C mutant-specific drug, it also issue drug specificity within pathway; only do drugs affect single mutational profiles, few pan-inhibitor exceptions, tumor genetic heterogeneity may give rise drug-resistant profiles. Furthermore, significant challenges targeting downstream Raf, especially BRaf isoform, lie paradoxical activation wild-type mutant inhibitors. literature review will delineate mechanisms MAPK pathway its possible mutations, illustrate how specific mutations pathogenesis cancers, compare available in-development treatments pathway.

Language: Английский

Citations

109
Hepatocellular Carcinoma: a Narrative Review on Current Knowledge and Future Prospects DOI Open Access

Basil Alawyia,

Constantina Constantinou

Current Treatment Options in Oncology, Journal Year: 2023, Volume and Issue: 24(7), P. 711 - 724

Published: April 27, 2023

Language: Английский

Citations

71
Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC DOI Open Access
Hyun-Mi Kim, Da Som Lee, Tae Hyeon An

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4495 - 4495

Published: April 26, 2021

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type contributes biological processes driving severity NAFLD, primary cause for development chronic diseases. In last 20 years, rate non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs treatment NASH, a class thiazolidinediones (TZDs) sometimes used improve failure despite risk side effects. Therefore, diagnosis, prevention, progression NASH important issues. this review, we will discuss pathogenesis NAFLD/NASH current promising pharmacological therapies NAFLD/NASH. Further, provide insights into “adipose-derived adipokines” “liver-derived hepatokines” diagnostic therapeutic targets HCC.

Language: Английский

Citations

100
Caryophyllene Oxide Induces Ferritinophagy by Regulating the NCOA4/FTH1/LC3 Pathway in Hepatocellular Carcinoma DOI Creative Commons

Zhiru Xiu,

Yilong Zhu,

Jicheng Han

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: July 11, 2022

Ferritinophagy is associated with tumor occurrence, development, and therapy effects. ferroptosis are regulated by iron metabolism closely connected. LC3 protein a key in autophagy. Following the binding of NCOA4 to FTH1, it links LC3Ⅱ lysosomes, symbol ferritinophagy. A ferritinophagy's inducer likely open new avenues for anticancer medication research development. In this study, we discovered that caryophyllene oxide has substantial inhibitory effect on HCCLM3 HUH7 cells, regulating level cellular oxidative stress, levels autophagy leading ferritinophagy-related phenomenon. Furthermore, results T-AOC, DPPH free radical scavenging rate, hydroxyl inhibition indicated can inhibit cell anti-oxidation. The examination process revealed promotes production accumulation intracellular reactive oxygen species lipid peroxidation. NCOA4, were found be targeted regulators oxide. Caryophyllene Ⅱ, FTH1 promote vivo, lower volume, significantly improve tissue, raise Fe2+ malondialdehyde serum. compound also reduce NRF2, GPX4, HO-1, expression levels. reduction inhibited GSH radical's capacities serum, promoted deposition tissue resulting growth. summary, our study mostly kills liver cancer cells through ferritinophagy-mediated mechanisms. conclusion, may used as ferritinophagy activator field antitumor drug

Language: Английский

Citations

56
Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway DOI Creative Commons
Zhihuai Wang, Yinjie Zhang, Yuhang Shen

et al.

Biology Direct, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 28, 2024

STAM Binding Protein Like 1 (STAMBPL1), functions as a deubiquitinase (DUB) and plays significant role in various types of cancers. However, its effect DUB participating the HCC tumorigenesis progression still unknown. In study, upregulation strong prognosis value STAMBPL1 were identified patients. Functionally, significantly promoted cells proliferation metastasis, it interacts with TRAF2 stabilize via deubiquitination at K63 residue. The stabilized by overexpression transfers P65 protein into nucleus activates WNT/PI3K/ NF-kb signaling pathway. 251-436 sites particularly interact 294-496 TRAF2, thereby exerting function removing ubiquitin molecules attached to TRAF2. Our research unveiled new mediating stabilization, activating WNT/PI3K/NF-kb pathway, suggesting potential novel biomarker therapeutic target for HCC.

Language: Английский

Citations

9
Alleviation of liver fibrosis by inhibiting a non-canonical ATF4-regulated enhancer program in hepatic stellate cells DOI Creative Commons

Lixian Yang,

Chuangye Qi,

Lu Si

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 9, 2025

Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify ATF4, master transcription factor in ER stress response, promotes by facilitating response-independent epigenetic program hepatic stellate cells (HSCs). Unlike its canonical role regulating UPR genes during stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene under fibrogenic conditions. HSC-specific depletion of suppresses vivo. Mechanistically, TGFβ resets orchestrate unique enhancer for the transcriptional activation pro-fibrotic EMT genes. Analysis human data confirms strong correlation between HSC expression and progression. Importantly, small molecule inhibitor targeting translation effectively mitigates fibrosis. Together, our findings mechanism promoting reveal new opportunities treating this otherwise non-targetable disease. lacks treatments. This study reveals drives activating pharmacological inhibition reduces fibrosis, offering an opportunity therapies.

Language: Английский

Citations

1
A promising mesoporous silica carrier material for the diagnosis and treatment of liver diseases: recent research advances DOI
Zihao Sun, Xiaofang Li

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The therapeutic diagnosis of liver diseases has garnered significant interest within the medical community.

Language: Английский

Citations

1
Biocidal and biocompatible hybrid nanomaterials from biomolecule chitosan, alginate and ZnO DOI

Chandrasekaran Karthikeyan,

Nagendran Tharmalingam, Kokkarachedu Varaprasad

et al.

Carbohydrate Polymers, Journal Year: 2021, Volume and Issue: 274, P. 118646 - 118646

Published: Sept. 9, 2021

Language: Английский

Citations

41