The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: March 25, 2024

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as fibrosis. Alcohol abuse, non-alcoholic fatty disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic injury. Exploring potential therapeutic targets understanding molecular mechanisms involved in fibrosis are essential for development effective interventions. The goal this comprehensive review is explain how PI3K/AKT signaling pathway contributes reduction target investigated through summary results from vivo vitro studies. Studies focusing on activation have shown significant decrease markers improvement function. emphasizes may prevent ECM synthesis hepatic stellate cell (HSC) activation, ultimately reducing fibrotic response. specific downstream effectors constitute rapidly developing field study. In conclusion, plays role attenuating Its complex regulating HSC production, demonstrated both , underscores its approach managing slowing progression. A provides valuable insights into future developments implications clinical applications.

Language: Английский

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Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3441 - 3441

Published: Feb. 8, 2023

Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients' survival and outcome pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies focused unravelling role tumor mutational burden (TMB), i.e., total number mutations per coding area genome, ascertain whether it can be considered reliable biomarker used either stratification HCC patients in subgroups different responsiveness immunotherapy, or prediction disease progression, particularly relation etiologies. review, we summarize advances study TMB TMB-related landscape, focusing their feasibility as guides therapy decisions and/or predictors clinical outcome.

Language: Английский

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Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1973 - 1973

Published: Feb. 6, 2024

The dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway can lead to uncontrolled cellular growth and tumorigenesis. Targeting PI3K its downstream substrates has been shown be effective in preclinical studies phase III trials with approval several inhibitors by Food Drug Administration (FDA) over past decade. However, limited clinical efficacy these inhibitors, intolerable toxicities, acquired resistances limit application inhibitors. This review discusses signaling pathway, alterations causing carcinogenesis, current novel adverse effects, resistance mechanisms, challenging issues, future directions

Language: Английский

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Role of p53 suppression in the pathogenesis of hepatocellular carcinoma

World Journal of Gastrointestinal Pathophysiology, Journal Year: 2023, Volume and Issue: 14(3), P. 46 - 70

Published: June 1, 2023

In the world, hepatocellular carcinoma (HCC) is among top 10 most prevalent malignancies. HCC formation has indeed been linked to numerous etiological factors, including alcohol usage, hepatitis viruses and liver cirrhosis. Among defects in a wide range of tumours, notably HCC, silencing p53 tumour suppressor gene. The control cell cycle preservation gene function are both critically important functions p53. order pinpoint core mechanisms find more efficient treatments, molecular research employing tissues main focus. Stimulated triggers necessary reactions that achieve arrest, genetic stability, DNA repair elimination DNA-damaged cells' responses biological stressors (like oncogenes or damage). To contrary hand, oncogene protein murine double minute 2 (MDM2) significant inhibitor MDM2 causes degradation, which turn adversely controls function. Despite carrying wt-p53, majority HCCs show abnormalities p53-expressed apoptotic pathway. High in-vivo expression might have two clinical impacts on HCC: (1) Increased levels exogenous cause cells undergo apoptosis by preventing growth through number pathways; (2) Exogenous makes susceptible various anticancer drugs. This review describes primary pathological mechanism, chemoresistance therapeutic HCC.

Language: Английский

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Investigation of the effects of Theranekron and Sorafenib treatments on carcinogenesis, apoptosis and biochemical profile in hepatocellular carcinoma in rats

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: 34(7), P. 750 - 760

Published: April 5, 2024

This study aimed to investigate the effects of

Language: Английский

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Toward a New Era in the Management of Hepatocellular Carcinoma: Novel Perspectives on Therapeutic Options and Biomarkers

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9018 - 9018

Published: May 19, 2023

Liver cancer remains a global health challenge and its incidence is growing worldwide [...]

Language: Английский

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FXR, MRP-1 and SLC7A5: New Targets for the Treatment of Hepatocellular Carcinoma

Technology in Cancer Research & Treatment, Journal Year: 2024, Volume and Issue: 23

Published: Jan. 1, 2024

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) rat model, so as to provide new therapeutic targets for gene therapy HCC. Sixty male Wistar rats were randomly divided into three groups. The experimental group given 0.2% diethylnitrosamine (DEN) by gavage with a dose 10 mg/kg, 3 times week, it stopped at 12 weeks. control physiological saline gavage, while sham operation did not receive anything gavage. At weeks, one was euthanized, changes livers recorded. procedure repeated After HCC only occurred group. confirming formation tumor through pathological examination, liver tissues taken from FXR, MRP-1 SLC7A5 detected. 7 weeks ate less, their weight significantly reduced. Three months later, detected 15 ratio FXR/GAPDH mRNA, MRP-1/GAPDH SLC7A5/GAPDH mRNA different among Under light microscope FXR protein, protein react respective antibodies, they showed granular expression. Every section included numbers positive cells each lower than that normal tissues, but higher suggesting drugs targeting may be strategies treatment

Language: Английский

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Evaluation of The Effects of Tarantula Cubensis Alcohol Extract and Sorafenib Treatments on P21 Protein, Total Antioxidant Capacity and Metabolic Profile in Experimental Rats Hepatocellular Carcinoma

Manas Journal of Agriculture Veterinary and Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 201 - 209

Published: Oct. 22, 2024

Hepatocellular carcinoma (HCC) is defined as the sixth most common cancer type and third in terms of cancer-related deaths. Tarantula cubensis alcohol extract (TCAE, Theranekron) a homeopathic medicine frequently used veterinary treatment papilloma, mammary adenocarcinoma necrotic disorders. The present study aimed to reveal effectiveness TCAE Sorafenib (S) HCC induced by Diethylnitrosamine (DEN) N-nitrosomorpholine (NMOR)-induced rats. Rats were randomly divided into 7 groups: Control (C), + (CT), S (CS), Cancer (CC), CC+TCAE (CCT), CC+S (CCS), CC+TCAE+S (CCTS). In CC group, values for glucose, triglyceride (TG) total antioxidant capacity (TAC) found be significantly higher than all other groups (p<0.001), while p21 levels lower (p<0.05). It determined an increase serum (p<0.05) significant decrease glucose TG (p<0.001) CCT, CCS CCTS compared group. Histopathological examination revealed that group showed morphology, caused tumor incidence size. As result, it can said alone and/or combined with chemotherapy drugs antiproliferative effects on cells HCC. combination therapy may potentially synergize improve magnitude durability antitumor responses patients

Language: Английский

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