Investigational New Drugs, Год журнала: 2023, Номер 41(1), С. 162 - 167
Опубликована: Фев. 1, 2023
Язык: Английский
Cancers, Год журнала: 2021, Номер 13(12), С. 3026 - 3026
Опубликована: Июнь 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
Язык: Английский
Процитировано
211
International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3778 - 3778
Опубликована: Март 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.
Язык: Английский
Процитировано
124
Cancers, Год журнала: 2021, Номер 13(20), С. 5059 - 5059
Опубликована: Окт. 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.
Язык: Английский
Процитировано
110
Current Treatment Options in Oncology, Год журнала: 2023, Номер 24(7), С. 711 - 724
Опубликована: Апрель 27, 2023
Язык: Английский
Процитировано
73
International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4495 - 4495
Опубликована: Апрель 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.
Язык: Английский
Процитировано
101
Frontiers in Pharmacology, Год журнала: 2022, Номер 13
Опубликована: Июль 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
Язык: Английский
Процитировано
57
Biology Direct, Год журнала: 2024, Номер 19(1)
Опубликована: Фев. 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.
Язык: Английский
Процитировано
10
JHEP Reports, Год журнала: 2025, Номер 7(4), С. 101312 - 101312
Опубликована: Янв. 8, 2025
Despite nearly 250 million people worldwide estimated to have chronic HBV infection, health-related quality of life (HRQOL) in HBV-related disease has not been well characterised. Here, we summarise existing data on HRQOL and quantify summary utility values by stage disease. Embase, Global Health, PubMed, Web Science were searched for articles investigating HRQOL. Meta-analyses scores pooled instrument; meta-regression was further adjusted the effect current health expenditure as a percentage gross domestic product (CHE/GDP), proxy importance healthcare perceived different countries. Twenty-two from 19 studies, comprising 10,311 patients, included. Of these 74% performed Western Pacific Region, 47% used EuroQoL-5D-3L instrument. found decrease with advancing stages Meta-regression showed following predicted mean infection: non-cirrhotic, 0.842; compensated cirrhosis, 0.820 (p = 0.474 compared non-cirrhotic); decompensated 0.722 0.001); hepatocellular carcinoma, 0.749 0.008). The type tool affected populations higher CHE/GDP associated values. Chronic infection impairs even when there is no evidence cirrhosis. particularly impaired advanced cirrhosis carcinoma. These results important implications global hepatitis elimination efforts are useful economic analyses. However, research needed, high-burden, low-income settings where lacking. This study, based 22 provides comprehensive synthesis impact B virus (HBV) patients' worldwide. findings, how living HBV, highlight patient-centred care holistic approaches management, at early cost-effectiveness analyses may help inform decision-making improving public policy towards viral hepatitis. study also underscores need low-to middle-income settings, effects treatment
Язык: Английский
Процитировано
1
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1
Journal of Materials Chemistry B, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
The therapeutic diagnosis of liver diseases has garnered significant interest within the medical community.
Язык: Английский
Процитировано
1