NOTCH1 regulates the DNA damage response and sorafenib resistance by activating ATM in hepatocellular carcinoma DOI
Jing Liu, Yan Yu,

Bin Xu

et al.

American Journal of Translational Research, Journal Year: 2024, Volume and Issue: 16(12), P. 7317 - 7329

Published: Jan. 1, 2024

This study investigates the mechanism underlying sorafenib resistance in hepatocellular carcinoma cells (HCC), focusing on DNA damage repair (DDR) pathways to develop targeted therapeutic strategies. Bioinformatics analysis was used screen genes associated with resistance, which further demonstrated by western blotting. Cell proliferation determined using EdU assay. The presence of binding sites between valproic acid (VPA) and NOTCH1 analyzed molecular docking. Comet flow cytometry assays evaluated cell cycle arrest induced VPA sorafenib-resistant cells, mechanistic insights gained via blotting co-immunoprecipitation (Co-IP). We found that NOTCH1/ATM axis plays a vital role prognosis patients liver cancer behavior cells. HCC resistant exhibited enhanced ability. Moreover, overexpression sorafenib-sensitive significantly increased proliferation. Conversely, silencing expression lines reduced their proliferative activity. Additionally, efficacy against sorafenib-resistance modulating NOTCH1/ATM/p-BRCA1/p-CHK2/γ-H2AX signaling homologous recombination (HR) Targeting ATM is promising strategy overcome HCC, particularly through combined use sorafenib.

Language: Английский

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access
Nilesh Kumar Sharma, Anjali Bahot,

Gopinath Sekar

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 680 - 680

Published: Feb. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Language: Английский

Citations

17
Lenvatinib in hepatocellular carcinoma: Resistance mechanisms and strategies for improved efficacy DOI
Y. Qin, Shisong Han, Yahan Yu

et al.

Liver International, Journal Year: 2024, Volume and Issue: 44(8), P. 1808 - 1831

Published: May 3, 2024

Hepatocellular carcinoma (HCC), one of the most prevalent and destructive causes cancer-related deaths worldwide, approximately 70% patients with HCC exhibit advanced disease at diagnosis, limiting potential for radical treatment. For such patients, lenvatinib, a long-awaited alternative to sorafenib first-line targeted therapy, has become key Unfortunately, despite some progress, prognosis remains poor because drug resistance development. However, molecular mechanisms underlying lenvatinib ways relief in are largely unknown lack systematic summary; thus, this review not only aims explore factors contributing HCC, but more importantly, summary methods conquer or mitigate resistance. The results suggest that abnormal activation pathways, transport, epigenetics, tumour microenvironment, cancer stem cells, regulated cell death, epithelial-mesenchymal transition, other involved development subsequent progression. To improve therapeutic outcomes inhibiting acquired resistance, combined therapies, nano-delivery carriers may be possible approaches.

Language: Английский

Citations

15
Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy DOI Creative Commons
Elias Kouroumalis, Ioannis Tsomidis, Argyro Voumvouraki

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1166 - 1166

Published: April 13, 2023

The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways critical for cell survival or death. balance between autophagy regulates liver turnover maintains intracellular homeostasis. However, the often dysregulated in many cancers, including HCC. may be either independent parallel one influence other. inhibit promote apoptosis, thus regulating fate cancer cells. In this review, concise overview HCC presented, with emphasis on new developments, role endoplasmic reticulum stress, implication microRNAs gut microbiota. characteristics associated specific disease also described brief description provided. initiation, progress metastatic potential reviewed experimental evidence indicating an interplay extensively analyzed. ferroptosis, recently pathway regulated death, presented. Finally, therapeutic implications drug resistance examined.

Language: Английский

Citations

23
Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight DOI Creative Commons
Anqi Li, Rui Wang, Yu-Qiang Zhao

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(6), P. 325 - 325

Published: June 8, 2024

Epigenetic and metabolic reprogramming alterations are two important features of tumors, their reversible, spatial, temporal regulation is a distinctive hallmark carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, new entry point for tumor therapy. Moreover, drives hepatocellular carcinoma (HCC) initiation progression, highlighting significance metabolism in this disease. Exploring inter-regulatory relationship between epigenetic modification has become one hot directions current research. As viral etiologies have given way to dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it urgent that complex molecular pathways linking them hepatocarcinogenesis be explored. However, how aberrant crosstalk modifications affects MASLD-induced HCC lacks comprehensive understanding. A better understanding linkages necessary improve treatment strategies. For reason, review examines interwoven landscape carcinogenesis context focusing regulating development interactions while also updating advances modification-based therapeutic drugs HCC.

Language: Английский

Citations

6
The Dual Role of LncRNAs in Hepatocellular Carcinoma: Friend and Foe DOI Creative Commons

Farzaneh Abam,

‪Saeid Ghorbian

Gastroenterology & Endoscopy, Journal Year: 2024, Volume and Issue: 2(4), P. 186 - 195

Published: June 4, 2024

In eukaryotes, RNA molecules called long non-coding RNAs (LncRNAs) have been found. Molecules that exceed 200 base pairs in length are incapable of coding for proteins. Studying the function LncRNAs cancer has main focus current investigation, which significantly impacted protein integrity and stability. can be regulated through various pathways, leading to chromatin changes methylation or as miRNA sponges. The most common type liver tumor worldwide is hepatocellular carcinoma (HCC), accounting around 80% subjects. Nonetheless, insufficiency trustworthy molecular markers remains a significant challenge HCC diagnosis treatment evaluation. HCC, such MEG3, MALAT1, HULC, HOTAIR, H19 dysregulation closely associated with expansion, metastasis, prognosis, diagnosis. primary goal this investigation was investigate newly discovered roles mechanisms pathophysiology cells identify potential therapeutic targets.

Language: Английский

Citations

4
Recent advancements in the small-molecule drugs for hepatocellular carcinoma (HCC): Structure-activity relationships, pharmacological activities, and the clinical trials DOI Open Access

Qichuan Deng,

Yü Huang, Jing Zeng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117343 - 117343

Published: Aug. 24, 2024

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies in world and sixth leading cause cancer death worldwide, it urgent to find safe effective drugs for treatment. As an important therapeutic method, small-molecule are continually being updated achieve improved effects. The purpose this study was investigate structural effects various FDA-listed sorafenib, cabozantinib, lenvatinib, regorafenib on corresponding HCC targets possible optimization methods, explore mechanism identifying potential that offer better efficacy fewer side

Language: Английский

Citations

4
Exosomal microRNA as a key regulator of PI3K/AKT pathways in human tumors DOI
Saade Abdalkareem Jasim, Abdulrahman T. Ahmed,

Aziz Kubaev

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(11)

Published: Oct. 14, 2024

Language: Английский

Citations

4
Drug resistance in TKI therapy for hepatocellular carcinoma: mechanisms and strategies DOI
Xue Jiang,

Xiaoying Ge,

Yueying Huang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217472 - 217472

Published: Jan. 1, 2025

Language: Английский

Citations

0
To construct and validate a risk score model of angiogenesis-related genes to predict the prognosis of hepatocellular carcinoma DOI Creative Commons

Duangui Gao,

Lu Yuan,

Tianpeng Jiang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 7, 2025

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality worldwide. Angiogenesis essential for HCC progression metastasis. Some angiogenesis-related genes promote this process, whereas other antiangiogenic inhibit growth Therefore, finding new potential biomarkers prognosis prediction treatment essential. Public RNAseq clinical data from TCGA GEO database, download GeneCards, MSigDB through single factor analysis Cox, LASSO build risk score-Cox regression model external validation verified GEO. Cox analysis, Kaplan Meier (KM) curve, ROC decision-curve will be used to evaluate examine score effect model. GSVA was assess variation gene sets between groups, ClBERSOFT, ESTIMATE, TIMER databases were analyze immune infiltration in single-cell level expression differences cells. Finally, three pairs tissues tissue adjacent by real-time fluorescent quantitative PCR (qRT_PCR) western blotting (WB) (ATP2A3 AEBP1 PNMA1, PLAT) HCC, knocked out HCCLM3 cells, which study biological function HCC. We established a prognostic assessment based on 13 significant associated LASSO-Cox analysis. The median divide these patients into high-risk low-risk group worse than that group. Through multivariate it found an independent predictor overall survival (OS). suggested predicted population showed higher activity purine, pyrimidine, riboflavin metabolic pathways. Compared group, tumor microenvironment reduction number cells promoting anti-tumor immunity increase inhibiting immunity, as well matrix components. On level, confirmed key (AEBP1, ATP2A3, PLAT, PNMA1) expressed differently liver cancer cell groups. qRT_PCR WB results AEBP1, PLAT highly compared tissue, proliferation, migration, invasion inhibited after knocking AEBP1. constructed novel models has guide development more personalized strategies patients. In addition, therapeutic target

Language: Английский

Citations

0
Extraction, GC-MS analysis, cytotoxic, anti-inflammatory and anticancer potential of Cannabis sativa female flower; in vitro, in vivo and in silico DOI Creative Commons
Waqas Safir, Arif Malik, Haleema Saadia

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 11, 2025

This work examines the anticancer activity, anti-inflammatory nature, and cytotoxicity of ethanol extract obtained from female flowers Cannabis sativa L using molecular methods in vitro , animal testing vivo as well computational simulations silico . From GC-MS analysis, following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), humulene. The antiproliferative activities determined on HeLa cells by MTT, Crystal Violet, Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality. bioinformatics analysis docking proved significant ligand-protein interactions CBD, THC, humulene cancer-associated proteins such PD-1/PD-L1, TNF-α, MMP-9. In breast cancer was first established Sprague-Dawley rats 7,12-dimethylbenz(a)anthracene (DMBA) then treated cannabinoids either singularly or combination. Detailed treatment demonstrated that use three simultaneously yielded best outcomes together tumor reduction. concentration serum biomarkers inflammation progression substantially reduced groups compared to control group, which proves synergistic effects these therapy. study emphasizes importance medical derivatives treatment.

Language: Английский

Citations

0