Iron deficiency in hepatocellular carcinoma cells induced sorafenib resistance by upregulating HIF-1α to inhibit apoptosis DOI Open Access
Zelong Gao, Dongyao Wang, Jianxin Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114750 - 114750

Published: April 22, 2023

Sorafenib is the first-line therapeutic agent for hepatocellular carcinoma (HCC), but drug resistance has become a major impediment. Previously we found that abnormal iron metabolism in HCC led to deficiency, whether it induces sorafenib during treatment of not yet disclosed. In this study, observed effects deficiency on and explored underlying mechanisms. The results revealed killing cells were weakened by effectively restored re-supplementation. ferroptosis indicators, including contents lipid hydroperoxide (LPO) malondialdehyde (MDA), level intracellular reactive oxygen species (ROS), expression glutathione peroxidase 4 (GPX4), significantly changed sorafenib-treated cells. However, sorafenib-induced apoptosis was inhibited deficiency. Notably, anti-apoptotic protein B-cell lymphoma-2 (BCL-2) elevated, expressions other apoptotic proteins, BCL2-associated X (Bax), caspase-3, caspase-9, Mechanistically, upregulated hypoxia-inducible factor 1 alpha (HIF-1α) increase BCL-2. Inhibition HIF-1α suppressed deficiency-induced BCL-2 resistance. summary, generated increasing BCL-2, which therefore These identified as new cells, would be an effective target alleviate

Language: Английский

Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy DOI
Amit G. Singal, Fasiha Kanwal, Josep M. Llovet

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(12), P. 864 - 884

Published: Oct. 26, 2023

Language: Английский

Citations

346
Predictors of early and late hepatocellular carcinoma recurrence DOI Creative Commons
Riccardo Nevola,

Rachele Ruocco,

Livio Criscuolo

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(8), P. 1243 - 1260

Published: Feb. 24, 2023

Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes affected by a high recurrence rate (up to 70% cases 5 years after treatment). HCC within 2 treatment defined as "early" generally caused occult intrahepatic spread primary neoplasm related tumor burden. A that occurs "late" de novo HCC, independent neoplasm. Early has significantly poorer prognosis outcome than late recurrence. Different pathogenesis corresponds different predictors risk early or An adequate knowledge predictive factors stratification guides therapeutic strategy post-treatment surveillance. Patients at should be referred with lowest when standardized combined adjuvant therapy regimens. This review aimed expose examine differences between

Language: Английский

Citations

102
Geographical similarity and differences in the burden and genetic predisposition of NAFLD DOI
Terry Cheuk‐Fung Yip, Eduardo Vilar‐Gómez, Salvatore Petta

et al.

Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1404 - 1427

Published: Sept. 5, 2022

NAFLD has become a major public health problem for more than 2 decades with growing prevalence in parallel the epidemic of obesity and type diabetes (T2D). The disease burden differs across geographical regions ethnicities. Variations metabolic diseases, extent urban–rural divide, dietary habits, lifestyles, risk protective alleles can contribute to such differences. rise led remarkable increase number cases cirrhosis, hepatocellular carcinoma, hepatic decompensation, liver‐related mortality related NAFLD. Moreover, is associated multiple extrahepatic manifestations. Most them are factors progression liver fibrosis thus worsen prognosis All these comorbidities complications affect quality life subjects Given huge size population NAFLD, it expected that patients, healthcare systems, economy will suffer from ongoing In this review, we examine areas ethnicities, together distribution some well‐known genetic variants We also describe special populations including patients T2D, lean pediatric population, concomitant diseases. discuss outcomes, patient‐reported economic

Language: Английский

Citations

79
METTL3-m6A-EGFR-axis drives lenvatinib resistance in hepatocellular carcinoma DOI
Lina Wang, Qingxia Yang,

Qianying Zhou

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 559, P. 216122 - 216122

Published: March 9, 2023

Language: Английский

Citations

69
Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase II study DOI Creative Commons
Tianqi Zhang,

Zhijun Geng,

Mengxuan Zuo

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 27, 2023

Abstract Hepatic arterial infusion chemotherapy (HAIC) using a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promise for hepatocellular carcinoma (HCC) patients classified under Barcelona Clinic Liver Cancer (BCLC) stage C. In China, the combined therapy camrelizumab apatinib is now an approved first-line approach inoperable HCC. This study (NCT04191889) evaluated benefit combining with HAIC-FOLFOX HCC in BCLC Eligible were given maximum six cycles HAIC-FOLFOX, along apatinib, until either disease progression or intolerable toxicities emerged. The primary outcome measured was objective response rate (ORR) based on Response Evaluation Criteria Solid Tumors (RECIST) v1.1. Thirty-five enrolled. Based RECIST v1.1 criteria, confirmed ORR stood at 77.1% (95% CI: 59.9% to 89.6%), control 97.1% 85.1% 99.9%). median progression-free survival 10.38 months 7.79 12.45). Patient quality life had transient deterioration within four treatment, generally recovered thereafter. most frequent grade ≥3 above treatment-related adverse events included reduced lymphocyte count (37.1%) diminished neutrophil (34.3%). camrelizumab, HAIC demonstrated encouraging results manageable safety concerns

Language: Английский

Citations

57
Imaging to Predict Prognosis in Hepatocellular Carcinoma: Current and Future Perspectives DOI
Maxime Ronot, Victoria Chernyak, Adam M. Burgoyne

et al.

Radiology, Journal Year: 2023, Volume and Issue: 307(3)

Published: April 4, 2023

The focus of hepatocellular carcinoma (HCC) research for many years has been on noninvasive diagnosis. Standardized systematic algorithms composed combinations precise features now serve as diagnostic imaging markers HCC and constitute a major innovation liver imaging. In clinical practice, the diagnosis is based primarily secondarily pathologic analysis if are not specific. Whereas accurate essential, next phase will likely encompass predictive prognostic markers. biologically heterogeneous malignancy because complex molecular, pathologic, patient-level factors that impact outcomes treatment. recent years, there have advances in systemic therapy to augment extend existing large cache local regional options. However, guideposts treatment decisions neither sophisticated nor individualized. This review provides an overview prognosis from patient feature level with future directions toward more individualized guidance. © RSNA, 2023 See also editorial by Fowler et al this issue.

Language: Английский

Citations

54
NOP2-mediated m5C Modification of c-Myc in an EIF3A-Dependent Manner to Reprogram Glucose Metabolism and Promote Hepatocellular Carcinoma Progression DOI Creative Commons
Hao Zhang,

Xiangyu Zhai,

Yanfeng Liu

et al.

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Mitochondrial dysfunction and glycolysis activation are improtant hallmarks of hepatocellular carcinoma (HCC). NOP2 is an S-adenosyl-L-methionine-dependent methyltransferase that regulates the cell cycle proliferation activities. In this study, found contributes to HCC progression by promoting aerobic glycolysis. Our results revealed was highly expressed in it associated with unfavorable prognosis. knockout combination sorafenib enhanced sensitivity, which, turn, led marked tumor growth inhibition. Mechanistically, we identified c-Myc expression m5C-modification manner promote Moreover, our m5C methylation induced mRNA degradation eukaryotic translation initiation factor 3 subunit A (EIF3A)-dependent manner. addition, increase glycolytic genes LDHA, TPI1, PKM2, ENO1. Furthermore, MYC zinc finger protein (MAZ) as major transcription directly controlled HCC. Notably, a patient-derived xenograft (PDX) model, adenovirus-mediated maximized antitumor effect prolonged survival PDX-bearing mice. cumulative findings novel signaling pathway MAZ/NOP2/c-Myc uncovered important roles modifications metabolic reprogramming. Therefore, targeting suggested be potential therapeutic strategy for treatment

Language: Английский

Citations

53
Liver diseases: epidemiology, causes, trends and predictions DOI Creative Commons

Can Gan,

Yuan Yuan, Haiyuan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Citations

6
Temporal trends and patterns for early- and late-onset adult liver cancer incidence vary by race/ethnicity, subsite, and histologic type in the United States from 2000 to 2019 DOI Creative Commons
Mei‐Chin Hsieh, Kendra L. Ratnapradipa, Laura S. Rozek

et al.

Cancer Causes & Control, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

To examine incidence trends and patterns for early- late-onset liver cancer. Liver intrahepatic bile duct (IBD) cancers diagnosed between 2000 2019 were acquired from 22 SEER registries. Variables included early-onset (20-49) vs. (50+), anatomic subsite, histologic type (hepatocellular carcinoma [HCC] IBD cholangiocarcinoma [ICC]), sex, race/ethnicity. Age-standardized rates calculated using SEER*Stat. Jointpoint regression analysis was employed to estimate the annual percent change (APC) average APC (AAPC) with pairwise comparisons trend by sex race/ethnicity stratified age subsite. cancer decreased among (AAPC [95% CI] - 2.39 [- 2.74, 2.07]) but increased patients (2.85 [2.71, 3.01]), primarily driven HCC (3.60 [3.50, 3.71]). both ages ICC annually increasing 7.92% (6.84, 9.26) 6.32% (5.46, 8.86) patients. Early-onset displayed comparable across racial/ethnic groups; however, showed more variation, particularly American Indian/Alaska Native/Asian Pacific Islander (AI/AN/API) populations, which experienced a significant decrease in incidence, thereby narrowing gap other groups. For IBD, an identical pattern of non-Hispanic Blacks (NHBs) compared Hispanics coincidence test p = 0.1522, parallel observed sexes (p 0.5087). Late-onset continues rise, except NHB AI/AN/API, where have started over past 4-5 years. Early increase all

Language: Английский

Citations

2
Oncolytic virus VG161 in refractory hepatocellular carcinoma DOI

Yinan Shen,

Xueli Bai, Qi Zhang

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

2