Imaging of N-Linked Glycans in Biological Tissue Sections Using Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry DOI
Miranda R. Weigand,

Alyssa M. Moore,

Hang Hu

et al.

Journal of the American Society for Mass Spectrometry, Journal Year: 2023, Volume and Issue: 34(11), P. 2481 - 2490

Published: Oct. 2, 2023

N-linked glycans are complex biomolecules vital to cellular functions that have been linked a wide range of pathological conditions. Mass spectrometry imaging (MSI) has used study the localization in cells and tissues. However, their structural diversity presents challenge for MSI techniques, which stimulates development new approaches. In this study, we demonstrate first time spatial mapping biological tissues using nanospray desorption electrospray ionization mass (nano-DESI MSI). Nano-DESI is an ambient technique previously metabolites, lipids, proteins tissue samples without special sample pretreatment. released from glycoproteins established enzymatic digestion with peptide N-glycosidase F, examined nano-DESI MSI. We formalin-fixed paraffin-embedded human hepatocellular carcinoma prostate both positive negative modes. examine 38 consisting high mannose, hybrid fucosylated, sialyated glycans. mode well-suited underivatized sialylated On-tissue MS/MS different adducts proves advantageous elucidation glycan sequence. This demonstrates applicability liquid extraction techniques samples, providing additional tool glycobiology research.

Language: Английский

Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells DOI
Jaya Lakshmi Thangaraj, Michael Coffey, Edith Lopez

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(9), P. 1327 - 1343.e5

Published: July 9, 2024

Language: Английский

Citations

16
Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma DOI Creative Commons
Bruno Sangro, Peter R. Galle, Robin Kate Kelley

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(23), P. 2790 - 2799

Published: May 28, 2024

In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.

Language: Английский

Citations

15
EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL DOI Creative Commons

Mingang Pan,

Muyu Luo,

Lele Liu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Jan. 29, 2024

Abstract Background Hepatocellular Carcinoma (HCC) is a matter of great global public health importance; however, its current therapeutic effectiveness deemed inadequate, and the range targets limited. The aim this study was to identify early growth response 1 (EGR1) as transcription factor target in HCC explore role assess potential gene therapy utilizing EGR1 for management HCC. Methods In study, both vitro vivo assays were employed examine impact on mouse model human organoid assay utilized Additionally, molecular mechanism underlying regulation expression suppression by investigated. Results results our investigation revealed notable decrease promoted multiplication cells xenografted tumors. On other hand, excessive hindered proliferation repressed development Furthermore, efficacy validated using models hepatoma models, thereby providing additional substantiation anti-cancer mechanistic analysis demonstrated that interacted with promoter region phosphofructokinase-1, liver type (PFKL), leading repression PFKL consequent inhibition PFKL-mediated aerobic glycolysis. Moreover, sensitivity tumors sorafenib found be increased EGR1. Conclusion Our findings suggest possesses tumor suppressor HCC, may offer benefits patients.

Language: Английский

Citations

14
Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma DOI Creative Commons
Xin Li,

Yu‐Fei Pan,

Yibin Chen

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 29, 2024

Abstract The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC remains limited, underlying mechanisms are still uncertain. Therefore, this study aimed characterize effects ATO By evaluating susceptibilities human murine cell lines treatment, we discovered that cells exhibited range sensitivity highlighting their heterogeneity. A gene signature comprising 265 genes was identified distinguish ATO-sensitive from ATO-insensitive cells. According signature, patients have also been classified differential features response. Our results showed induced reactive oxygen species (ROS) accumulation activation multiple death modalities, necroptosis ferroptosis, Meanwhile, elevated immunogenicity observed Similar were not We reported mitochondrial injury mtDNA release into cytoplasm tumors. This subsequently activated cGAS-STING-IFN axis, facilitating CD8 + T infiltration activation. found IFN pathway PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted anti-tumor response In summary, our data indicate heterogeneous responses exist significantly induces immunogenic (ICD) activates tumor-derived mtDNA-STING-IFN axis. These findings may offer new perspective on clinical warrant further study.

Language: Английский

Citations

13
Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients DOI
Maria Eva Argenziano, Mi Na Kim, Michele Montori

et al.

Hepatology International, Journal Year: 2024, Volume and Issue: 18(S2), P. 922 - 940

Published: July 16, 2024

Language: Английский

Citations

12
New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow DOI Open Access
Rafał Becht, Kajetan Kiełbowski, Michał Wasilewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1456 - 1456

Published: Jan. 25, 2024

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, C, and non-alcoholic fatty disease represent major risk factors of HCC. Multiple different treatment options are available, depending on Barcelona Clinic Cancer (BCLC) algorithm. Systemic reserved for certain patients in stages B who will not benefit from regional methods. In last fifteen years, arsenal available therapeutics has largely expanded, which improved outcomes. Nevertheless, all respond to these agents novel combinations drugs needed. this review, we aim summarize pathway trials investigating safety efficacy targeted immunotherapies since introduction sorafenib. Furthermore, discuss current evidence regarding resistance mechanisms potential targets advanced

Language: Английский

Citations

11
Integration of Clinical Trial Spatial Multiomics Analysis and Virtual Clinical Trials Enables Immunotherapy Response Prediction and Biomarker Discovery DOI
Shuming Zhang, Atul Deshpande, Babita K. Verma

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(16), P. 2734 - 2748

Published: June 11, 2024

Due to the lack of treatment options, there remains a need advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models human trials novel systemic therapies that improve outcomes for patients with cancer. Computational methods simulate tumors mathematically describe cellular and interactions are emerging as promising tools impact therapy entirely silico, potentially greatly accelerating delivery patients. To facilitate design dosing regimens identification potential biomarkers immunotherapy, we developed computational model track tumor progression at organ scale while capturing spatial heterogeneity HCC. This quantitative systems pharmacology was designed effects combination immunotherapy. initiated using literature-derived parameter values fitted specifics Model validation done comparison multiomics data neoadjuvant HCC clinical trial combining anti-PD1 immunotherapy multitargeted tyrosine kinase inhibitor cabozantinib. Validation proteomics imaging mass cytometry demonstrated closer proximity between CD8 T cells macrophages correlated nonresponse. We also compared output Visium transcriptomics profiling samples posttreatment resections another independent study monotherapy. Spatial confirmed simulation results, suggesting importance patterns vasculature TGFβ immune cell interactions. Our findings demonstrate incorporating mathematical modeling computer simulations high-throughput provides patient outcome prediction biomarker discovery. Significance: Incorporating an effective

Language: Английский

Citations

9
Identification and validation of PANoptosis-related LncRNAs prognosis system in hepatocellular carcinoma DOI Creative Commons
Qi Shu, Junfeng Zhu,

Jiaping Mo

et al.

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

Published: Feb. 19, 2025

Abstract Hepatocellular carcinoma (HCC) is one of the most common solid malignancies in world. Due to limited effectiveness current drug treatments, further research on HCC necessary. PANoptosis defined as an inflammatory RCD whose main features combine pyroptosis, apoptosis and necroptosis which cannot be explained by any these three RCDs alone. In HCC, risk stratification based PANoptosis-associated lncRNAs has clinical application potential. this study, we explored related PANoptosis-related (PRLs) analyzing significantly differentially expressed genes HCC. HCC-associated PRL scores were established WGCNA, LASSO analysis multivariate Cox assessment. Subsequently, verified prognostic ability score for patients, basis a assessment model its reliability. The relationship between immune infiltration well sensitivity was analyzed evaluate reference value model. Western blot PCR reliability bioinformatics results. observed suppression progression invasiveness following selected knockdown validated our Our results provide new evidence role

Language: Английский

Citations

1
Antitumor effects of BPCO on liver cancer cells DOI

Shan-Bin Li,

Tong-Shi-Yao Zhao,

Zhen Ye

et al.

Journal of Asian Natural Products Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Feb. 22, 2025

Esculetin is a coumarin compound with anticancer, antioxidant, and anti-inflammatory activities. In this study, we synthesized an esculetin derivative, 6,7-bis(Pentyloxy)-2H-Chromen-2-One (BPCO), through etherification. BPCO inhibited the proliferation of HepG2 cells in dose- time-dependent manner. It also cell migration, promoted apoptosis, caused cycle arrest at G1 phase. Additionally, downregulated expression levels Bcl-2 Bcl-XL upregulated Bax Bak. This study shows that inhibits hepatocellular carcinoma induces providing basis for further as antitumor agent.

Language: Английский

Citations

1
Overexpressed or hyperactivated Rac1 as a target to treat hepatocellular carcinoma DOI Creative Commons
Vincent Sauzeau, J. Beignet, Gérard Vergoten

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 179, P. 106220 - 106220

Published: April 9, 2022

Language: Английский

Citations

32