Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

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

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Biological Activity of Natural and Synthetic Peptides as Anticancer Agents

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7264 - 7264

Published: July 1, 2024

Cancer is one of the leading causes morbidity and death worldwide, making it a serious global health concern. Chemotherapy, radiotherapy, surgical treatment are most used conventional therapeutic approaches, although they show several side effects that limit their effectiveness. For these reasons, discovery new effective alternative therapies still represents an enormous challenge for tumour diseases. Recently, anticancer peptides (ACPs) have gained attention cancer diagnosis treatment. ACPs small bioactive molecules which selectively induce cell through variety mechanisms such as apoptosis, membrane disruption, DNA damage, immunomodulation, well inhibition angiogenesis, survival, proliferation pathways. can also be employed targeted delivery drugs into cells. With over 1000 clinical trials using ACPs, potential application in therapy seems promising. Peptides utilized conjunction with imaging agents molecular methods, MRI, PET, CT, NIR, improving detection classification cancer, monitoring response. In this review we will provide overview biological activity some natural synthetic common malignant tumours affecting people around world.

Language: Английский

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Realizing the Promise of Artificial Intelligence in Hepatocellular Carcinoma through Opportunities and Recommendations for Responsible Translation

Jurnal Online Informatika, Journal Year: 2024, Volume and Issue: 9(1), P. 70 - 79

Published: April 26, 2024

This study aims to provide an overview of the current state-of-the-art applications artificial intelligence (AI) and machine learning in management hepatocellular carcinoma (HCC), explore future directions for continued progress this emerging field. is a comprehensive literature review that synthesizes recent findings advancements application AI techniques across various aspects HCC care, including screening early detection, diagnosis staging, prognostic modeling, treatment planning, interventional guidance, monitoring response. The draws upon wide range published research studies, focusing on integration with diverse data sources, such as medical imaging, clinical data, genomics, other multimodal information. results demonstrate AI-based systems have shown promise improving accuracy efficiency screening, diagnosis, tumor characterization compared traditional methods. Machine models integrating clinical, genomic outperformed conventional staging predicting survival recurrence risk. recommendation potential optimize personalized therapy selection, while augmented reality can guide procedures real-time. Moreover, longitudinal may enhance assessment response monitoring. Despite these promising findings, highlights need rigorous multicenter prospective validation standardized datasets, thoughtful consideration ethical implications before widespread implementation technologies management.

Language: Английский

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Alkaloid-Based Modulators of the PI3K/Akt/mTOR Pathway for Cancer Therapy: Understandings from Pharmacological Point of View

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 402, P. 111218 - 111218

Published: Aug. 28, 2024

Language: Английский

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Modulation of Tumor-Associated Macrophages to Overcome Immune Suppression in the Hepatocellular Carcinoma Microenvironment

Cancers, Journal Year: 2024, Volume and Issue: 17(1), P. 66 - 66

Published: Dec. 29, 2024

Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components HCC microenvironment (TME) tumor-associated macrophages (TAMs), which play pivotal role in modulating growth, immune evasion, metastasis. Macrophages are divided into two subtypes: pro-inflammatory M1 anti-inflammatory M2, both may exist TME with altered function proportion. The M2 further subdivided four distinct suppressive subsets. TAMs generally counted as M2-like functions that exert significant influence on cancer progression ability tumors to escape surveillance. Their involvement responses via different mechanisms at local systemic levels has made them key target for therapeutic interventions seeking enhance treatment outcomes. How TAMs’ depletion influences primary interest immunotherapies. purpose this review delve recent progress TAM-targeting therapies. We will explore current theories, benefits, challenges associated or inhibition. manuscript concludes future directions potential implications clinical practice.

Language: Английский

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The microRNA landscape and regulatory network in Clonorchis sinensis-infected hepatocellular carcinoma: implications for tumor progression

Parasites & Vectors, Journal Year: 2025, Volume and Issue: 18(1)

Published: Feb. 21, 2025

Language: Английский

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From Vision Changes to Hospice: The Rapid Progression of Orbital Metastasis in Hepatocellular Carcinoma

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

Published: March 9, 2025

Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy with a high potential for metastasis, commonly involving the lungs, bones, and lymph nodes. However, orbital metastasis exceptionally rare presentation. This case describes 73-year-old man history of HCC, hypertension, type 2 diabetes neuropathy, chronic obstructive pulmonary disease (COPD), hepatitis C, cirrhosis, portal hypertension who presented two-week blurry vision in left eye, numbness on forehead, sensation fullness. He also reported episode unintentional bilateral upper extremity jerking followed by nausea vomiting. Examination revealed left-sided proptosis, imaging identified retrobulbar mass muscle involvement. Biopsy confirmed metastatic HCC. Despite initial referral Y-90 radiotherapy, patient was unable to undergo treatment due multiple hospitalizations unrelated conditions. Following diagnosis he experienced rapid functional decline, including falls, cognitive deterioration, loss independence activities daily living, ultimately requiring hospice care. underscores importance recognizing patterns especially patients presenting ocular symptoms. It highlights severe consequences delayed cancer critical role coordinated care managing complex patients. Clinicians must remain vigilant identifying unusual symptoms HCC facilitate early timely intervention advanced disease.

Language: Английский

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Circulating tumor DNA methylation markers for the early diagnosis of hepatocellular carcinoma

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 14, 2025

Hepatocellular carcinoma (HCC) is a major global health concern, being the sixth most common cancer and third leading cause of deaths worldwide. Less than 30% HCC patients are eligible for curative treatment, primarily due to diagnosis at advanced stages. This emphasizes importance early detection in improving survival outcomes. In this study, we investigated methylation levels certain genes miRNAs liquid biopsy developed methyl predictive model (MPM-8G). The AUC MPM-8G was found be significantly higher that AFP (alpha-fetoprotein) alone. When were combined, increased notably, indicating combined use offers superior diagnostic performance enhances accuracy detection. Furthermore, combination proved powerful tool HCC. study successfully identified differences from patients, construction diagnosis. impressive these markers underscores their potential further clinical application management

Language: Английский

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Clonorchis sinensis-infected hepatocellular carcinoma exhibits distinct tumor microenvironment and molecular features

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

Published: March 17, 2025

Clonorchis sinensis (Cs)-infected hepatocellular carcinoma (HCC) patients have a poorer prognosis than non-Cs-infected HCCs. However, the molecular mechanisms of Cs-infected HCC remain unclear. To address this, this study aims to uncover tumor microenvironment and features that may contribute these poor outcomes. The research involved bulk RNA sequencing paired adjacent tissue samples from 10 Cs + - patients. Differentially expressed genes were identified, followed by enrichment analyses reveal functional changes. Survival analysis top up- down-regulated in tumors was performed using TCGA database. Additionally, clinical data 1,461 retrospectively analyzed assess impact infection on microvascular invasion metastasis rates. In vitro assays also conducted excretory/secretory products (CsESPs) examine their effect cells HUVECs. We identified 785 up-regulated 675 compared tumors, enriched pathways related extracellular matrix remodeling immunosuppression. revealed are associated with prognosis. Clinical showed increased vitro, CsESPs enhanced migration promoted tube formation human umbilical vein endothelial cells. This provides novel insights into landscape underscores infection's role enhancing migration, angiogenesis. findings understanding parasitic infections cancer progression suggest potential prognostic markers for HCC.

Language: Английский

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A Chemotherapy Response-Related Gene Signature and DNAJC8 as Key Mediators of Hepatocellular Carcinoma Progression and Drug Resistance

Journal of Hepatocellular Carcinoma, Journal Year: 2025, Volume and Issue: Volume 12, P. 579 - 595

Published: March 1, 2025

Chemotherapy resistance in hepatocellular carcinoma presents a significant challenge to improved patient outcomes. Identifying genes associated with chemotherapy response can enhance treatment strategies and prognostic models. We analyzed the expression of response-related gene using TCGA GSE109211 cohorts. constructed model Least Absolute Shrinkage Selection Operator (LASSO) analysis assessed its efficacy Kaplan-Meier survival analysis. Additionally, we evaluated immune landscape mutation profiles between different (CRRG) subtypes. DNAJC8's role cell functions was further explored through knockdown experiments vitro vivo. Differential identified 220 common response. The incorporating seven key efficiently distinguished responders from non-responders indicated poorer overall for CRRG-high subtype. CRRG value correlated tumor stage grade, showed distinct patterns subtype exhibited an immune-suppressive phenotype higher PD-L1 CTLA-4. High DNAJC8 linked poor prognosis multiple Knocking down significantly inhibited proliferation, migration, invasion, reduced sorafenib IC50. seven-gene model, particularly DNAJC8, holds potential predicting serves as therapeutic target carcinoma.

Language: Английский

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