RNA nanotherapeutics for hepatocellular carcinoma treatment

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 965 - 992

Published: Dec. 2, 2024

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, particularly due to the limited effectiveness current therapeutic options for advanced-stage disease. The efficacy traditional treatments is often compromised by intricate liver microenvironment and inherent heterogeneity. RNA-based therapeutics offer promising alternative, utilizing innovative approach targeting aberrant molecular pathways modulating tumor microenvironment. integration nanotechnology in this field, through development advanced nanocarrier delivery systems, especially lipid nanoparticles (LNPs), polymer (PNPs), bioinspired vectors, enhances precision RNA therapies. This review highlights significant progress nanotherapeutics HCC treatment, covering micro (miRNA), small interfering (siRNA), message (mRNA), activating (saRNA) mediated gene silencing, protein restoration, activation, cancer vaccines, concurrent therapy. It further comprehensively discusses prevailing challenges within landscape provides forward-looking perspective on potential transform treatment.

Language: Английский

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Ethanol inhibits the growth and metastasis of hepatocellular carcinoma by inducing immunogenic cell death

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010472 - e010472

Published: Feb. 1, 2025

Immunogenic cell death (ICD) can elicit an adaptive immune response with significant antitumor effects. Percutaneous ethanol injection therapy has been applied as tumor ablation for small hepatocellular carcinoma (HCC). However, it was not clear whether ICD. The aim of this study is to investigate the role ICD inducer. HCC lines were treated low-concentration and markers, such calreticulin, high-mobility group box 1, ATP assayed. mouse vaccination-rechallenge assay used further confirm Western blot real-time PCR ICD-related endoplasmic reticulum (ER) stress signaling pathways. genes differential expression levels between primary distant tumors analyzed by nCounter gene expression. Intratumoral done abscopal effect. could induce in through unfolded protein responses initiated ER multiple cell-death injections had significantly direct effects models both subcutaneous orthotopic HCC. analysis revealed activation various immune-response pathways, notably those mediated CD8 T cells interferon pathway. Vaccinating mice ethanol-treated successfully inhibited metastasis intravenous intrasplenic models. Our results suggest that serve inducer Low-concentration potentially improve therapeutic immunity inducing substantial

Language: Английский

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USP37 as a novel regulator of NRF2 protein stability and chemoresistance in HCC

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 13, 2025

Chemoresistance is a prevalent issue in cancer, resulting poor prognosis. The transcription factor nuclear (erythroid-derived 2)-like 2 (NRF2), key regulator cellular antioxidant responses, implicated cell survival, proliferation, and chemoresistance. It represents promising target for treating Hepatocellular carcinoma (HCC). NRF2 activity has been recently revealed to be controlled by the ubiquitination process mediated KEAP1-CUL3 E3 ligase, highlighting importance of deubiquitination regulation. However, specific deubiquitinase (DUB) responsible liver cancer remains unclear. In this study, we demonstrate that Ubiquitin-Specific Protease 37 (USP37) acts as novel protein. Mechanistically, USP37 modulates stability through enzymatic activity-dependent deubiquitination. Additionally, interacts with facilitates its Elevated levels were associated higher protein samples from human patients. Importantly, knockdown results increased degradation enhances sensitivity chemotherapy. Overall, our findings manifested significant involvement USP37-NRF2 axis regulating therapeutic interventions HCC.

Language: Английский

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The IL-12/IL-23 Cytokine Family

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Prognostic nutritional index predicts survival in intermediate and advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy combined with PD-(L)1 inhibitors and molecular targeted therapies

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 3, 2025

This study aimed to evaluate the predictive efficacy of prognostic nutritional index (PNI) in patients with intermediate and advanced hepatocellular carcinoma (HCC) treated a regimen consisting hepatic arterial infusion chemotherapy (HAIC), PD-(L)1 inhibitors, molecular targeted therapies (MTTs). A retrospective analysis was performed on data 88 HCC received triple therapy between January 2020 August 2022 at three medical centers. Univariate multivariable analyses were conducted assess relationship PNI survival outcomes. The median follow-up 11.0 months (IQR: 8.0-17.0). cut-off value 38.6 determined using receiver operating characteristics (ROC) analysis. overall (OS) durations 29.0 8.0 high-PNI (≥ 38.6) low-PNI (≤ groups, respectively (HR = 0.306, 95% CI, 0.170-0.552, P < 0.001), progression-free (PFS) were16.0 6.0 months, 0.521, 0.303-0.896, 0.014). higher complete response rate observed group (17.5% vs. 3.2%, 0.033). univariate revealed that ≥ had an independent influence both OS 0.296; 0.159-0.551, 0.001) PFS 0.560; 0.318-0.987, 0.045). is objective convenient tool can potentially predict prognosis HAIC-based therapy.

Language: Английский

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Reduction in Liver Cancer Risk by Quercetin via Modulation of Urate Levels: Insights from Drug-Target Mendelian Randomization

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 449 - 449

Published: April 13, 2025

Background: Quercetin, a dietary flavonoid and widely used supplement, has hepatoprotective properties. Given its urate-lowering effects epidemiological evidence linking elevated serum urate levels to liver cancer risk, we tested whether quercetin reduces risk via modulation of by bioinformatics methods. Methods: We employed drug-target Mendelian randomization using genome-wide association study summary statistics from public databases (e.g., MRC-IEU) assess genetic associations, integrated these findings with GEO datasets (such as GSE138709 GSE179443) immune infiltration analyses tools like xCell, TIMER. Results: Our identified ABCG2-mediated elevation causal factor for hepatocellular carcinoma (OR = 1.001, p < 0.01), cholangiocarcinoma 3.424, fibrosis 2.528, 0.01). Single-cell transcriptomics revealed ABCG2 expression in endothelial cells, while analysis showed significant associations between both cell macrophage infiltration. Survival further indicated that was not associated poor prognosis or carcinoma. Conclusions: Considering quercetin’s multifaceted interactions BCRP/ABCG2, our support potential use preventive supplement hepatic diseases rather than an adjunctive therapy established cancer.

Language: Английский

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Targeting PCNA/PARP1 axis inhibits the malignant progression of hepatocellular carcinoma

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

Published: April 17, 2025

Introduction Proliferating cell nuclear antigen (PCNA) is associated with the proliferation and recurrence of various cancers, its high expression poor prognosis in hepatocellular carcinoma (HCC) patients. However, mechanistic role PCNA HCC progression remains poorly understood. This study aimed to investigate how regulates DNA damage repair cycle HCC, a focus on interaction poly (ADP-ribose) polymerase 1 (PARP1) therapeutic implications. Methods was targeted genetically pharmacologically cells assess effects arrest. Protein-protein interactions between PARP1 were validated through co-immunoprecipitation functional assays. The sensitivity inhibitor Olaparib evaluated under inhibition. Synergistic AOH1160 (a inhibitor) tested vitro vivo using assays, quantification, analysis. Prognostic relevance analyzed TCGA datasets. Results Targeting suppressed induced arrest cells. Mechanistically, identified as downstream target directly interacted PCNA. Inhibiting or activity increased inhibitor, Olaparib. In addition, synergistically inhibited proliferation, Elevated levels correlated unfavorable prognosis, supporting biomarker. experiments also confirmed that repression PCNA/PARP1 axis significantly reduced tumor growth. Discussion elucidates relationship regulating malignant highlight pivotal progression. correlation elevated underscores potential Repression inhibits both vivo. Collectively, provides foundation for therapies targeting axis.

Language: Английский

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Dihydroartemisinin alleviates diethylnitrosamine-induced hepatocarcinogenesis by targeting a novel MAZ/TRIM50 axis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114733 - 114733

Published: April 26, 2025

Language: Английский

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Racial/Ethnic Disparities and Immunotherapeutic Advances in the Treatment of Hepatocellular Carcinoma

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2446 - 2446

Published: July 3, 2024

Hepatocellular carcinoma (HCC) remains one of the leading causes death among many associated liver diseases. Various conventional strategies have been utilized for treatment, ranging from invasive surgeries and transplants to radiation therapy, but fail due advanced disease progression, late screening/staging, various etiologies HCC. This is especially evident within racially distinct populations, where incidence rates are higher treatment outcomes worse racial/ethnic minorities than their Caucasian counterparts. However, with rapid development genetic engineering molecular synthetic biology, novel presented promising results provided potential options. In this review, we summarize past treatments, how they shaped current HCC that may prove more effective in future.

Language: Английский

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ACYP2 functions as an innovative nano-therapeutic target to impede the progression of hepatocellular carcinoma by inhibiting the activity of TERT and the KCNN4/ERK pathway

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 12, 2024

An increasing body of evidence suggests that acylphosphatase-2 (ACYP2) polymorphisms are correlated with an increased susceptibility to a range malignancies. Nevertheless, its potential functions, molecular mechanisms in hepatocellular carcinoma (HCC) and whether it can be act as therapeutic target remain uninvestigated. Herein, ACYP2 was found lowly expressed HCC negatively tumor size, differentiation, microvascular invasion the prognosis patients. Functional investigations revealed overexpression inhibited proliferation metastasis cells while promoting apoptosis; knockdown had exact opposite effect. Additionally, observed distributed both cytoplasm nucleus cells. According mechanistic studies, expression potassium calcium-activated channel subfamily N member 4 (KCNN4) regulated by cytoplasmic ACYP2, resulting inhibition K

Language: Английский

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