IL-2-loaded liposomes modified with sorafenib derivative exert a synergistic anti-melanoma effect via improving tumor immune microenvironment and enhancing antiangiogenic activity

Asian Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер unknown, С. 101020 - 101020

Опубликована: Янв. 1, 2025

Immunotherapy with interleukin-2 (IL-2) in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors low immune cell infiltration despite its promise. To address these challenges, IL-2-So-Lipo, a novel liposomal formulation combining IL-2 sorafenib derivative, was developed an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles tumor growth. Sorafenib derivatives could target at melanoma-specific receptors, further enhancing specificity site. Our results demonstrated prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared or monotherapies, well their combination. In B16F10 melanoma model, found inhibit progression (tumor volume 108.01 ± 62.99 mm3) control group 1,397.13 75.55 mm3), improving therapeutic efficacy. This attributed targeted delivery promoted activation cytotoxic T lymphocytes. Additionally, encapsulation efficiency, promoting apoptosis suppressing angiogenesis. Mechanistically, kill by inducing shift towards response via facilitating polarization macrophages M1 phenotype. Furthermore, downregulated key proteins MAPK signaling pathway, exerting significant role mediating resistance sorafenib. These findings underscore potential promising strategy improve immunotherapy therapy cancers. Moreover, combination system overcame conventional therapy, offering synergistic approach outcomes for solid tumors.

Язык: Английский

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Application of multi-omics in hepatocellular carcinoma: new prospects for classification and precise diagnosis and treatment

Hepatoma Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Hepatocellular carcinoma (HCC) represents a significant global health challenge, with complex etiology and limited treatment options. The integration of multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, has revolutionized our understanding HCC, offering novel insights into its molecular underpinnings. This comprehensive review synthesizes the current knowledge on application in highlighting role disease classification, early detection, development targeted therapies. We discuss identification key driver mutations single nucleotide polymorphisms (SNPs) that enhance risk prediction models, implications for personalized medicine. approach facilitated discovery distinct HCC subtypes, each unique signatures tumor microenvironments (TME), which are critical predicting prognosis guiding strategies. Furthermore, we explore these findings precision medicine, emphasizing potential biomarker therapies, immune checkpoint blockade (ICB). concludes by underscoring transformative impact research clinical practice, heralding new era medicine promise improved patient outcomes.

Язык: Английский

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m6A epitranscriptomic modification in hepatocellular carcinoma: implications for the tumor microenvironment and immunotherapy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 17, 2025

Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and a leading cause of cancer-related deaths globally. The asymptomatic progression early-stage HCC often results in diagnosis at advanced stages, significantly limiting therapeutic options worsening prognosis. Immunotherapy, with immune checkpoint inhibitors (ICIs) forefront, has revolutionized treatment. Nevertheless, tumor heterogeneity, evasion, presence immunosuppressive components within microenvironment (TIME) continue to compromise its efficacy. Furthermore, resistance or non-responsiveness ICIs some patients underscores urgent need unravel complexities TIME design innovative strategies that enhance immunotherapeutic outcomes. Emerging evidence revealed pivotal role N6-methyladenosine (m6A), prominent RNA methylation modification, shaping HCC. By regulating stability translation, m6A influences immune-related factors, including cytokines molecules. This modification governs PD-L1 expression, facilitating escape contributing against ICIs. Advances this field have also identified m6A-related regulators as promising biomarkers for predicting immunotherapy response potential targets optimizing treatment review examines regulatory mechanisms HCC, focus on impact cells cytokine dynamics. It explores targeting pathways improve efficacy outlines emerging directions future research. These insights aim provide foundation developing novel overcome advance

Язык: Английский

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Monitoring Sorafenib Resistance and Efficacy in Hepatocellular Carcinoma Using [¹⁸F]Alfatide II and [¹⁸F]Fluorodeoxyglucose Positron Emission Tomography

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 23, 2025

Integrin αvβ3 expression is associated with sorafenib resistance in hepatocellular carcinoma (HCC). Therefore, monitoring its HCC may serve as a valuable indicator of the efficacy treatment. In this study, longitudinal positron emission tomography (PET) was performed to assess [18F]Alfatide II and [18F]fluorodeoxyglucose ([18F]FDG) suitable probes for evaluating treatment Huh-7 human (HCC) xenograft model. tumor cells were used establish both normal sorafenib-resistant cell lines, models developed. The mice categorized into four groups based on type treatment: nontreatment, treatment, received intragastric injections (30 mg/kg/day) or vehicle 15 consecutive days. Tumor size weight assessed throughout study. Longitudinal microPET/computed (CT) scans [18F]FDG acquired quantitatively measure angiogenesis days -2, 3, 7, 14 metabolism -1, 4, 8, following therapy initiation. uptake (ID%/gmean) each probe calculated. No significant difference observed between (P = 0.452); however, differed significantly two < 0.001). Sorafenib successfully inhibited growth, inducing differences 9 after 0.05). lesions changed day However, no change > PET imaging data validated through ex vivo immunohistochemistry analysis targeting integrin αvβ3, VEGF, GULT-1. more effective therapeutic model than [18F]FDG.

Язык: Английский

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Mechanism and Molecular Targets of Euphorbia fischeriana Steud Root Extract in Hepatocellular Carcinoma

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119707 - 119707

Опубликована: Март 1, 2025

Язык: Английский

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MicroRNAs as Sensitizers of Tyrosine Kinase Inhibitor Resistance in Cancer: Small Molecule Partnerships

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 492 - 492

Опубликована: Март 28, 2025

Tyrosine kinase inhibitors (TKIs) have revolutionized cancer treatments by being less toxic and improving the survival of patients. The greatest challenge to their success is resistance exhibited However, potential microRNAs (miRNAs) for sensitizing molecules TKIs has been well recognized, with several reports publishing promising results. Nonetheless, this therapeutic window faces challenges often-overlooked limitations. One most fundamental selecting optimal miRNA candidates clinical trials, as miRNAs are promiscuous regulate hundreds targets. In review, we describe how enhance sensitivity across various types cancer. We highlight limitations in achieving a successful collaboration between small (TKIs–miRNAs). Our focus on proposing workflow select suitable candidate, recommending available bioinformatics tools develop partnership miRNAs. hope that initial proposal will provide valuable support future research.

Язык: Английский

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Antitumor effects of dauricine on sorafenib-treated human lung cancer cell lines via modulation of HIF-1α signaling pathways

Medical Oncology, Год журнала: 2025, Номер 42(5)

Опубликована: Апрель 9, 2025

Язык: Английский

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High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3491 - 3491

Опубликована: Апрель 8, 2025

Hepatocellular carcinoma (HCC) is a lethal malignancy associated with drug resistance, resulting in poor prognosis. High mobility group box 1 (HMGB1) chromatin-binding protein that regulates HCC progression. The overexpression of HMGB1 has been found to promote tumorigenesis and resistance. In this study, we aimed investigate the role expression metastasis its impact on sorafenib oxaliplatin Tissue samples from patients (n = 48) were subjected immunohistochemistry. was correlated clinical pathology parameters. Moreover, cell line HuH-7 used study regulatory effect proliferation, adhesion, migration, invasion by using siRNA (small interfering RNA) silencing method. Furthermore, challenges performed determine sensitivity chemotherapeutic drugs (sorafenib oxaliplatin). significantly overexpressed tumor tissues, highlighted increment M1 advanced tumors immunoreactivity scores 2.61 6.50 for adjacent respectively (p-values 0.0035). involved mechanisms then described through suppression silencing. Notably, inhibition promoted sorafenib/oxaliplatin increasing toxicity about 13-18%. Our demonstrated shows potential as promising biomarker target treatment tumorigenesis, metastasis, chemo-drug

Язык: Английский

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Insights into Sorafenib resistance in hepatocellular carcinoma: Mechanisms and therapeutic aspects.

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104765 - 104765

Опубликована: Май 1, 2025

Язык: Английский

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Mechanisms of drug resistance in hepatocellular carcinoma

Biological Procedures Online, Год журнала: 2025, Номер 27(1)

Опубликована: Май 28, 2025

Язык: Английский

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