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RRM2-targeted nanocarrier enhances radiofrequency ablation efficacy in hepatocellular carcinoma through ferroptosis amplification and immune remodeling

ABSTRACT: RRM2-targeted nanocarrier enhances radiofrequency ablation efficacy in hepatocellular carcinoma through ferroptosis amplification and immune remodeling

PROVIDER: PRJNA1280041 | ENA |

REPOSITORIES: ENA

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	SRR34073393_1.fastq.gz	Fastqsanger.gz
	SRR34073393_2.fastq.gz	Fastqsanger.gz
	SRR34073395_1.fastq.gz	Fastqsanger.gz
	SRR34073395_2.fastq.gz	Fastqsanger.gz

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RRM2-targeted nanocarrier enhances radiofrequency ablation efficacy in hepatocellular carcinoma through ferroptosis amplification and immune remodeling

Project description:Hepatocellular carcinoma (HCC) is associated with high mortality rates despite the widespread application of radiofrequency ablation (RFA), which has limited therapeutic efficacy as a monotherapy. This study investigated ribonucleotide reductase M2 (RRM2) upregulation in post-RFA HCC tissues and developed a targeted nanoco-delivery system (red blood cell membrane/cRGD-modified pH-sensitive liposomes [sS@RBCM/cRGD-phLips]) to increase RFA efficacy through specific RRM2 knockout. RRM2 knockout synergistically amplified RFA-induced tumor cell death by promoting ferroptosis and immunogenic cell death. Mechanistically, RRM2 knockout upregulated the STAT1–IRF1–acyl-CoA synthetase long-chain family member 4 axis, which potentiated lipid peroxidation and ferroptosis. Furthermore, the nanocarrier system enhanced dendritic cell maturation and cytotoxic T cell infiltration, thereby remodeling the tumor immune microenvironment. In vivo experiments revealed that the combination of RFA- and RRM2-targeted nanoparticles significantly suppressed tumor growth and prolonged survival in HCC-bearing mice with minimal systemic toxicity. Notably, the dual-loaded nanoparticles also enhanced the efficacy of anti-programmed cell death protein 1 therapy, suggesting a promising combinatorial approach for HCC treatment. This study presents a novel therapeutic strategy that integrates RRM2-targeted gene editing with RFA, offering a robust and synergistic approach for improving HCC outcomes.

2025-06-25 | GSE300290 | GEO

Transcriptomics and proteogenomic characterization and immune response reveal imbalanced hepatocellular carcinoma ecosystem induced by incomplete radiofrequency ablation

Project description:We collected 5 pairs of HCC tissues with incomplete radiofrequency ablation before and during surgery, and a total of 10 samples were sequenced for proteome analysis. It was found that some genes had some changes in protein expression due to the thermal ablation effect caused by radiofrequency ablation.

2022-09-16 | PXD036767 |

N7-Methylguanosine tRNA modification promotes hepatocellular carcinoma metastasis after insufficient radiofrequency ablation

Project description:Radiofrequency heat ablation is an ideal radical cure for HCC treatment; however, insufficient radiofrequency ablation (IRFA) could lead to a high recurrence rate. N7-methylguanosine (m7G) on tRNAs is a heat-responding modification that is critical for yeast survival under high temperature, while its function and mechanism in HCC recurrence after IRFA are unknown. Here, we found that IRFA significantly up-regulates the level of m7G tRNA modification and its methyltransferase complex components METTL1 and WDR4 in multiple systems including HCC patient-derived xenograft (PDX) mouse, HCC tissues of patients, sublethal-heat-treated models of HCC cell lines and organoids. Functionally, gain- or loss-of function assays showed that METTL1 mediated m7G tRNA modification promotes HCC metastasis under sublethal heat exposure both in vitro and in vivo. Mechanistically, we found that METTL1 and m7G tRNA modification enhance the translation of SLUG and SNAIL in a codon frequency dependent manner under sublethal heat exposure. Overexpression of SLUG and SNAIL rescued the malignant potency of METTL1 knockdown HCC cells after sublethal heat stress. Our study uncovers the important physiological functions of m7G tRNA modification in heat stress responses and HCC recurrence after IRFA and suggests that targeting METTL1-m7G-SLUG and SNAIL axis could be a promising strategy to prevent HCC metastasis after radiofrequency heat ablation treatment.

2022-11-20 | GSE199966 | GEO

Transcriptomics characterization of hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (iRFA)

Project description:Transcriptomics characterization of hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (iRFA)

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The safety and efficacy of microwave ablation and radiofrequency ablation for colorectal cancer liver metastasis : A randomized controlled clinical trial

Project description:Interventions: Microwave ablation Radiofrequency ablation Primary outcome(s): The primary endpoint is the Modified RECIST evaluated by the CT scan taken after the first session of microwave ablation or radiofrequency ablation. Study Design: Parallel Randomized

| 2651257 | ecrin-mdr-crc

Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy

Project description:Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy

| PRJNA575144 | ENA

Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy

Project description:High-throughput RNA-seq analysis was performed using fresh residual CT26 tumors 3 days after incomplete radiofrequency abaltion (iRFA) as well as control tumors. We ound genes encoding damage-associated molecular patterns molecules (DAMPs), proinflammatory cytokines, chemokines, and genes associated with immunosuppression were overexpressed in the iRFA-treated tumor, indicating iRFA elicits inflammation and induces immunosuppression in residual tumors.

2019-10-02 | GSE138224 | GEO

Radiofrequency Ablation in Resectable Colorectal Lung Metastasis

Project description:Lung metastasectomy is the only therapeutic option to provide a long-survival in patients with colorectal lung metastases. Recent studies have shown that radiofrequency (RF) ablation is a safe and useful therapeutic option for the treatment of unresectable lung metastases. In this phase-II trial, clinical utility of lung RF ablation will be evaluated in patients with resectable colorectal lung metastases.

| 2062849 | ecrin-mdr-crc

Surgery With or Without Radiofrequency Ablation Followed by Irinotecan in Treating Patients With Colorectal Cancer That is Metastatic to the Liver

Project description:RATIONALE: Radiofrequency ablation uses high-frequency electric current to kill tumor cells. Combining radiofrequency ablation with surgery may kill more tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug after surgery and radiofrequency ablation may kill any remaining tumor cells. PURPOSE: Phase II trial to determine the effectiveness of surgery with or without radiofrequency ablation followed by irinotecan in treating patients who have colorectal cancer that is metastatic to the liver.

| 2007147 | ecrin-mdr-crc

Percutaneous Radiofrequency ablation for Pulmonary Metastasis from Colorectal Cancer: Phase II Clinical Trial

Project description:Interventions: Lung Radiofrequency Ablation Primary outcome(s): 3-year overall survival Study Design: Single arm Non-randomized

| 2629731 | ecrin-mdr-crc

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