The effects of sorafenib treatment on the Hep1-6 tumor tissue
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ABSTRACT:
PROVIDER: PRJNA1193538 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31586303_1.fastq.gz | Fastqsanger.gz | |||
| SRR31586303_2.fastq.gz | Fastqsanger.gz | |||
| SRR31586304_1.fastq.gz | Fastqsanger.gz | |||
| SRR31586304_2.fastq.gz | Fastqsanger.gz | |||
| SRR31586305_1.fastq.gz | Fastqsanger.gz |
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Project description:This study aimed to investigate the transcriptomic changes in subcutaneous Hepa1-6 tumor tissues of mice following intraperitoneal administration of sorafenib, a tyrosine kinase inhibitor, versus a control solvent. Mice were injected with either sorafenib or the control solvent four times, according to the experimental design. After the treatment period, tumor samples were collected and subjected to RNA sequencing (RNA-seq) to analyze the gene expression profiles. The results from this RNA-seq analysis provide insights into the molecular mechanisms underlying the response of Hepa1-6 tumors to sorafenib treatment, potentially identifying novel therapeutic targets and biomarkers for hepatocellular carcinoma.
2025-01-05 | GSE283371 | GEO
Project description:Hepatocellular carcinoma (HCC) activates platelets through the action of adjacent sinusoidal cells. Activated platelets bind to tumor-associated endothelial cells and release growth factors that promote tumor progression. We hypothesized that tumor inhibitors encapsulated in platelets would function as drug carriers for tumor therapy. We propose a therapeutic strategy for HCC using autologous platelets encapsulating multiple tyrosine kinase inhibitors in a rat chemically-induced HCC model. Sorafenib or lenvatinib was encapsulated in platelets isolated from tumor-bearing rats in vitro. The rats were divided into groups that received repeated intravenous injections (twice a week for 10 weeks) of the following materials: placebo, sorafenib (SOR), lenvatinib (LEN), autologous platelets, autologous platelets encapsulating sorafenib (SOR-PLT), and autologous platelets encapsulating lenvatinib (LEN-PLT). The therapeutic effect was then analyzed by ultrasonography (US) and histopathological analysis. Histopathological and US analysis demonstrated extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT, but not in other experimental groups. By liquid chromatography-mass spectrometry, more abundant sorafenib was detected in tumor tissues after SOR-PLT administration than in surrounding normal tissues, but no such difference in sorafenib level was observed with SOR administration. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC. We investigated the effect of the drug encapsulation process on the degradation of resident mRNA inherited from megakaryocytes in platelets.
2021-12-15 | GSE190863 | GEO
Project description:To investigate the impact of sorafenib treatment on gene expression in CD4+T cells, we performed RNA sequencing on CD4+T cells treated with sorafenib and on control CD4+T cells that were not treated with sorafenib. Specifically, our study focused on the expression of immune related genes, and we observed an downregulation in the expression of TCR genes.
2025-05-14 | GSE280959 | GEO
Project description:To investigate the impact of sorafenib treatment on gene expression in Th9 cells, we performed RNA sequencing on Th9 cells treated with sorafenib and on control Th9 cells that were not treated with sorafenib. Here, we found that the up regulation of genes about Il-9.
2025-05-14 | GSE280958 | GEO
Project description:OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression. Transcriptomic profile of subcutaneous Huh7 cells-derived tumors treated with sorafenib that developed acquired resistance to the drug (n=4), remain responsive to sorafenib (n=3) or were treated with brivanib after development of resistance (n=3). Gene profiling of hepatospheres generated from tumors with acquired resistance to sorafenib (n=3) and non-treated tumors (n=3) was also analyzed.
2016-06-16 | E-GEOD-73571 | biostudies-arrayexpress
Project description:To investigate the impact of sorafenib treatment on gene expression in Treg cells, we performed RNA sequencing on Treg cells treated with sorafenib and on control Treg cells that were not treated with sorafenib. Specifically, our study focused on the expression of immune-suppressive related genes, and we observed an upregulation in the expression of Tgf-β1 (Transforming Growth Factor-β1), Prf1 (Perforin 1), Gzma (Granzyme A), and Il10 (Interleukin 10).
2025-01-05 | GSE280126 | GEO
Project description:OBJECTIVE: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterize the role of tumor-initiating cells (T-ICs) and signaling pathways involved in sorafenib resistance. DESIGN: HCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: 1) Role of T-ICs by in vitro sphere formation and in vivo tumorigenesis assays using NOD/SCID mice, 2) Activation of alternative signaling pathways and 3) Efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, qRT-PCR) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in 2 independent cohorts. RESULTS: Sorafenib-acquired resistance tumors showed significant enrichment of T-ICs (164 cells needed to create a tumor) vs. sorafenib-sensitive tumors (13400 cells) and non-treated tumors (1292 cells), p<0.001. Tumors with sorafenib-acquired resistance were enriched with IGF and FGF signaling cascades (FDR<0.05). In vitro, cells derived from sorafenib-acquired resistant tumors and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumor growth and improved survival in sorafenib-resistant tumors. A sorafenib-resistance 175-gene signature was characterized by enrichment of progenitor-cell features, aggressive tumoral traits and predicted poor survival in 2 cohorts (n=442 HCC patients). CONCLUSION: Acquired resistance to sorafenib is driven by tumor initiating cells with enrichment of progenitor markers and activation of IGF and FGF signaling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.
2016-06-16 | GSE73571 | GEO
Project description:To address how serum cholesterol affected tumor progression, C57BL/6J mice were placed on either normal diet or high cholesterol diet for 4 weeks, and then Hep1-6 cells were subcutaneously injected into the right flanks of mice. We performed transcriptome sequencing analysis (RNA-seq) on tumor tissues from ND and HCD groups.
2019-02-03 | GSE124599 | GEO
Project description:We observed an increasing trend of nuclear SLC29A2 expression associated with high histological de-differentiation grades, metastasis and poor patient prognosis by immunohistochemical analysis of HCC tumors. Treatments of dipyridamole to SLC29A2 expressing SK-hep1 cells reduced cell viability and cell migration. To examine the anticancer activities of dipyridamole, transcriptome analysis was performed to detect the modulations of oncogenic SLC29A2 and the downstream signaling pathways.
2020-10-23 | GSE139583 | GEO
Project description:Mitochondrial damage-associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA), TFAM (transcription factor A, mitochondrial), and ATP, play crucial roles in the regulation of inflammatory environment in human diseases. However, the role of mitochondrial DAMPs in the regulation of tumor microenvironment (TEM) remains unclear. Herein we demonstrate that infiltration of M2 type tumor-associated macrophages (TAMs) was correlated with the resistance of hepatocellular carcinoma (HCC) to sorafenib. We found that cell free mtDNA in the plasma was significantly increased in sorafenib-resistant HCC mice. Sorafenib induced mitochondrial dysfunction and promoted the release of mtDNA into extracellular matrix of HCC. The mtDNAs were retaken by macrophages in the TME of HCC, activated TLR9 signaling on the endosome, and hence promoted the activation of NF-κB and the polarization of TAMs into M2. Application of DNase I to digest mtDNAs or depletion of macrophages with clodronate liposomes reduced the infiltration of M2 macrophage, decreased the growth of HCC, and sensitized the tumors to sorafenib. Furthermore, we showed that blocking the activation of TLR9 enhanced the therapeutic effect of sorafenib in HCC. Together, in the current study, we demonstrate that sorafenib treatment leads to the release of mtDNAs into TME in HCC, which in turn facilitates the polarization of TAMs into M2 macrophages through TLR9 activation and aggravates the resistance of HCC to sorafenib. Our study reveals a novel mechanism underlying circulating mtDAMPs in remodeling HCC microenvironment by reprograming the TAMs and provides a new strategy for improving the therapeutic effect of sorafenib and overcoming its resistance in HCC.
2025-03-12 | GSE270323 | GEO