Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA379714 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma
| PRJNA379711 | ENA
Project description:Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [Hep3B]
| PRJNA379715 | ENA
Project description:Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [Huh7]
| PRJNA379717 | ENA
Project description:Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [SNU761]
| PRJNA379716 | ENA
Project description:Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients’ survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
2017-03-19 | GSE96795 | GEO
Project description:Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients’ survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
2017-03-19 | GSE96794 | GEO
Project description:Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients’ survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
2017-03-19 | GSE96793 | GEO
Project description:Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients’ survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.
2017-03-19 | GSE96792 | GEO
Project description:Cancer cells voraciously consume nutrients to support their growth, exposing a metabolic vulnerability that can be therapeutically exploited. Here we show in hepatocellular carcinoma (HCC) cells, xenografts, and in patient-derived HCC organoids that fasting can synergistically sensitise resistant HCC to sorafenib. Mechanistically, sorafenib acts non-canonically as inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival. Fasting, through reduction in glucose and impeded AKT/mTOR-signalling, prevents this Warburg shift. p53 is necessary and sufficient for the sorafenib-sensitizing effect of nutrient restriction and crucial for improvement of sorafenib efficacy through intermittent fasting (IF) in an orthotopic HCC mouse model. Together, our data indicate IF and sorafenib as clinically actionable, rational combination therapy for HCC with intact p53 signalling. As HCC therapy is currently severely limited by resistance, these results should instigate clinical studies with the goal of improving therapy response in advanced-stage, and possibly even early-stage, HCC.
2022-02-16 | PXD022723 | Pride
Project description:Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (CelebrexM-BM-.) is a selective cyclooxygenase-2 (COX-2) inhibitor wich exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of combination, we investigated the expression profile of the combination-treated liver cancer cell lines, using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes, functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell line displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semiquantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomics analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies. To identify new potential mechanisms of combined action of celecoxib and sorafenib, their effects on global gene expression in both cell lines were investigated and compared using the DNA microarray technology. Agilent 44K Human Whole Genome Oligonucleotide Microarrays (containing ~44,000 genes) were used to identify global gene expression changes in the HepG2 and Huh7 hepatocellular carcinoma (HCC) cell lines, following simultaneous treatment with 50 M-BM-5M celecoxib and 7.5 M-BM-5M sorafenib for 48 hours. All microarray experiments (a total of four) were performed in duplicates applying dye-swaps to avoid labeling bias.
2013-03-21 | E-GEOD-45340 | biostudies-arrayexpress