Molecular characterization of type I IFN-induced cytotoxicity in bladder cancer cell lines reveals biomarkers of resistance II
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PROVIDER: PRJNA774790 | ENA |
REPOSITORIES: ENA
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Project description:Although anti-tumor activities of type I interferons (IFNs) have been recognized for decades, the molecular mechanisms contributing to clinical response remain poorly understood. The complex functions of these pleiotropic cytokines include stimulation of innate and adaptive immune responses against tumors as well as direct inhibition of tumor cells. In high-grade, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer, nadofaragene firadenovec, a non-replicating adenovirus administered locally to express the IFNα2b transgene, embodies a novel approach to deploy the therapeutic activity of type I IFNs while minimizing systemic toxicities. Deciphering which functions of type I IFN are required for clinical activity will bolster efforts to maximize the efficacy of nadofaragene firadenovec and other type I IFN-based therapies, and inform strategies to address resistance. As such, we characterized the phenotypic and molecular response of human bladder cancer cell lines to IFNα delivered in multiple contexts, including adenoviral delivery. We found that constitutive activation of the type I IFN signaling pathway is a biomarker for resistance to both transcriptional response and direct cytotoxic effects of IFNα. We present several genes that discriminate between sensitive and resistant tumor cells, suggesting they should be explored for utility as biomarkers in future clinical trials of interferon-based anti-tumor therapies.
2021-10-28 | GSE186610 | GEO
Project description:Molecular characterization of type I IFN-induced cytotoxicity in bladder cancer cell lines reveals biomarkers of resistance
| PRJNA774785 | ENA
Project description:Although anti-tumor activities of type I interferons (IFNs) have been recognized for decades, the molecular mechanisms contributing to clinical response remain poorly understood. The complex functions of these pleiotropic cytokines include stimulation of innate and adaptive immune responses against tumors as well as direct inhibition of tumor cells. In high-grade, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer, nadofaragene firadenovec, a non-replicating adenovirus administered locally to express the IFNα2b transgene, embodies a novel approach to deploy the therapeutic activity of type I IFNs while minimizing systemic toxicities. Deciphering which functions of type I IFN are required for clinical activity will bolster efforts to maximize the efficacy of nadofaragene firadenovec and other type I IFN-based therapies, and inform strategies to address resistance. As such, we characterized the phenotypic and molecular response of human bladder cancer cell lines to IFNα delivered in multiple contexts, including adenoviral delivery. We found that constitutive activation of the type I IFN signaling pathway is a biomarker for resistance to both transcriptional response and direct cytotoxic effects of IFNα. We present several genes that discriminate between sensitive and resistant tumor cells, suggesting they should be explored for utility as biomarkers in future clinical trials of interferon-based anti-tumor therapies.
2021-10-28 | GSE186609 | GEO
Project description:Molecular characterization of type I IFN-induced cytotoxicity in bladder cancer cell lines reveals biomarkers of resistance I
| PRJNA774791 | ENA
Project description:Although anti-tumor activities of type I interferons (IFNs) have been recognized for decades, the molecular mechanisms contributing to clinical response remain poorly understood. The complex functions of these pleiotropic cytokines include stimulation of innate and adaptive immune responses against tumors as well as direct inhibition of tumor cells. In high-grade, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer, nadofaragene firadenovec, a non-replicating adenovirus administered locally to express the IFNα2b transgene, embodies a novel approach to deploy the therapeutic activity of type I IFNs while minimizing systemic toxicities. Deciphering which functions of type I IFN are required for clinical activity will bolster efforts to maximize the efficacy of nadofaragene firadenovec and other type I IFN-based therapies, and inform strategies to address resistance. As such, we characterized the phenotypic and molecular response of human bladder cancer cell lines to IFNα delivered in multiple contexts, including adenoviral delivery. We found that constitutive activation of the type I IFN signaling pathway is a biomarker for resistance to both transcriptional response and direct cytotoxic effects of IFNα. We present several genes that discriminate between sensitive and resistant tumor cells, suggesting they should be explored for utility as biomarkers in future clinical trials of type I IFN-based anti-tumor therapies.
| S-EPMC8645427 | biostudies-literature
Project description:Background: Frankincense (Ru Xiang) and sandalwood (Tan Xiang) are ingredients used in traditional Chinese medicine, and have been recognized as cancer preventive and therapeutic agents. Hydrodistillation of frankincense gum resins and sandalwood heartwood to prepare essential oils is a method to extract biologically active ingredients from these plant-derived products. This study was designed to differentiate frankincense (Boswellia carterii) and sandalwood (Santalum album) induced anti-proliferative and pro-apoptotic activities in cultured human bladder cancer cells. Methods: Frankincense and sandalwood essential oils-mediated cytotoxicity was studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric assay. Essential oils-activated gene expression and pathway activation in human bladder cancer J82 cells were identified using high density microarray and bioinformatics techniques. Results: Human bladder cancer cells were more sensitive to immortalized normal bladder cells with suppressed viability following frankincense essential oil exposure. In contrast, both cancerous and normal bladder cells responded to sandalwood essential with similar levels of cytotoxicity. Based on microarray and bioinformatics analyses, genes responsible for suppressing biological processes and apoptosis were induced in J82 cells by both essential oils. Although both frankincense and sandalwood essential oils activated common ontologies and canonical pathways leading to suppressed J82 cell viability and apoptosis, each essential oil had unique property on these cells. For example, heat shock proteins and histone core were ongologies regulated by frankincense essential oil, whereas transcription regulation and G-protein couple receptor were ontologies unique to sandalwood essential oil treatment. In addition, NRF-2 mediated oxidative stress was implicated as the primary cause of frankincense essential oil-induced J82 cell death; in contrast, DNA damage and cell cycle arrest might be attributed to sandalwood essential oil-mediated cytotoxicity. Conclusion: Based on cell biology and comprehensive gene expression analysis, our results provide a preliminary, yet focused characterization of genetic responses to frankincense and sandalwood essential oils with respect to their proposed anti-neoplastic properties. Modern biomedical technologies are powerful tools to study biological responses following treatments with traditional Chinese medicine, which always consist of complex chemical constituents. To differentiate mechanisms of frankincense and sandalwood essential oils induced cytotoxicty in bladder cancer J82 cells, time-dependent transcriptoms expression was performed in cultured cells following essential oils treatments
2014-06-10 | E-GEOD-53171 | biostudies-arrayexpress
Project description:We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis. Number of samples: 32. We analyzed PBMC from 8 patients at baseline and after 3, 12 and 24 months of IFN-beta treatment
2010-12-18 | E-GEOD-26104 | biostudies-arrayexpress
Project description:We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.
2010-12-18 | GSE26104 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-28 | GSE186611 | GEO
Project description:Epigenetic priming to enhance CAR-T cell cytotoxicity in bladder cancer
| PRJNA692221 | ENA