Chemotherapy response in cholangiocarcinoma
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ABSTRACT:
PROVIDER: PRJNA547616 | ENA |
REPOSITORIES: ENA
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Project description:CCLP cholangiocarcinoma cells were transfected with CTRL inhibitor or MIR1249 inhibitor for 48 hours and treated with DMSO or chemotherapy (cisplatin and gemcitabine) for 48 hours before being collected and analysed for gene expression
2022-06-06 | GSE132328 | GEO
Project description:Cholangiocarcinoma is a cancer of the hepatic bile ducts that is typically detected at a stage too advanced for resection. Additionally, chemotherapy is of limited efficacy, hence, novel therapeutic approaches are urgently required, including targeting of the cancer stroma. A macrophage-derived signal, tumour necrosis factor-like weak inducer of apoptosis (TWEAK), binds to cell-surface fibroblast growth factor-inducible 14 (Fn14), on cholangiocarcinoma cells to induce cytokine and chemokine expression and secretion. These TWEAK-inducible factors from cholangiocarcinoma cells can also affect macrophage polarisation. We characterised proteins secreted by four well-characterised human cholangiocarcinoma cell lines in the presence or absence of recombinant human TWEAK (100 ng/ml), to discover novel TWEAK-inducible factors that could drive pro-tumour niche formation.
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Project description:Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the PD1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-CTLA-4 when combined with anti-PD1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels, and when combined with dual CTLA-4/PD1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient since CD8+ T cells from Cxcr3+/+ but not Cxcr3–/– mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti-CTLA-4 “priming” with chemotherapy followed by anti-PD1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.
2024-01-18 | GSE253627 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the PD1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-CTLA-4 when combined with anti-PD1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels, and when combined with dual CTLA-4/PD1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient since CD8+ T cells from Cxcr3+/+ but not Cxcr3–/– mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti-CTLA-4 “priming” with chemotherapy followed by anti-PD1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.
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Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma
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Project description:For patients with muscle-invasive bladder cancer, there are no biomarkers in clinical use that can identify patients that are sensitive or resistant to neoadjuvant chemotherapy. This study investigates how molecular subtypes impact pathological response and survival in 149 patients receiving preoperative cis-platin based chemotherapy by tumor classification using transcriptomic profiling and a 13-marker immunostaining panel. Furthermore, we explored to what extent gene expression signatures can predict chemotherapy response beyond molecular subtypes. We observed improved pathological response rates and survival outcomes for patients presenting with genomically unstable (GU) and urothelial-like (Uro) subtypes compared to the basal-squamous (BASQ) subtype following neoadjuvant chemotherapy and radical cystectomy. Also, SPP1, coding for osteopontin, displayed a clear subtype-dependent effect on chemotherapy response, confirmed at the protein level. Based on our findings, we hypothesize that urothelial cancer of the luminal-like GU- and Uro-subtypes are more responsive to cisplatin-based chemotherapy which may influence patient selection pending further research.
2021-11-19 | GSE169455 | GEO
Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma miRNAs expression in human cholangiocarcinoma/normal bile duct samples was measured after operation.Three independent experiments were performed using different patients for each experiment.
2013-06-10 | E-GEOD-47764 | biostudies-arrayexpress
Project description:Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. There is a lack of diagnostic and prognostic biomarkers. An improved understanding of proteomic changes associated with malignancy and identification of potential biomarkers can help improve the survival of patients. A workflow utilizing discovery mass spectrometry and verification by parallel-reaction monitoring was used to analyze surgically resected formalin-fixed paraffin embedded samples from distal cholangiocarcinoma patients and normal bile ducts in order to identify differentially expressed proteins. 20 tumors and 6 controls were successfully analyzed in the discovery experiment and 16 tumors and 9 controls in the PRM analysis. In the discovery experiment a total of 3057 proteins were identified. 87 proteins were found to be differentially expressed between the conditions (q<0.05 and fold change ≥2 or ≤0.5). 31 proteins were upregulated in the distal cholangiocarcinoma samples as compared to controls and 56 downregulated. Bioinformatic analysis revealed an abundance of the differentially expressed proteins to be associated with the tumor reactive stroma. Parallel-reaction monitoring verified 28 proteins as upregulated and 18 as downregulated. In conclusion several proteins without prior association with cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma samples and normal bile ducts. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis.
2020-09-09 | PXD017906 | Pride
Project description:Differential neoadjuvant chemotherapy response in urothelial carcinoma molecular subtypes
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Project description:Circulating exosomal microRNAs as predictive biomarkers of neoadjuvant chemotherapy response in breast cancer
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