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Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine

GSE281518 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/11/09 Platform GPL19057
Summary
Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) five-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and its potential in sensitizing PDAC to gemcitabine (G). PH potentiates the effects of G in in vitro, orthotopic mouse models, and a patient-derived xenograft model of PDAC. Proteomic and single-cell RNAseq analyses reveal that GPH treatment upregulates autophagy and ER stress-related transcripts. GPH treatment decreases the number of Ki67, FAP, and alpha-SMA-expressing fibroblasts with a decrease in autophagy-related transcripts. The GPH treatment increases M1 polarization, CD4+, and CD8+ T-cells and reduces the CD4+ and CD8+ Tregs. These effects of GPH were confirmed in paired biopsies obtained from patients treated in a clinical trial (NCT04524702).
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Direct links to NCBI, no account and no request form: the whole study as GSE281518_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1184174 and SRA study SRP544248. Searching any of these in the dataset finder brings you back here.

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