Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13526300_1.fastq.gz | Fastqsanger.gz | |||
| SRR13526300_2.fastq.gz | Fastqsanger.gz | |||
| SRR13526400.fastq.gz | Fastqsanger.gz | |||
| SRR13526301_1.fastq.gz | Fastqsanger.gz | |||
| SRR13526301_2.fastq.gz | Fastqsanger.gz |
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Project description:DNA methylation data of PAC PDX models before Gemcitabine treatment
| PRJNA695457 | ENA
Project description:DNA methylation data of PAC PDX models after Gemcitabine treatment
| PRJNA695458 | ENA
Project description:We report that eight gene products were downregulated in PA4 and PA16 PDX models by BET inhibitor JQ1 + gemcitabine, compared to vehicle controls.
2021-07-28 | GSE174023 | GEO
Project description:Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models faithfully recapitulate tumor-stroma interactions in PDAC, but conventional antibody-based immunoassay is largely inadequate to resolve or quantify tumor and stromal proteins. A species-deconvolved proteomics approach embedded in the ultra-high-resolution (UHR)-IonStar workflow can unambiguously quantify the proteins from tumor (human-derived) and stroma (mouse-derived) in PDX samples, enabling unbiased investigation of their proteomes with excellent quantitative reproducibility. With this strategy, 3 PDAC PDXs were analyzed. They were showed differential responses to treatment with Gemcitabine combined with nab-Paclitaxel (GEM+PTX), which is a first-line treatment regimen for PDAC. For each PDAC PDX, samples were collected after 24 hour and 192 hour with/without treatment, and each condition contained four biological replicates.
2023-07-05 | PXD042267 | Pride
Project description:The molecular basis underlying the known anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. We investigated the microRNA (miRNA)-modulatory effects of cranberry proanthocyanidin (PAC) and two of its main gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), in intestinal cells at homeostasis and in inflammatory conditions. Differentiated Caco-2BBe1 cells were pre-treated with PAC, DHPAA, or HPPA then stimulated with IL-1ß or not. Total RNA was used to profile the expression of 799 miRNAs. PAC, DHPAA, and HPPA generated subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not by PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, pre-treatment with PAC and DHPAA, but not HPPA, reversed the expression of 16 and two IL-1ß-induced miRNAs, targeting genes enriched in inflammatory and cancer pathways. These data suggest that in the absence of inflammation, PAC may be reliant on its transformation by the gut microbiota for its miRNA-modulatory effects, while in an inflammatory environment, both PAC and DHPAA counter inflammatory miRNA responses. This work provides a novel mechanism to characterize the bioactivity of cranberry and will inform cranberry utilization in nutritional strategies for the maintenance of intestinal homeostasis.
2024-03-27 | GSE237078 | GEO
Project description:Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC) but patients often show poor or complete lack of response to this agent. Molecular markers downstream of Gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. We identified potential secretory biomarkers of Gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC using cytokine arrays. We validated the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in primary pancreatic tumours and metastasis using both in vitro techniques and animal models. We identified potential pathways affected downstream of TIMP-1 using the Illumina Human H12 array. Our findings were validated in both primary and metastatic models of pancreatic cancer. Gemcitabine increases inflammatory cytokines including TIMP-1 in the KPC mouse model. TIMP-1 is upregulated in patients with pancreatic intraepithelial neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue. Additionally, we demonstrate that TIMP-1 plays a role in tumour proliferation and angiogenesis, while inhibition resensitises to gemcitabine and radiotherapy. Strikingly, serum TIMP-1 levels support the formation of liver metastasis through the recruitment of immunosuppressive cell populations, such as CD11b+Gr1+ myeloid cells and CD4+CD25+FOXP3+ Tregs to the hepatic microenvironment. Gemcitabine treatment results in upregulation of the pro-tumourigenic/pro-metastatic cytokine TIMP-1, which partially explains the therapeutic resistance and poor responses to this therapy in PDAC. Our study provides a rationale for the development and testing of TIMP-1 specific inhibitors in addition to chemo/radiotherapy.
2017-08-08 | GSE94891 | GEO
Project description:The proton-activated chloride (PAC) channel (also known as acid-sensitive outwardly rectifying anion channel, ASOR) plays a critical role in acid-induced cell death and endocytosis. However, little is known about the regulatory factors and binding partners of PAC. In this study, we discovered that transfer RNA (tRNA) interacts directly with PAC as an unexpected binding partner. Using cryo-electron microscopy, we determined that two PAC trimers and one co-purified tRNA molecule form a stable complex via a highly conserved KR motif, representing the closed conformation. tRNA is located on the intracellular side of PAC, blocking the channel pores. Furthermore, electrophysiological data showed that tRNA modulates chloride currents and channel open probability of PAC, thus protecting against acid-induced cell death. Our study provides insight into the regulation of PAC activity by cytosolic tRNA and extends the role of tRNAs in pathological and physiological events.
2024-06-28 | GSE216637 | GEO
Project description:Gemcitabine treatment shifts the intestinal microbiota of PC mice towards an inflammatory profile which may worsen mucositis and side effects observed upon chemotherapy. We explored the effect of a specific probiotics blend administered, with or without gemcitabine treatment, to PC xenografted mice.
2023-06-28 | E-MTAB-10676 | biostudies-arrayexpress
Project description:Chemoresistance to gemcitabine limits its clinical implementation for pancreatic ductal adenocarcinoma (PDAC). We previously generated an antibody drug conjugate (ADC) -like agent, EGFR/HER2 dual-targeting ligand-based lidamycin (DTLL), and studied the effect of DTLL combined with gemcitabine and the potential role of SMAD4 in the chemoresistance of PDAC. On the basis of SMAD4 profiles in in vitro and in vivo models, we investigated the antitumor effects of DTLL, gemcitabine and their combination, followed with mechanistic characterization. The results suggested that DTLL combination treatment with gemcitabine significantly repressed tumors with remarkably enhanced efficacy as compared to gemcitabine or DTLL alone given in either SMAD4-deficient/gemcitabine-resistant or SMAD4-sufficient/gemcitabine-sensitive cell line derived xenograft (CDX) and patient derived xenograft (PDX) tumors, respectively. Functional studies indicated that SMAD4 genetic status is responsible for SMAD4 protein level which determines different cellular susceptibility of PDAC. R100T mutation contributes to loss of SMAD4 protein and function with rapid protein degradation, leading to resistance to gemcitabine in PDAC cells. Moreover, DTLL significantly altered the protein half-life time and level of mutant and wild-type SMAD4 by inhibiting protein degradation at different velocities and distinctly changing the interaction of SMAD4 with TRIM33. Mechanism studies implied that DTLL combinational treatment might not only prevent from neoplastic proliferation via blockage of ATK/mTOR signaling and anti-apoptotic proteins (Bcl-2 and MCL1) mediated by impaired NF-B function in SMAD4-sufficient/gemcitabine-sensitive PDAC cells, but also restore the bioactivity of SMAD4 as a tumor suppressor to trigger its downstream NF-B-regulated signaling of cell apoptosis in SMAD4-deficient/gemcitabine-resistant tumors. In conclusion, SMAD4 is the key central mediator of not only the occurrence and development but also susceptibility in PDAC. DTLL sensitized gemcitabine efficacy via distinct action mechanisms based on SMAD4 profiles in SMAD4-sufficient/gemcitabine-sensitive and SMAD4-deficient/-resistant PDAC, respectively. Our findings provide insight into a rational SMAD4-directed precision treatment strategy and reveal a promising DTLL combination therapy to overcome chemoresistance in gemcitabine-resistant PDAC.
2022-03-02 | PXD031977 |