Similar Datasets
Project description:The aim of the study was to characterize a common molecular mechanism for paclitaxel resistance in Patu-T and Suit-2.028 PDAC cell lines. Despite the ATP-binding cassette (ABC) trasnsporters were already shown to be involved in various chemo-resistant forms of cancers but not in PDAC, the most likely impact of ABCB1 overexpression in PDAC cell models was taken into account in this dataset.
2024-01-26 | PXD040930 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel has been added to the arsenal of first line therapies, and the combination of gemcitabine and nab-paclitaxel has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying nab-paclitaxel (n-PTX) resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naive PDAC patients. To study the mechanisms of primary drug resistance, nab-paclitaxel-resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified in vivo, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of c-MYC in the nab-paclitaxel-resistant cells. Depletion of c-Myc restored nab-paclitaxel sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small molecule activator of protein phosphatase 2a (SMAP). Implications: The strategies we have devised, including the patient-derived primary cells and the unique drug resistant isogenic cells, are rapid and easily applied in vitro and in vivo platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis
2019-05-31 | GSE131762 | GEO
Project description:Aberrant tyrosine kinase activity can influence tumor growth and is regulated by phosphorylation. Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. We investigated phosphorylated kinases as target in PDAC. Mass spectrometry-based phosphoproteomic analysis was performed of PDAC cell lines to evaluate active kinases. Pathway analysis and inferred kinase activity was performed to identify novel targets. We investigated targeting of focal adhesion kinase in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Phosphoproteome analysis upon treatment was performed to evaluate signaling..PDAC cell lines portrayed high activity of multiple receptor tyrosine kinases. Non-receptor kinase, focal adhesion kinase (FAK), was identified in all cell lines by our phosphoproteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo. In conclusion, our study shows a high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel
2021-09-10 | PXD024548 | Pride
Project description:[original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries. Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes. Human left internal mammary artery (LIMA) was divided into three segments and and two of the segments were fitted with either a paclitaxel-eluting stent or a bare metal stent. The experiment includes three groups: control, paclitaxel-eluting stent, and bare metal stent, respectively. Each group includes four biological replicates (patients 1, 2, 4 and 5).
2010-03-07 | E-GEOD-19136 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma is a devastating disease with poor prognosis, commonly characterized by aberrant signaling. Phosphoproteomics provides a functional scaffold to unravel these complex signaling networks and to identify new targets. By a two-step sequential phospho-peptide enrichment, we generated the phosphoproteome for 9 PDAC cell lines (2 derived from PDX samples). By using integrative inferred kinase activity (INKA) scoring, we identified hyperactive phosphokinases that were subsequently matched to kinase inhibitors. In the absence of an oncogenic driver, low-dose kinase inhibitor combinations against multiple (parallel) activated kinases, provided higher efficacy as compared to single-drug treatment. Tailored low-dose combination strategies exhibited promising efficacy in vitro and in vivo, which may ultimately improve treatment outcomes in PDAC patients.
2023-05-09 | PXD036951 | Pride
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:Five Triple Negative Breast Cancer cell lines were exposed to increasing concentration of Paclitaxel untill they acquired resistance. In order to identify changes in gene expression associated with resistance to PTX, we performed gene expression profiling on parental and resistant cell lines. Of ~22000 genes surveyed by microarray analysis, 5.0%, 3.7%, 9.0%, 7.3%, and 5.4% of the genes showed changes in expression of 2-fold or greater (p value < 0.05) in BT20, SUM149, MDA-MB-231, MDA-MB-436 and MDA-MB-468 cell lines, respectively.
2017-02-28 | GSE90564 | GEO
Project description:We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with paclitaxel, to aide in identifing the mechnism of action of elesclomol. Experiment Overall Design: Hs 294T human melanoma cells were grown in vitro. They were seeded at a low density and were left untreated, treated with the vehicle, treated with elesclomol, treated with paclitaxel, or treated in combination with both elesclomol and paclitaxel. They were incubated for 6 hours before harvesting.
2008-06-19 | E-GEOD-11550 | biostudies-arrayexpress
Project description:To investigate the gene targets associated with paclitaxel resistance in EOC, we cultured A2780 and paclitaxel resistant A2780 (A2780-Taxol) cell lines.
2023-06-01 | GSE230667 | GEO
Project description:Cell cycle inhibitors, including paclitaxel, are among the most widely used and effective cancer therapies. However, several challenges limit the success of paclitaxel including drug resistance and toxic side effects. Paclitaxel is thought to act primarily by stabilizing microtubules and locking cells in a mitotic state. However, the resulting cytotoxicity and tumor shrinkage rates observed cannot be fully explained by this mechanism alone. Here we apply quantitative chemical cross-linking with mass spectrometry analysis to paclitaxel treated cells. Our results provide large scale measurements of relative protein levels and, perhaps more importantly, changes to protein conformations and interactions that occur upon paclitaxel treatment. Drug concentration dependent changes are revealed in known drug targets including tubulins, as well as many other proteins and protein complexes involved in apoptotic signaling and cellular homeostasis. As such this study provides insight into systems-level changes to protein structures and interactions which occur with paclitaxel treatment.
2019-11-21 | PXD015751 | Pride