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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human pancreatic cancer treated with masitinib combined with standard gemcitabine chemotherapy

ABSTRACT: Masitinib is a tyrosine kinase inhibitor of c-Kit, PDGFRÎ± and Î², and to some extent Lyn of the Src kinase family. We evaluated the therapeutic potential of masitinib in vitro on human pancreatic tumour cell lines and in vivo in a mouse model of human pancreatic cancer. Experiment Overall Design: Expression patterns of masitinib tyrosine kinase targets including c-Kit, PDGFRÎ± and PDGFRÎ² were determined in four pancreatic tumour cell lines by PCR. Proliferation assays were performed with masitinib alone or in combination with gemcitabine. To determine the in vivo effects of masitinib, Nog-SCID mice were injected subcutaneously with MiaPacaÂ2 cells, randomised 28 days later and received one of the following treatments: vehicle control p.o., masitinib p.o., gemcitabine i.p., or a combination of masitinib plus gemcitabine. Additionally, the transcriptome of MiaPacaÂ2 cells for each of these conditions was determined with Affymetrix arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Pascal FINETTI

PROVIDER: E-GEOD-17987 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Novel treatment of human pancreatic cancer using masitinib combined with standard gemcitabine chemotherapy

Project description:Masitinib is a tyrosine kinase inhibitor of c-Kit, PDGFRα and β, and to some extent Lyn of the Src kinase family. We evaluated the therapeutic potential of masitinib in vitro on human pancreatic tumour cell lines and in vivo in a mouse model of human pancreatic cancer.

2009-09-05 | GSE17987 | GEO

Low endothelial cell FAK expression reduces pancreatic ductal adenocarcinoma liver metastasis after gemcitabine treatment

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a high level of liver metastasis. Despite substantial advances, resistance to therapy, including gemcitabine, is still a major obstacle to improved progression free survival. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy induced angiocrine factors and chemosensitivity in malignant cells. However, the effect of EC-FAK regulated angiocrine signalling in chemosensitivity of metastatic PDAC remains unexplored. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC reduces liver metastasis and improves survival rates in gemcitabine treated, but not untreated, mice, without affecting primary tumour growth, tumour vascularization, blood vessel leakage or early metastatic events. Phosphoproteomics analysis show a downregulation of the MAPK/ RAF/ PAK signalling pathways in gemcitabine treated FAK-depleted ECs compared to gemcitabine treated WT ECs. Moreover, low levels of EC-FAK correlate with increased survival and reduced relapse in gemcitabine treated human PDAC patients, supporting the clinical relevance of our findings. Altogether, we have identified a new role of EC-FAK regulating PDAC liver metastasis upon gemcitabine treatment that impacts on survival.

2023-03-10 | PXD021542 | Pride

EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer

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2021-10-15 | MTBLS1925 | MetaboLights

Transcription profiling of mouse liver from tumor bearing animals by TSU68 treatment

Project description:The aim of this study was to investigate the inhibitory effect of TSU68, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRÎ²) and fibroblast growth factor receptor 1 (FGFR1), on colon cancer liver metastasis and to test the hypothesis that TSU68 modulates the microenvironment in the liver before the formation of metastasis. Experiment Overall Design: The human colon cancer TK-4 was implanted orthotopically into cecal walls of 6-week-old male BALB/c nu/nu mice (Clea Japan, Tokyo, Japan). The animals were treated with TSU68 (400 mg/kg/day, twice-daily, p.o.) or vehicle from 7 days after orthotopic implantation. After one week of drug administration, livers were removed and total RNA was extracted. Experiment Overall Design: We established four different groups of mice; non-tumor-bearing and treated with vehicle alone (NT-Co), non-tumor-bearing and treated with TSU68 (NT-TSU), tumor-bearing and treated with vehicle (T-Co), and tumor-bearing and treated with TSU68 (T-TSU). NT-Co, T-Co and T-TSU group were applied to microarray analysis.

2008-10-21 | E-GEOD-11808 | biostudies-arrayexpress

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2017-08-08 | GSE94891 | GEO

The miRNA profiling in PANC-1, PANC-1 GEM 100 and PANC-1 GEM1500 cells

Project description:Gemcitabine has been a first-line therapeutic agent for pancreatic ductal adenocarcinoma (PDAC) pancreatic cancer; however, acquisition of resistance to gemcitabine remains a major challenge. We analyzed miRNAs expression profiles by array-based miRNAs analysis between gemcitabine–resistant (PANC-1/GEM) and parental PANC-1 cells.

2016-12-31 | GSE79234 | GEO

mRNA-seq of gemcitabine resistant pancreatic cancer cell line subclones derived from BxPC3

Project description:We generated gemcitabine resistant subclones from the human pancreatic cancer cell line BxPC3 using chronic low dose exposure to gemcitabine. Three gemcitabine resistant subclones (BxGR-80C, BxGR-120C and BxGR-360C) were sequenced in addition to BxPC3 cells.

2021-12-21 | E-MTAB-11186 | biostudies-arrayexpress

A network-based strategy for prioritizing hits from chemical screening data by leveraging genetic, epigenetic and transcriptional datasets

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2017-10-31 | GSE70810 | GEO

RNA-seq data of nasopharyngeal carcinoma (NPC) cell and GO-PEG_erlotinib treatment

Project description:graphene oxide (GO) is found to be a promising novel anti-cancer drug carrier. Erlotinib, a tyrosine kinase inhibitor (TKI) acting on the epidermal growth factor receptor (EGFR), has been proved for locally advanced or metastatic non-small cell lung cancer (NSCLC) and in combination with gemcitabine for locally advanced or metastatic pancreatic cancer in 2004, but its study in nasopharyngeal carcinoma (NPC) is still limited. We designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as drug carriers, which was loaded with erlotinib and showed promising anticancer effect on NPC cells. Our results showed that GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be the potential therapeutic agents for treating NPC in the future.

2021-12-27 | GSE151195 | GEO

Expression profiling of budding cells in colorectal cancer suggests an EMT-like phenotype and molecular subtype switching

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2017-02-04 | E-MTAB-4065 | biostudies-arrayexpress

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