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Pancreatic Neoplasms: HELP
Articles by Annemieke Groen
Based on 1 article published since 2010
(Why 1 article?)
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Between 2010 and 2020, Annemieke Groen wrote the following article about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. 2010

Giovannetti, Elisa / Funel, Niccola / Peters, Godefridus J / Del Chiaro, Marco / Erozenci, Leyla A / Vasile, Enrico / Leon, Leticia G / Pollina, Luca E / Groen, Annemieke / Falcone, Alfredo / Danesi, Romano / Campani, Daniela / Verheul, Henk M / Boggi, Ugo. ·VU University Medical Center, Amsterdam, the Netherlands. ·Cancer Res · Pubmed #20460539.

ABSTRACT: MicroRNA-21 (miR-21) was reported to be overexpressed and contributes to invasion and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether miR-21 expression was associated with the overall survival (OS) of PDAC patients treated with gemcitabine and to provide mechanistic insights for new therapeutic targets. miR-21 expression was evaluated in cells (including 7 PDAC cell lines, 7 primary cultures, fibroblasts, and a normal pancreatic ductal cell line) and tissues (neoplastic specimens from 81 PDAC patients and normal ductal samples) isolated by laser microdissection. The role of miR-21 on the pharmacologic effects of gemcitabine was studied with a specific miR-21 precursor (pre-miR-21). Patients with high miR-21 expression had a significantly shorter OS both in the metastatic and in the adjuvant setting. Multivariate analysis confirmed the prognostic significance of miR-21. miR-21 expression in primary cultures correlated with expression in their respective tissues and with gemcitabine resistance. Pre-miR-21 transfection significantly decreased antiproliferative effects and apoptosis induction by gemcitabine, whereas matrix metalloproteinase (MMP)-2/MMP-9 and vascular endothelial growth factor expression were upregulated. Addition of inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin resulted in decrease of phospho-Akt and prevented pre-miR-21-induced resistance to the proapoptotic effects of gemcitabine. miR-21 expression correlated with outcome in PDAC patients treated with gemcitabine. Modulation of apoptosis, Akt phosphorylation, and expression of genes involved in invasive behavior may contribute to the role of miR-21 in gemcitabine chemoresistance and to the rational development of new targeted combinations.