interleukin-8 and enzastaurin

interleukin-8 has been researched along with enzastaurin* in 1 studies

Other Studies

1 other study(ies) available for interleukin-8 and enzastaurin

ArticleYear
Correlations of mRNA expression and in vitro chemosensitivity to enzastaurin in freshly explanted human tumor cells.
    Investigational new drugs, 2008, Volume: 26, Issue:3

    Enzastaurin (LY317615) is a novel serine/threonine kinase inhibitor, targeting Protein Kinase C-beta (PKC-beta), and PI3K/AKT pathways to inhibit angiogenesis and tumor cell proliferation. The aims of this study were to determine whether Enzastaurin has direct antitumor activity against freshly explanted tumor cells and to correlate mRNA expression of genes related to the proposed mechanism of action of enzastaurin with in vitro chemosensitivity.. Freshly biopsied tumor cells were studied using soft-agar cell cloning experiments (SACCE) to determine the in vitro chemosensitivity to enzastaurin. An aliquot of the same tumor specimens was shock-frozen and total RNA was isolated for standardized multiplex rt-PCR experiments for gene expression of PKC-beta1, PKC-beta2, IL-8, IL-8RA, IL-8RB, Glycogen Synthase Kinase 3 beta (GSK-3beta) and TGF-beta1. Correlations, threshold optimization, sensitivity, specificity, and efficiency were analyzed using the appropriate statistical methodologies.. Seventy-two tumor samples were collected and 63 were fully evaluable. Low levels of mRNA expression of GSK-3beta and high levels of mRNA expression of IL-8 were highly significantly correlated with chemosensitivity to enzastaurin. Optimization analyses demonstrated threshold values of 4,000 copies for IL-8 and three copies for GSK-3beta relative to 10(4) copies of beta-actin. However, no correlation between mRNA expression of PKC-beta1, PKC-beta2, IL-8RA, IL-8RB and chemosensitivity to enzastaurin was observed. Expression of TGF-beta1 mRNA was not detectable in the specimens investigated.. mRNA expression levels of IL-8 and GSK-3beta correlate with antitumor activity of enzastaurin. These results form a rational basis for clinical trials to evaluate the expression of these genes as potential predictors for treatment outcome after enzastaurin chemotherapy.

    Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Gene Expression; Glycogen Synthase Kinase 3; Humans; Indoles; Interleukin-8; Neoplasms; RNA, Messenger; Tumor Cells, Cultured

2008