Publications by authors named "William D Schrump"
Purpose: Recent insights regarding the pathogenesis of malignant pleural mesothelioma (MPM) provide new opportunities for targeted molecular therapies for this highly lethal disease. The present study was undertaken to examine the effects of the histone deacetylase inhibitor, Depsipeptide (DP) FK228, in conjunction with the cyclin-dependent kinase inhibitor, Flavopiridol (FLA), in cultured MPM cells.
Experimental Design: Proliferation and apoptosis in drug-treated, virally transduced, or control cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Apo-bromodeoxyuridine techniques.
Article Synopsis
- The study investigates how LY294002, an inhibitor of the phosphoinositide 3-kinase pathway, affects the sensitivity of lung and esophageal cancer cells to the chemotherapy drug paclitaxel (Taxol).
- Results showed a significant decrease in the cancer cells' resistance to paclitaxel when treated with LY294002, leading to enhanced apoptosis (cell death).
- The mechanism involved includes the inhibition of protein kinase B (Akt) activation and the suppression of nuclear factor-kappaB activity, both of which are linked to the cancer cells' survival and resistance to chemotherapy.
Objective: Treating cancer cells with depsipeptide, a novel antitumor agent currently in a phase II clinical trial, causes potent upregulation of p21/WAF1 expression and cell arrest at G1 and G2 checkpoints. p21/WAF1 upregulation, however, impedes the ability of depsipeptide to induce significant apoptosis. This study was designed to determine whether flavopiridol, a synthetic cyclin-dependent kinase inhibitor known to inhibit p21 expression in tumor cells, could enhance depsipeptide-mediated apoptosis in cultured lung and esophageal cancer cells.
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