Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycinReportar como inadecuado




Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Clinical and Experimental Medicine

, Volume 16, Issue 4, pp 585–592

First Online: 10 September 2015Received: 13 June 2015Accepted: 31 August 2015DOI: 10.1007-s10238-015-0387-9

Cite this article as: Ohbatake, Y., Fushida, S., Tsukada, T. et al. Clin Exp Med 2016 16: 585. doi:10.1007-s10238-015-0387-9

Abstract

Paclitaxel PTX which easily elutes into ascites is widely used to treat gastric cancer patients with peritoneal carcinomatosis PC, but clinical outcomes are suboptimal. Increased concentrations of α1-acid glycoprotein AGP, an important drug-binding protein, have been reported in the plasma and ascites of cancer patients. This study sought to clarify whether AGP binds to PTX and alters its anticancer effects. AGP concentrations were measured in the serum and ascites of gastric cancer patients with PC and in the serum of healthy volunteers. The in vitro effects of AGP and AGP plus erythromycin EM on PTX were evaluated by MTT assays in the gastric cancer cell lines. We also measured AGP concentrations in the ascites of PC model mice and examined the effects of EM plus PTX on PC. The mean AGP concentrations in the serum and ascites of gastric cancer patients with PC were 1524 and 834 μg-mL, respectively, higher than the mean AGP concentration of 650 μg-mL observed in the sera of healthy volunteers. AGP > 400 μg-mL significantly suppressed the cell growth inhibitory effect of PTX in vitro, but the co-administration of EM restored it. Elevated AGP concentrations were observed in the ascites of PC model mice. Administration of PTX alone did not markedly diminish PC, whereas co-administration of PTX and EM significantly reduced PC p = 0.011. AGP is an important regulatory factor modulating the anticancer activity of intraperitoneal PTX. The co-administration of PTX and EM may be effective in treating gastric cancer patients with PC.

Keywordsα1-Acid glycoprotein Gastric cancer Peritoneal carcinomatosis Paclitaxel Erythromycin AbbreviationsPTXPaclitaxel

PCPeritoneal carcinomatosis

AGPα1-Acid glycoprotein

EMErythromycin

5-FU5-Fluorouracil

MSTMedian survival time

IP-PTXIntraperitoneal PTX

TGF-βTransforming growth factor-β

DMEMDulbecco’s modified Eagle’s medium

FBSFetal bovine serum

RPMIRoswell Park Memorial Institute

MTT3-4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide

SDStandard deviation

IAPImmunosuppressive protein

MRPMultidrug resistance-associated protein

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Autor: Yoshinao Ohbatake - Sachio Fushida - Tomoya Tsukada - Jun Kinoshita - Katsunobu Oyama - Hironori Hayashi - Tomoharu Miyashi

Fuente: https://link.springer.com/







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