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Research ArticleClinical Studies

A Methionine-free Diet Associated with Nitrosourea Treatment Down-regulates Methylguanine-DNA Methyl Transferase Activity in Patients with Metastatic Cancer

EMILIE THIVAT, XAVIER DURANDO, AÏCHA DEMIDEM, MARIE-CHANTAL FARGES, MARYSE RAPP, ERIC CELLARIER, SAMUEL GUENIN, MICHEL D'INCAN, MARIE-PAULE VASSON and PHILIPPE CHOLLET
Anticancer Research July 2007, 27 (4C) 2779-2783;
EMILIE THIVAT
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  • For correspondence: Recherche.clinique@cjp.fr
XAVIER DURANDO
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AÏCHA DEMIDEM
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MARIE-CHANTAL FARGES
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MARYSE RAPP
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ERIC CELLARIER
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SAMUEL GUENIN
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MICHEL D'INCAN
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MARIE-PAULE VASSON
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PHILIPPE CHOLLET
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Abstract

Background: Methionine (MET) depletion used in association with chemotherapy improves the therapeutic index in animal models. This potentiating effect may be due to tumor cell sensitization to chloroethylnitrosoureas through their MET dependency and the down-regulation of O6-methylguanine-DNA methyltransferase (MGMT). Our purpose was to evaluate the impact of the association of a dietary MET restriction with nitrosourea treatment on MGMT activity in peripheral blood mononuclear cells (PBMCs). Patients and Methods: Six patients with metastatic cancer (melanoma and glioma) received 4 cycles of a MET-free diet with cystemustine (60 mg/m2). Results: MGMT activity in PBMCs decreased by an average of 13% from 553±90 fmol/mg before the diet to 413±59 fmol/mg after the diet + chemotherapy period (p=0.029). The decrease of MGMT activity was not affected by the duration of the MET-free diet period but seems to be correlated to the plasma MET depletion induced by the MET-free diet.

  • MGMT
  • methionine-free diet
  • CENU
  • melanoma
  • glioma
  • PBMC
  • methylguanine-DNA methyl transferase
  • Received January 11, 2007.
  • Revision received March 22, 2007.
  • Accepted March 27, 2007.
  • Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 27 (4C)
Anticancer Research
Vol. 27, Issue 4C
July-August 2007
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A Methionine-free Diet Associated with Nitrosourea Treatment Down-regulates Methylguanine-DNA Methyl Transferase Activity in Patients with Metastatic Cancer
EMILIE THIVAT, XAVIER DURANDO, AÏCHA DEMIDEM, MARIE-CHANTAL FARGES, MARYSE RAPP, ERIC CELLARIER, SAMUEL GUENIN, MICHEL D'INCAN, MARIE-PAULE VASSON, PHILIPPE CHOLLET
Anticancer Research Jul 2007, 27 (4C) 2779-2783;

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A Methionine-free Diet Associated with Nitrosourea Treatment Down-regulates Methylguanine-DNA Methyl Transferase Activity in Patients with Metastatic Cancer
EMILIE THIVAT, XAVIER DURANDO, AÏCHA DEMIDEM, MARIE-CHANTAL FARGES, MARYSE RAPP, ERIC CELLARIER, SAMUEL GUENIN, MICHEL D'INCAN, MARIE-PAULE VASSON, PHILIPPE CHOLLET
Anticancer Research Jul 2007, 27 (4C) 2779-2783;
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