A syngle cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in melanoma cell clones: role of o6-methylguanine-DNA methyltransferase and the mismatch repair system. (Articolo in rivista)

Type
Label
  • A syngle cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in melanoma cell clones: role of o6-methylguanine-DNA methyltransferase and the mismatch repair system. (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Alternative label
  • ALVINO E(1),CASTIGLIA D(2), CAPORALI E(3), PEPPONI R(3,6), CAPORASO P(3), LACAL PM(3), MARRA G(4), FISCHER F(4), ZAMBRUNO G(2), BONMASSAR E(5), JIRICNY J(4), D'ATRI S(3). (2006)
    A syngle cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in melanoma cell clones: role of o6-methylguanine-DNA methyltransferase and the mismatch repair system.
    in International journal of oncology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • ALVINO E(1),CASTIGLIA D(2), CAPORALI E(3), PEPPONI R(3,6), CAPORASO P(3), LACAL PM(3), MARRA G(4), FISCHER F(4), ZAMBRUNO G(2), BONMASSAR E(5), JIRICNY J(4), D'ATRI S(3). (literal)
Pagina inizio
  • 785 (literal)
Pagina fine
  • 797 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Impact Factor = 2.556 Citations = 17 su WEB of Knoledge e Scopus (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 29 (literal)
Rivista
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1) CNR, Institute of Neurobiology and Molecular Medicine, Tor Vergata Research Area, Rome, Italy (2) Laboratories of Molecular and Cell Biology,Istituto Dermopatico dell'Immacolata-IRCCS,Rome, Italy (3) Laboratories of Molecular Oncology,Istituto Dermopatico dell'Immacolata-IRCCS,Rome, Italy (4) Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland (5) Department of Neurosciences, University of Tor Vergata, Rome, Italy (5); (literal)
Titolo
  • A syngle cycle of treatment with temozolomide, alone or combined with O6-benzylguanine, induces strong chemoresistance in melanoma cell clones: role of o6-methylguanine-DNA methyltransferase and the mismatch repair system. (literal)
Abstract
  • Clinically achievable concentrations of temozolomide (TMZ) produce cytotoxic effects only in mismatch repair (MMR)-proficient cells endowed with low O6-methylguanine-DNA methyltransferase (MGMT) activity. Aim of the present study was to investigate the molecular mechanisms underlying acquired resistance of melanoma cells to TMZ and the effect of O6-benzylguanine (BG), a specific MGMT inhibitor, on the development of a TMZ-resistant phenotype. Three MMR-proficient melanoma cell clones with low or no MGMT activity were treated daily for 5 days with 50 micromol/l TMZ, alone or in combination with 5 micromol/l BG. Parental clones and sublines established after one or four cycles of treatment were analyzed for sensitivity to TMZ or TMZ+BG and for other parameters. The sublines established after one cycle of TMZ or TMZ+BG exhibited a marked increase in MGMT activity and resistance to TMZ alone. BG only partially reversed acquired resistance to the drug. In some cases, alterations in the MMR system accounted for MGMT-independent resistance to TMZ. Up-regulation of MGMT activity was associated with either demethylation of the MGMT promoter or hypermethylation of the body of the gene, and partially reversed by 5-aza-2'-deoxycytidine. The sublines established after four cycles of TMZ or TMZ+BG did not show a further increase in resistance to TMZ alone. However, two out of three sublines established after TMZ+BG treatment exhibited increased resistance to TMZ+BG. In conclusion, our data demonstrate that a single cycle of TMZ is sufficient to induce high levels of drug resistance in melanoma clones, principally, but not exclusively, via up-regulation of MGMT expression. Exposure to TMZ+BG favors the development of MGMT-independent mechanisms of TMZ resistance. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Prodotto
Autore CNR di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it