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Chinese Medical Journal ; (24): 1082-1087, 2011.
Article Dans Anglais | WPRIM | ID: wpr-239890

Résumé

<p><b>BACKGROUND</b>Our previous studies have demonstrated potent oncolysis efficacy of the E1A, E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here, we reported the feasibility and efficacy of AxdAdB-3 alone, or in combination with gemcitabine for treating renal cell carcinoma.</p><p><b>METHODS</b>Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1, TOS-2, TOS-3, TOS-3LN, SMKT-R3, SMKT-R4 and ACHN, and in normal human renal proximal tubule epithelial cells (RPTEC). AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model.</p><p><b>RESULTS</b>AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2, TOS-3, TOS-3LN, SMKT-R3 and SMKT-R4, while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone.</p><p><b>CONCLUSION</b>AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.</p>


Sujets)
Animaux , Humains , Mâle , Souris , Adenoviridae , Génétique , Métabolisme , Physiologie , Protéines E1A d'adénovirus , Génétique , Protéines E1B d'adénovirus , Génétique , Antimétabolites antinéoplasiques , Pharmacologie , Utilisations thérapeutiques , Néphrocarcinome , Traitement médicamenteux , Thérapeutique , Cycle cellulaire , Génétique , Lignée cellulaire , Lignée cellulaire tumorale , Prolifération cellulaire , Protéine membranaire apparentée au récepteur des coxsackievirus et adénovirus , Désoxycytidine , Pharmacologie , Utilisations thérapeutiques , Cytométrie en flux , Immunohistochimie , Souris de lignée BALB C , Souris SCID , Thérapie virale de cancers , Récepteurs viraux , Génétique , Métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe
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