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Correlation of methylprednisolone chemosensitivity in vitro with C3435T MDR1 polymorphism and clinical outcome in childhood acute lymphoblastic leukemia.

Correlation of methylprednisolone chemosensitivity in vitro ...

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第十五届国际药理学大会

作者： mirossay Ladislav Oravkinova Irina Tokarcikova Katarina Jamborova Erika Sarissky Marek Mojzis Jan mirossay andrej P.J.Safarik Univ. Fac. Med.Dept. Pharmacol.KosiceSlovak Republic. Pediatric Hospital Dept.Pediat.Oncol.KosiceSlovak Republic. P.J. Safarik Univ. Fac. Med.Dept.Pharmacol.KosiceSlovak Republic. P.J. Safarik Univ. Fac. Med.Dept.Pharmacol.KosiceSlovak Republic. P.J. Safarik Univ. Fac. Med.Dept.Pharmacol.KosiceSlovak Republic. P.J. Safarik Univ. Fac. Med.Dept.Pharmacol.KosiceSlovak Republic. P.J. Safarik Univ. Fac. Med.Dept.Pharmacol.KosiceSlovak Republic.

＜正＞ Objective: Cellular drug resistance measured at initial diagnosis is associated with an increased relapse risk and unfavorable clinical outcome in childhood ALL. In addition, the presence of adverse clinical prognostic factors such as age. and pro - B and T - lineage immunophenotype have been shown to be associated with cellular resistance to drugs in children with ALL. P - glycoprotein （Pgp）, the gene product of MDR1, confers multidrug resistance to a number of antineoplastic agents. A silent mutation in the exon 26 （C3435T） has been associated with altered expression and function of Pgp in tissues. Methods: MIT cytotoxicity assay, PCR alnalysis of C3435T polymorphism in MDR1 gene. Results: We compared the impact of C3435T polymorphism on in vitro chemosensitivity of leukemia cells to methylprednisolone. CC genotype carriers showed higher IC50 values in comparison with the carriers of CT or TT genotype. Statistical analysis Mann- Whitney U test showed P = 0.035. Conclusions: The group of patients with CC genotype seems to be more resistant to glucocorticoids, or at least methyprednisolone.

关键词： ALL MDR1 gene polymorphism glucocorticoid

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Proapoptotic effects of selected indole phytoalexins in cancer cells.

Proapoptotic effects of selected indole phytoalexins in canc...

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第十五届国际药理学大会

作者： Mojzis Jan Rlatova Martina Sarissky Marek Kutschy Peter Mojzisova Gabriela mirossay Ladislav P.J.Safarik Univ. Fac.Med.Dept.Pharmacol.KosiceSlovak Republic. P.J.Safarik Univ. Fac.Med.Dept.Pharmacol.KosiceSlovak Republic. P.J.Safarik Univ. Fac.Med.Dept.Pharmacol.KosiceSlovak Republic. P. J. Safarik Univ. Fac. Sri ***. Chem. Kosice Slovak Republic. P. J. Safarik Univ. Fac. Med.Dent. Exp. Med Kosice Slovak Republic. P.J.Safarik Univ. Fac. Med.. DeptPharmacol.KosiceSlovak Republic.

＜正＞ Objective: In the present work,we tested selected cruciferous indole phytoalexins for their antiproliferative and proapototic effects on cancer cell lines. Methods: MIT cytotoxicity assay,cell cycle analysis, apoptosis detection by flow cytometry or DNA ***: Our data indicate the highest activity of 1 - methoxybrasinine （MB）. The IC50 was 10 and 5 mmol/L in Jurkat and HL-60 leukemic cells, respectively . However, significant antiproliferative effect of all phytoalexines was also determined at concentration 0.5 mmol/L in both cell lines. In MB - treated cells we found significant increase in the fraction of cells with a sub - G0/G1 DNA content, which is considered to be a marker of cell death by apoptosis. Apoptosis was also confirmed by the annexin V staining and DNA fragmentation. Conclusions: MB exerted potent antiproliferative activity probably due to cell cycle arrest and apoptosis induction. Further studies are necessary to elucidate its mechanism of action, nevertheless, this compound might have a potential to enter pre-clinical trials as a new anticancer drug.

关键词： phytoalexms - cancer-apoptosis

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