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001-es BibID:	BIBFORM065233
Első szerző:	Canestraro, Martina
Cím:	Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders / Martina Canestraro, Sara Galimberti, Hakan Savli, Giuseppe Alberto Palumbo, Daniele Tibullo, Balint Nagy, Francesca Guerrini, Simona Piaggi, Naci Cine, Maria Rita Metelli, Mario Petrini
Dátum:	2010
ISSN:	0165-4608
Megjegyzések:	Both arsenic trioxide (ATO) and bortezomib show separate antileukemic activity. With the purpose of evaluating whether the combination of ATO and bortezomib would be an option for patients with acute leukemia, we incubated HL60 leukemic cells with ATO alone and in combination with bortezomib. ATO and bortezomib cooperated to induce cell death and to inhibit proliferation and apoptosis in a synergistic way. The combined treatment resulted in a stronger activation of caspase 8 and 9, moderate activation of caspase 3, and increased expression of Fas and tumor necrosis factor?related apoptosis-inducing ligand (TRAIL)-DR5 receptors. When bortezomib was added, some proapoptotic genes (CARD9, TRAIL) were upregulated, and some antiapoptotic genes (BCL2, BCL3, FLICE) were downregulated. When coincubated, approximately 80% of cells showed altered mitochondrial membrane permeability. Moreover, ATO alone and in combination with bortezomib abrogated DNA-binding activity of nuclear factor kappa beta (NF-?B). Gene expression assays showed that more deregulated genes were related to proliferation of leukocytes, tumorigenesis, control of cell cycle, hypoxia and oxidative stress, cytokines, PI3K-AKT, ERK-MAPK, EGF pathways, and ubiquitination. Finally, in three cases of acute myeloid leukemia, the addition of bortezomib to ATO significantly increased cytotoxicity. We conclude that the combination of bortezomib and ATO may be efficacious in the treatment of myeloid disorders.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban bortezomib synergestic antiproliferative
Megjelenés:	Cancer Genetics And Cytogenetics 199 : 2 (2010), p. 110-120. -
További szerzők:	Galimberti, Sara Savlı, Hakan Palumbo, Giuseppe Alberto Tibullo, Daniele Nagy Bálint (1956-) (molekuláris genetikus) Guerrini, Francesca Piaggi, Simona Cine, Naci Metelli, Maria Rita Petrini, Mario
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