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001-es BibID:	BIBFORM024234
Első szerző:	Jóna Ádám (belgyógyász, hematológus)
Cím:	The histone deacetylase inhibitor entinostat (SNDX-275) induces apoptosis in Hodgkin lymphoma cells and synergizes with Bcl-2 family inhibitors / Jóna A., Khaskhely N., Buglio D., Shafer J. A., Derenzini E., Bollard C. M., Medeiros L. J., Illés A., Ji Y., Younes A.
Dátum:	2011
ISSN:	0301-472X
Megjegyzések:	Based on promising in vitro and in vivo activity of several histone deacetylase inhibitors in Hodgkin lymphoma (HL), we investigated SNDX-275, an oral class 1 isoform-selective histone deacetylase inhibitors in HL-derived cell lines. MATERIALS AND METHODS: Proliferation and cell death were examined by MTS assay, Annexin V/propidium iodide, and fluorescence-activated cell sorting analysis. Gene and protein expression were measured by reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemical analysis. A multiplex assay was used to determine cytokines and chemokines. RESULTS: SNDX-275 induced cell death in a dose- and time-dependent manner with an IC(50) at the sub- and lower micromolar range at 72 hours. At the molecular level, SNDX-275 increased histone H3 acetylation, upregulated p21 expression, and activated the intrinsic apoptosis pathway by downregulating the X-linked inhibitor of apoptosis protein. SNDX-275 downregulated expression of antiapoptotic Bcl-2 and Bcl-xL proteins without altering Mcl-1 or Bax levels. Combination studies demonstrated that two Bcl-2 inhibitors (ABT-737 and obatoclax) significantly enhanced the effect of SNDX-275. SNDX-275 modulated the level of several cytokines and chemokines, including interleukin-12 p40-70, interferon-inducible protein-10, RANTES (regulated on activation, normal T expressed and secreted), interleukin-13, interleukin-4, and thymus and activation-regulated chemokine and variably induced the cancer/testis antigen expression of MAGE-A4 and survivin in HL cell lines. CONCLUSIONS: SNDX-275 has antiproliferative activity in HL cell lines, involving several mechanisms: induction of apoptosis, regulation of cytokines and chemokines, and alteration of cancer/testis antigens. Clinical investigation of SNDX-275 alone or in combination with Bcl-2 inhibitors is warranted in patients with HL. Phase 2 studies with SNDX-275 in HL are ongoing, and future clinical studies should investigate combinations with SNDX-275.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Experimental Hematology. - 39 : 10 (2011), p. 1007-1017. -
További szerzők:	Khaskhely, Noor Buglio, Daniela Shafer, Jessica A. Derenzini, Enrico Bollard, Catherine M. Medeiros, L. Jeffrey Illés Árpád (1959-) (belgyógyász, haematológus, onkológus) Ji, Yuan Younes, Anas
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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