A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: preliminary preclinical results

Leukemia
D CoradiniA Perbellini

Abstract

All-trans retinoic acid (ATRA) represents the therapy of choice for patients with acute promyelocytic leukemia (APL). However, patients often relapse due to ATRA-resistance. The molecular basis of APL alterations indicates that addition of a histone deacetylase inhibitor to ATRA may restore the sensitivity to retinoids. We explored the in vitro and in vivo effects of a novel retinoic/butyric hyaluronan ester (HBR) on a retinoic acid (RA)-sensitive human myeloid cell line, NB4, and on its RA-resistant subclone, NB4.007/6. In vitro, HBR induced growth arrest and terminal differentiation in RA-sensitive NB4 cells (as confirmed by an increased expression of CD11 family members and nitroblue tetrazolium assay), whereas it inhibited the growth of RA-resistant cells by apoptosis, paralleled by an increase in the levels of caspase 3 and 7. In vivo, HBR treatment of NB4-inoculated severe combined immunodeficient mice resulted in a statistically significant increase in survival time (P<0.0001), comparable to that induced by a maximum tolerated dose of RA alone. Also on P388-inoculated mice, HBR was active in contrast to RA that was completely ineffective. Present findings suggest that, owing to the simultaneous presence of RA and an hist...Continue Reading

References

Nov 12, 1998·Journal of the National Cancer Institute·R P WarrellP P Pandolfi
Apr 21, 1999·International Journal of Cancer. Journal International Du Cancer·D CoradiniA Perbellini

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Citations

Nov 26, 2015·Advanced Drug Delivery Reviews·Franco DosioElias Fattal
Oct 18, 2008·Carbohydrate Research·Claudia SorbiStefano Norbedo
Jun 7, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Giridharan Loghanathan MalarvizhiManzoor Koyakutty
Nov 17, 2011·Chemical Society Reviews·Shoshy Mizrahy, Dan Peer
Oct 8, 2016·Nanoscale·Kegang LiuPatrick Hunziker

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