In Vivo NCL Targeting Affects Breast Cancer Aggressiveness Through miRNA Regulation.

In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.

J Exp Med. 2013 Apr 22;
Pichiorri F, Palmieri D, De Luca L, Consiglio J, You J, Rocci A, Talabere T, Piovan C, Lagana A, Cascione L, Guan J, Gasparini P, Balatti V, Nuovo G, Coppola V, Hofmeister CC, Marcucci G, Byrd JC, Volinia S, Shapiro CL, Freitas MA, Croce CM

Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. HubMed – drug


The Beneficial Effect of Total Glucosides of Paeony on Psoriatic Arthritis Links to Circulating Tregs and Th1 Cell Function.

Phytother Res. 2013 Apr 23;
Wang YN, Zhang Y, Wang Y, Zhu DX, Xu LQ, Fang H, Wu W

Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-? and TNF-?), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ?25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug


Direct Synthesis of ?-N-Glycosides by the Reductive Glycosylation of Azides with Protected and Native Carbohydrate Donors.

Angew Chem Int Ed Engl. 2013 Apr 22;
Zheng J, Urkalan KB, Herzon SB

A simple and straightforward method for the stereocontrolled synthesis of ?-linked N-glycosides uses alkyl and aryl azides as the nitrogen source. The N-glycosides are formed in high yields and with high ? selectivities (typically >70?% yield, >15:1 ?:? selectivity). This approach is also amenable to the synthesis of N-glycosylated amino acids and peptides (see example, Fmoc=9-fluorenylmethoxycarbonyl). HubMed – drug