Yang D.,Laboratory of Dermatology |
Yang D.,St. Johns University |
Kathawala R.J.,St. Johns University |
Chufan E.E.,U.S. National Cancer Institute |
And 4 more authors.
Future Oncology | Year: 2014
Aim: This study aimed to investigate the mechanism of reversal of multidrug resistance mediated by ABC transporters with tivozanib (AV-951 and KRN-951). Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors. Materials & methods: ABCB1- and ABCG2-overexpressing cell lines were treated with respective substrate antineoplastic agents in the presence or absence of tivozanib. Results: The results indicate that tivozanib can significantly reverse ABCB1-mediated resistance to paclitaxel, vinblastine and colchicine, as well as ABCG2-mediated resistance to mitoxantrone, SN-38 and doxorubicin. Drug efflux assays showed that tivozanib increased the intracellular accumulation of substrates by inhibiting the ABCB1 and ABCG2 efflux activity. Furthermore, at a higher concentration, tivozanib inhibited the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2. Conclusion: We conclude that tivozanib at noncytotoxic concentrations has the previously unknown activity of reversing multidrug resistance mediated by ABCB1 and ABCG2 transporters. © 2014, Future Medicine Ltd. All rights reserved.
Xue F.,Laboratory of Dermatology |
Li X.,Ruijin Hospital |
Zhao X.,Ruijin Hospital |
Wang L.,Ruijin Hospital |
And 3 more authors.
PLoS ONE | Year: 2015
Background: Evidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood. Methods: We screened a cDNA library and identified potential RIG-I interacting partners that may play a role in psoriasis. Results: We found that serine/arginine-rich splicing factor 1 (SRSF1) could specifically interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA. We found SRSF1 associates with RNA polymerase III and RIG-I in a DNA-dependent manner. In addition, treatment with a TNFα inhibitor downregulated SRSF1 expression in peripheral blood mononuclear cells (PBMCs) from psoriasis vulgaris patients. Discussion: Based on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a critical link regarding how cytosolic DNA specifically activates aberrant IFN expression. These data may provide new therapeutic targets for the treatment of psoriasis. © 2015 Xue et al.
Chen G.,St. Johns University |
Chen R.,St. Johns University |
Zou C.,St. Johns University |
Yang D.,St. Johns University |
And 2 more authors.
Journal of Materials Chemistry B | Year: 2014
Uniform purified long polymer nanotubes with crosslinked poly(glycidyl methacrylate) as the backbone and a pendant poly(N-isopropyl acrylamide) layer attached to the inner surface as a thermo-responsive gating system were synthesized by a two-fold "grafting-from" strategy inside cylindrical alumina nanopores. To adapt such long polymer nanotubes to be efficient nanocarriers for the intracellular delivery of anti-cancer drugs, a sonication-induced scission method was used to 'cut' the long nanotubes into short fragments. The discontinuous volume transition property in response to the temperature change for the pendant poly(N-isopropyl acrylamide) layer inside the nanotubes results in a reversible 'closing/opening' gating mechanism to control loaded drug release from the nanotubes. Using doxorubicin (DOX) as a model drug, in vitro thermo-responsive drug release behaviour and the related kinetics were studied in detail. The pristine fragmented polymer nanotubes were found to have good biocompatibility in the test with KB-3-1 cancer cells although toxic in their monomeric forms. More importantly, cell toxicity assays for DOX-loaded fragmented polymer nanotubes presented excellent temperature and concentration-dependent cytotoxicity with a low IC50 of 1.4 μmol L-1. These results indicated that such polymer nanotubes with a thermo-responsive gating system have potential as effective anti-cancer drug delivery vehicles. © 2014 The Royal Society of Chemistry.