Gold nanorods are effective photothermal agents in diagnosis and treatment of cancer due to their specific near-infrared laser absorption. However, tumor photothermal therapy by nanorods alone is lack of targeting. Here, we described a novel nanocomplex made up of gold nanorods, porphyrin, and trastuzumab, called TGNs and investigated the TGN-mediated photothermal therapy as a potential alternative treatment of targeting HER2-positive breast cancers. By conjugating trastuzumab and porphyrin to the surface of gold nanorods, we have increased the targeting specificity and amplified the detecting effectiveness at the same time. TGN-mediated photothermal ablation by near-infrared laser led to a selective destruction of HER2-positive cancer cells and significantly inhibited tumor growth in mouse models bearing HER2 over-expressed breast cancer xenograft with less toxicity. Moreover, TGNs provided better therapeutic efficacy in comparison with the conventional molecule targeted therapy. Our current data suggest a highly promising future of TGNs for its therapeutic application in trastuzumab-resistant breast cancers.
Several reports have suggested that peripheral blood-based parameters are associated with host immunity response, which is an essential component of the pathogenesis and progression of cancer. The purpose of the present study was to identify the prognostic significance of various peripheral blood-based biomarkers and to determine the optimal cut-off value suitable for luminal breast cancer patients. We found that lymphocyte-to-monocyte ratio (LMR) was significant prognostic predictors. And the patients with a CEF regimen and LMR ratio ≥ 5.2 gained a good prognosis. This study suggested that the LMR could be regarded as an independent prognostic factor in luminal breast cancer patients. The elevated LMR level also had enhanced 5-fluorouracil sensitivity in luminal breast cancer patients.
Arsenic trioxide (As 2 O 3 ) is used to treat acute pro-myelocytic leukaemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As 2 O 3 can damage the hERG current via disturbing its trafficking to cellular membrane. Consistent with these findings, in this study, we reported that As 2 O 3 inhibited hERG channel at both protein and mRNA levels and damaged hERG current but did not affect channel kinetics. Further, we demonstrated that As 2 O 3 up-regulated miR-21 and miR-23a expression in hERG-HEK293 cells and neonatal cardiomyocytes. In addition, knockdown of miR-21 by its specific antisense molecules AMO-21 was able to rescue Sp1 and hERG inhibition caused by As 2 O 3 . Consistently, phosphorylation of NF-jB, the upstream regulatory factor of miR-21, was significantly up-regulated by As 2 O 3 . This finding revealed that regulation of the NF-jB-miR-21-Sp1 signalling pathway is a novel mechanism for As 2 O 3 -induced hERG inhibition. Meanwhile, the expression of Hsp90 and hERG was rescued by transfection with AMO-23a. And the hERG channel inhibition induced by As 2 O 3 was rescued after being transfected with AMO-23a, which may be a molecular mechanism for the role of As 2 O 3 in hERG trafficking deficiency. In brief, our study revealed that miR-21 and miR-23a are involved in As 2 O 3 -induced hERG deficiency at transcriptional and transportational levels. This discovery may provide a novel mechanism of As 2 O 3 -induced hERG channel deficiency, and these miRNAs may serve as potential therapeutic targets for the handling of As 2 O 3 cardiotoxicity.
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