Cancer initiation and proliferation is regulated by both epigenetic and genetic events with epigenetic modifications being increasingly identified as important targets for cancer research. DNA methylation catalyzed by DNA methyltransferases (DNMTs) is one of the essential epigenetic mechanisms that control cell proliferation, apoptosis, differentiation, cell cycle, and transformation in eukaryotes. Recent progress in epigenetics revealed a deeper understanding of the mechanisms of tumorigenesis and provided biomarkers for early detection, diagnosis, and prognosis in cancer patients. Although DNA methylation biomarker possesses potential contributing to precision medicine, there are still limitations to be overcome before it reaches clinical setting. Hence, the current status of DNA methylation biomarkers was reviewed and the future use in clinic was also predicted.
The microcavity effect in top-emitting quantum dot light-emitting diodes (TQLEDs) is theoretically and experimentally investigated. By carefully optimizing the cavity length, the thickness of the top Ag electrode and the thickness of the capping layer, very bright and efficient TQLEDs with external quantum efficiency (EQE) of 12.5% are demonstrated. Strong dependence of luminance and efficiency on cavity length is observed, in good agreement with theoretical calculation. By setting the normal-direction resonant wavelength around the peak wavelength of the intrinsic emission, highest luminance of 112 000 cd/m(2) (at a driving voltage of 7 V) and maximum current efficiency of 27.8 cd/A are achieved, representing a 12-fold and a 2.1-fold enhancement compared to 9000 cd/m(2) and 13.2 cd/A of the conventional bottom emitting devices, respectively, whereas the highest EQE of 12.5% is obtained by setting the resonant wavelength 30 nm longer than the peak wavelength of the intrinsic emission. Benefit from the very narrow spectrum of QDs and the low absorption of silver electrodes, the potential of microcavity effect can be fully exploited in TQLEDs.
We identified pyrvinium pamoate, an old anthelminthic medicine, which preferentially inhibits anchorage-independent growth of cancer cells over anchorage-dependent growth (∼10 fold). It was also reported by others to have anti-tumor activity in vivo and selective toxicity against cancer cells under glucose starvation in vitro, but with unknown mechanism. Here, we provide evidence that pyrvinium suppresses the transcriptional activation of GRP78 and GRP94 induced by glucose deprivation or 2-deoxyglucose (2DG, a glycolysis inhibitor), but not by tunicamycin or A23187. Other UPR pathways induced by glucose starvation, e.g. XBP-1, ATF4, were also found suppressed by pyrvinium. Constitutive expression of GRP78 via transgene partially protected cells from pyrvinium induced cell death under glucose starvation, suggesting that suppression of the UPR is involved in pyrvinium mediated cytotoxicity under glucose starvation. Xenograft experiments showed rather marginal overall anti-tumor activity for pyrvinium as a monotherapy. However, the combination of pyrvinium and Doxorubicin demonstrated significantly enhanced efficacy in vivo, supporting a mechanistic treatment concept based on tumor hypoglycemia and UPR.
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