Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies

In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types. This compound acts by two distinct mechanisms. First by activating the AMPK pathway induced by a mitochondrial disorder. Second by inhibition of MELK kinase activity, which induces cell cycle arrest and activation of DNA damage repair pathways by p53 and REDD1 activation. All of these mechanisms activate autophagic and apoptotic processes resulting in melanoma cell death. The strong efficacy of CRO15 to reduce the growth of melanoma xenograft sensitive or resistant to BRAF inhibitors opens interesting perspective.Subject terms: Melanoma, Cell death     

A waveguide imaging platform for live‐cell TIRF imaging of neurons over large fields of view

Large fields of view (FOVs) in total internal reflection fluorescence microscopy (TIRFM) via waveguides have been shown to be highly beneficial for single molecule localisation microscopy on fixed cells [1,2] and have also been demonstrated for short‐term live‐imaging of robust cell types [3‐5], but not yet for delicate primary neurons nor over extended periods of time. Here, we present a waveguide‐based TIRFM set‐up for live‐cell imaging of demanding samples. Using the developed microscope, referred to as the ChipScope, we demonstrate successful culturing and imaging of fibroblasts, primary rat hippocampal neurons and axons of Xenopus retinal ganglion cells (RGCs). The high contrast and gentle illumination mode provided by TIRFM coupled with the exceptionally large excitation areas and superior illumination homogeneity offered by photonic waveguides have potential for a wide application span in neuroscience applications.     

Fractionation of nucleosides and nucleoside-5'-mono-, di and triphosphates by thin layer chromatography in silufol]

New solvent systems--dioxane--isopropanol--water--ammonium (4:2:4:1) and dioxane--water--ammonium (6:4:1)--for rapid qualitative and quantitative estimation of nucleosides, nucleoside-5'-mono-, di- and triphosphates by thin layer chromatography is Silufol UV-254 are proposed. The Rf values for 40 ribo- and deoxyribonucleotides of these systems are given.