ADAM10 and ADAM17—Novel Players in Retinoblastoma Carcinogenesis

A disintegrin and metalloproteinase (ADAM) family proteins, acting as sheddases, are important factors in a number of pathologies, including cancer, and have been suggested as promising therapeutic targets. The study presented focuses on the involvement of ADAM10 and ADAM17 in retinoblastoma (RB), the most common malignant intraocular childhood tumor. A significant correlation between ADAM17 expression levels and RB laterality and RB staging was observed. Levels of ADAM10 or ADAM17 regulating miRNAs miR-145, -152, and -365 were significantly downregulated in RB cell lines, and reduced miR levels with simultaneously upregulated ADAM10 and ADAM17 expression were found in RB patients. The involvement of both ADAMs analyzed in ectodomain shedding of the neuronal cell adhesion molecule L1 (L1CAM), shown to induce pro-tumorigenic effects in RB, was confirmed. Lentiviral ADAM10 and ADAM17 single or ADAM10/17 double knockdown (KD) induced caspase-dependent apoptosis and reduced cell viability, proliferation, growth, and colony formation capacity of RB cells. Moreover, differential phosphorylation of the serine/threonine kinase AKT was observed following ADAM17 KD in RB cells. Chicken chorioallantoic membrane (CAM) assays revealed that ADAM17 and ADAM10/17 depletion decreases the tumorigenic and migration potential of RB cells in vivo. Thus, ADAMs are potential novel targets for future therapeutic RB approaches.     

Tresterweine

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Weins?uregehalt der 1932-er Moselmoste

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Zur Kenntnis und Beurteilung von Obstweinen

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Beitrag zur Kenntnis der chemischen Vorg?nge beim Lagern von Flaschenweinen

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Integral measurements with a plutonium inert matrix fuel rod in a heterogeneous light water reactor lattice

As part of PSI's validatory efforts for neutronics calculations pertaining to inert matrix fuel (IMF) deployment in light water reactors, first-of-their-kind integral measurements have been carried out at the PROTEUS facility employing a specially fabricated Pu-Er-Zr IMF rod in a heterogeneous (boiling water reactor) test lattice. Analogous experiments have also been conducted with MOX and “dummy” IMF rods, providing the basis for a systematic comparison of experimental and calculational results.