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The mixed solution containing Cu 2+ , Zn 2+ , and L-histidine presents strong acidity at room temperature, so that the coordination of Cu 2+ and imidazolyl in L-histidine is dominant on account of the protonation of the amino and the inhibition of carboxyl ionization

Xiong, ZM, ODonovan, M., Sun, L., et al

Fibroblasts produce large amounts of collagen (mainly types I and III) in this process, forming initial fibrous structures at the injury interface

Previous attempts of targeting signaling cascades in neurofibroma microenvironment through imatinib mesylate administration, a dual SCF/cKIT inhibitor, have shown modest response rates limited only to small tumors [53] ( Cabozantinib, an inhibitor of multiple tyrosine kinases among which c-Kit, vascular endothelial growth factor (VEGF) receptor (VEGFR)2, MET, RET, FMS-related RTK 3 (FLT3) and TAM family receptors (tyrosine kinases AXL, TYRO3 and MERTK) is now under study in a phase II trial against progressive or symptomatic, inoperable PN ( as it has shown promising results in Nf1-mutant mice [54]