A woman had undergone excision for primary melanoma of the left heel and dissection of groin lymph nodes. The recurrent tumor on the lateral left lower leg developed six months ago and the depigmented plaques spread extensively on the left lower limb. The depigmented macules were localized to the left lower limb and were not seen in other areas.
View Article and Find Full Text PDFGrowth factor receptors are activated through dimerization by the binding of their ligands and play pivotal roles in normal cell function. However, the aberrant activity of the receptors has been associated with cancer malignancy. One of the main causes of the aberrant receptor activation is the overexpression of receptors and the resultant formation of unliganded receptor dimers, which can be activated in the absence of external ligand molecules.
View Article and Find Full Text PDFAlthough growth factors have great therapeutic potential because of their regenerative functions, they often have intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides have recently emerged as promising chemical entities for designing synthetic alternatives to growth factors. However, their applications in vivo have been recognized as a challenge because of their susceptibility to nucleases and limited distribution to a target tissue.
View Article and Find Full Text PDFReplacing expensive and thermally unstable growth factors with synthetic alternatives has been an important issue in stem cell-based regenerative medicines. Here we developed DNA aptamer-assemblies that act as functional mimics of basic fibroblast growth factor (bFGF), one of the essential factors for stem cell culture. The most potent aptamer assembly named TD0, composed solely of 76-mer single-stranded DNA, could support the self-renewal and pluripotency of induced pluripotent stem cells (iPSCs).
View Article and Find Full Text PDFThe reprogramming of receptor-ligand interactions affords an opportunity to direct cells to respond to user-defined external cues. Although this has often been achieved via the genetic engineering of receptors, an alternative, nongenetic approach is highly demanded. In this article, we propose the design of oligonucleotide-based synthetic switches that feature the ability to reprogram the ligand specificity of the growth factor receptor.
View Article and Find Full Text PDFOligonucleotide-based hepatocyte growth factor (HGF) mimetics are described. A DNA aptamer to Met, a cognate receptor for HGF, was shown to induce Met activation when used in dimer form. The most potent aptamer dimer, ss-0, which was composed solely of 100-mer single-stranded DNA, exhibited nanomolar potency.
View Article and Find Full Text PDFDirectional cell migration induced by the stiffness gradient of cell culture substrates is known as a subset of the mechanical-cue-induced taxis, so-called mechanotaxis, typically durotaxis toward hard region. To establish the general conditions of biomaterials to manipulate the mechanotaxis, the effect of the shape of the elasticity transition boundary between hard and soft regions of a substrate on mechanotaxis should be systematically determined as well as the conditions of elasticity gradient strength. Here, as a simplified factor of expressing variations in the shape of the elasticity boundary in living tissues, we focus on the curvature of the elasticity boundary.
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