ABSTRACT
The EphA2 receptor tyrosine kinase is overexpressed in most solid tumors and acts as the major driver of tumorigenesis. In this study, we developed a novel approach for targeting the EphA2 receptor using a 2'-fluoro-modified pyrimidine RNA aptamer termed ATOP. We identified the ATOP EphA2 aptamer using a novel bioinformatics strategy that compared aptamers enriched during a protein SELEX using recombinant human EphA2 and a cell-internalization SELEX using EphA2-expressing MDA231 tumor cells. When applied to EphA2-expressing tumor cell lines, the ATOP EphA2 aptamer attenuated tumor cell migration and clonogenicity. In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.
ABSTRACT
Although less common than peripheral myelin protein 22 (PMP22) duplication, there are mutations in myelin protein zero (MPZ) responsible for Charcot-Marie-Tooth disease (CMT) with a number of different clinical profiles. We report here a novel MPZ homozygous mutation, with a peculiar pattern characterized by a late-onset demyelinating profile. In addition, the patient presented brain white matter lesions seemingly ascribable to the mutation.
