A Case of Giant Congenital Melanocytic Nevus Treated with Combination Therapy of Autologous Mesh-skin Grafts and Cultured Epithelial Autografts.

Surgical excision of a giant congenital melanocytic nevus (GCMN) results in a full-thickness skin defect that is usually difficult to reconstruct even with tissue expansion or skin grafting. Here, we report the first case of GCMN treated with a combination of cultured epithelial autografts (CEAs) and mesh-skin grafts to reconstruct a large skin defect after surgical excision. A 14-month-old girl had a GCMN occupying 20% of the total body surface area of her neck and back. A 5-stage, full-thickness excision was performed between the age of 14 and 25 months. In each intervention, the wound after excision was covered with 1:6 mesh-skin grafts and CEAs, except for the neck, where patch skin grafts and CEAs were used. The skin grafts and CEAs were engrafted without shedding and epithelialization was completed within 3-4 weeks. Eighteen months after the last surgery, a mesh-like scar remained, with no recurrence or severe contracture observed. The cosmetic appearances of the donor sites (the scalp and lower abdomen) were acceptable. The application of CEAs with mesh-skin grafts has been established for the treatment of severe burns. This combined method also provides a possible option for the treatment of GCMNs.

Structure-activity studies on the fluorescent indicator in a displacement assay for the screening of small molecules binding to RNA.

A series of xanthone and thioxanthone derivatives with aminoalkoxy substituents were synthesized as fluorescent indicators for a displacement assay in the study of small-molecule-RNA interactions. The RNA-binding properties of these molecules were investigated in terms of the improved binding selectivity to the loop region in the RNA secondary structure relative to 2,7-bis(2-aminoethoxy)xanthone (X2S) by fluorimetric titration and displacement assay. An 11-mer double-stranded RNA and a hairpin RNA mimicking the stem loop IIB of Rev response element (RRE) RNA of HIV-1 mRNA were used. The X2S derivatives with longer aminoalkyl substituents showed a higher affinity to the double-stranded RNA than the parent molecule. Introduction of a methyl group on the aminoethoxy moiety of X2S effectively modulated the selectivity to the RNA secondary structure. Methyl group substitution at the C1' position suppressed the binding to the loop regions. Substitution with two methyl groups on the amino nitrogen atom resulted in reducing the affinity to the double-stranded region by a factor of 40%. The effect of methyl substitution on the amino nitrogen atom was also observed for a thioxanthone derivative. Titration experiments, however, suggested that thioxanthone derivatives showed a more prominent tendency of multiple binding to RNA than xanthone derivatives. The selectivity index calculated from the affinity to the double-stranded and loop regions suggested that the N,N-dimethyl derivative of X2S would be suitable for the screening of small molecules binding to RRE.

Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging.

We have designed and evaluated UTX-12 as a novel fluorescent pH probe for tumor hypoxia imaging. UTX-12 consists of a p-nitro benzyl moiety, which is a latent hypoxia-selective leaving group activated by nitro reduction, directly linked to SNARF. Although UTX-12 itself is colorless and non-fluorescent in aqueous solution, nitro reduction triggers the release of SNARF which has well-characterized long wavelength absorption and fluorescence that is sensitive to pH. The resultant SNARF, released intracellularly by enzymatic reduction of UTX-12, allows measurement of pH by pH-dependent dual emission shifts. UTX-12 showed clear differences in fluorescence behavior between hypoxic and aerobic conditions in liver microsomes and inside V79 cells. These data are confirmation that UTX-12 is biologically reduced inside tumor cells and the released SNARF should monitor intracellular pH of tumor cells selectively with reduced background signal.