ABSTRACT
The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma skin cancers centers on cumulative genomic instability caused by inefficient DNA repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent translesion replication past these DNA lesions generate distinct molecular signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since previous efforts to develop experimental strategies to enhance the repair capacity of basal keratinocytes have been limited, we have engineered the N-terminally truncated form (Δ228) UV endonuclease (UVDE) from Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT. Further, a NLS was engineered onto a pyrimidine dimer glycosylase from Paramecium bursaria chlorella virus-1 (cv-pdg-NLS). Purified enzymes were encapsulated into liposomes and topically delivered to the dorsal surface of SKH1 hairless mice in a UVB-induced carcinogenesis study. Total tumor burden was significantly reduced in mice receiving either UVDE-TAT or UVDE-NLS-TAT versus control empty liposomes and time to death was significantly reduced with the UVDE-NLS-TAT. These data suggest that efficient delivery of exogenous enzymes for the initiation of repair of UVB-induced DNA damage may protect from UVB induction of squamous and basal cell carcinomas.
Subject(s)
Carcinogenesis/radiation effects , DNA Repair , Skin Neoplasms/prevention & control , Ultraviolet Rays , Animals , DNA Repair Enzymes/administration & dosage , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , Mice, Hairless , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/metabolismABSTRACT
La presencia de apendicitis aguda en una hernia inguinal es un hecho infrecuente, con un 0,13 por ciento de los casos. Esta rara condición se conoce como Hernia de Amyand. La forma de presentación habitual es la de una hernia inguinal complicada. Es por este motivo que el diagnóstico preoperatorio de apendicitis requiere de una alta sospecha clínica, realizándose mayoritariamente durante la cirugía. El estudio de imágenes, en particular la tomografía axial computada, han sido utilizados para confirmar este diagnóstico. El tratamiento recomendado es la apendicectomía y la reparación primaria de la hernia en el mismo tiempo operatorio. No se debe utilizar prótesis por el riesgo de infección y fístula de muñón apendicular. Debido a lo excepcional de esta patología, presentamos el caso de un hombre de 75 años que se manifestó como una hernia inguinal complicada y cuyo diagnóstico se realizó en pabellón luego de abrir el saco.
