RESUMO
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel ß3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
Assuntos
Apoptose/efeitos dos fármacos , Endometriose/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Endometriose/patologia , Endométrio/patologia , Células Epiteliais/metabolismo , Feminino , Humanos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Papio , Biblioteca de Peptídeos , Peptídeos/metabolismo , Doenças Peritoneais/tratamento farmacológico , Doenças Peritoneais/patologiaRESUMO
Ten laboratory strains of oral microorganisms and 17 recent clinical isolates were examined for their ability to concentrate fluoride from a 1 ppm (0.05 mM NaF( fluoride solution. The laboratory strains concentrated the ion from two- to six-fold over the surrounding media. Clinical isolates of Actinomyces concentrated the ion to similar levels to the laboratory strains of this organism; however, clinical isolates of Streptococcus mutans and S. sanguis concentrated the fluoride significantly less than any of the laboratory strains examined.
