Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation

Otite externa necrotizante com paralisia facial periférica bilateral: relato de caso e revisão da literatura Necrotizing external otitis with periferic bilateral facial palsy: case report and literature review

A otite externa necrotizante (OEN), conhecida no passado como otite externa maligna, é uma infecção potencialmente letal que começa usualmente no conduto auditivo externo e se estende à base do crânio ocorrendo, principalmente, em pacientes diabéticos idosos e que a despeito de antibioticoterapia prolongada está associada à morbidade elevada e mortalidade significante. Os autores apresentam o caso de um paciente adulto, diabético, com OEN e paralisia facial periférica bilateral que evoluiu com cura da infecção, porém sem melhora da paralisia.<br>Necrotizing external otitis (NEO), known in the past as malignant external otitis, is a potencial letal infection which begins usually in the external ear canal and spreads to the base of the skull. It occurs mainly in diabetic elderly patients who despite prolonged antibioticotherapy is associated to high morbidity and significant mortality. The authors present a case of an adult diabetic patient who developed NOE associated with bilateral periferic facial palsy evoluting with cure of the infection but without facial improvement