Impact of Distraction Osteogenesis Maxillary Expansion on the Internal Nasal Valve in Obstructive Sleep Apnea.

OBJECTIVE: To assess the effect of distraction osteogenesis maxillary expansion (DOME) on objective parameters of the internal nasal valve and correlate findings with subjective outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: After Institutional Review Board approval, included subjects were those with obstructive sleep apnea, had undergone DOME from September 2014 to April 2018, and had cone beam computed tomography scans available before and after expansion. Measurement of the internal nasal valve parameters was performed with Invivo6 Software (version 6.0.3). Interrater reliability of all pre- and postexpansion parameters was measured. Patient-reported outcome measures included the Nasal Obstruction and Septoplasty Effectiveness Scale (NOSE) and Epworth Sleepiness Scale scores, and correlation between objective and subjective outcomes were evaluated by Spearman correlation analysis. RESULTS: Thirty-two subjects met inclusion criteria. All showed significant improvement in their subjective outcomes as well as an increase in their internal valve parameters. Significant correlation was observed between increased angles and improvement in postexpansion NOSE score (right angle, P = .024; left angle, P = .029). CONCLUSION: DOME widens the internal nasal valve objectively (dimensions), which correlates significantly with subjective improvement (NOSE scores).

HSP90 Inhibitor SNX5422/2112 Targets the Dysregulated Signal and Transcription Factor Network and Malignant Phenotype of Head and Neck Squamous Cell Carcinoma.

Heat shock protein 90 (HSP90) is a chaperone protein that stabilizes proteins involved in oncogenic and therapeutic resistance pathways of epithelial cancers, including head and neck squamous cell carcinomas (HNSCCs). Here, we characterized the molecular, cellular, and preclinical activity of HSP90 inhibitor SNX5422/2112 in HNSCC overexpressing HSP90. SNX2112 inhibited proliferation, induced G2/M block, and enhanced cytotoxicity, chemosensitivity, and radiosensitivity between 25 and 250 nM in vitro. SNX2112 showed combinatorial activity with paclitaxel in wild-type (wt) TP53-deficient and cisplatin in mutant (mt) TP53 HNSCC lines. SNX2112 decreased expression or phosphorylation of epidermal growth factor receptor (EGFR), c-MET, v-akt murine thymoma viral oncogene homolog 1 (AKT), extracellular signal-regulated kinases (ERK) 1 and 2, inhibitor κB kinase, and signal transducer and transcription factor 3 (STAT3), corresponding downstream nuclear factor κB, activator protein-1, and STAT3 reporter genes, and target oncogenes and angiogenic cytokines. Furthermore, SNX2112 enhanced re-expression of TP53 and targets p21WAF1 and PUMA, while TP53 inhibitor Pifithrin or siRNA attenuated the antiproliferative activity of SNX2112 in wtTP53 HNSCC in vitro. Prodrug SNX5422 similarly down-modulated key signal targets, enhanced TP53 expression and apoptosis, and inhibited proliferation, angiogenesis, and tumorigenesis in a wtTP53-deficient HNSCC xenograft model. Thus, HSP90 inhibitor SNX5422/2112 broadly modulates multiple key nodes within the dysregulated signaling network, with corresponding effects upon the malignant phenotype. Our data support investigation of SNX5422/2112 in combination with paclitaxel, cisplatin, and radiotherapy in HNSCC with different TP53 status.