In an effort to identify a clinical biomarker for lung cancer, we used cDNA microarray and 2D protein analyses to demonstrate that increased Fas-associated death domain (

The presence of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) is the strongest determinant of patient prognosis. Owing to the impact of nodal metastases on patient survival, a system for sensitive and accurate detection is required. Clinical staging of lymph nodes is far less accurate than pathological staging. Pathological staging also suffers limitations because it fails to detect micrometastasis in a subset of nodal specimens. To improve the sensitivity of existing means of diagnosing metastatic disease, many advocate the use of molecular markers specific for HNSCC cells. MicroRNA (miRNA) are short noncoding segments of RNA that posttranscriptionally regulate gene expression. Approximately one third of all miRNA will exhibit substantial tissue specificity. Using a quantitative reverse transcription-polymerase chain reaction-based assay, we examined the expression of microRNA-205 (mir-205) across tissues and demonstrated that its expression is highly specific for squamous epithelium. We applied this assay to tissue samples, and we could detect metastatic HNSCC in each positive lymph node specimen, whereas benign specimens did not express this marker. When compared to metastases from other primary tumors, HNSCC-positive lymph nodes were distinguishable by the high expression of this marker. Using an in vitro lymphoid tissue model, we were able to detect as little as one squamous cell in a background of 1 million lymphocytes. By combining the sensitivity of quantitative reverse transcription-polymerase chain reaction with the specificity of mir-205 for squamous epithelium, we demonstrate a novel molecular marker for the detection of metastatic HNSCC.

Objectives/Hypothesis The purposes of this preclinical study were to investigate histologic and rheologic outcomes of Microendoscopy of Reinke’s space (MERS)-guided minithyrotomy and to assess its instrumentation. Study Design Human cadaveric and in vivo animal study. Methods Three human cadaveric larynges were treated with MERS-guided placement of Radiesse VoiceGel and immediately evaluated histologically for biomaterial location. In the second part of this investigation, two scarred porcine larynges were treated with MERS-guided placement of HyStem-VF and rheologically evaluated 6 weeks later. Student t tests determined differences in viscoelastic properties of treated/untreated vocal folds. Sialendoscopes and microendoscopes were subjectively compared for their visualization capacity. Results MERS imaged the subepithelial area and vocal ligament, guiding both tissue dissection and biomaterial positioning. Sialendoscopes provided adequate visualization and feature incorporated working channels. Enhanced image clarity was created in a gas-filled rather than saline-filled environment, per rater judgment. Histological analysis revealed desirable biomaterial positioning with MERS. Per rheological analysis, viscoelastic properties of the MERS-treated porcine vocal folds compared to uninjured vocal folds 6 weeks following treatment did not statistically differ. Conclusions MERS-guided laryngoplasty using sialendoscopes yielded satisfactory biomaterial positioning in the short-term and normalized rheologic tissue properties in the long-term, contributing to proof of concept for MERS in the treatment of scarring. Strengths of MERS include direct, real-time visualization of Reinke’s space and an ability to manipulate surgical instruments parallel to the vocal fold edge while maintaining an intact epithelium. Future work will explore the clinical utility of MERS for addressing scarring, sulcus vocalis, and other intracordal processes.

We confirm the feasibility of minimal-access arytenoid adduction and abduction through development of a new technique and device.

Squamous cell carcinoma of the head and neck (SCCHN) is a major health problem worldwide, with over 45,000 new cases predicted to occur in the United States in 2009. Adjuvant therapies that can augment established treatments for SCCHN without causing significant additional morbidity are needed for this disease. Cyclooxygenase-2 (COX-2) inhibition has emerged as a potential adjuvant to established treatment regimens for SCCHN with this concept in mind, as COX-2 is known to be overexpressed in SCCHN. Celecoxib is a COX-2 specific NSAID with known antineoplastic activity against many human tumors, and is currently being used in clinical trials as a chemopreventive agent and adjuvant to established chemotherapy and radiation therapy protocols. The underlying mechanism of celecoxib toxicity remains poorly understood. Previous work from our laboratory has demonstrated marked inhibition of cell cycle progression through the G1 phase and induction of apoptosis following treatment with celecoxib in SCCHN, leading to cell cycle phase-specific toxicity to S and G2 phase cells and induction of p21waf1/cip1 with downstream inhibition of nuclear E2F activity. We therefore hypothesize that decreasing the observed cell cycle inhibition induced by celecoxib treatment may augment celecoxib toxicity by inducing cells to progress through more highly toxic cell cycle phases during celecoxib exposure. Further understanding of the mechanism of G1 arrest following celecoxib administration is therefore needed to effectively exploit this potential toxicity. MicroRNAs have been implicated in the control of cell cycle transition in several recent publications in stem cells and human cancers, and we believe that they may be involved in the cell cycle arrest seen after celecoxib treatment in SCCHN. To evaluate this hypothesis, SCCHN cells were exposed to celecoxib for 24 hours and G1 arrest was confirmed via flow cytometry. RNA and protein were extracted from celecoxib-treated and control cells and microRNA expression profiles were established by quantitative real-time PCR microarray analysis. Alterations in cell cycle gene expression across the cell cycle were assessed by similar microarray, and targets were confirmed by further western blotting and PCR analysis. Correlations between microRNA alterations in celecoxib-treated cells and cell cycle control genes were observed and extrapolated. These data provide a microRNA and cell cycle gene expression signature for celecoxib treatment in SCCHN, and further illustrate the potential role that microRNA expression plays in control of G1 cell cycle checkpoint kinetics and subsequent celecoxib toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3009.