Genevieve A. Andrews

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.

Mutation of p53 in head and neck squamous cell carcinoma correlates with Bcl‐2 expression and increased susceptibility to cisplatin‐induced apoptosis

The p53 protein, a well‐known tumor suppressor that functions primarily as a transcription factor, initiates cell cycle arrest and apoptosis after genotoxic stress. The antiapoptotic regulator Bcl‐2 is a downstream modulator of p53‐induced apoptosis. Loss of function of the p53 tumor suppressor through mutation is an important event that contributes to cellular transformation. Mutation of p53 is one of the most common genetic alterations in squamous cell carcinomas of the head and neck (SCCHN). We hypothesized that p53 mutation is associated with Bcl‐2 expression and susceptibility to apoptosis in SCCHN.

Postradiotherapy neck dissection for head and neck squamous cell carcinoma: pattern of pathologic residual carcinoma and prognosis.

For patients with head and neck cancer who were treated using primary radiotherapeutic approaches, the pattern of pathologic residual carcinoma in the neck dissection specimen and its effect on clinical outcome remains unknown.

Incidence of Venous Thromboembolism in Otolaryngology–Head and Neck Surgery

OBJECTIVE To examine the incidence of venous thromboembolic disease in the otolaryngology-head and neck surgery (OTO-HNS) patient population. DESIGN, SETTING, AND PATIENTS Review of medical records for all patients undergoing a surgical procedure during fiscal years 2008 to 2011 (July 1, 2008, through June 30, 2011) at an academic tertiary care medical center. INTERVENTION A total of 59 884 total surgical procedures among all the surgical services. MAIN OUTCOME MEASURES The incidence of deep venous thrombosis and pulmonary embolism. RESULTS There were 5616 otolaryngology procedures performed during the study period. Clinically evident deep venous thrombosis developed in 3 patients; 2 of these patients also developed a pulmonary embolism. The overall incidence of deep venous thrombosis and pulmonary embolism in OTO-HNS was 0.05% and 0.035%, respectively. All patients who developed deep venous thrombosis or a pulmonary embolism in the OTO-HNS population were inpatients being treated for cancer. There were no deep venous thromboses or pulmonary emboli in patients undergoing same-day or overnight surgery or in patients without an active cancer. The OTO-HNS service had significantly lower rates of venous thromboembolism than did most other surgical specialties despite lower rates of adherence to venous thromboembolism prophylaxis guidelines. CONCLUSIONS The incidence of deep venous thrombosis and pulmonary embolism among the OTO-HNS patient population at our academic center is lower than the incidence reported in previous studies (range, 0.1%-0.3%) and is significantly lower than the incidence observed in other surgical specialties. It is likely that patient- and specialty-specific factors as well as the more aggressive use of venous thromboembolism prophylaxis during recent years are at least partially responsible for the decreased incidence in our population.

Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model.

We investigated the effects of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR‐2) and epidermal growth factor receptor (EGFR), alone and in combination with paclitaxel in an orthotopic mouse model of human head and neck squamous cell carcinoma (HNSCC).

Current practices in venous thromboembolism prophylaxis in otolaryngology–head and neck surgery

There has been recent investigation into the incidence of venous thromboembolism in otolaryngology, but the current utilization of venous thromboembolic (VTE) prophylaxis among practicing otolaryngologists remains largely unknown.

HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells.

The purpose of this study was to identify mechanisms of innate resistance to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Specifically, we analyzed the role of HRAS mutations in erlotinib resistance.

Technical refinement of ultrasound-guided transoral resection of parapharyngeal/retropharyngeal thyroid carcinoma metastases.

The transoral approach to the parapharyngeal and retropharyngeal space (PPS/RPS) for the management of well‐differentiated thyroid carcinoma (WDTC) has been previously described in other articles. However, limited exposure with this approach can be a challenge.

Nonsurgical management of oropharyngeal, laryngeal, and hypopharyngeal cancer: The Fox Chase Cancer Center experience

Oropharyngeal, laryngeal, and hypopharyngeal cancer treatment has changed at our institution, but survival outcomes have not been evaluated.