Citations

Abstract Objective The prevalence and mortality for head and neck cancer (HNC) has not improved significantly in the last several decades. It is the sixth most common cancer with an estimated 600,000 new cases diagnosed worldwide every year and has ∼50% 5-year survival rate. Of these, 47000 new cases are diagnosed in the US annually. The most common risk factors for HNC are tobacco and alcohol use but a growing subset is also attributed to human papillomavirus (HPV) infection. Late stage HNCs are treated with a combination of surgery, radiation, and chemotherapy (often platinum-based), but the cancers treated with platinum-based chemotherapy often develop drug resistance. Identification of target genes using high-throughput RNAi (HT-RNAi) gene-silencing technology has become an increasingly popular method in the field of cancer research. The objective of our study is to use this functional genomics based approach to identify genes that, when silenced, increase the sensitivity of the platinum drugs. This would possibly help us in identifying potentiators of platinum-based drugs to more effectively treat HNC patients. Methods We performed drug dose response (DDR) experiments on nine HNC cell lines; including two are HPV-positive lines, to identify cisplatin-resistant and -sensitive cancer cell lines. To identify sensitizers of cisplatin response, we used a siRNA library targeting 572 kinases. Each kinase is represented by two different siRNA sequences in the library. Based on the data mined from published literature on head and neck cancer as well as genes thought to confer a functional relationship between HPV infection and HNC, a more focused siRNA library was also designed and included in the screening. Cell lines were reverse transfected with the siRNAs in a 384 well format, dosed with cisplatin after 24 hours and the plates were read 72 hours later. Results We calculated the inhibitory concentrations using DDR experiments for all the nine HNC cell lines and identified cisplatin-resistant (UMSCC47 and SCC9) and -sensitive (Cal27, UMSCC14C, and SCC090) HNC cell lines. HT-RNAi experiments have been performed on the cisplatin-resistant cell lines, one of which is HPV-positive. After data analysis, confirmation of silencing and validation of drug modulation will be done on a subset of candidate genes. Conclusions HNC patients with surgically non-resectable tumors could have improved treatment with chemotherapeutic drugs; however, acquired drug resistance often inhibits a successful treatment. Identification of sensitizing targets may provide hope for a better outcome, but may also allow for use of smaller doses of more toxic drugs, such as cisplatin. In addition, this study may also identify alternate genes that can be targeted in the subset of HPV-positive HNC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5136. doi:1538-7445.AM2012-5136

Background Oral steroids are commonly used in the management of chronic rhinosinusitis (CRS) with and without nasal polyps (CRSwNP and CRSsNP, respectively). Past reports have included evaluation of the evidence for the use of oral steroids in CRS subtypes. However, a review with evidence‐based recommendations for all CRS subtypes has never been performed. The purpose of this article is to provide a comprehensive, evidence‐based approach for the utilization of oral steroids in the management of CRS. A systematic review of the literature was performed following recommendations of the Clinical Practice Guideline Manual, Conference on Guideline Standardization, and Appraisal of Guidelines and Research Evaluation. Inclusion criteria were: adult population ≥18 years old; CRS; oral steroids as the treatment group; and clearly defined primary clinical end‐point. This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Methods A systematic review of the literature was performed following recommendations of the Clinical Practice Guideline Manual, Conference on Guideline Standardization, and Appraisal of Guidelines and Research Evaluation. Inclusion criteria were: adult population ≥18 years old; CRS; oral steroids as the treatment group; and clearly defined primary clinical end‐point. This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Results This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Conclusion Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC.