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Biomedical subjects

Michael S Benninger

Publications and source records attributed to Michael S Benninger.

At least 19 recordsLinked to original sources
PubMed2006

Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a), and MTAP genes in head and neck squamous cell carcinoma.

OBJECTIVE: To identify the extent and the smallest region of loss for CDKN2B(INK4b), CDKN2A(ARF,INK4a), and MTAP. Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines and are common in squamous cell carcinoma of the head and neck (HNSCC). This complex region encodes the tumor suppressor genes cyclin-dependent kinase 2B (CDKN2B) (p15(INK4b)) and CDKN2A (p14(ARF), p16(INK4a)) and the housekeeping gene methylthioadenosine phosphorylase (MTAP). DESIGN: A targeted probe panel designed to finely map the region of 9p21 loss comprised 3 probes for CDKN2B(INK4b), 7 for CDKN2A(ARF, INK4a), and 3 for MTAP and was interrogated using the multiplex ligation-dependent probe amplification assay (MLPA). The MLPA genomic copy number alterations for CDKN2A were validated using real-time polymerase chain reaction. SUBJECTS: Six HNSCC primary (A) and recurrent or metastatic (B) cell lines were examined: UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B. RESULTS: Cell line UMSCC-11B retained all 9p loci tested in the region. Cell lines UMSCC-17A/B indicated homozygous deletion of CDKN2A(ARF, INK4a) starting at p16(INK4) exon 1alpha to include exons 2 and 3. Homozygous loss was indicated for CDKN2B(INK4b) and CDKN2A(ARF,INK4a) in UMSCC-11A, and UMSCC-81A. Cell line UMSCC-81B indicated retention of all 9p loci except for exon 1alpha (p16(INK4a)). Selective loss of the 3' end of MTAP was observed in UMSCC-11A. Genomic alterations by fine-mapping MLPA were validated at the DNA level for CDKN2A. CONCLUSIONS: We identified exon 1alpha (p16(INK4a)) as the smallest region of loss in the CDKN2A(ARF, INK4a) gene. The frequency and precise loss of CDKN2B(INK4b), CDKN2A(ARF, INK4a), and MTAP in the prognosis of 9p21-deleted HNSCC may provide impetus for use of these targets as therapeutic biomarkers in head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed2006

Epigenetic events of disease progression in head and neck squamous cell carcinoma.

OBJECTIVE: To examine the promoter methylation status of the 22 cancer genes and their contribution to disease progression in 6 head and neck squamous cell carcinoma (HNSCC) cell lines. DESIGN: A panel of 41 gene probes, designed to interrogate 35 unique genes with known associations to cancer including HNSCC, was interrogated for alterations in gene copy number and aberrant methylation status (22 genes) using the methylation-specific multiplex ligation-dependent probe amplification assay. SUBJECTS: Primary (A) and recurrent or metastatic (B) HNSCC cell lines UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B are described. RESULTS: Nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT, ESR1, and DAPK1, were aberrantly methylated. The most frequently hypermethylated genes were APC and IGSF4, observed in 3 of 6 cell lines, and TP73 and DAPK1, observed in 2 of 6. For KLK10 and IGSF4, TIMP3 and FHIT, and TP73, in UMSCC-11B, UMSCC-17B, and UMSCC-81B, respectively, promoter hypermethylation was a disease progression event, indicating complete abrogation of tumor suppressor function for KLK10, IGSF4, and TIMP3 and gene silencing of 1 of 2 copies of TP73. Hypermethylation of IGSF4, TP73, CDH13, ESR1, DAPK1, and APC were primary events in UMSCC-17A. CONCLUSIONS: Gene silencing through promoter hypermethylation was observed in 5 of 6 cell lines and contributed to primary and progressive events in HNSCC. In addition to genetic alterations of gains and losses, epigenetic events appear to further undermine a destabilized genomic repertoire in HNSCC.

Carcinoma, Squamous Cell↗
PubMed2006

Endoscopically directed middle meatal cultures versus maxillary sinus taps in acute bacterial maxillary rhinosinusitis: a meta-analysis.

OBJECTIVE: The aim of this study was to verify the correlation of endoscopically directed middle meatal (EDMM) cultures with maxillary sinus tap and culture (MST) in acute bacterial rhinosinusitis (ABRS). STUDY DESIGN AND METHODS: Meta-analysis of the previous literature, unpublished data, and a prospective trial supported by the Sinus & Allergy Health Partnership. EDMM and MST cultures were obtained and their results compared. Inclusion for both the unpublished and prospective trial as well as prior published literature in the meta-analysis required the studies to compare EDMM versus MST in the acute setting of bacterial rhinosinusitis with both symptomatic and radiologic evidence of ABRS. RESULTS: Three articles and 1 national presentation were identified for inclusion. Additional data from unpublished studies and the prospective trial were combined. The pooled data consisted of 126 patients with 131 culture pairs. For known pathogenic bacteria for ABRS and in comparison to MST, EDMM had a sensitivity of 80.9%, a specificity of 90.5%, a positive predictive value of 82.6%, a negative predictive value of 89.4%, and an overall accuracy of 87.0% (95% confidence interval, 81.3%-92.8%); 70.5% (12/17) of false positive culture pairs were of known pathogens for ABRS that would not be expected to be contaminants. CONCLUSIONS AND SIGNIFICANCE: This meta-analysis shows that EDMM is a highly sensitive and accurate culture method for acute ABRS and may be more sensitive than MST given the presence of pathogenic bacteria not found on antral lavage. EDMM is a viable, and possibly preferred, culture method for determining antimicrobial efficacy and bacterial resistance patterns. EBM RATING: A-1a.

Endoscopy↗
PubMed2006

Diagnosis and management of laryngopharyngeal reflux disease.

PURPOSE OF REVIEW: The recent findings and up-to-date practice guidelines for diagnosing, evaluating, and treating gastro-esophageal reflux disease are discussed. RECENT FINDINGS: The patient complaints for reflux disease are crucial in diagnosis. Although physical examination findings may correlate with laryngopharyngeal reflux, these findings may not improve after an adequate course of treatment. Behavioral modifications are a critical part of improving reflux; however, weight loss has not been shown to improve laryngopharyngeal reflux disease. Patients who used proton-pump inhibitors and histamine blockers were shown to have increased risk of developing Clostridium difficile infections. Laryngopharyngeal reflux has been shown to be a better predictor of Barrett's esophagus than gastroesophageal reflux, although specific screening recommendations have not been determined. SUMMARY: Current studies in laryngopharyngeal reflux demonstrate that improvements in physical examination findings are not a reliable way of determining patient improvement. An empiric trial of therapy is the best diagnostic test for laryngopharyngeal reflux. Future studies will examine the role of transnasal esophagoscopy in the screening of the laryngopharyngeal reflux patient for Barrett's esophagus.

Gastroesophageal Reflux↗
PubMed2005

An approach to the diagnosis and management of acute bacterial rhinosinusitis.

The management of patients presenting with nasal congestion, rhinorrhea and facial pressure poses a challenge due to the nonspecific nature of these symptoms. A systematic approach to diagnosing acute bacterial rhinosinusitis is essential prior to offering therapies. This review offers an overview of current definitions, diagnostic algorithms and medical therapies available for the management of acute bacterial rhinosinusitis. Antimicrobial use for acute bacterial rhinosinusitis is substantial and carries a major impact on regional resistance patterns.

Acute Disease↗