RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC

Effects of quaternary ammonium silane coatings on mixed fungal and bacterial biofilms on tracheoesophageal shunt prostheses

Two quaternary ammonium silanes (QAS) were used to coat silicone rubber tracheoesophageal shunt prostheses, yielding a positively charged surface. One QAS coating [(trimethoxysilyl)-propyidimethylocta-decylammonium chloride] was applied through chemical bonding, while the other coating, Biocidal ZF, was sprayed onto the silicone rubber surface. The sprayed coating lost its stability within an hour, while the chemically bonded coating appeared stable. Upon incubation in an artificial throat model, allowing simultaneous adhesion and growth of yeast and bacteria, all coated prostheses showed significant reductions in the numbers of viable yeast (to 12% to 16%) and bacteria (to 27% to 36%) compared with those for silicone rubber controls, as confirmed using confocal laser scanning microscopy after live/dead staining of the biofilms. In situ hybridization with fluorescently labeled oligonucleotide probes showed that yeasts expressed hyphae on the untreated and Biocidal ZF-coated prostheses but not on the QAS-coated prostheses. Whether this is a result of the positive QAS coating or is due to the reduced number of bacteria is currently unknown. In summary, this is the first report on the inhibitory effects of positively charged coatings on the viability of yeasts and bacteria in mixed biofilms. Although the study initially aimed at reducing voice prosthetic biofilms, its relevance extends to all biomedical and environmental surfaces where mixed biofilms develop and present a problem

Prediction of survival and therapy outcome with C-11-tyrosine PET in patients with laryngeal carcinoma

Choosing the optimal treatment for an individual with squamous cell carcinoma of the head and neck is a difficult challenge because of the unpredictable clinical behavior of this malignancy. A reliable method for assessing the clinical behavior and predicting the radiocurability of tumors would assist in the therapy strategy and prognosis. This study evaluated whether quantitative PET using L-[1-C-11]-tyrosine (TYR) has predictive value for survival and therapy outcome in patients with primary squamous cell carcinoma of the larynx. Methods: Thirty-four patients with histologically confirmed laryngeal carcinomas underwent dynamic C-11-TYR PET before receiving definitive therapy. Various methods for quantification of tumor activity were used: assessment of protein synthesis rate (PSR), calculation of standardized uptake value, and estimation of tumor-to-nontumor ratio. Treatment consisted of radiotherapy (n = 20) or surgery (n 14). The median follow-up was 40 mo. Results: All malignancies were identified correctly, with no false-negative results. Cumulative survival was compared between patients with tumor PSR equal to or higher than the median (2.0 nmol/ml/min) and those with tumor PSR lower than the median and was found not to be significantly different (P 0.07). When the radiotherapy group was evaluated separately, the difference in survival was significant (P = 0.03; 5-y survival, 30% vs. 73%) and high C-11-TYR uptake correlated with poor prognosis. In multivariate analysis, PSR was an independent predictor for survival. Because differences (P = 0.08) between patients with and patients without recurrence were not significant, no predictive value of PSR for disease recurrence could be demonstrated. Conclusion: Prediction of survival of patients undergoing radiotherapy for laryngeal squamous cell carcinoma is feasible primarily by using C-11-TYR PET to quantify activity before treatment

Treatment outcome of bone-anchored craniofacial prostheses after tumor surgery

BACKGROUND. Percutaneous endosseous implants have acquired an important place in the prosthetic rehabilitation of patients with craniofacial defects. The objective of this study was to evaluate the clinical outcome of the use of endosseous implants in the orbital and auricular region as well as to assess the satisfaction of patients with implant-retained craniofacial prostheses after tumor surgery. METHODS. The clinical outcome and patient satisfaction of implant-retained prostheses in the auricular and orbital region were evaluated in a group of 26 patients with facial defects after tumor surgery. by using standardized questionnaires and a clinical assessment. Twelve patients (n = 31 implants) received the implants during ablative tumor surgery, from which 7 patients (n = 20 implants) were treated with radiation therapy after surgery (mean, 65 grays [Gy]). Fourteen patients (n = 44 implants) received the implants after the tumor surgery, from which 5 patients (n = 21 implants) were irradiated after ablative surgery (mean, 54.4 Gy), but before implant placement. RESULTS: No implants were lost in patients who had not undergone irradiation (100%), whereas 5 implants were lost in the irradiated group (87.8%). The overall implant survival rate was 93.3%. The peri-implant tissues had a healthy appearances and no cases of osteoradionecrosis occurred. When compared with patients treated with conventional adhesive retained facial prostheses, satisfaction was higher in patients treated with implant-retained facial prostheses. CONCLUSIONS. From this study, it is concluded that implant-retained facial prostheses are better tolerated than adhesive retained prostheses and offer an improvement in the quality of life. Radiotherapy is not a contraindication for the use of osseointegrated implants in the maxillofacial region, but the loss of implants is higher than in nonirradiated sites. (C) 2001 American Cancer Society

F-18-FLT PET for visualization of laryngeal cancer:Comparison with F-18-FDG PET

The feasibility of F-18-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with F-18-FDG PET. Methods: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected F-18-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) F-18-FLT and attenuation-corrected F-18-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) F-18-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on F-18-FDG PET and F-18-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for F-18-FLT and F-18-FDG. Wilcoxon nonparametric testing was used for comparison of F-18-FDG with F-18-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of F-18-FDG PET and F-18-FLT PET. Two-tailed P value