P2X receptors are ion channels gated by extracellular ATP. We report here cloning of a P2X 2 receptor splice variant (P2X2_2) carrying a 207 bp deletion in the intracellular Cterminus and the analysis of the corresponding genomic structure of the P2X 2 gene. P2X 2 _2 is as highly expressed as the original P2X 2 sequence in various tissues. ATP-activated currents mediated by heterologous expressed P2X 2 or P2X2_ 2 receptors showed significant differences in desensitization time constants and steady-state currents in the continuous presence of ATP. These results imply functional differences between cells differentially expressing these P2X 2 isoforms.
We investigated whether there is a relationship between loss of p16(INK4a) protein expression and p53 alterations in head and neck squamous cell carcinomas (HNSCCs). For this purpose, immunohistochemistry was performed on tissue microarrays of 664 tumours; this represents the largest HNSCC cohort studied for molecular biomarkers. Loss of p16(INK4a) protein expression was associated with aberrant p53 expression (negative or overexpressed) in the total cohort, and with TP53 mutations in 200 tumours analysed (p < 0.0001 each). Both loss of p16(INK4a) expression and p53 alterations differed significantly across both tumour sites and stages, being more prevalent in the hypopharynx than in the other tumour sites and in advanced tumour stages. As a possible link between p53 status and p16(INK4a) loss, we found that increased DNA methyltransferase 1 protein levels occurred preferentially in tumours with aberrant p53 (p = 0.001) and negative p16(INK4a) expression (p = 0.0004). In the total cohort, there was a borderline significant difference in patient survival across three p16(INK4a) expression levels (negative, positive, high), with loss of p16(INK4a) expression showing shortest survival. It is suggested that loss of p16(INK4a) expression and p53 alterations should be viewed as related events involved in the early carcinogenic process.
The TOI-14 constitutes the first worldwide-validated, disease-specific instrument to measure HR-QOL in adults with CTO. Due to its ease of use, it can be utilized both in the outcome research and in clinical routine.
Objective: The treatment strategy of squamous cell carcinoma of the nasal vestibule (SCCNV) is controversial. The objective of this study is to investigate the role of surgery, which is the preferred treatment option at our institution. Design: This was a monocentric prospective study of patients that were diagnosed with SCCNV between 2005 and 2013. Material and Methods: Twenty-six patients were included. Tumors were staged using the UICC (7th edition) TNM classification of nasal cavity cancer and the classification proposed by Wang. The primary treatment was surgery in all patients. Survival data were statistically analyzed using the Kaplan-Meier method. The median follow-up time was 6 years. Results: Using the UICC classification, 9/26 tumors were staged as pT1 (35%), 7/26 as pT2 (27%), and 10/26 as pT4a (39%). Using the classification by Wang, 9/26 tumors were staged as pT1 (35%), 15/26 as pT2 (58%), and 2/26 as pT3 (8%). Reconstruction was performed using an implant-retained prosthesis in 50% of patients and by plastic surgery in the remaining 50%. Only 2/26 patients (8%) needed adjuvant radiation therapy. The five-year recurrence-free survival (RFS) was 86.7%, disease-specific survival was 96.2% and overall survival was 91.8% after five years. Conclusion: Surgery in SCCNV gives an excellent prognosis and minimized the need for radiotherapy.
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