ABSTRACT
PURPOSE: The Sino-Nasal-Outcome-Test-22 (SNOT-22) represents the reference questionnaire to assess symptoms, health-related quality-of-life (HRQOL) and treatment-response in patients with chronic rhinosinusitis (CRS). The SNOT-22 has been validated for various languages, yet no validation is available for the German version. Thus, we provide a validation of the SNOT-22 for German. METHODS: In this prospective observational study 139 CRS-patients and 36 control-participants were included. CRS-patients completed the German-SNOT-22 before treatment (T0) and four (T1), twelve (T2) and 48 weeks after inclusion (T3). At T0, Mackay-Naclerio-, Lund-Mackay- and Brief-Symptom-Inventory-18 (BSI-18) scores were collected as external reference for the German-SNOT-22 and its subscales. At T1, T2, and T3 health-transition-items (HTIs) were raised to explore responsivity. Control-participants completed the German-SNOT-22 at T0. Reliability (internal consistency, item-total correlation), validity (concurrent validity, discriminatory validity) and responsiveness (distribution- and anchor-based) were explored for the German-SNOT-22. RESULTS: At T0, the mean German-SNOT-22 total-score for CRS patients was 38.0 (± 20.9) and responded to treatment (T1 = 26.3 ± 19.1; T2 = 25.8 ± 20.6; T3 = 20.5 ± 16.3). For control-participants, the mean total-score at T0 was 15.1 (±10.9). The German-SNOT-22 was reliable (excellent internal consistency α = 0.93; good overall item-total correlations r = 0.39-0.85), valid (significant correlations between Mackay-Naclerio-, Lund-Mackay- and BSI-18 scores, all r > 0.39, p < 0.01) and responsive (significant correlations between HTIs and mean change in German-SNOT-22 total-score F = 9.57, p < 0.001). CONCLUSION: The German-SNOT-22 validated here matches the original SNOT-22. It is a reliable, valid and responsive questionnaire to assess symptoms, HRQOL and treatment-response in CRS-patients. Good psychometric properties were observed.
Subject(s)
Psychometrics/methods , Quality of Life/psychology , Rhinitis/diagnosis , Rhinitis/psychology , Sino-Nasal Outcome Test , Sinusitis/psychology , Adolescent , Adult , Aged , Chronic Disease , Female , Germany , Humans , Language , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Sinusitis/diagnosis , Young AdultABSTRACT
BACKGROUND: Epithelial to mesenchymal transition (EMT) promotes therapy resistance in head and neck cancer (HNC) cells. In this study, EMT was quantified in HNC tumor samples by the cellular co-localization of cytokeratin/vimentin, Ecadherin/ßcatenin and by Slug expression. METHODS: Tissue samples from HNC patients were stained with antibody pairs against cytokeratin/vimentin and E-cadherin/ß-catenin. Epithelial-mesenchymal co-localization was quantified using immunofluorescence multichannel image cytometry. Double positivity was confirmed using confocal microscopy. Slug was semi-quantified by 2 specialists and quantified by bright field image cytometry. RESULTS: Tumor samples of 102 patients were investigated. A loss of E-cadherin positive cells (56.9 ± 2.6% vs. 97.9 ± 1.0%; p < 0.0001) and E-cadherin/ß-catenin double positive cells (15.4 ± 5.7% vs. 85.4 ± 1.2%; p < 0.0001) was observed in tumor samples. The percentage of Slug positive cells was increased in tumor samples (12.1 ± 3.6% vs. 3.2 ± 2.6%; p = 0.001). Ordinal Slug scores judged by two specialists closely correlated with percentage of Slug-positive cells (Spearman's rho = 0.81; p < 0.001). Slug score correlated negatively with the percentage of E-cadherin positive cells (r = 0.4; p = 0.006), the percentage of E-cadherin/ß-catenin positive cells (r = 0.5; p = 0.001) and positively with cytokeratin/vimentin positive cells (r = 0.4, p = 0.003). CONCLUSION: EMT can be assessed in HNC tumor probes by cytokeratin/vimentin co-expression and loss of E-cadherin/ß-catenin co-expression. Slug score provides a convenient surrogate marker for EMT.
ABSTRACT
Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects.
