Type III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)-28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls. All type III IFN family members were detected in ductal and acinar epithelia of MSGs from both SS patients and sicca controls. IFN-λ2/IL-28A and IFN-λ3/IL-28B were also expressed in infiltrating mononuclear cells. In SS patients with intermediate MSG lesions, the epithelial expression of IFN-λ2/IL-28A was more intense compared to sicca controls (P < 0·05). The receptor IFN-λR1/IL-28Ra was detected in all types of cells except fibroblasts, and was exceptionally strong in plasmatocytoid dendritic cells, indicating that they are susceptible to type III IFN-mediated regulation. In the periphery, only IFN-λ1/IL-29 was detected in the sera and was elevated significantly in SS patients with intermediate MSG inflammatory lesions compared to sicca controls (P = 0·0053). None of the type III IFNs was expressed constitutively in resting SGECs; they were all induced readily by TLR-3 stimulation, suggesting that the in-situ epithelial expression can be attributed to local microenvironment. Type III IFNs are expressed in MSGs in a similar pattern to type I IFNs and their expression is probably subjected to micro-environmental regulation, suggesting that they are implicated in the inflammatory processes occurring in the affected exocrine glands.
This was an open, randomized, cross-over study comparing the efficacy and acceptability of aqueous nasal suspensions of budesonide, 200 micrograms b.i.d. and beclomethasone dipropionate (BDP), 100 micrograms q.i.d., each given for 6 weeks to patients with perennial rhinitis and a history of allergy. Forty men and women aged 18-65 years with perennial rhinitis diagnosed at least 1 year previously, were recruited for study provided they had at least two of the following symptoms of rhinitis--blocked nose, runny nose, itching nose or sneezing. They were requested to record the presence or absence of nasal and ocular symptoms on a severity scale of 0-3 (none, mild, moderate, severe) in daily diary cards. The sum of the nasal scores was calculated to give the total nasal symptom score. Mean individual symptom scores and total symptom score were calculated for each treatment. Thirty-seven patients completed the study. The mean total nasal symptom score was significantly lower during budesonide (2.13) than during BDP (2.75), P = 0.001. There were significantly fewer reports of blocked nose (P = 0.004), runny nose (P = 0.0005) and sore eyes (P = 0.047) during budesonide treatment compared with BDP. Four patients reported adverse events during budesonide treatment (two had nosebleeds and two nasal dryness) and three patients during BDP treatment (two had nasal dryness and one gastric discomfort). A significantly greater proportion of patients stated a preference for budesonide than for BDP on the basis of effect (P = 0.0001), side-effects (P = 0.01), and overall (P = 0.0001).
Overexpression of Epidermal Growth Factor Receptor (EGFR) and also of cell cycle control proteins, such as cyclin D1 is a frequent event in squamous cell carcinoma of the larynx (LSSC). Our aim was to correlate their protein levels with telomerase catalytic subunit (h-TERT) expression. Using tissue microarray technology, fifty-five paraffin embedded histologically confirmed primary LSSCs and also ten dysplastic lesions were cored at a diameter of 1.5 mm. Immunohistochemistry (IHC) was performed by the use of anti-EGFR, anti-cyclin D1, and anti-h TERT monoclonal antibodies. Chromogenic in situ hybridization (CISH) analysis was also applied using EGFR gene and chromosome 7 probes, respectively. EGFR, cyclin D1 and h-TERT protein overexpression was observed in 48/55 (87.2%), 19/55 (34.5%) and 21/55 (38.1%) carcinoma cases, respectively. EGFR protein expression was statistically associated with grade (P=0.01), and also with stage (P=0.001) of the examined tumors. Borderline statistical significance was assessed correlating overall cyclin D1 expression to h TERT expression (P=0.06). Simultaneous up regulation of the three proteins was established in 7/55 (12.7%) cases, correlated to the stage of the tumors (P=0.05). EGFR gene amplification was observed in 7/65 (10.7%) carcinomas and dysplasias, whereas chromosome 7 aneuploidy was detected in 4/65 (6.1%) of those cases.Simultaneous up regulation of EGFR, cyclin D1 and h TERT proteins correlates with advanced stage in LSCC. EGFR gene amplification and not only protein over expression maybe is the eligible criterion for targeted therapeutic strategies in those patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.