Microenvironment Changes (in pH) Affect VEGF Alternative Splicing

Vascular endothelial growth factor-A (VEGF-A) has several isoforms, which differ in their capacity to bind extracellular matrix proteins and also in their affinity for VEGF receptors. Although the relative contribution of the VEGF isoforms has been studied in tumor angiogenesis, little is known about the mechanisms that regulate the alternative splicing process. Here, we tested microenvironment cues that might regulate VEGF alternative splicing. To test this, we used endometrial cancer cells that produce all VEGF isoforms as a model, and exposed them to varying pH levels, hormones, glucose and CoCl2 (to mimic hypoxia). Low pH had the most consistent effects in inducing variations in VEGF splicing pattern (VEGF121 increased significantly, p < 0.001, when compared to VEGF145, 165 or 189). This was accompanied by activation of the p38 stress pathway and SR proteins (splicing factors) expression and phosphorylation. SF2/ASF, SRp20 and SRp40 down-regulation by siRNA impaired the effects of pH stimulation, blocking the shift in VEGF isoforms production. Taken together, we show for the first time that acidosis (low pH) regulates VEGF-A alternative splicing, may be through p38 activation and suggest the possible SR proteins involved in this process

Parotid gland tumors in Northern Greece: a 7-year retrospective study of 207 patients

Introduction: Parotid gland neoplasms represent a heterogenous group of tumors, either benign or malignant. The diagnosis and management of parotid gland tumors is complicated by their relative infrequency and their diverse biologic behavior. Aim: The aim of this study is to investigate the epidemiological characteristics, the recurrence rates and the surgical approach employed for parotid gland tumors in Northern Greece. Material and methods: This is a single-center retrospective study. All patients admitted to the ENT department of “G. Papanikolaou” General Hospital of Thessaloniki from January 2012 to June 2019 with the diagnosis of parotid gland tumor were included in the study. Patients with incomplete charts and patients that underwent revision surgeries were excluded. Chi-squared tests were used to assess the associations between variables. Results: A total of 207 patients with a mean age of 54.97 (range 16–91) were included in the study. Benign neoplasms accounted for 87.9% of the cases. Warthin’s tumor was the most common neoplasm encountered, with an incidence of 46.8%, followed by pleomorphic adenoma (31.9%). There was a higher incidence of parotid gland tumors in males and smokers (P = 0.025, P = 0.001 respectively). The majority of the patients were treated with an extracapsular resection (60.4%) or with a partial superficial parotidectomy (22.6%). In 12 cases (5.7%), there was a recurrence of the lesion. The most common complications encountered were facial nerve injury, Frey’s syndrome and hematoma formation. Conclusions: Parotid gland tumors are typically benign, non-aggressive tumors, more frequently seen in men than women. There is a positive association between smoking and parotid gland tumor development. Comprehensive information regarding recurrence and complication rates is presented