Search

In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions. Targeted analysis of glucose metabolism pathways demonstrated a tendency towards a shift from tricarboxylic acid cycle (Krebs cycle) to glycolysis and anabolic reactions in cells treated with Poly(A:U). Glycolysis assays confirmed that TLR3 stimulation enhanced the capacity of malignant cells to switch from oxidative phosphorylation to extra-mitochondrial glycolysis. We found evidence that HIF-1α is involved in this process: addition of the TLR3 agonist resulted in a higher cell concentration of the HIF-1α protein, even in normoxia, whereas knocking-down TLR3 resulted in a lower concentration, even in hypoxia. Finally, we assessed TLR3 expression by immunohistochemistry in a series of 7 HNSCC specimens and found that TLR3 was detected at higher levels in tumors displaying a hypoxic staining pattern. Overall, our results demonstrate that TLR3 stimulation induces the Warburg effect in HNC cells in vitro, and suggest that TLR3 may play a role in tumor adaptation to hypoxia.

Background: The objective of this study was to report 11 cases of malignant head and neck paraganglioma and to compare their epidemiological, clinical, and genetic characteristics, their natural history and their treatment with those of a series of 131 benign paragangliomas., Patients and Methods: Retrospective analysis of 142 patients with head and neck paraganglioma managed between 2001 and 2008. Age at the time of diagnosis, gender, primary tumour site, presence of other non-head/neck paragangliomas and/or metastases diagnosed by imaging (CT, MRI, Octreoscan or (18)F-FDG PET), histology, urinary catecholamine and metanephrine levels, family history, and genetic test results were recorded., Results: This series comprised 131 benign head and neck paragangliomas, mostly observed in women with a mean age at diagnosis of 45 years and a predominance of tympanojugular sites (followed by carotid and vagal sites) with 5% of secreting tumours and 20% of multifocal tumours. Eleven patients (7.7%) with a 1:1 sex ratio presented criteria of malignancy. These patients, with a lower mean age (38 years), predominantly presented carotid lesions with a higher rate of secreting and multifocal tumours, 27% and 46% respectively. The main sites of metastases were bone and lymph nodes. No tympanic paragangliomas were observed., Conclusions: Malignant paragangliomas are mainly observed in young patients with multifocal tumours, particularly carotid tumours, and are predominantly related to subunit SDH-B mutation. The work-up in these high-risk patients must include whole body scintigraphy and spine MRI. Malignancy is not necessarily associated with a poor short-term prognosis due to the slow course of the disease., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: First Bite Syndrome (FBS) is a rare pain syndrome sometimes occurring after surgery of the upper cervical region. It presents as excruciating pain, triggered at the beginning of a meal by chewing, swallowing or even simple contact with generally acidic food, waning on subsequent bites and recurring with identical features after pausing for several minutes or at the next meal., Objectives: Retrospective review of 17 patients who developed FBS after upper cervical surgery., Results: Seventeen patients developed FBS between 1999 and 2010 following surgery for paraganglioma in eight cases, vagal or sympathetic schwannoma in five cases (including one malignant tumour), pleiomorphic adenoma in three cases and Warthin's tumour of the deep lobe of the parotid in one case. The cervical sympathetic trunk was sacrificed in 10 cases and the external carotid artery was ligated in six cases. Horner's sign was observed postoperatively in 12 patients. The characteristic pain of FBS was triggered by chewing or simple contact with essentially acidic food., Conclusion: FBS must be identified by the head and neck surgeon and distinguished from the usual postoperative pain. The generally accepted hypothesis is that of sympathetic denervation with parasympathetic secretory hyperactivity, but Horner's sign was present in only 12 of the 17 patients of our series, suggesting that other pathogenic mechanisms may be involved. FBS is difficult to treat, but the pain gradually becomes less severe. The patient must be informed about this rare complication that can impact on postoperative quality of life., (Copyright © 2013. Published by Elsevier Masson SAS.)