Toll-like receptors (TLR) expressed on inflammatory cells play a key role in host defense against pathogens, benefiting the host. TLR are also expressed on tumor cells. To evaluate the role of TLR in tumor cells, we investigated TLR4 signaling effects on human head and neck squamous cell carcinoma (HNSCC). Tumor tissues were obtained from 27 patients with laryngeal and 12 with oral cavity cancers. Normal mucosa was obtained from 10 patients with nonneoplastic disorders. Smears for bacteria were taken from all patients during surgery. TLR4 expression in tumors and HNSCC cell lines (PCI-1, PCI-13, and PCI-30) was detected by reverse transcription-PCR and immunohistochemistry. Cell growth, apoptosis, nuclear factor-κB (NF-κB) translocation, and MyD88 and IRAK-4 expression, as well as Akt phosphorylation were measured following tumor cell exposure to the TLR4 ligand lipopolysaccharide (LPS). Tumor cell sensitivity to NK-92–mediated lysis was evaluated in 4-hour 51Cr-release assays. Cytokine levels in HNSCC supernatants were measured in Luminex-based assays. TLR4 was expressed in all tumors, HNSCC cell lines, and normal mucosa. The TLR4 expression intensity correlated with tumor grade. LPS binding to TLR4 on tumor cells enhanced proliferation, activated phosphatidylinositol 3-kinase/Akt pathway, up-regulated IRAK-4 expression, induced nuclear NF-κB translocation, and increased production (P < 0.05) of interleukin (IL)-6, IL-8, vascular endothelial growth factor, and granulocyte macrophage colony-stimulating factor. TLR4 triggering protected tumor cells from lysis mediated by NK-92 cells. TLR4 ligation on tumor cells supports HNSCC progression.
Objectives PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME expression in tumors interferes with retinoic acid receptor (RAR) signaling thus promoting tumor progression. Here, we study PRAME expression in head and neck squamous cell carcinoma (HNSCC) to determine its potential clinical significance. Materials and Methods PRAME expression in HNSCC was evaluated by immunohistochemistry in tissue microarrays of primary tumors (n=53), metastatic lymph nodes (n=8) and normal oral mucosa (n=11). Biopsies of dysplastic oral lesions (n=12) were also examined. PRAME expression levels in tissues were correlated with markers of poor prognosis in HNSCC. PRAME mRNA in HNSCC cell lines and in normal immortalized human keratinocytes (HaCaT cell line) was measured by qRT-PCR, and the protein expression by flow cytometry and western blots. Results PRAME was expressed in HNSCC cell lines and HNSCC lesions. PRAME expression in dysplastic mucosa was variable. No or only weak expression was found in normal cells or tissues. PRAME expression levels significantly correlated with the tumor grade, size, nodal involvement and the clinical status of HNSCC patients. Conclusions Elevated PRAME expression associates with clinicopathologic markers of poor outcome in HNSCC and might identify potential candidates with pre-cancerous lesions for chemoprevention with retinoids.
PurposeThe objective of this study was to analyse 51 patients with intracranial complications of sinusitis treated in the Department of Otolaryngology and Laryngeal Oncology at Poznań University of Medical Sciences from 1964 to 2016.Materials and methodsMales made up a significant portion of study participants at 70.5%. Treatment included simultaneous removal of inflammatory focal points in the paranasal sinuses and drainage of cerebral and epidural abscesses and subdural empyemas under the control of neuronavigation preceded by the implementation of broad-spectrum antibiotics continuously for 4 weeks. Seventy-three intracranial complications were found among 51 patients. Of the 51 patients, 25 had frontal lobe abscesses (including multiple abscesses). Other complications included the following: 16 epidural abscesses, 9 subdural empyemas, 15 meningitis cases, 3 intracerebral abscesses, 3 sinus thrombosis cases and 2 patients with cerebritis. Co-occurrence of these complications worsened the state of the patient and increased the duration of treatment. Patients with frontal lobe abscesses had a better prognosis and less pronounced neurological symptoms in recent years versus earlier treatment approaches.ConclusionsSimultaneous treatment of intracranial complications of sinusitis is an effective treatment method that has minimal burden for the patient. From 1964 to 1978, three deaths (17%) were reported among patients with these complications. Since 1978, no deaths were reported in the clinic.
Cerebral abscesses remain one of the most severe complications related with inflammation of the middle ear. Both the operative methods and the postoperative care evolved (introduction of surgical microscope, new generation of antibiotics), the preoperative diagnostics facilitating the diagnosis and localization of the abscess progressed; nonetheless, the principles underlying the operative treatment remained unchanged. Neuronavigation constitutes a very important and supportive element in the management of otogenic brain abscesses.
The risk of developing intracranial sinogenic complications is low but invariably present and should be included in the differential diagnosis. Since the incidence of intracranial complications may increase in the course of prevailing viral infection, it should raise diagnostic vigilance.
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