Clinical characteristics and prognostic factors of malignant tumors involving pterygopalatine fossa.

BACKGROUND: To identify the clinical characteristics and prognostic factors of malignancies involving the pterygopalatine fossa (PPF). METHODS: Fifty-seven patients who underwent curative surgery for malignant tumor involving PPF were reviewed. RESULTS: The rates for three-year local control (LC), five-year disease-free survival (DFS) and five-year overall survival (OS) were 55.4%, 34.5%, and 52.7%, respectively. Perineural invasion (PNI) of the maxillary nerve with facial numbness (symptomatic V2 PNI) (P = .04) and cranial involvement (P = .03) were predictors for poor OS. Symptomatic V2 PNI was also a significant predictor for poor LC (P = .05) and DFS (P = .03). Within the subgroup analysis of patients with pathologically confirmed V2 PNI, asymptomatic V2 PNI patients had significantly better LC (71.2% vs 31.8%, P = .05) and DFS (43.8% vs 17.3%, P = .05) compared to symptomatic patients. CONCLUSION: Malignant tumors involving the PPF have diverse pathologies and a poor prognosis. Symptomatic V2 PNI may be an independent poor prognostic factor.

Expression of membrane-bound mucins in human nasal mucosa: different patterns for MUC4 and MUC16.

OBJECTIVE: To acquire basic information concerning the function of the membrane-bound mucin MUC16 in nasal mucosa compared with the best-characterized membrane-bound mucin, MUC4. DESIGN: In vitro study using semiquantatitive reverse transcription-polymerase chain reaction analysis and immunoassay. SETTING: Yeungnam University College of Medicine. SUBJECTS: We examined the nasal polyps obtained during endoscopic sinus surgery in 10 patients, the normal ethmoid sinus mucosa obtained from 10 patients, and human nasal polyp epithelial (HNPE) cells. MAIN OUTCOME MEASURES: Gene expression of MUC4 and MUC16 in nasal polyps and normal nasal mucosa. In addition, we evaluated the effect of 4 physiologically relevant agents, including retinoic acid, interleukin 1beta, phorbol 12-myristate 13-acetate (PMA), and dexamethasone, on the expression of MUC4 and MUC16 in HNPE cells at the gene and protein levels. RESULTS: In nasal polyps, MUC4 was upregulated compared with normal nasal mucosa (P = .009), whereas MUC16 expression did not differ between nasal polyps and normal nasal mucosa. Retinoic acid and interleukin 1beta increased MUC4 expression at the gene and protein level in HNPE cells, whereas MUC16 expression was not affected. Unlike retinoic acid and interleukin 1beta, PMA and dexamethasone increased MUC16 expression, whereas they had no significant effect on MUC4 expression. CONCLUSIONS: Expression of MUC4 and MUC16 are regulated differently in nasal mucosa. Dexamethasone and PMA are potent mediators for the expression of MUC16 in nasal polyps.

Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathway.

Leptin, an adipocyte-secreted hormone that regulates food intake and metabolic response, has been recently reported to increase in the serum during inflammatory airway disease associated with mucus-hypersecretion. We investigated the effects of leptin on mucin expression in human airway epithelial cells and the signaling pathways. The expression of the leptin receptor was evaluated in human nasal mucosa and NCI-H292 cells. Leptin-induced expression of major respiratory mucins in NCI-H292 cells was analyzed. Mutant leptin, which acts as a receptor antagonist, and specific inhibitors of extracellular signal-regulated kinase (ERK1/2), p38 and Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) were used. Leptin receptors were expressed in the nasal mucosa and NCI-H292 cells. Treatment with leptin significantly increased the expression of MUC5AC and MUC5B in NCI-H292 cells; these effects were blocked by mutant leptin. The cells activated by leptin showed increased ERK1/2, p38, and STAT3 phosphorylation. Leptin-induced MUC5B expression was blocked by the ERK1/2 and p38 pathway inhibitors, but not by the JAK2/STAT3 pathway inhibitor. Leptin might significantly contribute to the production of major gel-forming mucins by direct stimulation of airway epithelial cells and the activation of leptin receptors coupled with the activation of ERK1/2 or p38, but not the JAK2/STAT3 pathway.

Expression of leptin receptor in nasal polyps: leptin as a mucosecretagogue.

OBJECTIVES/HYPOTHESIS: Leptin is a pleiotropic hormone that regulates food intake and metabolic and endocrine functions. Serum leptin levels have been reported to be increased in patients with allergic rhinitis and nasal polyposis; however, the explanation for this is unclear. We aimed to demonstrate the differential expression of leptin receptors in normal human nasal mucosa and nasal polyps, and to elucidate the effects of leptin on mucin gene expression in human nasal polyp epithelial cells. STUDY DESIGN: Case-control and in vitro study. METHODS: Normal ethmoid sinus mucosa was obtained from 10 subjects and used as a control; nasal polyps were obtained from 10 patients. Leptin receptor expression was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Leptin-induced expression of major respiratory mucins (MUC5AC and MUC5B) in the human nasal polyp epithelial cells was determined using RT-PCR and enzyme-linked immunosorbent assay. RESULTS: The leptin receptor expression was stronger in the nasal polyps than in the normal nasal mucosa. In human nasal polyp epithelial cells, leptin increased the expression of MUC5AC and MUC5B, in a dose- and time-dependent manner, at the gene and protein levels. Leptin-induced mucin expression was inhibited by the leptin receptor antagonist. CONCLUSIONS: The increased expression of leptin receptors in nasal polyps implies leptin has a certain role in nasal polyposis. In addition, leptin appears to induce the expression of MUC5AC and MUC5B through leptin receptors in the human nasal polyp epithelial cells.

Expression of glutaredoxin-1 in nasal polyps and airway epithelial cells.

BACKGROUND: Glutaredoxins (GRX)-1 is glutathione-dependent oxidoreductase. However, the role of these enzymes remains unknown in airway inflammatory diseases. Therefore, we aimed to establish the expression pattern of GRX-1 in the nasal polyps (NPs) and to assess the regulatory mechanisms associated with GRX-1 expression in interleukin (IL)-1 beta-treated airway epithelial cells. METHODS: The expression of GRX-1 in NPs and normal nasal mucosa were analyzed by reverse-transcription polymerase chain reaction and immunohistochemical staining. IL-1 beta-induced reactive oxygen species (ROS) formation and GRX-1 expression in the airway epithelial cells was determined by flow cytometry and immunoassay. RESULTS: The expression level of GRX-1 in NPs was significantly higher than in the normal nasal mucosa (p < 0.05). GRX-1 was highly expressed in the surface epithelial cells and the submucosal glandular cells in the NPs. IL-1 beta increased the intracellular ROS formation and GRX-1 expression in airway epithelial cells. The inhibition of IL-1 beta-induced ROS production by N-acetyl-cystein, an ROS scavenger, reduced GRX-1 expression. Diphenyleneiodonium and apocynin, NADPH oxidase inhibitors, did not abolish IL-1 beta-induced ROS formation and GRX-1 expression, whereas budesonide attenuated it. CONCLUSION: High GRX-1 expression in NPs might be a primary defense against chronic inflammatory oxidative stress in nasal mucosa. IL-1 beta-induced up-regulation of GRX-1 in airway epithelial cells is probably mediated by ROS. Glucocorticoids can regulate IL-1 beta-induced ROS formation and GRX-1 expression.

Up-regulation of neutrophil gelatinase-associated lipocalin in cholesteatoma.

CONCLUSION: Neutrophil gelatinase-associated lipocalin (NGAL) and Ki-67 expression were up-regulated in cholesteatoma and the expression pattern of NGAL in the epithelial layer was inversely related to the expression of Ki-67. Therefore, NGAL may be related to dysregulated differentiation in the keratinocytes during the development of a cholesteatoma. OBJECTIVES: We investigated the differential expression and localization of NGAL in middle ear cholesteatoma and compared the results to normal external auditory canal (EAC) skin. We also compared the expression and localization of NGAL with the expression and localization of Ki-67 in middle ear cholesteatoma. SUBJECTS AND METHODS: Tissue samples from middle ear cholesteatomas and normal EAC skin were obtained from 20 patients undergoing middle ear surgery. NGAL mRNA expression was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of NGAL protein was analyzed by Western blot. NGAL and Ki-67 were localized by immunohistochemical staining. RESULTS: A significantly greater expression of the NGAL mRNA was observed in cholesteatoma epithelium than in normal EAC skin (p < 0.05). NGAL was detected in the granular layer of cholesteatoma. However, NGAL was scarcely expressed in normal EAC skin. Ki-67 was detected predominantly in the basal and parabasal layers of cholesteatoma epithelium.

Mucoepidermoid carcinoma of the submandibular gland after chemotherapy in a child.

Second malignant neoplasms (SMNs) have become a concern in survivors of childhood malignancy. Although there are many reports describing SMN in patients treated for childhood cancer, salivary gland tumors rarely appear in these reports. Radiotherapy is a well-known risk factor for the development of secondary salivary gland malignancies after the treatment of childhood cancer. However, it is not well known whether chemotherapy itself treatment increases the risk of salivary gland malignancies. We report a child case with mucoepidermoid carcinoma of the submandibular gland as a SMN after chemotherapy alone for acute myeloid leukemia.

Expression of neutrophil gelatinase-associated lipocalin in nasal polyps.

OBJECTIVE: To investigate the expression and localization of neutrophil gelatinase-associated lipocalin (NGAL), an antimicrobial peptide, in the normal nasal mucosa and human nasal polyps. Neutrophil gelatinase-associated lipocalin has been identified as a key element in the innate host defense system. However, scant knowledge exists about the expression of NGAL in the human sinonasal tract. DESIGN: Prospective study. SETTING: Academic medical center. PATIENTS: Normal inferior turbinate mucosa was obtained from 10 patients who were undergoing augmentation rhinoplasty. The nasal polyps were obtained from 10 patients who were undergoing endoscopic sinus surgery for chronic rhinosinusitis with polyps. INTERVENTIONS: We performed semiquantitative reverse transcription-polymerase chain reaction, immunohistochemical staining, and Western blot analysis. MAIN OUTCOME MEASURES: We analyzed the expression of the NGAL messenger RNA (mRNA) and localization of the NGAL protein. RESULTS: The NGAL mRNA and NGAL protein were highly expressed in the nasal polyps. The ratio of NGAL mRNA to glyceraldehyde-3-phosphate dehydrogenase mRNA in the nasal polyps was greater compared with that in the normal turbinate mucosa (P = .002). The NGAL protein was observed in the epithelium, the infiltrating inflammatory cells, and the submucosal gland of the nasal polyps, but it was very rarely detected in the normal nasal mucosa. CONCLUSION: Expression of NGAL is upregulated in nasal polyps, and additional work is needed to reveal the possible role of NGAL in the defense systems of the nasal mucosa and the process of polyp formation.

Actinomycosis of the paranasal sinus.

OBJECTIVE: To report clinical characteristics and treatment outcomes of actinomycosis of the paranasal sinus. STUDY DESIGN: Retrospective review. SUBJECTS AND METHODS: The medical records of six patients with actinomycosis of the paranasal sinus between 1998 and 2006 were analyzed. RESULTS: There were no immunocompromised patients and all lesions were unilateral. Only one patient had a history of an oroantral fistula due to facial trauma. On CT scan, all patients had unilateral opacification of the maxillary sinus with focal calcified densities. All cases underwent endoscopic sinus surgery followed by relatively short-term antibiotic administration, and there was no recurrence. CONCLUSIONS: Chronic unilateral maxillary sinusitis, a calcified density in the involved sinus on radiological studies, and unresponsiveness to antibiotics are characteristics of actinomycotic sinusitis. Surgical removal of the involved tissues and the restoration of sinus ventilation seem to be important factors for treating the disease.

Interleukin-1beta induces MUC2 gene expression and mucin secretion via activation of PKC-MEK/ERK, and PI3K in human airway epithelial cells.

Interleukin 1beta(IL-1beta), a proinflammatory cytokine, is related with inflammatory diseases and it up-regulates MUC2 gene expression and mucin secretion. This study was designed to investigate the signal transduction pathway of the IL-1beta-mediated MUC2 gene expression and mucin secretion in human airway epithelial cells. In cultured human airway NCI-H292 epithelial cells, the steady state of the mRNA level of MUC2 gene expression and mucin secretion induced by IL-1beta were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme immunoassay, and immunoblot analysis. To observe the signal pathway of the IL-1beta-mediated MUC2 gene expression and mucin secretion, we used several specific inhibitors. PD98059 (MEK/ERK inhibitor) suppressed IL-1beta-mediated MUC2 gene expression and mucin secretion, while SB203580 (p38 inhibitor) did not. Ro31-8220 (PKC inhibitor) inhibited IL-1beta-mediated MUC2 gene expression and mucin secretion. It inhibited ERK phosphorylation, but did not inhibit p38 phosphorylation. LY294002 (PI3K inhibitor) also suppressed MUC2 expression, but did not inhibit any MAPKs phosphorylation. These results suggest that the IL-1beta-mediated MUC2 gene expression and mucin secretion in NCI-H292 cells are regulated through activation of the PKC-MEK/ERK pathway, and that PI3K is also involved in the IL-1beta-mediated MUC2 gene expression and mucin secretion.