Hyun Jik Kim

The Role of Nox4 in Oxidative Stress–Induced MUC5AC Overexpression in Human Airway Epithelial Cells

Mucus hypersecretion is a prominent manifestation in patients with chronic inflammatory airway diseases, and MUC5AC is a major airway mucin. It is well known that reactive oxygen species (ROS) may be involved in the pathogenesis of various inflammatory airway diseases. The purpose of this study was to identify which secreted mucin genes are induced by exogenous hydrogen peroxide and the mechanism by which these genes are up-regulated in normal human nasal epithelial (NHNE) cells. Exogenous H(2)O(2) induced the ligand-independent activation of epidermal growth factor receptors (EGFR) and the subsequent activation of ERK1 mitogen-activated protein kinase, resulting in the induction of intracellular ROS generation. Through this signal pathway, exogenous H(2)O(2) markedly induced overexpression of the MUC5AC gene alone. In addition, Nox4, a subtype of nonphagocytic NADPH oxidase, was found to play a key role in intracellular ROS generation and exogenous H(2)O(2)-induced MUC5AC gene expression in NHNE cells.

Results of salvage therapy after failure of initial treatment for advanced olfactory neuroblastoma

INTRODUCTION Olfactory neuroblastoma is a very aggressive tumour with high rates of locoregional recurrence and distant metastasis. Therefore, salvage therapy plays an important role in control of these neoplasms. In this study, we present our experience and treatment outcomes for salvage therapy in patients with recurrent olfactory neuroblastoma. MATERIAL AND METHODS We retrospectively analysed 17 patients treated for advanced olfactory neuroblastoma during the last 15 years. RESULTS The disease-free 5-year survival rate was 48% in all patients and 42% in the 17 patients with recurrence or distant metastasis. Salvage therapy was performed in 6 of 8 patients with recurrence or metastasis and proved successful in 50% of them. In the patients with locoregional recurrence, the success rate of salvage radiotherapy plus neck dissection was superior to salvage chemotherapy alone. In addition, 17% of the patients with distant metastasis after initial treatment died after salvage therapy. In 15% of patients with a clinical stage N0 at initial diagnosis, nodal recurrence developed and was successfully treated with salvage therapy. CONCLUSION Complete surgical resection, including craniofacial resection and postoperative radiotherapy without elective neck dissection, is the preferred approach in the treatment of advanced olfactory neuroblastoma. In locoregional recurrence, successful salvage therapy may include selective neck dissection and radiotherapy, but in cases of distant metastasis, the prognosis was poor.

Crosstalk between platelet-derived growth factor-induced Nox4 activation and MUC8 gene overexpression in human airway epithelial cells.

Reactive oxygen species (ROS) contribute to chronic airway inflammation, and NADPH oxidase (Nox) is an important source of ROS. However, little is known of the role that ROS play in chronic upper respiratory tract inflammation. We investigated the mechanism of ROS generation and its association with mucin gene overexpression in the nasal epithelium. The level of platelet-derived growth factor (PDGF) expression was increased in sinusitis mucosa, and high-level PDGF expression induced intracellular ROS, followed by MUC8 gene overexpression in normal human nasal epithelial cells. Knockdown of Nox4 expression with Nox4 siRNA decreased PDGF-induced intracellular ROS and MUC8 expression. Infection with an adenovirus containing Nox4 cDNA resulted in Nox4 overexpression and increased intracellular levels of ROS and MUC8 expression. PDGF and Nox4 overexpression are essential components of intracellular ROS generation and may contribute to chronic inflammation in the nasal epithelium through induction of MUC8 overexpression.

Clinical Effect of Surgical Correction for Nasal Pathology on the Treatment of Obstructive Sleep Apnea Syndrome

Objectives This study aimed to evaluate the hypothesis that relief of nasal obstruction in subjects with obstructive sleep apnea (OSA) would lead to reduce OSA severity and to discuss the available evidence on the clinical efficacy of nasal surgery as a treatment modality for OSA. Study Design Twenty-five subjects who had reduced patency of nasal cavity and narrowing of retroglossal or retropalatal airways were diagnosed with OSA and underwent nasal surgery, such as septoplasty or turbinoplasty to correct nasal pathologies. The effect of the surgery on nasal patency was quantified by measuring minimal cross-sectional area (MCA) using acoustic rhinometry. The watch-PAT-derived respiratory disturbance index (RDI), apnea and hypopnea index (AHI), lowest oxygen saturation, and valid sleep time were measured before and after nasal surgery. Results The present study shows that the AHI and RDI decreased significantly and the lowest oxygen saturation and valid sleep time rose after nasal surgery in 25 OSA subjects. In addition, a reduction in subjective symptoms was observed in subjects and mean MCA increased after nasal surgery. Fourteen subjects were classified as responders and 11 subjects as non-responders. Responders showed considerable improvement of their subjective symptoms and the AHI and RDI were significantly lower after surgery. We found that the changes between pre- and post-operative AHI and RDI values were minimal in 11 non-responders. However, daytime somnolence and REM sleep time improved after nasal surgery in non-responders. Conclusions Our study provides evidence that the surgical treatment of nasal pathology improves nasal airway patency and reduces OSA severity in 56% subjects. Furthermore, correction of nasal pathology appears to result in improved sleep quality in both responder and non-responders OSA subjects.

Analyzing serum eosinophil cationic protein in the clinical assessment of chronic rhinosinusitis.

Background Eosinophil cationic protein (ECP) is a major granule–derived protein with cytotoxic activity found in eosinophils and has been known as a useful marker of allergic inflammation. In this study, we assessed the clinical significance of ECP in chronic inflammation of the nasal mucosa by evaluating the relationship between eosinophil activity and serum ECP concentration in a cohort of subjects with or without chronic rhinosinusitis (CRS) and allergic rhinitis (AR). Methods We retrospectively reviewed the medical records of 492 subjects and analyzed eosinophil percentage in nasal smears, serum eosinophil counts, serum ECP concentrations, symptom scores, CT scores, the size of nasal polyp, and recurrence of CRS at follow-up. Results Elevated serum ECP concentration was closely related with higher eosinophil expression in all subjects nasal smears and sera. CRS subjects without AR had a higher percentage of immune cells that were eosinophils compared with control subjects and it was similar to subjects’ with AR only or with both CRS and AR. CRS subjects without AR also had significantly higher serum ECP concentrations and eosinophil counts compared with control subjects. Additionally, serum ECP concentration was significantly correlated with CT scores, symptom scores, polyp size, and recurrence rate in CRS subjects without AR. Conclusion Serum ECP concentration can be used as a marker of local and systemic eosinophil expression. We conjecture that although serum ECP elevation may not be specific in AR, analysis of serum ECP concentration could be particularly useful in estimating the progression and prognosis of CRS.

Activation of c‐Myb transcription factor is critical for PMA‐induced lysozyme expression in airway epithelial cells

Lysozyme is a major component of airway epithelial secretions, acts as cationic anti‐microbial protein for innate immunity. Although lysozyme plays an important role in airway defense and is a key component of airway secretions under inflammatory conditions, little is understood about the regulation of its expression and the associated signaling pathway. We wanted to examine whether Phorbol 12‐myristate 13‐acetate (PMA), one of PKC activators, treatment of the airway epithelial cell line NCI‐H292 increases lysozyme gene expression. In this study, we sought to determine which signal molecules are involved in PMA‐induced lysozyme gene expression. We found that PKC and mitogen‐activating protein/ERK2 kinase are essential for PMA‐induced lysozyme expression and also mediate the PMA‐induced activation of c‐Myb protein. We identified a proximal region of the lysozyme promoter essential for promoter activity containing c‐Myb transcription factor binding site. Additionally, by site‐directed promoter mutagenesis, we identified that c‐Myb preferred the CAA motif of the −85/−73 region of the lysozyme promoter. Finally, we showed that overexpression of c‐Myb without PMA treatment increased the lysozyme promoter activity and protein expression. From these results, we conclude that PMA induces overexpression of lysozyme via ERK1/2 MAP kinase—c‐Myb signaling pathways in NCI‐H292 cells. J. Cell. Biochem. 111: 476–487, 2010.

A case of the nasal cavity fungus ball.

Fungus balls in the nasal cavity are an extremely rare finding. We described a case of the fungus ball in the nasal cavity of a 61‐year‐old man, which was successfully removed by endoscopic sinus surgery. To the best of our knowledge, this report is the third case in the English literature. In addition, we propose the diagnosis of the ‘nasal cavity fungus ball’.

One-Stage Reconstruction for Midfacial Defect after Radical Tumor Resection

A serious midface defect involving resection of squamous cell carcinoma originating from the hard palate was treated by an unusual reconstructive strategy. After tumor resection, surgical reconstruction was accomplished in one stage using one free flap with one distant and local flap: a radial forearm flap to reconstruct the upper lip, a forehead flap to reconstruct the external nose, a cantilever calvarial bone graft to replace the nasal skeleton and a nasolabial flap and split thickness skin graft to cover the internal nasal lining. The rationale for this one-stage reconstruction and the problems associated with midfacial reconstruction after wide tumor excision are discussed.

A modified midfacial degloving approach for the treatment of unilateral paranasal sinus tumours.

PURPOSE The midfacial degloving approach (MFDA) is the primary option for the removal of benign and malignant sinonasal tumours. However, the classic MFDA does not compensate for the fact that most benign and malignant paranasal sinus (PNS) tumours are unilateral and the incisions may lead to some unnecessary complications?. Surgical exposure is limited to the upper and deep part of the PNS. Modifications of the classical MFDA that minimize complications and improve surgical field exposure are warranted. PATIENTS The medical records of 27 consecutive patients who had undergone surgery using a modified MFDA for treatment of unilateral benign or malignant tumours from 2000 to 2006, were reviewed. RESULTS We developed and performed a modified MFDA utilizing a hemigingivobuccal incision, a transfixion incision, mucosal detachment of the pyriform aperture and separation of the upper lateral cartilage from the nasal bone in 27 patients with unilateral benign (85%) or malignant (15%) PNS neoplasms. Adequate surgical exposure was achieved in all cases. No technical problems and no intraoperative complications related to the surgical procedure were encountered. CONCLUSION Our modified MFDA provides sufficient surgical exposure for the removal of unilateral malignant or benign PNS tumours with few surgical or cosmetic complications.