Jeong-Soo Woo

Protective role of superoxide dismutase in rat eustachian tubal mucosa against acute otitis media induced by upper respiratory tract infection

Superoxide dismutase has been known to play a role as an anti-oxidative system against oxidative injury during acute inflammation. To investigate the role of superoxide dismutase in eustachian tubal mucosa during acute otitis media (AOM), an animal model was made. Sprague-Dawley rats were inoculated with Streptococcus pneumoniae through the nasal cavity following development of virus-induced upper respiratory infection. The animals were divided into three groups according to their tympanic cavity conditions following bacterial inoculation; inoculated animals with no resultant AOM (no-AOM), animals with resultant AOM (AOM) and animals with resolving otitis media (recovery). The changes of superoxide dismutase in each tubal mucosa were compared with that of the normal control using immunohistochemistry and immunoblotting methods. On Western blot, there were little changes of optical density and surface area in no-AOM (213.5 +/- 22.4, 13.2 +/- 0.8 mm2) and recovery group (219.3 +/- 18.7, 14.8 +/- 0.7 mm2) compared to the normal control (223.5 +/- 26.2, 16.7 +/- 0.4 mm2). However, a marked decrease was found in the AOM model (167.6 +/- 19.3, 6.5 +/- 0.9 mm2). These findings suggest that superoxide dismutase may play a role in protecting tubal mucosa from free radical injury during AOM.

Efficacy of ultrasound-guided core needle gun biopsy in diagnosing cervical lymphadenopathy

OBJECTIVE Ultrasound-guided fine needle aspiration cytology (US-FNA) is useful for diagnosing cervical lymphadenopathy. However, FNA, has a high false negative rate, especially in patients with lymphoma. Ultrasound-guided core needle gun biopsy (US-CNB) has recently become important for diagnosing cancers, but its value remains undetermined. This study evaluates the efficacy of US-CNB, performed in an outpatient setting, in diagnosing cervical lymphadenopathy and the spectrum of related diseases. MATERIALS AND METHODS This retrospective study included 79 subjects who were not squamous cell carcinoma suspects and did not have a history of malignancy between January 2006 and July 2009. A US-CNB was performed on enlarged cervical lymph nodes (>1.0cm) in all subjects. Diagnostic sensitivity, specificity, and accuracy of US-CNB in differentiating between malignant and benign lymphadenopathy were evaluated. All enrolled subjects underwent a planned US-FNA before the study US-CNB was performed. Results of US-CNB and US-FNA were compared. RESULTS The correct histopathological diagnoses were made in 73 of 79 subjects (91.1%) using US-CNB samples. Of these, the most common diagnoses were reactive hyperplasia (26 subjects), Kikuchis disease (17 subjects), tuberculous lymphadenitis (15 subjects), lymphoma (8 subjects), and metastatic carcinoma (3 subjects). The US-CNB was very good at differentiating between malignant and benign lymphadenopathy, with a diagnostic sensitivity, specificity, and accuracy of 91.6%, 100%, and 98.6%, respectively. Additionally, US-CNB was more accurate than US-FNA in identifying lymphoma (88.8% vs. 11.1%) and Kikuchis disease (89.4% vs. 29.4%). No US-CNB related-complications were observed. CONCLUSION The US-CNB is safe, effective, and has a high diagnostic yield for cervical lymphadenopathy. The US-CNB may also be useful for diagnosing lymphoma and Kikuchis disease.

Expression of Neutrophil Gelatinase—Associated Lipocalin in Human Salivary Glands:

Objectives: We performed an observational study of RNA and protein expression in human tissue to examine the distribution of neutrophil gelatinase–associated lipocalin (NGAL) in normal and chronic inflammatory salivary tissues, and to investigate the expression level of NGAL in inflammatory conditions of salivary glands. Methods: Normal salivary gland tissues and tissue samples of salivary glands with chronic sialadenitis were obtained. Expression of NGAL was investigated by reverse transcriptase–polymerase chain reaction, and semiquantitative analysis of these results was also performed. The differential localization and amount of immunoreactivity to NGAL protein was evaluated by immunohistochemistry and Western blot analysis in normal salivary gland tissues and salivary glands with chronic sialadenitis. Results: NGAL messenger RNA transcripts were detected in the tissues from the salivary glands with chronic sialadenitis, but only a small amount was detected in the tissues from the normal salivary glands. A weak expression of NGAL protein was occasionally seen in a few ductal epithelial cells of normal salivary gland tissue. However, in tissue samples from glands with chronic sialadenitis, the NGAL protein was expressed strongly in ductal epithelial cells and infiltrating inflammatory cells. Conclusions: These results imply that NGAL is associated with the regulation of inflammation in salivary glands.

Anti-cancer effects of disulfiram in head and neck squamous cell carcinoma via autophagic cell death

Background Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anti-cancer effects in various malignant tumors. In this study, we investigated the anti-cancer effects and mechanism of DSF in HNSCC. Methods Head and neck squamous carcinoma cell lines (FaDu and Hep2) were used to analyze the anti-cancer effects of DSF. The anti-cancer effects of DSF were confirmed in vivo using a xenograft tumor model. Results The anti-cancer effects of DSF in HNSCC were found to be copper (Cu) dependent. Specifically, DSF/Cu markedly inhibited HNSCC at a concentration of 1 μM. After DSF/Cu administration, production of reactive oxygen species (ROS) was remarkable starting at 0.5 μM, suggesting that the inhibitory effects of DSF/Cu on HNSCC are mediated through the formation of ROS. The levels of phospho-JNK, phospho-cJun and phospho-p38 were increased after DSF/Cu treatment while levels of phospho-Akt were decreased. These results suggested that the inhibitory effects of DSF/Cu on HNSCC cells involve ROS formation and down-regulation of Akt-signaling. Through these molecular mechanisms, DSF ultimately induce the inhibitory effects on HNSCC cell lines mainly through autophagic cell death, not apoptotic cell death. Lastly, we investigated the clinical relevance of DSF/Cu using a HNSCC xenograft animal model, which showed that tumor growth was remarkably decreased by DSF (50 mg/kg injection). Conclusion In treating patients with HNSCC, DSF may contribute to improved HNSCC patient’s survival. The characteristic anti-cancer effects of DSF on HNSCC may suggest new therapeutic potential for this medication in HNSCC patients.

Analysis of efficacy and safety of core-needle biopsy versus fine-needle aspiration cytology in patients with cervical lymphadenopathy and salivary gland tumour

In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.

Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa

OBJECTIVE To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

Expression of Oncostatin M in Chronic Obstructive Sialadenitis of the Submandibular Gland

Objectives: We investigated the expression of oncostatin M messenger RNA (mRNA) and protein in normal submandibular glands and those with chronic obstructive sialadenitis and localized the expression of o costatin M protein. Methods: Submandibular glands from 10 patients with chronic obstructive sialadenitis as a study group and 10 normal submandibular glands as a control group were examined. Oncostatin M mRNA extracted from submandibular gland was used for reverse transcription–polymerase chain reaction and analyzed semiquantitatively. The difference in expression level of oncostatin M protein between the 2 groups was analyzed through Western blot analysis, and oncostatin M protein was localized immunohistochemically. Results: The expression levels of oncostatin M mRNA and protein were significantly increased in the study group. The protein was predominantly localized in ductal epithelia and infiltrating inflammatory cells and was more strongly expressed in the study group also. Conclusions: Oncostatin M is expressed in both chronic obstructive sialadenitis and normal submandibular gland, and is up-regulated in chronic obstructive sialadenitis. These results suggest that oncostatin M is involved in the pathologic process of chronic obstructive sialadenitis. However, the physiologic role in normal glands, as well as a possible role in the development of chronic obstructive sialadenitis, remains to be elucidated.