Retraction: Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells.

[This retracts the article on p. 83 in vol. 11, PMID: 28386380.].

Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells.

BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions (CO2 5%/O2 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and 150 µg/mL) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence. Accordingly, associated EMT-related transcriptional factors, Snail and Smad, were also evaluated. RESULTS: Hypoxia increased expression of N-cadherin and reduced expression of E-cadherin. Mechanistically, E-cadherin levels were recovered during hypoxia by silencing hypoxia inducible factor (HIF)-1α or administering wheatgrass extract. Wheatgrass inhibited the hypoxia-mediated EMT by reducing the expression of phosphorylated Smad3 (pSmad3) and Snail. It suppressed the hypoxia-mediated EMT processes of airway epithelial cells via HIF-1α and the pSmad3 signaling pathway. CONCLUSION: These results suggest that wheatgrass has potential as a therapeutic or supplementary agent for HIF-1-related diseases.

Protective Effect of Tempol against Cisplatin-Induced Ototoxicity.

One of the major adverse effects of cisplatin chemotherapy is hearing loss. Cisplatin-induced ototoxicity hampers treatment because it often necessitates dose reduction, which decreases cisplatin efficacy. This study was performed to investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells were exposed to 30 µM cisplatin for 24 h with or without a 2 h pre-treatment with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL) assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric oxide synthase expression were evaluated using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured to assess the effects of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by confocal microscopy, and the mitochondrial membrane potential was measured to investigate whether Tempol protected against cisplatin-induced mitochondrial dysfunction. Cisplatin treatment decreased cell viability, and increased apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction. Tempol pre-treatment before cisplatin exposure significantly inhibited all these cisplatin-induced effects. These results demonstrate that Tempol inhibits cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role against cisplatin-induced ototoxicity.

Epithelial-myoepithelial carcinoma arising from the subglottis: a case report and review of the literature.

BACKGROUND: Epithelial-myoepithelial carcinoma is an extremely rare disease that usually occurs in the parotid gland but can occur in a variety of sites such as the nasal cavity, paranasal sinus, and base of the tongue. CASE PRESENTATION: We report a rare case of epithelial-myoepithelial carcinoma, which developed in the subglottic region. A 78-year-old Korean woman visited our hospital complaining of hoarseness, which had developed 1 month previously. Flexible laryngoscopy showed a round mass that blocked approximately 80 % of the tracheal diameter. Complete excision of the mass was carried out under general anesthesia, using a transoral approach. Epithelial-myoepithelial carcinoma was diagnosed following immunohistochemical analysis. CONCLUSIONS: We report a rare case of epithelial-myoepithelial carcinoma that occurred in the subglottic region. To the best of our knowledge, only one other case has been reported since this disease was first identified approximately 40 years ago.

Role of autophagy in cisplatin-induced ototoxicity.

OBJECTIVE: Hearing loss is a major side effect of cisplatin chemotherapy. Although cell death in cisplatin-induced ototoxicity is primarily caused by apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not fully understood. Autophagy is generally known as a pro-survival mechanism that protects cells under starvation or stress conditions. However, recent research has reported that autophagy plays a functional role in cell death also. This study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity in an auditory cell line. METHODS: Cultured HEI-OC1 cells were exposed to 30 µM cisplatin for 48 h, and cell viability was tested using MTT assays. To evaluate whether autophagy serves to cell death after cisplatin exposure, western blotting and immunofluorescence staining for LC3-II were performed. Markers of two autophagy-related pathways, mTOR and class III PI3K, were also investigated. RESULTS: The formation of the autophagic protein LC3-II in response to 30 µM cisplatin increased with time. The early upregulation of autophagy exerted cytoprotective activity via the class III PI3K pathway. But later increase in autophagy induced cell death by suppressing the mTOR pathway. CONCLUSION: Our results prove that autophagy could induce cell death during cisplatin-induced ototoxicity, and modulating the autophagic pathway might be another strategy against cisplatin-induced ototoxicity.

A case of pharyngeal injury in a patient with swallowed toothbrush: a case report.

BACKGROUND: Otolaryngologists encounter cases of various foreign bodies in the oral and pharyngeal regions. One commonly found foreign body is a fish bone, ingested in most cases by carelessness or an accident. These foreign materials are removed by endoscopy or through a simple procedure. However, hypopharyngeal damage is rarely caused by a foreign body in the pharynx following the swallowing of a toothbrush. CASE PRESENTATION: A 44-year-old Asian male visited the emergency room with chief complaints of intraoral pain and dysphagia that had started on the same day. The patient had paranoid-type schizophrenia that began 10 years ago; he had been hospitalized and was being treated at another clinic, and was transferred to the emergency room by the medical staff after swallowing a toothbrush. We successfully removed a toothbrush located within the pharynx of a patient with a history of a psychologic disorder via surgery and conservative treatment. CONCLUSION: The case with this patient, and a rapid diagnosis as well as treatment is imperative. The presence and state of a foreign body must be determined through a careful physical examination and imaging, followed by the immediate removal of the foreign body, all while keeping in mind the possibility of accompanying damage to nearby tissues.

Protective effect of silymarin against cisplatin-induced ototoxicity.

OBJECTIVES: Silymarin is a plant extract with strong antioxidant properties in addition to anti-inflammatory and anticarcinogenic actions. The aim of this study was to investigate the potential preventive effect of silymarin on cisplatin ototoxicity in an auditory cell line, HEI-OC1 cells. METHODS: Cultured HEI-OC1 cells were exposed to cisplatin (30 µM) with or without pre-treatment with silymarin (50 µM). Cell viability was evaluated using MTT assay. Hoechst 33258 staining was used to identify cells undergoing apoptosis. Western blot analysis was done to evaluate whether silymarin inhibits cisplatin-induced caspase and PARP activation. Cell-cycle analysis was done by flow cytometry to investigate whether silymarin is capable of protecting cisplatin-induced cell cycle arrest. RESULTS: Cell viability significantly increased in cells pretreated with silymarin compared with cells exposed to cisplatin alone. Pre-treatment of silymarin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining. Cisplatin increased cleaved caspase-3 and PARP on Western blot analysis. However, pre-treatment with silymarin inhibited the expression of cleaved caspase-3 and PARP. Silymarin did attenuate cell cycle arrest and apoptosis in HEI-OC1 cells. CONCLUSIONS: Our results demonstrate that silymarin treatment inhibited cisplatin-induced cytotoxicity in the auditory cell line, HEI-OC1. Silymarin may be a potential candidate drug to eliminate cisplatin induced ototoxicity.

Large perforation of hypopharynx secondary to anterior cervical approach : a complicated case.

Perforation of the hypopharynx, which can occur after anterior cervical approach, is a very rare type of complication. If diagnosed late, it can lead to very fatal course, such as mediastinitis and hematosepsis. Therefore, a precise and prompt diagnosis is crucial. When conservative treatment alone is not expected to heal the perforated site or is likely to lead to serious complications, surgical treatment becomes necessary. This report demonstrates that surgical intervention performed immediately after an early diagnosis can lead to the successful treatment of a large perforation in the hypopharynx on a 58-year-old male patient.

Clear cell myoepithelial carcinoma in the base of the tongue: Case report and review of the literature.

Clear cell myoepithelial carcinoma is a very rare disease which develops primarily in the parotid gland. To date, only 17 cases of clear cell myoepithelial carcinoma have been reported worldwide. Among them, only three cases developed in the minor salivary gland in the oral cavity. No cases developed in the base of the tongue. Here, we report a new case of clear cell myoepithelial carcinoma that developed in the tongue base of a 52-year-old female patient. A mass was discovered on the left side of the tongue base. We successfully removed the mass through suprahyoid pharyngotomy approach. The light microscopy examination and various immunohistochemical stainings revealed clear cell myoepithelial carcinoma. During a two year follow-up period, there was no recurrence or local or distant metastasis.

Nasal hemangiopericytoma causing oncogenic osteomalacia.

Oncogenic osteomalacia is a rare cause that makes abnormalities of bone metabolism. Our case arose in a 47-year-old woman presenting a nasal mass associated with osteomalacia. We excised the mass carefully. After surgery, it was diagnosed as hemangiopericytoma and her symptoms related with osteomalacia were relieved and biochemical abnormalities were restored to normal range. We report and review a rare case of nasal hemangiopericytoma that caused osteomalacia.

Gunshot injury to the anterior arch of atlas.

Penetrating injuries to the upper cervical spine resulting from gunshots are rare in South Korea due to restrictions of gun use. Moreover, gunshot wounds to the upper cervical spine without neurological deficits occur infrequently because of the anatomic location and surrounding essential structures. We present an uncommon case involving the surgical removal of a bullet located in the anterior arch of first cervical vertebra (C1) via a transoral approach without neurological complications or subsequent mechanical instability.

Usefulness of the melanoma antigen gene (MAGE) in making the differential diagnosis between pleomorphic adenoma and adenoid cystic carcinoma.

OBJECTIVE: The aim of this study was to examine the clinical usefulness of the melanoma antigen gene (MAGE) in making the differential diagnosis between pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC). In addition, using real-time reverse transcriptase polymerase chain reaction (RT-PCR), we examined which melanoma antigen gene was actually expressed in each tumour. MATERIALS AND METHOD: Immunohistochemical staining was performed on samples of paraffin-embedded tissue specimens. Fifty-eight patients were diagnosed as PA (n  =  31), ACC (n  =  17), and nontumoral salivary tissue (n  =  10) using MAGEA and MAGEA4. Using primers that could express MAGEA1, -A2, -A3, -A4, -A6, -A10, and -A12 subtypes, real-time RT-PCR was performed in three cases of PA and four cases of ACC that occurred in fresh tissues. RESULT: We found no immunohistochemical expression of MAGEA or MAGEA4 in the nontumoral tissue. There was a mild degree of expression with no statistical significance in cases of PA. In ACC, however, in 17 cases (100%) and 16 cases (95%), there was a positive reaction to MAGEA and MAGEA4, respectively. In the RT-PCR analysis, PA showed no MAGE gene expression. However, both MAGEA3 and MAGEA4 were expressed in ACC. CONCLUSION: These results suggest that MAGE could be used as a biologic marker in the differential diagnosis between PA and ACC. Our results also indicate that the expression of MAGE, as confirmed in the RT-PCR analysis, could be used as an alternative method for the early diagnosis of salivary gland tumours.

Granular cell tumor on larynx.

Granular cell tumors (GCTs) are uncommon neoplasm. They can originate in any part of the body. The most common sites of origin are in the head and neck, while the larynx is a relatively uncommon location. Patients affected with a laryngeal GCT typically present with persistent hoarseness, stridor, hemoptysis, dysphagia, and otalgia but, the tumor may be asymptomatic. Care must be taken to differentiate this lesion from others due to the presence of pseudo-epitheliomatous hyperplasia which overlies the GCT and may occasionally mimic squamous cell carcinoma. Therefore, a confirmative diagnosis should be made histopathologically and should be supported by immunohistochemical staining. These tumors are treated by complete surgical resection. Examining the complete removal of the tumor through securing a negative free margin is considered to be a consequential procedure. We experienced a 64-yr-old man with a laryngeal granular cell tumor involving the right true vocal cord. He was treated by surgical resection under a fine dissection laryngomicroscope. Here we present this case and a review of literature.

Clinical significance of the expression of galectin-3 and Pim-1 in laryngeal squamous cell carcinoma.

BACKGROUND: Because advanced-stage squamous cell carcinoma of the larynx undergoes a generally poor hospital course, the prognostic significance of squamous cell carcinoma in the larynx was evaluated to identify those features associated with aggressive biologic behaviour according to the immunologic and histopathologic characteristics. Molecular prognostic and predictive factors have been extensively studied in different cancers over the past decades, and some of these factors were found to be useful in diagnosis, follow-up, or even treatment of some malignant tumours. AIMS: To concretize the pathogenesis of malignant tumours in the larynx and to examine the possible prognostic factors related to malignancy. METHODS: To assess the significance of galectin-3 and Pim-1 protein in laryngeal tumours and their correlation with prognostic factors, samples from 77 patients with squamous cell carcinoma of the larynx were studied immunohistochemically. We examined the correlations of galectin-3 and Pim-1 protein expression according to tumour stage, nodal status, clinical stage, and histologic differentiation to investigate the clinical significance. RESULTS: Squamous cell carcinoma showed increased galectin-3 and Pim-1 expression in the more advanced clinical stage, tumour stage, and nodal status. CONCLUSIONS: The pathogenetic role of galectin-3 and Pim-1 expression in laryngeal squamous cell carcinoma indicates that galectin-3 and Pim-1 might be used as a possible prognostic factor.

Relation between proinflammatory mediators and epithelial-mesenchymal transition in head and neck squamous cell carcinoma.

Increasing evidence suggests that the tumor microenvironment plays an important role in tumor progression and oncogenesis. Various proinflammatory mediators contribute to tumor proliferation, neoangiogenesis, invasion, metastasis, and resistance to cancer therapy such as hormonal therapy and chemotherapy. The major causes of death related to head and neck squamous cell carcinoma (HNSCC) include cervical node and distant metastases. Epithelial-mesenchymal transition (EMT) has been identified to play a key role in mediating the tumor invasion and metastasis of carcinomas. Herein, the relationship between proinflammatory mediators and EMT in HNSCC was investigated. Immunohistochemical expression of interleukin-1 ß (IL-1ß), cyclooxygenase-2 (COX-2), Slug and E-cadherin in relationship to histologic differentiation, clinical stage and nodal status was evaluated in 146 surgical specimens of HNSCC. A correlation was noted between increased expression of IL-1ß and nodal status, as well as increased expression of COX-2 and histologic differentiation, clinical stage and nodal status. Increased Slug expression was correlated with histologic differentiation and clinical stage. Decreased E-cadherin expression was correlated with histologic differentiation and nodal status. A significant relationship was observed between IL-1ß and COX-2. However, a significant inverse correlation was noted between Slug and E-cadherin. A significant relationship was observed between increased proinflammatory mediator IL-1ß/COX-2 expression and increased EMT marker Slug/E-cadherin expression. These results indicate that proinflammatory mediators IL-1ß and COX-2 may induce EMT through an increase in Slug and a decrease in E-cadherin. The present findings suggest that various anti-inflammatory agents could be used as an adjuvant treatment modality with anti-cancer chemotherapeutic drugs in HNSCC.

Development of guideline for rating the physical impairment of otolaryngologic field.

We develop a guideline for rating the physical impairment of otolaryngologic fields. Assessment of hearing disturbance and tinnitus required physical examination, pure tone audiometry, speech audiometry, impedance audiometry, brainstem evoked response audiometry, Bekesy audiometry, otoacoustic emission test, and imaging examination. History taking, physical examination, and radiological examination for the vestibular organ and brain, righting reflex test, electronystagmography, and caloric test are taken for evaluation of balance disorder. Olfactory function tests include University of Pennsylvania Smell Identification test, Connecticut Chemosensory Clinical Research Center test, T and T olfactometry and Korean Version of Sniffin's Sticks test. Medical history and physical examination is mandatory to evaluatezseverity of respiration difficulty. Examinations include flexible fiberoptic nasopharyngoscope, bronchoscopy, simple soft-tissue radiography films of upper airway and high resolution computed tomography. Evaluation of mastication and swallowing are history taking, physical examination, examination for upper jaw, lower jaw, and temporomandibular joint, dental examination and radiological studies. Endoscopy and esophagography are also needed. Voice disorder is evaluated based on physical examination, oral pharynx and larynx endoscopy, larynx stroboscopy, hearing assessment, laryngeal electromyography, sound analysis test, aerodynamic test, electroglottography, and radiologic examination. Articulation disorder is assessed by picture consonant articulation test. These are position articulation test, Lee-Kim Korean articulation picture and speech intelligibility assessment.

An inflammatory myofibroblastic tumor of the nasal dorsum.

Inflammatory myofibroblastic tumor of the nose is an uncommon benign proliferative lesion that clinically mimics a neoplastic process. Our case arose in a 4-year-old girl presenting with a mass in the nasal dorsum. The mass was completely excised without any difficulty under general anesthesia. This tumor is a localized and completely benign lesion. Surgical resection is proper management for this condition.

Lipoblastoma arising from the submandibular region.

A lipoblastoma is a rare, benign tumor arising from embryonic white fat. The tumors occur primarily in infancy and early childhood and commonly arise from the limbs and the trunk, but neck involvement is extremely rare. Our case arose in a 22-month-old male presenting with a rapidly enlarging soft mass in the right submandibular area. Lipoblastoma was diagnosed by histologic evaluation, the mass was completely removed, and there was no recurrence at 1-year follow-up.

Fine-needle aspiration cytology of a lipoblastoma: a case report.

A lipoblastoma is a rare benign tumor of immature white fat, and more than 90% of lipoblastomas occur before the age of 3 years. The diagnosis of a lipoblastoma is mostly dependent on a histopathological examination of a surgically excised specimen. However, an accurate preoperative diagnosis is essential for the planning of surgery, particularly for a lesion of the head and neck area. We experienced a case of a cervical lipoblastoma of a 23-month-old boy. A preoperative fine-needle aspiration biopsy showed the sample as moderately cellular and showed fragments of mature and immature adipose tissues containing a large number of capillary vessels. There were numerous lipoblast-looking cells with a multivacuolated cytoplasm, and the nuclei were small, compressed by vacuoles, and centrally located. According to the cytological findings, the lesion was diagnosed as a benign adipose tumor suggestive of a lipoblastoma. Subsequent surgical excision confirmed the diagnosis of the fine-needle aspiration biopsy. The cytologic features of lipoblastoma are not well known because of the rarity of the lesion. However, the fine-needle aspiration cytological features of a lipoblastoma are sufficiently characteristic to make a specific preoperative diagnosis.

A low level of nicotine-induced chemoresistance in a KB cell line.

Cigarette smoking is closely associated with the induction of head and neck squamous cell carcinomas (HNSCC). Nicotine is an important component in cigarette smoke that can activate the growth-promoting pathways and facilitate the development of cancer. As nicotine is currently used in replacement therapy for smoking cessation in different forms, from skin patches to the oral route, numerous studies have investigated the effect of nicotine on the body, but the results have been equivocal. The aim of this study was to investigate the effect of nicotine on cancer chemotherapy. The status of the cell death-related proteins after treatment with nicotine was determined and compared to the effect of anticancer drugs such as cisplatin and etoposide in the presence or absence of nicotine in the KB cell line. Nicotine induced Bad phosphorylation in association with the suppression of apoptosis. The inhibition rate of cells pre-treated with nicotine prior to anticancer drug exposure was significantly decreased when compared to cells exposed to anticancer drugs only (P<0.01). Collectively, this suggests that nicotine may alter chemo-resistance and carcinogenesis via the anti-apoptotic pathway in HNSCC, and chemotherapy for HNSCC should be performed in the absence of nicotine in patient blood.