Galanin and its receptors, GALR1 and GALR2, are tumor suppressors and represent therapeutic targets in head and neck squamous cell carcinoma (HNSCC). In the present study, it was demonstrated that ...the re‑expression of GALR1 in GALR1 and GALR2‑negative HNSCC cells suppresses tumor cell proliferation. This is mediated via extracellular‑regulated protein kinase‑1/2 (ERK1/2)‑dependent effects on the cyclin‑dependent kinase inhibitors (CKI) and cyclin D1. In combination with galanin, GALR2 also suppressed proliferation by increasing CKI and decreasing cyclin D1 levels. In contrast to GALR1, overexpression of GALR2 also induced caspase‑3‑dependent apoptosis. It was identified that in GALR2‑transfected cells, galanin induced activation of ERK1/2 and suppressed cell proliferation. Galanin stimulation also decreased the expression of cyclin D1 and induced apoptotic DNA ladder formation in GALR2‑transfected cells. Pretreatment with the ERK1/2‑specific inhibitor U0126 and pertussis toxin prevented the suppression of cyclin D1 expression, however did not affect DNA ladder formation. In conclusion, GALR2 expression in the presence of galanin exerts antitumor effects via cell cycle arrest and apoptotic pathways, and reactivation of these pathways may have therapeutic benefits in HNSCC.
Interleukin-6 (IL-6) is a multifunctional regulator of immune response and hematopoiesis. Recently, it has been reported that expression of IL-6 is correlated with prognosis in various cancer ...patients. In this study, we investigated whether the proliferation and invasion potential of head and neck squamous cell carcinomas (HNSCCs) were influenced by IL-6. All HNSCC cell lines, HEp-2, HSC-2, HSC-4, and SAS, were tested by reverse transcription-polymerase chain reaction (RT-PCR) and expressed the IL-6 receptor (IL-6R), and glycoprotein 130, which is responsible for signal transduction. HEp-2, HSC-2, and HSC-4 also produced IL-6. IL-6 inhibited the proliferation of HSC-2 and SAS, but the invasion potential of all the cell lines increased. Moreover, IL-6 down-regulated soluble IL-6R expression. Anti-IL-6R antibody abrogated the inhibited proliferation and increased invasion induced by IL-6. IL-6 stimulation also induced the extracellular regulated protein kinase 1/2 activation and increased vascular endothelial growth factor release. These results suggest that IL-6 can directly influence cell proliferation and the invasion potential as the first step of tumor metastasis.
Abstract Objective Recurrent epistaxis as a manifestation of hereditary hemorrhagic telangiectasia (HHT) is usually difficult to control. Although no treatment is regarded to be completely ...efficacious, nostril closure is considered a modality of choice for the most severe cases. The cessation of airflow resulting from this procedure can stop bleeding by minimizing risk factors. However, loss of nasal functions is a disadvantage of nostril closure. We conducted a questionnaire survey of patients who underwent nostril closure surgery, regarding the effects and disadvantages of the operation. Methods Seven patients were asked questions on issues including frequency and severity of epistaxis pre- and post-operatively, satisfaction of treatment, and impairment in daily living activities. Results Most patients reported complete cessation of bleeding. Some still had bleeding, but the frequency and severity were far lower. No transfusions were required in any of the cases. Patients reported some disadvantages, for example, respiratory, olfactory, and phonatory issues. Six out of seven patients were very satisfied with the outcome of surgery. Conclusion Nostril closure surgery can remarkably reduce frequency and volume of epistaxis. Our survey indicated that satisfactory results were achieved. However, difficulties caused by complete nasal obstruction varied. Thus, individualized coping strategies are required.
Abstract Objective In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis ...(CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy. Methods Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200 mg/day) alone (monotherapy group) or CAM (200 mg/day) in combination with SCMC (1500 mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score. Results Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P = 0.001). In addition, objective findings, including characteristics of nasal discharge ( P = 0.008) and post-nasal discharge ( P = 0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 ( P < 0.001), and were not significantly different between groups. Conclusion The results indicated that long-term combination therapy with SCMC at a dose of 1500 mg/day and CAM at a dose of 200 mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS.
Objective: To investigate pediatric foreign body cases in the aerodigestive tract, and to elucidate the characteristic problems in Japan.
Methods: A total of 310 pediatric patients (age 15 or below), ...gathered from two medical university hospitals (University of Tokyo and Jichi Medical School), were included in this study. Data were collected by retrospective chart review and were statistically analyzed.
Results: Two-year-olds were the most common patients, and the range from age 1 to age 4 included 67.7% of all the patients. The most involved sites were the nose (39.4%) and the pharynx (38.4%), followed by the esophagus (12.9%) and the trachea-bronchi (6.5%). Fish bones and toys were the representative foreign bodies (30.7 and 13.6%, respectively). Other foreign bodies often encountered included coins, food, candy, peanuts and nuts, and batteries. The type of foreign body was closely related to the site in which foreign bodies were lodged: 77.3% of foreign bodies in the pharynx were fish bones, and toys were the most common impacted foreign body in the nose. In the esophagus, representative impacted foreign bodies were coins (35.7%), but disk-type battery ingestion has been increasing in recent years. Although most foreign bodies in the esophagus were safely removed, one case of a disk-type battery had a serious sequela. In the trachea-bronchi, peanuts, food, cotton, and coins were impacted. A rigid bronchoscope was basically used to remove foreign bodies, but in some cases, a fine flexible endoscope, with a channel for fiber forceps, was useful, because it could be inserted into narrow bronchi. Advance of a flexible endoscope will make it an excellent tool for diagnosis and management of the trachea-bronchial foreign body.
Conclusions: Fish bones in the pharynx, which were closely related to Japanese eating habits, and toys in the nose, were the typical foreign bodies encountered in this study. In the esophagus, an increased incidence of disk-type battery ingestion has become a serious problem in recent years. Since prevention is the most essential way to manage foreign body cases, feedback from studies to public education should be encouraged.
Abstract Objective The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life ...(QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity. Methods The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity. Results Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test–retest reliability was r = 0.890 and the internal consistency was α = 0.903. For validity, the concurrent validity was r = 0.162 when compared with objective findings in the nasal cavity, and was r = 0.431 when compared with the score for general physical condition, which evaluate the patient's general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers ( p < 0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve) = 0.775. Conclusion The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS.
Primary involvement of the salivary glands in small cell carcinoma is rare, and has one of the worst prognoses of salivary gland neoplasms. However, it has been reported that some cases have a ...favorable outcome, although the prognostic factors are still under consideration. Multidisciplinary therapy was usually required to achieve long-term survival. Recently, a resemblance of some small cell carcinomas of the salivary gland to cutaneous Merkel cell carcinoma was suggested; the latter have the potential for spontaneous regression, which is related to a favorable clinical outcome.
We present a locoregional advanced parotid small cell carcinoma with multiple lymph node metastases in an 87-year-old Asian woman. The tumor was controlled by surgery alone, and nine-year disease-free survival was achieved without any adjunctive therapy. To the best of our knowledge, this is the longest reported follow-up of head and neck small cell carcinoma.
We believe this to be the first case of small cell carcinoma with involvement of the salivary glands reported in the literature with a good outcome after surgery alone without any adjunctive therapy.
This study was performed to clarify the relationship between fibrinolytic components and the pathology of allergy, particularly that during the development of nasal allergy and nasal tissue changes. ...Intranasal OVA challenge after sensitization by i.p. administration of OVA induced a higher level of excess subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that the decrease of proteolytic activity inhibits the removal of subepithelial collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness, production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN-gamma in splenocyte culture medium increased significantly. Histopathologically, there were marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in immune response.
Background. Pleomorphic adenoma (PA) is a benign tumour that mainly arises from salivary glands, and PA of the external auditory canal (EAC) is very rare. The objective of this study was to clarify ...the clinical presentation and treatment of PA of the EAC. Method. The authors present a case of PA arising from the EAC together with a literature review. Results. A 40-year-old man complained of hearing loss and foreign-body sensation of the right ear. Clinical and radiological examinations revealed a well-defined tumour limited to the EAC, with no connection to the parotid gland. Preoperative fine-needle aspiration cytology findings were characteristic of PA. The tumour was removed en bloc with the overlying skin. Conclusion. PA of the EAC is very rare, and methods to rule out malignancy before treatment are lacking. Thus, long-term follow-up is necessary, because malignant tumours are common in the EAC and PA has malignant potential.
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