原発性シェーグレン症候群の唾液腺におけるリンパ球浸潤とアクアポリン5の分布異常について

Objectives: Patients with Sjögren's syndrome (SS) suffer from impaired saliva secretion due to an autoimmune destruction of salivary glands. Based upon its abnormal distribution in SS salivary glands, a potential role for the water channel protein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. Methods: The immunohistochemical distribution of AQP5 was compared in minor salivary gland (MSG) biopsies obtained from primary SS with a variety of lymphoid cells infiltration in MSG, and healthy volunteers. Results: Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, biopsies from SS patients with both moderate and severe lymphoid infiltration revealed AQP5 expression diffusely at the cytoplasm of the acinus. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the acini. Biopsies of SS patients exhibited lower labeling indices (LI) at the apical membrane compared with biopsies from control subjects. The LI of the acini obtained from SS patients with both moderate and severe lymphoid infiltration showed no difference. Conclusions: Abnormal distribution of AQP5 in salivary gland acini could be responsible for a loss of saliva secretion, and this abnormal distribution is likely to develop during the stage of moderate lymphoid infiltration in salivary gland.博士（医学）・乙1334号・平成26年3月17

Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

INTRODUCTION: Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. RESULTS: Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. CONCLUSION: These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas

頭頸部癌におけるREG Ⅲ の発現と予後

Identification of a reliable biomarker for predicting prognosis in head and neck cancers is highly desirable and has long been sought. There have been several reports that members of the regenerating gene (REG) family are highly expressed in chronic inflammation and in tumors of the digestive organs. In addition, it has been described in several reports that REG expression is associated with the progression of digestive cancers. In the present study, we evaluated the effect of REG expression on the prognosis of hypopharyngeal cancer. We investigated 37 cases with hypopharyngeal squamous cell carcinoma, determined REG mRNA expression, which is easily detected in formalin-fixed paraffin-embedded tissues using the real-time reverse transcriptase-polymerase chain reaction method, and evaluated the survival rate using the Kaplan-Meier method. According to these results, REG Ⅲ mRNA expression was significantly associated with prolonged survival. Therefore, we constructed hypopharyngeal cancer cell lines transfected with REG Ⅲ and assessed the cell proliferation and chemosensitivity and/or radiosensitivity in vitro. Cells transfected with REG Ⅲ exhibited significantly lower cell proliferation and higher chemosensitivity and/or radiosensitivity compared with the control cells. These data suggest that REG Ⅲ may be a reliable biomarker of prognosis in hypopharyngeal cancer. This is the first report concerning the association of REG Ⅲ expression and the prognosis of head and neck squamous cell carcinoma including hypopharyngeal cancer.博士（医学）・甲第625号・平成27年3月16日本文のリンク：http://dx.doi.org/10.3892/or.2013.2521Copyright © Spandidos Publications 201

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma

Background: The tumor–node–metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. Methods: The revised system was evaluated using a large database of ATC patients. Results: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). Conclusion: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B