Kahori Seto

Real-time tissue elastography for the diagnosis of lymph node metastasis in oral squamous cell carcinoma.

We compared conventional ultrasound (US) B-mode, color Doppler and elastographic assessment of lymph node (LN) stiffness against pathological findings from surgical samples, to determine the most useful factors for identifying LN metastases. Seventy-one LNs in 19 patients with oral squamous cell carcinoma (OSCC) were examined. Using our new system, elastography images were scored from 1-5. The score 1-4 were correlated with the blue area of each LN, which indicated increased stiffness: (1) none; (2) < 50%; (3) 50%; or (4) > 50%. A score 5 indicated central necrosis and did not correlate with the blue area. We found significant differences in minimal diameter, shape index, margin, internal structure, hilus presence or absence, elastography score and percentage of blue area between metastatic and nonmetastatic LNs. Stepwise regression analysis identified elastography score 3-5 as an independent significant LN metastatic factor, suggesting that our scoring system may be useful for accurately diagnosing metastatic LNs.

Pharmacoepidemiology in Japan: medical databases and research achievements

Pharmacoepidemiology involves development of new models to predict safety in the development stages of pharmaceutical products, development of various guidelines and policy related to clinical trials, pharmacovigilance, establishment and implementation of risk management in postmarketing studies, and cost-effectiveness research in medical and social welfare sectors. Evaluations of safety, efficacy, and costs of pharmaceutical products must be developed in a different way. More recently, “big data” in medicine have become the driving force behind epidemiological studies that attempt to solve questions in the clinical setting. Furthermore, it is important to pursue cost-effectiveness considering the government’s financial condition. Epidemiologic and economic research utilizing epidemiological data linked to cost data will provide scientific evidence for appropriate distribution of health resources.

Peroxiredoxin I plays a protective role against UVA irradiation through reduction of oxidative stress

BACKGROUND Exposure of skin to long-wave UV radiation (UVA) increases the cellular levels of reactive oxygen species (ROS), which have been linked to apoptosis induction through the damage of lipids, proteins, and nucleic acids. Peroxiredoxin I (Prx I) is one of a family of antioxidant proteins that plays a protective role against oxidative damage; however the role of Prx I in UVA-induced damage remains to be clarified. OBJECTIVE Here we investigated the protective role of Prx I against UVA-induced changes using mouse embryonic fibroblasts (MEFs) derived from Prx I homozygous knockout (Prx I (-/-)) mice. METHODS Prx I (-/-) and wild-type (Prx I (+/+)) MEFs were subjected to UVA irradiation, and the resulting apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blotting. RESULTS Prx I (-/-) MEFs showed enhanced sensitivity to UVA treatment, exhibiting increased apoptosis and ROS production compared to Prx I (+/+) MEFs. Consistent with the increase in apoptosis, p53 expression was significantly higher, while Bcl-2, Bcl-xL, and Nrf2 expressions were all lower in Prx I (-/-) versus (+/+) MEFs. The UVA-induced inflammatory response was upregulated in Prx I (-/-) MEFs, as indicated by increased expressions of IκB, TNFα, and IL-6. Evidence was presented indicating that Prx I impacts these pathways by modifying critical signaling intermediates including p53, IκB, and Nrf2. CONCLUSION Our results indicate that Prx I plays a protective role against UVA-induced oxidative damage by controlling ROS accumulation. Both the UVA-induced apoptotic and inflammatory signals were found to be modulated by Prx I.

Secondhand smoke and incidence of dental caries in deciduous teeth among children in Japan: population based retrospective cohort study.

Study question Does maternal smoking during pregnancy and exposure of infants to tobacco smoke at age 4 months increase the risk of caries in deciduous teeth? Methods Population based retrospective cohort study of 76 920 children born between 2004 and 2010 in Kobe City, Japan who received municipal health check-ups at birth, 4, 9, and 18 months, and 3 years and had information on household smoking status at age 4 months and records of dental examinations at age 18 months and 3 years. Smoking during pregnancy and exposure of infants to secondhand smoke at age 4 months was assessed by standardised parent reported questionnaires. The main outcome measure was the incidence of caries in deciduous teeth, defined as at least one decayed, missing, or filled tooth assessed by qualified dentists without radiographs. Cox regression was used to estimate hazard ratios of exposure to secondhand smoke compared with having no smoker in the family after propensity score adjustment for clinical and lifestyle characteristics. Study answer and limitations Prevalence of household smoking among the 76 920 children was 55.3% (n=42 525), and 6.8% (n=5268) had evidence of exposure to tobacco smoke. A total of 12 729 incidents of dental caries were observed and most were decayed teeth (3 year follow-up rate 91.9%). The risk of caries at age 3 years was 14.0% (no smoker in family), 20.0% (smoking in household but without evidence of exposure to tobacco smoke), and 27.6% (exposure to tobacco smoke). The propensity score adjusted hazard ratios of the two exposure groups compared with having no smoker in the family were 1.46 (95% confidence interval 1.40 to 1.52) and 2.14 (1.99 to 2.29), respectively. The propensity score adjusted hazard ratio between maternal smoking during pregnancy and having no smoker in the family was 1.10 (0.97 to 1.25). What this study adds Exposure to tobacco smoke at 4 months of age was associated with an approximately twofold increased risk of caries, and the risk of caries was also increased among those exposed to household smoking, by 1.5-fold, whereas the effect of maternal smoking during pregnancy was not statistically significant. Funding, competing interests, data sharing This study was supported by a grant in aid for scientific research 26860415. The authors have no competing interests or additional data to share.

Negative expression of N- acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis

N-acetylglucosaminyltransferase V (GnT-V), an enzyme with a key role in the branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of many solid tumors. Here we searched for correlations between the clinical features of patients with oral squamous cell carcinoma (OSCC) and GnT-V expression in the tumor, and we studied the feasibility of using GnT-V as a marker for oral cancer prognosis. Samples from 68 patients with OSCC were examined by immunohistochemistry using antibodies against GnT-V. Correlations between the expression level of GnT-V in the tumor and patient clinical features were statistically analyzed. Positive GnT-V expression was found in 48 cases (70.6%), and negative GnT-V expression was found in 20 cases (29.4%). Negative GnT-V expression was associated with mode of invasion by multiple logistic regression analysis (OR: 3.605; P = 0.048). Biological characteristics of tumors and the Ki-67 labeling index were higher in tumors with negative GnT-V expression than in those with positive GnT-V expression, although the difference was not significant (P = 0.176). Patients with negative GnT-V expression had significantly shorter survival than those with tumors having positive GnT-V expression (5-year survival rate, 58.2% and 86.5%, respectively; P = 0.025). Negative GnT-V expression was a significant unfavorable prognostic factor for OSCC (hazard ratio, 4.246; P = 0.045). The loss of GnT-V expression is a likely indicator of tumors with high potential of tumor invasion and poor prognosis in OSCC patients.

Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy

It is known that the interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4Rα-lytic hybrid peptide composed of binding peptide to IL-4Rα and cell-lytic peptide and reported that the designed IL-4Rα-lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4Rα. Here, we evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5 μM. We also showed that IL-4Rα-lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4Rα-lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.

Radiation-Induced Carotid Artery Stenosis in a Patient with Carcinoma of the Oral Floor

Radiation-induced carotid artery stenosis (RI-CS), a life-threatening condition, can occur after external radiation for head and neck cancer. We here describe a case of asymptomatic RI-CS in a 73-year-old patient treated with chemoradiotherapy and radical neck dissection for a basaloid squamous cell carcinoma of the oral floor. Stenosis of the left carotid artery, diagnosed as RI-CS, showed on an MRI performed 1.5 years after radiotherapy. Blood from the left side of the anterior cerebral artery and the middle anterior artery was flowing to the brain through the anterior and posterior communicating arteries, so no stent surgery or other treatment was necessary. The cancer has not recurred during approximately 5 years of followup after radiotherapy, and the patient has had no adverse effects from the RI-CS since it was diagnosed 3.5 years ago. This case emphasizes the necessity of early scrutiny for RI-CS in patients given radiotherapy for oral cancer.