Clinicopathological Significance of S100A10 Expression in Lung Adenocarcinomas

Katono, Ken,Sato, Yuichi,Jiang, Shi-Xu,Kobayashi, Makoto,Saito, Keita,Nagashio, Ryo,Ryuge, Shinichiro,Satoh, Yukitoshi,Saegusa, Makoto,Masuda, Noriyuki Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.1

Background: S100A10, of the S100 protein family, is reported to be involved in cancer cell invasion and metastasis. The aims of the present study were to immunohistochemically examine S100A10 expression in surgically resected lung adenocarcinomas, and evaluate any relationships with clinicopathological parameters and prognosis of patients. Materials and Methods: S100A10 expression was immunohistochemically studied in 202 consecutive resected lung adenocarcinomas, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A10 expression on survival. Results: S100A10 expression was detected in 65 of the 202 (32.2%) lung adenocarcinomas, being significantly correlated with poorer differentiation (P =0.015), a higher pathological TNM stage (stages II and III) (P=0.004), more frequent and severe intratumoral vascular invasion (P=0.001), and a poorer prognosis (P=0.030). However, S100A10 expression was not an independent predictor of survival after controlling for clinicopathological factors. Conclusions: The present study reveals that S100A10 is expressed in a subset of lung adenocarcinomas, and this is related to some clinicopathological parameters, although further studies are required to confirm the correlation between S100A10 expression and prognosis of lung adenocarcinoma patients.

EGFR Mutation Genotype Impact on the Efficacy of Pemetrexed in Patients with Non-squamous Non-small Cell Lung Cancer

Igawa, Satoshi,Sato, Yuichi,Ishihara, Mikiko,Kasajima, Masashi,Kusuhara, Seiichiro,Nakahara, Yoshiro,Otani, Sakiko,Fukui, Tomoya,Katagiri, Masato,Sasaki, Jiichiro,Masuda, Noriyuki Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

Measurement of Exhaled Nitric Oxide in Children: A Comparison Between NObreath® and NIOX VERO® Analyzers

Yoko Inoue,Sakura Sato,Tetsuharu Manabe,Eishi Makita,Masako Chiyotanda,Kyohei Takahashi,Hitoshi Yamamoto,Noriyuki Yanagida,Motohiro Ebisawa 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

Purpose: Few studies have compared fractional exhaled nitric oxide (FeNO) measurement by NIOX VERO® (NOV) and other devices in children. Moreover, there is no agreement between differences in FeNO values obtained using different devices in adults. Here, we compared FeNO values obtained using NOV and NObreath® (NOB) systems to derive a correction equation for children. Methods: Eighty-eight participants (age 7–15 years) who were diagnosed with atopic bronchial asthma and visited Sagamihara National Hospital as outpatients between January and April of 2017 were included. We measured FeNO values obtained using NOB and NOV, and analyzed them using Wilcoxon tests and Altman-Bland plots. Results: The median age of the participants was 11.5 years, and the scored Asthma Control Test (ACT) or Childhood ACT (C-ACT) was 25 (interquartile range, 24–25) or 26 (24–27). NOB and NOV values were significantly different (31 [14–52] versus 36 [20–59] ppb; P = 0.020) and strongly correlated (r = 0.92). An equation to convert NOB values into NOV values was derived using linear regression as follows: log NOV = 0.7329 × log NOB + 0.4704; NOB for 20, 40, 58, 80 and 100 ppb corresponded to NOV for 27, 44, 59, 73 and 86 ppb. Thus, NOB < 58 ppb suggested NOB < NOV, whereas NOB > 58 ppb suggested NOB > NOV. Conclusions: NOB and NOV values were strongly correlated. Participants whose FeNO values were relatively low represented NOB < NOV, whereas those whose FeNO values were relatively high represented NOB > NOV.

Oral Immunotherapy in Food Allergy: Where Are We Now?

Özdemir Pınar Gökmirza,Sato Sakura,Yanagida Noriyuki,Ebisawa Motohiro 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.2

Food allergy (FA) has become more prevalent and problematic in the last 2 decades, and it poses important individual, social, and economic burdens. Besides treating reactions induced by accidental exposure and periodic evaluation for acquiring natural tolerance, the primary management approach is still allergen avoidance as a global standard. However, an active therapeutic approach that can raise the reaction threshold or accelerate tolerance is needed. This review aimed to provide an overview and the latest evidence of oral immunotherapy (OIT), which has recently been used in the active treatment of FA. FA immunotherapy, particularly OIT, is gaining considerable interest, and substantial effort has been made to integrate this active treatment into clinical practice. Consequently, growing evidence has been obtained regarding the efficacy and safety of OIT, particularly for allergens such as peanuts, eggs, and milk. However, several issues need to be addressed regarding the availability, safety, and long-term effects of this intervention. In this review, we summarize currently available information regarding tolerance-inducing immune mechanisms of OIT, data on efficacy and safety, gaps in current evidence, and ongoing research to develop new therapeutic molecules in order to enhance safety.

Cervical nerve roots and the dural sheath: a histological study using human fetuses near term

Kei Kitamura,Masahito Yamamoto,Yoshinosuke Hirota,Noriyuki Sato,Toshimasa Machida,Noboru Ishikawa,Hitoshi Yamamoto,Gen Murakami,Shinichi Abe 대한해부학회 2020 Anatomy & Cell Biology Vol.53 No.4

We have previously reported that the thoracolumbar posterior nerve root shows a tortuous epidural course, based on studies of human fetuses near term. For comparison with the cervical nerve, examinations were conducted using frontal, sagittal and horizontal sections of cervical vertebrae from 22 fetuses at 30-38 weeks of gestation. The cervical nerve root showed a short, straight and lateral course near the zygapophysial joint. Multiple rather than single bundles of the cervical posterior root seemed to account for the majority of sensory nerve fibers innervating the upper extremity. Fasciculation of rootlets was evident near the thoracolumbar spinal cord, whereas it was seen in the dural pocket at the nerve exit from the dural sac although both sites were subdural. As in the thoracolumbar region, the nerve sheath was continuous with the dura mater and independently surrounded each of the anterior and posterior roots. Radicular arteries were few in the cervical region. In 2 of the 22 fetuses (31 weeks and 33 weeks), there was a segmental, unilateral abnormality of nerve rootlet fasciculation where the dorsal root ganglion was located lateral or peripheral to the intervertebral region. Long nerve roots running inferiorly are a necessary adaptation to the delayed and marked growth of the thoracolumbar vertebral column. In children, the cervical nerve roots are likely to be affected by movement or dislocation of the vertebrae. The segmental abnormality of the cervical nerve root may be linked to rare variations in the brachial plexus.

S100A16 is a Prognostic Marker for Lung Adenocarcinomas

Saito, Keita,Kobayashi, Makoto,Nagashio, Ryo,Ryuge, Shinichiro,Katono, Ken,Nakashima, Hiroyasu,Tsuchiya, Benio,Jiang, Shi-Xu,Saegusa, Makoto,Satoh, Yukitoshi,Masuda, Noriyuki,Sato, Yuichi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

Yanagita, Kengo,Nagashio, Ryo,Ryuge, Shinichiro,Katono, Ken,Jiang, Shi-Xu,Tsuchiya, Benio,Nakashima, Hiroyasu,Fukuda, Eriko,Goshima, Naoki,Saegusa, Makoto,Satoh, Yukitoshi,Masuda, Noriyuki,Sato, Yuich Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. Materials and Methods: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. Results: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinumbased chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). Conclusions: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.