Faculty Profiles - TOYOOKA Shinichi

Unique circulating microRNAs in relation to EGFR mutation status in Japanese smoker male with lung adenocarcinoma Reviewed

Sachio Ito, Yoshihiro Kamoto, Akiko Sakai, Kaori Sasai, Tatsuro Hayashi, Shinichi Toyooka, Hiroshi Katayama

Oncotarget 8 ( 70 ) 114685 - 114697 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：Impact Journals LLC

The incidence of lung adenocarcinoma has been increasing recently in smokers. The molecular target therapy has been developed for lung adenocarcinoma patients harboring EGFR gene mutation. However, the treatment modalities for patients without mutation are currently limited. Thus, analysis of EGFR gene mutation status at early stage is important strategy to classify the patients for improving treatments and prognosis efficiently. This study aimed to identify microRNA (miRNA) signature in relation to mutation status in EGFR gene in early stage of lung adenocarcinoma male patients with smoking history. MiRNA profiles were assessed by microarray in paired plasma and tissue pooled from 10 EGFR wild type (EGFR-wt) and 10 EGFR mutated (EGFR-mut) patients. Expressions of selected miRNAs were verified further by real-time qRT-PCR in 83 plasma samples consisting of 55 EGFR-wt patients and 28 EGFR-mut patients and their correlation with clinicopathological parameters and EGFR gene mutation status were evaluated. We found that seven miRNAs (miR-16-5p, miR-23a-3p, miR-103a-3p, miR122-5p, miR-223-3p, miR-346 and miR-451a) were differentially expressed in stage I and stage I+II. Especially, miR-23a-3p was only miRNA shown higher expression in EGFR-wt patients than EGFR-mut patients. Thus, our findings could be useful non-invasive biomarkers to differentiate mutation status in EGFR gene in smoker lung adenocarcinoma male patients.

DOI： 10.18632/oncotarget.21425

Scopus

ß-1,3-galactosyl-O-glycosyl-glycoprotein ß-1,6-N-acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility. Reviewed

Sumardika IW, Youyi C, Kondo E, Inoue Y, Ruma IMW, Murata H, Kinoshita R, Yamamoto KI, Tomida S, Shien K, Satoh H, Yamauchi A, Futami J, Putranto EW, Hibino T, Toyooka S, Nishibori M, Sakaguchi M

Oncol Res 2017

Role of surgery in N2 NSCLC: pros Reviewed

Kazuhiko Shien, Shinichi Toyooka

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 46 ( 12 ) 1168 - 1173 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

The optimal management of clinical N2 Stage IIIA non-small cell lung cancer is still controversial. For a cure of locally advanced IIIA/N2 non-small cell lung cancer, the control of both local regions and possible distant micrometastases is crucial. Chemotherapy is generally expected to prevent distant recurrence. For local tumor control, radiotherapy or surgery has been adopted singly or in combination. If a complete resection can be safely performed, surgery remains the strongest modality for 'eradicating' local disease. Many retrospective studies have reported a possible survival benefit of induction treatment followed by surgery in selected patients with IIIA/N2 non-small cell lung cancer; however, randomized Phase III trials have failed to demonstrate the superiority of induction treatment followed by surgery over chemoradiotherapy, mainly because of the heterogeneity of the N2 status. IIIA/N2 non-small cell lung cancer consists of a heterogeneous group of disease ranging from microscopically single station to radiologically bulky ipsilateral multi-station mediastinal lymph node involvement. A recent definition proposed by the American College of Chest Physicians classified non-small cell lung cancer based on the N2 status, such as discrete or infiltrative type, and recommendations were made according to this N2 status, with definitive chemoradiotherapy recommended for infiltrative clinical N2 and definitive chemoradiotherapy or induction treatment followed by surgery recommended for other cases. Thus, the introduction of a multimodality treatment strategy seems to be necessary for the improved prognosis of non-small cell lung cancer patients with IIIA/N2 disease. In this review, we discuss the role of surgery and the optimal surgical management for patients with IIIA/N2 non-small cell lung cancer.

DOI： 10.1093/jjco/hyw125

Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells. Reviewed International journal

Satomi Saho, Hiroki Satoh, Eisaku Kondo, Yusuke Inoue, Akira Yamauchi, Hitoshi Murata, Rie Kinoshita, Ken-Ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I Made Winarsa Ruma, I Wayan Sumardika, Chen Youyi, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Shuta Tomida, Yoshihiko Sakaguchi, Ken Saito, Hidekazu Iioka, Nam-Ho Huh, Shinichi Toyooka, Masakiyo Sakaguchi

Cancer microenvironment : official journal of the International Cancer Microenvironment Society 9 ( 2-3 ) 93 - 105 2016.12

Language：English Publishing type：Research paper (scientific journal)

S100A11, a small Ca2+ binding protein, acts extracellularly as a mediator of cancer progression. That raises the question of how a protein that lacks the classical secretory signal is able to be secreted outside cells without being damaged. Some insights into this question have been obtained, and there has been accumulating evidence indicating a pivotal role of a non-classical vesicle-mediated pathway using lysosomes or peroxisomes for the protein secretion. To obtain a more precise insight into the secretory mechanism of S100A11, we first screened representative cancer cells exhibiting significantly active secretion of S100A11. From the results of profiling, we turned our attention to aggressive cancer mesothelioma cells. In mesothelioma cells, we found that abundant dimeric S100A11 was produced selectively in the peroxisome after transportation of monomeric S100A11 through an interaction with PEX14, a peroxisome membrane protein, resulting in peroxisomal secretion of dimerized S100A11. In an extracellular environment in vitro, dimerized S100A11 promoted mesothelial cell invasion indirectly with the help of fibroblast cells. Overall, the results indicate that the peroxisome functions as an essential vesicle for the production of dimerized S100A11 and the subsequent secretion of the protein from mesothelioma cells and that peroxisome-mediated secretion of dimerized S100A11 might play a critical role in mesothelioma progression in a tumor microenvironment.

DOI： 10.1007/s12307-016-0185-2

Usefulness of Thoracoscopic Debridement for Chronic Empyema after an Extrapleural Pneumonectomy Reviewed

Hidejiro Torigoe, Shinichi Toyooka, Hiromasa Yamamoto, Junichi Soh, Shinichiro Miyoshi

ACTA MEDICA OKAYAMA 70 ( 6 ) 507 - 510 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We present the case of a 65-year-old Japanese man diagnosed with chronic empyema (without a bronchopleural fistula) that occurred 7 months after he underwent an extrapleural pneumonectomy for right malignant pleural mesothelioma (MPM). Following thoracic drainage and irrigation for 1 month, we performed surgery by a thoracoscopic approach, in light of his general condition. We performed debridement and removal of the Gore-Tex polytetralluoroethylene (PTFE) patch that had been used for the reconstruction of the diaphragm and the pericardium. The empyema had not relapsed when he died from recurrence of the MPM at 4 months after the thoracoscopic surgery. This patient's case suggests that thoracoscopic debridement and patch removal can be a therapeutic option for not only early-stage (exudative or fibrinopurulent) empyema but also late-stage (organized and chronic) empyema without a bronchopleural fistula, particularly for patients in poor general condition.

DOI： 10.18926/AMO/54816

Interaction of cytokeratin 19 head domain and HER2 in the cytoplasm leads to activation of HER2-Erk pathway Reviewed

Tomoaki Ohtsuka, Masakiyo Sakaguchi, Hiromasa Yamamoto, Shuta Tomida, Katsuyoshi Takata, Kazuhiko Shien, Shinsuke Hashida, Tomoko Miyata-Takata, Mototsugu Watanabe, Ken Suzawa, Junichi Soh, Chen Youyi, Hiroki Sato, Kei Namba, Hidejiro Torigoe, Kazunori Tsukuda, Tadashi Yoshino, Shinichiro Miyoshi, Shinichi Toyooka

SCIENTIFIC REPORTS 6 39557 2016.12

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

HER2 is a receptor tyrosine kinase and its upregulation via activating mutations or amplification has been identified in some malignant tumors, including lung cancers. Because HER2 can be a therapeutic target in HER2-driven malignancies, it is important to understand the molecular mechanisms of HER2 activation. In the current study, we identified that cytokeratin 19 (KRT19) binds to HER2 at the inside face of plasma membrane. HER2 and KRT19, which were concurrently introduced to a human embryonic kidney 293 T cells, revealed an association with each other and resulted in phosphorylation of HER2 with the subsequent activation of a downstream Erk-associated pathway. A binding assay revealed that both the NH2-terminal head domain of KRT19 and the COOH-terminal domain of HER2 were essential for their binding. To investigate the impact of the interaction between HER2 and KRT19 in lung cancer, we examined their expressions and localizations in lung cancers. We found that KRT19 was highly expressed in HER2-positive lung cancer cells, and KRT19 and HER2 were co-localized at the cell membrane. In conclusion, we found that KRT19 intracellularly binds to HER2, playing a critical role in HER2 activation.

DOI： 10.1038/srep39557

NSCLCにおける分子バーコードシークエンス分析による複数の低頻度変異の検出(Detection of multiple low-frequency mutations by molecular-barcode sequencing in NSCLC)

難波圭, 冨田秀太, 枝園和彦, 鳥越英次郎, 佐藤博紀, 山本寛斉, 宗淳一, 佃和憲, 三好新一郎, 豊岡伸一

肺癌 56 ( 6 ) 639 - 639 2016.11

腸型肺腺癌の1切除例

清水大, 三好健太郎, 目崎久美, 枝園和彦, 杉本誠一郎, 山本寛斉, 宗淳一, 豊岡伸一, 大藤剛宏, 三好新一郎

肺癌 56 ( 6 ) 682 - 682 2016.11

Development of an annually updated Japanese national clinical database for chest surgery in 2014 Reviewed

Shunsuke Endo, Norihiko Ikeda, Takashi Kondo, Jun Nakajima, Haruhiko Kondo, Kohei Yokoi, Masayuki Chida, Masami Sato, Shinichi Toyooka, Koichi Yoshida, Yoshinori Okada, Yukio Sato, Meinoshin Okumura, Munetaka Masuda, Koji Chihara, Hiroaki Miyata

General Thoracic and Cardiovascular Surgery 64 ( 10 ) 569 - 576 2016.10

Language：English Publisher：Springer-Verlag Tokyo

Objectives: A national clinical database (NCD) adopted an “Internet-based collection” in 2011. An NCD specializing in chest surgery was launched based on the NCD system in 2014. The system was linked to the board certification as the second level in the hierarchy of the specialty of chest surgery and accreditation of educational institutions for chest surgery. Here, we report the status of the NCD for chest surgery in 2014 and clarified its registration rate and its accuracy. Methods: Chest surgeries undertaken in Japan since January 1st, 2014 until the end of the same year were registered through an Internet-based system until April 8th, 2015. The registration rate was compared with the annual survey conducted by the Japanese Association for Thoracic Surgery (JATS) from 2011 to 2014. The rate of accurate inputting was measured by an Internet-based audit in reference to 563 anonymous operative notes of patients presented by 106 chest surgeons at the time of renewal for board certification for chest surgery. Results: A total of 88,112 chest-surgical procedures were registered from 1000 chest surgery units (CSUs). Distribution of procedures by thoracic disease was almost identical to that of the annual survey conducted by JATS. However, the NCD had 4260 more registered procedures compared with the annual survey. The Internet-based audit showed that inter-rater agreement between Internet-based data and operative notes in any item was &gt
94Â %. Conclusions: The NCD system can sustainably provide important and up-to-date information relating to preoperative status, oncology, and best practice for chest surgery in Japan.

DOI： 10.1007/s11748-016-0697-1

Scopus

悪性胸膜中皮腫におけるS100A11の働き

佐藤博紀, 山本寛斉, 難波圭, 鳥越英次郎, 下田篤志, 吉岡貴裕, 枝園和彦, 宗淳一, 豊岡伸一

日本癌学会総会記事 75回 J - 1061 2016.10

Long-Term Survival after Radiofrequency Ablation of Lung Oligometastases from Five Types of Primary Lesions: A Retrospective Evaluation Reviewed

Kenichi Omae, Takao Hiraki, Hideo Gobara, Toshihiro Iguchi, Hiroyasu Fujiwara, Yusuke Matsui, Shinichi Toyooka, Takeshi Nagasaka, Susumu Kanazawa

JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 27 ( 9 ) 1362 - 1370 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Purpose: To conduct a retrospective evaluation of long-term survival after radiofrequency (RF) ablation for lung oligometastases from 5 types of primary lesions.
Materials and Methods: The study population consisted of 123 patients with lung oligometastases from colorectal cancer (CRC), non small-cell lung cancer, hepatocellular carcinoma, esophageal cancer, and renal-cell carcinoma treated with RF ablation. Lung oligometastases were defined as 1-5 Metastases confined to the lung while the primary cancer and other metastases were eradicated. Overall survival (OS) and recurrence-free survival (RFS) were estimated for-the overall study population and for patients with each type of primary lesion. The OS and RFS rates were compared with those of the patients with any of the other four primary lesion types. Finally, various variables were analyzed to determine what factors influenced OS and RFS.
Results: The Median follow-up was 45.7 months; and the 5-year-OS and RFS rates for all 123 patients Were 62% and 25%, respectively, The OS :time for patients with metastases from. CRC was significantly longer (P = .042); it was significantly shorter (P = .022) in patients with metastases from esophageal cancer. Longer disease-free interval was significantly (P = .015) associated with better OS. There was no variable significantly associated with OS and RFS on multivariate analyses.
Conclusions: Data from this single-center study appear promising in terms of long-term survival after RF ablation of lung oligometastases from 5 primary lesions.

DOI： 10.1016/j.jvir.2016.05.017

The Feasibility of Median Sternotomy With or Without Thoracotomy for Locally Advanced Non-Small Cell Lung Cancer Treated With Induction Chemoradiotherapy Reviewed

Hiroki Sato, Shinichi Toyooka, Junichi Soh, Katsuyuki Hotta, Kuniaki Katsui, Hiromasa Yamamoto, Seiichiro Sugimoto, Takahiro Oto, Susumu Kanazawa, Katsuyuki Kiura, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 102 ( 3 ) 985 - 992 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background. This study aimed to compare the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy and to investigate the feasibility of a median sternotomy for locally advanced non-small cell lung cancer (NSCLC) after induction chemoradiotherapy.
Methods. The medical records of patients with locally advanced NSCLC who underwent induction chemoradiotherapy followed by surgery at our institution between January 1999 and September 2014 were reviewed. We compared the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy.
Results. A total of 102 NSCLC patients were the subjects of this study. Among them, 31 patients underwent surgery with a median sternotomy approach and 71 patients underwent surgery with a lateral thoracotomy. Patients in the median sternotomy group had a significantly higher rate of postoperative arrhythmia than those in the lateral thoracotomy group (p = 0.0028). However, all the complications were manageable, and no treatment-related deaths occurred in the median sternotomy group. Regarding the prognosis, the 5-year overall survival rate was 72.7%, and the 2-year recurrence-free survival rate was 66.5% in the entire population. No significant differences in overall survival or recurrence-free survival were observed between the 2 approaches.
Conclusions. Whereas the lateral thoracotomy approach is a standard procedure, our experience suggests that a median sternotomy approach for locally advanced NSCLC after induction chemoradiotherapy is a feasible procedure and can be a surgical option. (C) 2016 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2016.03.092

Study about the Efficacy of Metformin to Immune Function in Cancer Patients Reviewed

Mototsugu Watanabe, Hiromasa Yamamoto, Shingo Eikawa, Kazuhiko Shien, Tadahiko Shien, Junichi Soh, Katsuyuki Hotta, Jun Wada, Shiro Hinotsu, Toshiyoshi Fujiwara, Katsuyuki Kiura, Hiroyoshi Doihara, Shinichiro Miyoshi, Heiichiro Udono, Shinichi Toyooka

ACTA MEDICA OKAYAMA 70 ( 4 ) 327 - 330 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

A study to evaluate the effect of metformin on the immune system was commenced in July 2014. Metformin is one of the most commonly prescribed drugs for type 2 diabetes, and previous studies have reported that metformin has an anti-tumor effect. The aim of this study is to evaluate the efficacy of metformin on the immune system in human cancer patients in vivo. The primary outcome parameter will be the rate change in the population of CD8(+) T cells, which produce multiple cytokines.

DOI： 10.18926/AMO/54514

Randomized feasibility study of S-1 for adjuvant chemotherapy in completely resected Stage IA non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 0701 Reviewed

Junichi Soh, Norihito Okumura, Masao Nakata, Hiroshige Nakamura, Minoru Fukuda, Masafumi Kataoka, Shinsuke Kajiwara, Yoshifumi Sano, Motoi Aoe, Kazuhiko Kataoka, Katsuyuki Hotta, Keitaro Matsuo, Shinichi Toyooka, Hiroshi Date

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 46 ( 8 ) 741 - 747 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Objective: The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA ( tumor diameter, 2-3 cm) non-small-cell lung cancer.
Methods: Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 ( 80-120 mg/body/day) followed by a 2-week rest ( Group A), or the 2-week oral administration of S-1 ( 80-120mg/body/day) followed by a 1-week rest ( Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan-Meier method with log-rank test.
Results: Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B ( P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B ( P = 0.237). There were no treatment-related deaths. Patients with grade 3/ 4 toxicities were significantly more frequent in Group A ( 40.5%) than in Group B ( 15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups.
Conclusions: The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA ( tumor diameter, 2-3 cm) non-small-cell lung cancer.

DOI： 10.1093/jjco/hyw062

胸腔鏡下拡大胸腺摘除術を施行した重症筋無力症の1例

尾山貴徳, 野田卓男, 納所洋, 谷本光隆, 牧佑歩, 宗淳一, 豊岡伸一, 三好新一郎, 柴田敬, 井上拓志, 吉永治美

日本小児科学会雑誌 120 ( 7 ) 1142 - 1142 2016.7

Yesl is the key molecule for the resistance to trastuzumab in breast cancer, and dasatinib overcomes the resistance Reviewed

Yamamoto Hiromasa, Takeda Tatsuaki, Kanzaki Hirotaka, Suzawa Ken, Namba Kei, Sato Hiroki, Torigoe Hidejiro, Watanabe Mototsugu, Maki Yuho, Soh Junichi, Asano Hiroaki, Tsukuda Kazunori, Miyoshi Shinichiro, Kitamura Yoshihisa, Sendo Toshiaki, Toyooka Shinichi

CANCER RESEARCH 76 2016.7

The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells. Reviewed International journal

Yuho Maki, Yasumitsu Nishimura, Shinichi Toyooka, Junichi Soh, Kazunori Tsukuda, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoka, Tsuyoshi Ueno, Norimitsu Tanaka, Hiromasa Yamamoto, Hiroaki Asano, Megumi Maeda, Naoko Kumagai-Takei, Suni Lee, Hidenori Matsuzaki, Takemi Otsuki, Shinichiro Miyoshi

Oncology letters 11 ( 5 ) 3308 - 3316 2016.5

Language：English Publishing type：Research paper (scientific journal)

Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.

DOI： 10.3892/ol.2016.4412