研究者詳細 - 豊岡　伸一

Contralateral pneumothorax in bullous lung after pneumonectomy: report of two cases. 査読

Masashi Furukawa, Takahiro Oto, Shinichi Toyooka, Junichi Soh, Masaomi Yamane, Shinichiro Miyoshi

General thoracic and cardiovascular surgery 61 ( 1 ) 35 - 7 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Contralateral pneumothorax after pneumonectomy is potentially fatal. We experienced two cases of right pneumothorax after left pneumonectomy in which the patients had multiple bullae in the right lung. Case 1 involved a 49-year-old man with non-small-cell lung cancer (NSCLC) who underwent left pneumonectomy after induction chemoradiotherapy. Eleven months after surgery, he had pneumothorax and was treated with chest tube drainage and pleurodesis. He was discharged but died of recurrent pneumothorax 1 month later. Case 2 involved a 57-year-old man with NSCLC who had left pneumonectomy. Five months after surgery, he had pneumothorax and was treated with chest tube drainage. Because of prolonged air leak, ligation of the ruptured bulla was performed with a percutaneous cardiopulmonary support system on standby. No pneumothorax recurrence occurred for 2 years. Although management of pneumothorax after pneumonectomy is challenging, surgical intervention may be useful and necessary especially when there is high risk of recurrent pneumothorax.

DOI： 10.1007/s11748-012-0112-5

The impact of prolonged cold preservation on the graft function and gene expression levels in an experimental lung transplantation model 査読

Osamu Yoshida, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Shinichi Toyooka, Takahiro Oto, Yoshifumi Sano, Shinichiro Miyoshi

SURGERY TODAY 43 ( 1 ) 81 - 87 2013年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Ischemia reperfusion injury (IRI) remains a significant cause of morbidity and mortality after lung transplantation. Early growth response-1 (EGR1) drives the expression of inflammatory mediators and has an important role in IRI. We hypothesized that the severe IRI caused by a long preservation induces a specific expression pattern of EGR1 and its target genes which would correlate with the lung graft function.
SD rat lungs were preserved at 4 A degrees C for 3 or 18 h, then transplanted and reperfused. Pulmonary grafts were evaluated for the blood gas oxygenation and pathological findings. The intra-graft mRNA levels of EGR1 and its downstream target genes were measured by real-time PCR. A Western blotting analysis of the EGR1 expression was used to validate the changes in the protein level.
There was upregulation of EGR1, MIP-2 and PAI-1 when there was prolonged hypothermic preservation. The expression levels of MIP-2 and PAI-1 were observed to increase for up to 4 h in the 18 h preserved lungs. There were no differences in the expression levels of IL-1 beta and ICAM-1 between the lungs subjected to short and long periods of ischemia.
Our data showed that prolonged hypothermic graft preservation deteriorates the pulmonary graft function, which was associated with the induction of EGR1 and its downstream target genes, which may aggravate IRI following lung transplantation.

DOI： 10.1007/s00595-012-0234-5

DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies (Retraction of vol 10, pg 2928, 2004) 査読

Takao Takahashi, Narayan Shivapurkar, Jyotsna Reddy, Hisayuki Shigematsu, Kuniharu Miyajima, Makoto Suzuki, Shinichi Toyooka, Sabine Zoechbauer-Mueller, Johannes Drach, Gunjan Parikh, Yingye Zheng, Ziding Feng, Steven H. Kroft, Charles Timmons, Robert W. McKenna, Adi F. Gazdar

CLINICAL CANCER RESEARCH 19 ( 1 ) 307 - 307 2013年1月

Bronchoplasty to adjust mismatches in the proximal and distal bronchial stumps during bronchial sleeve resection of the left lower lobe and lingular division. 査読国際誌

Toyooka S, Soh J, Oto T, Miyoshi S

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 43 ( 1 ) 182 - 183 2013年1月

Induction chemoradiotherapy is superior to induction chemotherapy for the survival of non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis 査読

Shinichi Toyooka, Katsuyuki Kiura, Kazuhiko Shien, Kuniaki Katsui, Katsuyuki Hotta, Susumu Kanazawa, Hiroshi Date, Shinichiro Miyoshi

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 15 ( 6 ) 954 - 960 2012年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

OBJECTIVES: The purpose of this study was to compare the clinical outcomes of induction chemoradiotherapy and chemotherapy and to identify the prognostic factors for non-small-cell lung cancer patients with mediastinal lymph node metastasis who were treated with induction therapy.
METHODS: Between August 1995 and December 2010, 50 non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis were scheduled to receive induction therapy followed by surgery. Irinotecan plus cisplatin was used for induction chemotherapy from June 1995 to April 1999, and docetaxel plus cisplatin with concurrent radiation at a dose of 40-46 Gy has been used for induction chemoradiotherapy since May 1999.
RESULTS: Thirty-five patients were treated with induction chemoradiotherapy and 15 were treated with induction chemotherapy. For the entire population, the 3-year and 5-year overall survival rates were 64.1 and 53.9%, respectively, and the 1-year and 2-year disease-free survival rates were 70.0 and 53.1%, respectively. Among the clinicopathological factors, the chemoradiotherapy group exhibited longer overall survival and disease-free survival than the chemotherapy group (overall survival, P = 0.0020; disease-free survival, P = 0.015). Pathological downstaging was also significantly associated with favorable overall survival (P = 0.0042) and disease-free survival (P = 0.021). A multivariate analysis showed that chemoradiotherapy (P = 0.0099) and pathological downstaging (P = 0.039) were independent prognostic factors.
CONCLUSIONS: Our results indicated that induction chemoradiotherapy was superior to induction chemotherapy with regard to the outcome of non-small-cell lung cancer patients with mediastinal lymph node metastasis.

DOI： 10.1093/icvts/ivs412

Impact of age on epidermal growth factor receptor mutation in lung cancer 査読

Tsuyoshi Ueno, Shinichi Toyooka, Kenichi Suda, Junichi Soh, Yasushi Yatabe, Shinichiro Miyoshi, Keitaro Matsuo, Tetsuya Mitsudomi

LUNG CANCER 78 ( 3 ) 207 - 211 2012年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

Aging is one of the best, but rarely referred, risk factors for various types of cancer including lung cancer, because age could be a surrogate for accumulation of genetic events in cancers. Smoking inversely associates with the presence of epidermal growth factor receptor (EGFR) mutation in lung cancer, but its strong confounding with age and sex makes it difficult to evaluate sole impact of age. To clarify an impact of age on EGFR mutation, we conducted a cross-sectional study based on data of 1262 lung cancer patients. The associations between EGFR mutation and age, considering sex, smoking and histology, were evaluated using logistic regression models. In multivariate analysis, we found a significant increase of EGFR mutation prevalence by increase of age (p-trend = 0.0004). Consistent trend was observed among never-smoking females (p-trend = 0.011) and never-smoking males also showed similar trend although not significant. These were consistently observed when we limit the subject to those with adenocarcinoma. In conclusion, age independently associates with EGFR mutation among lung cancer. Positive association between EGFR mutation and age among never-smokers regardless of sex might indicate that EGFR mutation occurs cumulatively by unidentified internal/external factors other than smoking. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2012.09.006

MicroRNA miR-34b/c Enhances Cellular Radiosensitivity of Malignant Pleural Mesothelioma Cells 査読

Yuho Maki, Hiroaki Asano, Shinichi Toyooka, Junichi Soh, Takafumi Kubo, Kuniaki Katsui, Tsuyoshi Ueno, Kazuhiko Shien, Takayuk Muraoka, Norimitsu Tanaka, Hiromasa Yamamoto, Kazunori Tsukuda, Takumi Kishimoto, Susumu Kanazawa, Shinichiro Miyoshi

ANTICANCER RESEARCH 32 ( 11 ) 4871 - 4875 2012年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT INST ANTICANCER RESEARCH

Background: We previously reported that epigenetic silencing of microRNA-34b1c (miR-34b/c) plays an important role in the pathogenesis of malignant pleural mesothelioma (MPM). We examined the impact of miR-34b/c restoration on the radiosensitivity of MPM cells. Materials and Methods: We established stable miR-34b/c and scramble transfectants of two MPM cell lines, H2052 and H28. We examined these transfectants by clonogenic survival assay, phosphorylated his-tone H2AX (gamma H2AX) foci assay, cell-cycle analysis, and western blotting. Results: The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells. gamma H2AX foci assay showed that DNA double-strand break repair was delayed in miR-34b/c transfectants. The proportion of sub-G(1) phase cells was increased in miR-34b/c transfectants after irradiation. miR-34b/c inhibited expression of cyclin-D1, cyclin-dependent kinase 416, B-cell lymphoma-2 (BCL-2) and increased cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after irradiation. Conclusion: Our results indicate that miR-34b/c enhances radiosensitivity by promoting radiation-induced apoptosis and suggested that miR-34b/c might be a useful therapeutic molecule to enhance radiotherapy in MPM.

Knockdown of the Epidermal Growth Factor Receptor Gene to Investigate Its Therapeutic Potential for the Treatment of Non-Small-Cell Lung Cancers 査読

Kazuhiko Shien, Tsuyoshi Ueno, Kazunori Tsukuda, Junichi Soh, Kenichi Suda, Takafumi Kubo, Masashi Furukawa, Takayuki Muraoka, Yuho Maki, Norimitsu Tanaka, Hiromasa Yamamoto, Katsuyuki Kiura, Tetsuya Mitsudomi, Shinichi Toyooka, Shinichiro Miyoshi

CLINICAL LUNG CANCER 13 ( 6 ) 488 - 493 2012年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CIG MEDIA GROUP, LP

Epidermal growth factor receptor (EGFR) can be a therapeutic target in non-small-cell lung cancer with EGFR activation, even if EGFR mutation is not present. By contrast, EGFR cannot be a target when EGFR is not activated, even if EGFR protein is expressed. For acquired resistant cells to EGFR-tyrosine kinase inhibitors, EGFR can be a target if those cells depend on EGFR and are not driven by other oncogenes.
Background: Epidermal growth factor receptor (EGFR) is often overexpressed in non small-cell lung cancer (NSCLC). Anti-EGFR agents, including EGFR-tyrosine kinase inhibitors are considered to be effective when a drug-sensitive EGFR mutation is present. However, inherent and acquired resistances are major problems of EGFR-targeting therapies. In this study, we performed EGFR knockdown by using small interfering RNAs in NSCLC cell lines to examine the significance of targeting EGFR for NSCLC therapy. Methods: We treated 13 NSCLC cell lines, including 8 EGFR mutant and 5 EGFR wild type by using gefitinib or small interfering RNAs against EGFR (siEGFR). Three cell lines (PC-9-GR1, RPC-9, and HCC827-ER) were experimentally established with acquired resistance to EGFR-tyrosine kinase inhibitors. The antitumor effect was determined by using an 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt (MTS) or colony formation assay. The protein expression was evaluated by using Western blotting. Results: All 13 cell lines expressed EGFR protein, and siEGFR downregulated EGFR protein expression in all. The cell viability was suppressed by siEGFR in 6 of 8 EGFR-mutant cell lines (suppressed 57%-92% of control cells), including PC-9-GR1 and RPC-9. The NCI-H1650 and HCC827-ER harbored EGFR mutations but were not suppressed. Of note, PTEN (phosphatase and tensin homolog) was deleted in NCI-H1650, and c-MET was amplified in HCC827-ER. It was not suppressed in any of the EGFR wild-type cells except in the NCI-H411, in which EGFR is phosphorylated, which indicates its activation. Conclusions: Analysis of the results indicated that EGFR can be a therapeutic target in NSCLCs with EGFR activation. In contrast, targeting EGFR is not appropriate for tumors in which EGFR is not activated, even if EGFR is expressed.

DOI： 10.1016/j.cllc.2012.02.003

微小乳頭状肺腺癌におけるEGFR、K-ras、EML4-ALKの変異の様式(EGFR, K-ras and EML4-ALK mutational profile of lung adenocarcinomas with micropapillary component)

DIRECT THERAPEUTIC EFFECT OF REIC/DKK-3-ENCODING ADENOVIRAL VECTOR FOR NON-SMALL CELL LUNG CANCER 査読

Yamamoto Hiromasa, Tanaka Norimitsu, Toyooka Shinichi, Watanabe Masami, Sakaguchi Masakiyo, Soh Junichi, Shien Kazuhiko, Furukawa Masashi, Asano Hiroaki, Tsukuda Kazunori, Nasu Yasutomo, Huh Nam-ho, Kumon Hiromi, Miyoshi Shinichirou

JOURNAL OF THORACIC ONCOLOGY 7 ( 11 ) S463 2012年11月

正常中皮細胞におけるmicroRNA34の抑制効果 Tiny RNA drives mesothelial cell mad

田中則光, 豊岡伸一, 宗淳一, 佃和憲, 枝園和彦, 古川公之, 村岡孝幸, 牧佑歩, 上野剛, 久保孝文, 山本寛斎, 浅野博昭, 大槻剛巳, 三好新一郎

日本癌治療学会誌 47 ( 3 ) 1275 - 1275 2012年10月

古川公之, 宗淳一, 豊岡伸一, 枝園和彦, 三好健太郎, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 三好新一郎

肺癌 52 ( 5 ) 671 - 671 2012年10月

まれなEGFR変異を有する肺腺癌の1例

木村紘爾, 山根正修, 豊岡伸一, 古川公之, 難波圭, 三好健太郎, 山本寛斉, 宗淳一, 大藤剛宏, 三好新一郎

肺癌 52 ( 5 ) 650 - 650 2012年10月

新規に樹立した悪性胸膜中皮腫細胞株の分子生物学的解析

山本寛斉, 多田龍平, 枝園和彦, 古川公之, 宗淳一, 三村雄輔, 片山英樹, 青江啓介, 岡部和倫, 松本常男, 豊岡伸一, 三好新一郎

肺癌 52 ( 5 ) 550 - 550 2012年10月

Basal segmental auto-transplantation after pneumonectomy for advanced central lung cancer 査読

Takahiro Oto, Katsuyuki Kiura, Shinichi Toyooka, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 42 ( 3 ) 579 - 581 2012年9月

記述言語：英語出版者・発行元：OXFORD UNIV PRESS INC

In patients with central lung cancer that extensively involves the bronchus/pulmonary artery, a double-sleeve lobectomy is often difficult to perform. We describe a case of post-pneumonectomy basal segmental auto-transplantation using a lung preservation technique that uses cold low-potassium dextran glucose solution to protect the lung graft from ischaemia-reperfusion injury during the ex situ division of the segmental graft and the pathological investigations for the clearance of the surgical margins. A right basal segmental auto-transplantation procedure was performed in a patient with stage-IIIA squamous cell lung cancer. This technique could allow extensive pulmonary resection while minimizing the loss of pulmonary reserve.

DOI： 10.1093/ejcts/ezs224

Intrathoracic irrigation with arbekacin for methicillin-resistant Staphylococcus aureus empyema following lung resection 査読

Tsuyoshi Ueno, Shinichi Toyooka, Junichi Soh, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 15 ( 3 ) 437 - 441 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

OBJECTIVES: Empyema is a well-known complication following lung resection. In particular, empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) is difficult to treat. Here, we present our experience of MRSA empyema treated with local irrigation using arbekacin.
METHODS: Six patients consisted of 4 males and 2 females with an average age of 65.7 years. They developed MRSA empyema following lung resection and were treated at our institution between 2007 and 2011. Cases comprised four primary and one metastatic lung cancer, and 1 patient was a living lung transplantation donor. The surgical procedure consisted of four lobectomies, one segmentectomy and one wedge resection. After diagnosis of MRSA empyema, anti-MRSA drugs were administered intravenously in all cases. In addition, arbekacin irrigation at a dose of 100 mg dissolved in saline was performed after irrigation with saline only.
RESULTS: The average number of postoperative days for the diagnosis of MRSA empyema was 13 (range 4-19). The period of irrigation ranged from 6 to 46 days. Arbekacin irrigation did not induce nephrotoxicity or other complications, and no bacteria resistant to arbekacin was detected in the thoracic cavity. We re-operated on 1 case because he had pulmonary fistula and severe wound infection. At the time of removing the thoracic catheter, MRSA in the pleural effusion disappeared completely in 3 patients. The period until MRSA concentration in the pleural effusion became negative after starting arbekacin irrigation ranged from 4 to 9 days. In the remaining cases, in which MRSA did not disappear, the catheter was removed because of no inflammatory reaction after stopping irrigation and clamping the catheters. All patients were discharged from our institution without thoracic catheterization and no patients had relapsed during the follow-up period ranging from 6 to 44 months.
CONCLUSIONS: Irrigation of the thoracic cavity with arbekacin proved to be an effective, safe and readily available method for treating MRSA empyema following lung resection.

DOI： 10.1093/icvts/ivs285

Takotsubo cardiomyopathy associated with pulmonary resections after induction chemoradiotherapy for non-small cell lung cancer. 査読

Shinichi Toyooka, Satoshi Akagi, Masashi Furukawa, Kazufumi Nakamura, Junichi Soh, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

General thoracic and cardiovascular surgery 60 ( 9 ) 599 - 602 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Takotsubo cardiomyopathy (TTC), also known as transient left ventricular (LV) apical ballooning syndrome, is characterized by transient LV dysfunction. We present the case of a 72-year-old man who was diagnosed as having TTC after surgery for two lung tumors. The patient was treated with induction chemoradiotherapy (CRT) followed by pulmonary resections for double primary non-small cell lung cancers (NSCLC): cT4N1M0 disease in the right lung and cT2N0M0 in the left lung. Induction CRT was performed. A right upper lobectomy was initially performed, and a left upper divisionectomy was subsequently performed. At 3 days after the second surgery, he developed dyspnea and general fatigue accompanied by a T-wave inversion on electrocardiography (ECG). An echocardiogram revealed akinesis at the apex with a 30 % ejection fraction. He was diagnosed as having TTC and recovered with supportive care. This case is the first report of TTC occurring after tri-modality therapy for NSCLC.

DOI： 10.1007/s11748-012-0058-7

Resection of the entire first rib for fibrous dysplasia using a combined posterior-transmanubrial approach 査読

Masashi Furukawa, Junichi Soh, Shinichi Toyooka, Toshifumi Ozaki, Shinichiro Miyoshi

General Thoracic and Cardiovascular Surgery 60 ( 9 ) 584 - 586 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 27-year-old woman presented with pain of the left anterior chest of 2-year duration. Chest X-ray revealed a mass in the upper-left lung field and chest computed tomography (CT) a 6-cm first-rib tumor. CT-guided biopsy was performed and the tumor diagnosed as fibrous dysplasia. Because of continued pain, surgery was deemed necessary. Surgery began with the use of the posterior approach in the prone position to expose the first thoracic vertebra and detach the first rib at the costotransverse joint. After transitioning to the spine position, the transmanubrial approach was used to resect the tumor en bloc with the left first rib. Histological examination revealed the tumor to be fibrous dysplasia. Postoperative recovery was uneventful. The outcomes of this case suggest that the combined posterior-transmanubrial approach described here is a safe, successful approach for first-rib resection of a space-occupying tumor that yields good cosmetic results. © The Japanese Association for Thoracic Surgery 2012.

DOI： 10.1007/s11748-012-0044-0

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