Faculty Profiles - TOYOOKA Shinichi

Suppression of Inflammatory Cytokines During Ex Vivo Lung Perfusion With an Adsorbent Membrane Reviewed

Tomokazu Kakishita, Takahiro Oto, Shiro Hori, Kentaroh Miyoshi, Shinji Otani, Sumiharu Yamamoto, Naohisa Waki, Osamu Yoshida, Mikio Okazaki, Masaomi Yamane, Shinichi Toyooka, Yoshifumi Sano, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 89 ( 6 ) 1773 - 1781 2010.6

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

Background. Lung grafts can be perfused ex vivo for 2 hours without edema formation; however, prolonged ex vivo lung perfusion (EVLP) eventually induces lung injury. This study evaluated the change in proinflammatory cytokines of the perfusate during EVLP and investigated the effect of cytokine removal using an adsorbent membrane.
Methods. Porcine heart-lung blocks were harvested after electrically induced cardiac arrest and underwent 12-hour EVLP with an adsorbent membrane (membrane group: n = 5) and without an adsorbent membrane (control group: n = 6).
Results. In the control group, both tumor necrosis factor-alpha and interleukin 8 levels were elevated in the perfusate 2 hours after perfusion. Although tumor necrosis factor-alpha and interleukin 8 levels were significantly lower in the membrane group than in the control group during the EVLP period, there was no significant difference in oxygenation, pulmonary vascular resistance, edema formation, or myeloperoxidase activity between the two groups.
Conclusions. Tumor necrosis factor-alpha and interleukin 8 levels of the perfusate were elevated during EVLP. Although adverse effects of these inflammatory cytokines were anticipated, removal of inflammatory cytokines by the adsorbent membrane did not improve lung function during prolonged EVLP. Factors other than the cytokines may play a major role in causing lung injury during EVLP. Further research is needed to investigate the real mechanism of lung graft injury during prolonged EVLP and to establish longer EVLP duration for graft treatment. This strategy could contribute to the salvage of potentially damaged lungs, especially from cardiac death donors, and to expansion of the donor pool. (Ann Thorac Surg 2010; 89: 1773-81) (C) 2010 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2010.02.077

Calcineurin Inhibitor-Related Cholestasis Complicating Lung Transplantation Reviewed

Takahiro Oto, Mikio Okazaki, Ken Takata, Moritoki Egi, Masaomi Yamane, Shinichi Toyooka, Yoshifumi Sano, Gregory I. Snell, Keiji Goto, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 89 ( 5 ) 1664 - 1665 2010.5

Language：English Publisher：ELSEVIER SCIENCE INC

Hepatotoxicity, including cholestasis, is a rare but significant complication of treatment with calcineurin inhibitors. Timely life-saving therapy with revision of immunosuppression is mandatory. A 43-year-old woman with pulmonary hypertension was found to have severe cholestasis (serum bilirubin up to 35 mg/dL) after a living-donor lobar lung transplantation. Calcineurin-inhibitor cholestasis markedly improved after withdrawal of the calcineurin inhibitor, initiation of sirolimus, and interleukin-2 receptor blockade. Awareness of the diagnostic criteria of this rare posttransplant complication is important to initiate timely therapy. (Ann Thorac Surg 2010;89:1664-5) (C) 2010 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2009.09.081

Frequent silencing of tumor suppressive MicroRNA-34b/c by aberrant methylation in malignant mesothelioma Reviewed

Kubo Takafumi, Toyooka Shinichi, Tsukuda Kazunori, Asano Hiroaki, Sakaguchi Masakiyo, Soh Junichi, Ueno Tsuyoshi, Yamamoto Hiromasa, Yamane Masaomi, Oto Takahiro, Nasu Yasutomo, Matsui Hideki, Huh Nam Ho, Miyoshi Shinichro

CANCER RESEARCH 70 2010.4

肺癌診療の分子生物学的展開肺腺癌の遺伝子異常はどこまで解明されたか? EGFR、KRAS遺伝子変異・増幅を中心に肺腺癌に迫る

宗淳一, 豊岡伸一, 山本寛斉, 重松久之, 上野剛, 久保孝文, 浅野博昭, 山根正修, 佃和憲, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 24 ( 3 ) 372 - 372 2010.4

肺移植後急性拒絶反応と抗ドナー特異的抗体価の推移急性拒絶発症を予見できるか

三好健太郎, 佐野由文, 岡崎幹生, 山根正修, 豊岡伸一, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 24 ( 3 ) 416 - 416 2010.4

肺癌特異的癌抑制遺伝子であるLKB1遺伝子不活化メカニズムに関する検討

宗淳一, 豊岡伸一, 山本寛斉, 重松久之, 上野剛, 久保孝文, 浅野博昭, 山根正修, 佃和憲, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 24 ( 3 ) 501 - 501 2010.4

肺癌診療の分子生物学的展開 EGFR変異肺癌に対する治療戦略現在と今後

豊岡伸一, 宗淳一, 大谷弘樹, 小林成行, 久保孝文, 上野剛, 山本寛斉, 山根正修, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 24 ( 3 ) 373 - 373 2010.4

EGFRチロシンキナーゼ阻害剤に対する耐性株の樹立と分子生物学的特徴の検討

上野剛, 豊岡伸一, 宗淳一, 治田賢, 久保孝文, 浅野博昭, 佃和憲, 山根正修, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 24 ( 3 ) 500 - 500 2010.4

EGFR阻害剤耐性を示すEGFR変異陽性肺癌細胞株に対するHeat shock protein 90阻害剤の抗腫瘍効果の検討

宗淳一, 豊岡伸一, 小林成行, 山本寛斉, 土手秀樹, 大谷弘樹, 久保孝文, 治田賢, 上野剛, 安藤翠, 荻野敦子, 木浦勝行, 三好新一郎

組織培養研究 29 ( 1 ) 122 - 123 2010.3

EGFRチロシンキナーゼ阻害剤に対する耐性株の樹立と分子生物学的特徴の検討

上野剛, 豊岡伸一, 治田賢, 佃和憲, 宗淳一, 浅野博昭, 久保孝文, 村岡孝幸, 牧佑歩, 山根正修, 大藤剛宏, 三好新一郎

組織培養研究 29 ( 1 ) 59 - 59 2010.3

肺癌細胞株におけるTAE226の変異型EGFRチロシンキナーゼ特異的な不活化作用とその抗腫瘍効果の検討

宗淳一, 豊岡伸一, 大谷弘樹, 高岡宗徳, 阪口正清, 治田賢, 久保孝文, 山本寛斉, 浅野博昭, 佃和憲, 木浦勝行, 許南浩, 猶本良夫, 三好新一郎

組織培養研究 29 ( 1 ) 121 - 121 2010.3

Triplet Chemotherapy with Cisplatin, Docetaxel, and Irinotecan for Patients with Recurrent or Refractory Non-small Cell Lung Cancer Reviewed

Nobukazu Fujimoto, Katsuyuki Kiura, Nagio Takigawa, Yoshiro Fujiwara, Shinichi Toyooka, Shigeki Umemura, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto

ACTA MEDICA OKAYAMA 64 ( 1 ) 33 - 37 2010.2

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

We examined the feasibility of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer (NSCLC), retrospectively. Twenty five patients (21 men and 4 women) with NSCLC and good performance status who were :E 70 years old were analyzed. The median age was 58 years. Most patients had performance status 1 (16/25), stage IV disease (18/25) and adenocarcinoma-histology (16/25). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2; the cycle was repeated every 3 weeks. The objective response rate was 39.1% (95% confidence interval: 18.7-59.5%). The median survival time and actual 2-, 3-, and 5-year survival rates were 14.3 months, 32%, 20%, and 8%, respectively. Of note, only 6 patients were treated with gefitinib at the recurrence after triplet chemotherapy; of these, 4 (67%) achieved a partial response, which might result in favorable survival. Grade 3/4 toxicities consisted of neutropenia (100%), neutropenic fever (56%), nausea/vomiting (40%), and diarrhea (16%); no cases of treatment-related death occurred. Triplet chemotherapy showed impressive survival data in our clinical trial, but proved too toxic for use in treating patients with NSCLC in the clinical practice.

DOI： 10.18926/AMO/32866