Development of the new clinical cure to overcome pemetrexed tolerance for malignant pleural mesothelioma

• Project/Area Number: 26461159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tottori University
• Principal Investigator: SHIMIZU EIJI 鳥取大学, 医学部, 教授 (50187449)
• Co-Investigator(Kenkyū-buntansha): 高田 美也子 鳥取大学, 医学部, プロジェクト研究員 (50523643) ; 千酌 浩樹 鳥取大学, 医学部附属病院, 教授 (90283994)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Kousuke 鳥取大学, 医学部附属病院, 助教 (60529402) ; MIYAKE Naomi 鳥取大学, 医学部, 特任教員 (90747205)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 悪性胸膜中皮腫 / ペメトレキセド / 臨床呼吸器学 / 胸膜中皮腫 / 耐性

Outline of Final Research Achievements

Pemetrexed is used as chemotherapy of the malignant pleural mesothelioma, however, the resistance for pemetrexed is now increasing problem. Therefore, we made pemetrexed-resistant cell lines. Using these cell lines, we searched for the resistant related molecules and pathways and a new clinical cure to overcome pemetrexed resistance. As a result, we found that increasment of the expression of Akt in resistant cell lines. Finally, for a conquest cure for the resistance, we demonstrated that the combination therapy of pemetrexed and BEZ235 has significant antitumor effect for the premetrexed resistant cell lines, and that this combination is potential promising therapy to overcome pemetrexed resistance in malignant pleural mesothelioma.

Research Products

• [Journal Article] Resolvin E1 Inhibits Osteoclastogenesis and Bone Resorption by Suppressing IL-17-induced RANKL Expression in Osteoblasts and RANKL-induced Osteoclast Differentiation. (2018)
  • Author(s): Yonago Acta Med. 2018 Mar 28;61(1):8-18. eCollection 2018 Mar.
  • Journal Title: Yonago Acta Med Volume: 61 Pages: 8-18
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of antigen‐positive toxin‐negative enzyme immunoassay results for the diagnosis of toxigenic Clostridium difficile infection (2018)
  • Author(s): Akamatsu Y, Morishita S, Okamoto R, Okada K, Kitaura T, Miyake N, Yamaguchi K, Nakamoto M, Shimohiro H, Takata M, Yamasaki A, Burioka N, Shimizu E.
  • Journal Title: The Journal of Medical Investigation Volume: 65 Issue: 1.2 Pages: 131-135
  • DOI: 10.2152/jmi.65.131
  • NAID: 130006575562
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Development of fever following first administration of zoledronate as a prognostic factor in advanced non-small cell lung cancer patients with bone metastases. (2017)
  • Author(s): Izumi H, Igishi T, Yamasaki A, Takeda K, Yanai M, Tanaka N, Sakamoto T, Nishii-Ito S, Touge H, Kodani M, Matsumoto S, Kawasaki Y, Shimizu E.
  • Journal Title: Mol Clin Oncol Volume: 7 Pages: 1000-1004
  • DOI: 10.3892/mco.2017.1447
  • Peer Reviewed / Open Access
• [Journal Article] An onion farmer with a case of hypersensitivity pneumonitis caused by Aspergillus niger. (2017)
  • Author(s): Sakamoto T, Yamasaki A, Funaki Y, Harada T, Okazaki R, Hasegawa Y, Sueda Y, Fukushima T, Morita M, Yamamoto A, Kodani M, Shimizu E.
  • Journal Title: Respir Med Case Rep Volume: 23 Pages: 60-62
  • DOI: 10.1016/j.rmcr.2017.12.002
  • Peer Reviewed / Open Access
• [Journal Article] A case of lung abscess successfully treated by transbronchial drainage using a guide sheath. (2017)
  • Author(s): Izumi H, Kodani M, Matsumoto S, Kawasaki Y, Igishi T, Shimizu E.
  • Journal Title: Respirol Case Rep Volume: 5 Issue: 3 Pages: 228-230
  • DOI: 10.1002/rcr2.228
  • NAID: 120007146980
  • Peer Reviewed / Open Access
• [Journal Article] γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells. (2017)
  • Author(s): Fukushima T, Yamasaki A, Harada T, Chikumi H, Watanabe M, Okazaki R, Takata M, Hasegawa Y, Kurai J, Yanai M, Yamamoto A, Sueda Y, Halayko AJ, Shimizu E.
  • Journal Title: Yonago Acta Med Volume: 60 Pages: 16-23
  • NAID: 120005999117
  • Peer Reviewed / Open Access
• [Journal Article] DNA-PK Inhibition by NU7441 Enhances Chemosensitivity to Topoisomerase Inhibitor in Non-Small Cell Lung Carcinoma Cells by Blocking DNA Damage Repair. (2017)
  • Author(s): Yanai M, Makino H, Ping B, Takeda K, Tanaka N, Sakamoto T, Yamaguchi K, Kodani M, Yamasaki A, Igishi T, Shimizu E.
  • Journal Title: Yonago Acta Med Volume: 60 Pages: 9-15
  • NAID: 120005999118
  • Peer Reviewed / Open Access
• [Journal Article] Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema. (2017)
  • Author(s): Takeda K, Yamasaki A, Igishi T, Kawasaki Y, Ito-Nishii S, Izumi H, Sakamoto T, Touge H, Kodani M, Makino H, Yanai M, Tanaka N, Matsumoto S, Araki K, Nakamura H, Shimizu E.
  • Journal Title: Anticancer Res Volume: 37 Pages: 765-771
  • Peer Reviewed / Open Access
• [Journal Article] A novel SLC34A2 mutation in a patient with pulmonary alveolar microlithiasis. (2017)
  • Author(s): Izumi H, Kurai J, Kodani M, Watanabe M, Yamamoto A, Nanba E, Adachi K, Igishi T, Shimizu E.
  • Journal Title: Hum Genome Var Volume: 26 Issue: 1 Pages: 1647-1647
  • DOI: 10.1038/hgv.2016.47
  • Peer Reviewed / Open Access
• [Journal Article] A case of proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) positive/IgG4-related lung disease. (2017)
  • Author(s): Touge H, Tomita K, Yamasaki A, Shimizu E.
  • Journal Title: Respir Med Case Rep Volume: 20 Pages: 92-94
  • DOI: 10.1016/j.rmcr.2017.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary intravascular large B-cell lymphoma successfully treated with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone immunochemotherapy: Report of a patient surviving for over 1 year. (2016)
  • Author(s): Nishii-Ito S, Izumi H, Touge H, Takeda K, Hosoda Y, Yamasaki A, Kuwamoto S, Shimizu E, Motokura T.
  • Journal Title: Mol Clin Oncol. Volume: 5 Issue: 6 Pages: 689-692
  • DOI: 10.3892/mco.2016.1063
  • NAID: 120007144887
  • Peer Reviewed
• [Journal Article] Association between Outdoor Fungal Concentrations during Winter and Pulmonary Function in Children with and without Asthma. (2016)
  • Author(s): Watanabe M, Noma H, Kurai J, Hantan D, Burioka N, Nakamoto S, Sano H, Taniguchi J, Shimizu E.
  • Journal Title: Int J Environ Res Public Health Volume: 28
  • Peer Reviewed
• [Journal Article] Difference in interleukin-8 transcriptional activity induced in THP-G8 cells by particulate matter collected in winter and summer in western Japan. (2015)
  • Author(s): Watanabe M, Kurai J, Minato S, Noma H, Sano H, Saito R, Aiba S, Oshimura M, Hatakeyama K, Yamasaki A, Shimizu E.
  • Journal Title: J Med Invest Volume: 62 Pages: 145-148
  • NAID: 130005099161
  • Peer Reviewed
• [Journal Article] Favorable effect of the combination of vinorelbine and dihydropyrimidine dehydrogenase; inhibitory fluoropyrimidine in EGFR; mutated lung adenocarcinoma: retrospective and in vitro studies. (2015)
  • Author(s): Izumi H, Touge H, Igishi T, Makino H, Nishii-Ito S, Takata M, Nakazaki H, Ueda Y, Matsumoto S, Kodani M, Kurai J, Takeda K, Sakamoto T, Yanai M, Tanaka N, Nirodi CS, Shimizu E.
  • Journal Title: Int J Oncol Volume: 46 Issue: 3 Pages: 989-998
  • DOI: 10.3892/ijo.2015.2815
  • Peer Reviewed / Open Access
• [Journal Article] A novel point-of-care system for high-speed real-time polymerase chain reaction testing for epidermal growth factor receptor mutations in bronchial lavage fluids after transbronchial biopsy in patients with non-small cell lung cancer (2015)
  • Author(s): Sakamoto T, Kodani M, Takata M, Chikumi H, Nakamoto M, Nishii-Ito S, Ueda Y, Izumi H, Makino H, Touge H, Takeda K, Yamasaki A, Yanai M, Tanaka N, Igishi T, Shimizu E
  • Journal Title: Int J Oncol Volume: 46 Issue: 4 Pages: 1473-1480
  • DOI: 10.3892/ijo.2015.2875
  • Peer Reviewed / Open Access
• [Journal Article] A new rapid method for detecting epidermal growth factor receptor mutations in non-small cell lung cancer (2015)
  • Author(s): Takata M, Chikumi H, Matsunami K, Kodani M, Sakamoto T, Hashimoto K, Nakamoto M, Okada K, Kitaura T, Matsumoto S, Kurai J, Yamasaki A, Igishi T, Burioka N, Shimizu E
  • Journal Title: Oncol Rep Volume: 33 Issue: 3 Pages: 1040-1048
  • DOI: 10.3892/or.2015.3716
  • Peer Reviewed / Open Access
• [Presentation] 滑膜線維芽細胞におけるω‐3系脂肪酸由来抗炎症脂質メディエーターの抗炎症効果やRANKL発現抑制効果についての検討 (2017)
  • Author(s): 岡崎亮太、長谷川泰之、舟木佳弘、末田悠里子、原田智也、山崎章、清水英治
  • Organizer: 第61回日本リウマチ学会学術集会
• [Presentation] トシリズマブ投与後にマクロファージ活性化症候群を発症し,自然軽快した成人発症スティル病の1例 (2017)
  • Author(s): 末田悠里子、原田智也、舟木佳弘、岡崎亮太、長谷川泰之、山崎章、清水英治
  • Organizer: 第61回日本リウマチ学会学術集会
• [Presentation] 骨芽細胞におけるResolvin E1のPGE2産生抑制効果とその機序についての検討 (2017)
  • Author(s): 舟木佳弘、長谷川泰之、末田悠里子、原田智也、岡崎亮太、山崎章、清水英治
  • Organizer: 第61回日本リウマチ学会学術集会
• [Presentation] SMARCA4-deficient thoracic sarcomaに対して放射線治療が奏功した１例 (2017)
  • Author(s): 武田賢一、桑本聡史、田原誉敏、田中那津美、矢内正晶、小谷昌広、牧野晴彦、山口耕介、坂本智宏、清水英治
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] Nivolumabで治療した非小細胞肺癌患者の中枢神経系転移 (2017)
  • Author(s): 田中那津美、武田賢一、矢内正晶、牧野晴彦、泉大樹、井岸正、清水英治
  • Organizer: 第26回日本がん転移学会学術集会
• [Presentation] 肺癌標的分子としてのULBP2の役割と治療戦略 (2016)
  • Author(s): 清水英治
  • Organizer: 第25回日本がん転移学会学術集会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-22
  • Invited
• [Presentation] 肺癌細胞におけるEGFR阻害剤耐性獲得時の浸潤能とその機序の検討 (2014)
  • Author(s): 高田美也子、泉大樹、千酌浩樹、三宅直美、牧野晴彦、井岸正、清水英治
  • Organizer: 第23回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール（金沢市）
  • Year and Date: 2014-07-11
• [Book] 内科学 (2017)
  • Author(s): 鰤岡直人、清水英治
  • Total Pages: 4
  • Publisher: 朝倉書店
• [Book] 今日の治療指針2017 (2017)
  • Author(s): 清水英治
  • Total Pages: 1
  • Publisher: 医学書院