Lung fibrosis caused by Gefitinib therapy for lung cancer with EGFR mutation
| Project/Area Number |
24590438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Japanese Foundation for Cancer Research (2013-2014)
National Defense Medical College (2012) |
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Principal Investigator |
MATSUBARA Osamu 公益財団法人がん研究会, その他部局等, 研究員 (40107248)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Yuichi がん研究所, 病理部, 部長 (80222975)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 肺線維症 / 間質性肺炎 / 病理発生機序 / EGFR変異肺癌 |
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| Outline of Final Research Achievements |
Gefitinib therapy is very effective for lung cancer with epithelial growth factor receptor (EGFR) mutation, but it sometimes causes interstitial pneumonia/lung fibrosis. The important pathohistology shows destruction of alveolar structures, activation of fibroblastic foci and an increase of myofibroblasts. We studied pathological materials of video-assisted thoracoscopic surgery (VATS) lung biopsy, using 20 cases including 5 Gefitinib therapy cases and 10 controls to examine molecular mechanism of activation. Immunohistochemically myofobroblasts were positive for a-SMA, vimentin, desmin and regenerated pneumocytes were positive for TGF-b and CTGF. Pneumocytes revealed apoptosis. Myofibroblasts are thought to appear by epithelial mesenchymal transformation (EMT). Proteome analysis showed the difference of protein expression of some proteins, such as annexin A3, plastin-2, Hsp 27 and Hsp 70. We now have examined again to confirm the results.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer2014
Author(s)
Kikuchi R, Kikuchi Y, Tsuda H, Maekawa H, Kozaki K, Imoto I, Tamai S, Shiotani A, Iwaya K, Sakamoto M, Sekiya T, Matsubara O
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Journal Title
Hum Cell
Volume: 27(3)
Pages: 121-8
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Novel Mechanism of EML4-ALK Rearrangement Mediated by Chromothripsis in a Patient-Derived Cell Line2014
Author(s)
Kodama T, Motoi N, Ninomiya H, Sakamoto H, Kitada K, Tsukaguchi T, Satoh Y, Nomura K, Nagano H, Ishii N, Terui Y, Hatake K, Ishikawa Y
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Journal Title
J Thorac Oncol
Volume: 9(11)
Pages: 1638-46
Related Report
Peer Reviewed / Open Access
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[Journal Article] A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for completely resected high-grade pulmonary neuroendocrine carcinoma (large cell neuroendocrine carcinoma and small cell lung cancer)2014
Author(s)
Kenmotsu H, Niho S, Ito T, Ishikawa Y, Noguchi M, Tada H, Sekine I, Watanabe S, Yoshimura M, Yamamoto N, Oshita F, Kubota K, Nagai K
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Journal Title
Lung Cancer
Volume: 84(3)
Issue: 3
Pages: 254-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study2014
Author(s)
Thunnissen E, Noguchi M, Aisner S, Beasley MB, Brambilla E, Chirieac LR, Chung JH, Dacic S, Geisinger KR, Hirsch FR, Ishikawa Y, Kerr KM, Lantejoul S, Matsuno Y, Minami Y, Moreira AL, Pelosi G, Petersen I, Roggli V, Travis WD, Wistuba I, Yatabe Y, Dziadziuszko R, Witte B, Tsao MS, Nicholson AG
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Journal Title
J Thorac Oncol
Volume: 9(9)
Pages: 1354-62
Related Report
Peer Reviewed / Open Access
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