2010 Fiscal Year Final Research Report
Targeting advanced non small cell lung cancer in vivo by pulmonary surfactant -adenovirus-mediated gene transfer
| Project/Area Number |
20390369
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Okayama University |
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Principal Investigator |
MATSUOKA Jyunji Okayama University, 大学院・医歯薬学総合研究科, 教授 (30332795)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAZAWA Takuya 川崎医科大学, 医学部, 講師 (20379845)
ONO Toshiro 岡山大学, 自然生命科学研究支援センター, 准教授 (50185641)
MOMINOKI Katsumi 岡山大学, 自然生命科学研究支援センター, 准教授 (70304615)
TANAKA Noriaki 岡山大学, 大学院・医歯薬学総合研究科, 教授 (10127566)
YAMATSUJI Tomoki 岡山大学, 岡山大学病院, 助教 (40379730)
NAOMOTO Yoshio 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (00237190)
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| Co-Investigator(Renkei-kenkyūsha) |
TSUTYA Tomoshi 長崎大学, 医学部・歯学部附属病院, 医員 (30437884)
TANAKA Hirotosh 東京大学, 医科学研究所, 准教授 (00171794)
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| Project Period (FY) |
2008 – 2010
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| Keywords | surfactant protein / non small cell lung cancer / adenovirus / KRas / intratracheal administration / TTF1 |
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| Research Abstract |
Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to dysfunctional lung cells that reside within an intricate lung structure. To investigate whether pulmonary surfactant enhances the efficacy of intratracheal instillation of a therapeutic virus to target advanced non small cell lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into an advanced lung cancer model mouse intratracheally with or without surfactant. A therapeutic adenovirus that induces cell death only in lung cancer cells was constructed by combining a lung cancer specific promoter fused to cytotoxic E1A. This adenovirus was intratracheally injected into the KRAS or KRASlung cancer model mice (CCSP-rtTA/Tet-op・K-Ras4bG12D bitransgenic mice or CCSP-rtTA/Tet-op・K-Ras4bG12D・p53- tripletransgenic mice) in the presence/absence of pulmonary surfactant. Intratracheally-injected therapeutic adenovirus with pulmonary surfactant spread to airways as well as to the alveolar region of the lung and caused reduction of lung tumors developed in the lung cancer model mice. The therapeutic adenovirus without pulmonary surfactant spread only to airways and had ten times less effectiveness in tumor reduction. Here, we demonstrate that pulmonary surfactant is an efficient tool to intratracheally deliver a therapeutic virus to treat advanced lung cancer in vivo.
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[Journal Article] Targeting KRAS Mutation-bearing Lung Cancer In Vivo by Pulmonary Surfactant-Adenovirus-mediated Gene Transfer.2010
Author(s)
Fukazawa T, Maeda Y, Matsuoka J, Ono T, Mominoki K, Yamatsuji T, Shigemitsu K, Morita I, Murakami I, Tanaka H, Durbin ML, Naomoto Y.
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Journal Title
Anticancer Research. 125
Pages: 4925-4935
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[Presentation]2010
Author(s)
深澤拓也
Organizer
岡山癌免疫研究会
Place of Presentation
岡山
Year and Date
2010-06-22
