Development of the novel peptide-based therapeutics for the molecular targeting agent-resistant lung cancers.
| Project/Area Number |
23590442
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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 | Aichi Cancer Center Research Institute |
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Principal Investigator |
KONDO Eisaku 愛知県がんセンター(研究所), 腫瘍病理学部, 部長 (30252951)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Ken 愛知県がんセンター(研究所), 腫瘍病理学部, リサーチレジデント (70426584)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺がん / 分子標的 / 耐性機構 / ペプチド / 分子標的薬 |
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| Research Abstract |
We aimed to characterize the distinct molecular response to gefitinib between the drug-resistant and drug-sensitive lung adenocarcinoma cells in order to learn about therapeutics based on the molecular information. Consequently, we found a specific increase in p14^<ARF> expression in gefitinib-sensitive lung adenocarcinoma clones, which was absent in gefitinib-resistant clones. Moreover, we identified the amino acid residues spanning from 38 to 65 as a functional core of mitochondrial p14^<ARF> (p14 38-65 a.a.), which reduced the mitochondrial membrane potential and caused caspase-9 activation. The synthesized peptide covering the p14 38-65 a.a.induced growth suppression of the gefitinib-resistant clones without affecting non-neoplastic cells. These findings suggest that the region of p14^<ARF> 38-65 a.a. is critical in the pharmacological action of gefitinib against EGFR-mutated lung adenocarcinoma cells and has potential utility in the therapeutics of gefitinib-resistant cancers.
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Report
(3 results)
Research Products
(54 results)
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[Journal Article] Lineage-specific growth inhibition of NK cell lines by FOXO3 in association with Akt activation status.2012
Author(s)
Karube K, Tsuzuki S, Yoshida N, Arita K, Liu F, Kondo E, Ko YH, Ohshima K, Nakamura S, Kinoshita T, Seto M.
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Journal Title
Exp Hematol.
Volume: (Epub ahead of print)
Related Report
Peer Reviewed
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[Journal Article] Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems.2012
Author(s)
Kondo E, Saito K, Tashiro Y, Kamide K, Uno S, Furuya T, Mashita M, Nakajima K, Tsumuraya T, Kobayashi N, Nishibori M, Tanimoto M, Matsushita M.
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Journal Title
Nature Commun.
Volume: 3
Pages: 951-963
Related Report
Peer Reviewed
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[Journal Article] TGF-・ synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.2012
Author(s)
Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H and Sekido Y.
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Journal Title
J. Exp. Med.
Volume: 209(3)
Pages: 479-94
Related Report
Peer Reviewed
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[Journal Article] Lineage-specific growth inhibition of NK cell lines by FOXO3 in association with Akt activation status.2012
Author(s)
Karube K, Tsuzuki S, Yoshida N, Arita K, Liu F, Kondo E, Ko YH, Ohshima K, Nakamura S, Kinoshita T, Seto M.
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Journal Title
Exp. Hematol.
Volume: 40
Issue: 12
Pages: 1005-1015
DOI
Related Report
Peer Reviewed
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[Journal Article] NFATc1 affects mouse splenic B cell function by controlling the calcineurin-NFAT signaling network.2011
Author(s)
Bhattacharyya S, Deb J, Patra AK, Thuy Pham DA, Chen W, Vaeth M, Berberich-Siebelt F, Klein-Hessling S, Lamperti ED, Reifenberg K, Jellusova J, Schweizer A, Nitschke L, Leich E, Rosenwald A, Brunner C, Engelmann S, Bommhardt U, Avots A, Muller MR, Kondo E and Serfling E.
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Journal Title
J. Exp. Med.
Volume: 208(4)
Pages: 823-39
Related Report
Peer Reviewed
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[Journal Article] miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg.2011
Author(s)
Yamamoto M, Kondo E, Takeuchi M, Harashima A, Otani T, Tsuji-Takayama K, Yamasaki F, Kumon H, Kibata M and Nakamura S.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Potent anti-tumor killing activity of the multifunctional Treg cell line HOZOT against human tumors with diverse origins.2011
Author(s)
Inoue T, Tashiro Y, Takeuchi M, Otani T, Tsuji-Takayama K, Okochi A, Mukae Y, Koreishi M, Yamasaki F, Kumon H, Nakamura S, Kibata M and Kondo E.
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Journal Title
Int. J. Oncol.
Volume: 38(5)
Pages: 1299-1306
Related Report
Peer Reviewed
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