| Project/Area Number |
14370777
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tohoku University |
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Principal Investigator |
ABE Takaaki Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (80292209)
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| Co-Investigator(Kenkyū-buntansha) |
UNNO Michiaki Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (70282043)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2003: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2002: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | organic anion transporter / LST-2 / cancer / Methothrexate / adenovirus / 抗癌剤 / メトトレキセート / ホルモン |
|---|
| Research Abstract |
One approach to the development of targeted cancer chemotherapy exploits increased uptake of the agent into neoplastic cells. In this scenario, higher concentrations of the agent in cancer cells are responsible for differential killing while the low concentration in normal human cells decreases side effects.
We have isolated the organic anion transporter OATP/LST family which exclusively expressed in various gastrointestinal cancers. We have established LST-1 and LST-2 recombinant adenoviruses, termed AdLST-1 and AdLST-2. In vivo effects of the combination of MTX with the adenoviruses were estimated in a subcutaneous tumor model using SCID mice. Tumors treated with AdLST-1/MTX or AdLST-2/MTX grew more slowly than those treated with Adβ-gal/MTX. Whole-body autoradiographs confirmed that incorporation of [^3H]-MTX in tumors of mice treated with AdLST-1/MTX and AdLST2/MTX. Our observations strongly support the possibility that overexpression of influx pumps is a new avenue in the enhancement of cancer chemotherapy.
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