| Project/Area Number |
13470270
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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 | Mie University |
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Principal Investigator |
TAKAO Motoshi Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (30263007)
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| Co-Investigator(Kenkyū-buntansha) |
NOBORI Tsutomu Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60106995)
YADA Isao Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80093152)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Lung cancer / Chemotherapy / Chemosensitivity test / MTAP / MTX / L-alanosine / MTA / プリン新生合成酵素阻害剤 / CD-DST法 / 感受性試験 / 遺伝子変遺 / プリン代謝 / Translational research |
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| Research Abstract |
Following are our conclusion of MTAP study on resected non-small cell lung cancer without preoperative treatment.
1. Diagnosis of MTAP deficiency in lung cancer
Negative expression of MTAP on IHC using MTAP-MoAb and MTAP gene deletion on RT-PCR were found in 36 (44.4%) of 81 cases and in 24 (32.9%) of 73 cases. The rate concordance between two methods was 63/70 (90%) with significant correlation (p<.001). Hypermethylation in the MTAP promoter lesion was observed in all seven samples showing positive PCR and negative IHC results. IHC was specific enough to diagnose MTAP deficiency in solid tumor as lung cancer.
2. Correlation of IHC between on MTAP and on P16 of P53
Concordance of expression pattern on IHC was found in 71% between MTAP and p16 (MTAP(+)/p16(+) in 35 of 65 cases and MTAP(-)/p16(-) in 11 of 65) showing significant correlation (p<.001), but in only 45% between MTAP and p53 without any correlation.
3. In vitro test for Selective chemotherapy by purine de novo synthesis targeting MTAP deficiency in lung cancer
MTAP status did not affect the chemosensitivity of MTX nor L-ALA in the culture condition without MTA (ie. Ineffective status for salvage pathway of purine synthesis). Although ddition of MTA in culture medium had no effect on chemosensitivity of MTX nor L-ALA in MTAP (-) cancer cells, it decreased inhibition rate from 60.5% to 42.3% (p<.05) and from 55.7% to 29.9% (P<.001) in MTAP (+) cancer cells when it was tested with MTX and L-ALA, respectively.
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