| Project/Area Number |
15390441
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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 |
Cerebral neurosurgery
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
IMAHORI Yoshio KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR, 医学研究科, 助教授 (80191899)
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| Co-Investigator(Kenkyū-buntansha) |
MINEURA Katsuyoshi KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, PROFESSOR, 医学研究科, 教授 (70134103)
SASAHIMA Hiroyasu KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSOCIATE PROFESSOR, 医学研究科, 講師 (80196188)
TAKAHASHI Yoshinobu KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSISTANT PROFESSOR, 医学研究科, 助手 (90347451)
INOUE Yasuo KYOTO PREFECTURAL UNIVERSITY OF MEDICINE, ASSISTANT PROFESSOR, 医学研究科, 助手 (60363975)
ONO Kouji KYOTO UNIVERSITY, KURRI, PROFESSOR, 原子炉実験所, 教授 (90122407)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Glioma / angiogenesis / VEGF / in situ hybridization / positron-labeled antisense / PET / aminoacid transport / fluoroboronophenylalanine / 血管新生 / VEGF / ポジトロン標識antisense / antisense / in vivo hybridization / Brigati標識プローブ |
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| Research Abstract |
Angiogenesis in cancer and brain tumor plays an important role in proliferation and invasion. Expression of the mRNAs of vascular endothelial growth factor(VEGF) and their receptors accelerate tumor proliferation together with tumor angiogenesis. Elucidation of expression of the mRNAs in vivo is a problem to be solved. In the present study we attempted basic research for imaging of expression of mRNA by positron emission tomography(PET) with positron labeled antisense oligo deoxynucleic acid (ODN). In experiment using in situ hybridization method, DNA-sequence dependent images of VEGFmRNA expression were successfully obtained. Positron labeled antisense ODNs were obtained easily by C-11 ethylketene method. Sequence of positron labeled antisense oligonucleotide probe for VEGFmRNA was optimized as 5'-TGG TGA GGT TTG ATC CGC AT-3' and it was checked from the result of in situ hybridization. Correlation of the Brigati stain method probe by the in situ hybridization method and ^<11>C-activi
… More
ty was observed using the sequence. As for the result, positive correlation was observed in each activity by in situ hybridization ; the Brigati probe and the positron activity antisense. Using C-11 labeled mRNA antisense oligonucleotide probe, when hybridization efficiency was compared using antisense-BioMag and sense-BioMag, the increase in 35% of affinity was observed in sense-BioMag fraction, and it was proved that a specific binding takes place to a base-sequence specificity. Imaging of the angiogenesis by positron emission tomography was performed by ^<18>F-fluoroboronophenylalanine-PET since amino acid transport increased with angiogenesis of a brain tumor. As a result, with the malignant brain tumor case, it was suggested increase in a tumor blood vessel by angiogenesis accompanied with an increase in aminoacid transport.
This result suggested the possibility for visualization of the expression of VEGF mRNA. In conclusion these studies demonstrated that visualization of the expression of mRNAs in vivo is possible based on DNA sequence manner by positron labeling ODN antisense method. Less
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