| Project/Area Number |
09470146
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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 |
Respiratory organ internal medicine
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YAMAKIDO Michio Hiroshima University Faculty of Medicine, Professor, 医学部, 教授 (50034103)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Hiroyuki Hiroshima University Medical Hospital, Research Associate, 医学部・附属病院, 助手 (80274075)
HIYAMA Keiko Hiroshima University Faculty of Medicine, Research Associate, 医学部, 助手 (60253069)
ISHIOKA Shinichi Hiroshima University Faculty of Medicine, Assistant Professor, 医学部, 講師 (10191868)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | telomerase / lung cancer / PAN / antisense RNA / adenovirus vector / gene therapy |
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| Research Abstract |
Telomerase is essential for the indefinite proliferation of human cells. Its activity is detected in more than 80% of human malignant neoplasmas. Since the activation of telomerase is associated with cellular immortality, it offers the possibility that anti-telomerase strategies would be new anti-cancer therapeutics.
1. Peptide nucleic acids (PNA) - mediated inhibition of telomerase activity in various cancer cell, lines including LoVo, A549 and HeLa cells was evaluated. The antisense PNAS against RNA portion of telomerase (hTR) or catalytic domain (hTRT) demonstrated little inhibition, indicating that cellular uptake might be a limiting factor.
2. An adenovirus vector expressing antisense mRNA against hThT was constructed. Telomerase activities in human cancer cells infected with the vector were not inhibited. The results indicate that the construct of the vector needs to be further investigated.
3. Transcriptionally targeted killing of carcinoembryonic antigen (CEA)-producing adenocarcinoma cells was investigated using adenovirus vectors carrying a CEA promoter to express herpes simplex thymidine kinase. LoVo cells infected with the vector showed higher sensitivity to ganciclovir than HeLa cells infected with same vector. In combination with anti-telomerase strategy, these results would provide a rationale for transcriptionally targeting with reduced toxicity to normal cells.
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