| Project/Area Number |
06671360
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Thoracic surgery
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| Research Institution | Dokkyo University |
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Principal Investigator |
CHIMOTO Masayuki Dokkyo Univ.Sch.Med., Lecture, 医学部, 講師 (40191902)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Koichiro Dokkyo Univ.Sch.Med., Professor, 医学部, 教授 (60009488)
YASUDA Shin-ichi Dokkyo Univ.Sch.Med., Instractor, 医学部, 研究員 (60133279)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Lung cancer / Growth inhibition / Molecular analysis / Antisense oligonucleotide / 肺炎 / 癌遺伝子 |
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| Research Abstract |
Usually the specificity of basis on cell cytotoxity for cancer chemotherapy has been dependent upon the uptake ratio of drugs to difference of originate in cell growth between tumor and normal cells. In advance tumor account of most of tumors, because getting good results by long prognosis of chemotherapy for patients was insufficient, now new drugs and therapy are expected eagerly. Then we made plan for the specific inhibition of tumor cell growth in lung cancer by oligonucleotides, founded on information of cell biology. The target gene we chose were transforming growth factor-alpha (TGF-alpha), which we considered the high expression on lung cancer, frequency of crisis, and having resistance for chemotherapy in adenocarcinoma.
We produced phosphorothioate-modified antisense oligonucleotide spanning the 3-end codons of TGF-alpha mRNA.Analysis of TGF-alpha mRNA expression in cancer cell lines by RT-PCR,we observed 7 lines of lung cancer and osteosarcoma line, and especially strong expression of these gene were shown in 3 lung cancer cell lines. Antisense oligonucleotide suppressed the growth of HPC-93EP cells, which expressed TGF-alpha gene strongly, the effect was on dose dependent manner, on other hand the sense oligonucleotide had no effect. TGF-alpha antisense oligonucleo-tide decreased TGF-alpha mRNA and protein expression when analyzed by RT-PCR and flow cytometry.
Thus antisense oligonucleotide to growth factor might be promising as a possible therapy for lung cancers.
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