| Project/Area Number |
05044157
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Hamamatsu Univ. |
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Principal Investigator |
OHNO Ryuzo hamamatsu Univ.School of Medicine professor, 医学部, 教授 (70093002)
大野 龍三 (1995) 浜松医科大学, 医学部, 教授
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| Co-Investigator(Kenkyū-buntansha) |
SHOU Dong Shanghai Second Medical Univ.Lecturer, 医学部, 講師
CHEN Sai-juan Shanghai Second Medical Univ.Lecturer, 医学部, 講師
CHEN Zhu Shanghai Second Medical Univ.professor, 医学部, 教授
WANG Zen-yi Shanghai Second Medical Univ.professor, 医学部, 教授
TAKESHITA Akihiro Hamamatsu Univ.School of Medicine Assistant, 医学部, 助手 (00242769)
NAOE Tomoki Nagoya Univ.Associate professor, 医学部, 助教授 (50217634)
OHNISHI Kazunori Hmamatsu Univ.school of Medicine Lecturer, 医学部, 講師 (80252170)
CHUO Dong 上海第二医科大学, 医学部, 講師
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | all-trans retinoic acid / acute promyelocytic leukemia / Vitamin A / PML / As_2O_3 / Am-80 / apoptosis / retinoid / cytoplasmic retinoic acid binding protein / レチノイン酸 / 分子生物学 / PML遺伝子 / RAR遺伝子 |
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| Research Abstract |
The partners of this cooperative project, Prof.Z.Wang et al. at the Shanghai Second Medical School, reported for the first time in the world in 1998 that all-trans retinoic acid (ATRA), an active form of Vitamin A, produced 93% complete remission (CR) in acute promyelocytic leukemia (APL) as a differentiation therapy. After having a Joint Meeting of Japanese and Chinese Societies of Hematology in 1960, we started the ATRA therapy for chemotherapy-refractory APL, and confirmed its remarkable effectiveness in APL producing more than 80% of CR.Nowadays more than 60% of newly diagnosed APL patients are cured with ATRA and subsequent chemotherapy.
This project mainly focused on the mechanism how ATRA works on APL from a molecular biological point on view. We have exchanged not only the knowledge and information on this point but also materials such as APL cells of patients from both countries and a monoclonal antibody, which had been produced in our laboratory, against the PML protein, the product of a plausible responsible gene on the leukemogenesis of APL.We have also exchanged newest information on a new promising therapy using As_2O_3 which is a main component of a Chinese traditional medicine against leukemia, and which reportedly produced more than 90% CR in APL by Chinese traditional medical doctors, and on our new synthetic retinoid, Am-80, with a low affinity to the cytoplasmic retinoic acid binding protein, an increase of which is one of the reasons of ATRA resistance. Am-80 produced more than 50% CR in APL which relapsed from ATRA-induced remission and is generally resistant to the re-treatment with ATRA.As_2O_3 seems to have a different mechanism of action from ATRA, since it not only induces differentiation but causes apoptosis in NB-4 cells, APL-derived cultured cells as well as APL cells from patients.
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