| Project/Area Number |
63870107
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| Research Category |
Grant-in-Aid for Developmental Scientific Research.
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KASUGA Tsutomu Tokyo Med. Den. Univ., Sch. Med., Professor, 医学部, 教授 (40114748)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Soji Tokyo Med. Den. Univ., Sch. Med., Professor, 医学部, 教授 (80013829)
KITAGAWA Masanobu Tokyo Med. Den. Univ., Sch. Med., Assistant, 医学部, 助手 (10177834)
YAMADA Ichiro Tokyo Med. Den. Univ., Sch. Med., Assistant, 医学部, 助手 (90182518)
ITO Shosuke Fujita-Gakuen Univ., Sch. Hyg., Professor, 衛生学部, 教授 (70121431)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1989: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1988: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Malignant melanoma / Melanin precursor / 4-S-cysteaminylphenol / Radiosensitivity / Radiosensitization / メラニン前駆物質 / 4ーSーcysteaminylphenol / 4ーSーcyteaminylphenol / 放射線併用効果 / 相乗効果 / G2@M期ブロック / in vivo / in vitro |
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| Research Abstract |
A. The combination effect of 4-S-cysteasinylphenol (4-S-CAP) and radiation was examined. 4-S-CAP decreased the shoulder width of the survival curve of HMV-I melanoma cells. However, the same treatment with 4-S-CAP did not significantly affect the radiation sensitivity of HeLa S3 cells. Many investigators have demonstrated that the large shoulder in the survival curve of melanoma cells may be related to the poor radiation response that has been clinically observed in human melanoma. Thus, 4-S-CAP may be an effective means of overcoming the large shoulder in melanoma cells. 4-S-CAP inhibited the sublethal damage repair in melanoma cells in the split-dose experiment. Further, 4-S-CAP inhibited the potentially lethal damage (PLD) repair in melanoma cells during their plateau phase.
B. The LD^<50> value of 4-S-CAP was 467<plus-minus>32 mg/kg in C57BL/6J male mice (12-16 weeks age). The ip injection of 4-S-CAP (300 mg/kg) for 5 days showed a significant effect on the tumor growth inhibition a
… More
nd survival interval elongation in B16 melanoma-bearing mice. The combination experiment of 4-S-CAP (300 ig/kg) and radiation (5 Gy) showed no significant potentiating effect of 4- S-CAP on the radiation action in the growth inhibition of B16 melanoma. The lung colony formation experiment showed that 4-S-CAP decreased the colony formation rate significantly, as compared to the untreated controls.
C. We synthesized four new analogues of 4-S-CAP, i.e., N-acetyl-4S-CAP (N-Ac- 4-S-CAP), 4-S-homocysteaminylphenol (4-S-HomoCAP), alpha-methyl-4-S-cysteaminyl- phenol (alpha-Me-4-S-CAP), and N,N-dimethyl-4-S-cysteaminylphenol (N,N-DiMe-4-S- CAP). The depigmenting effect for the hair follicle melanocytes in mice was the most prominent in N-Ac-4-S-CAP (98%), followed by alpha-Me-4-S-CAP (89%) and 4-S-CAP (87%). The effect on the inhibition of the lung colony formation was about 70% in 4-S-CAP and N-Ac-4-S-CAP, respectively. These data suggest that N-Ac-4-S-CAP may be a new antitumor agent in the management of melanomas. Less
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