| Project/Area Number |
13671364
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kurume University |
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Principal Investigator |
SHIROUZU Kazuo Kurume University, School of Medicine, Professor, 医学部, 教授 (20216203)
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| Co-Investigator(Kenkyū-buntansha) |
OGATA Yutaka Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (20177124)
TSUDA Hideaki Kurume university, School of Medicine, Professor, 医学部, 教授 (10080920)
吉田 祥吾 久留米大学, 医学部, 助手 (30191589)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | antineoplaston A10, AS2-1 / G1 cell arrest / apoptosis / demethylation / colorectal metastasis to the liver / post-operative adjuvant chemotherapy / randomized clinical trial / hepatic arterial infusion chemothera / アンチネオプラストン / AS2-1 / A10-I / 大腸癌 / G1細胞休止 / アポトーシス / p16 / p21 / サイクリン / A-10 / 同所性大腸癌治癒切除モデル / 補助療法 |
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| Research Abstract |
(in vitro study)
Antineoplaston AS2-1 inhibited colon cancer cell (KM12SM, SW620, SW1417, Colo206, HCTI16) proliferation in a dosage-and time-dependent manner through G1 cell arrest and induction of apoptosis. AS2-1 up-regulated the protein expression of cyclin D and cyclin E, and down-regulated the protein expression of p-16 and p21, resulting down-regulated the protein level of phosphorylated Rb in KM12SM and HCT116 cells. Five mg/ml of AS2-1 induced apoptosis in tumor cells through down-regulation of XIAP and up-regulation of caspase 3 and caspase 8. Methyl scan DNA chip study revealed that AS2-1 normalized or reduced the hyper methylation in various genes.
(in vivo study)
AS2-1 inhibited the growth and tumorigenecity of implanted colon tumors (KM121SM, HCT116) into the subcutis in nude mice. AS2-1 showed significant reduction in lung metastasis and prolongation of survival time using removal model of orthotopically implanted colon cancer in nude rats.
(Clinical study)
We have conducted a randomized control study after hepatectomy in colorectal metastasis to the liver. Hepatic arterial infusion chemotherapy using 5-FU with or without antineoplastons was performed in 64 patients between 1998 and 2004. There was no significant difference in disease-free survival rate between the two groups, however the survival rates in antineoplaston group was tended to be higher than that in the control group. Further follow-up should be necessary to conclude usefulness of antineoplastons.
Antineoplastons would be effective in colorectal cancer in particular in adjuvant setting in combination with cytotoxic chemotherapeutic agents.
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