| Project/Area Number |
07671365
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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 | The University of Tokyo |
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Principal Investigator |
FUJII Yuzo INST.of MED.SCIENCE,Dpt. of CLINICAL ONCOLOGY,INSTRUCTOR, 医科学研究所, 講師 (40143515)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGIE Hironobu INST.of MED.SCIENCE,Dpt. of SURGERY CLINICAL,ASSOCIATE, 医科学研究所, 助手 (30212278)
MORI Shigero INST.of MED.SCIENCE,Dpt. of PATHOLOGY,PROFFESSOR, 医科学研究所, 教授 (30010424)
NARIUCHI Hideo INST.of MED.SCIENCE,Dpt. of ALLERGY,PROFFESSOR, 医科学研究所, 教授 (10012741)
MATSUZAWA Akio INST.of MED.SCIENCE,Dpt. of EXPERIMENTAL ANNIMALS,ASSOCIATE PROFFESSOR, 医科学研究所, 助教授 (50012745)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | spontaneous liver metastasis / LMFS / HCFU / Inhibition of metastasis / ND2001 / p-53 / point mutation / chemotherapy / 浸潤 |
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| Research Abstract |
A new spontaneous liver metastasis model from LMFS tumor, that is a retroperitoneal sarcoma of BALB/c mouse origin, was reported. After a subcutaneous injection of LMFS cells in the footpad, amptation of the leg was performed and killed at day 25 under anesthesia. The LMFS cells proliferated at the inoculation site and all mice operated after day 15 had metastatic nodules spontaneously in the liver, and liver weight was relation with tumor growth in the liver. (1) The combination therapy of operation and HCFU was examined against the footpad injection model. The foot of injection side was amputated in day 12 with or without HCFU administration and mice were sacrified at day 33. The results shows operation with chemotherapy is most useful treatments against liver metastases. (2) We examined the inhibitory effect of Sodium D-Glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam ; ND2001) upon liver metastases of the LMFS tumor. The ND2001 showed neither cytocidal nor antitumor activity. Both the invasive activity (in vitro) and liver metastasis (in vivo) was reduced by ND2001. These results suggested that ND2001 inhibited liver metastases at the invasive step into the basement membrane and may have a potential of anti-metastatic drug. (3) Using PCR-SSCP analysis, we examined p53 gene mutations in DNA samples extracted from LMFS cells. Both of the LMFS cells and the metastatic liver tumor, a mobility shift in SSCP analysis was detected in exon 5 and exon 7. By direct sequencing, the position of the mutations were distributed as follows : exon 5 (codon 176) and exon 7 (codon 248) and all were point mutations. In vitro growth of the retroviral-p53-infected LMFS cells were greatly suppressed and cells might undergo apoptosis. The p53 protein was detected in the retroviral-p53-infected LMFS cells.
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