| Project/Area Number |
12460138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60163804)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Nobuo The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60107414)
MASUDA Kenichi The University of Tokyo, Graduate School o Agricultural and Life Sciences, assistant, 大学院・農学生命科学研究科, 助手 (40313077)
OHNO Koichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (90294660)
OKUDA Masaru Yamaguchi University, Faculty of Agriculture, assistant, 農学部, 助手 (10325243)
HISASUE Masaharu Azabu University, Faculty of Veterinary Medicine, assistant, 獣医学部, 助手 (80333144)
阪口 雅弘 国立感染症研究所, 免疫部, 主任研究官 (20170590)
白石 明郎 三共株式会社, 第三生物研究所, (研究職)所次長
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2001: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2000: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | Tumor marker / Telomere / Telomerase / Multidrug resistance / MDM2 / Feline leukemia virus / Clonarity / P-glycoprotein / P糖蛋白質 / イヌ / DNAワクチン / Cry j 1 / T細胞エピトープ / アトピー性皮膚炎 / 犬 / 猫 / P53 / P糖蛋白 |
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| Research Abstract |
In order to show the usefulness of tumor markers in veterinary medicine, we measured a variety of tumor markers in dogs and cats with neoplastic diseases in small animal practice. During the 2 years for the present study, we investigated the usefulness of tumor markers classified into 6 categories : (1) serum (plasma) tumor marker, (2) intracellular telomerase and telomerase reverse transcriptase, (3) expression of P-53 and MDM2 and mutation of p53 gene, (4) cell clonarity, (5) chromosome abberation, and (6) P-glycoprotein (P-gp) associated with multidrug resistance. Major results of the present study are as follows.
1.We measured the telomere length and intracellular telomerase activity in canine mammary tumors and found that telomerase activity could be used as a tumor marker.
2.We examined the sequence of p53 gene in naturally occurring tumors in dogs and cats and found that p53 gene was mutated in approximately 50% of the dog tumors, therefore, found that mutation of p53 gene could b
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e used as a tumor marker in dogs. Moreover, a large number of dog tumors were shown to have an overexpression of MDM2 (a protein inhibiting P-53) which could be a candidate of new tumor marker.
3.Southern blot analysis using exogenous feline leukemia virus (FeLV) was carried out in the peripheral blood samples and biopsy specimens of tumors, bone marrows and lymph modes. As a result, monoclonal or oligoclonal cell population was detected in neoplastic deseases (leukemia and myelodysplastic syndrome, MDS) and it was found that the cell clonality could be used as a new tumor marker in FeLV-infected cats.
4.Nucleotide sequences of canine and feline mdr (multidrug resistance) genes that encodes P-gp were determined. Expressions of mdr RNA and P-gp protein were examined by RT-PCR and immunohistochemistry using a monoclonal antibody directed P-gp (C219), respectively, in tumor cells. By the treatment with antineoplastic drugs in conjunction with P-gp inhibitor, response to the chemotherapy was shown to be improved. Less
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