| Project/Area Number |
15592095
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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 |
Surgical dentistry
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
MORIKAWWA Hidehiro Tohoku University, Graduate School of Dentistry, Asistant Professor, 大学院・歯学研究科, 助手 (60302155)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Shiro Tohoku University, Hospital, Lecturer, 病院・講師 (80230069)
CHIBA Masatoshi Tohoku University, Graduate School of Dentistry, Asistant Professor, 大学院・歯学研究科, 助手 (70261526)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | oral squamous cell carcinoma / cancer chemotherapy / Dihydropyrimidine dehydrogenase / 5-fluorouracil / cisplatin / side effect / RT-PCR / mRNA / Dihydro pyrimidine dehydrogenase |
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| Research Abstract |
To evaluate the influence of 5-FU based on the dihydropyrimidine dehydrogenase (DPD) expression in normal and tumor cells, we examined immunohistochemical expression of DPD in tissue sections of oral squamous cell carcinoma. The result of immunohistochemistry was different according to whether formalin-fixed and paraffin-embedded tissue sections or fresh frozen tissue sections were used. Moreover stainability of DPD varied from place to place even on the same section. On the other hand, to evaluate the influence of 5-FU on normal cells, the induction of apoptosis in human peripheral mononuclear cells by 5-UF was examined. However the correlation with the mRNA expression of the apoptosis-associated proteins and actual induction of apoptosis could not be clarified. Consequently it seemed to be difficult to forecast the induction of actual apoptosis from the mRNA expression of the apoptosis-associated proteins in the peripheral blood cells obtained from the patients. Previously we experienced a patient who had a serious side effect caused by administering 5-FU. The DPD activity of the patient was considerably lower than the level that has been reported. For such a case, the evaluation of DPD activity before administering 5-FU could become a very effective index. However, since evaluation of the DPD activity of the tumor cells was difficult, and meaning of the mRNA expression of the apoptosis-associated proteins was obscure, as mentioned above, more examinations are necessary for showing the effectiveness of the preoperative assessment of the DPD activity in patients of large majority. Recently we started the development of a new cancer chemotherapy that was able to administer 5-FU even to the patients with low DPD activity in the normal tissue, and we obtained a promising, basic data that suggested a possible method by which effectiveness could be maintained even if the amount of use of 5-FU was decreased.
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