| Project/Area Number |
15590325
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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 |
Human pathology
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| Research Institution | Fukuoka University |
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Principal Investigator |
SUZUMIYA Junji Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (70206556)
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| Co-Investigator(Kenkyū-buntansha) |
OHSHIMA Koichi Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (50203766)
NABESHIMA Kazuki Fukuok University, School of Medicine, Associate Professor, 医学部, 助教授 (40189189)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | non-Hodgkin's lymphoma / Diffuselarge B cell lymphoma / Chemotherapy / CHOP therapy / Chemo-resistance / DNA microarray / 悪性リンパ腫 / DLBCL / cDNAマイクロアレイ / mRNA / 非ホジキンシンパ腫 / びまん性大細胞型B細胞リンパ腫 |
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| Research Abstract |
[Background and Purpose] The standard therapy is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy for advanced diffuse large B-cell lymphoma (DLBCL) patients. About 80% patients of DLBCL reach the remission by CHOP therapy, but the remain of patients are resistant to this therapy. We studied the difference of genetic characteristics between the chemo-sensitive and chemo-resistant groups using cDNA microarray
[Patients and Methods] We selected 6 patients of CHOP-sensitive and 7 of CHOP-resistant DLBCL. We analyzed the gene expression profile of both CHOP-sensitive and CHOP-resistant groups by cDNA microarray using Cancer chip version 4.0 (Takara Bio company, Otsu, Japan).
[Results] To clarify CHOP-resistant predictor genes, we chose genes that were differentially expressed between CHOP-resistant and sensitive groups (p<0.05) in student t-test. Moreover, we selected the genes within these genes, which of CHOP-resistant group were differentiated positively or negatively more than three times of that of CHOP-sensitive group. Hierarchical clustering showed the clearly different pattern in CHOP-resistant and sensitive groups using these selected genes. There were 8 up-regulated genes included PRAME (Preferentially expressed antigen of melanoma) in CHOP-resistant group and one down-regulated gene, CD79a in CHOP-sensitive group. Furthermore, we studied the relationship, between the expression of PRAME and clinical course using RT-PCR. PRAME was positive in 23 of 77 patients with DLBCL. The survival of PRAM E positive patients was shorter than that of PRAME negative patients (p=0.0565). PRAME was positive in 12 of 45 patients having disease free survival. The prognosis of PRAME positive patients was significantly poorer than that of negative patients (p=0.037).
[Conclusion] The expression of PRAME predicts the resistance of CHOP therapy in DLBCL
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