| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Research Abstract |
Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type I (HTLVI), and the histology usually indicates a pleomorphic type, but the histology is not uniform. To clarify the relation between the histological classification and prognosis, we reclassified 572 cases with nodal T-cell lymphoma. In all cases, the clonal integration of HTLV-I proviral DNA was examined, using a Southern blot analysis. 572 cases were classified into 3 groups ; (A) the cases with clonal integration [247 cases], (B) cases with AThA, and those without clonal integration of HTLV-I proviral DNA [66 cases}, (C) cases without A ILA [259 cases]. Group A clinically showed a poorer prognosis than groups B and C. In conclusion, group Awas determined to be ATLL (HTLV-I associated T-cell lymphoma). (Br J haematol 1998, 101, 703-11)
ATLL demonstrate clonal chromosome abnormalities, but the karyotypes are very complicated in both number and structure. There are no specific ka
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ryotype abnormalities in ATLL. We investigated the integration site of HTLY-I, using inverse-PCR and FISH. The random integration was confirmed. In 15 of the 18 cases, the chromosomes with HTLV-I integration showed abnormalities, and, especially in 2 cases with simple chromosome abnonnalities, HILV-I integrated int the abnormal chromosome, but not into the normal chromosome. The HTLY-I proviral integration thus seems to, be associated with chromosome abnormalities. (Cancer Letters 1998, 132, 203-12)
The recently identified decoy receptor 3 (DcR3) binds to Fa.sL and inhibits FasL-induced apoptosis, and is considered to play a role in the immune escape system of neoplastic cells. We analysed the amplification and expression of DcR3, using dot blot and in situ hybridization (ISH), in 45 cases, which included 17 cases with Epstein-Barr virus (EBV) associated lymphorna, 7 cases with adult T-cell leukemia lymphoma (AILL). EBV-associated PAL and NKL exhibited DcR3 amplification and expression in lymphoma cells. AILL also showed DcR3 expression and amplification. The DcR3 expression was not in the reactive cells. (Cancer Letter, 2000, 160, 89-97)
The BUB gene is a component of the mitotic checkpoint in budding yeast. Recently, human homologues of the BUB were identified and mutant alleles of hBUB1 and hBUBR1 were detected in two colorectal tumor cell lines. We examined the role of checkpoint gene in the chromosomal abnormalities of ATLL by investigating mutations of hBUB1 and hBUBR1, and MIN of replication errors of BAX, insulin-like growth factor, and transforming growth factor type II. Significant mutations/deletion of hBUB1 or hBUBR1 were detected in 4 of 10 cases with ATLL. In contrast, only one of eight B cell lymphomas showed nonsense mutation of hBUBR1.None of the ATLL and B cell lymphomas showed MIN. (Cancer Letters, 2000, 158, 141-50) Less
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