| Project/Area Number |
14570141
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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 | Osaka University |
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Principal Investigator |
HOSHIDA Yoshihiko Osaka University, Hospital, Assistant professor, 医学部附属病院, 助手 (40324777)
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| Co-Investigator(Kenkyū-buntansha) |
HONGYO Tadashi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90271569)
AOZASA Katsuyuki Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (30115985)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Autoimmune disease / Lymphproliferative disorders / Malignant lymphoma / Rheumatoid disease / Epstein-Barr virus / immunosuppressive state / PCR-SSCP / p53 |
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| Research Abstract |
Excess of intractable malignancies such as post-transplantation lymphoproliferative disorders (PT-LPD) in patients receiving organ transplantation is well-known : depressed immunosurveillance induced by the use of immunosuppressive agents for prevention of rejection is regarded to be causative for cancer development. In this study, we analyzed mechanism for development of intractable LPD in transplant recipients and patients with autoimmune diseases (AID).
1) Gene mutation analysis in PT-LPD of T-and NK/T-cell types.
In western countries, majority of cases with PT-LPD are B-cell-derived and Epstein-Barr virus (EBV) -associated. In Japan, PT-LPD of T-and NK/T-cell types are not uncommon among renal transplant patients (Int J Cancer 2001). Mutations of p53 (exon 4 -8) were analyzed in twelve cases with PT-LPD of T-and NK/T-cell types by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing.p53 gene mutations were detected in all of 5 cas
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es of peripheral T-cell lymphoma, 3 of S (60%) cases of ATL, and one of two cases of NK/T cell lymphoma.p53 gene mutations are common in peripheral T-cell lymphoma including ATL in renal transplant recipients (Lab Invest 2002).
2) Clinicopathological features of LPD developing in rheumatoid arthritis (RA) and other AID.
LPD occasionally develop in individuals with immune deficiencies such as immunosuppressive conditions and AID. The clinicopathologic features and virus status were analyzed in 53 cases with LPD developing in RA and other AID, LPD developed after a longer interval between the onset of AID and the diagnosis of LPD in patients with RA than those in other AID. These patients showed the much favorable prognosis compared to those in other AID. Medication of RA with NSAID might work to suppress tumor growth, and thus might have contributed to favorable prognosis of LPD in RA. EBV might play a role in pathogenesis of T-cell and polymorphic B-cell LPD and Hodgkin lymphoma (HL) in AID (Int J Cancer 2004).
3) Gene mutations in LPD developing in AID.
Mutations of p53 tumor suppressor gene are associated with a poor prognosis in varying types of malignancies including sporadic B-cell lymphoma of aggressive type. p53 gene mutations were examined in 45 cases with LPD which developed in patients with prior history of AID. The frequency (46.6%) of p53 gene mutation in AID-LPD was much higher than that in the sporadic NHL (6-15%). Patients with p53 gene mutations showed less favorable prognosis than those without in not only B-cell but also T-cell NIIL developing in AID.
4) Clinicopathological features of methotrexate (MTX)-LPD
Administration of MTX for AID, most commonly RA, is regarded as causative for LPD, thus MTX-LPD is described separately in World Health Organization classification for lymphoid neoplasms. However, information for MTX-LPD is quite limited in Japan. Then nation-wide survey of MTX-LPD in Japan was conducted, revealing the clinicopathologic differences from Western countries: higher frequency of DLB CL, shorter duration between the diagnosis of RA and LPD, and much lower EBV positive rate (in submission). Less
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