2002 Fiscal Year Annual Research Report

移植片対腫瘍効果に関する基礎的及び臨床的研究

Research Project

Project/Area Number	14030063
Research Institution	Kyushu University
Principal Investigator	原田実根九州大学, 大学院・医学研究院, 教授 (00019621)
Co-Investigator(Kenkyū-buntansha)	権藤久司九州大学, 医学部附属病院, 講師 (10253428) 大塚輝久九州大学, 医学部附属病院, 助教授 (20185317) 中野修治九州大学, 大学院・医学研究院, 助教授 (40164248) 宮本敏浩九州大学, 医学部附属病院, 助手 (70343324) 長藤宏司九州大学, 医学部附属病院, 助手 (60343323)
Keywords	固形腫瘍 / 抹消血幹細胞 / 移植 / 同種免疫 / 腫瘍抗原 / ミニ移植 / 骨髄非破壊的
Research Abstract	44歳から64歳までの固形腫瘍患者で、化学療法や放射線療法に抵抗性となった患者を対象に、フルダラビン/エンドキサン、フルダラビン/ブスルファン、フルダラビン/TBIを前処置とし、シクロスポリン/メソトレキサートによるGVHD予防にて同種末梢血幹細胞移植を施行した。症例は計8名(膵癌5例、胃癌・大腸癌・腎癌各1例)である。7例において完全キメラの状態を確認した。100日以内の移植関連死亡は認められず、最良総合効果は、膵癌の4例にPRを認めた。GVHDは、急性3例、慢性は3例中1例に認められた。100日以内の腫瘍死は3例、100日以降が2例であった。現在評価可能の6例において、100日以内の移植関連死は認められず、8例中7例において完全キメラを達成した。以上より、本療法は固形腫瘍患者に対しても安全に施行することが可能であった。腎癌およびその他の固形癌に対して、本療法は国内外にて積極的に行われつつある。また奏功率とGVHDの強い相関も示されている。進行期膵臓癌は極めて予後が悪いが、今回5症例中4症例でPRという極めて有望な成績が得られた。今後は腎癌、膵臓癌については症例数を増やし、どのような病態で同種末梢血幹細胞移植療法が有効なのか、その因子の同定を行う予定である。GVHDと抗腫瘍効果の密接な関係を認めることから、抗腫瘍効果は腫瘍特異抗原よりminor histocompatibility抗原を介して起きている可能性が高いと推測される。したがって、抗腫瘍効果が確認された症例で、ドナーとレシペントのminor histocompatibility抗原の差違の有無を検討中である。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Shimoda K, Harada M, et al.: "Partial impairment of IL-12 and IL-18signaling in Tyk2-deficient mice"Blood. 99. 2094-2099 (2002)
[Publications] Kogawa K, Harada M, et al.: "Expression of AIRE gene in peripheral monocyte / dendric cell lineage"Imunology Letters. 80. 195-198 (2002)
[Publications] Kohara H, Harada M, et la.: "Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxy-camptothecin, and irradiation in a Cisplatin-resistant haman small cell lung cancer cell line"Clin Cancer Res. 8. 287-292 (2002)
[Publications] Nakase K, Harada M, et al.: "Overexpression of novel short isoforms of Helios in a patient with T-cell acute lympoblastic leukemia"Exp Hematol. 30. 313-317 (2002)
[Publications] Yakushiji K, Harada M, et al.: "Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation : comparison of an antigenemia assay and quantitative real-time polymerase chain reaction"Bone Marrow Transplant. 29. 599-606 (2002)
[Publications] Fujii N, Harada M, et al.: "Expression of minor histocompatibility antigen, HA-1, in solid tumor cell"Transplantation. 73. 1137-1141 (2002)
[Publications] Kobayashi S, Harada M, et al.: "A filter that prevents the spread of mail-attachment-type Trojan horse computer worms"J Medical Systems. 29. 221-225 (2002)
[Publications] Ota S, Harasa M, et al.: "Cellular processing of a multibranched lysine core with tumor antigen peptides and presentation of peptide epitopes recognized by cytotoxic T lymphocytes on antigen-presenting cells"Cancer Res. 62. 1471-1476 (2002)
[Publications] Numata A, Harada M, et al.: "Therapy-related chronic myelogenous leukaemia following autologous stem cell transplantation for Ewing's sarcoma"Br J Haematol. 117. 613-616 (2002)
[Publications] Kogawa K, Harada M, et al.: "Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1(APS-1)associated with compound heterozygous novel AIRE gene mutations"Clin Immunol. 103. 277-283 (2002)
[Publications] kawai H, Harada M, et al.: "Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy"Lung Cancer. 35. 305-314 (2002)
[Publications] Miyake K, Harada M, et al.: "Genetically determined interferon-γ production influences the histological phenotype of lupus nephritis"Rheumoatology. 41. 518-524 (2002)
[Publications] Nakashima H, Harada M, et al.: "Assochiation between IL-4 genotype and IL-4 production In the Japanese population"Genes and Immunity. 3. 107-109 (2002)
[Publications] Nagano S, Harada M, et al.: "Molecular mechanisms of LPS-induced COX-2 ezpression in human neutrophils. Involvement of MAPK pathway and regulation by anti-inflammatory cytokines"Int Immunol. 14. 733-740 (2002)
[Publications] Fujii N, Harada M, et al.: "Differentiation of monoblastic cell line UG3 into leukemic dendritic cells"Int Oncol. 21. 617-620 (2002)
[Publications] Mori T, Harada M, et al.: "Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation"Japanese Heart Journal. 43(3). 249-261 (2002)
[Publications] Makita M, Harada M, et al.: "Antilung cancer effect of WT1-specific cytotoxic T lymphocytes"Clin Cancer Res. 8. 2626-2631 (2002)
[Publications] Yoshino T, Harada M, et al.: "Expression of cutaneous lymphocyte antigen is associated with a poor outcome of nasal-type natural Killer-cell lymphoma"Br J Haematol. 118. 482-487 (2002)
[Publications] Kodani T, Harada M, et al.: "A phasIII randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with adavanced non-small cell lung cancer : long-term follow-up results and analysis of prognostic factors"Lung Cancer. 36. 313-319 (2002)
[Publications] Shibakura M, Harada M, et al.: "Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells"Br J Haematol. 118. 419-425 (2002)
[Publications] Shimoda K, Harada M, et al.: "TyK2 is reguired for the induction and nuclear translocation of Daxx which regulates IFN-α-induced suppression of B lymphocyte formation"J Immunol. 169. 4707-4711 (2002)
[Publications] Horiuch T, Harada M, et al.: "Molecular basis for Human complement C7 polymorphisms, C7^*3 and C7^*4"Bioch Biophy Res Comm. 298. 450-455 (2002)
[Publications] Takata I, Harada M, et al.: "Daily Low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer"Acta Medica Okayama. 56. 261-266 (2002)
[Publications] Kozuka T, Harada M, et al.: "Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization"Transfusion. 42. 1514-1522 (2002)
[Publications] Sakugawa T, Harada M, et al.: "Correlation between histological evaluation and PCR-based clonality analysis of gastric MALT lymphomas treated by eradication of Helicobacter pylori"J Clin Exp Hematopathology. 42. 61-66 (2002)
[Publications] Odashiro K, Harada M, et al.: "Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts-Infuences of cardiac hypertrophy and isoproterenol-"Circulation Jounal. 66. 1161-1167 (2002)
[Publications] Fujii N, Harada M, et al.: "Multilineage involvement in hypereosinophilic syndrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8"Br J Haematol. 119. 716-719 (2002)
[Publications] 下田和哉, 原田実根: "4.輸血・免疫血液認定医・専門医のための内科学レビュー2002"総合医学社. 356 (2002)
[Publications] 長藤宏司, 原田実根: "骨髄異形成症候群における造血幹細胞移植-どのようなケースに、どのような時期に、どのような移植を行うか?EBM血液疾患の治療2003-2004"中外医学社. 740 (2002)
[Publications] 長藤宏司, 原田実根: "造血幹細胞移植の原理と実際シミュレーション内科血液疾患を探る"長井書店. 229 (2002)

2002 Fiscal Year Annual Research Report

移植片対腫瘍効果に関する基礎的及び臨床的研究

Principal Investigator

原田 実根 九州大学, 大学院・医学研究院, 教授 (00019621)

Research Products

[Publications] Shimoda K, Harada M, et al.: "Partial impairment of IL-12 and IL-18signaling in Tyk2-deficient mice"Blood. 99. 2094-2099 (2002)

[Publications] Kogawa K, Harada M, et al.: "Expression of AIRE gene in peripheral monocyte / dendric cell lineage"Imunology Letters. 80. 195-198 (2002)

[Publications] Kohara H, Harada M, et la.: "Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxy-camptothecin, and irradiation in a Cisplatin-resistant haman small cell lung cancer cell line"Clin Cancer Res. 8. 287-292 (2002)

[Publications] Nakase K, Harada M, et al.: "Overexpression of novel short isoforms of Helios in a patient with T-cell acute lympoblastic leukemia"Exp Hematol. 30. 313-317 (2002)

[Publications] Yakushiji K, Harada M, et al.: "Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation : comparison of an antigenemia assay and quantitative real-time polymerase chain reaction"Bone Marrow Transplant. 29. 599-606 (2002)

[Publications] Fujii N, Harada M, et al.: "Expression of minor histocompatibility antigen, HA-1, in solid tumor cell"Transplantation. 73. 1137-1141 (2002)

[Publications] Kobayashi S, Harada M, et al.: "A filter that prevents the spread of mail-attachment-type Trojan horse computer worms"J Medical Systems. 29. 221-225 (2002)

[Publications] Ota S, Harasa M, et al.: "Cellular processing of a multibranched lysine core with tumor antigen peptides and presentation of peptide epitopes recognized by cytotoxic T lymphocytes on antigen-presenting cells"Cancer Res. 62. 1471-1476 (2002)

[Publications] Numata A, Harada M, et al.: "Therapy-related chronic myelogenous leukaemia following autologous stem cell transplantation for Ewing's sarcoma"Br J Haematol. 117. 613-616 (2002)

[Publications] Kogawa K, Harada M, et al.: "Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1(APS-1)associated with compound heterozygous novel AIRE gene mutations"Clin Immunol. 103. 277-283 (2002)

[Publications] kawai H, Harada M, et al.: "Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy"Lung Cancer. 35. 305-314 (2002)

[Publications] Miyake K, Harada M, et al.: "Genetically determined interferon-γ production influences the histological phenotype of lupus nephritis"Rheumoatology. 41. 518-524 (2002)

[Publications] Nakashima H, Harada M, et al.: "Assochiation between IL-4 genotype and IL-4 production In the Japanese population"Genes and Immunity. 3. 107-109 (2002)

[Publications] Nagano S, Harada M, et al.: "Molecular mechanisms of LPS-induced COX-2 ezpression in human neutrophils. Involvement of MAPK pathway and regulation by anti-inflammatory cytokines"Int Immunol. 14. 733-740 (2002)

[Publications] Fujii N, Harada M, et al.: "Differentiation of monoblastic cell line UG3 into leukemic dendritic cells"Int Oncol. 21. 617-620 (2002)

[Publications] Mori T, Harada M, et al.: "Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation"Japanese Heart Journal. 43(3). 249-261 (2002)

[Publications] Makita M, Harada M, et al.: "Antilung cancer effect of WT1-specific cytotoxic T lymphocytes"Clin Cancer Res. 8. 2626-2631 (2002)

[Publications] Yoshino T, Harada M, et al.: "Expression of cutaneous lymphocyte antigen is associated with a poor outcome of nasal-type natural Killer-cell lymphoma"Br J Haematol. 118. 482-487 (2002)

[Publications] Kodani T, Harada M, et al.: "A phasIII randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with adavanced non-small cell lung cancer : long-term follow-up results and analysis of prognostic factors"Lung Cancer. 36. 313-319 (2002)

[Publications] Shibakura M, Harada M, et al.: "Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells"Br J Haematol. 118. 419-425 (2002)

[Publications] Shimoda K, Harada M, et al.: "TyK2 is reguired for the induction and nuclear translocation of Daxx which regulates IFN-α-induced suppression of B lymphocyte formation"J Immunol. 169. 4707-4711 (2002)

[Publications] Horiuch T, Harada M, et al.: "Molecular basis for Human complement C7 polymorphisms, C7^*3 and C7^*4"Bioch Biophy Res Comm. 298. 450-455 (2002)

[Publications] Takata I, Harada M, et al.: "Daily Low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer"Acta Medica Okayama. 56. 261-266 (2002)

[Publications] Kozuka T, Harada M, et al.: "Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization"Transfusion. 42. 1514-1522 (2002)

[Publications] Sakugawa T, Harada M, et al.: "Correlation between histological evaluation and PCR-based clonality analysis of gastric MALT lymphomas treated by eradication of Helicobacter pylori"J Clin Exp Hematopathology. 42. 61-66 (2002)

[Publications] Odashiro K, Harada M, et al.: "Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts-Infuences of cardiac hypertrophy and isoproterenol-"Circulation Jounal. 66. 1161-1167 (2002)

[Publications] Fujii N, Harada M, et al.: "Multilineage involvement in hypereosinophilic syndrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8"Br J Haematol. 119. 716-719 (2002)

[Publications] 下田 和哉, 原田 実根: "4.輸血・免疫血液 認定医・専門医のための内科学レビュー2002"総合医学社. 356 (2002)

[Publications] 長藤 宏司, 原田 実根: "骨髄異形成症候群における造血幹細胞移植-どのようなケースに、どのような時期に、どのような移植を行うか?EBM血液疾患の治療2003-2004"中外医学社. 740 (2002)

[Publications] 長藤 宏司, 原田 実根: "造血幹細胞移植の原理と実際 シミュレーション内科 血液疾患を探る"長井書店. 229 (2002)

原田実根九州大学, 大学院・医学研究院, 教授 (00019621)

[Publications] Horiuch T, Harada M, et al.: "Molecular basis for Human complement C7 polymorphisms, C7^3 and C7^4"Bioch Biophy Res Comm. 298. 450-455 (2002)

[Publications] 下田和哉, 原田実根: "4.輸血・免疫血液認定医・専門医のための内科学レビュー2002"総合医学社. 356 (2002)

[Publications] 長藤宏司, 原田実根: "骨髄異形成症候群における造血幹細胞移植-どのようなケースに、どのような時期に、どのような移植を行うか?EBM血液疾患の治療2003-2004"中外医学社. 740 (2002)

[Publications] 長藤宏司, 原田実根: "造血幹細胞移植の原理と実際シミュレーション内科血液疾患を探る"長井書店. 229 (2002)