1991 Fiscal Year Annual Research Report

自己造血幹細胞移植におけるがん治療の基礎的臨床的研究

Research Project

Project/Area Number	03151015
Research Institution	The University of Tokyo
Principal Investigator	浅野茂隆東京大学, 医科学研究所, 教授 (50134614)
Co-Investigator(Kenkyū-buntansha)	中畑龍俊信州大学, 医学部, 講師 (20110744) 須田年生自治医科大学, 講師 (60118453) 帯刀益夫東北大学, 抗酸菌研究所, 教授 (10099971) 小澤敬也東京大学, 医科学研究所, 助教授 (30137707) 小川一誠癌研究会, 癌化療センター, 部長 (70124245)
Keywords	造血幹細胞 / ストロ-マ細胞 / 造血因子 / SCF / GーCSF / 自家骨髄移植 / 未梢血幹細胞移植
Research Abstract	造血幹細胞のin vitro増幅系の確立を目指した基礎研究として、造血幹細胞ならびにその支持組織であるストロ-マ細胞の解析を行った。マウス造血幹細胞の純化の研究では、Lin^ー,Scaー1^+,cーkit^+細胞群に未分化造血幹細胞が多く含まれ、その増殖刺激にはSCF(stem cell factor),ILー3,ILー6などの組合せが有効であることを明らかにした。また、さらにIFNーγを併用すると造血幹細胞の増殖に対して促進的に作用することが判明した。SCF/cーkit系の重要性についてはin vivoにおいても抗cーkitモノクロ-ナル抗体の投与実験により確認した。ストロ-マ細胞に関しては、胎児肝や脾由来の赤血球造血を支持するストロ-マ細胞株、MーCSF遺伝子に変異を有する大理石病(op/op)マウス由来のストロ-マ細胞株などを樹立し、その機能解析を進めた。また、マウス胚由来のC3H10T1/2線維芽細胞の5ーazacytidineによる分化誘導系を利用し、前脂肪細胞の造血支持能が高いことを確認した。さらに、造血支持にはSCF以外の未知のストロ-マ因子も重要であることを示唆するデ-タを得た。臨床面では、悪性リンパ腫に対しGーCSFと自家骨髄移植を組み合せた集学的治療のプロトコ-ルを作成し、パイロットスタディを行った。骨髄性白血病に対する骨髄移植ではGーCSF併用前処置法についてさらに症例を重ね、その有効性が確認された。末梢血幹細胞移植に関しては、GーCSF投与による造血幹細胞採取の効率化を試み、至適採取時期、生着に必要なCFUーGM数などの決定を行った。また、PCR法の応用により残存がん細胞の検出を行い、その臨床的意義を検討した。以上、本研究班ではGーCSFを中心としたサイトカインをがん治療へ導入すると共に、今後のさらに広範な臨床応用に向けた基礎研究の基盤づくりを行うことができた。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] S.Asano: "Beneficial effect of recombinant human glycosylated granulocyte colony-stimulating factor in marrow-transplanted patients:Results of muticenter phase II/III study." Transplant.Proc.23. 1701-1703 (1991)
[Publications] S.Asano: "Several approaches to improvement of interferon-alpha therapy in chronic myelogenous leukemia (CML)" Eur.J.Cancer.
[Publications] S.Asano: "Human G-CSF:Its basic aspects and clinical application" Am.J.Pediat.Hematol/Oncol.
[Publications] S.Okada: "Effect of interleukin 3,interleukin 6,and granulocyte colony-stimulating factor on sorted murine splenic progeniror cells" Exp.Hematol.19. 42-46 (1991)
[Publications] H.Ema: "Multipotent and committed CD34^+ cells in bone marrow transplantation" Jap.J.Cancer Res.82. 547-552 (1991)
[Publications] T.Tanaka: "Stimulatory effects of granulocyte colony-stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice" Blood. 77. 2597-2602 (1991)
[Publications] N.Yanai: "Endotherial cells create hematopoietic inductive microenvironment preferential to erythropoiesis in mouse spleen" Cell Structure and Function. 16. 87-93 (1991)
[Publications] H.Kodama: "Response of newly established mouse myeloid leukemic cell lines to MC3T3-G2/PA6 preadipocytes and hemopoetic factors" Blood. 77. 49-54 (1991)
[Publications] M.Ogawa: "Expression and function of c-kit in hemopoietic progenitor cells" J.Exp.Med.174. 63-71 (1991)
[Publications] Y.Takaue: "Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autograft treatment of childhood acute leukemia/lymphoma with high-risk features" Cancer. 67. 1830-1837 (1991)
[Publications] Y.Kawano: "Synergistic effect of human recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic blood progenitors" Blood. 77. 1-4 (1991)
[Publications] T.Mukaiyam: "High-dose chemotherapy with autologous hematopoietic stem cell transplant for cancers" Excerpta Medica. 6. 114-119 (1991)
[Publications] K.Ozawa: "Regulatory production of granulocyte colony-stimulating factor (G-CSF) by stromal cells." Hematopoietic Growth Factors. 55-81 (1991)
[Publications] J.Tsunoda: "In vivo stem cell function of interleukin-3-induced blast cells." Blood. 78. 318-322 (1991)
[Publications] S.Okada: "Enrichment and characterization of murine hemopoietic stem cells that express c-kit molecule expression and function of c-kit molecule" Blood. 78. 1706-1712 (1991)
[Publications] K.Naganuma: "Requirement of both interleukin 3 and interleukin 6 for the growth of primitive hemopoietic progenitors" Inter.J.Hematol.54. 273-279 (1991)
[Publications] T.Imai: "Interleukin-6 supports human megakaryocytic proliferation and differentiation in vitro" Blood. 78. 1969-1974 (1991)
[Publications] Y.Matsuya: "Continued blood cell formation in the spherical bodies in a long-term mouse spleen culture" Blood. 77. 1211-1217 (1991)

1991 Fiscal Year Annual Research Report

自己造血幹細胞移植におけるがん治療の基礎的臨床的研究

Principal Investigator

浅野 茂隆 東京大学, 医科学研究所, 教授 (50134614)

Research Products

[Publications] S.Asano: "Beneficial effect of recombinant human glycosylated granulocyte colony-stimulating factor in marrow-transplanted patients:Results of muticenter phase II/III study." Transplant.Proc.23. 1701-1703 (1991)

[Publications] S.Asano: "Several approaches to improvement of interferon-alpha therapy in chronic myelogenous leukemia (CML)" Eur.J.Cancer.

[Publications] S.Asano: "Human G-CSF:Its basic aspects and clinical application" Am.J.Pediat.Hematol/Oncol.

[Publications] S.Okada: "Effect of interleukin 3,interleukin 6,and granulocyte colony-stimulating factor on sorted murine splenic progeniror cells" Exp.Hematol.19. 42-46 (1991)

[Publications] H.Ema: "Multipotent and committed CD34^+ cells in bone marrow transplantation" Jap.J.Cancer Res.82. 547-552 (1991)

[Publications] T.Tanaka: "Stimulatory effects of granulocyte colony-stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice" Blood. 77. 2597-2602 (1991)

[Publications] N.Yanai: "Endotherial cells create hematopoietic inductive microenvironment preferential to erythropoiesis in mouse spleen" Cell Structure and Function. 16. 87-93 (1991)

[Publications] H.Kodama: "Response of newly established mouse myeloid leukemic cell lines to MC3T3-G2/PA6 preadipocytes and hemopoetic factors" Blood. 77. 49-54 (1991)

[Publications] M.Ogawa: "Expression and function of c-kit in hemopoietic progenitor cells" J.Exp.Med.174. 63-71 (1991)

[Publications] Y.Takaue: "Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autograft treatment of childhood acute leukemia/lymphoma with high-risk features" Cancer. 67. 1830-1837 (1991)

[Publications] Y.Kawano: "Synergistic effect of human recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic blood progenitors" Blood. 77. 1-4 (1991)

[Publications] T.Mukaiyam: "High-dose chemotherapy with autologous hematopoietic stem cell transplant for cancers" Excerpta Medica. 6. 114-119 (1991)

[Publications] K.Ozawa: "Regulatory production of granulocyte colony-stimulating factor (G-CSF) by stromal cells." Hematopoietic Growth Factors. 55-81 (1991)

[Publications] J.Tsunoda: "In vivo stem cell function of interleukin-3-induced blast cells." Blood. 78. 318-322 (1991)

[Publications] S.Okada: "Enrichment and characterization of murine hemopoietic stem cells that express c-kit molecule expression and function of c-kit molecule" Blood. 78. 1706-1712 (1991)

[Publications] K.Naganuma: "Requirement of both interleukin 3 and interleukin 6 for the growth of primitive hemopoietic progenitors" Inter.J.Hematol.54. 273-279 (1991)

[Publications] T.Imai: "Interleukin-6 supports human megakaryocytic proliferation and differentiation in vitro" Blood. 78. 1969-1974 (1991)

[Publications] Y.Matsuya: "Continued blood cell formation in the spherical bodies in a long-term mouse spleen culture" Blood. 77. 1211-1217 (1991)

浅野茂隆東京大学, 医科学研究所, 教授 (50134614)