1998 Fiscal Year Annual Research Report

抗がん剤の骨髄抑制に対する可溶性G-CSF受容体の予防効果

Research Project

Project/Area Number	10153249
Research Institution	Kyushu University
Principal Investigator	仁保喜之九州大学, 医学部, 教授 (60091287)
Co-Investigator(Kenkyū-buntansha)	浅野嘉延九州大学, 医学部, 助手 (60271110) 権藤久司九州大学, 医学部, 助手 (10253428) 岡村孝九州大学, 医学部, 助手 (30136436) 岡村精一九州大学, 医学部, 講師 (20136435)
Keywords	可溶性G-CSF受容体 / G-CSF / 造血前駆細胞 / 抗がん剤 / 骨髄抑制 / CHO細胞
Research Abstract	抗がん剤治療において骨髄抑制の副作用は必発であり、白血球減少の程度が抗がん剤の投与可能量を規定する。この骨髄抑制は増殖期にある造血前駆細胞が抗がん剤により障害を受けやすいことに起因する。そこで本研究では、造血前駆細胞を静止期に停めることで抗がん剤による骨髄抑制を予防する方法の基礎的検討を行った。まず最初に、未熟な造血前駆細胞にもG-CSF受容体が存在し、G-CSFの作用で顆粒球系へ旺盛に分化増殖することを証明した。我々は昨年度、G-CSF受容体細胞外部分と免疫グロブリンFc部分のキメラ蛋白を用いて、可溶性G-CSF受容体がG-CSFの作用を競合的に阻害することを明らかにした。これらの事実は、可溶性G-CSF受容体を先行投与して内因性G-CSFの作用をブロックすれば、造血前駆細胞が白血球へ分化増殖する過程を一時的に抑制し、抗がん剤による白血球減少を予防する可能性を裏付けた。そこで、可溶性G-CSF受容体の投与安全性を考察する基礎的なデータとして、生体内の生理的な動態を検討した。ウエスタンブロットにて血清中に可溶性G-CSF受容体が存在することを、RT-PCRにて骨髄細胞が成熟するに従い可溶性G-CSF受容体の遺伝子発現が高率になることを明らかにした。このような基礎的なデータを積み重ねると同時に、従来の報告と構造が異なる新型の可溶性G-CSF受容体を発見した。CHO細胞に遺伝子導入して従来型と新型の可溶性G-CSF受容体を作成したが、G-CSFの作用に対する阻害効果に差はなかった。現在、CHO細胞を用いて可溶性G-CSF受容体を大量に作成中である。今後は作成した可溶性G-CSF受容体をマウスに先行投与し、抗がん剤による骨髄抑制の予防効果を検討する予定である。抗がん剤による骨髄抑制の予防法が確立できれば、より安全で有効な抗がん剤治療が可能になると期待される。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] Niho Y.: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Acta Haematol.99. 165-170 (1998)
[Publications] Niho Y.: "Fas/Fas ligand and hematopoietic progenitor cells." Curr.Opin.Hematol.5・3. 163-165 (1998)
[Publications] Shibata S.: "Analysis of the granulocyte colony-stimulating factor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome." Eur.J.Haematol.60. 197-201 (1998)
[Publications] Kanaji T.: "A common genetic polymorphism (46 C to T sucstitution) in the 5-untranslated region of the coagulation factor XII gene is associated with low translation sfficiency and decrease in plasma factor XII level." Blood. 91・6. 2010-2014 (1998)
[Publications] Yamaoka K.: "Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-asimulating factor production in human monocytes." J.Immunol. 160. 838-845 (1998)
[Publications] Horiuch T: "A non-sense mutation at arg^<95> is predominant in complement 9 deficiency in Japanese." J.Immunol.160. 1509-1513 (1998)
[Publications] Fujishima H.: "Interferon-α and γ inhibit the growth and neoplastic potential of V-src-transformed human epithelial cells by reducing src tyrosine kinase activity." Int.J.Cancer. 76. 423-429 (1998)
[Publications] Niiro H.: "MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes." Biochem. Bioph. Re.Co.250. 200-205 (1998)
[Publications] Kojima T: "Genetic basis of human complement C8- α-γ deficiency." J.Immunol.161・1. 3763-3766 (1998)
[Publications] Murakami Y.: "Constitutive activation of Jak-2 and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line." J.Cell Physiol.175. 220-228 (1998)
[Publications] Otsuka T.: "Growth inhibition of leukemic cells by (-)-epigallocatechin gallate,the main constituent of green tea." Life Sciences. 63・16. 1397-1403 (1998)
[Publications] Asano Y.: "Action of interleukin-3 on the prolideration of leukaemic progenitor cells from patients with acute myeloblastic leukaemia." Clin.Lab.Haenatol.20. 225-229 (1998)
[Publications] Tokunaga Y.: "Effect of thrombopoietin on proliferation of blasis from CD7-positive acute myelogenous leukaemia." Br.J.Haematol.102. 1232-1240 (1998)
[Publications] Higuchi M.: "Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis." Scand.J.Clin.Lab.Invest.58. 429-432 (1998)
[Publications] Ichiki Y.: "Analysis of T-cell receptor β of the T-cell clones reactive to the human PDC-E2 163-176 peputide in the context od HLA-DR53 in patients with primary biliary cirrhosis." Hepatology. 26・3. 728-733 (1998)
[Publications] Akashi T.: "Proliferation of CD3 B220 single-positive normal T cell was suppressed in B-cell-deficient Ipr mice." Immunology. 93. 238-248 (1998)
[Publications] Kimura Y.: "Attachment of hepatitis C virus to cultured cells:A novel predictive factor for successful interferon therapy." J.Med.Virology. 56. 25-32 (1998)
[Publications] Nagafuchi S.: "Intradermal administration of viral vaccines." Rev.Med.Virol.8. 97-111 (1998)
[Publications] Niho Y.: "Molecular and genetic approaches to diesease." Kyushu Univ.Press(Editor:Yoshiyuki Niho), 198 (1998)
[Publications] 仁保喜之: "内科学進歩のトピックス" 九州大学出版会(編集:仁保喜之,石橋大海), 394 (1998)

1998 Fiscal Year Annual Research Report

抗がん剤の骨髄抑制に対する可溶性G-CSF受容体の予防効果

Principal Investigator

仁保 喜之 九州大学, 医学部, 教授 (60091287)

Research Products

[Publications] Niho Y.: "Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes." Acta Haematol.99. 165-170 (1998)

[Publications] Niho Y.: "Fas/Fas ligand and hematopoietic progenitor cells." Curr.Opin.Hematol.5・3. 163-165 (1998)

[Publications] Shibata S.: "Analysis of the granulocyte colony-stimulating factor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome." Eur.J.Haematol.60. 197-201 (1998)

[Publications] Kanaji T.: "A common genetic polymorphism (46 C to T sucstitution) in the 5-untranslated region of the coagulation factor XII gene is associated with low translation sfficiency and decrease in plasma factor XII level." Blood. 91・6. 2010-2014 (1998)

[Publications] Yamaoka K.: "Activation of STAT5 by lipopolysaccharide through granulocyte-macrophage colony-asimulating factor production in human monocytes." J.Immunol. 160. 838-845 (1998)

[Publications] Horiuch T: "A non-sense mutation at arg^<95> is predominant in complement 9 deficiency in Japanese." J.Immunol.160. 1509-1513 (1998)

[Publications] Fujishima H.: "Interferon-α and γ inhibit the growth and neoplastic potential of V-src-transformed human epithelial cells by reducing src tyrosine kinase activity." Int.J.Cancer. 76. 423-429 (1998)

[Publications] Niiro H.: "MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes." Biochem. Bioph. Re.Co.250. 200-205 (1998)

[Publications] Kojima T: "Genetic basis of human complement C8- α-γ deficiency." J.Immunol.161・1. 3763-3766 (1998)

[Publications] Murakami Y.: "Constitutive activation of Jak-2 and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line." J.Cell Physiol.175. 220-228 (1998)

[Publications] Otsuka T.: "Growth inhibition of leukemic cells by (-)-epigallocatechin gallate,the main constituent of green tea." Life Sciences. 63・16. 1397-1403 (1998)

[Publications] Asano Y.: "Action of interleukin-3 on the prolideration of leukaemic progenitor cells from patients with acute myeloblastic leukaemia." Clin.Lab.Haenatol.20. 225-229 (1998)

[Publications] Tokunaga Y.: "Effect of thrombopoietin on proliferation of blasis from CD7-positive acute myelogenous leukaemia." Br.J.Haematol.102. 1232-1240 (1998)

[Publications] Higuchi M.: "Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis." Scand.J.Clin.Lab.Invest.58. 429-432 (1998)

[Publications] Ichiki Y.: "Analysis of T-cell receptor β of the T-cell clones reactive to the human PDC-E2 163-176 peputide in the context od HLA-DR53 in patients with primary biliary cirrhosis." Hepatology. 26・3. 728-733 (1998)

[Publications] Akashi T.: "Proliferation of CD3 B220 single-positive normal T cell was suppressed in B-cell-deficient Ipr mice." Immunology. 93. 238-248 (1998)

[Publications] Kimura Y.: "Attachment of hepatitis C virus to cultured cells:A novel predictive factor for successful interferon therapy." J.Med.Virology. 56. 25-32 (1998)

[Publications] Nagafuchi S.: "Intradermal administration of viral vaccines." Rev.Med.Virol.8. 97-111 (1998)

[Publications] Niho Y.: "Molecular and genetic approaches to diesease." Kyushu Univ.Press(Editor:Yoshiyuki Niho), 198 (1998)

[Publications] 仁保喜之: "内科学進歩のトピックス" 九州大学出版会(編集:仁保喜之,石橋大海), 394 (1998)

仁保喜之九州大学, 医学部, 教授 (60091287)