2001 年度実績報告書

抗体療法及びがんの前臨床試験研究

研究課題

研究課題/領域番号	12217127
研究機関	名古屋市立大学
研究代表者	上田龍三名古屋市立大学, 医学部, 教授 (20142169)
研究分担者	吉川和宏愛知医科大学, 医学部, 講師 (60109759) 折戸悦郎名古屋市立大学, 医学部, 講師 (60204294) 佐藤滋樹名古屋市立大学, 医学部, 助教授 (80254283)
キーワード	抗体療法 / リモデリング / 抗ガングリオシド抗体 / FLT3遺伝子 / 抗ケモカインレセプター抗体 / ウィルス発癌
研究概要	申請者らは20年以上に亘り続けてきた基盤的抗体作製技術を用いたがんの「抗体療法」の方向性に、分子標的療法の観点からの基礎的および臨床的研究成果の獲得、およびtranslation researchの実践を目指してきた。1)抗体のリモデリングでは99mTc標識可能な抗変異EGFR抗体を作成し生体内における腫瘍集積性、抗体結合マグネタイトリポソームと磁場照射による腫瘍の温熱療法でのHspを介した腫瘍縮小効果を確認し、抗体の臨床応用に向けて飛躍的進歩につながる可能性を見出した。2)肺小細胞癌において抗ガングリオシド抗体のJNK/SAPKの活性化を介したアポトーシスを介した抗腫瘍効果、シスプラチンなどの抗癌剤のcytotoxicityを大きく亢進させることを見出しあらたな分子標的候補を同定した。3)クラスIIIレセプターチロシンキナーゼであるFLT3が急性骨髄性白血病(AML)で高頻度に変異型FLT3を認め予後不良因子であることを認め、この変異型FLT3遺伝子は腫瘍増殖能を有しHerbimycin A がHSP90を介してその効果を発揮することを明らかにしAMLの悪性度進展の一機構を解明した。4)抗ケモカインレセプター抗体のT細胞系腫瘍株の増殖抑制効果および免疫染色による迅速診断法を見出し、成人T細胞性白血病(ATL)の多くはCCR4陽性Th2タイプのリンパ腫瘍で、皮膚浸潤とCCR4発現の相関性を明らかにした。5)本邦でのB型肝炎ウイルスgenotypeに基づく肝癌発症リスクの同定法、また肝癌を若年発症する台湾でのgenotype B型の特異的なgenotype C型へのrecombinationを発見し、ウイルス肝癌のリスク因子の同定に成功した。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Hanamura, I.: "Ectopic expression of MAFB gene in human myeloma cells carrying(14;20)(q32;q11)chromosomal translocations"Jpn.J.Cancer Res.. 92. 638-644 (2001)
[文献書誌] Yamamoto, Y.: "Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies"Blood. 97・8. 2434-2439 (2001)
[文献書誌] Inagaki, H.: "API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma"Am.J.Pathology. 158・2. 699-709 (2001)
[文献書誌] Kosugi, H.: "In vivo effects of a histone deacetylase inhibitor,FK228,on human acute promyelocytic leukemia in NOD/Shi-scid/scid Mice"Jpn.J.Cancer Res.. 92. 529-536 (2001)
[文献書誌] Inagaki, H.: "Clonality assay of hematopoietic disorders:significance of the buccal epithelium as non-hematopoietic control and of 95% rejection limit as a novel criterion for monoclonality"Jpn.J.Cancer Res.. 92. 1305-1312 (2001)
[文献書誌] Kato, M.: "Pregnancy-associated cytotoxic lymphoma:a repor of four cases"Int.J.Haematol.. 74. 186-192 (2001)
[文献書誌] Eguchi, M.: "GPHN,a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24):Genes"Chromosomes & Cancer. 32. 212-221 (2001)
[文献書誌] Yamaguchi, M.: "De novo CD5+ positive diffuse large B-cell lymphoma:a clinicopathologic study of 109 patients"Blood. 99. 815-821 (2001)
[文献書誌] Ogisu, N.: "Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis"Int.Medicine. 40・3. 201-207 (2001)
[文献書誌] Yoshida, S.: "Ganglioside GD2 in small cell lung cancer cell lines:enhancement of cell proliferation and mediation of apoptosis"Cancer Res.. 61. 4244-4252 (2001)
[文献書誌] Sugauchi, F.: "A novel variant genotype C of hepatitis B virus identified in isolates from Australian aborigines:complete genome sequence and phylogenetic relatedness"J.General Virology. 82. 883-892 (2001)
[文献書誌] Fujita, J.: "Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis"Annals of the Rheumatic Diseases. 60・3. 281-283 (2001)
[文献書誌] Kato, H.: "Determination of hepatitis B virus genotype G by polymerase chain reaction with hemi-nested primers"J.Virological Methods. 98. 153-159 (2001)
[文献書誌] Ding, X.: "Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai,China"Intervirology. 44. 43-47 (2001)
[文献書誌] Ruzibakiev, R.: "Risk factors and seroprevalence of hepatitis B virus,hepatitis C virus,and human immunodeficiency virus infection in Uzbekistan"Intervirology. 44. 327-332 (2001)
[文献書誌] Tsuboi, K.: "Lymphoid blastic crisis of chronic myelogenous leukemia with inv(16)(p13;q22)"Leukemia Res.. (in press).
[文献書誌] Naoe, T.: "Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia:increased early death after chemotherap"Leukemia. 16. 203-208 (2002)
[文献書誌] Kato, H.: "Hepatitis B e antigen in sera from individuals infected with hepatitis B virus of genotype G"Hepatology. (in press).

2001 年度 実績報告書

抗体療法及びがんの前臨床試験研究

研究代表者

上田 龍三 名古屋市立大学, 医学部, 教授 (20142169)

研究成果

[文献書誌] Hanamura, I.: "Ectopic expression of MAFB gene in human myeloma cells carrying(14;20)(q32;q11)chromosomal translocations"Jpn.J.Cancer Res.. 92. 638-644 (2001)

[文献書誌] Yamamoto, Y.: "Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies"Blood. 97・8. 2434-2439 (2001)

[文献書誌] Inagaki, H.: "API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma"Am.J.Pathology. 158・2. 699-709 (2001)

[文献書誌] Kosugi, H.: "In vivo effects of a histone deacetylase inhibitor,FK228,on human acute promyelocytic leukemia in NOD/Shi-scid/scid Mice"Jpn.J.Cancer Res.. 92. 529-536 (2001)

[文献書誌] Inagaki, H.: "Clonality assay of hematopoietic disorders:significance of the buccal epithelium as non-hematopoietic control and of 95% rejection limit as a novel criterion for monoclonality"Jpn.J.Cancer Res.. 92. 1305-1312 (2001)

[文献書誌] Kato, M.: "Pregnancy-associated cytotoxic lymphoma:a repor of four cases"Int.J.Haematol.. 74. 186-192 (2001)

[文献書誌] Eguchi, M.: "GPHN,a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24):Genes"Chromosomes & Cancer. 32. 212-221 (2001)

[文献書誌] Yamaguchi, M.: "De novo CD5+ positive diffuse large B-cell lymphoma:a clinicopathologic study of 109 patients"Blood. 99. 815-821 (2001)

[文献書誌] Ogisu, N.: "Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis"Int.Medicine. 40・3. 201-207 (2001)

[文献書誌] Yoshida, S.: "Ganglioside GD2 in small cell lung cancer cell lines:enhancement of cell proliferation and mediation of apoptosis"Cancer Res.. 61. 4244-4252 (2001)

[文献書誌] Sugauchi, F.: "A novel variant genotype C of hepatitis B virus identified in isolates from Australian aborigines:complete genome sequence and phylogenetic relatedness"J.General Virology. 82. 883-892 (2001)

[文献書誌] Fujita, J.: "Non-specific interstitial pneumonia as pulmonary involvement of systemic sclerosis"Annals of the Rheumatic Diseases. 60・3. 281-283 (2001)

[文献書誌] Kato, H.: "Determination of hepatitis B virus genotype G by polymerase chain reaction with hemi-nested primers"J.Virological Methods. 98. 153-159 (2001)

[文献書誌] Ding, X.: "Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai,China"Intervirology. 44. 43-47 (2001)

[文献書誌] Ruzibakiev, R.: "Risk factors and seroprevalence of hepatitis B virus,hepatitis C virus,and human immunodeficiency virus infection in Uzbekistan"Intervirology. 44. 327-332 (2001)

[文献書誌] Tsuboi, K.: "Lymphoid blastic crisis of chronic myelogenous leukemia with inv(16)(p13;q22)"Leukemia Res.. (in press).

[文献書誌] Naoe, T.: "Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia:increased early death after chemotherap"Leukemia. 16. 203-208 (2002)

[文献書誌] Kato, H.: "Hepatitis B e antigen in sera from individuals infected with hepatitis B virus of genotype G"Hepatology. (in press).

2001 年度実績報告書

上田龍三名古屋市立大学, 医学部, 教授 (20142169)