1999 Fiscal Year Annual Research Report

分子標的治療の臨床応用へのアプローチ

Research Project

Project/Area Number	09255104
Research Institution	Nagoya City University
Principal Investigator	上田龍三名古屋市立大学, 医学部, 教授 (20142169)
Co-Investigator(Kenkyū-buntansha)	真弓忠範大阪大学, 大学院・薬学研究科, 教授 (00098485) 遠藤啓吾群馬大学, 医学部, 教授 (10115800) 山口俊晴京都府立医科大学, 助教授 (90111327) 大野竜三浜松医科大学, 教授 (70093002) 花井陳雄協和醗酵, 東京研究所, 主任研究員
Keywords	分子標的 / 抗体療法 / 分子誘導療法 / 癌組織血管 / 糖鎖抗原GM2,GD2 / ヒト化抗体 / チオレドキシン / サロゲイトマーカー
Research Abstract	本課題では現実に臨床応用の可能性が高まってきた抗体療法、分化誘導療法の研究を推進すると共に、がん化学療法における薬剤耐性および感受性からレドックス制御系、シグナル伝達系をとりあげ研究を行った。 1.抗体療法に関して 1)癌組織血管内皮細胞に対するモノクローナル抗体(TES-23)の作製に成功し、がん組織血管を標的にするミサイル療法の可能性が進展した(真弓)。2)糖鎖抗原には腫瘍特異性が有り、抗GD2抗体がアポトーシスを誘発すること(上田)、ヒト化糖鎖抗体の作製に成功し、GD3とIL-2融合抗体はマウス腫瘍の転移を顕著に抑制(花井)し、糖鎖抗原が癌治療の標的となることを明らかにした。3)臨床応用では、造血幹細胞移植におけるCD10,CD6抗体によるpurging効果の第1,2相研究(上田)。I-131で標識した抗CD20抗体(遠藤)、カリキアマイシン結合ヒト化抗CD33抗体(CMA-676)(大野)の前臨床研究、大腸癌に対するキメラ抗体と抗癌剤複合体(chA7-NCS)の第1相試験(山口)が施行された。 2.分化誘導療法に関しては、deoxycoformycin と deoxyadenosineおよびその誘導体の併用により単球性白血病細胞にアポトーシスを誘導し、in vivoで併用効果を認めた(本間)。臨床的には分化誘導剤(ATRA)耐性のAPL白血病に対して、新規分化誘導剤Am80の有効性を実証した。 3.化学療法剤の新規分子標的に関しては、1)チオレドキシンの結合蛋白質(TBP-2)を同定し、TBP-2がチオレドキシンの活性を負に制御することや、HTLV-Iによる細胞のトランスフォーメーションへの関心を明らかにした。(淀井)。 2)Cytostatic薬(UCN-01、E7070、YTA0040)の抗腫瘍効果に関わるsurrogateマーカーともなるべき標的分子を同定した(西條)。

Research Products

(27 results)

All Other

All Publications (27 results)

[Publications] Ueda, R.: "How can we predict and prevent the occurrence of therapy-related leukemias?"Jpn. J. Clin. Oncol.. 29・1. 1-2 (1999)
[Publications] Kato, T.: "Amino acid substitutions in NS5A region of GB virus C and response to interferon therapy"J. Med. Virol.. 57. 376-382 (1999)
[Publications] Ohba, K.: "Seroprevalence of hepatitis B virus, hepatitis C virus and GB virus-C infections in Siberia"Epidemiology Infection. 122. 139-144 (1999)
[Publications] Ueda, R.: "Clinical application of molecular diagnosis for cancer patients : Symposium on present stayus of clinical oncology"Int. Medicine. 38・2. 183-186 (1999)
[Publications] Nitta, M.: "Multiple myeloma preceding the development of chronic myelogenous leukemia"Int. J. Hematol. 69. 170-173 (1999)
[Publications] Sato, Y.: "Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma"J. Gastroenterol. 34. 1-8 (1999)
[Publications] Saito, H.: "Challenges in Cancer Metastasis"Cancer Chenotherapy and Pharmacology. 43. S1-S2 (1999)
[Publications] Mizokami, M.: "Mutation patterns for two flaviviruses: hepatitis C virus and GB virus C/hepatitis G virus"FEBS Letters. 450. 294-298 (1999)
[Publications] Inagaki, H.: "Prognostic significance of CD44v6 in diffuse large b-cell lymphoma"Modem Pathology. 12・5. 547-552 (1999)
[Publications] Kiyoi, H.: "Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia"Blood. 93. 3074-3080 (1999)
[Publications] Iida, S.: "Chromosomal rearrangement of the PAX-5 locus in lymphoplasmacytic lymphoma with t(9;14)(p13;q32)"Leukemia and Lymphoma. 34・1-2. 25-33 (1999)
[Publications] Kato, H.: "High prevalence and phylogenetic analysis of TT-virus infection in Mongolia"Virus Res.. 60. 171-179 (1999)
[Publications] Cao, K.: "TT virus infection among IVDUs in south western China"Scand J. Infect. Dis. 31. 21-25 (1999)
[Publications] Kato, T.: "High prevalance of TT virus infection in Japanese patients with liver diseases and in blood donors"J. Hepatol.. 31. 221-227 (1999)
[Publications] Kondo, T.: "Microsatellite instability associated with hepatocarcinogenesis"J. Hepatol. 31. 529-536 (1999)
[Publications] Kikuchi, M.: "Concurrent existence of antitopoisomerase I and anticentromere antibodies"厚生院紀要. 25. 29-40 (1999)
[Publications] Miyawaki, S.: "Comparison of leukopenia between cytarabine and behenoyl cytarabine in JALSG AML-89 consolidation therapy. The Japan Adult Leukemia Study Group"Int. J. Hematol. 70. 56-57 (1999)
[Publications] Ding, X.: "Prevalence of TT virus and GBV-C infections among patients with liver diseases and the general population in Shanghai, China"Virus Genes. 19. 51-58 (1999)
[Publications] Harada, S.: "Molecular and immunological dissection of diffuse large B cell lymphoma : CD5+, and CD5- with CD10^+ groups may constitute clinically relevant subtypes"Leukemia. 19. 51-58 (1999)
[Publications] Yoshida, S.: "Detection of MUM1/IRF4-IgH fusion in multiple myeloma"Leukemia. 13. 1441-1447 (1999)
[Publications] Niimi, T.: "Vitamin D receptor gene polymorphism in patients with sarcoidosis"Am. J. Respir. Crit. Care Med.. 160. 1107-1109 (1999)
[Publications] Yoshinouchi, T.: "Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia"Eur. Respir J.. 14. 579-584 (1999)
[Publications] Kato, T.: "Development of a TT virus DNA quantification system using real-time detection PCR"J. Clnical Microbiol.. 38・1. 94-98 (2000)
[Publications] Mori, T.: "Aberrant overexpression of 53BP2 mRNA in luug cancer cell lines"FEBS Letters. 425. 124-128 (2000)
[Publications] Zhao, M.: "In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor"Leukemia. (in press). (2000)
[Publications] Iida, S.: "Detection of MUM1/IRF4-LgH fusion in multiple myeloma"Leukemia. (in press). (2000)
[Publications] Takeyama, T.: "Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors"Int. J. Hematol.. ( in press). (2000)

1999 Fiscal Year Annual Research Report

分子標的治療の臨床応用へのアプローチ

Principal Investigator

上田 龍三 名古屋市立大学, 医学部, 教授 (20142169)

Research Products

[Publications] Ueda, R.: "How can we predict and prevent the occurrence of therapy-related leukemias?"Jpn. J. Clin. Oncol.. 29・1. 1-2 (1999)

[Publications] Kato, T.: "Amino acid substitutions in NS5A region of GB virus C and response to interferon therapy"J. Med. Virol.. 57. 376-382 (1999)

[Publications] Ohba, K.: "Seroprevalence of hepatitis B virus, hepatitis C virus and GB virus-C infections in Siberia"Epidemiology Infection. 122. 139-144 (1999)

[Publications] Ueda, R.: "Clinical application of molecular diagnosis for cancer patients : Symposium on present stayus of clinical oncology"Int. Medicine. 38・2. 183-186 (1999)

[Publications] Nitta, M.: "Multiple myeloma preceding the development of chronic myelogenous leukemia"Int. J. Hematol. 69. 170-173 (1999)

[Publications] Sato, Y.: "Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma"J. Gastroenterol. 34. 1-8 (1999)

[Publications] Saito, H.: "Challenges in Cancer Metastasis"Cancer Chenotherapy and Pharmacology. 43. S1-S2 (1999)

[Publications] Mizokami, M.: "Mutation patterns for two flaviviruses: hepatitis C virus and GB virus C/hepatitis G virus"FEBS Letters. 450. 294-298 (1999)

[Publications] Inagaki, H.: "Prognostic significance of CD44v6 in diffuse large b-cell lymphoma"Modem Pathology. 12・5. 547-552 (1999)

[Publications] Kiyoi, H.: "Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia"Blood. 93. 3074-3080 (1999)

[Publications] Iida, S.: "Chromosomal rearrangement of the PAX-5 locus in lymphoplasmacytic lymphoma with t(9;14)(p13;q32)"Leukemia and Lymphoma. 34・1-2. 25-33 (1999)

[Publications] Kato, H.: "High prevalence and phylogenetic analysis of TT-virus infection in Mongolia"Virus Res.. 60. 171-179 (1999)

[Publications] Cao, K.: "TT virus infection among IVDUs in south western China"Scand J. Infect. Dis. 31. 21-25 (1999)

[Publications] Kato, T.: "High prevalance of TT virus infection in Japanese patients with liver diseases and in blood donors"J. Hepatol.. 31. 221-227 (1999)

[Publications] Kondo, T.: "Microsatellite instability associated with hepatocarcinogenesis"J. Hepatol. 31. 529-536 (1999)

[Publications] Kikuchi, M.: "Concurrent existence of antitopoisomerase I and anticentromere antibodies"厚生院紀要. 25. 29-40 (1999)

[Publications] Miyawaki, S.: "Comparison of leukopenia between cytarabine and behenoyl cytarabine in JALSG AML-89 consolidation therapy. The Japan Adult Leukemia Study Group"Int. J. Hematol. 70. 56-57 (1999)

[Publications] Ding, X.: "Prevalence of TT virus and GBV-C infections among patients with liver diseases and the general population in Shanghai, China"Virus Genes. 19. 51-58 (1999)

[Publications] Harada, S.: "Molecular and immunological dissection of diffuse large B cell lymphoma : CD5+, and CD5- with CD10^+ groups may constitute clinically relevant subtypes"Leukemia. 19. 51-58 (1999)

[Publications] Yoshida, S.: "Detection of MUM1/IRF4-IgH fusion in multiple myeloma"Leukemia. 13. 1441-1447 (1999)

[Publications] Niimi, T.: "Vitamin D receptor gene polymorphism in patients with sarcoidosis"Am. J. Respir. Crit. Care Med.. 160. 1107-1109 (1999)

[Publications] Yoshinouchi, T.: "Myofibroblasts and S-100 protein positive cells in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial pneumonia"Eur. Respir J.. 14. 579-584 (1999)

[Publications] Kato, T.: "Development of a TT virus DNA quantification system using real-time detection PCR"J. Clnical Microbiol.. 38・1. 94-98 (2000)

[Publications] Mori, T.: "Aberrant overexpression of 53BP2 mRNA in luug cancer cell lines"FEBS Letters. 425. 124-128 (2000)

[Publications] Zhao, M.: "In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor"Leukemia. (in press). (2000)

[Publications] Iida, S.: "Detection of MUM1/IRF4-LgH fusion in multiple myeloma"Leukemia. (in press). (2000)

[Publications] Takeyama, T.: "Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors"Int. J. Hematol.. ( in press). (2000)

上田龍三名古屋市立大学, 医学部, 教授 (20142169)