Development of new antitumor drugs and apoptotic signal transudation - Application to feline leukemia and canine lymphoma -

抗肿瘤新药开发及细胞凋亡信号转导-在猫白血病和犬淋巴瘤中的应用-

基本信息

  • 批准号:
    12460135
  • 负责人:
  • 金额:
    $ 9.22万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2001
  • 项目状态:
    已结题

项目摘要

Clinically, the combination treatment of solid tumor cells with an anticancer drug and radiation was widely used to enhance cell killing. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd) and 2-chrolo-deoxyadenosine (Cl-Ade) was newly developed as anticancer drugs to induce cell death by inhibiting RNA synthesis. In this study, we examined whether the exposure of these anticancer drugs or /and ionizing radiation to human gastric adenocarcinoma MKN45 cells, human lekemia cell line MOLT-4 cells induce apoptosis and canine lymphoma cell line CL-1. In MOLT-4 cells, Fas expression and caspase 8/3 activation apoptotic cell death was observed after treatment of Cl-Ade, followed by apoptotic cell death. 2Cl-Ade and ECyd showed to induce apoptotic cell death in canine lymphoma cell CL-1 cells. MKN45 cells were treated with 0.1 μM ECyd for 1 h before irradiation. After irradiation with 20 Gy, apoptotic as well as swelling cells were morphologically discriminated by fluorescence microscopy … More combined with propidium iodide staining or electron microscopy and were scored. When cells were treated with ECyd alone, only 5 % of either apoptotic or necrotic cells appeared. When cells were exposed to X rays alone, about 5 % of apoptotic and about 45 % of swelling cells appeared. However, when cells were exposed to X rays in the presence of 0.1 μM ECyd, about 25 % of total cells was apoptotic cells and about 10 % of total cells was swelling cells. Apoptosis induced by treating cells with ECyd and X irradiation was significantly reduced by the treatment with Ac-DEVD-CHO (caspase 3 inhibitor) or TPCK (chymotrypsin-like protease inhibitor).These results suggested that caspase 3 and chymotrypsin-like proteases were responsible for apoptosis induced by co-treatment with ECyd and X rays. In this study, it was demonstrated that co-treatment of MKN45 cells with ECyd and X rays activated G2-phase-linked apoptotic signaling associated with caspase 3 and chymotrypsin like protease. These data may provide useful information to develop clinical treatment of radiation combined with anticancer drugs for solid tumors. Less
在临床上,实体瘤细胞与抗癌药物和放射的组合治疗被广泛用于增强细胞杀伤。1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)cytosine(ECyd)和2-chrolo-deoxyadenosine(Cl-Ade)是新近开发的通过抑制RNA合成诱导细胞死亡的抗癌药物。在这项研究中,我们研究了这些抗癌药物或/和电离辐射暴露于人胃腺癌MKN 45细胞,人白血病细胞系MOLT-4细胞和犬淋巴瘤细胞系CL-1是否诱导凋亡。在MOLT-4细胞中,Cl-Ade处理后观察到Fas表达和caspase 8/3激活的凋亡细胞死亡,随后观察到凋亡细胞死亡。2Cl-Ade和ECyd可诱导犬淋巴瘤细胞CL-1凋亡。照射前用0.1 μM ECyd处理MKN 45细胞1 h。20戈伊照射后,荧光显微镜下观察凋亡细胞和肿胀细胞 ...更多信息 结合碘化丙啶染色或电子显微镜检查,并进行评分。当细胞单独用ECyd处理时,仅出现5%的凋亡或坏死细胞。当细胞单独暴露于X射线时,出现约5%的凋亡和约45%的肿胀细胞。然而,当细胞在0.1 μM ECyd存在下暴露于X射线时,约25%的总细胞为凋亡细胞,约10%的总细胞为肿胀细胞。Ac-DEVD-CHO(caspase 3抑制剂)和TPCK(糜蛋白酶样蛋白酶抑制剂)可明显抑制ECyd和X射线联合诱导的细胞凋亡,提示caspase 3和糜蛋白酶样蛋白酶参与了ECyd和X射线联合诱导的细胞凋亡。在这项研究中,它被证明,共同处理的MKN 45细胞与ECyd和X射线激活G2期相关的凋亡信号与caspase 3和糜蛋白酶样蛋白酶。这些数据可能为开发放射联合抗癌药物治疗实体瘤的临床治疗提供有用的信息。少

项目成果

期刊论文数量(130)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tsuji et al.: "Neuroprotective effect of α-phenyl-N-tert-butylnitrone in gerbil hippocampus is mediated by the mitogen-activated protein kinase pathway and heat shock proteins"Neuroscience Letters. 282. 41-44 (2000)
Tsuji 等人:“α-苯基-N-叔丁基硝酮在沙鼠海马中的神经保护作用是由丝裂原激活蛋白激酶途径和热休克蛋白介导的”神经科学快报 282. 41-44 (2000)。
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
Yamamori et al.: "Roles of P38 MAPK, PKC and PI3-K in the signaling pathways of NADPH oxidase activation and phagocytosis in bovine polymorphonuclear leukocytes"FEBS Letter. 467. 253-258 (2000)
Yamamori 等人:“P38 MAPK、PKC 和 PI3-K 在牛多形核白细胞 NADPH 氧化酶激活和吞噬作用信号通路中的作用”FEBS Letter。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kashiwakura et al.: "Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells"European Journal of Pharmacology. 437. 19-25 (2002)
Kashiwakura等人:“氨磷汀对巨核细胞祖细胞增殖和分化的影响”欧洲药理学杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
H.Abe ら: "Superoxide generation from human polymorphonuclear leukocytes by liposome encapsulated hemoglobin"Artif Cells Blood Substit Immobil Biotechnol. 29. 275-283 (2001)
H. Abe 等人:“通过脂质体封装的血红蛋白从人多形核白细胞中产生超氧化物”Artif Cells Blood Substit Immobil Biotechnol。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
稲浪 修 ら: "酸化ストレスと細胞内シグナル伝達"放射線科学. 43. 104-112 (2000)
Osamu Inanami 等人:“氧化应激和细胞内信号转导”放射学科学 43. 104-112 (2000)。
  • DOI:
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  • 期刊:
  • 影响因子:
    0
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KUWABARA Mikinori其他文献

KUWABARA Mikinori的其他文献

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{{ truncateString('KUWABARA Mikinori', 18)}}的其他基金

The defect of biodefense mechanisms in bovine leukocyte adhesion deficiency syndrome (BLAD) as observed from signal transduction pathway
从信号转导途径观察牛白细胞粘附缺陷综合征(BLAD)生物防御机制的缺陷
  • 批准号:
    09460133
  • 财政年份:
    1997
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Steric visualization of diseased organs of laboratory small animals by three-dimensionally reconstructing MRI method
三维重建MRI方法对实验室小动物病变器官的立体可视化
  • 批准号:
    09556064
  • 财政年份:
    1997
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Spin-trapping detection of nitric oxide (NO) production from macrophage during matuation
自旋捕获检测巨噬细胞成熟过程中一氧化氮 (NO) 的产生
  • 批准号:
    07660387
  • 财政年份:
    1995
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design of the MRI probe applicable to discrimination of the fine histological changes in brauns of laboratory animals
适用于辨别实验动物内脏细微组织学变化的MRI探头设计
  • 批准号:
    05556051
  • 财政年份:
    1993
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
Utilization of Spin-Trapping Reactions for Effective Detection of DNA Damage
利用自旋捕获反应有效检测 DNA 损伤
  • 批准号:
    04680207
  • 财政年份:
    1992
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Possibility of Electron Spin Resonance Spectroscopy as a Diagnostic Technique in Immunodeficiency Syndrome of Domestic Animals
电子自旋共振光谱作为家畜免疫缺陷综合症诊断技术的可能性
  • 批准号:
    01560333
  • 财政年份:
    1989
  • 资助金额:
    $ 9.22万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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间变性淋巴瘤激酶基因(Anaplastic Lymphoma Kinase,ALK)功能研究及其小分子抑制剂斑马鱼筛选模型的建立
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RNA helicases; switched paralogue dependency as an exploitable vulnerability in aggressive B cell lymphoma.
RNA解旋酶;
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    EP/Y030303/1
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    2024
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    $ 9.22万
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Optimisation of small molecule inhibitors for effective targeting of phospholipase C gamma in T-cell lymphoma
优化小分子抑制剂以有效靶向 T 细胞淋巴瘤中的磷脂酶 C γ
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Chromatin-binding deubiquitinase MYSM1 as a putative drug target for cMYC-driven B cell lymphoma
染色质结合去泛素酶 MYSM1 作为 cMYC 驱动的 B 细胞淋巴瘤的推定药物靶点
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    478278
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    2023
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Artificial Intelligence analysis of the immune-checkpoint and immuno-oncology in B-cell non-Hodgkin lymphoma
B 细胞非霍奇金淋巴瘤免疫检查点和免疫肿瘤学的人工智能分析
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    23K06454
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    2023
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基于三级淋巴结构内 B 细胞的分析阐明原发性眼内恶性淋巴瘤的新治疗靶点
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开发一种简单的诊断方法和新的疗法来改善患有消化性淋巴瘤的狗的预后
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