INNOVATION FOR TISSUE-SPECIFIC RADIO-SENCITIZATION OF SELECTIVE INHIBITOR OF CYCLO-OXYGENASE 2 (COX-2)

环加氧酶 2 (COX-2) 选择性抑制剂的组织特异性放射增敏创新

• 批准号: 14570858
• 负责人: MATSUMOTO Akira
• 金额: $ 2.24万
• 依托单位: FOUNDATION FOR BIOMEDICAL RESEARCH AND INNOVATION (2003)Kobe University (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570858/
• 关键词: CYCLO-OXYGENASE 2; APOPTOSIS; TUMOR CELL DEATH; CARBOXYPEPTIDASE B; NEURONAL DEATH; RADIO-SENCITIZATION; BETA-AMYLOID; ALZHEIMER'S DISEASE; シクロオキシゲナーゼ2; COX-2阻害剤; 放射線治療; 血管新生因子; 前立腺癌; 血管肉腫; 併用療法

It is a well-known fact that there iis a great difference in radiosensitivity between actively replicating tumor cell and differentiated neurons without replicating activity. In this research project, we focused on cyclo-oxygenase 2 (COX-2) inhibitors, whose inhibitory action of cell replication is recognized in many tumor cell linse, and carboxypeptidase B (HBCPB) which exhibits inhibitory activity for cell toxicity be dissociation of beta-amyloid oligomer, and snslyzed their functions with regard to apoptosis induction.COX-2 study : Using human hemangiosarcoma cell line (ISO-HAS), following analyses were performed.Effects in tumor growth and angiogenesis by co-usage of irradiation and NS-389, a selective COX-2 inhibitor.Relationship of COX-2 effect and VEGF protein expression.As for results, cell viability was decreased by NS-389 in a dose dependent fashion, and the VEGF-protein expression was increased by irradiation also in a dose-dependent manner, which was inhibited by co-usage of NS-398. Therefore, it seems that NS-389 has a co-usage effect with irradiation, and its cell growth inhibitory effect is relevant to VEGF.HBCPB study : As a typical example of non-replicating cell, using rat hippocampus primary neuron culture system was used. In this system, neuro-toxicity of beta-amyloid 1-42 oligomer, and its dissociation by human brain carboxypeptidase B (HBCPB) were analyzed especially with respect to apoptosis induction.As a result, this system induced no effects in the COX-2 prostaglandin lineage, and suggests that these are independent regulation system for selective cell death to keep homeostasis.

众所周知的事实是，在没有复制活性的情况下，主动复制肿瘤细胞和分化的神经元之间存在很大的差异。在该研究项目中，我们专注于环氧酶2（COX-2）抑制剂，在许多肿瘤细胞Linse中识别出细胞复制的抑制作用，而羧肽酶B（HBCPB）表现出对细胞毒性的抑制活性的抑制作用。 -Cox-2研究：使用人血管肉瘤细胞系（ISO-HAS），对淀粉样蛋白的寡聚物进行了SNSLESLESLEZ，并进行了分析后进行分析。 389，一种选择性COX-2抑制剂。cox-2效应和VEGF蛋白表达的关系。作为结果，ns-389以剂量依赖性的方式降低了细胞活力，而在辐射中也通过辐照增加了VEGF蛋白质的表达，也会增加剂量依赖性的方式，被NS-398的合作所抑制。因此，NS-389似乎对辐照具有共同效应，其细胞生长抑制作用与VEGF.HBCPB研究相关：作为非复制细胞的典型例子，使用了大鼠海马原发性神经元培养系统。在该系统中，分析了β-淀粉样蛋白1-42低聚物的神经毒性，尤其是在诱导凋亡的结果中分析了人脑羧肽酶B（HBCPB）的神经毒性。由于结果，该系统在COX-2前列腺素谱系，并建议这些是独立的调节系统，用于选择性细胞死亡以保持体内平衡。

项目成果

Kaji, Y. et al.: "Proton two-dimensional chemical shift imaging for evaluation of prostate cancer : External surface coil vs. endorectal"J.Magn.Reson.Imaging. 16. 697-706 (2002)

Kaji, Y. 等人：“用于评估前列腺癌的质子二维化学位移成像：外表面线圈与直肠内”J.Magn.Reson.Imaging。

Matsuyama, S., Matsumoto, A.: "Epibetidine induces long-term ostentation (LTP) via activation of α4β2 nicotinic acetyl-Choline receptors (nAChRs) in vivo in the intact mouse dentate gyrus : both α4β2"J.Pharmacol.Sci.. 93. 180-187 (2003)

Matsuyama, S., Matsumoto, A.：“Epibetidine 通过激活完整小鼠齿状回体内的 α4β2 烟碱乙酰胆碱受体 (nAChR) 来诱导长期炫耀 (LTP)：两者都是 α4β2”J.Pharmacol.Sci。 . 93. 180-187 (2003)

Matsuyama, S.et al.: "Impaired long-term potentiation in vivoin the dentate gyrus of pituitary adenylate cyclase-activating polypeptide (PACAP) or PACAP type 1 receptor-mutant mice."Neuroreport. 14. 2095-2098 (2003)

Matsuyama, S.等人：“垂体腺苷酸环化酶激活多肽 (PACAP) 或 PACAP 1 型受体突变小鼠的齿状回体内长期增强作用受损。”Neurreport。

Matsuyama, S., Matsumoto, A.: "Epibetidine induces long-term potentiation (LTP) via activation of α4β2 nicotinic acetyl-Choline receptors (nAChRs) in vivo in the intact mouse dentate gyrus : both α7 and α4β2"J.Pharmacol.Sci.. 93. 180-187 (2003)

Matsuyama, S., Matsumoto, A.：“Epibetidine 通过激活完整小鼠齿状回体内的 α4β2 烟碱乙酰胆碱受体 (nAChR) 来诱导长时程增强 (LTP)：α7 和 α4β2”J.Pharmacol。科学.. 93. 180-187 (2003)

Sasaki R: "Angiosarcoma treated with radiotherapy : impact of tumor type and size on outcome"Int J Radiat Oncol Biol Phys. 54・2. 1032-1040 (2002)

Sasaki R：“放射治疗的血管肉瘤：肿瘤类型和大小对结果的影响”Int J Radiat Oncol Biol Phys 54・2（2002）。