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，活跃复制的肿瘤细胞与无复制活性的分化神经元在放射敏感性上存在很大差异。在本研究项目中，我们重点研究了环加氧酶2 （COX-2）抑制剂和羧肽酶B (HBCPB)，前者在许多肿瘤细胞中都有抑制细胞复制的作用，后者在β -淀粉样蛋白寡聚物的解离中表现出抑制细胞毒性的活性，并分析了它们在诱导细胞凋亡方面的功能。COX-2研究：使用人血管肉瘤细胞系（ISO-HAS），进行以下分析。辐照与选择性COX-2抑制剂NS-389共同使用对肿瘤生长和血管生成的影响。COX-2效应与VEGF蛋白表达的关系。结果表明，NS-389辐照后细胞活力呈剂量依赖性降低，vegf -蛋白表达呈剂量依赖性增加，但与NS-398共用可抑制vegf -蛋白表达。因此，NS-389似乎与辐照具有共用作用，其抑制细胞生长的作用与VEGF有关。HBCPB研究：作为典型的非复制细胞，采用大鼠海马原代神经元培养系统。在这个系统中，我们分析了β -淀粉样蛋白1-42寡聚物的神经毒性，以及它在人脑羧肽酶B （HBCPB）中的解离作用，特别是在细胞凋亡诱导方面。因此，该系统在COX-2前列腺素谱系中没有引起任何影响，这表明它们是选择性细胞死亡以保持体内平衡的独立调控系统。

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., 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)

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。

Hinata, N. et al.: "Radiation induces p53-dependent cell apoptosis in bladder cancer cells with wild-type-p53 but not in p53-mutated bladder cancer cells."Urol.Res.. 31. 387-396 (2003)

Hinata, N. 等人：“辐射在野生型 p53 的膀胱癌细胞中诱导 p53 依赖性细胞凋亡，但在 p53 突变的膀胱癌细胞中则不然。”Urol.Res.. 31. 387-396 (2003)