Studies on new molecular therapeutic approach for radiation pneumonitis

放射性肺炎分子治疗新方法的研究

• 批准号: 15390256
• 负责人: SONE Saburo
• 金额: $ 7.55万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390256/
• 关键词: radiation pneumonitis; CD13; aminopeptidase N; macrophages; bestatin; Aminopeptidase N

The cell-surface glycoprotein CD13 first identified in leukocytes of the myeloid series is identical to aminopeptidase N (EC 3.4.11.2). In this study, we examined here the significance of CD13/aminopeptidase N in radiation-induced pulmonary fibrosis using an animal model. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in rats with radiation pneumonitis at 2-4 weeks after the irradiation than in control rats. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from rats with radiation pneumonitis at higher levels than in those from control rats. Higher chemotactic activity for lymphocytes was detected in the BALF from rats with radiation pneumonitis than that from control rats, and the activity was significantly decreased by the treatment with bestatin, a specific aminopeptidase inhibitor, indicating that CD13/aminopeptidase N expressed in AM may have a role in T lymphocyte involvement in radiation pneumonitisn and the pathogenesis of alveolitis in this disorder. Our results suggest that bestatin may be useful for the treatment of radiation pneumonitis. We are now testing the effect of oral administration of bestatin in animal model of radiation pneumonitis.

首先在髓系白细胞中发现的细胞表面糖蛋白CD13与氨基肽酶N(EC 3.4.11.2)完全相同。在这项研究中，我们利用动物模型研究了CD13/氨基肽酶N在放射性肺纤维化中的意义。放射性肺炎大鼠照射后2~4周，支气管肺泡灌洗液(BALF)中氨基肽酶活性明显高于对照组。放射性肺炎大鼠肺泡巨噬细胞(AM)中可检测到CD13/氨基肽酶N蛋白，其相对分子质量约为150kD。放射性肺炎大鼠BALF中淋巴细胞趋化活性明显高于正常大鼠，经氨基肽酶抑制剂Bestatin处理后，其活性明显降低，提示AM表达的CD13/氨基肽酶N可能参与了放射性肺炎的T淋巴细胞参与和肺泡炎的发病机制。我们的结果提示贝斯汀对放射性肺炎的治疗可能是有效的。我们现在正在测试口服贝斯汀对放射性肺炎动物模型的影响。

项目成果

Parathyroid hormone-related protein (PTHRP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice

• DOI: 10.1002/ijc.11586
• 发表时间: 2004-02-10
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Miki, T;Yano, S;Sone, S
• 通讯作者: Sone, S

Expression of toll-like receptor 4 on dendritic cells is significant for anticancer effect of dendritic cell-based immunotherapy in combination with an active component of OK-432, a streptococcal preparation

• DOI: 10.1158/0008-5472.can-03-4005
• 发表时间: 2004-08-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Okamoto, M;Furuichi, S;Sato, M
• 通讯作者: Sato, M

Combined therapy with a new bisphosphonate, minodronate and chemotherapy for multiple organ metastasis of small cell lung cancer cells in severe combined immunodeficient mice.

新型双膦酸盐、米诺膦酸盐和化疗联合治疗严重联合免疫缺陷小鼠小细胞肺癌细胞的多器官转移。

• 发表时间: 2003
• 期刊: Clin Cancer Res 9
• 作者: Yano S;Sone S et al.
• 通讯作者: Sone S et al.

Molecular mechanisms of angiogenesis in non‐small cell lung cancer, and therapeutics targeting related molecules

• DOI: 10.1111/j.1349-7006.2003.tb01469.x
• 发表时间: 2003-06
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: S. Yano;Y. Nishioka;H. Goto;S. Sone

Increased macrophage inflammatory protein-1α and -1β in BAL fluid of bronchiolitis obliterans organizing pneumonia

• DOI: 10.1046/j.1440-1843.2003.00496.x
• 发表时间: 2003-12-01
• 期刊: RESPIROLOGY
• 影响因子: 6.9
• 作者: Asano, T;Ogushi, F;Sone, S
• 通讯作者: Sone, S