Not only angiogenesis but also inflammation participate in the pathophysiology of brain radiation necrosis

不仅血管生成而且炎症也参与脑放射性坏死的病理生理学

• 批准号: 24659658
• 负责人: MIYATAKE Shin-Ichi
• 金额: $ 2.41万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659658/
• 关键词: 脳放射線壊死; ＶＥＧＦ; bevacizumab; 炎症; 虚血; 血管内皮増殖因子; ベバシズマブ; VEGF; HIF-1 a; CXCL12; CXCR4; 血管新生

Surgical specimens of symptomatic RN in the brain were retrospectively reviewed by histological and immunohistochemical analyses using hematoxylin and eosin (H&E) staining as well as immunohistochemical staining.The most prominent vasculature was identified as thin-walled leaky angiogenesis, i.e., telangiectasis surrounded by prominent interstitial edema.Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive reactive astrocytes and CD68/hGLUT-5-positive cells (mainly microglias). VEGF caused leaky angiogenesis followed by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines seemed to aggravate the RN edema. Both angiogenesis and inflammation might be caused by the regulation of HIF-1a, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.

通过组织学和免疫组织化学分析使用苏木精和曙红（H＆E）染色以及免疫组织化学染色，通过组织学和免疫组织化学分析进行回顾性综述。表型渗透了围产核病区域：GFAP阳性反应性星形胶质细胞和CD68/HGLUT-5阳性细胞（主要是小胶质细胞）。 VEGF引起渗漏的血管生成，然后在RN中进行周围水肿。表达CXCL12的GFAP阳性细胞可能会吸引表达CXCR4的CD68/HGLUT5阳性细胞进入销售区域。这些表达促炎细胞因子的CD68/HGLUT5阳性细胞似乎加剧了RN水肿。血管生成和炎症都可能是由HIF-1A的调节引起的，HIF-1A被称为VEGF和CXCL12/CXCR4趋化因子轴的反式激活剂。

项目成果

薬事承認を目指した多施設共同研究、第３項先進医療

旨在药品审批的多中心联合研究，第3节先进医疗

• 发表时间: 2013
• 作者: 宮武伸一;寺坂俊介;井内俊彦;別府高明;荒川芳輝;田部井勇助;成田善孝;中村英夫;坪井康次;永根基雄;古瀬元雅;三輪和弘;杉山一彦;阿部竜也;武笠晃丈;寺崎瑞彦;隈部俊宏
• 通讯作者: 隈部俊宏

Bevacizumab for progressive radiation necrosis with the nuclear medicine diagnosis:

贝伐珠单抗治疗进行性放射性坏死并进行核医学诊断：

• 发表时间: 2013
• 作者: 宮武伸一;寺坂俊介;井内俊彦;別府高明;荒川芳輝;田部井勇助;成田善孝;中村英夫;坪井康次;永根基雄;古瀬元雅;三輪和弘;杉山一彦;阿部竜也;武笠晃丈;寺崎瑞彦;隈部俊宏;Miyatake S
• 通讯作者: Miyatake S

Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases

• DOI: 10.1093/neuonc/not020
• 发表时间: 2013-06-01
• 期刊: NEURO-ONCOLOGY
• 影响因子: 15.9
• 作者: Miyatake, Shin-Ichi;Furuse, Motomasa;Ono, Koji
• 通讯作者: Ono, Koji

脳ｊ放射線壊死の成因と治療 －高度医療（第３項先進医療）の申請

脑放射性坏死的原因和治疗 - 高级医疗护理申请（第3项高级医疗护理）

• 发表时间: 2012
• 期刊: 脳神経外科ジャーナル
• 作者: Hiramatsu R;Kawabata S;Furuse M;Miyatake S;Kuroiwa T;Shin-Ichi Miyatake;Sun Wei;Shinji Kawabata;宮武伸一;宮武伸一
• 通讯作者: 宮武伸一

Symptomatic Radiation Necrosis Diagnosed by Amino Acid PET

氨基酸 PET 诊断症状性放射性坏死

• 发表时间: 2013
• 期刊: Bevacizumab Treatment for Jpn J Clin Oncol
• 作者: Motomasa Furuse;Naosuke Nonoguchi;Shinji Kawabata;Erina Yoritsune;Masatsugu Takahashi;Taisuke Inomata;Toshihiko Kuroiwa and Shin-Ichi Miyatake
• 通讯作者: Toshihiko Kuroiwa and Shin-Ichi Miyatake