292. Int J Radiat Oncol Biol Phys.

292. Int J Radiat Oncol Biol Phys. 2003 Oct 1;57(2):563-72.

Soluble TGFbeta type II receptor gene therapy ameliorates acute radiation-induced
pulmonary injury in rats.

Rabbani ZN(1), Anscher MS, Zhang X, Chen L, Samulski TV, Li CY, Vujaskovic Z.

Author information:
(1)Department of Radiation Oncology, Duke University Medical Center, Durham, NC
27710, USA.

PURPOSE: To assess whether administration of recombinant human adenoviral vector,
which carries soluble TGFbeta1 Type II receptor (TbetaRII) gene, might reduce the
availability of active TGFbeta1 and thereby protect the lung from
radiation-induced injury.
METHODS AND MATERIALS: Female Fisher 344 rats were given a single 30 Gy dose of
right hemithoracic irradiation 24 h after the injections of control (AdGFP) or
treatment (AdexTbetaRII-Fc) vectors. Different end points were assessed to look
for lung tissue damage.
RESULTS: There was a significant increase in the plasma level of soluble TbetaRII
24 h and 48 h after injection of treatment vector. In the radiation (RT) +
AdexTbetaRII-Fc group, there was a significant reduction in respiratory rate at 4
weeks after treatment as compared to the RT-alone group. Histologic results
revealed a significant reduction in lung damage and decrease in the number and
activity of macrophages in the RT + AdexTbetaRII-Fc group as compared to the
RT-alone group. The tissue level of active TGFbeta1 was significantly reduced in
rats receiving RT + AdexTbetaRII-Fc treatment. There was also an upregulation of
transmembrane TbetaRII in lung tissue in the RT-alone group as compared to the RT
+ gene therapy rats.
CONCLUSIONS: This study shows the ability of AdexTbetaRII-Fc gene therapy to
induce an increase in circulating levels of soluble receptors, to reduce the
tissue level of active TGFbeta1, and consequently to ameliorate acute
radiation-induced lung injury.

PMID: 12957270 [PubMed - indexed for MEDLINE]

結果 (中文) 1:

292.Int J 辐射 Oncol 生物学与物理 2003 Oct 1; 2:563 72。可溶性 TGFbeta 类型 II 受体基因治疗改善急性辐射诱导大鼠的肺损伤。拉巴尼 ZN(1)，Anscher 女士，张某、 陈 L、 Samulski 电视、 李 CY，Vujaskovic Z。作者信息︰(1)辐射部肿瘤，杜克大学医学中心，达勒姆，数控27710，美国。目的︰ 评估是否重组人类的腺病毒载体，管理运载可溶性 TGFbeta1 II 型受体 (TbetaRII) 基因，可能会减少可用性的活动 TGFbeta1，从而保护从肺辐射损伤。方法和材料︰ 女性 Fisher 344 大鼠分别给予 30 Gy 单次右半照射 24 h 后的控制 (AdGFP) 注射或治疗 (AdexTbetaRII Fc) 向量。不同的终结点被评定为看对肺组织损伤。结果︰ 有了显著增加血浆水平的可溶性 TbetaRII24 小时和 48 小时后注射治疗矢量。在辐射 (RT) +AdexTbetaRII-Fc 组显著降低呼吸速率在还有 4周治疗后的相比，RT 单独的组。组织学结果显示肺损伤显著减少，数量减少和在 RT + AdexTbetaRII-Fc 巨噬细胞活性组相比RT 单组。积极 TGFbeta1 组织水平显著降低中大鼠接受 RT + AdexTbetaRII-Fc 治疗。另外，还有的上调跨膜 TbetaRII RT RT 单独组肺组织+ 基因治疗大鼠。结论︰ 本研究表明 AdexTbetaRII-Fc 基因治疗的能力诱导循环水平的可溶性受体，以减少增加积极 TGFbeta1 组织水平，从而改善急性辐射引起的肺损伤。PMID: 12957270 [PubMed-索引为 MEDLINE]

結果 (中文) 3:

292。j的放射肿瘤学的生物物理。10月1日2003；57（2）：563-72。可溶性TGFβⅡ型受体基因治疗对急性放射性大鼠肺损伤。Rabbani ZN（1），Zhang X，Chen L，安舍MS萨穆尔斯基电视，李朝阳，Vujaskovic Z.作者信息：（1）放疗科，北卡罗莱纳州达勒姆的杜克大学医学中心，NC27710、USA.目的：评价重组人腺病毒载体是否管理，进行可溶性TGFbeta1 II型受体（TbetaRII）基因，可以减少主动TGFbeta1可用性和从而保护肺辐射损伤。方法与材料：雌性大鼠344只，给予单剂量30右hemithoracic照射24 h控制注射后（AdGFP）或治疗（adextbetarii FC）向量。不同的结束点进行了评估，看看肺组织损伤。结果：有可溶性TbetaRII血浆水平显著增加治疗载体注射后24 h和48 h。在辐射（大）+adextbetarii FC组，有呼吸速率显著降低4治疗后数周与单纯放疗组相比。组织学结果揭示了肺损伤的数量和减少显着减少和减少巨噬细胞的活性在RT + adextbetarii FC组相比，单独组。主动TGFbeta1组织水平明显降低接受RT + adextbetarii FC治疗大鼠。也有上调跨膜TbetaRII肺组织单独放疗组相比，RT+基因治疗大鼠。结论：本研究显示adextbetarii FC基因治疗的能力诱导可溶性受体的循环水平的增加，以减少主动TGFbeta1组织水平从而改善，急性放射性肺损伤。发表于：12957270 [ PubMed索引数据库]