Regional and organ-level responses to local lung irradiation in sheep.
Regional and organ-level responses to local lung irradiation in sheep.
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DOI：
10.1038/s41598-021-88863-8
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发表时间：
2021-05-05
影响因子：
4.6
通讯作者：
Lawrence J
中科院分区：
文献类型：
--
作者：
Collie D;Wright SH;Del-Pozo J;Kay E;Schwarz T;Parys M;Lawrence J
在放射治疗中，肺是一个剂量限制器官。这可能会限制肿瘤的控制，当努力计划限制辐射引起的肺损伤（RILI）的可能性。了解决定放射诱导肺纤维化易感性的因素将有助于预防和管理RILI，并可能导致更有效的个性化放疗治疗。由于区域和器官水平反应的相互作用可能形成RILI的慢性后果，我们试图在羊模型中描述反应的两个方面。在14天内按5份剂量（每组剂量6 Gy）给予左肺实质固定体积，同时限制对侧肺剂量。通过计算机断层扫描（CT）记录放射学变化，以确定在d21、d63和d171 （n = 2）以及d21、d147和d227 （n = 2）时放射暴露肺相对于未暴露肺的差异。在尸检样本中评估大体和组织学上的肺变化，以确定慢性肺对辐射的反应。从基于纹理的放射学特征分析来看，与对照肺相比，辐照后的肺显示出放射性密度降低和均匀性增加。尸检时，胸膜表面的苍白很容易确定辐射场，在固定肺标本的切面也很明显。苍白的程度和均匀性反映了辐射暴露肺肺泡间隔毛细血管中红细胞的稀疏存在。这些变化与对侧控制肺微血管扩张和充血形成对比。对照急性RILI绵羊肺容量的测量数据表明，间质胶原继续沉积在放射性暴露的肺场中。在慢性反应期间，整体肺血管增加，内皮细胞标志物（CD31）的表达增加；然而，辐照后的肺部血管密度持续下降，且与肺胶原呈负相关。其他器官水平的反应包括α平滑肌肌动蛋白（ASMA）的表达增加，增殖细胞数量增加（Ki67阳性），以及表达树突状细胞-溶酶体相关膜蛋白（DC-LAMP）抗原的细胞。在这个模型中，对RILI的慢性反应在整个器官和局部肺水平上都受到影响。虽然暴露于辐射的长期后果包括胶原蛋白在辐射场的持续沉积，但器官水平的反应还包括血管化增加和ASMA、Ki67和DC-LAMP的表达增加。中断这些方面之间的相互作用可能影响放射治疗后对肺纤维化的易感性。我们提倡大型动物模型系统的重要性，以寻求这些机会，在同一主题中随着时间的推移并行地针对局部，器官水平和系统机制。
Lung is a dose-limiting organ in radiotherapy. This may limit tumour control when effort is made in planning to limit the likelihood of radiation-induced lung injury (RILI). Understanding the factors that dictate susceptibility to radiation-induced pulmonary fibrosis will aid in the prevention and management of RILI, and may lead to more effective personalized radiotherapy treatment. As the interaction of regional and organ-level responses may shape the chronic consequences of RILI, we sought to characterise both aspects of the response in an ovine model. A defined volume of left pulmonary parenchyma was prescribed 5 fractions of 6 Gy within 14 days while the contralateral lung dose was constrained. Radiographic changes via computed tomography (CT) were documented to define differences in radio-exposed lung relative to non-exposed lung at d21, d63 and d171 (n = 2), and at d21, d147 and d227 (n = 2). Gross and histologic lung changes were evaluated in samples derived at necropsy examination to define the chronic pulmonary response to radiation. Irradiated lung demonstrated reduced radio-density and increased homogeneity as evidenced from texture based radiomic feature analysis, relative to the control lung. At necropsy, the radiation field was readily defined by pallor on the pleural surface, which was also evident on the cut surface of fixed lung specimens. The degree and homogeneity of pallor reflected the sparse presence of erythrocytes in alveolar septal capillaries of radiation-exposed lung. These changes contrasted with dilated and congested microvasculature in the contralateral control lung. Referencing data to measurements made in control lung volumes of sheep experiencing acute RILI indicated that interstitial collagen continues to deposit in the radio-exposed lung field. Overall lung vascularity increased during the chronic response, as evidenced by increased expression of endothelial cell marker (CD31); however, vascularity was consistently decreased in irradiated lung and was negatively correlated with lung collagen. Other organ-level responses included increased expression of alpha smooth muscle actin (ASMA), increased numbers of proliferating cells (Ki67 positive), and cells expressing the dendritic cell-lysosomal associated membrane protein (DC-LAMP) antigen. The chronic response to RILI in this model is effected at both the whole organ and local lung level. Whilst the long-term consequences of exposure to radiation involved the continued deposition of collagen in the radiation field, organ-level responses also included increased vascularization and increased expression of ASMA, Ki67 and DC-LAMP. Interrupting the interplay between these aspects may influence susceptibility to pulmonary fibrosis after radiotherapy. We advocate for the importance of large animal model systems in pursuing these opportunities to target local, organ-level and systemic mechanisms in parallel within the same subject over time.
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DOI：
10.1016/s0360-3016(01)01685-6
发表时间：
2001-11-01
影响因子：
7
作者：
Hernando, ML;Marks, LB;Lind, PA
通讯作者：
Lind, PA
影响因子：
3.3
作者：
Harder, Eileen M.;Park, Henry S.;Decker, Roy H.
通讯作者：
Decker, Roy H.
合成层状脂质的雾化可缓解大型动物模型中辐射诱导的肺损伤。
影响因子：
4.6
作者：
Collie D;Murchison JT;Wright SH;McLean A;Howard L;Del-Pozo J;Smith S;McLachlan G;Lawrence J;Kay E;Schwarz T;Parys M
通讯作者：
Parys M
DOI：
10.1016/s0360-3016(99)00183-2
发表时间：
1999-09-01
影响因子：
7
作者：
Graham, MV;Purdy, JA;Perez, CA
通讯作者：
Perez, CA
影响因子：
9.6
作者：
Hanania, Alexander N.;Mainwaring, Walker;Ludwig, Michelle
通讯作者：
Ludwig, Michelle