Radiotherapy (RT) is a common and effective non-surgical treatment for thoracic solid tumors, and radiation-induced lung injury (RILI) is the most common side effect of radiotherapy. Even if RT is effective in the tre...Radiotherapy (RT) is a common and effective non-surgical treatment for thoracic solid tumors, and radiation-induced lung injury (RILI) is the most common side effect of radiotherapy. Even if RT is effective in the treatment of cancer patients, severe radiation pneumonitis (RP) or pulmonary fibrosis (PF) can reduce the quality of life of patients and may even lead to serious consequences of death. Therefore, how to overcome the problem of accurate prediction and early diagnosis of RT for pulmonary toxicity is very important. This review summarizes the related factors of RILI and the related biomarkers for early prediction of RILI.展开更多
Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-...Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.展开更多
Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were ...Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.展开更多
Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were ra...Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by immunohistochemistry.Results：（1） Radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray,which can simulate the development and evolution of RILI.展开更多
目的:观察虎杖对放射性肺损伤大鼠肺组织TGF-β1蛋白、Smad3,Smad4,Smad7mRNA表达的影响,探讨虎杖防治放射性肺损伤的作用机理。方法:随机将180只清洁级雄性SD大鼠分为正常对照组、虎杖预防组、虎杖当天组、虎杖28天组、DXM治疗组,共6组...目的:观察虎杖对放射性肺损伤大鼠肺组织TGF-β1蛋白、Smad3,Smad4,Smad7mRNA表达的影响,探讨虎杖防治放射性肺损伤的作用机理。方法:随机将180只清洁级雄性SD大鼠分为正常对照组、虎杖预防组、虎杖当天组、虎杖28天组、DXM治疗组,共6组,每组30只,除正常对照组外,其余各组均给予直线加速器全胸单次照射18Gy。虎杖预防组于照射前1周开始灌服虎杖流浸膏,虎杖当天治疗组于造模后第1天开始每日予虎杖流浸膏灌胃,虎杖28天治疗组于造模后第28天开始每日予虎杖流浸膏灌胃,地塞米松治疗组造模后第1天开始每日予地塞米松灌胃用药4周,4周后予1 m L/100 g生理盐水灌胃,正常对照组和模型组予等容积的生理盐水灌胃。每组分别于1、2、3、4、6、8周随机处死4只大鼠,取右肺下叶组织,免疫组化法观察肺组织TGF-β1蛋白表达的变化,RT-PCR法检测肺组织Smad3、Smad4、Smad7mRNA的表达。结果:各组照射后大鼠肺组织均有TGF-β1、Smad3、Smad4不同程度的表达,模型组显著高于正常对照组(P<0.01),各虎杖治疗组与DXM治疗组表达有不同程度下降,与模型组比较有显著差异(P<0.01)。而模型组Smad7的表达显著低于正常对照组(P<0.01)。各虎杖治疗组smad7表达较模型组均有升高,其中虎杖预防组Smad7-mRNA表达在第1周时下降,第2周后表达持续增加,与模型组比较有差异(P<0.05),虎杖当天治疗组在第3周后表达增加,与模型组比较有显著差异(P<0.01)。虎杖预防组与虎杖当天治疗组在第6、8周时表达高于DXM治疗组,有显著差异(P<0.01);虎杖28天治疗组在第6周后Smad7-mRNA表达高于模型组,但与DXM治疗组比较无显著性差异(P>0.05)。结论:虎杖能够降低TGF-β1蛋白的表达,抑制受体激活性蛋白Smad3的表达,下调通用性蛋白Smad4的表达,促进抑制性蛋白Smad7的表达,从而抑制放射性肺损伤大鼠肺脏中TGF-β/Smad信号传导通路的激活,因此虎杖有一定的预防放射性肺损伤的作用。展开更多
文摘Radiotherapy (RT) is a common and effective non-surgical treatment for thoracic solid tumors, and radiation-induced lung injury (RILI) is the most common side effect of radiotherapy. Even if RT is effective in the treatment of cancer patients, severe radiation pneumonitis (RP) or pulmonary fibrosis (PF) can reduce the quality of life of patients and may even lead to serious consequences of death. Therefore, how to overcome the problem of accurate prediction and early diagnosis of RT for pulmonary toxicity is very important. This review summarizes the related factors of RILI and the related biomarkers for early prediction of RILI.
基金Supported by grants from the Fundamental Research for South-Central University for Nationalities(No.PJS140011604)Chen Xiaoping Foundation Development of Science and Technology of Hubei(No.CXPJJH11800004-015)
文摘Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.
文摘Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.
基金This work was supported by the National Natural Science Foundation of China （NSFC） grants （Youth Fund, No. 81101043 ）, Jiangsu Province Natural Science Foundation （No. BK2011178）, the Priority Academic Program Development of Jiangsu Higher Education Institutions （PAPD 2011-0318）, and Key Project of Nanjing Medical University Technology Development Fund （No. 2008NMUZ051）.
文摘Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography perfusion.Methods：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were sham-radiated.All rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral lungs.The pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by immunohistochemistry.Results：（1） Radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray,which can simulate the development and evolution of RILI.
文摘目的:观察虎杖对放射性肺损伤大鼠肺组织TGF-β1蛋白、Smad3,Smad4,Smad7mRNA表达的影响,探讨虎杖防治放射性肺损伤的作用机理。方法:随机将180只清洁级雄性SD大鼠分为正常对照组、虎杖预防组、虎杖当天组、虎杖28天组、DXM治疗组,共6组,每组30只,除正常对照组外,其余各组均给予直线加速器全胸单次照射18Gy。虎杖预防组于照射前1周开始灌服虎杖流浸膏,虎杖当天治疗组于造模后第1天开始每日予虎杖流浸膏灌胃,虎杖28天治疗组于造模后第28天开始每日予虎杖流浸膏灌胃,地塞米松治疗组造模后第1天开始每日予地塞米松灌胃用药4周,4周后予1 m L/100 g生理盐水灌胃,正常对照组和模型组予等容积的生理盐水灌胃。每组分别于1、2、3、4、6、8周随机处死4只大鼠,取右肺下叶组织,免疫组化法观察肺组织TGF-β1蛋白表达的变化,RT-PCR法检测肺组织Smad3、Smad4、Smad7mRNA的表达。结果:各组照射后大鼠肺组织均有TGF-β1、Smad3、Smad4不同程度的表达,模型组显著高于正常对照组(P<0.01),各虎杖治疗组与DXM治疗组表达有不同程度下降,与模型组比较有显著差异(P<0.01)。而模型组Smad7的表达显著低于正常对照组(P<0.01)。各虎杖治疗组smad7表达较模型组均有升高,其中虎杖预防组Smad7-mRNA表达在第1周时下降,第2周后表达持续增加,与模型组比较有差异(P<0.05),虎杖当天治疗组在第3周后表达增加,与模型组比较有显著差异(P<0.01)。虎杖预防组与虎杖当天治疗组在第6、8周时表达高于DXM治疗组,有显著差异(P<0.01);虎杖28天治疗组在第6周后Smad7-mRNA表达高于模型组,但与DXM治疗组比较无显著性差异(P>0.05)。结论:虎杖能够降低TGF-β1蛋白的表达,抑制受体激活性蛋白Smad3的表达,下调通用性蛋白Smad4的表达,促进抑制性蛋白Smad7的表达,从而抑制放射性肺损伤大鼠肺脏中TGF-β/Smad信号传导通路的激活,因此虎杖有一定的预防放射性肺损伤的作用。
