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Radiation-induced lung injury is a common complication of thoracic malignant tumor radiotherapy and severe nuclear accident injury. Currently, there is no effective treatment on this injury. Mesenchymal stem cells (MSCs) are a group of cells with multi-directional differentiation potential and they can protect lung tissue from radiation damage by homing to the injured site and differentiating to the damaged tissues, secreting cytokines and immune regulation. Further, the genetically modifying mesenchymal stem cells have not only the main characteristics of MSCs, but also can efficiently and stably express or knock down a certain of target genes, thereby enhancing or reducing the sensitivity of mesenchymal stem cells to various physiological stimulus and enhancing its therapeutic effect in radiation-induced lung injury, providing new ideas and new strategies for clinical treatment. This paper reviewed the relevant research progress in recent years.
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Objective To study the therapeutic effect of Tibetan medicine Flos Saussureae combined with glucocorticoid for progressive stage of radiation pneumonia.Methods A total of 65 post-chemotherapy radiation pneumonia patients with esophageal carcinoma were randomized into western medicine group(20 cases),combined group (21 cases) and Flos Saussureae group (24 cases),which were treated with prednisone (1 mg/kg,orally),prednisone (0.5 mg/kg,orally) plus Flos Saussureae Injection (2 mL/d,by intramuscular injection),and Flos Saussureae Injection (4 mL/d,by intramuscular injection) respectively.The medication lasted for 6 weeks.Before and after treatment,we investigated the scores of chest high resolution CT(HRCT),Leicester Cough Questionnaire (LCQ) scores,6-minute walk distance,pulmonary function indexes of vital capacity (VC),total lung capacity (TLC) and diffusion function DLco,and arterial oxygen partial pressure(PO2).Results (1) The scores of HRCT,6-minute walk distance and LCQ scores of the combined group were improved as compared with those of western medicine group and Flos Saussureae group (P ＜ 0.05).The improvement of psychological scores,social function scores and overall socres of LCQ in Flos Saussureae group was superior to that in western medicine group (P ＜0.05).(2)After treatment,pulmonary function indexes and PO2 of the combined group and Flos Saussureae group were improved compared with those of western medicine group (P ＜ 0.05),and the improvement of DLco and PO2 of the combined group was superior to that of Flos Saussureae group (P＜ 0.05).Conclusion Flos Saussureae Injection combined with glucocorticoid exerts certain therapeutic effect for progressive stage of radiation pneumonia,and large-dose Flos Saussureae Injection is beneficial to the improvement of symptoms and imaging features of the patients.
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Objective To investigate the protective effect of lentivirus-mediated silencing information regulation protein 6(SIRT6)overexpression on radioactive lung injury in rats.Methods 72 male 150-200 g Wistar rats were randomly divided into three groups(n=24).The 6 MV-X-ray linear accelerator was used to irradiate the lungs.The rats in each group were injected with normal saline(TNF-α)were measured at 1, 2, 4, and 8 weeks after radiotherapy(Lent-SIRT6), and the levels of tumor necrosis factor-α(TNF-IL-6 and IL-1β were measured by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.Results The alveolar wall and alveolar stroma were normal in the control group.The alveolar wall of the irradiated group was thickened and fibrosis, and a large number of hypertrophic fibrous tissues were found in the alveolar stroma.The alveolar wall of Lent-SIRT6 group was thickened And alveolar stromal fibrosis symptoms were lighter than the irradiation group.Compared with the control group, the levels of serum TNF-α and IL-6, neutrophil count and the levels of TNF-α, IL-6 and IL-1β in the liver tissue were significantly higher than those in the control group (P<0.05).The lentiviruses overexpressing SIRT6 could alleviate the abnormalities caused by radiation (P<0.05).The difference was statistically significant (P<0.05).Conclusion SIRT6 can effectively inhibit the inflammatory reaction, reduce the lung injury symptoms of radiation pneumonia, and have some protective and prevention effect on lung injury.
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Objective To investigate the clinical effect of lung equivalent uniform dose (LEUD)-based predictive model for radiation pneumonitis (RP) induced by volumetric modulated arc therapy (VMAT) and to determine the optimal a value.Methods A total of 65 patients with primary lung cancer who received VMAT from July 2015 to February 2016 were divided into RP group and non-RP group according to the presence or absence of RP after radiotherapy.Their dose-volume histogram (DVH) data and other data were obtained and analyzed by the self-compiled numerical analysis program.The LEUD values in the two groups were calculated at a=[-50, 50], and then the a value was identified when the relative difference of LEUD between the two groups was maximal.The paired t test was used for analyzing the differences in V5, V20, V30, minimum lethal dose (MLD), and LEUD (aoptimal) between the two groups.A Pearson correlation analysis was used to determine the correlation of Vdose and LEUD (aoptimal) with RP.The logistic regression method was used to establish the predictive model of RP.Results The maximum relative difference in LEUD between RP group and non-RP group was obtained at a=0.3(627.94 cGy vs.510.23 cGy, relative difference[R]=23.07%).R decreased slowly at t=[-50,-5], increased sharply at t=[-5, 0], and reached the maximum value at a=0.3.After a rapid decrease at a=[0.3, 4], R decreased slowly at a=[4, 50].The correlation analysis of the traditional physical volume dose threshold also showed that the LEUD (at a=0.3) was correlated with V5, V10, V20, and MLD (r=0.929, P<0.05).Conclusions For patients receiving VMAT for thoracic cancer, LEUD (at a=0.3) can distinguish between patients with and without RP.Therefore, LEUD is recommended to be<510 cGy.A combination of LEUD and conventional physical dose has a good clinical predictive value for RP under non-uniform irradiation.
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Objective To evaluate the clinical effect of Tanreqing in the treatment of radiation pneumonia. Methods 75 patients with radiation pneumonia were randomly divided into treatment group and control group according to the registration of this study.38 cases in the treatment group treated by Tanreqing,antibiotics and glucocorticoid,while 37 cases in the control group was given antibiotics and glucocorticoid.Then,the therapeutic efficacy was compared.Results From the chest routine scan result and the clinical symptom release,the excellence rate of the treatment group was 68.4%,which of the control group was 43.2%,there was statistically significant difference between the two groups (χ2 =4.823,P =0.028 ).Conclusion Treating radiation pneumonia with Tanreqing has good effect,and it is worthy of clinical application.
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Objective: To analyze the feasibility of omitting clinical target volume (CTV) for patients with stage III non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Methods: Data of 105 patients with stage III NSCLC who were hospitalized and received IMRT in Department of Radiotherapy of Peking University Cancer Hospital from January 2008 to November 2012 were retrospectively analyzed. There were 73 cases of squamous cell carcinoma and 32 cases of adenocarcinoma. Of 105 cases, 55 were irradiated with target volume without CTV, and 50 cases were irradiated with CTV. Dose prescription was 95% planning target volume (PTV) 54-63 Gy/27-35 fx/5.4-7.0 weeks. Results: In the arm without CTV and arm with CTV, the local relapse rates were 32.7% and 32.0%, and the distant metastasis rates were 56.4% and 48.0%, respectively (P > 0.05). The median progression-free survival was 9 months in both groups. The 1-year, 2-year and 3-year survival rates in irradiation with target volume without CTV group were 74.5%, 43.6% and 23.6%, respectively; which were 70.0%, 46.0% and 20.0%, respectively in irradiation with target volume with CTV group (all P > 0.05). The grades 1-2 radiation pneumonia rates in irradiation with target volume without CTV group and with CTV group were 94.5% (52/55) and 82.0% (41/50), respectively, and the grades 3-4 radiation pneumonia rates were 5.5% (3/55) and 18.0% (9/50), respectively (P = 0.044). Conclusion: Omitting CTV for patients with stage III NSCLC treated with IMRT can not increase the rates of local recurrence and distant metastasis, and not decrease the progression-free survival and overall survival, but obviously decrease the rate of grades 3-4 radiation pneumonia.
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Objective To investigate the therapeutic effects and mechanism of anti-radiation pneumonia decoction(ARPD) on radiation induced lung fibrosis in rats.Methods One hundred and five male SD rats in a SPF grade were divided into Chinese medicine group,single radiation group and control group by random digits table method,with 35 in each group.After anesthetization,rats in Chinese medicine and single radiation groups were exposed to 6 MV X-rays at the dose of 15Gy.Rats in Chinese medicine group were treated with ARPD at the dosage of 10 ml·kg-1 ·d-1 once a day,but rats in single radiation group did not receive ARPD treatment.Rats in control group were treated with neither irradiation nor drugs.Five rats of each group were killed and the lung tissues and blood samples were collected at 15,30,60,75,90,105 and 140 d.The pathological changes of lung tissues were observed and the tissue protein and gene expressions of TGF-β1,PAI-1 and collagen type Ⅲ(C Ⅲ) were assayed by Western blot and RT-PCR.ELISA was used to detect serum TGF-β1 and plasma PAI-1.Tissue and serum HYP were determined by acid hydrolysis and alkaline hydrolysis methods respectively.Results Inflammation was found in the lung tissues of all the exposed rats.Obvious pathological lung fibrosis was found at 60 d,the inflammation and the fibrosis in treated group were slighter than those in single radiation group.In Chinese medicine group,the protein and gene expression levels of TGF-β1,PAI-1,C Ⅲ 30 d(Protein:t =2.49-3.74,t =2.63-4.57 and t =2.76-3.83;Gene:t =2.59-4.33,t =2.83-4.62 and t =2.83-3.96,P＜0.05),serum TGF-β1 and plasma PAI-1 15 dlater (t =2.85-6.27 and t =3.69-5.27,P＜0.05),and the levels of tissue and serum HYP60 dlater (t=3.65-4.40 and t =6.56-3.75,P＜0.05),all of them were lower than those in single radiation groups.There were significant positive correlations between tissue TGF-β1 and PAI-1 as well as C Ⅲ (Protein expression:r =0.604,0.759,P ＜0.05;Gene expression:r=0.519,0.816,P＜0.05).Conclusions ARPD may inhibit the pulmonary fibrosis by decreasing the levels of TGF-β1,PAI-1 and C Ⅲ.
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Objective To observe the protective effect of acetylcysteine against radiation pneumonia.MethodsTotal of 80 patients who were inoperable were randomly allocated into treatment group and control group.Using conformal radiation technology and the total dose was 65 ～ 75Gy.The patients in treatment group were given acetylcysteine and radiotherapy;the patients in control group were given radiotherapy only.ResultsAll patients were treated radiotherapy.The effective rate( CR and PR) of treatment group was 90％,and that of control group was 85％(P ＞ 0.05);The incidence of acute radiation pneumonia and pulmonary fibrosis in treatment group were 15％ and 20％,respectively;and that of control group were 33％ and 45％ respectively.There was significant difference between the two groups ( P ＜ 0.05 ).ConclusionUsing acetylcysteine during radiotherapy could prevent radiation pneumonia in the non-small cell lung cancer patients.
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Objective To investigate the effect of Pingfei Oral Liquid (POL) on the distribution of mast cells (MCs) and the expression of interleukin 6 (IL-6) in the lung tissue of radiation pneumonia rats. MethodsForty-five SD rats were randomized into 3 groups : normal control,model group and POL group. The rat model of radiation lung fibro-sis was set up by a single X-ray dose of 20Gy irradiation over the whole chest of the rats. POL (20 g·kg-1·d-1,once a day, five times a week) was given orally one week before irradiation and the treatment lasted 5 weeks. MCs in the lung tissue were stained with toluidine blue firstly and then were counted 2, 4 and 8 weeks after irradiation. IL-6 protein expression of lung tissue was measured by immunohistochemical assay 8 weeks after irradiation, and mRNA ex-pression was determined with RT-PCR 4 weeks after irradiation. ResultsIt's showed the aggregation of large amount of pulmonary mast cells and increase of IL-6 protein expression 8 weeks after irradiation (P < 0.01).IL-6 mRNA expression in the irradiated lung of rats increased 4 weeks after irradiation (P < 0. 01). POL could reduce the aggrega- tion of MCs (P < 0. 01) and the expression of IL-6 protein (P < 0. 01) and mRNA (P < 0. 05) in the lung tissue. ConclusionPOL can prevent radiation pneumonia in rats by reducing the aggregation of mast cells and inhibiting IL-6 expression in the lung tissue.
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BACKGROUND: One of the limitation during the irradiation of malignant tumor is hazard to normal tissue although it is important and effective tool for treating malignant tumor. We studied the role of interleukin-1 alpha (IL-1alpha) and interleukin-6 (IL-6) in the radiation-induced lung injury especially on fibrosis. METHODS: We irradiated right-side lungs of thirty Sprague-Dawley rats with single fraction of 20 Gy and then sacrificed the animals until 20th week at intervals of two weeks. Both irradiated and unirradiated lung tissues were stained hematoxilin and eosin, Masson trichrome, reticulin and immunohistochemical staining for IL-1alpha and IL-6. The degree of the staining for IL-1alpha and IL-6 were examined semiquantitatively. RESULTS: Two weeks after irradiation interstitial edema and capillary congestion appeared, followed by increase of the monocytes infiltration and proteinaceous material during 4th and 8th week. After eight weeks of irradiation, collagen and reticulin fibers were detected along alveolar wall. 12th to 20th week, fibrosis in interstitium, decreased number of alveoli and thickening of bronchial wall were observed. The degree of immunohistochemical staining for IL-1alpha and IL-6 was increased rapidly during the first three week and then decreased slowly, but remain incresed until 20th week. CONCLUSION: Our Study demonstrate the early and persistent elevation of cytokines IL-1alpha and IL-6 by immunohistochemical stain in rat lung following pulmonary irradiation. We think cytokines are produced immediately after irradiation, make collagen genes turn on and perisist until the expression of late effects become apparent pathologically and clinically.