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Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.
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Objective:To investigate the effect of low-dose ionizing radiation on blood cell parameters of radiation workers.Methods:A total of 124 staff members engaged in radiology were selected into the observation group, and they were divided into 4 subgroups of physicians, physicists, technicians, and maintainer according to their jobs. A total of 130 non-radiation-related staff members from the same hospital were selected into the control group. Blood cell parameters of peripheral blood of all subjects from 2016 to 2019 were collected, and the differences in blood cell parameters between the radiation group and the control group as well as 4 subgroups of the control group were analyzed and compared, and the correlation between the differences in blood cell parameters and the cumulative radiation dose was compared.Results:Compared with the control group, the white blood cell count, neutrophil count, red blood cell count and hemoglobin count in the observation group were lower than those in the control group (all P<0.05). There are no significant differences in cumulative radiation dose among different types of work (all P>0.05). Correlation analysis showed that the blood cell parameters of peripheral blood cells were not significantly correlated with the cumulative radiation dose. The blood cell count changes after 4-year low-dose ionizing radiation between the physicist group, the technician group and the maintainer sub-group were significantly different (all P<0.05), but the above differences were not related to the cumulative radiation dose (all P>0.05). Conclusions:Under the same exposure and protection conditions, the blood cell counts of different radiation-related workers are not significantly different, and the long-term cumulative radiation dose has no significant correlation with blood cell parameters. Therefore, peripheral blood cell parameters can no longer be used as a good indicator to reflect radiation damage, and it is urgent to find more convenient, intuitive and sensitive indicators of radiation damage.
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Objective:To evaluate the efficacy and safety of thoracic radiotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) with different metastatic sites.Methods:A retrospective analysis was performed among 830 ES-SCLC patients who were admitted to our hospital from 2010 to 2019. They all received the first-line chemotherapy and had no progression after chemotherapy. 341 patients of them received thoracic radiotherapy after chemotherapy. The main endpoint was overall survival. The Chi-square test was used to compare the categorical data including gender and age, etc. Univariate survival analysis was estimated by Kaplan-Meier method and the log-rank test was used to compare the survival curves between two groups. A multivariate prognostic analysis was made by the Cox proportional hazard model.Results:In all the patients, the overall survival (OS) was 12.4 months. The patients with thoracic radiotherapy had significantly higher OS than the patients without thoracic radiotherapy (15.2 months vs.10.8 months, P<0.001). Thoracic radiotherapy significantly improved the OS in patients without liver metastasis (16.0 months vs.11.4 months, P<0.001) in the oligometastatic patients. But for the oligometastatic patients with liver metastasis, the OS benefit was not significant (14.2 months vs. 10.6 months, P=0.072). For polymetastatic patients without liver metastasis, thoracic radiotherapy offered significant OS benefits (14.5 months vs.10.9 months, P<0.001), but for the polymetastatic patients with liver metastasis, the OS was not improved with thoracic radiotherapy (10.2 months vs.9.2 months, P=0.715). Conclusions:In ES-SCLC patients, thoracic radiotherapy provides significant OS benefits in patients with oligometastases ES-SCLC without liver metastasis and for the liver metastatic patients may also benefit from thoracic radiotherapy based on the effectiveness of chemotherapy. In patients with multiple metastases, thoracic radiotherapy only improves the OS in patients without liver metastasis, but does not improve the prognosis in patients with liver metastasis.
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Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.
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Objective:To evaluate the survival outcome and toxicity of hypofractionated radiotherapy (45 Gy/15f) in patients with locally advanced/advanced non-small cell lung cancer (NSCLC) who are ineligible for conventional fractionated radiotherapy.Methods:The early efficacy, survival and toxicity of inoperable patients ( n=64) with locally advanced/advanced NSCLC patients admitted to Cancer Hospital of Tianjin Medical University from 2014 to 2018 were retrospectively analyzed. Hypofractionated radiotherapy (45 Gy/15f) were performed by using intensity-modulated radiotherapy or volumetric-modulated arc therapy technologies on Pinnacle 9 planning system. Results:The median follow-up time was 26 months. The early efficacy was available in 58 patients: complete response for 2 cases (3%), partial response for 22(38%), stable disease for 28(44%) and progressive disease for 6(9%), respectively. The local control rate was 90%. The median time to progression (TTP) and the median overall survival (OS) for all patients was 8.2 months and 21.0 months, respectively. The 1-, 2-and 3-year TTP rate was 37%, 28%, 14% and the OS rate was 66%, 43% and 27%, respectively. The incidence of esophagitis was 17%( n=11), 19%( n=12) for radiation pneumonitis and 20%( n=13) for myelosuppression. No grade ≥3 esophagitis or pneumonia was found. Conclusion:Hypofractionated radiotherapy (45 Gy/15f) is efficacious and safe for patients with locally advanced/advanced NSCLC, which yields controllable adverse events.
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Objective:To investigate the role of concurrent chemoradiotherapy in the treatment of limited-stage small cell lung cancer (LS-SCLC) and the impact of the number of chemotherapy cycle during radiotherapy (RT) on clinical prognosis.Methods:Patients with LS-SCLC treated with definitive radiotherapy from May, 2008 to September, 2016 were included in the study. The primary endpoint was overall survival (OS), which was calculated from the start of treatment to the date of death or last follow-up. The effect of the number of concurrent chemotherapy cycle and other clinical factors on clinical efficacy was analyzed. Survival analysis was performed with Kaplan- Meier method, and multivariate analysis was performed with Cox regression model. Results:Three hundred and seventeen patients were eligible for the analysis. Among them, 129 patients received sequential chemoradiotherapy and 188 patients received concurrent chemoradiotherapy. Among patients receiving concurrent chemoradiotherapy, 86 patients received 1 cycle of concurrent chemotherapy and 102 cases of 2 cycles of concurrent chemotherapy. The median follow-up time was 22.47 months. Multivariate survival analysis showed that only clinical stage, timing of RT administration and prophylactic cranial irradiation (PCI) were the independent prognostic factor for OS. The median OS in patients who received 1 cycle and 2 cycles of concurrent chemotherapy during RT were 33.8 months and 30.4 months ( P=0.400). No matter in elder patients or in younger patients, in early RT group or in late RT group and application of PCI or not, the number of concurrent chemotherapy cycle exerted no significant impact on OS. The incidence of grade 3 or above adverse events was 20% in the 1-cycle concurrent chemotherapy group, and 13.7% in the 2-cycle concurrent chemotherapy group. Conclusions:Concurrent chemoradiotherapy is the standard treatment of LS-SCLC. Two cycles of concurrent chemotherapy during RT is not necessarily superior to 1 cycle of concurrent chemotherapy. The optimal number of concurrent chemotherapy cycle during RT need to be studied in a large prospective randomized clinical trial.
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Objective@#To explore the effect of nutritional status pre-and during chemoradiotherapy on the prognosis of patients with limited- stage small cell lung cancer (LS-SCLC).@*Methods@#We retrospectively collected medical records of 172 LS-SCLC patients undergoing concurrent chemoradiotherapy in our hospital from 2000 to 2014, with 126 males and 46 females. The data of complete blood count and hepatic and renal function were collected before initial treatment, before radiotherapy, 4 weeks during radiotherapy, and 1 month after complete of treatment. The prognostic nutritional index(PNI)was calculated. Kaplan-Meier method was used to calculate the survival rate. Log-rank test was performed used to compare the survival differences between groups. Multivariate prognostic analysis was performed using Cox regression model.@*Results@#The median overall survival (OS) was 21 months, with median progression-free survival (PFS) of 11 months. At the beginning of treatment, patients with pre-treatment PNI ≥ 53 had significantly superior OS (median 37 vs 15 months, P=0.001) and PFS (median 16 vs 10 months, P=0.017). Patients with pre-treatment hemoglobin ≥140 g/L and <140 g/L had an median OS of 32 months and 17 months (P=0.019), and median PFS of 16 months and 9 months (P=0.040), respectively. During chemoradiation, patients with elevated hemoglobin had similar median OS compared with those had decreased hemoglobin (27 vs 18 months, P=0.063, but superior median PFS (15 vs 9 months, P=0.017). Multivariate analysis revealed that prophylactic cranial irradiation, pre-treatment hemoglobin ≥140 g/L, and pretreatment PNI ≥53 were independent predictors of OS and PFS in patients with LS-SCLC.@*Conclusion@#Pre-treatment nutritional status and the changes of nutritional status during chemoradiotherapy is significantly associated with the prognosis of patients with limited-stage small cell lung cancer. The patients with better pre-treatment nutritional status have a better prognosis.
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Large cell neuroendocrine carcinoma is not very common, and it has a high degree of malignancy and invasion, outcome is also poor. Even LCLC is defined as non-small cell lung cancer, its biological and clinical characteristics, prognostic factors are similar to small cell lung cancer. The treatment for LCLC is still controversial. The research progress on comprehensive treatment of lung large cell neuroendocrine carcinoma was reviewed.
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Large cell neuroendocrine carcinoma is not very common,and it has a high degree of malignancy and invasion,outcome is also poor.Even LCLC is defined as non-small cell lung cancer,its biological and clinical characteristics,prognostic factors are similar to small cell lung cancer.The treatment for LCLC is still controversial.The research progress on comprehensive treatment of lung large cell neuroendocrine carcinoma was reviewed.
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Extensive-stage small cell lung cancer (ES-SCLC) accounts for approximately two-thirds of all SCLCs. Chemotherapy is still the main treatment, supplemented with radiotherapy and other comprehensive treatments. Although sensitive to chemotherapy and radiotherapy, almost all ES-SCLCs are vulnerable to treatment resistance and have high recurrence rates. Therefore, novel therapies are needed to improve treatment efficacy. The recent advances in radiotherapy for ES-SCLC include prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT). Moreover, immunotherapy has shown good antitumor activity, and immune-checkpoint inhibi-tors may become an important breakthrough in SCLC treatment. This article briefly reviewed the clinical research on radiotherapy and immunotherapy for advanced-stage SCLC.
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Genomic instability with increased DNA damage accumulations and partial DNA repair defects is more dependent on exist-ing DNA repair pathways, leading to disturbance in restoration of completely chemoradiation-induced DNA damage and finally induc-ing resistance to chemoradiation. The discovery of poly (ADP-ribose) polymerase inhibitors (PARPis) has sparked interest in synergistic reactions to kill tumor cells that are deficient in homologous recombination repair. Currently, under FDA approval of PARPis on ad-vanced ovarian cancer, clinical trials for several PARPis are being conducted to assess toxicities, efficacies, and benefits of drugs as monotherapy or in combination with radiation or other chemotherapeutic agents for ovarian, breast, prostate, rectal, lung, pancreatic, peritoneal, head and neck, and brain cancers;squamous cell carcinomas;sarcomas;and others. In this review, we focus on outlining the molecular mechanisms and clinical developments of approved PARPis and the emerging confusions in ongoing clinical trials and practice.
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The granulocyte-macrophage colony-stimulating factor(GM-CSF)can effectively induce the proliferation of tumor-associat-ed immunocytes as a hematopoietic factor;therefore,the fact that GM-CSF can induce systemic antitumor immune responses has at-tracted much attention.Radiotherapy,as one of the main treatment approaches of cancer,can kill tumor cells directly,and has an ef-fect on anti-tumor immunity.Several clinical studies have shown that radiotherapy combined with the GM-CSF can induce an abscopal effect and confer favorable therapeutic effects for cancer.Herein,we review the research progress on GM-CSF,and radiotherapy com-bined with GM-CSF in tumor treatment.
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Objective:To observe the locoregional recurrence and survival of stageⅢA-N2 non-small cell lung cancer (NSCLC) after in-duction chemotherapy and surgery, to analyze the prognosis influenced by nodal downstaging, and to explore the necessity for postop-erative radiotherapy. Methods:A total of 116 cases of stageⅢA-N2 NSCLC were treated with induction chemotherapy and surgery be-tween January 2009 and June 2014. These cases underwent R0 resection. Kaplan-Meier method was employed to calculate the local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of the patients. Log-rank test was con-ducted to compare the differences between groups. Cox models were used to perform multivariate analysis. Results:The median fol-low-up of the patients was 24.42 months. The numbers of patients with pN0, pN1, and pN2 were 40 (34.5%), 16 (13.8%), and 60 (51.7%), respectively. The 3-year local recurrence rates of patients with pN0, pN1, and pN2 were 27.5%, 56.2%, and 51.7%, respectively. In the group treated with adjuvant chemotherapy, the 3-year local-recurrence rates of patients with pN0, pN1, and pN2 were 26.9%, 58.3%, and 46.2%, respectively. Multivariate analysis revealed that the significant predictor of LRFS was pN0 during the surgery. The LRFS of patients with pN0 was greater than that of the patients with pN1 (P=0.048). The LRFS of patients with pN1 was not significantly associated with that of patients with pN2 (P=0.314). The 5-year OS rate of the groups was 46.6%. The multivariate analysis also demon-strated that pT1, pN0-1, and induction chemotherapy effects were associated with OS. The patients with pN2 yielded a poorer OS than those with pN0 and pN1 (P<0.05). The patients with pN0 did not significantly differ from those with pN1 in terms of OS (P=0.412). Conclu-sion:Although the occurrence of pathologic downstaging is a well-known positive prognostic indicator after stageⅢ-N2 NSCLC is sub-jected to chemotherapy, the local-recurrence rate of nodal-downstaged patients remains high, even when they receive adjuvant che-motherapy. Therefore, new postoperative strategies after induction chemotherapy and surgery should be developed.
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As a DNA damage sensor,poly (ADP-ribose) polymerase (PARP) is involved in a wide variety of cellular activities,such as DNA damage repair.PARP inhibitors regulate a series of cellular activities by inhibiting PARP function,which have become a focus of current research.Recently,several in vivo and in vitro studies showed that PARP inhibitors combined with radiotherapy effectively enhanced the efficacy of radiotherapy.This paper reviews the research advances in the mechanisms of action of PARP inhibitors and their combination with radiotherapy.
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<p><b>OBJECTIVE</b>The aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Expressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed.</p><p><b>RESULTS</b>The positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015).</p><p><b>CONCLUSIONS</b>Our findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.</p>
Subject(s)
Humans , Aurora Kinase A , Metabolism , Carcinoma, Non-Small-Cell Lung , Metabolism , Mortality , General Surgery , Cyclin-Dependent Kinase Inhibitor p21 , Metabolism , Immunohistochemistry , Ki-67 Antigen , Metabolism , Lung Neoplasms , Metabolism , Mortality , General Surgery , Prognosis , Survival Analysis , Survival Rate , Tumor Suppressor Protein p53 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical value of Physiologic Ability and Surgical Stress (E-PASS) and modified Estimation of Physiologic Ability and Surgical Stress (mE-PASS) scoring systems in predicting the mortality and surgical risk of gastric cancer patients, and to analyze the relationship between the parameters of E-PASS and early postoperative complications.</p><p><b>METHODS</b>Clinical data of 778 gastric cancer patients who underwent elective surgical resection in Tianjin Medical University General Hospital from Jan. 2010 to Jan. 2014 were analyzed retrospectively. E-PASS and mE-PASS scoring systems were used to predict the mortality of gastric cancer patients, respectively. Univariate and unconditioned logistic regression analyses were performed to assess the relationships between nine parameters of E-PASS system and early postoperative complications.</p><p><b>RESULTS</b>E-PASS and mE-PASS systems were used to predict the mortality in the death group and non-death group. The Z value was -5.067 and -4.492, respectively, showing a significant difference between the two groups (P<0.05). AUCs of mortality predicted by E-PASS and mE-PASS were 0.926 and 0.878 (P>0.05), and the prediction calibration of postoperative mortality showed statistically non-significant difference (P>0.05) between the E-PASS and mE-PASS prediction and actual mortality. Univariate analysis showed that age, operation time, severe heart disease, severe lung disease, diabetes mellitus, physical state index and ASA classification score are related to postoperative complications (P<0.05 for all). Unconditioned logistic regression analysis showed that severe lung disease, diabetes mellitus, ASA classification score and operation time are risk factors for early postoperative complications (P<0.05 for all).</p><p><b>CONCLUSIONS</b>Both mE-PASS and E-PASS scoring system have good consistency in the predicting postoperative mortality and actual mortality, and both are suitable for clinical application. Moreover, the mE-PASS scoring system is clinically more simple and convenient than E-PASS scoring system. Preoperative severe lung disease, diabetes mellitus, ASA classification score and operation time are independent factors affecting the early postoperative complications.</p>
Subject(s)
Humans , Age Factors , Area Under Curve , Diabetes Complications , Elective Surgical Procedures , Homeostasis , Lung Diseases , Operative Time , Postoperative Complications , Mortality , Postoperative Period , Predictive Value of Tests , Regression Analysis , Retrospective Studies , Risk Assessment , Methods , Risk Factors , Stomach Neoplasms , Mortality , General Surgery , Stress, PhysiologicalABSTRACT
Objective To investigate the clinicopathological characteristics and prognosis in patients with node-negative gastric cancer.Methods Between January 2004 and December 2013,clinicopathological characteristics of 300 patients with node-negative gastric cancer who underwent radical gastrectomy in Tianjin Medical University General Hospital were retrospectively analyzed.Results The 1-,3-,and 5-year overall survival rates for patients with node-negative gastric cancer was 80％,69％ and 63％ respectively.The univariate analysis showed that tumor size,histologic type and depth of invasion had significant effects on the survival (P ＜ 0.05).Multivariate analysis for these factors showed that tumor size (RR:1.800,95 ％ CI:1.120-2.891,P =0.015),histologic type (RR:1.982,95 ％ CI:1.291-3.042,P =0.002) and depth of invasion (RR:1.464,95％ CI:1.213-1.767,P =0.000) were independent prognostic survival factors.Conclusions Tumor size,histologic type and depth of invasion are important prognostic factors of patients with node-negative gastric cancer.
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Objective:To determine the relationship between the curative effect of chemo radiotherapy and brain metastasis in limited-disease small cell lung cancer (LD-SCLC). Methods:Data of 149 patients with LD-SCLC who had undergone chemoradiother-apy between April 2009 and April 2012 were analyzed. The curative effect of chemoradiotherapy was evaluated using RECIST version 1.1, which includes complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD). The objective relief includes CR and PR. Survival was analyzed using Kaplan-Meier method.χ2 text was used to analyze the correlation between the factors. Results:The median overall survival (OS) was 20.0 months, and the 3-year OS rate was 33.0%. Brain metastasis occurred in 43 (28.8%) out of the 149 patients. Among the 43 cases, 12 (29.3%), 9 (11.8%), and 22 (68.8%) had CR, PR, and SD/PD, respectively (P=0.007). The curative effect of chemoradiotherapy correlates with the rate of brain metastasis (17.8%vs. 68.8%, P=0.027). Signifi-cant differences were found between the curative effect and the brain metastasis-free survival (BMFS) (P=0.005). The 2-year BMSF for CR patients was 79.5%, and the corresponding 2-year BMSF for PR, SD, and PD patients was 71.9%, 45.8%, and 49.6%, respectively. Further analysis showed that the performance of prophylactic cranial irradiation (PCI) had an important effect on the OS (P=0.007) of patients who achieved objective relief. Conclusion:The BMFS of patients with LD-SCLC who achieved CR after chemoradiotherapy is favorable, with low rate of brain metastasis. Patients who received PCI had a better OS. Thus, we suggest that timely PCI should be considered for the patients who achieved CR.
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Objective:To investigate the inhibitory effects of halofuginone on radiation-induced pulmonary injury and to explore the therapeutic mechanism of this drug. Methods:A total of 72 healthy female C57BL/6 mice were randomized into 4 groups, namely, control, irradiation, halofuginone, and irradiation plus halofuginone groups, with 18 mice in each group. No treatment was performed in the control group. In the halofuginone group, the halofuginone lavage was conducted once a day, with a continuous course treatment for a month or until sacrifice of the mice. In the therapeutic alliance group, the treatment mode was the same as that in the halofuginone group. Then, a 6MV-X ray single fraction irradiation was performed after the completion of a 15-day intragastric administration. At 24 h, 1 week, 2 weeks, 4 weeks, 12 weeks, and 20 weeks after the irradiation, 3 mice from each group were randomly sacrificed, and total lung tissues were harvested. The lung was dissected to prepare pathological sections. The sections were stained with hematoxylin and eosin staining (H&E) to explore morphologic changes. The protein and mRNA expression levels of TGF-β1 were analyzed by a combi-nation of immunohistochemistry and polymerase chain reaction. The level of hydroxyproline was also measured. Results: The out-comes of H&E staining showed that halofuginone markedly ameliorated the acute pulmonary inflammation and fibrosis induced by irra-diation. The combination group had a lower level of hydroxyproline than the irradiation group, with statistically significant differences at 20 weeks after irradiation (P=0.037). The protein and mRNA expression levels of TGF-β1 were higher in the irradiation and combi-nation groups than in the control group and (or) halofuginone group at different time points (P<0.05). The combination group had lower TGF-β1 protein expression than the irradiation group at different time points, with statistically significant differences at 2, 4, 12, and 20 weeks after the irradiation (P<0.05). Meanwhile, TGF-β1 mRNA level was lower in the combination group than in the irradiation group only at 4 and 12 weeks after the irradiation (P<0.05). Conclusion:Halofuginone can ameliorate the irradiation-induced lung inflamma-tion and fibrosis probably by inhibiting the radiation-induced TGF-β1 expression. Therefore, halofugione is expected to be a therapeu-tic drug for preventing irradiation injury of the lung.
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Radiotherapy is important for cancer treatment. However, some patients still experience relapse and exhibit radiation resistance. Mammalian target of rapamycin (mTOR) is the main effector molecule in PI3K/AKT signaling. This molecule is found in two structurally and functionally distinct multi-protein complexes known as the mTOR complex 1 and mTOR complex 2. The mTOR signaling pathway controls the growth, proliferation, survival, and apoptosis of cancer cells. This pathway is closely related to tumori-genesis and treatment response, and is used in sensitizing radiotherapy. mTOR inhibitors regulate radio-sensitization through multiple mechanisms, including cell cycle alterations, DNA repair modulation, and tumor hypoxia reduction. Preclinical studies showed that mTOR inhibitors with tolerable toxicity may be used as an effective modality to overcome radio-resistant tumors. Responses to mTOR inhibitors vary depending on the cell lines. Molecular markers can be used to select suitable patients. Further studies are needed to com-pletely understand the use of mTOR inhibitors in radio-sensitization.