1.The effects of γ-ray radiation on hematopoiesis and T lymphocyte subset function
Wenxiu HAN ; Zhiyin ZHENG ; Liming YIN ; Ruilan GAO
Chinese Journal of Radiological Medicine and Protection 2014;34(3):172-175,187
Objective To observe the effects of whole body γ-ray radiation on hematopoiesis and cytokines related to T cell subsets in mouse,to detect the expression of transcription factors of splenic T cell subsets,and to investigate the correlation between hematopoiesis injury and abnormal immune function.Methods Totally 50 BALB/c mice were divided into radiation group and blank control group with the random number table method.The former group were given 5.5 Gy 60Co γ-ray radiation on whole body and another received sham radiation.The numbers of white blood cells and platelets of radiation group were counted at 4,8,12 and 20 d after radiation,and these numbers of blank control mice were counted only at 20 d.Hematopoietic tissue proliferation was evaluated by biopsy sections of mice femur.The contents of Th1,Th2,and Th17 in peripheral blood were detected with cytometric bead array (CBA).The expressions of T-bet/GATA-3 and RORγt/Foxp3 proteins related to the differentiation of T cell subsets in spleen tissue were measured by Western blot.Results The numbers of white blood cells and platelets of radiation group mice were reduced obviously (t WBC =18.48,15.72,9.79,3.30; t PLT =22.52,19.74,11.78,4.70,P < 0.05) compared with blank control group.Biopsy sections showed that bone marrow hematopoietic cells of the radiated mice were less than those of blank group,and adipocytes became more.At 8 d,the marrow suppressions were more obvious than those at 20 d.Serum contents of Th1 cytokines IFN-γ,TNF-α and Th2 cytokines IL-4,IL-6 in the radiation group were higher than those in the blank control group at 8 and 12 d(t IFN-γ =2.93,3.36,t TNF-α =6.09,8.11,6.43,4.49,tIL-4 =4.49,3.18,t IL-6=5.11,8.67,6.67,8.55,P<0.05).IL-17A secreted mainly by Th17 cells was also higher than the blank (t =3.68,6.24,5.32,4.06,P < 0.05).Compared with the blank control group,the expression of T-bet protein increased significantly (t =5.64,2.75,3.56,4.65,P < 0.05),and the expressions of GATA-3,RORγt,and Foxp3 proteins decreased at 4,8 and 12 d except the RORγt at 20 d (tRORγt =6.79,4.31,4.47,tGATA-3 =3.88,8.06,2.84,3.23,tFoxp3 =10.00,8.06,2.89,5.93,P< 0.05).Conclusions 5.5 Gy whole body γ-ray radiation inhibits bone marrow hematopoiesis of BALB/c mice and makes the differentiation and function of T cells to be abnormal,which may be associated with bone marrow hematopoiesis obstacle.
2.Correlation between residual level of DNA double-strand breaks and the radiosensitivity of cancer cells
Jianxiang SUN ; Weijian SUN ; Jianli SUI ; Pingkun ZHOU
Chinese Journal of Radiological Medicine and Protection 2008;28(5):495-498,529
Objective To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients,and to explore the predictor of radiotherapy responses of cancers. Methods DNA double-strand breaks (DSBs) were induced by 60Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results A wide variation of radiosensitivity, e.g. The survival parameter of D0 varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radioseusitivity (D0 or SF2). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy.
3.Roles of microRNAs and their target genes in predicting chemoradiotherapy efficacy of rectal cancer
Qiliang PENG ; Yuxin LIN ; Xuye YUAN ; Yaqun ZHU
Chinese Journal of Radiological Medicine and Protection 2016;36(10):743-748,752
Objective MicroRNAs (miRNAs) play important roles in the chemoradiotherapy efficacy of rectal cancer (RC).This study aimed to screen the chemoradiotherapy-associated microRNAs and their target genes of RC through bioinformatics approaches in order to promote the fundamental study of RC chemoradiotherapy.Methods The chemoradiotherapy-associated microRNAs were manually searched through the published papers via PubMed and its target genes were identified by comprehensively analyzing these public data of microRNA-mRNA and gene expression profiles.Both gene ontology (GO) and pathway analysis of the target genes were performed by DAVID and IPA programs,respectively.Results A total of 38 microRNAs were collected from PubMed,and 3 545 putative target genes were inferred from the integrated microRNA-mRNA associations,among them,131 were differentially expressed (DE) (P < 0.05) in the selected gene expression profile (GSE35452).The GO and pathway enrichment analyses indicated that the DE genes were closely involved in the responses of chemoradiotherapy of RC.Conclusions These microRNAs and their regulated DE genes may contribute to the molecular mechanism of the differential efficacy of RC chemoradiotherapy,which may provide a theoretical reference for predicting the response of RC to chemoradiotherapy.
4.Investigation of the frequency of medical radiation exposure in Ningxia region
Yanling SUN ; Guicai LU ; Hongcheng LI ; Qingyu KONG ; Xuli JI
Chinese Journal of Radiological Medicine and Protection 2016;36(10):757-760,779
Objective To understand the allocation of radiological diagnostic equipment and the frequency of medical radiation exposure in the medical institutions in Ningxia region,in order to provide the basis for the reasonable application of medical radiation technology.Methods The general survey in the form of the questionnaires was used to investigate and analyze the medical radiation usage of medical X-ray diagnostics,interventional radiology,nuclear medicine and radiotherapy in Ningxia region medical institutions.Results The frequency of X-ray diagnostic radiography in Ningxia region was 727.9 per 1 000 population in 2014.The frequency of X-ray photography examination was the highest,525.2 per 1 000 population,followed bv the frequency of CT scanning,147.9 per 1 000.For others,the frequency was radiotherapy 6.0 per 1 000 population,nuclear medicine 1.8 per 1 000 and interventional radiology 3.8 per 1 000,respectively.These differences were of statistical significance in frequency of X-ray diagnostic examination in five cities' medical institutions in Ningxia (X2 =162 280.7,P < 0.05),also in all medical institutions at different levels (x2 =902 485.2,P < 0.05) and for both frequency of X-ray photography examination and CT scanning in these institutions (x2 =471 574.9,181 887.1,P < 0.05).Conclusions Of the X-ray diagnostic radiography,the CT scanning has becoine a major means next only to the X-ray photography examination.There are differences in frequency of X-ray diagnostic examination in the medical institutions at different levels in different cities of the region.The related regulatory authorities should strengthen the supervision and management of radiation protection in mnedical institutions,to ensure the justification of diagnostic radiology and radiotherapy.
5.Randomized controlled trial of icotinib concurrent with thoracic radiotherapy for treating advanced non-small cell lung cancer (NSCLC)
Jianfang WANG ; Caiping SUN ; Jianjiang LIU ; Wanli YE ; Xialin CHEN
Chinese Journal of Radiological Medicine and Protection 2017;37(4):269-272,281
Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95% CI:12.2-17.4) in group A and 13.2 months (95% CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3% and 61.2%,respectively.The ORR were 78.0% vs.57.1% (x2 =5.16,P =0.028),and the DCR were 95.1% vs.92.9% (P>0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.
6.Role of replication protein A in the radioresistance of esophageal cancer cell line and its mechanism
Dahai YU ; Chong ZHOU ; Ye TIAN
Chinese Journal of Radiological Medicine and Protection 2012;32(4):347-349,368
Objective To evaluate the effect of replication protein A (RPA) gene suppression on the radiosensitivity of esophageal cancer cells (TE-1R ) and underlying mechanism. Methods A radioresistant human esophageal cancer cell line TE-1 R was screened out by fractionated irradiation to TE-1 cells,then siRPA1 or siRPa2 was transfected to TE-1R cells.The untransfected (Con) group and nonsense siRNA transfected (NC) group were set as control groups.The survival was measured with colony-forming assay and the cell cycle distribution was measured with flow eytometry.Results Compared with the Con and NC groups,the protein expression of RPA1 and RPA2 decreased significantly 48 h after siRPA1 and siRPA2 transfection.The D0,Dq,and SF2 values reduced from 2.09,1.70,0.85 in NC group to 1.67,0.71,0.44 and 1.82,0.89,0.51 in siRPAl and siRPA2 transfection groups,respectively.Accordingly,the sensitization enhancement ratios of Dq were 2.39 and 1.91,respectively.The G2/M arrest in siRPA1 and siRPA2 transfection groups increased from (18.701 3.14)% of NC group to (26.95 ± 3.96)% and (25.28 ± 2.74) % (t =2.827,2.853,P <0.05),respectively.Conclusions Knocking down of RPA1 or RPA2 genes can enhance the raidosensitivity of human esophageal cancer cells TE-1R,where the inhibition of radiation-induced sublethal damage repair may be involved.Accordingly,RPA may become a new target of radiosensitization in esophageal cancer.
7.Preparation and in vitro evaluation of chitosan nanoparticles containing 5-[125Ⅰ] Iodo-2'deoxyuridine
Chen YANG ; Fenju LIU ; Miaoli SONG ; Hanbin ZHONG ; Yan SHI
Chinese Journal of Radiological Medicine and Protection 2010;30(6):650-653,700
Objective To prepare the chitosan nanoparticles loading 5-[125Ⅰ] Iodo-2'-deoxyuridine (125Ⅰ-UdR-CS-DLN) at 100-200 nm in diameter, and analyze the characteristic of drug sustained-releasing and tumor targeting. Methods Orthogonal experimental design and One-way analysis were applied to optimize the preparation of 125Ⅰ-UdR-CS-DLN using tripolyphosphate cross-linking. Dynamic dialysis was utilized to investigate the in vitro releasing characteristics of the nanoparticles. The tumor targeting effect of the nanoparticles was observed with laser confocal microscopy. Results The optimal conditions for preparing the nanoparticles at particle diameters (70. 39 ± 5.12 ) nm (PDI 0. 16 ± 0. 012 ) were 1 g/L of CS, 2 g/L of TPP, stirring rate 600 r/min, relative molecular mass of CS 3 × 103. The TEM results showed that the exterior of the nanoparticles was spheroid, with a uniform and fine dispersivity. The optimized condition with the initial 125Ⅰ-UdR concentration of 2. 96 MBq/ml at pH5 provided the highest loading capacity (1253. 55 MBq/g) and the highest entrapment rate (42. 35% ). The in vitro releasing curves of 125Ⅰ-UdR-CS-DLN followed Higuchi equation, shown a characteristic of long-acting preparation.Laser confocal microscopy observations approved that the tumor cells uptake of FITC-CS-nanoparticles were significantly more than that of normal cells. Conclusions Chitosan nanoparticles loading 125Ⅰ-UdR at diameters range 127. 81 ± 15. 25 nm (PDI 0. 240 ± 0. 035 ) were successfully prepared with the optimized conditions, and showed a characteristic of sustained-releasing and tumor targeting. The chitosan-based nanotechnology provided a new and efficient approach for the application of 125Ⅰ-UdR in intracellular radiotherapy for tumor.
8.Evaluation of radiation dose in multislice spiral CT scan for children embedded teeth
Hongbo XIA ; Xiaohong WANG ; Lihai SONG ; Changying ZHENG ; Guangyu XU ; Kun XIANG
Chinese Journal of Radiological Medicine and Protection 2010;30(1):75-76,78
Objective To evaluate the radiation dose in both low radiation dose and to conventional radiation dose mode in multislice spiral CT scan for children with embedded teeth,and explore the lowest conditions of exposure in multislice spiral CT scan for children embedded teeth.Methods Eighty cases of children with embedded teeth examined by 16 slices spiral CT were divided into 5 ,25,125 and 250 mAs scanning groups.The scanned pictures of four groups were evaluated by two chief physicians and three associate chief physicians in the radiological department with double blind method.The CTDI_w and DLP in different radiation dose mode were recorded and analyzed with statistics.Results All the four groups scanned pictures in different radiation dose mode could accurately show the structure and the adjacency relation of embedded teeth.Even though the resolution of scanned pictures in S mAs group were inferior to the other three groups on bone trabecula,gingiva and their surrounding soft tissue,it still could meet the requirements of examination.The average DLP in 5 mAs group was only 2% of value in 250 mAs group.Conclusions MSCT in 5 mAs group can not only meet the requirements of examination,but also reduce the radiation dose to patients to the greatest extent.
9.An efficiency calibration method without a radioactive source using BOMAB phantom and Monte Carlo simulation for Inspector 2000 gamma spectroscopy system
Fuli ZHANG ; Decheng QU ; Guoshan YANG ; Mingmin ZHENG
Chinese Journal of Radiological Medicine and Protection 2009;29(4):432-434,448
Objective To establish an efficiency calibration method without a radioactive source for Inspector 2000 gamma spectroscopy system.Methods At the fwst step,geometry parameters of the detector were properly specified by comparisons of FEPE(Full Energy Peak Efficiency)between Monte Carlo(MC)calculations and the average measured values of HPGe and NaI detectors using point sources(137 Cs).The differences between calculations and measurements were generally within ±10% for gamma rays.Then,Monte Carlo simulation was used to evaluate the counting efficiency of Nal(TI)and HPGe detectors for BOMAB phantoms.Corresponding efficiency curves and functions were fitted.Results The counting efficiency received from the fitted efficiency functions had a good agreement with those from MC simulation.The bias for Nal detector ranged from-19% to 18%,while the bias for HPGe detector ranged from-11% to 17%.The above errors were totally acceptable in the on-site deployment during nuclear and radiological emergency events.Conclusions Monte Carlo method is simple,time and laborsaving in determing the counting efficiency of gamma spectroscopy system.
10.Preliminary detection of expression changes of human mitochondrial COXI,ND1 and ND6 gene induced by 60Co γ-rays
Yuwen LI ; Jiangbin FENG ; Xue LU ; Deqing CHEN ; Qingjie LIU
Chinese Journal of Radiological Medicine and Protection 2009;29(2):125-128,142
Objective To explore the changes of human mitochondrial COXI,ND1 and ND6 genes expression induced by ionizing irradiation.Methods Changes of human COXI,ND1 and ND6 gene expression were detected by RT-PCR and Real-time PCR 8 h after the irradiation in human lymphoblastoid cell lines,which were exposed to 1-10 Gy 60Co γ-rays.And the dose-effect relationships between expression changes of the genes and the doses were analyzed.The changes of these three genes expression were also analyzed at different post-radiation time-points between 0.5 h and 72 h after irradiation of 5 Gy in order to explore the time-effect.Results The expression of three genes COXI,ND1 and ND6,showed either the dose-effect or the time-effect after irradiation.The gene expression levels of three genes up-regulated generally and the peak change time-point was 4 h after irradiation.Conclusion Ionizing radiation,msht induce the changes of mitochondrial gene expression,and the gene expression level is up-regulated.