If loosely defined,an abscopal effect occurs when localized irradiation affects the whole organism.In recent years,distant tumor regression and normal tissue damage after localized irradiation have been concerned by immuno-oncologists.However,the mechanisms of this effect are still far from clear.Mounting evidences suggest that the generation of abscopal effects is closely related to immune regulation.Radiotherapy might become a systemic tumor-treatment modality by enhancing immune function and played an important role in every stage of tumor development and prognosis.For the moment,targeting the immune checkpoint has become an attractive approach for malignant tumor therapy.Preclinical data have revealed that a strong abscopal effect could be effectively induced by the co-treatement of immune checkpoint inhibitors and irradiation,which could recruit antitumor T cells and achieve a powerful antitumor effect.This review discusses current progress and perspectives of abscopal effects in the combination of radiotherapy and immunotherapy.

Objective To measure the difference of radiosensitivity between small and large intestines toward high dose of radiation and investigate the role of stem cells in this difference.Methods C57BL/6 male mice,6-8 weeks old,were randomly divided as control group and radiation group received 19 Gy whole body γ-ray irridiation.Large and small intestines of the mice were collected 6,12,24,48,72 and 96 h after radiation.The proliferation and apoptosis of the large and small intestines and their stem cells were then detected by immunochemistry,and the change of stem cell number in the large and small intestines were detected by in-situ hybridization.Results HE staining showed that 19 Gy γ-ray irradiation caused more severe injury in the small intestine,and all the crypt in the small intestine were extinct at 48 h post-radiation.However,the proliferation index of crypt in the large intestine was as high as 0.23 (t =4.67,P ＜0.05).Compared with the small intestine,the apoptotic index of epithelial cells in the crypt of large intestine was much lower at 12 and 24 h after irradiation (t =-1.92,-2.42,P＜0.05).The apoptotic population of stem cells in the small intestine at 12 and 24 h post irradiation were significantly lower than that in the large intestine (t =-1.98,-2.33,P ＜ 0.05),and the number of stem cell in the large intestine was significantly higher than that in the small intestine 24,48 h after radiation (t =1.98,3.31,P ＜0.05).Conclusions The radiosensitivity of small intestine toward high dose of irradiation is significantly higher than that of the large intestine,where the difference in radiosensitivity of stem cells between large intestine and small intestine may be involved.

Cumulative evidence demonstrated that the chromatin modification plays important roles in the processes of DNA replication,transcription,repair and recombination.Both of the generation of DNA lesions and the activation of DNA damage response (DDR) to ionizing radiation could be affected by the chromatin modifications.This paper reviewed the recent research progresses in the chromatin structure modifications and its role in DDR,especially the influence of characteristic chromatin structure and histone modification on the radiation sensitivity of tumor cells.

Objective To study the role of caspase 3 in ischemic brain damage of rats, and further understand the molecular mechanisms of ischemic cerebral vascular disease.Methods Rat models of the left middle cerebral artery (MCA) occlusion/reperfusion were made using a modification of the intraluminal sature method of Longa established by Belayev, infarct zones were confirmed by 2,3,5 triphenyltetrazolium chloride (TTC) staining, and caspase 3 expression on brain sections at the mRNA and active protein level was detected with in situ hybridization and immunohistochemistry technique, respectively.Results After 2 hours of left MCA ischemia followed by 24 hours of reperfusion, obvious infarct in the MCA dominate regions was confirmed by TTC staining; low levels of caspase 3 mRNA, and fewer of its active protein expression was found in normal brains, sham brains and contralateral brains of MCAO rats; both caspase 3 mRNA and activated protein expression in ipsilateral region were increased after 24 hours of recirculation, and even higher levels were detected at 48 hours of reperfusion.Conclusion Apoptotic mechanism might involve in delayed neuronal death after cerebral ischemia, and caspase 3 might play an important role in ischemic neuronal injury.

Objective To investigate cadmium induced adaptive responses (AR) to either toxicant challenge or irradiation and also the role of PI3K family in the AR. Methods Cells were pre-treated with 0.1 or 1 μmol/L cadmium and then challenged by 50, 100 μmol/L cadmium or 1, 2 Gy γ-rays irradiation. Micronucleus induction was measured to evaluate the magnitude of AR. In some experiments, cells were treated with wortmannin during and after pretreatment. Results Cadmium of sub-lethal concentration could induce AR in all the cells toward 50 μmol/L cadmium or 1 Gy irradiation. When challenged by 50 μmol/L CdCl1, EM-C11 cells had an AR less apparent than the other two cell lines. Moreover, treatment of cells with wortmannin eliminated the AR in all three cell lines. Conclusions The magnitudes of AR in adapted cells may be related to multiple factors, such as DNA repair capacity, the priming and challenging dose of cadmium or irradiation. SSB rather than DSB repair is mainly involved in the cadmium induced AR and this cellular response may be mediated through ATM pathway.

Objective To study the relationships between serum uric acid levels in adult male patients with the risk factors of metabolic syndrome and insulin resistance.Methods In the persons undergone health check up in General Hospital of PLA in 2006,blood pressure(BP),body mass index(BMI),waistline,total and HDL cholesterol,serum triglycerides,fasting blood glucose(FBG),serum creatine(Cr)and uric acid(SUA)concentrations were measured.To the subjects without diabetes mellitus,75g oral glucose tolerance test(75g-OGTT)was given.Comparison was made on the components of MS between high SUA group(HUA)and normal SUA group(NUA).Logistic regression analysis was made to examine the relationship between UA and the symptom components of MS.The subjects without diabetes mellitus were then divided into 4 groups according to SUA levels,and then the relationships were analyzed between the levels of symptom components and the prevalence of MS among the different SUA groups.Results The mean age of the 1399 adult males was 56.3 ? 21.0 years.Among them the patients with hyperuricemia accounted for 14.37%.The levels of BMI,waistline,triglyceride,low density lipoprotein cholesterol,FBG,post prandial blood glucose(PBG),SBP and DBP were higher in HUA than that in NUA,while the HDL-C was lower.The incidence of MS in HUA group was higher with an increased SUA level compared with that in NUA group(P

Objective To investigate the effects of long-term low-dose radiation (LDR) of γ-rays on the proliferation and radiosensitivity of human lymphoblast cells HMy2.CIR (HMy) and to elucidate the underlying mechanism.Methods HMy cells were divided into control group and long-term LDR group.For the long-term LDR treatment,HMy cells were fractionally exposed to a low dose of γ-rays,which could enhance cell proliferation,3 times per week for 4 weeks.After the long-term LDR exposure,part of the control and long-term LDR exposed cells were further irradiated with a challenging dose (2 Gy) of γ-rays.Then cell proliferation and radiosensitivity were assayed by CCK-8 kit,cell apoptosis,and γ-H2AX formation was measured by flow cytometry.Gene expressions of cyclinD1,PCNA,bcl-2 and bax were detected by RT-PCR.Results The long-term LDR significantly increased cell proliferation (t =9.607,P ＜ 0.01) accompanied with up-regulation of cell cycle regulation gene cyclinD1 (t =6.869,P ＜ 0.01),proliferation regulation gene PCNA (proliferating cell nuclear antigen) (t =9.229,P ＜ 0.01) and bcl-2 gene (t =2.662,P ＜ 0.05),but decreased the expression of pro-apoptotic gene bax (t =19.908,P ＜0.01) in HMy cells.Compared to untreated cells,the long-term LDR decreased cell radiosensitivity (t =8.896,P ＜ 0.01),including apoptosis induction (t =4.762,P ＜ 0.01) and γ-H2AX formation (t =10.264,P＜0.01).Conclusions The long-term LDR promoted cell proliferation by up-regulating cell cycle related genes,while it reduced the radiosensitivity of HMy cells with acquisition of apoptotic resistance.

Objective To investigate the dose-response of micronuclei (MN) frequency in the lymphocytes irradiated with or without combination of α-particles and γ-rays. Methods Human lymphoblast cells HMy2.CIR were irradiated with 0 - 1 Gy of α-particles,0 - 5 Gy of γ-rays,and 0.025 -0.5 Gy of α-particles followed by different doses of γ-rays,respectively.The micronuclei (MN) in the irradiated cells were measured with the cytokinesis block technique,and the dose-responses of MN were established under different irradiation conditions.Results For γ-ray irradiation,the dose-response of MN was well-fit by the linear-quadratic model with an equation Y =c + αD + βD2.For α-particle irradiation,the MN induction increased linearly with the dose less than 0.250 Gy. But when the dose of α-particles increased continually,the dose-response curve bended and could be well fit with the BaD model Y =c + αD + σ[ 1 - exp( - δD) ] exp( - βD) where radiation-induced bystander effect (RIBE) was indicated.For the combined exposure,the dose-response of MN was similar to that of γ-irradiation when the dose of α-particles was lower than 0.1 Gy,but it was similar to that of α-irradiation when the dose of α-particles was higher.When the dose of α-particles was 0.2 and 0.5 Gy,MN induced by the mixed radiation were significantly higher than the sum of corresponding irradiation alone ( t =5.22 - 11.86,P ＜ 0.05 ).Conclusions The radiation damage of α-particles differs from that of γ-rays,where RIBE may be involved.The combination irradiation of α-particles and γ-rays has a synergistic effect on radiation damage of lymphoblast cells.

Objective: To study caspase-3 activities and the neuroprotective effect of caspase-3 inhibitor Ac-DEVD-CMK in primary cultures of rat hippocampal neurons during hypoxia/reoxygenation (H/R). Methods: After pretreated with Ac-DEVD-CMK or the vector DMSO fo 1 h, primary cultures of rat hippocampal neurons were induced to hypoxia for 3 h, followed by 12 to 48 h of reoxygenation. The neuronal viability was estimated by MTT assay, and caspase-3 cellular activities were measured by a colorimetric method using Ac-DEVD-pNA as a substrate. Results: During H/R, the cultured rat hippocampal neuronal viability gradually decreased, and caspase-3 activities in the primary cultures of rat hippocampal neurons were significantly increased, and peaked at 24 h of reoxygenation. Caspase-3 activities were decreased in the neurons pretreated with Ac-DEVD-CMK in a dose dependent manner. Conclusion: Delayed neuronal death is detected in cultured hippocampal neurons during H/R, and apoptosis mediated by caspase-3 may play an important role in it, and caspase-3 inhibitor has a neuroprotective effect on them.

Objective To evaluate the effect of gamma irradiation on the proliferation,differentiation,and mineralization of murine osteoblastic cells,and to investigate the related molecular mechanism.Methods Osteoblastic cells were irradiated by different doses (0,0.5,1.0,2.0,5.0 Gy)of 137Cs γ-rays.Cell morphology was observed with a microscopy,cell viability was analyzed by MTT assay,and ALP activity was analyzed by the methods of enzyme histochemistry and PNPP.Meanwhile,gene expressions of ALP,osteocalcin (OC),collagen Ⅰ,osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) were measured by semi-quantified RT-PCR.Results Cell viability decreased with the radiation doses over 1.0 Gy ( t =6.197 - 18.677,P ＜ 0.05 ).After radiation with a dose over 2.0 Gy,the cell number and the junctions of cell protrusions decreased,the cells had low refractivity and the activity and mineralization ability of ALP were also inhibited ( t =2.790 -2l.374,P ＜0.05).In addition,the expressions of ALP and OC mRNA were down-regulated significantly (t =3.563 -16.508,P ＜ 0.05) when the radiation dose was higher than 0.5 Gy,and the expressions of OPG,OPG/RANKL mRNA were down-regulated ( t =12.942,4.954,P ＜ 0.05 ) at 5 Gy.But the expressions of collagen Ⅰ and RANKL mRNA were not affected by irradiation.Conclusions The osteoblastic cells were significantly influenced by γ-irradiation,including morphological changes,inhibition of cell proliferation,differentiation and mineralization ability. Meanwhile,mRNA expressions of ALP and OC were downregulated.OPG/RANKL may be a main pathway of osteoblastic cell damage under high dose radiation.