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Objective:To explore the effect of metastatic lymph node ratio (MLR) on the prognosis of adjuvant radiotherapy for stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection.Methods:According to the inclusion and exclusion criteria, a total of 590 patients diagnosed with stage-Ⅲ gastric cancer (excluding adenocarcinoma of esophagogastric junction) were included in this study from the SEER database between 2010 and 2016. No more than 15 lymph nodes were examined in all patients. Among them, 291 patients received surgery combined with adjuvant chemotherapy (surgery + chemotherapy group), and 299 patients received surgery combined with adjuvant radiochemotherapy (surgery + radiochemotherapy group). These two groups were treated with 1∶1 propensity score matching (PSM). We retrospectively analyzed the effect of MLR on prognosis of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection, and evaluated the significance of postoperative adjuvant radiotherapy among patients with different MLR.Results:According to the analysis result of area under curve (ROC), 0.5 was defined as the best cut-off point of MLR. In the two groups of patients with stage-Ⅲ gastric cancer included in the study, the median survival time was 23 months in the surgery + radiochemotherapy group, and the 1 -, 3 -, and 5-year overall survival (OS) ratio were 77.1%, 33.2% and 22.8%, respectively. The median survival time was 21 months in the surgery + chemotherapy group, and the 1 -, 3 -, and 5-year OS ratio were 72.2%, 33.6% and 23.1%, respectively. There was no statistically significant difference between the two groups in OS. The result of subgroup analysis showed that there was no statistically significant difference in OS between the surgery + radiochemotherapy group and the surgery + chemotherapy group among patients with MLR≤0.5, while OS of the surgery + radiochemotherapy group was significantly better than the surgery + chemotherapy group among patients with MLR>0.5( χ2=8.542, P < 0.05). Multivariate Cox regression analysis showed that race, T stage, N stage, MLR and adjuvant radiotherapy were the important factors affecting OS of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection( Wald=8.544, 7.547, 10.925, 18.047, 10.715, P < 0.05). After PSM, there was no statistically significant difference in OS between the two groups. The result of subgroup analysis showed that there was no statistically significant difference in OS between the surgery + radiochemotherapy group and the surgery + chemotherapy group among patients with MLR≤0.5, while OS of the surgery + radiochemotherapy group was significantly better than the surgery + chemotherapy group among patients with MLR>0.5( χ2=6.944, P < 0.05). Multivariate Cox regression analysis showed that race, T stage, N stage, MLR and adjuvant radiotherapy were the important factors affecting OS of stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection ( Wald=7.154, 8.023, 7.744, 17.016, 4.149, P < 0.05). The result of prognosis analysis of two groups before and after PSM were consistent. Conclusions:MLR is an important prognostic factor for stage-Ⅲ gastric cancer patients with no more than 15 lymph nodes dissection. The OS of patients with MLR ≤ 0.5 can′t benefit from postoperative adjuvant radiotherapy, while patients with MLR > 0.5 should be advised to receive postoperative adjuvant radiotherapy to improve the prognosis.
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Objective:To investigate the effect of chemotherapy combined with postoperative adjuvant radiotherapy on the overall survival (OS) of early and advanced (Ⅰ-Ⅱ A and Ⅱ B-Ⅳ) small cell neuroendocrine carcinoma of the cervix (SCNEC)patients and analyze the prognostic factors. Methods:The Surveillance, Epidemiology and End Result (SEER) database was used to search and screen out 269 SCNEC patients who received chemotherapy from 2004 to 2016. These patients were divided into four groups according to different treatment regimens: chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group. Kaplan-Meier curve was utilized to compare the OS of SCNEC patients with stage Ⅰ-Ⅱ A and Ⅱ B-Ⅳ with different treatment regimens. Log-rank test and Cox regression analysis were used to evaluate significant clinicopathological factors on prognosis. Results:For patients with stage Ⅰ-Ⅱ A, the 5-year OS rate of chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group were 39.9%, 71.7%, 24.5% and 0, respectively. Among patients with stage Ⅰ-Ⅱ A, chemotherapy + surgery group had a better prognosis ( HR 0.403, 95% CI: 0.112-1.112, P=0.047) than chemotherapy + postoperative radiotherapy group. For stage Ⅱ B-Ⅳ patients, the 5-year OS rate of the chemotherapy + postoperative radiotherapy group, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group were 35.2%, 24.3%, 17.7% and 0, respectively. Among patients with stage Ⅱ B-Ⅳ, chemotherapy + surgery group, chemotherapy + radiotherapy group and chemotherapy-alone group all had worse prognosis ( HR 1.726, 95% CI: 0.944-3.157; HR 1.605, 95% CI: 0.968-2.661; HR 5.632, 95% CI: 3.143-10.093, P<0.05) than chemotherapy + postoperative radiotherapy group, respectively. In addition, the patients whose age ≤60 years old and tumor diameter<4 cm had a worse prognosis compared to those older than 60 years old ( HR 7.868, 95% CI: 3.032-20.415; HR 1.465, 95% CI: 1.006-2.435, P<0.05)and tumor diameter≥4 cm ( HR 2.576, 95% CI: 1.056-6.287; HR 1.965, 95% CI: 1.026-3.766, P<0.05). Conclusions:Chemotherapy combined with postoperative adjuvant radiotherapy can′t improve the OS of patients with early (Ⅰ-Ⅱ A) SCNEC, but can significantly improve the OS of advanced (Ⅱ B-Ⅳ) patients. Age, tumor size and treatment regimens are independent risk factors.
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Objective@#To evaluate the effect of down-regulating SALL4 on the radiosensitivity of leukemia cells, aiming to provide new ideas for improving radiosensitivity of leukemia patients.@*Methods@#Human acute myeloid leukemia cell line HL-60 infected with shRNA SALL4 and shRNA control lentivirus was classified into the Lv-shSALL4 group and Lv-shNC group. The levels of SALL4 mRNA and protein in cells were detected by RT-PCR and Western blot. The infected cells treated with 8 Gy dose irradiation were assigned into the Lv-shSALL4+ radiation and Lv-shNC+ radiation groups. The cell apoptosis was detected by flow cytometry. The levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins in cells were determined by Western blot. The cells in the Lv-shSALL4 and Lv-shNC groups were exposed to 0, 2, 4, 6 and 8 Gy irradiation. The radiosensitivity ratio was determined by cell clone test.@*Results@#The level of SALL4 in the Lv-shSALL4 group was significantly lower than that in the Lv-shNC group (P<0.05). The cell apoptosis rate was significantly increased, the levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins were remarkably up-regulated in cells compared with those in the Lv-shNC group (all P<0.05). The cell proliferation ability in the Lv-shSALL4+ radiation was significantly reduced, the cell apoptosis rate was considerably increased, the levels of cleaved Caspase-3, cleaved Caspase-9 and Bax proteins were significantly up-regulated compared with those in the Lv-shSALL4 and Lv-shNC+ radiation groups (all P<0.05). The cell radiosensitization ratio in the Lv-shSALL4 group was 1.323.@*Conclusion@#Down-regulating SALL4 can increase the radiosensitivity of leukemic cells, inhibit the cell proliferation and induce the apoptosis of leukemic cells.
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Objective To investigate the application of CT image and cone beam computed tomography (CBCT) image registration based on 3D Slicer software in image-guided radiotherapy for uterine cervical neoplasms. Methods Based on 3D Slicer software and Slicer RT toolkit, 10 positioning CT images and 50 CBCT images of 10 patients with uterine cervical neoplasms in Henan Provincial People's Hospital between January 2018 and October 2018 had rigid registration and b-spline deformation registration respectively. The dice similarity coefficient (DSC) and Hausdorff distance (HD) of the bladder, rectum, femoral head, spinal cord, and body of CT-CBCT images were compared by using paired t-test before and after the registration. Results Pre-registration, rigid registration and after b-spline deformation registration of CT images and CBCT images, the DSC in the bladder (0.459±0.177, 0.528±0.184, 0.542±0.187, respectively), the rectum (0.564±0.141, 0.632±0.091, 0.684±0.097, respectively), the femoral head (0.695±0.088, 0.833± 0.030, 0.865±0.027, respectively), the spinal cord (0.587±0.119, 0.746±0.085, 0.834±0.032, respectively) and the body surface (0.922±0.013, 0.948±0.011, 0.959±0.009, respectively) showed an increased trend; HD in the bladder (12.8±7.2, 12.2±7.1, 11.7±7.3, respectively), the rectum (5.0±1.8, 4.4±1.2, 3.4±1.2, respectively), the femoral head (3.6±1.2, 1.8±0.5, 1.5 ±0.5, respectively), the spinal cord (4.0 ±1.0, 2.7 ±1.3, 1.8 ±0.5, respectively) and the body surface (6.3±2.1, 5.2±2.0, 4.3±2.0, respectively) showed a decreased trend. The differences of pairwise comparison in the same parts were statistically significant (all P < 0.05). Conclusions Both rigid registration and b-spline deformation registration of CT-CBCT images based on 3D Slicer softwarecan improve the radiotherapy accuracy of uterine cervical neoplasms, and b-spline deformation registration has more significant advantages.
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Objective To evaluate the effect of down-regulating SALL4 on the radiosensitivity of leukemia cells,aiming to provide new ideas for improving radiosensitivity of leukemia patients.Methods Human acute myeloid leukemia cell line HL-60 infected with shRNA SALL4 and shRNA control lentivirus was classified into the Lv-shSALL4 group and Lv-shNC group.The levels of SALL4 mRNA and protein in cells were detected by RT-PCR and Western blot.The infected cells treated with 8 Gy dose irradiation were assigned into the Lv-shSALL4 + radiation and Lv-shNC+radiation groups.The cell apoptosis was detected by flow cytometry.The levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins in cells were determined by Western blot.The cells in the Lv-shSALL4 and Lv-shNC groups were exposed to 0,2,4,6 and 8 Gy irradiation.The radiosensitivity ratio was determined by cell clone test.Results The level of SALL4 in the Lv-shSALL4 group was significantly lower than that in the Lv-shNC group (P＜0.05).The cell apoptosis rate was significantly increased,the levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins were remarkably up-regulated in cells compared with those in the Lv-shNC group (all P＜ 0.05).The cell proliferation ability in the Lv-shSALL4 + radiation was significantly reduced,the cell apoptosis rate was considerably increased,the levels of cleaved Caspase-3,cleaved Caspase-9 and Bax proteins were significantly up-regulated compared with those in the Lv-shSALL4 and Lv-shNC+ radiation groups (all P＜0.05).The cell radiosensitization ratio in the Lv-shSALL4 group was 1.323.Conclusion Down-regulating SALL4 can increase the radiosensitivity of leukemic cells,inhibit the cell proliferation and induce the apoptosis of leukemic cells.
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Objective To investigate the effect of Zinc finger E-box binding homeobox protein 1 (ZEB1) on the radiosensitivity of gastric cancer cells AGS and its possible mechanism. Methods AGS cells were irradiated by X-rays at different doses (0, 2, 4, 6, and 8 Gy). Western blot was used to observe the expression of ZEB1 in cells. AGS cells, in logarithmic growth phase, were transfected with of ZEB1 gene or its interference plasmids, the corresponding control plasmids ( pcDNA3. 1 ) and negative control interference plasmids. They were classified as overexpression ZEB1 group, silencing ZEB1 group, control group and negative control group, respectively. The effect of overexpression and silencing ZEB1 on the survival of AGS cells after irradiation were analyzed by colony formation assay. The cell apoptosis rate was analyzed by flow cytometry. The expressions of histone H2A (H2AX), phosphorylated H2AX (γ-H2AX) and telangiectasia mutated gene (ATM) were detected by Western blot. Results The expression of ZEB1 in AGS cells was dependent on radiation dose (F=58. 57, P<0. 05). Overexpression of ZEB1 increased AGS cells viability, inhibitedγ-H2AX expression (t=12. 18, P<0. 05), blocked cell apoptosis (t=7. 27, P<0. 05) and up-regulated ATM expression in time-dependent manner after irradaition (F=165. 70, P <0. 05). Silencing ZEB1 reduced AGS cells viability, increased γ-H2AX expression ( t =12. 88, P<0. 05) and cell apoptosis (t =8. 36, P <0. 05), and down-regulated of ATM expression (F=44. 80, P<0. 05). Conclusions ZEB1 regulates the radiosensitivity of gastric cancer AGS cells by up-regulating ATM expression.
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Objective To evaluate the clinical efficacy of compound matrine injection combined with fentanyl transdermal patch in the treatment of elderly patients with advanced gastric cancer.Methods A total of 100 elderly patients with advanced gastric cancer were enrolled in this study.All patients were randomly divided into the observation group (n =50) given compound matrine injection plus Fentanyl transdermal patch and the control group given fentanyl transdermal patch alone(n=50).The analgesic efficacy,quality of life and adverse reaction were evaluated and compared between the two groups.Results The analgesic efficacy was significantly higher in the observation group[76％(38/50)]than in the control group[(44％),(x2=4.46,P＜0.05)].Before treatment,the life quality scores were similar between two groups.After treatment,the life quality score of the two groups was significantly improved as compared with pre-treatment.In addition,life quality score was significantly higher in the observation group than in control group(t=8.61,P＜0.05).After treatment,only mild adverse events were observed in two groups,with no significant difference in adverse events between the two groups(x2 =0.00,P＞0.05).Conclusions Compound matrine injection plus Fentanyl transdermal patch are safe and effective in the treatment of carcinoma pain in elderly patients with advanced gastric cancer.
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Objective To investigate whether miR?485?3p plays a role in regulation of radiosensitivity of gastric cancer cells by targeting TLR1. Methods Quantitative real?time PCR and Western blot were used to determine the expression of miR?485?3p and TLR1, respectively. The interaction between miR?485?3p and TLR1 was verified by target prediction software ( DIANA, TargetScan, and miRanda) and dual luciferase reporter assay. Gastric cancer MGC803 cells transfected with miR?485?3p mimic or TLR1 siRNA were exposed to irradiation. Apoptosis assay, colony formation assay, and MTT assay were used to evaluate the changes in radiosensitivity of gastric cancer cells. Dual luciferase reporter assay was used to determine the effects of miR?485?3p overexpression and TLR1 silencing on the activity of NF?κB. Western blot was used to study the effects of miR?485?3p overexpression and TLR1 silencing on NF?κB target genes. Results In gastric cancer cells exposed to radiation, the expression of miR?485?3p was downregulated and the expression of TLR1 was upregulated. TLR1 was predicted to be the target of miR?485?3p by target prediction software. Dual luciferase reporter assay further confirmed TLR1 as the direct target of miR?485?3p. miR?485?3p negatively regulated the expression of TLR1. The overexpression of miR?485?3p, as well as TLR1 silencing, increased the apoptosis rate of cells, reduced colony formation and cell proliferation, and enhanced the radiosensitivity of the cells. Both miR?485?3p overexpression and TLR1 silencing reduced the activity of NF?κB and downregulated the expression of multiple NF?κB target genes. Conclusions miR?485?3p enhances the radiosensitivity of gastric cancer cells probably by targeting TLR1 and regulating the NF?κB signaling pathway.
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Objective To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1 α),vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor-D (VEGF-D)in hypoxic environment as well as the relationship between HIF-lα and VEGF-D.Methods Human esophageal cancer cell line EC9706 was cultured under hypoxia environment for 6,12 and 24 h,the cell radiosensitivity was evaluated by survival curve.HIF-1 α siRNA was constructed and transfected into human EC9706 cells.Protein expressions of HIF-1 α,VEGF-A and VEGF-D were analyzed by Western blot before and after RNA interference.Results EC9706 cells under hypoxia showed radioresistance with a SF2 of 0.62 higher than that of normoxic cells of 0.43.Moreover,the protein expressions of HIF-1α,VEGF-A and VEGF-D were all increased (F =205.24,227.88,130.55,P ＜0.05) due to hypoxia treatment.On the contrary,after HIF-1α siRNA transfer,the protein expressions of HIF-1α,VEGF-A and VEGF-D in EC9706 cells were not influenced by hypoxia treatment.Conclusions EC9706 cells in hypoxic environment was radioresistance,and the upexpressions of HIF1α,VEGF-A and VEGF-D may be involved.
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Objective To investigate the effect of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts and the underlying mechanisms.Methods The mouse model was established by injecting EC9706 cells subcutaneous in nude mice.When the tumors were 100 mm3 in size,the mice were divided into 4 groups randomly withcontrol group with no treatment; irradiation group with 8 Gy 6 MV Xrays at 1 and 8 d each time; AG1024-treatment group with 30 μg/(kg-d) AG1024 injected intraperitoneally (ip) 5 times a week for two weeks ; combination group:receiving both 30 μg/(kg· d)-1 AG1024 ip and irradiation of 8 Gy X-rays.The diameters of the tumors were measured every 3 days.The mice were sacrificed and the weights of tumors were measured at 15 d after treatment.Tumor inhibition rate was calculated.The cell cycle was examined by flow cytometry.The expression of cell cycle protein D1 (CyclinDl) of the tumors were detected by immunohistochemical staining.Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used to detect the cell apoptosis in the tumor tissue.Results The tumor weight in the irradiation group,AG1024-treatment group and combination group were significantly decreased compared with the control group,and the inhibition rate were 39.16％,18.73％,57.04％,respectively (F =13.566,P ＜ 0.05).After treatment with AG1024 and irradiation,tumor tissue cells were significantly accumulatedin the G0/G1 and G2/M phases and decreased in S phase compared to the irradiation group (t =-6.654,-16.738,12.871,P ＜ 0.05).The CyclinD1 expression of the combination group was significantly decreased compared with the control group.In the combination group,the apoptotic cells were detected by TUNEL assay.Conclusions IGF-1R inhibitor AG1024 could change the cell cycle and induce cell apoptosis,which might result in the enhancement of radiosensitivity on the esophageal cancer xenografts.
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0.05),the survival time was prolonged(P