With the hereotopic heart transplantation, immune tolerance induced by portal venous inoculation of donor spleen cells was studied.Methods:The recipient rats received donor spleen cells through portal vein combined with of cyclosporine A(CsA).The NK cell activity and IL-2, IFN-y expression of recipient spleen cells were detected. Results: Hie inoculation of donor spleen cells through the portal vein could significandy prolong survival time of heart allografts.IL- 2, IFN-y expression of recipient spleen lymphocytes and the recipient NK cell activity was also inhibitied.Conclusion:The inoculation of donor spleen cells through the portal vein could induce immune tolerance.The suppression of IL-2-NK-IFN-y immunologic net may be an important mechanism of portal vein tolerance.

OBJECTIVETo investigate the mechanism of immune escape in renal cell carcinoma(RCC).

METHODSFas and FasL expressions were examined by immunohistochemical technique in 44 RCC patients, with the Ki67 expression and apoptosis of tumor infiltrating lymphocytes(TIL) monitored simultaneously. Cytokines including IL2 and IFN alpha were used to induce the expression of the renal carcinoma cell lines 786-0 cells. Combination treatment of 786-0 with cytokines and Anti-Fas monoclonal antibody (FasAb) was used to induce apoptosis. FasL function was assessed by in vitro co-culture assays using renal cancer cells 786-0 and Fas-sensitive Jurkat T-cells.

RESULTS(1) Fas expression rate in RCC(22.8%) was lower than that in the controlled normal kidney tissues(53.8%, P < 0.01). FasL expression rate in RCC (46.5%) was higher than that in the controlled normal kidney tissues (23.2%, P < 0.01). That of Ki67 was 32.8%, with the expressions of Fas and Ki67 showing a negative correlation (r = -0.62, P < 0.05). In contrast, the expressions of FasL and Ki67 showed a positive correlation. (r = 0.93, P < 0.01). The Fas expression of stage I was significantly higher than that of stages III and IV. The expression rate of FasL in RCC was significantly increased with RCC stage (P < 0.01). (2) The apoptotic rate of TIL in RCC (33.9%) was significantly higher than that of the normal kidney tissues (3.5%, P < 0.01). The expression of FasL and the apoptotic rate of TIL in RCC gave a positive correlation (r = 0.96, P < 0.01). (3) Fas expression rate in 786-0 cells was 13.7%. The apoptotic rate mediated by FAsAb was 9.6%. IFN alpha was able to up-regulate the Fas expression and subsequently augment the FasAb-mediated apoptosis in 786-0 cells. But IL2 did not show similar effects. (4) The FasL expression rate of 786-0 was 18.6%. FasL expressed by 786-0 cells was able to induce apoptosis of Jurkat T-cells in co-culture assays and the apoptosis of Jurkat T-cells was significantly lowered after blocking the effect of FasL with Fas-neutralizing antibody NOK-2, giving the apoptotic rates of 14.9% and 2.0%, respectively, the difference therein is statistically significant (P < 0.01).

CONCLUSIONDown-regulation of Fas expression and up-regulation of FasL-expression are the mechanisms through which the RCC cells escape from immune attack.

Adult ; Aged ; Carcinoma, Renal Cell ; immunology ; Fas Ligand Protein ; Female ; Humans ; Ki-67 Antigen ; immunology ; Kidney Neoplasms ; immunology ; Male ; Membrane Glycoproteins ; immunology ; Middle Aged ; fas Receptor ; immunology

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.

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.

Objective:To explore the clinical application of the electronic portal imaging device (EPID) based on the linear accelerator produced by Shanghai United Imaging Healthcare Co., Ltd. (UIH) to in vivo dose verification. Methods:A total of 68 patients (32 cases with head and neck tumors, 16 cases with chest tumors, and 20 cases with abdomen and pelvis tumors) who were treated with volumetric modulated arc therapy (VMAT) in the Henan Provincial People′s Hospital were selected in this study. Each patient underwent the pre-treatment dose verification using an Arccheck device (Pre Arccheck), the pre-treatment dose verification using an EPID (Pre EPID), and the in vivo dose verification using an EPID (In vivo EPID). Moreover, the position verification based on fan beam computed tomography (FBCT) was also performed for each patient in the first three treatments and then once a week. The patients were treated when the setup error in any direction ( x: left-right, y: head-foot, z: vertical) was less than 3 mm; otherwise, position correction would be conducted. The three-dimensional setup deviation d was calculated according to setup errors x, y, and z. Results:The γ passing rates of dose verifications Pre EPID and In vivo EPID of 68 patients were (99.97±0.1)% and (94.15±3.84)%, respectively, significantly different from that (98.86±1.48)% of the Pre Arccheck dose verification ( t = -6.12, 9.43; P < 0.05). The γ passing rates of the chest, abdomen and pelvis, and head and neck in the In vivo EPID dose verification showed no significant differences ( P > 0.05). The difference in the γ passing rates (5.56±3.72)% between dose verifications Pre EPID and first In vivo EPID was unrelated to the three-dimensional setup deviation d (1.46±1.51 mm) ( P > 0.05). As the treatment proceeded, the γ passing rate of In vivo EPID gradually decreased from (94.15±3.84)% in the first week to (92.15±3.24)% in the fifth week. From the third week to the fifth week, the γ passing rates of In vivo EPID were significantly different from those in the first week ( t = 2.48, 2.75, 3.09, P < 0.05). Conclusions:The setup errors within 3 mm do not affect the γ passing rate of in vivo dose verification. The clinically acceptable threshold for the γ passing rate of in vivo EPID needs to be further determined. In addition, in vivo dose verification can support the clinical application of adaptive radiotherapy to a certain extent.

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.