Purpose:The aim of this study was to evaluate the clinical efficacy and toxicity of treatment with gemcitabine and cisplatin for hormone independent prostate cancer.Methods:18 cases of advanced hormone independent prostate cancers who received castration and antiandrogen medicines were confirmed to have multiple bone metastatic carcinomas by emission computed tomography(ECT), and hepatic , adrenal and intracranial metastasis were found respectively each in 1 patient, and the value of PSA(prostatic special antigen) had on ascending trend in all patients. Gemcitabine 1000 mg/m~(2) +NS 100 ml was administered by intravenous drip on days 1,8 and cisplatin 100 mg/m~(2) +NS 500 ml was administered by intravenous drip on day 1 or cisplatin 30 mg/m~(2) +NS 250 ml was administered by intravenous drip on days 1 to 5 in each 28-day cycle.Results:Levels of PSA descent to normal titer(

With the further researches on the immune mechanisms in tumor,more and more scholars notice the phenomenon that radiation activates the immunity,and find that radiotherapy causes immunity suppression is one-sided.Although body's anti-tumor immunity can be enhanced by radiotherapy,in clinical,we observe that patients who receive radiotherapy cannot avoid tumor recurrence and metastasis.Researches show that tumor microenvironment makes the immune checkpoint pathway abnormally activated.Therefore,the combination of radiotherapy and immune checkpoint inhibitor can change the tumor microenvironment,and can improve the therapeutic effect.

Generally speaking,the organism can maintain the stability of T cells.The lymphopeniainduced homeostatic proliferation of T cells could be driven by the recognition of autoantigen including tumor antigen in the absence of foreign antigens or inflammatory signals.This process can break tumor-induced immune tolerance and induce a powerful antitumor immunity.It is confirmed that some negative immune molecules are recruited during the homeostatic proliferation,then the antitumor immunity will be impaired.

Objective To investigate whether soluble PD-1 overexpression in 4T1 senescence tumor cells enhances the anti-tumor effect of senescence tumor cell vaccine (STCV) against breast tumor cells in a tumor-bearing mouse model. Methods 4T1 cells were treated with interferon-γ (IFN-γ) and the expression of PD-L1 was detected by flow cytometry. CCK8 assay was used to compare the cell proliferation activity between 4T1 cells and 4T1 cells infected by a lentiviral vector of sPD-1 (4T1/sPD-1 cells), and the expressions of sPD-1 mRNA and protein in 4T1/sPD-1 cells were detected using qPCR and Western blotting. The culture supernatant of 4T1/sPD-1 cells was added in 4T1 cells pre-treated with IFN-γ, and PD-1-positive 4T1 cells were detected with flow cytometry. Senescenceβ-galactosidase staining kit was used to detect the senescent 4T1 and 4T1/sPD-1 cells following exposure to X-ray radiation and Veliparib. Balb/c mice bearing subcutaneous 4T1 tumor xenografts were treated with injections of PBS, 4T1 STCV, or 4T1/sPD-1 STCV, and tumor growth was observed. Results Stimulation with IFN-γconcentration-dependently up-regulated PD-L1 expression by as much as (84.80 ± 1.03)％ in 4T1 cells (P<0.001). sPD-1 overexpression in 4T1 cells did not significantly affect the cell proliferation. Treatment of 4T1 cells with 4T1/sPD-1 cell culture supernatant significantly increased the proportion of PD-1 + cells from (6.893 ± 0.271)％ to (55.450 ± 0.555)％ (P<0.001). X-ray irradiation combined with Veliparib caused obvious senescence in 4T1 and 4T1/sPD-1 cells. In the tumor-preventing experiment, tumor formation occurred in all the mice in PBS group;28.787％of the mice in 4T1 STCV group and 55.556％in 4T1/sPD-1 STCV group showed no tumor formation. In the tumor treatment experiment, tumor formation occurred in all the mice in PBS groups while in 4T1 STCV and 4T1/sPD-1 STCV groups, 11.111％ and 38.89％ of the mice were tumor-free during the observation period, respectively. Conclusions Senescence tumor cells vaccine has anti-tumor effect against breast cancer in mice, and sPD-1 over-expression can enhance this effect of the vaccine.

Objective To investigate whether soluble PD-1 overexpression in 4T1 senescence tumor cells enhances the anti-tumor effect of senescence tumor cell vaccine (STCV) against breast tumor cells in a tumor-bearing mouse model. Methods 4T1 cells were treated with interferon-γ (IFN-γ) and the expression of PD-L1 was detected by flow cytometry. CCK8 assay was used to compare the cell proliferation activity between 4T1 cells and 4T1 cells infected by a lentiviral vector of sPD-1 (4T1/sPD-1 cells), and the expressions of sPD-1 mRNA and protein in 4T1/sPD-1 cells were detected using qPCR and Western blotting. The culture supernatant of 4T1/sPD-1 cells was added in 4T1 cells pre-treated with IFN-γ, and PD-1-positive 4T1 cells were detected with flow cytometry. Senescenceβ-galactosidase staining kit was used to detect the senescent 4T1 and 4T1/sPD-1 cells following exposure to X-ray radiation and Veliparib. Balb/c mice bearing subcutaneous 4T1 tumor xenografts were treated with injections of PBS, 4T1 STCV, or 4T1/sPD-1 STCV, and tumor growth was observed. Results Stimulation with IFN-γconcentration-dependently up-regulated PD-L1 expression by as much as (84.80 ± 1.03)％ in 4T1 cells (P<0.001). sPD-1 overexpression in 4T1 cells did not significantly affect the cell proliferation. Treatment of 4T1 cells with 4T1/sPD-1 cell culture supernatant significantly increased the proportion of PD-1 + cells from (6.893 ± 0.271)％ to (55.450 ± 0.555)％ (P<0.001). X-ray irradiation combined with Veliparib caused obvious senescence in 4T1 and 4T1/sPD-1 cells. In the tumor-preventing experiment, tumor formation occurred in all the mice in PBS group;28.787％of the mice in 4T1 STCV group and 55.556％in 4T1/sPD-1 STCV group showed no tumor formation. In the tumor treatment experiment, tumor formation occurred in all the mice in PBS groups while in 4T1 STCV and 4T1/sPD-1 STCV groups, 11.111％ and 38.89％ of the mice were tumor-free during the observation period, respectively. Conclusions Senescence tumor cells vaccine has anti-tumor effect against breast cancer in mice, and sPD-1 over-expression can enhance this effect of the vaccine.

OBJECTIVE: To investigate whether interleukin-12 (IL-12) over-expression in malignant melanoma B16 cells affects the expression level of programmed death-1 (PD-1) on T cells in mice during immune microenvironment reconstruction. METHODS: B16 cells were transfected with an IL-12 expression lentiviral vector, and IL-12 over-expression in the cells was verified qPCR and ELISA. Plate cloning assay was used to compare the cell proliferation activity between B16 cells and B16/IL-12 cells. The expression of IL-12 protein in B16/IL-12 cells-derived tumor tissue were detected by ELISA. C57BL/6 mice were inoculated with B16 cells or B16/IL-12 cells, and 14 days later the proportion of T cells with high expression of PD-1 in the tumor-draining lymph nodes was detected by flow cytometry. Mouse models of immune reconstitution established by 650 cGy X-ray radiation were inoculated with B16 (B16+RT group) or B16/IL-12 (B16/IL-12+RT group) cells, with the mice without X-ray radiation prior to B16 cell inoculation as controls. Tumor growth in the mice was recorded at different time points, and on day 14, flow cytometry was performed to detect the proportion of T cells with high PD-1 expression in the tumor-draining lymph nodes and in the tumor tissue. RESULTS: B16 cells infected with the IL-12-overexpressing lentiviral vector showed significantly increased mRNA and protein levels of IL-12 ( < 0.001) without obvious changes in cell viability (>0.05). B16/IL-12 cells expressed higher levels of IL-12 than B16 cells ( < 0.01). In the tumor-bearing mouse models, the proportion of CD4 PD-1 T cells was significantly lower in B16/IL-12 group than in B16 group ( < 0.01). In the mice with X-ray radiation-induced immune reconstitution, PD-1 expressions on CD4 T cells ( < 0.05) and CD8+ T cells ( < 0.01) were significantly higher in B16+ RT group than in the control mice and in B16/IL-12+RT group ( < 0.01 or 0.001); the tumors grew more slowly in B16/IL-12+RT group than in B16 + RT group ( < 0.001). CONCLUSIONS During immune microenvironment reconstruction, overexpression IL-12 in the tumor microenvironment can reduce the percentage of PD-1 T cells and suppress the growth of malignant melanoma in mice.
Animals ; CD8-Positive T-Lymphocytes ; Cell Line, Tumor ; Immune Reconstitution ; Interleukin-12 ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment

Objective:To study the influence of environmental radiation of radiotherapy workplace on the stereotactic radiation therapy(SRT) plan absolute dose verification with plastic scintillator detector Exradin W1.Methods:The computed tomography (CT) image of the stereotactic dose verification phantom (SDVP) was scanned and imported into the treatment planning system. Three schemes, including 3 cm × 3 cm to 20 cm × 20 cm square gradient field irradiation, virtual planning target volume(PTV) non-coplanar arcs irradiation and 10 cases of volumetric modulated arc radiotherapy SRT (VMAT SRT) clinical plan verification, were measured with or without a home-made shield over the photodiode. Measurements were recorded to analyze the impact of environmental radiation on dose measurement under different conditions.Results:The noise effect of the photodiode increased with the the lager open field size, and decreased with the reduced distance between the photodiode and isocenter. The contribution of photodiode noise effect increase with the lager non-coplanar arc field size, with the largest up to 4.16%. As for the clinical SRT plan verification measurement, the relative difference between the SRT plan measurements and treatment planning system(TPS) before and after shielding were (1.39±1.05)% and (0.59±1.03)%, respectively ( t=-5.343, P < 0.05). and for W1 vs. A16 microchamber was (1.22±1.56)% and (0.42±1.42)%, respectively ( t=-5.414, P < 0.05). Conclusions:The measurements of Exradin W1 are in good agreement with the TPS result and the ionization chamber measurements, but its accuracy is easily affected by the environmental radiation of radiotherapy workplace. To measure non-coplanar radiation, the photodiode should be placed as far away as possible from the isocenter and be properly shielded, which can effectively improve the accuracy and stability of the measurement and provide a strong guarantee for clinical precision radiotherapy.

Objective:To compare carotid endarterectomy (CEA) and carotid artery stenting (CAS) in perioperative, medium and long term prognosis of patients with carotid artery stenosis.Methods:A retrospective analysis was performed on 1 329 cases of carotid artery stenosis treated at Department of Vascular Surgery, Beijing Anzhen Hospital from Jan 2011 to Aug 2020, as all cases being divided into CAS group and CEA group.Results:There were significant differences in age ( t=0.098, P=0.023) and drinking habits ( χ2=8.055, P=0.005) between the two groups. There were more unstable plaques in CEA group ( χ2=4.392, P=0.038), and more bilateral lesions in CAS group ( χ2=9.673, P=0.038). In perioperative period, there were more mannitol use in CEA group ( χ2=78.614, P<0.001), more incision/puncture site complications ( χ2=5.158, P=0.035), lung infection ( χ2=6.355, P=0.013), cerebral hyperperfusion syndrome (CHS) ( χ2=5.158, P=0.035) and extracranial nerve injury ( χ2=23.760, P<0.001) in CEA group than in CAS group, and more acute renal failure in CAS group ( χ2=10.393, P=0.001). There was no significant difference in survival rate and ischemic stroke, myocardial infarction, cerebral hemorrhage and renal insufficiency between the two groups (all P>0.05). The mean survival time of CAS group was 53.195 months (95% CI: 52.040-54.350), and 54.492 months (95% CI: 53.790-55.195) in CEA group ( P=0.051). Conclusions:Patients in CEA group had more unstable plaque and a lower perioperative stroke rate. CEA group had higher risk of CHS,while CAS was with lower postoperative lung infection rate and less wound local complications. There was no significant difference in long-term survival between the two groups.

Objective To investigate the epidemiological characteristics and impact factors on hospitalization of Plasmodium vivax (P.vivax) since initiation of national malaria elimination program, so as to facilitate the adjustment of technical guideline in response to the epidemic changing of malaria in China. Methods The data of individual P. vivax case (probable and confirmed) and population during 2011-2014 were collated from China National Notifiable Infectious Disease Reporting Information System, and the data of epidemiological investigation for individual P. vivax case (imported and indigenous) during 2011-2014 were collected from China Parasite Disease Prevention and Control Information System. All of the data didn 't include China's Hongkong, Macao, Taiwan and foreign cases. The risk factors on hospitalization were explored by multiple factors variable binary classification unconditioned logistic regression model. Results During study period of four years, a total of 5 656 Plasmodium vivax cases were detected. Among them, 69.9% (3 951 cases) were imported cases and 30.1% (1 705 cases) were autochthonous cases. The male cases accounted for 82.7%of all cases. Among the autochthonous cases, 535 cases (31.4%) occurred in the cross-bordering areas, and 577 cases (33.8%) were reported in the junction of difference provinces. The amount of autochthonous cases decreased from 1 363 cases in 2011 to 53 cases in 2014, and the county affected by autochthonous cases was shrunk from 185 counties to 10 counties. The proportion of autochthonous cases introduced by domestic migrants increased constantly, which reached 41.5%in 2014. The imported cases were detected from 614 counties of 30 provinces, who were originated from 57 overseas countries of 4 continents, with Southeast Asia being the leading origins (2 772 cases, 70.2%). There were 1 494 cases hospitalized for treatment, with the male (OR=1.41, 95%CI: 1.16-1.71), 14 years old and younger (OR=2.26, 95%CI:1.44-3.56), and oversea imported cases (OR=2.73, 95%CI:2.30-3.25) were the high risk group for hospitalization. Conclusion The scale and scope of P. vivax occurrence decreased dramatically since initiation of malaria elimination grogram in 2010. However, the risk of P. vivax introduction by the overseas imported cases and domestic migrants should be highlighted.

Objective To investigate the epidemiological characteristics and impact factors on hospitalization of Plasmodium vivax (P.vivax) since initiation of national malaria elimination program, so as to facilitate the adjustment of technical guideline in response to the epidemic changing of malaria in China. Methods The data of individual P. vivax case (probable and confirmed) and population during 2011-2014 were collated from China National Notifiable Infectious Disease Reporting Information System, and the data of epidemiological investigation for individual P. vivax case (imported and indigenous) during 2011-2014 were collected from China Parasite Disease Prevention and Control Information System. All of the data didn 't include China's Hongkong, Macao, Taiwan and foreign cases. The risk factors on hospitalization were explored by multiple factors variable binary classification unconditioned logistic regression model. Results During study period of four years, a total of 5 656 Plasmodium vivax cases were detected. Among them, 69.9% (3 951 cases) were imported cases and 30.1% (1 705 cases) were autochthonous cases. The male cases accounted for 82.7%of all cases. Among the autochthonous cases, 535 cases (31.4%) occurred in the cross-bordering areas, and 577 cases (33.8%) were reported in the junction of difference provinces. The amount of autochthonous cases decreased from 1 363 cases in 2011 to 53 cases in 2014, and the county affected by autochthonous cases was shrunk from 185 counties to 10 counties. The proportion of autochthonous cases introduced by domestic migrants increased constantly, which reached 41.5%in 2014. The imported cases were detected from 614 counties of 30 provinces, who were originated from 57 overseas countries of 4 continents, with Southeast Asia being the leading origins (2 772 cases, 70.2%). There were 1 494 cases hospitalized for treatment, with the male (OR=1.41, 95%CI: 1.16-1.71), 14 years old and younger (OR=2.26, 95%CI:1.44-3.56), and oversea imported cases (OR=2.73, 95%CI:2.30-3.25) were the high risk group for hospitalization. Conclusion The scale and scope of P. vivax occurrence decreased dramatically since initiation of malaria elimination grogram in 2010. However, the risk of P. vivax introduction by the overseas imported cases and domestic migrants should be highlighted.