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OBJECTIVE: To observe the antitumor effect of (131)I-17-allylamino-17-demethoxygeldanamycin ((131)I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application. METHODS: (131)I-17-AAG was prepared by the reaction of 17-AAG with Na [(131)I] in the presence of hydrogen peroxide. The effects of (131)17-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis. RESULTS: Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7 +/- 5.3%, 57.3 +/- 4.3%, and 63.7 +/- 3.1%, in Na(131)I group, 17-AAG group, and (131)I-17-AAG group, respectively. The inhibition rate in the (131)I-17-AAG group differed significantly between N(a131)I group and 17-AAG group (F = 229.49, P < 0.001). Following 48 h of treatment with the drug in each group, flow cytometry analysis indicated that detected sub-G peaks (black) were 1.54 +/- 0.13%, 5.72 +/- 1.05%, 12.97 +/- 1.44%, and 20.65 +/- 1.36%, in dimethyl sulfoxide (DMSO) group, Na(131)I group, 17-AAG group, and (131)I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the (131)I-17-AAG group were significantly smaller than those in the DMSO group (F = 24.18, P < 0.001) or the (131)I group (F = 20.68, P < 0.001). Histopathological and TUNEL analyses showed that (131)I-17-AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in (131)I-17-AAG was significantly lower than that in the DMSO group or (131)I group. CONCLUSIONS: (131)I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. (131)I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor.
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Apoptosis/efectos de la radiación , Benzoquinonas/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Radioisótopos de Yodo/uso terapéutico , Lactamas Macrocíclicas/uso terapéutico , Radiofármacos/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Masculino , Ratones , Ratones Desnudos , Resultado del TratamientoRESUMEN
Objective:To evaluate the efficacy and safety of nimotuzumab combined with definitive radiotherapy in the treatment of inoperable locally advanced oral and maxillofacial squamous cell carcinoma.Methods:A total of 33 patients with inoperable locally advanced oral and maxillofacial squamous cell carcinoma admitted to the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from March 2015 to December 2019 were retrospectively selected as the research objects. The treatment regimen was all targeted therapy (nimotuzumab) combined with definitive radiotherapy, with or without chemotherapy, and the efficacy and safety of the treatment were analyzed. The primary endpoints were optimal response and overall survival (OS) , and the secondary endpoints were optimal duration of response (DOR) and progression-free survival (PFS) . The survival curve was drawn using the Kaplan-Meier method, the survival rate of the patients was analyzed, and the related adverse reactions were counted.Results:Of the 33 patients, there were 20 cases of complete remission (CR) , 5 cases of partial remission (PR) , 5 cases of stable disease (SD) , 2 cases of progressive disease (PD) , and 1 case could not be evaluated. The objective response rate was 75.8% (25/33) , and the disease control rate was 90.9% (30/33) . The mean OS of all cases was 54.5 months, and the 5-year OS rate was 57.0%. The mean DOR of the overall cases was 57.2 months, and the 5-year DOR rate was 64.4%. The mean PFS of the overall cases was 54.4 months, and the 5-year PFS rate was 59.8%. The 5-year OS rates of CR, PR and SD patients were 83.6%, 20.0% and 0 ( χ2=20.07, P<0.001) , the 5-year DOR rates were 85.0%, 20.0% and 0 ( χ2=16.89, P<0.001) , and the 5-year PFS rates were 84.0%, 20.0% and 0 ( χ2=15.91, P<0.001) . The OS, DOR and PFS of patients with CR were significantly better than those of patients with PR and SD (all P<0.05) . The 5-year OS rates of patients with oropharyngeal cancer and oral cancer were 62.5% and 40.6% ( χ2=1.67, P=0.197) , the 5-year DOR rates were 73.3% and 44.0% ( χ2=1.34, P=0.247) , and the 5-year PFS rates were 68.8% and 40.9% ( χ2=1.13, P=0.289) , with no statistically significant differences, but oropharyngeal cancer patients still showed a certain advantage. Common adverse reactions included oral mucositis and hematological toxicity, most of which were grade 1-2. Two (6.1%) patients had rash, and two (6.1%) patients had nausea and vomiting, which were considered to be related to nimotuzumab. All adverse reactions were relieved after symptomatic treatments. Conclusion:For patients with locally advanced oral and maxillofacial squamous cell carcinoma who are not suitable for surgery, the choice of nimotuzumab combined with definitive radiotherapy has a relatively satisfactory efficacy and survival rate, with good safety and high clinical value.
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OBJECTIVE@#To explore the application value of MAR algorithm in metal artifact removal of CT simulator.@*METHODS@#CT phantom with titanium plate was scanned using conventional algorithms and MAR algorithms, respectively. Artifact index(AI), contrast-to-noise ratio(CNR) and AI values at different slices were used to analyze the artifact images.@*RESULTS@#In artifact index, MAR algorithm (10.28±2.60) is significantly lower than conventional algorithm (20.65±5.04); In contrast-to-noise ratio index, MAR algorithm (7.81±1.12) is better than conventional algorithm (5.61±1.36). The above indicators were statistically significant in both algorithms (P<0.01). In the slices affected by metal artifacts, the artifact index decreased by 21.72%~88.40% after the MAR algorithm.@*CONCLUSIONS@#MAR algorithm can significantly reduce the metal artifacts and improve the clinical value of CT data.
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Algoritmos , Artefactos , Metales , Fantasmas de Imagen , Titanio , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE@#To explore the high-risk fault risk of CT simulator and the main causes of the risk, and to put forward effective risk management strategies.@*METHODS@#The failure mode and effect analysis method was used to identify and control the operational fault risk of CT simulator.@*RESULTS@#5 major fault components, 8 fault failure models and 17 failure causes were analyzed. The top 5 failure causes are:anode target surface burn caused by direct scanning without warming up the tube (590.4), tube failure (518.2), burnout of joints caused by aging of high voltage cables (424.2), motor carbon brush wear (304.8) and belt break (296.4).@*CONCLUSIONS@#The failure mode and effect analysis method can effectively identify the risk of equipment failure, and thus specifically formulate risk management and control measures to ensure the normal operation of equipment and the safety of doctors and patients.
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Humanos , Falla de Equipo , Gestión de Riesgos , Métodos , Tomografía Computarizada por Rayos X , Estándares de ReferenciaRESUMEN
OBJECTIVE@#To establish a set of evaluation system of digital radiography clinical value and provide foundation for the maturity assessment of digital radiography.@*METHODS@#The evaluation system of clinical value of digital radiography was established by literature survey,expert consultation,and percentage weight method.@*RESULTS@#The expert authority coefficients were 0.81 and 0.88,respectively.After two rounds of consultation,variation coefficients of each item ranged from 0 to 0.207,and the coefficient coordination were 0.599.The index system consisted of 5 first-level indexes and 12 second-level indexes.The weights of first-level indexes such as image quality,safety,usability,economic and social indicators share of the weight are 0.298,0.294,0.199,0.121 and 0.088 respectively.@*CONCLUSIONS@#A completed and scientific evaluation system was established,which provides a scientific assessment tool for clinical value of digital radiography.
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Técnica Delphi , Intensificación de Imagen Radiográfica , Estándares de ReferenciaRESUMEN
Objective To investigate the effect of ionizing radiation on the expression of NKG2D ligand on the surface of oral squamous cell carcinoma cell line SCC25 and its cytotoxicity to tumor cells.Methods When SCC25 cells were cultured into logarithmic growth phase,they were randomly designed as control (without treatment) and experimental group (2 Gy ionizing radiation treatment) by drawing lots.Flow cytometry was used to detect the expressions of NKG2D ligands major histocompatibility complex class Ⅰ chainrelated molecule (MIC)A,MICB,UL16 binding protein (ULBP)1 on the surface of SCC25 in the control group and the experimental group cultured for 24 h.Real-time fluorescence quantification polymerase chain reaction (RT-PCR) was used to detect the changes of NKG2D ligand mRNA expression on SCC25 cell surface after 24 h culture in the experimental group and the control group.The cells were prepared and divided into blank control group (NC),2 Gy ionizing radiation group (R),NK1 group (target ratio was 5 ∶ 1),NK2 group (target ratio was 20 ∶ 1),NK1 + R group (target ratio was 5 ∶ 1,2 Gy ionizing radiation),NK2 + R group (target ratio was 20 ∶ 1,2 Gy ionizing radiation).After each group was cultured for 24 h,the killing abilities of ionizing radiation and natural killer (NK) cells to oral squamous cell carcinoma SCC25 cells were detected by CCK8.Results Flow cytometry experiment showed that,among the NKG2D ligands,the MICA fluorescence values of experimental group and control group were respectively 21.04 ± 0.39,22.90 ± 0.40 (t =2.465,P =0.069),MICB fluorescence values were 27.58 ± 0.50,29.83 ± 1.05 (t =1.936,P =0.125),and ULBP1 fluorescence values were 21.04 ± 0.40,21.78 ± 0.50 (t =1.154,P =0.313).This indicated that after ionizing radiation on SCC25,the NKG2D ligand MICA,MICB,ULBP1 expression increased slightly,but the differences were not statistically significant.RT-PCR indicated that mRNA expressions of MICB,ULBP1 were significantly different between the control group and the experimental group (t =18.334,P =0.000;t =6.381,P =0.008).The expressions of the experimental group were respectively 6.49,1.64 times as those of the control group.The results of CCK8 showed that,there was a significant difference in cell killing ability among NK1 group,NK2 group and NC group (F =344.600,P =0.000),suggesting that NK cells could kill tumor cells,and the higher ratio of NK cells and SCC25,the stronger killing effect.The comparison between R group and NC group showed that the difference in cell killing ability was not statistically significant (P =0.567).NK1 + R group and NK1 group were compared and the difference was not statistically significant (P =0.915).There was no significant difference between NK2 + R group and NK2 group (P =0.678).This showed that the killing effect of ionizing radiation was weak.Conclusion Ionizing radiation can increase the mRNA expression of NKG2D ligands MICB and ULBP1.This may provide a new way for tumor immunotherapy.The killing effect of ionizing radiation on cells is not obvious.It may be related to low radiation dose and only 24 h for cell culture.
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Objective To investigate the effect of ionizing radiation on the expression of NKG2D ligand on the surface of oral squamous cell carcinoma cell line SCC25 and its cytotoxicity to tumor cells.Methods When SCC25 cells were cultured into logarithmic growth phase,they were randomly designed as control (without treatment) and experimental group (2 Gy ionizing radiation treatment) by drawing lots.Flow cytometry was used to detect the expressions of NKG2D ligands major histocompatibility complex class Ⅰ chainrelated molecule (MIC)A,MICB,UL16 binding protein (ULBP)1 on the surface of SCC25 in the control group and the experimental group cultured for 24 h.Real-time fluorescence quantification polymerase chain reaction (RT-PCR) was used to detect the changes of NKG2D ligand mRNA expression on SCC25 cell surface after 24 h culture in the experimental group and the control group.The cells were prepared and divided into blank control group (NC),2 Gy ionizing radiation group (R),NK1 group (target ratio was 5 ∶ 1),NK2 group (target ratio was 20 ∶ 1),NK1 + R group (target ratio was 5 ∶ 1,2 Gy ionizing radiation),NK2 + R group (target ratio was 20 ∶ 1,2 Gy ionizing radiation).After each group was cultured for 24 h,the killing abilities of ionizing radiation and natural killer (NK) cells to oral squamous cell carcinoma SCC25 cells were detected by CCK8.Results Flow cytometry experiment showed that,among the NKG2D ligands,the MICA fluorescence values of experimental group and control group were respectively 21.04 ± 0.39,22.90 ± 0.40 (t =2.465,P =0.069),MICB fluorescence values were 27.58 ± 0.50,29.83 ± 1.05 (t =1.936,P =0.125),and ULBP1 fluorescence values were 21.04 ± 0.40,21.78 ± 0.50 (t =1.154,P =0.313).This indicated that after ionizing radiation on SCC25,the NKG2D ligand MICA,MICB,ULBP1 expression increased slightly,but the differences were not statistically significant.RT-PCR indicated that mRNA expressions of MICB,ULBP1 were significantly different between the control group and the experimental group (t =18.334,P =0.000;t =6.381,P =0.008).The expressions of the experimental group were respectively 6.49,1.64 times as those of the control group.The results of CCK8 showed that,there was a significant difference in cell killing ability among NK1 group,NK2 group and NC group (F =344.600,P =0.000),suggesting that NK cells could kill tumor cells,and the higher ratio of NK cells and SCC25,the stronger killing effect.The comparison between R group and NC group showed that the difference in cell killing ability was not statistically significant (P =0.567).NK1 + R group and NK1 group were compared and the difference was not statistically significant (P =0.915).There was no significant difference between NK2 + R group and NK2 group (P =0.678).This showed that the killing effect of ionizing radiation was weak.Conclusion Ionizing radiation can increase the mRNA expression of NKG2D ligands MICB and ULBP1.This may provide a new way for tumor immunotherapy.The killing effect of ionizing radiation on cells is not obvious.It may be related to low radiation dose and only 24 h for cell culture.
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Tumor radiation therapy (RT)can affect the immune system.Latest studies show that appropriate RT can activate the immune system through regulating tumor microenvironment,activating immune cells and releasing danger signals,and can produce bystander or abscopal effect.With the development of clini-cal biomarkers research and clinical trials about RT combined with immunotherapy,it is expected to change the traditional pattern of tumor treatment.
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This study presents a dosimetric optimization effort aiming to compare noncoplanar field (NCF) on 3 dimensions conformal radiotherapy (3D-CRT) and coplanar field (CF) on intensity-modulated radiotherapy (IMRT) planning for postocular invasion tumor. We performed a planning study on the computed tomography data of 8 consecutive patients with localized postocular invasion tumor. Four fields NCF 3D-CRT in the transverse plane with gantry angles of 0-10 degrees , 30-45 degrees , 240-270 degrees , and 310-335 degrees degrees were isocentered at the center of gravity of the target volume. The geometry of the beams was determined by beam's eye view. The same constraints were prepared with between CF IMRT optimization and NCF 3D-CRT treatment. The maximum point doses (D max) for the different optic pathway structures (OPS) with NCF 3D-CRT treatment should differ in no more than 3% from those with the NCF IMRT plan. Dose-volume histograms (DVHs) were obtained for all targets and organ at risk (OAR) with both treatment techniques. Plans with NCF 3D-CRT and CF IMRT constraints on target dose in homogeneity were computed, as well as the conformity index (CI) and homogeneity index (HI) in the target volume. The PTV coverage was optimal with both NCF 3D-CRT and CF IMRT plans in the 8 tumor sites. No difference was noted between the two techniques for the average D(max) and D(min) dose. NCF 3D-CRT and CF IMRT will yield similar results on CI. However, HI was a significant difference between NCF 3D-CRT and CF IMRT plan (p < 0.001). Physical endpoints for target showed the mean target dose to be low in the CF IMRT plan, caused by a large target dose in homogeneity (p < 0.001). The impact of NCF 3D-CRT versus CF IMRT set-up is very slight. NCF3D-CRT is one of the treatment options for postocular invasion tumor. However, constraints for OARs are needed.
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Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Orbitales , Radiometría , Dosificación Radioterapéutica , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Objective:To analyze survival in patients with advanced oral cancer from prospective clinical trials. Methods:From 2008 to 2010, 256 patients with oral cancer at clinical stage III/IVA were randomly categorized into two groups. Patients in the experi-mental group received neo-adjuvant chemotherapy, surgery, and post-operative radiation, and patients in the control group underwent surgery and post-operative radiation. All patients were routinely followed-up after treatments. Survival was analyzed using Kaplan–Meier method and log-rank test, and differences were considered statistically significant at P value lower than 0.05. Results: Each group was composed of 128 patients. With the median follow-up period of 60 months, the 5-year overall survival rate was 61.7%and the disease-free survival rate was 53.9%. The overall survival rate (P=0.350) and the disease-free survival rate (P=0.160) were not sig-nificantly different between the experimental and control groups. Patients with positive pathological response to neo-adjuvant chemo-therapy exhibited significantly improved overall survival (P<0.05). Conclusion:Radical surgery should be emphasized to improve the prognosis of oral cancer. Functional reconstruction could also improve the quality of life and survival of patients. Despite that neo-adju-vant chemotherapy could not improve the survival of patients with advanced oral cancer in entirety, it could benefit patients exhibiting positive treatment responses.
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Objective To investigate the mechanism of extremely low frequency electromagnetic field (ELF-EMF) and X-ray irradiation on liver carcinoma cell lines BEL-7402. Methods Liver carcinoma cell lines BEL-7402 had been incubated with ELF-EMF (100 Hz, 0.7 mT, 30 min, 3 days) after X-ray irradiation at different doses (0, 2, 4, 6, 8,10 Gy). The cells were observed on morphologic changes with scanning electron microscope. Flow cytometry and gene microarray were used to investigate the mechanism of cell apeptosis. Results ELF-EMF plus X-ray induced apoptosis on BEL-7402 was observed under scanning electron microscope.When X-irradiation was 2, 4, 6, 8 and 10 Gy, the apoptosis ratios of combined group and only X-irradiation group were 10.0%, 14.5%, 4.3%, 5.1%, 7.1% and 0.1%, 8.1%, 0.1%, 0.4%, 2.2% (P < 0.05) on flow cytometry. The result of microarray indicated that 1465 genes were up-regulated and 1108 down*regulated in the ELF-EMF plus X-ray group in comparison with the control group. The change rates of 110 apoptosis related genes were above 2 times, which including 71 up-regulated and 39 down-regulated. Gene microarray showed that ELF-EMF and X-ray irradiation had a mainly effect on different gene of apoptosis paths (CDC25 and CHKI, ATM, p38, PTEN, p53, G1/S, Fas, G2/M, Cell Cycle, Apoptosis and Caspase). The same genes of ELF-EMF plus X-ray group were showed 13 in ELF-EMF group and 42 in X-ray group. Conclusions Apoptosis paths were significantly different between ELF-EMF and X-irradiation. ELF-EMF cooperates with X-irradiation on inducing BEL-7402 cell apoptosis.