1.A preliminary study of three-dimensional conformal radiotherapy with different clinical target volumes for esophageal cancer
Shuchai ZHU ; Jinrui XU ; Zhikun LIU ; Jingwei SU ; Juan LI
Chinese Journal of Radiation Oncology 2014;23(2):127-130
Objective To investigate the value of prophylactic irradiation to the lymphatic drainage area in radical three-dimensional conformal radiotherapy (3DCRT) and to evaluate the efficacy and adverse effects of 3DCRT with different clinical target volumes.Methods A retrospective analysis was performed on the records of 219 esophageal cancer patients without distant metastasis who received 3DCRT from January 2005 to December 2010.One hundred and five patients received involved-field irradiation (IFI) with a total dose of 54-66 Gy;114 patients received elective nodal irradiation (ENI) with a total dose of 46-52 Gy; the prescribed dose to the primary lesion was 56-70 Gy.The Kaplan-Meier method was used to calculate local control (LC) and overall survival (OS) rates,and the log-rank test was used for univariate prognostic analysis.Results The 1-,3-,and 5-year sample sizes were 219,172 and 67,respectively.The 1-,3-,and 5-year LC rates for IFI group were 63.0%,39.1%,and 27.2%,respectively,versus 70.5%,53.3%,and 51.7% for ENI group (x2 =6.22,P =0.013) ;the 1-,3-,and 5-year OS rates for IFI group were 67.6%,24.9%,and 15.0%,respectively,versus 73.7%,45.1%,and 26.0% for ENI group (x2=5.04,P =0.025).The univariate stratified analysis showed that the LC and OS rates were significantly higher in the ENI group than in the IFI group for patients with middle-or lower-thoracic primary lesion or N0 disease (P=0.007,0.015;P=0.054,0.013).Conclusions For esophageal cancer patients with middle-or lower-thoracic primary lesion or without lymph node metastasis,prophylactic irradiation to the lymphatic drainage area can increase LC and OS rates.
2.Body temperature and prognosis in patients with massive hemispheric infarction in acute phase
Jingwei ZHAO ; Yingying SU ; Tiantian LIU ; Weibi CHEN
International Journal of Cerebrovascular Diseases 2009;17(7):506-510
in order to maintain a normal temperature range.
3.Early prediction of malignant midge cerebral artery infarction with bedside electroencephalography
Jingwei ZHAO ; Yingying SU ; Xia LI ; Lin WANG ; Tiantian LIU
International Journal of Cerebrovascular Diseases 2010;18(2):81-86
Objective To investigate the possibility and accuracy of predicting malignant middle cerebral artery infarction (mMCAI) with bedside electroencephalography (EEG). Methods Thirty-five patients with massive hemispheric infarction (MHI) underwent bedside EEG monitoring within 48 h of onset. The EEG indicators were interpreted blindly, and the clinical, laboratory and imaging parameters were analyzed. The patients were divided into mMCAI group and non-mMCAI group according to whether they had occurred mMCAI or not within 7 days of onset. The differences of EEG indicators, clinical, laboratory and imaging parameters between the 2 groups were compared. When the parameters of significant difference and statistical significance appeared the odds ratio (OR) of occurring mMCAI were analyzed, and their accuracy of predicting mMCAI was calculated. Results Of the 35 patients with MHI, 20 were in the mMCAI group and 15 were in the non-mMCAI group. There were significant differences in the EEG indicators (infarction on the contralateral side, including disintegration of occipital α rhythm, generalized slow-wave, dominant frequency wave low amplitude, regional attenuation without delta [RAWOD]pattern, and absence of EEG reactivity), clinical parameters (nausea accompanied with vomiting), and imaging parameters (the infracted area more than the entire MCA territory, and midline shifting 3 to 5 mm at the level of septum pellucidum) between the 2 groups (P < 0. 05). Of those, the risk of mMCAI was the highest in patients with disintegration of occipital a rhythm on the contralateral side of infarction (P = 22. 67, 95% CI 3. 89-132. 10). The sensitivity of predicting mMCAI was 85. 0%, the specificity was 80.0%, the positive predictive value was 85.0%, and the negative predictive value was 80. 0%, which were superior to other EEG indicators and clinical or imaging parameters. Conclusions Bedside EEG indicators can early predict mMCAI, moreover, the predictive accuracy is superior to the clinical and imaging parameters.
4.Effect of RNA interference for MDC1 gene on cell cycle and expression of related proteins in esophageal carcinoma cells after X-ray radiation
Zhikun LIU ; Shuchai ZHU ; Jingwei SU ; Juan LI ; Wenbin SHEN
Chinese Journal of Radiation Oncology 2015;(6):708-713
Objective To apply RNA interference technique for reducing the expression of MDC1 gene in esophageal carcinoma cell line ECA109, observe the changes in cell cycle and radiosensitivity after radiation, and discuss related mechanisms. Methods Three pairs of effective interference sequences and negative control sequences were synthesized for MDC1 mRNA sequence, and a recombinant plasmid was constructed with the vector pSIH1?H1?copGFP. RT?PCR and Western blot were used to determine the expression levels of MDC1 mRNA and protein. Colony?forming assay was applied to measure radiosensitivity, flow cytometry to determine cell cycle, Western blot to determine the expression of CHK1 and CHK2 proteins, and laser scanning confocal microscope to observe the number of MDC1 blotches inside the nucleus. One?way analysis of variance was used to analyze the differences between groups. Results The pSIH1?H1?copGFP plasmid was constructed successfully and ECA109 cells were infected to obtain ECA109M cells with stable transfection. The expression levels of MDC1 mRNA and protein in ECA109M cells were lower than those in ECA109N and ECA109 cells ( P= 0. 032 and 0. 041, respectively ) . After 5?Gy radiation, ECA109M cells had a lower proportion of G2+M cells than ECA109N and ECA109 cells ( P=0. 026) . After 5?Gy radiation, ECA109, ECA109N, and ECA109M cells had similar expression levels of CHK1 and CHK2 proteins ( P= 0. 345 and 0. 451, respectively ) , and ECA109M cells had a lower expression level of CHK2 T68 protein than ECA109 and ECA109N cells ( P=0. 012) . ECA109 cells had a D0 value of 3. 06 Gy and an SF2 value of 0. 91;the D0 values for ECA109N and ECA109M cells were 2. 90 Gy and 1. 88 Gy, respectively, and the SF2 values for them were 0. 89 and 0. 84, respectively ( P=0. 021 and 0. 037, respectively ) . Conclusions RNA interference can reduce the expression levels of MDC1 protein and cell cycle?related proteins, release cell cycle arrest, and enhance radiosensitivity in esophageal carcinoma ECA109 cells.
5.Lentivirus mediated RNAi silence esophageal MDC1 Eca109 cell gene expression of the influence of nude mouse transplantation tumor radiosensitivity
Zhikun LIU ; Shuchai ZHU ; Jingwei SU ; Juan LI ; Wenbin SHEN
Chinese Journal of Radiation Oncology 2016;25(7):753-758
Objective To investigate the effects of inhibition of MDC1 protein expression on xenografted tumors in nude mice,and to observe the histopathological and cellular changes in nude mice.Methods Three pairs of effective and control short hairpin RNA targeting MDC1 mRNA were designed and cloned into the pSIH1-H1-copGFP vector.Real-time PCR and Western blot were used to determine the mRNA and protein expression of MDC1.After selection by copGFP reporter gene,cells were divided into negative transfection group (ECA109-N) and MDC1 transfection group (ECA109-M).The transfected cells were injected into nude mice.The mice were divided into ECA109 group,ECA109-N group,and ECA109-M group.Each group was divided into irradiation subgroup and non-irradiation subgroup.The changes in tumor size after irradiation were evaluated in each group.Western blot was used to measure the expression of CHK1,CHK2,and CHK2T68 in xenografted tumors.Flow cytometry was used to analyze the cell cycle distribution and apoptosis of tumor cells in nude mice.The variance analysis was used to compare the mean of multiple groups,and the SNK-q test was used in the two two groups.Results The pMDC1-shRNA plasmid was successfully constructed and used to transfect ECA109 cells.ECA109-M cells were obtained by stable transfection with the recombinant plasmid.All inoculated nude mice survived with visible xenografted tumors at the underside of the paw in about one week.There was no swelling and wound in inoculation sites.There was no significant difference in tumor size between different groups (P>0.05).The tumor growth in the ECA109 group and the ECA109-N group significantly slowed down after irradiation with a dose of 15 Gy (P<0.05).Compared with the other two groups,the ECA109-M group had a significant smaller tumor size,significantly slower relative tumor growth,and significantly higher growth inhibition (all P<0.05).The q value of the ECA109-M group was 1.36.In the ECA109-M group,there were no significant changes in the protein expression of CHK1 and CHK2 after irradiation (P> 0.05);however,the phosphorylation of CHK2T68 protein was significantly reduced after irradiation (P<0.05).There were no significant differences in cell cycle distribution or the proportion of apoptotic cells in tumor tissue between the three groups (P>0.05).Conclusions Inhibition of MDC1 protein expression by RNA interference can effectively inhibit the growth of xenografted tumors after irradiation in the nude mice by increasing their radiosensitivity.
6.Effect of protein tyrosine phosphatase non-receptor type 12 (PTPN12) downregulation on the radiosensitivity of non-small cell lung cancer
Wenxia HU ; Zhikun LIU ; Weili ZHANG ; Scott WELFORD ; Jingwei SU
Chinese Journal of Clinical Oncology 2016;43(7):285-290
Objective: To identify the relationship between the expression of protein tyrosine phosphatase non-receptor type 12 (PTPN12) and radiotherapy effect in non-small cell lung cancer (NSCLC) tissues and to determine whether PTPN12 deficiency can sensi-tize lung cancer cells to irradiation. Methods: From September 2013 to October 2014, 92 NSCLC patients undergoing radiotherapy with or without platinum-based combination chemotherapy were analyzed retrospectively. Before the treatment, PTPN12 expression was detected through immunohistochemistry. After the completion of radiotherapy, the patients' responses were assessed and radio-therapeutic efficacy analyzed. The human NSCLC cell line H1299 was infected with shPTPN12 knockdown, and colony survival assay was analyzed after irradiation. Chi-square test was used to examine the correlation between PTPN12 expression and clinicopathologi-cal characteristics. Univariate analyses and Logistic regression test were used to analyze the relationship between clinicopathological characteristics and radiotherapeutic response. Results: Patients with low PTPN12 expression were more sensitive to radiotherapy than those with high PTPN12 expression (80.0%vs. 57.1%, P=0.018). Multivariate analysis showed that PTPN12 expression was the on-ly independent predictor of radiotherapeutic response in NSCLC. The H1299-shPTPN12-knockdown cells were sensitive to irradiation. Conclusions:The results of the study indicated that downregulation of PTPN12 improved the radiosensitivity of NSCLC cells.
7.Analysis the long-term effect of 375 patients with esophageal carcinoma treated by three-dimensional conformal radiotherapy
Juan LI ; Shuchai ZHU ; Yuxiang WANG ; Zhikun LIU ; Wenbin SHEN ; Jingwei SU
Chinese Journal of Radiation Oncology 2012;21(4):334-338
ObjectiveTo analyze the outcomes and prognostic factors of advanced esophageal carcinoma treated by three-dimensional conformal radiotherapy (3DCRT).MethodsFrom Jul 2001 to Dec 2006.375 patients with esophageal carcinoma treated by 3DCRT were retrospectively analyzed of which Ⅰ stage 9,Ⅱ stage 106,Ⅲ stage 158,Ⅳstage 102.The short-term effect,1-,3-,5-year local regional control rates and survival rates were investigated.The local regional control rates and survival rate were calculated by the Kaplan-Meier method. Univariate prognostic factor was analyzed by Logrank method.Multivariate prognostic factor was analyzed using Cox regression model.ResultsThe follow-up rate was 94.7%.The numbers of patients followed-up with 5 years was 191.The 1-,3-and 5-year local control rates were 80.5%,53.7%,44.9%respectively.The 1-, 3-and 5-year survival rates were 67.2%,29.4%,19.0%respectively.Univariate analysis showed the significant prognostic factors included the degree of dysphagia,tumor length,the largest diameter of lesion in CT image,T stage,N stage,clinical TNM stage,grades of acute radiation-induced esophagitis and grades of acute radiation-induced pneumonery ( x2 =46.75,18.52,30.24,42.53,32.71,75.68,7.13,4.64,P =0.000,0.000,0.000,0.000,0.000,0.000,0.008,0.031 ).Multivariate analysis revealed tumor length,clinical TNM stage,chemotherapy and grades of acute radiationinduced esophagitis were independent prognostic factors (x2 =6.70,18.00,4.87,1.1 8,P =0.030,0.000,0.027,0.011 ).Conclusions3DCRT is effective and feasible in treatment of the advanced esophageal carcinoma.Tumor lesion length,clinical TNM stage,chemotherapy and grades of acute radiation-induced esophagitis are independent prognostic factors for survival of patients.
8.MMP-9,uPA and uPAR proteins expression and its prognostic significance in esophageal squamous cell carcinoma treated by radiotherapy
Shuchai ZHU ; Yafei WANG ; Jingwei SU ; Yuxiang WANG ; Wenbin SHEN ; Juan LI
Chinese Journal of Radiation Oncology 2008;17(4):263-267
Objective To explore the the prognostic significance of MMP-9,uPA and uPAR protein expression and its relationship with clinical-pathologic factors in esophageal squamous cell carcinoma treated by radiotherapy.Methods MMP-9,uPA and uPAR protein expression was measured in 59 esophageal car cinomas and 41 peri-carcinoma tissues with immunohistochemistry.The relationship between the protein expression and the clinical-pathological parameters was analyzed,and the prognostic factors in esophageal squamous cell carcinoma treated by radiotherapy alone was evaluated.Results The rates of positive expression of MMP-9.uPA and uPAR were 85%,76%and 78%in esophageal carcinoma and 39%,49%and 44%in peri-carcinoma tissues(x2=22.54,8.04 and 12.18;P=0.000,0.005 and 0.000).The rates of positive expression of MMP-9 was 79%and 100%when the depth of tumor invasion was≤2 am and>2 cm(P=0.048),respectively.The expression of uPA was significantly correlated with the status of fat interspace between the esophageal lesion and the vertebra in CT seaning image.When the fat interspace existed and disappeared,the rates of strong positive expression was 44%and 70%,respectively(χ2=4.21,P=0.040).The positive expression rate of uPA was significantly correlated with distant metastasis.which was 100%in patients with distant metastasis and 68.89%in those without distant metastasis(χ2=4.12,P=0.042).r11}lepositive expression rate of MMP-9.uPA and uPAR did not affect the prognosis and the short-term result of esoph.ageal carcinoma treated by radiotherapy alone.Conclusions The protein expression of MMP-9,uPA and uPAR may correlate with local infiltration and distant metastasis in esophageal squamous cell carcinoma.Protein expression may not influence the prognosis of esophageal carcinoma treated by radio therapy,though long time followed-up is stil needed.
9.Three-dimensional conformal radiotherapy of early stage esophageal carcinoma
Wenbin SHEN ; Shuchai ZHU ; Juan LI ; Jingwei SU ; Zhikun LIU ; Youmei LI
Chinese Journal of Radiation Oncology 2011;20(1):32-35
Objective To analyze the result of3-dimensional conformal radiotherapy(3DCRT)and operation of early stage esophageal carcinoma. Methods Ninety-three patients with early stage esophageal carcinoma were treated with 3DCRT from October 2000 to December 2006. The total dose was 50 -70 Gy/25 -35F/5 -7 w. Toxicities and survival rates were evaluated by Kaplan Meier method and the factors of death were analyzed. Results In the 3DCRT group, 79, 42 and 13 cases were followed up for at least 1-,3-,and 5-year, respectively. Follow-up rate was 100%. The 1-, 3-, and 5-year actuarial survival rates were 84% ,50% and 29%, respectively, with a median survival time of 37.0 months. The 1-, 3-, and 5-year local control rates were 83% ,63% and 55% ,respectively. The 1-, 3-, and 5-year disease free survival rates were 83% ,49% and 28%, respectively. The 1-, 3-, and 5-year metastasis free survival rates were 84%,51% and 28%, respectively. There were significant influence on the prognosis of age, the state of food taken before treatment, the pain of chest and back, the disease region, the tumor length in x-ray, the maximuminfiltration depth in CT scan, the preliminary curative effect and the no operation in univariate analysis. The Cox multivariate model showed that age, the pain of chest and back, the disease region and the tumor length in X-ray were independent prognostic factors. In the operation group, 80,46 and 16 cases were followed up for at least 1-,3-,and 5-year, respectively. Follow-up rate was 100%. The 1-, 3-, and 5-year actuarial survival rates were 86% ,62% and 41%, respectively, with a median survival time of 47.8 months. Conclusion Three-dimensional conformal radiotherapy is one of the best radiation treatment regimen for early esophageal carcinoma.
10.Analysis of acute radiation injury in non-small cell lung cancer treated by three-dimensional conformal radiotherapy
Yanli CUI ; Shuchai ZHU ; Zhikun LIU ; Jingwei SU ; Juan LI ; Wenbin SHEN ; Yuxiang WANG
Chinese Journal of Radiological Medicine and Protection 2010;30(3):320-323
Objective To analyze the influencing factors with radiation induced injury of nonsmall cell lung cancer(NSCLC)treated by three-dimensional conformal radiotherapy,in order to supply he reference criteria for optimize the treatment planning of NSCLC, further to improve the local control rate and quality of life of NSCLC patitents.Method From Aug 2000 to Dec 2004,107 NSCLC patients received three-dimensional conformal radiotherapy were enrolled in this study.In all the patients,48 patients accepted three dimensional conformal radiotherapy(3D-CRT),the other 59 patients accepted conventional radiotherapy(CRT)before later-course of 3D-CRT.All of the patients received the prescription dose between 60-78 Gy and the median dose 66 Gy.Results In the 107 patients,the rate of radiation induced injury was 62.6%.and the rate of≥2 grade was 38.3%.23 cases were classified in grade 2,14 cases in grade 3,4 cases in grade 4.Univariate analysis showed chronic obstructive pulmonary disease,number of beams field,lung mean dose,lung V5-V40 were important influencing factors on radiation induced injury.Further more,lung mean dose,lung V20 and chronic obstructive lung disease were likely to be the independent factors of radiation induced injury by Logistic model.Conclusions lung mean dose,chronic obstructive lung disease and lung V20 were the independent influencing factors on irradiated induced injury.