2.Bioinformatics analysis of VP1 protein of coxsackievirus A6
Hongbo LIU ; Guangfei YANG ; Weilin OU ; Guanxin SHEN
Chinese Journal of Immunology 2016;32(4):536-541
Objective:To predict the basic physicochemical properties ,structure and function ,and linear B-cell epitopes of the capsid protein VP1 of coxsackievirus A6(CVA6).Methods: The amino acid sequence of the CVA6 VP1 was analyzed using Bioedit software and various online tools including SubLoc ,TargetP and the others from ExPASy Bioinformatics Resource Portal.Results: The CVA6 VP1 protein was a hydrophilic protein with a relative molecular weight of 33.6 kD and an isoelectric point of 7.92.This protein containsed 24 phosphorylation sites , but no signal peptide , transmembrane domains and possible fatty acylation sites.Its secondary structure was characterized by the richest random coils , and 48.52 percent of its amino acid residues exposed at the solution inter-face.Epitope prediction by Bepipred showed a number of potential B cell epitopes in the protein ,the highest antigenicity index among them located in the region of amino acids residue 155-165.Conclusion:The basic physicochemical properties ,structure and function characteristics ,and potential linear B-cell epitopes of CVA 6 VP1 were successfully predicted , which laid foundations for the further study on the protein and the preparation of vaccines and immunological diagnostic reagents for CVA 6 infection.
3.Increase of hypoxia level induced by bevacizumab decreases the combined effect of bevacizumab and irradiation in CNI-H1441 xenografts in mice
Guangfei OU ; Itasaka SATOSHI ; Lihua ZENG ; Shibuya KEIKO ; Junlin YI ; Harada HIROSHI ; Hiraoka MASAHIRO
Chinese Journal of Radiation Oncology 2010;19(4):358-363
Objective To evaluate the impact of the hypoxia induced by bevacizumab on the antitumor effect in combining with irradiation in CNI-H441 xenografts in mice. Methods Bevacizumab of 5 mg/kg mouse for groups of control, bevacizumab alone, irradiation alone, earlier combination (EC), and later combination (LC) were initially injected peritoneally. Single irradiation of 14 Gy (122Sc γ-ray) was given at the 4th hour for the group of irradiation alone, 24th hour for EC group, and 72nd hour for LC group after the initial injection. Tumor hypoxia, micro vessels density and permeability of tumor vasculature,pathological responses, apoptosis, and tumor growth delay curve were evaluated after using bevacizumab and/or irradiation. Results Although it was lower than the control at the 24 hr after using bevacizumab (3. 1 × 106: 6.1 × 106 ;t = - 1.73 ,P > 0. 05), the HIF-1α rapidly increased to 3 - 4 times and 2 - 3 times of the control at day 3 (7.4 × 106: 20. 4 × 106; t = 2. 36, P < 0. 05) and lasted until day 10, which was consistent with the changes of tumor function vessels count. The count of residual micro vessel density count in LC group was higher than that in groups of EC and irradiation at day 3 after irradiation (9. 33: 3. 17;t =- 2. 43, P < 0. 05). The apoptotic count of tumor cells was lower in LC group than that in EC group (23.33: 43.83; t= 2.54, P< 0.05, at day 3 after radiation). Tumor growth delay time of LC groupwas shorter than that of EC groups (10. 5 days vs. 23. 0 days , t = 2. 67 , P < 0. 05) . Conclusions Hypoxia level induced by bevacizumab decreases the antitumor effect in later combination of bevacizumab and irradiaion. It shows a time window that determines whether the combination of bevacizumab and irradiation will be benefit or diverse.
4.Association of single nucleotide polymorphisms with radiation-induced esophagitis
Li ZHANG ; Luhua WANG ; Ming YANG ; Wei JI ; Lujun ZHAO ; Weizhi YANG ; Zongmei ZHOU ; Guangfei OU ; Dongxin LIN
Chinese Journal of Radiation Oncology 2008;17(3):175-179
Objective To evaluate the relationship between single nucleotide polymorphism(SNP) of candidate genes and radiation-induced esophagitis (RIE) in patients with lung cancer. Methods Between Jan. 2004 and Aug. 2006,170 patients with pathologically diagnosed lung cancer were enrolled in this study. The total target dose was 45-70 Gy( median 60 Gy). One hundred and thirty-two patients were treated with three-dimensional conformal radiotherapy(3DCRT) and 38 with two-dimensional radiotherapy(2DRT).Forty-one patients received radiotherapy alone, 78 received sequential chemoradiotherapy and 51 received concurrent chemoradiotherapy. Thirty-seven SNPs in 20 DNA repair genes were analyzed by using PCR-based restrieted fragment length polymorphism(RFLP). These genes were apoptosis and inflammatory cytoking genes including ATM, ERCC1, XRCC3, XRCC1, XPD, XPC, XPG, NBS1, STK15, ZNF350, ADPRT,TP53, FAS, FASL, CYP2D6 * 4, CASPASE8, COX2,TGF-β, CD14 and ACE. The endpoint was grade ≥2 R I E. Results Forty of the 170 patients developed grade ≥2 R I E, including 36 in grade 2 and 4 in grade 3. Univariate analysis revealed that radiation technique and concurrent chemoradiotherapy were statistically significant relatives to the incidence of R I E (P = 0. 032,0.049) , and both of them had the trend associating with the esophagitis( P = 0.072,0. 094 ). An increased incidence of esophagitis was observed associating with the TGF-β1-509T and XPD 751 Lys/Lys genotypes ( χ2 = 5.65, P = 0.017 ;χ2 = 3.84, P = 0. 048 )in multivariate analysis. Conclusions Genetic polymorphisms in TGF-β1 gene and XPD gene have a significant association with radiation-induced esophagitis.
5.Comparison of postoperative three-dimensional conformal radiotherapy with conventional radiotherapy for non-small cell lung cancer
Honghai DAI ; Wei JI ; Lühua WANG ; Guangfei OU ; Jun LIANG ; Qinfu FENG ; Zefen XIAO ; Dongfu CHEN ; Jima Lü ; Zongmei ZHOU ; Hongxing ZHANG ; Weibo YIN
Chinese Journal of Radiation Oncology 2009;18(2):96-100
Objective To compare postoperative three-dimensional conformal radiotherapy (3DCRT) and conventional radiotherapy (CR) in patients with non-small-cell lung cancer (NSCLC). Methods From Nov. 2002 to Mar. 2006,162 patients with stage ⅠB~ⅢB NSCLC receiving postoperative radiotherapy in our department were restrospetcively analyzed. Among them,86 received 3DCRT and 76 re-ceived CR. The survival outcome, pattern of failure and treatment-related side effects in both groups were an-alyzed. Results The median follow-up was 29.4 months in the 3DCRT group and 24 months in the CR group. The 1-,2- and 3-year local-regional free survival was 97.5% ,83.2% and 83.2% in 3DCRT group, and 84.3% ,76.0% and 65.6% in CR group(χ2= 5.46, P = 0.019), respectively. No statistically signifi-cant difference was found in the overall survival, disease-free survival or distant metastasis-free survival be-tween the two groups. The local-regional failure rate was statistically different between the two groups (14.5% vs 33.3% ,χ2 =7.70,P =0.006). The incidence of distant metastasis in the two groups was simi-lar. Radiation pneumonitis of NCI CTC grade 2-3 occurred in 10 patients(11.6%)in 3DCRT group and 18 (23.7%) in CR group,which was statistically different(χ2 =4.10,P=0.043). Conclusions Postopera-tive 3DCRT for NSCLC provides a better local-regional control and lower incidence of radiation pneumonitis compared with CR.
6.Treatment results of radiotherapy for medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer
Li ZHANG ; Lvhua WANG ; Hongxing ZHANG ; Dongfu CHEN ; Zefen XIAO ; Mei WANG ; Qinfu FENG ; Jun LIANG ; Zongmei ZHOU ; Guangfei OU ; Jima LV ; Weibo YIN
Chinese Journal of Radiation Oncology 2008;17(2):101-105
Objective To retrospectively analyze treatment results of radiotherapy for medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer. Methods Between Jan.2000 and Dec.2005,fifty-eight such patients were enrolled into the database analysis,including 37 with clinical stage Ⅰ and 21 with stage Ⅱ disease.Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy.Fortythree patients were treated with 3-D conformal radiotherapy(3D-CRT)and 15 with conventional radiotherapy.Results The 1-,2-and 3- year overall survival rates were 85%,54%and 30%,and the median survival time was 26.2 months for the whole group.The corresponding figures were 88%,60%,36%and 30.8 months for cancer-specific survival:84%,64%,31%and 30.8 months for Stage Ⅰ disease;81%,47%,28%and 18.8 months for Stage Ⅱ disease;95%,57%,33%and 30.8 months for 3D-CRT group and 53%,44%,24%and 15.3 months for conventional radiotherapy group.By logrank test,tumor volume,pneumonitis of Grade Ⅱ or higher and weight loSS more than 5%showed statistically significant impact on overall survival.Tumor volume was the only independent prognostic factor in Cox muhivariable regression.Pneumonitis and esophagitis of Grade Ⅱ or higher were 16%and 2%,respectively.Age and lung function before treatment had a significant relationship with pneumonitis.Failure included the local recurrence(33%)and distant metastasis(21%).There was no difference between the treatment modalities and failure sites. Conclusions For medically inoperable early stage non-small cell lung cancer patients,tumor volume is the most important prognostic factor for overall survival.The conformal radiotherapy marginally improves the survival.The age and pulmonary function are related to the incidence of treatment induced pneumonitis.
7.Variation of gross tumor volume and clinical target volume definition for lung cancer
Jun LIANG ; Minghui LI ; Dongfu CHEN ; Jima Lü ; Guangfei OU ; Zhouguang HUI ; Guishan FU ; Zhong ZHANG ; Rong ZHENG ; Jianrong DAI ; Lühua WANG
Chinese Journal of Radiation Oncology 2011;20(4):282-285
Objective To study the variation of gross tumor volume (GTV) and clinical target volume (CTV) definition for lung cancer between different doctors.Methods Ten lung cancer patients with PET-CT simulation were selected from January 2008 to December 2009.GTV and CTV of these patients were defined by four professors or associate professors of radiotherapy independently.Results The mean ratios of largest to smallest GTV and CTV were 1.66 and 1.65, respectively.The mean coefficients of variation for GTV and CTV were 0.20 and 0.17, respectively.System errors of CTV definition in three dimension were less than 5 mm, which was the largest in inferior and superior (0.48 cm,0.37 cm,0.32 cm;F=0.40,0.60,0.15,P=0.755,0.618,0.928).Conclusions The variation of GTV and CTV definition for lung cancer between different doctors exist.The mean ratios of largest to smallest GTV and CTV were less than 1.7.The variation was in hilar and mediastinum lymphanode regions.System error of CTV definition was the largest (<5 mm) in cranio-caudal direction.
8.Efficacy of three-dimensional conformal radiotherapy for 132 patients with esophageal carcinoma
Jie JIANG ; Qifeng WANG ; Zefen XIAO ; Luhua WANG ; Dongfu CHEN ; Qinfu FENG ; Zongmei ZHOU ; Jima LV ; Guangfei OU ; Jun LIANG ; Weibo YIN
Chinese Journal of Radiation Oncology 2009;18(1):47-51
Objective To evaluate the efficacy of three-dimensional conformal radiation therapy (3DCRT) for esophageal carcinoma and identify prognostic factors in this patient group.Methods From May 2002 to Jun 2005,132 patients with unresectable or inoperable esophageal cancer were treated with 3DCRT in our hospital.Their chnical data were analyzed retrospectively.ResultsThe 1-and 2-year local control rates was 65.4% and 52.1% in the whole group,respectively.The overall 1-and 2-year survival rate was 50.7% and 32.2% ,respectively.The median survival time was 13 months.The 1-and 2-year survival rate was 56.7%and 36.7% in stageⅠ + Ⅲ ,respectively,with 35.2% and 14.7% in stage IV.The median survival time were 15 months and 9 months for stage Ⅰ +Ⅲ and Ⅳ,respectively(x2 = 8.17,P = 0.004). Of patients with stage Ⅰ + Ⅲ disease who were absent of perforation sign before radiotherapy,with lesion length less than 8.0 cm and whole course given by 3DCRT,the 1-and 2-year survival rate was 73.0% and 49.9%,respectively.Univariate analysis revealed that condition of alimentation,absence of perforation sign, short lesion length,early TNM stage were associated with good survival.Multivariate analysis confirmed that absence of perforation sign and lesion length were independent prognostic factors for survival. Conclusions 3DCRT is effective for esophageal carcinomas in terms of survival and local control.Further improvement could be achieved with muhi-modality treatment.Absence of perforation sign and lesion length are independ ent prognostic factors for survival.
9.A Retrospective Study for the Limited-stage Small Cell Lung Cancer Patients with Combined Modality Treatment:An Analysis of 234 Patients
Zongmei ZHOU ; Dongfu CHEN ; LvHua WANG ; Jun LIANG ; Kai WANG ; Shiping ZHANG ; Zefen XIAO ; Hongxin ZHANG ; Qinfu FENG ; Guangfei OU ; Xiangru ZHANG ; Weibo YIN
Journal of Medical Research 2006;0(05):-
Objective To evaluate the treatment effects of chemotherapy comparing with chemotherapy and radiotherapy in the limited-stage small cell lung cancer (SCLC). Methods 234 patients were cyto-pathologically diagnosed and staged as limited small cell lung cancer. The patients were treated with combined chemotherapy and radiotherapy,in which 22 cases were treated by alone chemotherapy (C),39 patients by chemotherapy plus radiotherapy(C+R),and 173 cases by combined chemotherapy and radiotherapy + chemotherapy (C+R+C). The chemotherapy regimen included CE (or PE),CAP or CAV for 4~6 cycles. Irradiation treatment covering the primary tumor,the ipsilateral hilar nodes and mediastinum was delivered once daily with 6 megavoltage X-ray beam to a median irradiation does of 56 Gy being given in 5~6 weeks. Results The 1-,2-,3-,and 5-year overall survival rates were 76.5%,38.2%,25.3%,15.6% respectively,and the median survival time (MST) was 19 months. There was a significantly difference on the survival rate between C+R+C group and C+R group or C group (P
10.Factors predicting radiation toxicity in the treatment of three-dimensional conformal radiotherapy for lung cancer.
Yingjie WANG ; Lvhua WANG ; Qinfu FENG ; Dongfu CHEN ; Hongxing ZHANG ; Zefen XIAO ; Zongmei ZHOU ; Guangfei OU ; Lujun ZHAO ; Zhong ZHANG ; Ke ZHANG ; Weibo YIN
Chinese Journal of Lung Cancer 2005;8(5):454-458
BACKGROUNDThe lung and esophagus are always damaged during radiation on thoracic tumors to a certain extent. This study is to report the incidence of radiation pneumonitis and radiation esophagitis and to analyze the factors as predictors of radiation toxicity in the treatment of three-dimensional conformal radiotherapy (3DCRT) for lung cancer.
METHODSBetween March 1999 and September 2003, 112 lung cancer patients treated with 3DCRT were reviewed at this Hospital. This population consisted of 87 men and 25 women, including 97 cases of non-small cell lung cancer and 15 of small cell lung cancer. The median age was 64 years old. Radiotherapy was delivered at 2Gy fraction, 5 fractions per week. The median total dose was 60Gy.
RESULTSGrade 2 or more acute radiation pneumonitis developed in 7.1% (8/112) of patients while grade 2 or more late radiation pneumonitis appeared in 1.8% (2/112) of patients. Acute radiation esophagitis was observed in 8.9% (10/112) of patients with grade 2. No clinical and physical factor was relative to acute radiation pneumonitis by univariate and multivariate analysis. In the entire population, the univariate analysis revealed that many parameters (pre-treatment weight loss more than 5%, chemotherapy and concurrent chemotherapy) were significantly associated with acute radiation esophagitis. Multivariate analysis revealed that pre-treatment weight loss more than 5% was the most important risk factor for acute radiation esophagitis (P= 0.016).
CONCLUSIONSNo clinical and physical factor is relative to acute radiation pneumonitis and pre-treatment weight loss more than 5% is the most important risk factor for acute radiation esophagitis in this study.