AIM:To observe the effect of plumbagin on the mRNA and protein expression of nicotinamide ade -nine dinucleotidephosphate oxidase 4 ( Nox4 ) , reactive oxygen species ( ROS ) level and protein expression of α-smooth muscle actin (α-SMA) in the HSC-LX2 cells stimulated with transforming growth factor β1 (TGF-β1) in vitro.METH-ODS:HSC-LX2 cells were cultured in vitro and divided into blank group, model group, high-, medium-and low-dose (2, 1.5 and 1 μmol/L) plumbagin groups .After incubated with each drug for 72 h, the mRNA expression of Nox4 was detec-ted by RT-PCR.ROS levels were tested by in situ loading probe method.The protein contents of Nox4 and α-SMA were measured by Western blot .RESULTS:Compared with model group , after treated with plumbagin for 72 h, the mRNA ex-pression of Nox4, ROS level and α-SMA protein were significantly decreased in high-and medium-dose plumbagin groups (P<0.01).CONCLUSION:Plumbagin inhibits the activation of HSC-LX2 cells via decreasing the expression of Nox4, thus decreasing ROS levels .

Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer.Methods Between January 2009 and December 2014,167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital.After surgery,12 patients were treated with external beam radiotherapy,56 patients with chemoradiotherapy (CRT),and 17 patients with chemotherapy.Overall survival (OS),local recurrence,and toxicities were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％.The median OS time was 10.3 months,and the 2-year OS rate was 22％.The median progression-fiee survival (PFS) time was 6.3 months,and the 2-year PFS rate was 9.9％.The cancer-specific survival (CSS) time was 11.2 months,and the 2-year CSS rate was 23.6％.In the patients treated with IORT alone at doses of＜15 Gy,15 Gy and＞15 Gy,the median OS times were 6.2 months vs.9.1 months vs.22.2 months,and the 1-year OS rates were 10.0％ vs.39.6％ vs.74.4％ (P=0.000).Among the patients receiving postoperative adjuvant therapy,those treated with IORT+CRT had the best survival,with a median OS time of 11.6 months (P=0.033).The univariate analysis showed that IORT dose (P =0.000),tumor size (P =0.006),and IORT applicator diameter (P =0.007) were prognostic factors.The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors.Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer.After protecting surrounding organs,increasing the IORT dose can improve the survival.IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities.

Background and purpose: Cancer stem cells (CSCs) isolated from human glioma are cancer-initiating cells and sources of tumor recurrence in brain tumors. The poor outcome of glioma is because cancer stem cells can not be eradicated. This article was aimed to explore the resistance of CSCs to chemotherapeutic agents and expression of drug-resistance enzymes in glioma cancer stem cells. Methods: Cancer stem cells from U251 were isolated by using magnetic sorting. The proliferation inhibitory effects of Vumon-26 (Vm-26), bischloronitrosourea (BCNU) and diamminedichloroplatinum (DDP) on U251-CSC and U251 were examined by drug sensitivity testing in vitro (MTT assay) and the apoptosis rates were observed by flow cytometry. Western blot was performed to examine the expression of three drug-resistance enzymes including LRP, MGMT and Topo Ⅱα. Results: Chemotherapeutic agents had a more obvious inhibitory effect on U251 than U251-CSC, as well as higher apoptosis rates. LRP, MGMT and Topo Ⅱα expression were significantly higher in U251-CSC as compared to U251, Conclusion: Glioma stem cells showed strong capability of tumor's resistance to chemotherapeutic agents including Vm-26, BCNU and DDP. This resistance is probably contributed by the CD133 positive cell with higher expression of on LRP, MGMT and Topo Ⅱα.

Objective To investigate the treatment outcome and failure in patients with primary mediastinal large B-cell lymphoma(PMBL). Methods Between Jan. 1992 and Oct. 2006, a total of 46 patients with pathologically confirmed PMBL were reviewed, including 14 with Ann Arbor Stage I disease, 23 with Stage Ⅱ disease,3 with Stage Ⅲ disease and 6 with Stage Ⅳ disease. Stage Ⅰ+Ⅱ disease was present in 80% of the patients. All patients were treated with chemotherapy ,and 29 also received radiotherapy. Twenty-seven patients(59%) were treated with first generation regimen(CHOP),9(20%) with third generation regimens (MACOP-B, ProMACE/CytaBOM, m-BACOD, or ProMACE-MOPP), and 10(22%) with high-dose chemotherapy (HDCT/APBSCT). Rituximab was administered to 16 patients (35%). For most patients who received radiotherapy,an involved field was used with a median dose of 45 Gy in 23 fractions.Results The rate of complete remission, partial remission and progression disease was 41%, 30% and 24% ,respectively. The 5-year overall survival rate(OS) for all patients was 35%. The 2- and 5-year OS was 79% and 63% for stage Ⅰ+Ⅱ and 51% and 0 for stage Ⅲ+Ⅳ ,respectively(X2=4.35 ,P=0. 037).The 2-year progression free survival rate was 63 % and 11%, respectively (X2=17.77, P=0.1300). The 5-year OS was 80% for the patients with CR,50% for those with PR,and 0 for those with progression disease(X2= 19.58 ,P=0.003 ). With a median follow-up of 22 months, progression disease and relapse occurred in 19 patients. Conclusions Survival of patients with advanced stage PMBL is poor. Further studies areneeded to confirm the optimal treatment. Radiotherapy often plays a pivotal role in local control.

Objective To investigate the efficacy and toxicity of postmastectomy hypofractionation radiotherapy in patients with high-risk breast cancer. Methods Postmastectomy radiation of 43.5 Gy in 15 fractions of 2.9 Gy over 3 weeks was delivered to 38 patients with breast cancer. The incidence of acute radi-ation toxicity and lecoregional recurrence was evaluated. Results With a median follow up of 13 months, all patients were alive. No patient had locoregional recurrence within radiation field. Five (13%) had dis-tant metastases. Five (13%) developed grade 3 radiation dermatitis at 2 to 3 weeks after the course of radia-tion. Three (8%) had grade 2 radiation pneumonitis. Conclusions Hypofractionation radiation of 43.5 Gy in 15 fractions of 2.9 Gy over 3 weeks is effective in the near time for patients with high-risk breast cancer after mastectomy, and the acute toxicities are tolerable.

Objective To evaluate the clinical features, treatment outcome, and prognostic factors in patients with primary Waldeyer’ s ring diffuse large B?cell lymphoma (WR?DLBCL). Methods This study included 200 patients with a confirmed diagnosis of primary WR?DLBCL admitted to our hospital from 2000 to 2013, who consisted of 50 stage I patients, 125 stage II patients, and 25 stage III?IV patients. Most patients received 4?6 cycles of CHOP or CHOP?based chemotherapy with or without involved field radiotherapy (Waldeyer′s ring+cervical lymph node region). Results The 5?year sample size was 71. The 5?year overall survival (OS), progression?free survival (PFS), and locoregional control (LRC) rates for the whole group were 78%, 72%, and 87%, respectively. In the 175 early stage patients, chemoradiotherapy resulted in significantly higher OS, PFS, and LRC than chemotherapy alone (86% vs. 70%, P= 0?? 001;84% vs. 58%, P= 0?? 000;97% vs. 66%, P= 0?? 000). Univariate analysis showed that age, tumor size, stage, lactate dehydrogenase level, and International Prognostic Index were prognostic factors for OS, PFS, and LRC ( P= 0?? 000?0?? 036), while the prognostic factors for PFS also included Eastern Cooperative Oncology Group score and cervical nodal involvement (P= 0?? 018). Multivariate analysis showed that age and stage were prognostic factors for OS and LRC (P= 0?? 003?0?? 022), and age was the prognostic factor for PFS (P= 0?? 000). Conclusions WR?DLBCL has distinct clinical features and favorable prognoses. For early stage patients, combined?modality therapy results in significantly higher OS, PFS, and LRC.

Objective To reduce the radiation dose to the hematopoietic bone marrow (hBM) and acute hematologic toxicity (HT) in patients with rectal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods The previously untreated patients with rectal cancer were enrolled in a prospective study.Pelvic magnetic resonance imaging ( MRI) was used to determine and delineate the distribution of hBM,and dose limitations were set (V5<95%,V10<90%,V20<80%,V30<65%).The neoadjuvant therapeutic regimen included concurrent IMRT (95% PTV 50 Gy/25 fractions,2 Gy/fractions),oxaliplatin 50 mg/m2 , qw,and capecitabine 1650 mg/m2 ,1 fractions/d (twice a day during radiotherapy).Results A total of 35 patients were enrolled and completed the therapeutic regimen.The incidence of grade 2-4 HT was 31.4%;among these patients, 9 ( 26%) experienced leucopenia, 6 ( 17%) experienced neutropenia, 1 ( 3%) experienced erythropenia,and 1(3%) experienced thrombocytopenia.No patients experienced grade ≥3 anemia.The multivariate logistic linear regression analysis showed that hBM-V5 was significantly correlated with the lowest counts of leukocytes ( P=0.005),neutrophils ( P=0.002),and platelets ( P=0.017).Conclusions The radiation dose to the hBM in the pelvis on MRI is significantly correlated with the incidence and severity of acute HT in patients with rectal cancer undergoing neoadjuvant concurrent chemoradiotherapy.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT01863420.

Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity?modulated radiation therapy ( IMRT) plans and volumetric modulated arc therapy ( VMAT) and to identify the best IMRT plan for patients with primary mediastinal B?cell lymphoma ( PMBCL) . Methods A total of 16 patients ( 8 males and 8 females) with early?stage ( Ann?Arbor stageⅠ) PMBCL were enrolled in this study,with doses of 45 Gy for primary gross tumor volume ( PGTV) and 40 Gy for planning target volume (PTV).Four plans were designed for each patient,consisting of static IMRT (5F?IMRT,7F?IMRT,9F?IMRT) and VMAT,and the target dosimetric distribution,normal tissue radiation dose,and efficiency of each plan were evaluated. The difference of dose was analyzed by analysis of variance. Results The mean conformity index ( CI) and homogeneity index ( HI) for PGTV in 5F?,7F?,9F?IMRT and VMAT were 1. 01 and 1. 10, 1. 01 and 1. 10, 1. 01 and 1. 10, and 1. 01 and 1. 11 ( P= 0. 963 and 0. 843) ,respectively,while these two indices for PTV were 1. 04 and 1. 22,1. 03 and 1. 19,1. 03 and 1. 17, and 1. 08 and 1. 14( P=0. 964 and 0. 969) ,respectively. The parameters of volume and dose were similar on normal tissue ( P= 0. 192?1. 000 ) . The treatment time and number of monitor units in 9F?IMRT were significantly higher than those in other static IMRT plans and VMAT ( P=0. 000,0. 000) ,and among these plans,VMAT had the lowest number of monitor units ( 13 345. 0 MU) and the shortest treatment time ( 5. 9 min) . Conclusions The target volume coverage of 7F?and 9F?IMRT is better than that of 5F?IMRT and VMAT.For early?stage PMBCL,VMAT is not superior to IMRT in terms of dosimetry,especially with a larger area of low?dose radiation to the breast,but it is highly efficient in practice.

Objective To analyze clinical characteristics of diffuse large B-cell lymphonma(DL BCL) of Waldeyer's ring(WR-DLBCL) comparing with those of nodal DLBCL(N-DLBCL).Methods 181 patients consecutively diagnosed as primary WR-DLBCL(80) or N-DLBCL(101) were retrospectively reviewed.According to Ann Arbor staging system,57,83,26 and 15 patients had stage Ⅰ ,Ⅱ ,Ⅲ and Ⅳ disease,respectively.Patients with stageⅠ-Ⅱ disease were treated with chemotherapy and radiotherapy, whereas patients with stage Ⅲ-Ⅳ disease received primary chemotherapy. Results Comparing with N-DL BCL,pafients with WR-DLBCL presented with more stage Ⅱdiseases,more frequent involvement of adjacent organs and tissues,less B-symptoms,less involvement of spleen and lower lactate dehydrogenase (LDH) and β2-microglobulin(β2M) level.The 5-year overall survival(OS) rate of all patients was 76% for WR-DLBCL and 56% for N-DLBCL(x2 =2.43,P=0.119) ,respectively.The corresponding OS rate for stage Ⅰ and Ⅱ diseases was 78% for WR-DLBCL and 58% for N-DLBCL(X2 = 2.76,P =0.097),respectively.On univa riate analysis,elevated LDH,IPI and elevated β2 M were prognostic predictors for WR-DLBCL patients, whereas elevated β2 M,bulky tumor and IPI were associated with poor OS for N-DLBCL patients.On multiva riate analysis,elevated LDH and β2M were prognostic predictors for all patients. Conclusions Comparing with N-DLBCL,WR-DLBCL represents distinct clinical features and prognosis.

Objective The aim of this study was to investigate whether the addition of neoadjuvant chemoradiotherapy ( NACRT ) to surgery can improve outcomes better than neoadjuvant chemotherapy in terms of rate of R0 resection, pathological complete response ( pCR ) and side effects. Methods This exploratory study included primary gastric adenocarcinoma patients staged as clinical T4N0 or anyTN1-3. Intensity modulated radiotherapy was delivered of 40 to 50 Gy in 22 to 25 fractions,5 days/week.Concurrent chemotherapy regimens included S-1 or Capecitabine or a combination of Paclitaxel plus Carboplatin.Results Eleven eligible patients were enrolled. R0 and R2 resections were performed in 9 ( 9/11) and 1 patients, respectively.Peritoneal metastasis was found in 1 case during exploratory laparotomy.The pCR was observed in 1 patient with R0 resection ( 1/10 ) . Ten cases completed radiotherapy and 8 cases completed chemotherapy. Nausea ( 3/11 ) , vomit ( 2/11 ) and anorexia ( 2/11 ) were the most common Grade 3 toxicities. Conclusions NACRT showed an acceptable toxicity and promising activity in locally advanced gastric adenocarcinoma.