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 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.

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 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.

Objective To compare the acute toxicities between two prospective, non-randomize phase Ⅱ trials on adjuvant radiochemotherapy of capecitabine with or without oxaliplatin in patients with stage Ⅱ and Ⅲ rectal cancer. Methods From March 2005 to November 2007,based on two fulfilled phase Ⅰ studies,two phase Ⅱ trials were launched respectively to further observe the tolerance and toxicity. In one tria1,118 patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT trial), with radio-therapy of DT50 Gy/25 F/5 wks to the pelvis, and capecitabine at a dose of 1600 mg/m2/d(d1-d14,3 weeks per cycle). In the other trial, 90 patients received concurrent oxaliplatin, capecitabine and radiothera-py(Cap-Oxa-CRT trial), with the same radiotherapy schedule, while oxaliplatin at a dose of 70 mg/m2(d1, d8) and capecitabine of 1300 mg/m2/d(d1-d14,3 weeks per cycle). Results There was no significant difference in the delay of radiotherapy (10.2% vs 6.7%, X2=0.80, P=0.460) or chemotherapy (9.3% vs 19.1%, X2=4.80,P=0.090) between Cap-CRT and Cap-Oxa-CRT trials. Grade 1-4 leukopenia,diar-rhea and nausea were the most common acute side-effects in the both trials, accounting for 70.2%, 65.9% and 42.3%, respectively. When comparing with Cap-CRT trial, Cap-Oxa-CRT trial had significantly more grade 1-4 non-hemotological toxicities, mainly in Gl,including nausea (68.9% vs 22.0%, X2=46.90, P= 0.000), diarrbea(76.7% vs 57.6%, X2=13.50, P=0.009), fatigne(47.8% vs 13.7%, X2=18.90,P= 0.000), hand-foot syndrome (14.4% vs 4.2%, X2=7.10, P=0.029), and inappetence (50.0% vs. 27.9%, X2 = 25.70, P=0.000), but not in hematological toxities of leukopenia, anemia or thrombocytope-nia. Of all the patients,grade 3 and grade 4 toxicities were diarrhea(24.0% and 1.0%),leukopenia(4.3% and 0.0%),radiation-induced dermatitis(3.8% and 0.0%),cramping abdominal pain(1.0% and 0.0%) and fatigue(0.5% and 0.0%). Only grade 3 and 4 diarrhea was significantly more in Cap-Oxa-CRT trial than in Cap-CBT trial(33.0% vs 18.6%, X2=5.90,P=0.023). Conclusions For patients with stage Ⅱ and Ⅲ rectal cancer,both the postoperative concurrent radiochemotherapy regimens are tolerable,though Cap-Oxa-CRT trial has more grade 3 and 4 diarrhea.

Objective To analyze the acute and late toxicities in patients with prostate cancer trea-ted with hypofractionated intensity-modulated radiotherapy (IMRT). Methods Between June 2006 and June 2008, 37 patients with prostate cancer were treated with hypofractionated IMRT. The clinical target vol-ume (CTV) was the prostate, seminal vesicles and pelvic lymph nodes in 24 patients, the prostate and semi-hal vesicles in 12, and only the tumor bed in 1. The dose per fraction was 2.3 - 2.8 Gy, with 2.7 Gy in 26 patients. The minimal dose was 62.5-75.0 Gy to the prostate and seminal vesicles, and 50 Gy to the pelvic lymph nodes. Results The median follow-up was 14 months. None of the patients experienced grade 4 a-cute gastro-intestinal (GI) toxicity. Grade 1, 2 and 3 acute GI toxicity occurred in 24.3%, 35.1% and 2.7% of the patients, respectively. The rectal V50>27% and V55>20% were highly significantly associat-ed with grade ≥1 acute GI toxicity. Grade 1,2 and 3 acute genitourinary (GU) toxicity occurred in 68%, 0% and 3% of the patients, respectively. The bladder V50> 10% was significantly associated with grade ≥1 acute GU toxicity. The incidence of late GI toxicity was low. No grade ≥3 late GI toxicity was observed. The incidence of late grade 1 and 2 GI toxicity was 24% and 5%, respectively. The rectal V65> 10% was highly significantly associated with grade ≥1 late GI toxicity. No late grade 4 GU toxicity was observed. The incidence of grade 1, 2 and 3 late GU toxicity was 49%, 11% and 3%, respectively. Grade ≥2 late GU toxicity was correlated with V40, V50 and mean dose of the bladder. Conclusions Acute and late toxicity of hypofractionated IMRT is acceptable in patients with prostate cancer.

Objective To analyze the clinical features and treatment outcomes of extranodal diffuse large B-cell lymphoma(DLBCL). Methods Ninety-nine consecutively diagnosed patients with extranodal DLBCL were reviewed. All patients were confirmed by a combination of morphologic and immunohistochemi-cal evaluation. The primary sites of extranodal DLBCL were the gastrointestine(n = 32) ,central nerve system (CNS)/testis(n=14) ,and other sites (n = 53). Results Extranodal DLBCL was characterized by a pre-dominance in old males,less frequency of B symptorns,a large proportion of stage Ⅰ-Ⅱ disease and low in-ternational prognostic factor(IP1) score. The 5-year overall survival(OS) rate for all patients was 78.9%. The corresponding OS rate was 82.5% for gastrointestinal origin, 37.0% for CNS and testis origin and 74.6% for other organ origin, respectively. On univariate analysis, performance status, IPI score and more than one extranedal site involvement were the prognostic predictors for 5-year OS. Conclusions Being a heterogeneous group of lymphomas, extranedal DLBCL has good prognosis except those derived from the CNS and testis.

Objective To evaluate the toxicities and long-term survival of a pilot study of radical surgery followed by concurrent capecitabine and radiotherapy for stage Ⅱ/Ⅲ rectal cancer patients.Methods From March 1,2005 to December 31,2007,131 pathologically proved stage Ⅱ and Ⅲ rectal cancer patients received radical surgery followed by chemoradiotherapy and adjuvant chemotherapy.Capecitabine was delivered daily in twice,for 2 weeks followed by a 2nd cycle after a rest of 7 days during radiotherapy,with the dosage of 1600 mg/m2/d.Three-dimensional conformal radiotherapy was encouraged to the dose of 50 Gy in 25 fractions,and Oxaliplatin/5-fluorouracil or leucovorin based adjuvant chemotherapy was recommended.Results Grade 3 +4 toxicities during concurrent chemoradiotherapy were observed in 28.2％ of patients.The follow-up rate was 93.9％.The 3-year overall survival (OS),locoregional-free survival and distant metastasis-free survival rates were 85.1％,96.7％ and 79.5％,respectively.Among the 31 patients with relapse,5 had loco-regional recurrence and 28 had distant metastasis.Univariate analysis indicated that patients with low and moderate-low differentiated adenocarcinoma,no adjuvant chemotherapy,stage ⅢC disease or positive lymph node ratio (LNR) more than 30％ had lower OS ( x2 =15.49,15.85,8.80 and 9.76,P ＝ 0.000,0.000,0.011 and 0.002 ).Patients with N2 disease had more loco-regional recurrence.Patients with stage ⅢC,without adjuvant chemotherapy,or LNR more than 30％ were at higher risk of distant metastasis ( x2 =6.51,11.57 and 9.70,P =0.034,0.001 and 0.002 ).However,patients who didn ' t receive adjuvant chemotherapy were likely to have low differentiated adenocarcinoma and T4 stage disease ( x2 =7.20,6.48,P =0.027,0.039).Conclusions After radical surgery and concurrent eapecitabine and radiotherapy for stage Ⅱ/Ⅲ rectal cancer patients,loco-regional recurrence rate is pretty low.Distant metastasis is the main treatment failure.

ObjectiveTo evaluate the long-term survival and treatment failure patterns for patients with stage Ⅰ adenocarcinoma in the lower rectum after local excision with or without adjuvant radiotherapy.MethodsFrom Jan.2000 to Dec.2008,Seventy-seven patients with rectal cancer received local excision.Among them,41 received adjuvant radiotherapy.Fifty-four patients were pathologically proven as T1,the other 23 as T2.Patients were classified into low-and high-risk groups according to tumor grade,the length of tumor,surgical margin,circumference ratio of tumor/rectum and T stage.Survival rates and prognostic factors were estimated by Kaplan-Meier method,and comparisons were made by the Logrank test.Results Fourty patients were followed up more than 5 years.The 5-year locoregional recurrence-free survival (LRFS)and overall survival (OS)rates were 83％and 82％for the whole group.There were no significant differences in 5-year LRFS and OS rates in low-risk patients between local excision alone and local excision followed by adjuvant radiotherapy ( 86％ ∶ 83％,x2 =0.29,P =0.588 and 100％ ∶ 100％,x2 =1.50,P =0.221 ).In high-risk patients,the 5-year LRFS were similar (80％ ∶ 82％,x2 =0.27,P =0.600),but the OS were significantly different (92％∶ 66％,x2 =4.64,P =0.031 ) between local excision alone and local excision followed by adjuvant radiotherapy.By univariate analysis,large tumor size,positive margin,poor differentiation,tumor located less than 5 cm from anal verge and pT2 stage were poor prognostic factors for OS.The overall relapse rate for the whole group was 29％,and 70％ of them were locoregional relapse.The 5-year OS for patients treated with radical salvage surgery after local relapse was 69％.Conclusions For stage Ⅰ lower-sited rectal cancer,low-risk patients can achieve good result after local excision alone.The role of adjuvant radiotherapy in high-risk patients needs further evaluation.Local relapse is the main cause of failure,and salvage surgery after local relapse can provide long-term survival.