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Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.
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Objective@#To evaluate the safety and efficacy of helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique in the treatment of unresectable biliary tract cancers.@*Methods@#The data of 23 patients with unresectable biliary tract cancer who received tomotherapy-based hypofractionated radiotherapy at Comprehensive Cancer Centre of Drum Tower Hospital,the Affiliated Drum Tower Clinical College of Nanjing Medical University between February 2015 and October 2017 were analyzed. There were 10 males and 13 females, aged from 40 to 85 years(median:58 years). Pathological type included intrahepatic cholangiocarcinomas(n=11), gallbladder cancers(n=6),extrahepatic cholangiocarcinomas(n=6). The irradiated sites covered primary tumors and areas of local invasion,including metastatic lymph nodes which were confined to the abdominal or retroperitoneal space. Dose escalation was achieved using simultaneously integrated boost(SIB) technique, and simultaneous integrated protection(SIP)technique was used to protect gastrointestinal tracts and other adjacent organs. Cox regression modal and Kaplan-Meier analysis were used to analyze the associations between patients′ characteristics and overall survival(OS).@*Results@#The median total radiation dose was 54 Gy(range: 28-72 Gy)and median biologically effective dose(BED)was 74.4 Gy(range: 37.8-115.2 Gy).The median planning target volume(PTV)was 445.79 cm3(range:126.02-950.12 cm3). Based on the various PTV,patients received 2.4-6.0 Gy/fraction with 8-28 fractions. The local control rate was 65.2% and the median OS was 11.3 months(range:2.1-31.9 months).The most common cause of death was out-field failure and only 3 patients died of in-field failures. The longest survival was 31.9 months. BED≥70 Gy significantly improved OS,compared to BED<70 Gy(16.8 months vs.5.1 months)(HR=0.146, 95%CI:0.028-0.762, P=0.022). No patients developed grade ≥4 toxicities.@*Conclusions@#Helical tomotherapy-based hypofractionated radiotherapy is effective and well tolerated for patients with unresectable biliary tract cancer. The dose escalation with higher BED could improve the survival for such patients.
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Objective Based on the previous research that the ethanolic extract from traditional Chinese medicine fructus forsythiae (Lianqiao) can obviously inhibit cancer cells in vitro, the article aimed to investigate the anti-proliferation effects of dammar-24-ene-3β-acetate-20S-ol (DM) extracted from fructus forsythiae on gastric cancer cells and its mechanism.Methods MTT assay was used to assess the anti-proliferation effects of DM on gastric cancer cells including SGC-7901, BGC-823, and MKN-45 in vitro.There were MKN-45 control group and its low dose and high dose groups, BGC-823 control group and its low dose and high dose groups, SGC-7901 control group and its low dose and high dose groups in the experiment.Flow cytometry was used to analyze the cell apoptosis rate.Cellquest software was used to analyze the results and record the ratio of cells at different cycles.DCFH-DA probe was applied to detect the ROS levels of blank control group, docetaxol group and DM group.The reaction system of microtubule assembly test was set with 10?mol/L docetaxol, 50 or 100 μmol/L DM final density and no medicine in blank control group.The readings of UV spectrophotometer were recorded.Microtubule assembly assay and microtubule immunofluorescence staining were applied to investigate the effects of DM on microtubule system.Results The inhibition ratio of 50 μg/L DM on the proliferation three gastric cell lines were all above 80%, with IC50s of MKN-45 11.72±1.35 μg/mL, BGC-823 17.19±0.82 μg/mL, SGC-7901 7.55±0.79 μg/mL.8 days′ low density culturing at 48 hours after 2 μg/mL DM treatment, compared with control group, the number of cell clones significantly reduced without much change in clone size, while 48 hours after 10 μg/mL DM treatment, besides a few clones of BGC-823, there were just several megascopic clones of SGC-7901 and MKN-45.In comparison with apoptotic cell ratio in MKN-45 control group[(21.1±2.5)%], its low dose group and high dose group resulted in significant rise of apoptotic cell ratio[(25.1±1.3)% and (55.2±2.3)%] (P0.05).In comparison with MKN-45 control group, the ratio of cells at S phase decreased in its low dose group[(14.5±2.7)% vs (12.3±3.3)%,P>0.05].In comparison with BGC-823 control group, the ratio of cells at S phase increased in its low dose group[(12.2±5.4)% vs (20.2±2.1)%,P<0.05].In comparison with SGC-7901 control group, the ratio of cells at S phase increased in its low dose group[(21.5±3.8)% vs (31.3±2.6)%,P<0.05].From the detection of intracellular active oxygen after DM treatment, dose-dependent ROS level increased in all three cell lines 48 hours after 10μg/mL and 50μg/mL DM treatment.From the results of microtubule immunofluorescence staining, 48 hours after the treatment of IC50 docetaxol and 10μg/mL DM, the fluorescence signals were in local concentration and disorder.Conclusion Dammar-24-ene-3β-acetate-20S-ol demonstrated anti-proliferation effects due to the apoptosis induced by cell cycle arrest at S phase.
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Background and purpose:The growth,metastasis,relapse and the prognosis of tumor are correlated with tumor angiogenesis.Therefore,target to angiogenesis and antiangiogenic therapy has become one of the hot points in cancer research field.Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration.This is metronomic chemotherapy or antiangiogenic chemotherapy.Traditional Chinese medicine has an effect on tumor control.In recent years,we discovered that some traditional Chinese medicine have an antiangiogenic effect.This experiment aimed to study the antiangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection(CRSFI) in vitro and in vivo. Methods :We used MTT method to observe the influence of oxaliplatin and composite radix sophora flavescentis injection on human umbilical vein endothelial cells(HUVEC) or LoVo proliferation.The influence of oxaliplatin and composite radix sophora flavescentis injection on HUVEC migration was evaluated by transwell.Chick embryo chorioallantoic membrane(CAM)model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results :The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC.Oxaliplatin(2 ?g/ml) and composite radix sophora flavescentis Injection(25 ?l/ml) could inhibit the prolifetation of HUVEC;the rate of inhibition were 31.6%,32.1% respectively;the rate of the two drugs combination was 54.4%.So when combined,they had synergistic effect.There was coordinate repression to migration of HUVEC in vitro when we used oxaliplatin(0.5 ?g/ml) and composite radix sophora flavescentis injection(6.25 ?l/ml).They also suppressed angiogenesis of CAM in vivo. Conclusions :This experiment showed that low dose oxaliplatin combined with composite radix sophora flavescentis injection has anti-angiogenic synergetic ability in vivo and the ability of inhibiting the growth of the cells in vitro.
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Purpose:To study the effects of hydroxycamptothecin with thermotherapy on anti-angiogenesis in vitro and in vivo. Methods:We chose human microvascular endothelial cell (HMVEC) culture and chick embryo choriallantoic membrane (CAM) model and used MTT and number-calculating methods to observe hydroxycamptothecine on HMVEC’s proliferation , sprouts and CAM blood vessels’ formation.Results:The survival rate of endothelial cells was in the range of (68.2%)-44.7% within the dose of 20-40 ng/ml and 5-80 ng/ml and was negatively correlated with the concentration (correlation coefficient was -0.906,-0.469,P=0.00003,0.0051). Hydroxycamptothecine could significantly suppress the endothelial cells’ proliferation and the sprouts. Hydroxycamptothecine could significantly suppress CAM vessels. The survival rate of HepG II cells is in the range 100%-90% within the dose of 5-80 ng/ml. There was no cytotoxicity.There was a synergestic anti-angiogenetic effect when hydroxycamptothecin (20 ng/ml) was combined with thermotherapy in vitro while there was additive effect when hydroxycamptothecin (40 ng/ml) was combined with thermotherapy in vitro.Conclusions:This experiment shows that small doses of hydroxycamptothecine (20-40 ng/ml) with thermotherapy has anti-angiogenetic synergestic or additive effect on proliferation and migration both in vivo and in vitro.
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AIM To study the influence of four extracts of traditional Chinese medicinal materials(sodium cantharidinate, matrine, cinobufotain and sodium ferlate) on the proliferation of human lung cancer A549 cell line and breast cancer MCF7 cell line;the possible mechanism of sodium ferlate on the inhibition of A549 cells. METHODS The inhibition of cell proliferation was determined by MTT assay and cell cycle was determined by flow cytometry. RESULTS All four extracts of traditional Chinese medicinal materials showed growth inhibition to breast cancer MCF7 cells while only sodium ferlate showed inhibition to lung cancer A549 cells. Synergistic inhibition was found when sodium ferlate was combined with each of the three commonly-used chemotheraputic drugs. Sodium ferlate could induce A549 cell apoptosis. CONCULSION The inhibition of cell proliferation induced is by sodium cantharidinate, matrine, and cinobufotain is quite different between different cancer cell lines. Sodium ferlate can inhibit cancer cell proliferation and show synergistic action while combined with chemotheraputic drugs. The mechanism of sodium ferlate on A549 cell proliferation seem to be related to the cell apoptosis.