ABSTRACT
Objective:To explore the independent prognostic factors of primary osteosarcoma patients under 20 years old after radical surgery, so as to predict the prognosis and survival of patients.Methods:The clinicopathological data of 1 339 patients with primary osteosarcoma diagnosed and registered in the National Cancer Institute Surveillance, epidemiology and outcome database (SEER) from 1984 to 2014 were retrospectively analyzed. Kaplan Meier method was used to calculate the survival rate of patients. Log rank test was used to evaluate the survival difference. Cox multivariate analysis was used to determine the independent prognostic factors of osteosarcoma after radical surgery factor.Results:The results of primary osteosarcoma patients undergoing radical surgery found that 34 cases (2.54%) aged 0-5 years old, 236 cases (17.63%) aged 6-10 years old, and 600 cases (44.81%) aged 11-15 years old and 469 cases (35.02%) aged 16-20 years old. The median survival time was 68 months. Among them, 757(56.53%) were male and 582(43.47%) were female. Among the 1 339 cases, 986 were white (73.64%), followed by black 230(17.18%), and 123 other races (9.18%). Multivariate analysis revealed that males ( HR=1.242; 95% CI:1.024-1.505), axial osteosarcoma ( HR=1.589; 95% CI:1.179-2.166), and regional invasion of osteosarcoma ( HR=1.470; 95% CI:1.156-1.870), distant metastasis ( HR=3.536; 95% CI:2.725-4.589) were independent risk factors for overall survival. Other types of osteosarcoma ( HR=0.471; 95% CI:0.285-0.779) were independent protective factors for overall survival. Conclusions:Based on the SEER database, this study identified independent prognostic factors for patients with primary osteosarcoma under the age of 20 who underwent radical surgery, which will help clinicians formulate individualized medical strategies and predict patients′ prognosis.
ABSTRACT
OBJECTIVE： To establish the method for content determination of the related substance in fudosteine raw material and its preparations. METHODS： Fudosteine or its preparations produced by 8 domestic enterprises were taken as samples. HPLC method （external standard） was used to determine the contents of impurities A， B and C. The separation was performed on MGⅡ C18 column with mobile phase consisted of 0.12％ sodium hexane sulfonate solution （pH 2.0） at flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， column temperature was 35 ℃ and sample size was 20 μL. The contents of impurities E， F， G were determined by HPLC method （principal component self-contrast method with correction factor）. The separation was performed on Altech Altima C18 column with mobile phase consisted of 0.05 mol/L phosphate buffer-acetonitrile- water （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was set at 200 nm， and the column temperature was 30 ℃. The sample size was 20 μL. RESULTS： The linear ranges of impurity A， B， C， E， F and G were 0.446-22.291， 0.202-20.158， 0.101-12.082， 0.111 0-11.100， 0.210 4-10.520， 0.221 6-11.080 μg/mL， respectively. The limits of detection were 5.57， 1.01， 1.99， 2.22， 4.21， 4.43 ng， respectively. The limits of quantitation were 11.14， 2.02， 3.98， 4.45， 8.42， 8.85 ng， respectively. The relative correction factors of impurities E， F and G were 0.91， 1.42 and 1.73， respectively； their relative retention time were 0.88， 1.95 and 3.08. RSDs of precision （n＝6） and stability [impurity A （4 h，n＝3）， other impurities （24 h，n＝7）] tests were all lower than 2.0％. The average recoveries were 98.0％， 97.3％， 102.4％， 99.4％， 98.9％， 96.4％， respectively； RSDs were 1.4％， 1.5％， 1.1％， 0.9％， 1.2％， 0.5％ （n＝9）， respectively. Total contents of substances in fudosteine raw material or its preparation produced by 8 enterprises were all lower than 1.1％. CONCLUSIONS： Established method is sensitive and specific. The method can be used for the quantitative study on related substances in fudosteine raw material and its preparations．
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of heat shock protein 90 (HSP90) inhibitor (17-DMAG) and oxaliplatin on the proliferation and invasion of colorectal cancer.</p><p><b>METHODS</b>After 17-DMAG, oxaliplatin and half-dose combination of 2 drugs processing colorectal cancer SW480 and HCT116 cell lines, CCK8 assay was applied to detect cell viability. RT-PCR and Western blot were used to detect the expression level of the apoptosis-related molecules. Transwell chemokine axis experiment and Western blot were employed to detect cell invasion ability and the expression level of tumor metastasis-associated protein.</p><p><b>RESULTS</b>The growth of SW480 and HCT116 cells was inhibited after the administration of 17-DMAG and oxaliplatin(P<0.05) in dose- and time-dependent manner. Processed by 17-DMAG 100 nmol/L, oxaliplatin 50 mg/L and half-dose combination of 2 drugs, transcription level of the apoptosis inhibitory gene (Bcl-2) in SW480 and HCT116 cells was decreased, the level of apoptosis promoting gene (Bax) transcription and protein PARP-1 spliceosome expression was increased, and the above trend was more obvious when using half-dose combination of 2 drugs. Transwell chemokine axis experiments showed the penetrating relative percentage and expression level of MMP9 and integrin β3 decreased, especially for half-dose combination of 2 drugs.</p><p><b>CONCLUSION</b>17-DMAG and oxaliplatin can co-inhibit the proliferation and invasion of colorectal cancer.</p>
Subject(s)
Humans , Antineoplastic Agents , Apoptosis , Benzoquinones , Cell Proliferation , Cell Survival , Colorectal Neoplasms , HCT116 Cells , Lactams, Macrocyclic , Neoplasm Invasiveness , Organoplatinum CompoundsABSTRACT
Objective To detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand (hTRAIL) in vivo,by using a novel double expressing adenoviral vector encoding hTRAIL and firefly luciferase ( luc ) gene ( ad -luc-hTRAIL),in which luc was used as reporter gene.Methods Lung cancer A549 cell xenografts in 16 nude mice models were established in subcutaneous inoculation way,the adenovirus vectors ( ad-luc-hTRAIL,ad-hTRAIL,ad-luc) and phosphate buffer saline (PBS) (n =4) as control were injected into tumor respectively.The size of the tumor was measured at different time points (4,7,10,14,21,28 d)after injection.The activity of luciferase in surface of the tumor was detected in vivo by using high-sensitivity cooled-charged coupled device(CCD) camera.The expression of hTRAIL was demonstrated by immunohistochemistry staining after sacrificing the animals at different time points,and immunohistochemical scores (IHS) were measured. The apoptosis rate of tumor cells was detected by using TUNEL and calculated. Analysis of variance,the paired t test and linear correlation analysis was used for the statistics. Results The growing speed of tumour xenografts was more slowly in ad-luc-hTRAIL and ad-hTRAIL groups than PBS group (t =2.71,2.72,P ＜ 0.05 ).The tumor volumes of ad-luc-hTRAIL,ad-hTRAIL,ad-luc and PBS groups 28 days after injection were (208.4 ± 42.3 ),( 181.5 ±23.9),( 403.1 ± 54.0 ) and ( 427.0 ± 59.3 ) mm3, respectively. There was no significant difference between ad-luc group and PBS group(t =2.07,P ＞ 0.05).The expression of luciferase in ad-luc-hTRAILgroup reached its peak at 7th day ( 1.37 ± 1.04),and then decreased quickly.The IHS and apoptosis rate in ad-luc-hTRAIL and ad-hTRAIL groups reached their peaks at 7th day,the peak values of IHS were 6.25 ±2.06 and 6.5 ± 2.89,the peak values of apoptosis rate were (60.75 ± 8.06 ) ％ and ( 61.50 ± 8.47 ) ％,respectively.The amount of luciferase expression ( absolute number of photons detected by CCD camera)was linear positive correlated with IHS and apoptosis rate ( rphotons/IHs =0.942,rph /rate =0.842,rIHs/rate =0.887,P ＜ 0.05 ).Conclusion The target gene hTRAIL can be transfected into lung cancer A549 cell xenografts nude mice models efficiently with a high level expression,and the therapeutic effect of hTRAIL can be monitored by detecting the expression of luc.
ABSTRACT
Objective To detect the expression and effect of human tumor necrosis facctor related apoptosis-inducing ligand(hTRAIL)in vitro by using a novel double expressing adenoviral vector encoding hTRAIL and firefly lueiferase (luc) gene (Ad-hTRAIL-luc),in which luc wag used, as reporter gene.Methods A549 cells were transduced with the adenoviral vector encoding enhanced green fluorescent protein (EGFP) gene(Ad-EGFP)at variable multiplicity of infection(MOI).Adenoviral transducfion efficiency wag determined 48 h later.A549 cells were transduced with Ad-hTRAIL-luc at variable MOI.and the following tests were performed 48h later,respectively:the expressive ratio of hTRAIL and the apeptotic ratio of A549 cells were meagnred by flow eytometer;counts per minute(cpm)of luminescence were measurde by scintiUation counters. A549 cells were transduced with Ad-luc at variable MOI, and cpm of luminescence was measured by scintillation counters 48 h later. After A549 cells were transduced with AdhTRAIL-luc,the expressive ratio of hTRAIL,the apoptotic ratio of A549 cells and cpm of luminescence were analyzed by one-way ANOVA.The positive ratio of EGFP and cpm of luminescence (Ad-luc) were analyzed bv nonparametric ANOVA.Results After A549 cells were transfected with Ad-hTRAIL-luc,the expressive ratio of hTRAIL on the cell membrane of the groups were(2.37±0.04)/,(3.16±0.03)/,(3.64±0.03)/,(3.96±0.02)/,(4.24±0.02)/,(4.34±0.02)/ respectively,which showed significant difference between each other (P＜0.01);and the apoptotic ratio of A549 cells were (1.52±0.04)/,(2.93±0.02)/,(3.39±0.02)/,(3.64±0.02)/,(3.86±0.02)/,(4.08±0.02)/,(4.20±0.02)/,respectirely,and it showed significant difference between each other (P＜0.01);cpm of luminescence were 465 561±26 801,1 038 576±29 417,937 655±23 197,786 432±20 028,524 288±16 338,401 566±15 961,respectively,and it also showed significant difference between each other(P＜0.01).There was a positive relationship between the expressive ratio of hTRAIL and cell apoptotic ratio of A549 cells (r=0.984,P＜0.01).Conclusion The double expressing adenoviral vector Ad-hTRAIL-luc can transfer luc and hTRAIL gene to A549 cells efficiently,and the activity of luc may reflect the effect of hTRAIL as well as the expression of hTRAIL.
ABSTRACT
Objective To discuss the clinical value of CT-guided percutaneous embedding of 125I seeds in combined chemotherapy with TP regime for non-small cell lung cancer(NSCLC). Methods Thirty two patients with NSCLC received CT-guided percutancous embedding of 125I particles, TP chemotherapy plan (paclitaxcl 135 mg/m2 /d1, cisplatin 75 mg/m2/d2 ～ 4 ) for four cycles after operation. The follow-up CT for observing therapeutic effects at 1, 3, 6, 12 month after 125I seeds implantation was undertaken. Results All cases were controlled effectively after one month revealed by CT follow up. The efficiency of tumor curing at 3, 6, 12 month were 87.5%, 90.63%, 92.31% respectively. None of the patients showed radiation injury and particle migration, and all of them had only slight side effects. Conclusion CT-guided percutaneous embedding of 125I seeds in combination with chemotherapy for non-small cell lung cancer is an effective and safe method, possessing valuable utilization clinically.