BACKGROUND: Herterologous antigen has strong immunogenicity and easily induces immunological response. Introduction of herterologous antigen into tumor may induce a serial of immunological reactions in the tumor and may reverse the immunosuppression of tumor microenvironment to treat tumor.OBJECTIVE: To evaluate the antitumor efficacy of intratumoral injection of human erythrocyte membrane antigens in micebearing S180 sarcoma.METHODS: Kunming mice bearing S180 sarcoma model were established and treated with 5 g/L human erythrocyte membrane antigens suspension or normal saline for five days. Tumor volume was calculated before the first injection and 3, 7, and 14 days after the first injection. In addition, the tumor cells in combination with human erythrocyte membrane antigens group, the njectionof saline group (the control group), and the injection of human erythrocyte membrane antigens or saline group (pre-immunized by suspension of human erythrocyte of blood group type A). Another 60 mice bearing S180 sarcoma were established and subjected to the above pre-immunization and injection of saline or human erythrocyte membrane antigens. Six mice selected from each group were sacrificed 14 days after the first injection, and tumors were weighed, followed by histological examination. Survival of remainders in each group was observed.RESULTS AND CONCLUSION: Tumor volumes in each group increased gradually. Tumor volumes in the human erythrocyte membrane antigens injection group, the tumor cells in combination with human erythrocyte membrane antigens group, and the human erythrocyte membrane antigens injection group (immunized) were smaller than the control group, Intratumoral injection of human erythrocyte membrane antigens significantly reduced tumor weights. Tumor necrosis, infiltration of inflammatory cells such as lymphocytes were observed in tumor tissues section examination following the intratumoral injection of human erythrocyte membrane antigens. The mouse survival time showed no statistical difference among different groups. Intratumoral injection of heteroloaous ervthrocvte membrane antiaens can inhibit tumor arowth of S180 sarcoma bearina mice.

Most of the anticancer drugs have some limitations in clinical application,such as poor solubility,low targeting and cytotoxicity to normal tissue and organ.The application of drug carriers offers a solution of these problems to a certain extent.In recent years,some materials such as polymers,liposomes,carbon nanotubes (CNTs) were used as carriers of anticancer drugs.The utilization of these carriers improved drug targeting and reduced adverse reactions by targeted modification of carriers which ensured the slow release of the drugs and maintained the plasma concentration.In these carriers,CNTs,as a novel nano-material,have attracted more attention in nanomedical applications.CNTs not only possess nanoscaled diameter,hollow structure and large aspect ratio,resulting in large drug capacity,but also can selectively absorb near infrared lights and transform them into thermal energy,according to the research finding.The functionalized drug-loaded CNTs in combination with thermotherapy shows potential,which is expected to become a new targeting therapy of cancer.In this paper,the basic structure of CNTs,the application of CNTs as drug carriers,and the recent development of functionalized CNTs as drug carriers combined with thermotherapy in tumor therapy were summarized.

Objective To explore the methods of therapy in lung cancer patients with bone metastases, and evaluate the effects and side effects of Strontium-89 palliative therapy in lung cancer patients with bone metastases. Methods About 56 cases of bronchiogenic cancer patients with bone metastases who did not receive any radiotherapy, according to 1.48×10~7 Bq/person/time, using standard intravenous injection ~(89)Sr as treatment. Follow-up 6 months, assess according to the following parameters: pain and frequency of pain were given quantized value and got pain score, using T test for comparing the pain score. According to before and after treatment bone imaging showed the size of focus and change of the number, upgrade focus therapy effect. Examine (CEA) and (NSE), using T test for changes before and after treatment. Using T test for changes of LEU and platelet after treatment. Results After treatment for 6 months, for 77 % patients are alleviating pain (43/56), the pain went off of 13 patents, account for 23 percent of the total. The pain score from 7.3±3.6 before treatment decrease to 5.3±3.4 after treatment, dropping obviously. After treatment, the focus regressed in 14 cases, decreased in 5 cases, total efficiency is 34 %. Before and after treatment, CEA from (33.64±18.15)μg/L obviously decreased to (t=4.26, P<0.01) to (21.36±11.65) μg/L, NSE from (27.16±10.12) μg/L obviously decreased to (t=4.26, P<0.05) to (12.56±4.23) μg/L. After treatment, LEU and platelet decreased to the lowest, LEU decreased about 27.9 %, platelet decreased about 19.7 %, after 3 months,normal rate of blood picture is 75 %(42/56). Conclusion The method of strontium-89 palliative therapy in lung cancer patients with bone metastases is good, safe and has little side effects, it can improve the quality of patients life.

Objective To explore the effects of surface functionalized multi-walled carbon nanotubes (FMWCNTs) on the cytotoxicity of human peripheral blood mononuclear cell (PBMC).Methods Five different types of MWCNTs (hydroxylated,carboxylated,aminated,nickel-plated and pristine MWCNTs (P-MWCNTs)) with the same diameter and length were evaluated the dispersion and characterizations in physiological salt solution by transmission electron microscopy.PBMC were isolated by density gradient centrifugation from human peripheral blood,and 5 types of MWCNTs were ultrasonically dispersed in serum-containing medium respectively.After incubation with PBMC for 12,24,48 or 72 h,cytotoxicity was detected by CCK-8 kits.Results All the MWCNTs had well dispersion,especially the F-MWCNTs.Cytotoxicity results showed that all types of MWCNTs could induced PBMC death,and presented dose-dependence manner and a certain degree of time-dependence manner.Compared with the P-MWCNTs,F-MWCNTs changed cytotoxicity statistically,with the hydroxylated,carboxylated,aminated MWCNTs weakened,aminated MWCNTs significant (P＜0.05),nevertheless the nickel-plated MWCNTs increased.Compared with the P-MWCNTs (25 μg/ml),cell viability of PBMC after 24 and 48 h incubation with the same dose of nickelplated MWCNTs both decreased,and the differences was statistically significant (P＜0.01,P＜0.05).Conclusions The functional group modification affects not only the MWCNTs dispersion in medium,but also the cytotoxicity of the MWCNTs on PBMC.

Objective To analyze features and diagnostic value of imageology of the early peripheral lung carcinoma.Methods The dynamic changes of early peripheral lung carcinoma confirmed pathologically in 21 cases were retrospectively analysed.The imaging features in combination with pathological data were also analysed.Results All of 21 cases,16 cases were the tubercle type(76.1%),3 cases were the spot type(14.3%) and 2 cases were the vacuole type(9.6%).Conclusion The typical imaging features of early peripheral lung carcinoma are few,the dynamic observation of the disease is of relatively high value in diagnosis.

Objective To study the adsorption effect of activated charcoal suspension on paraquat (PQ) in gastrointestinal tract of beagles exposed to PQ.Methods Twenty healthy male beagles were randomly divided into experimental group and control group,with 6 beagles in each group.20％ PQ solution (a dose of 30 mg/kg) was prescribed through stomach for beagles in both groups.After exposure to PQ for 30 minutes,the beagles in experimental group were given activated charcoal suspension (1.0 g/kg of type Ⅰ activated charcoal powder mixed with 100 mL of normal saline) by gavage,while the control group was only given equal volume of normal saline.After exposure to PQ for 10 minutes,30 minutes,and 1,2,4,8,12,24,and 48 hours,blood was collected from hepatic portal veins and peripheral veins to detect the PQ concentration change in the plasma.The toxicokinetics software DAS 2.1.1 was applied to analyze PQ concentration and compare the change in toxicokinetics parameters between the both groups.The change in vital signs including heart rate (HR),respiratory rate (RR) and pulse oxygen saturation (SpO2) was dynamically monitored 10 minutes before exposure,4 hours and each day from the 1st to the 7th day after exposure.Results After exposure to PQ,the poison concentration in the plasma of hepatic portal veins and peripheral veins in the control group rose quickly and reached peak 4 hours later.It fell quickly at first,and fell slowly 8 hours later.But in the experimental group,the increase rate to the peak was significantly slow.Besides,PQ peak fell more obviously than that in the control group and it was about 50％ of the control group (μg/L:123.50 ± 11.67 vs.255.18 ± 12.29 in blood from hepatic portal veins,122.35± 11.72 vs.250.86± 11.15 in blood from peripheral veins).After 8 hours it fell much more quickly than that of the control group.After exposure to PQ for 48 hours,PQ concentration in the plasma was still lower than that of the control group (μg/L:0.53 ± 0.18 vs.15.98 ± 5.58 in blood from hepatic portal veins,0.31 ± 0.01 vs.15.03 ± 4.82 in blood from peripheral veins,both P ＜ 0.01).With the toxicokinetics analysis,compared with the control group,the maximum concentration (Cmax) and area under the curve (AUC) of PQ in the plasma of hepatic portal veins and peripheral veins in the experimental group were significantly decreased [Cmax (μg/L):125.07 ± 9.49 vs.255.18 ± 12.29 in blood from hepatic portal veins,123.38 ± 9.52 vs.250.86 ± 11.15 in blood from peripheral veins;AUC (mg· L-1· h-1):1.6±0.2vs.3.3 ± 0.4 in blood from hepatic portal veins,1.5 ± 0.2 vs.3.2 ± 0.3 in blood from peripheral veins],time to the peak (Tmax) of PQ was slowed (hours:5.3 ± 1.9 vs.4.0 ± 0.0 in blood from hepatic portal veins,4.7 ± 1.5 vs.4.0 ± 0.0 in blood from peripheral veins),and PQ plasma half-life (t1/2) and mean retention time (MRT) were significantly shortened [t1/2 (hours):3.8 ± 1.2 vs.15.4± 3.7 in blood from hepatic portal veins,3.5 ± 1.0 vs.15.5 ± 2.7 in blood from peripheral veins;MRT (hours):8.0± 1.5 vs.13.4± 1.2 in blood from hepatic portal veins,7.6± 1.3 vs.13.3± 1.2 in blood from peripheral veins;all P ＜ 0.01].After exposure to PQ,HR and RR in both the experimental group and the control group increased and reached to the peak about the 4th day and then the increase rate began to slow down gradually;SpO2slowed down gradually and reached to the valley about the 4th day and then it began to recover,but the change range of vital signs in the experimental group was smaller than that of the control group,and the parameters were significantly better than those of control group [4-day HR (bpm):134.50±3.00 vs.142.00±6.43,4-day RR (times/min):31.00±0.58 vs.34.33±0.94,4-day SpO2:0.900±0.006 vs.0.873±0.005,all P ＜ 0.05].Conclusion Activated charcoal administrated at 30 minutes after PQ poisoning can slow down the increase rate of PQ concentration in the plasma,decrease the peak concentration and has less influence on vital signs in beagles.

Objective: To determine the scavenging effect and the change of metabolism of paraquat (PQ) using hemoperfusion (HP) once and twice within 12 hours after intoxication and explore the better scheme of HP. Methods: 18 beagles were randomly divided into 3 groups. Single HP group, Double HP group and Control group. Peripheral veins blood was collected at different times within 48 hours after exposure in each group. Toxin concentration was measured, analyzed and compared among 3 groups. Results: 6 hours after exposure, Single HP group and Double HP group has finished the first HP treatment, and the concentration of PQ was lower than that of the control group, the difference was statistically significant (P<0.05) . 10 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . 12 hours after exposure, Double HP group has finished the second HP treatment, the concentration of PQ was significantly lower than that of Single HP group and Control group (P<0.05) . 24 hours and 48 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . Statistical difference were not observed in toxicokinetical parameters among 3 groups (P>0.05) . Conclusion HP treatment once and twice within 12 hours after intoxication could effectively reduce the toxin concentration in the peripheral veins blood after HP for about 4 hours, then the toxin concentration would return to the same level as Control group quickly. It was suggested that at the beginning of poisoning, HP treatment once or twice could not significantly change the metabolism of paraquat.

Objective To analyze the characteristics and to evaluate the application of quantitative CT spectral parameters in patients with suspected lung cancer.Methods One hundred and thirty two patients with occupying lesions of the lung underwent chest plain and two-phase contrast enhanced CT scan with gemstone spectral imaging (GSI) mode.The CT images of patients with confirmed lung cancer by pathological evidence were analyzed with GSI viewer.Optimal energy value supplying optimal contrast-tonoise ratio (CNR) was recorded.The CT values of lesions at 40 keV,70 keY and optimal energy level were measured.Spectral curve slope at different intervals of 40-70 keV,40-100 keV and 40-140 keV was computed.Effective atomic number (Zeff),iodine concentration (IC) and water concentration (WC) were measured and analyzed by statistical methods.Results Sixty six patients with confirmed lung cancer were included in the analysis.The optimal energy values for optimal CNR on plain scan,arterial phase and venous phase were (63.09±5.33) keV,(52.65±6.44) keV and (54.06±5.53) keV,respectively.The difference of CT values at different energy levels on each scan phase was statistically significant (F=4.561,P=0.025).The spectral curve slope values among three different energy intervals were significantly different (F=2.137,P＜0.001).The differences of the slope between arterial phase and venous phase at same energy interval were not significant (40-70 keY:t=1.165,P=0.248;40-100 keV:t=1.102,P=0.274;40-140 keV:t=1.118,P=0.268).Zeff on plain scan,arterial phase and venous phase was 7.73±0.14,8.35±0.37 and 8.39±0.30,respectively.There was positive correlation between IC and Zeff on enhanced phase (arterial phase:r=0.998,P＜0.001;venous phase:r=0.998,P＜0.001).Conclusion CT spectral imaging can supply the optimal energy value for optimal CNR.CT value at optimal energy level and spectral curve slope at 40-140 keV are suitable for analysis.IC and Zeff can be used jointly in evaluation of patients with suspected lung cancer.

VEGF nanoparticle (VEGF-NP) was prepared by a multi-emulsification technique using a biodegradable poly-dl-lactic-co-glycolic (PLGA) as matrix material. The nanoparticles were characterized for size, VEGF loading capacity, and in vitro release. VEGF-NP and naked VEGF plasmid were intramuscularly injected into the ischemia site of the rabbit chronic hindlimb ischemia model and the efficiency of VEGF-NP as gene delivery carrier for gene therapy in animal model was evaluated. Gene therapuetic effect was assessed evaluated by RT-PCR, immunohistochemistry and angiography assay. The average size of VEGF-NP was around 300 nm. The encapsulation efficiency of VEGF was above 96%. Loading amount of VEGF in the nanoparticles was about 4%. In vitro, nanoparticles maintained sustained-release of VEGF for two weeks. Two weeks post gene injection the capillary density in VEGF-NP group (81.22 per mm2) was significantly higher than that in control group (29.54 mm2). RT-PCR results showed greatly higher VEGF expression in VEGF-NP group (31.79au * mm) than that in naked VEGF group (9.15 au * mm). As a carrier system for gene therapy in animal model, VEGF-NP is much better than naked DNA plasmid. The results demonstrate great possibility of using NP carrier in human gene therapy.
Animals ; Disease Models, Animal ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; chemistry ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Plasmids ; Polyglycolic Acid ; chemistry ; Rabbits ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVE： To prepare insoluble anti-tumor drug-loading polymer micelles， and to increase inhibitive effect of insoluble anti-tumor drug. METHODS： Chitosan （CSO） and stearic acid （SA） were used to prepare blank micelles （CSO-SA）， then modified with mPEG and folic acid （FA） to prepare PEG-CSO-SA and FA-PEG-CSO-SA. Characteristic functional groups of CSO-SA， PEG-CSO-SA and FA-PEG-CSO-SA were detected by infrared spectroscopy. The morphology of micelles was observed by transmission electron microscopy. The particle size and Zeta potential of micelles were measured by laser particle size analyzer. Osthole （OST） was used as the model drug and drug-loading micelles （FA-PEG-CSO-SA/OST） were prepared by dialysis. MTT assay was used to detect the inhibitory rate of FA-PEG-CSO-SA， OST solution and FA-PEG-CSO-SA/OST to human liver cancer cell HepG2. Half inhibitory concentration （IC50） was calculated. RESULTS： FA-PEG-CSO-SA was successfully prepared. CSO-SA， PEG-CSO-SA， FA-PEG-CSO-SA were oval in shape； particle sizes were （96.01±5.99）， （112.93±1.06）， （216.01±4.76） nm （n＝3） and Zeta potentials were （39.30±1.75）， （38.03±2.91）， （15.17±2.10） mV （n＝3）， respectively. Encapsulation efficiency and drug-loading amount of OST in FA-PEG-CSO-SA were （84.47±2.07）％ and （16.01±0.90）％ （n＝3）， respectively. The inhibition rates of FA-PEG-CSO-SA to HepG2 cells were＜20％. IC50 of OST solution and FA-PEG-CSO-SA/OST to HepG2 cells were （62.08±5.21）， （27.49±0.50） μg/mL （n＝3）， respectively. CONCLUSIONS： Prepared FA-PEG-CSO-SA can significantly increase inhibitive effect of insoluble drug OST to HepG2 cells， and it is expected to become a new anti-tumor drug carrier.