Objective To investigate the function of transferrin-DNA complex,transported by transferrin(Tf)and trans-arterial injection via interventional approach be the duel-target-orientated delivery and the transferring into malignant cells to get more effective therapy.Methods p53-LipofectAMINE ligand with different concentrations of Tf(0,10,25,50,100?g)transfected the 4 strains including LM6、Hep3B、YY and L02 in vitro to evaluate the gene transfeetion efficiency through western blot.Then,after setting up the VX2 hepatocarcinoma models,we delivered the Tf-p53-LipofeetAMINE complex into the hepatic arteries via interventional techniques to analyse the transfection efficiency in vivo.Results Tf,within the range of 10 100?g,could increase gene transfection efficiency mediated by liposome,and the efficiency increases with the raise of Tf concentration.Combination with interventional technique to inject Tf-DNA complex into tumor arteries,gene transfeetion efficiency was enhanced in rabbit models.Conclusion Tf can enhance gene- liposome transfection efficiency,furthermore with combination of interventional catheter technique,there would be a potential duel-target-orientated gene therapy method.(J Intervent Radiol,2007,16:99-103)

Objective To investigate the effects of intratumoral implantation of ~(32)P-CP-PLLA seeds on the normal canine liver tissue and to exolore the metabolism of ~(32)P-CP-PLLA seeds implanted in the liver of experimental dogs.Methods Twelve beagles were enrolled in this study.The dogs were randomly and equally divided into four groups:group A(185 MBq),group B(370 MBq),group C(740 MBq)and group D(0 MBq).By using laparotomy procedure ~(32)P-CP-PLLA seeds were implanted into dog's liver.CT scan was performed before operation as well as before the dog was sacrificed.All dogs were sacrificed three months after the implantation.Before the procedure and 1,2,4,8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted.One dog from group B and group C was selected respectively and was fed in a metabolic cage.Within one month after the procedure the cpm in feces and in urine was determined every 24 hours.One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1,2,4,8 and 12 weeks after the implantation,and SPECT imaging was also performed at the same time.Pathologic study,both macroscopic and microscopic(including optical and electronic microscopy)was made to observe the liver damage after the dog was sacrificed.The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean±standard deviation((x)±s).Results Two months after the procedure,serological examination found that the serum alkaline phosphatase(BKP)in both group Band group C was significantly higher than that in other groups,the difference was statistically significant (P ＜0.05),and the BKP levels returned to normal in three months.The postoperative 30-day inspection of the urine showed that the radioactive particles slowly released into the body and eliminated from the body with the urine and feces,mainly through the renal excretion.The 30-day cumulative percentage of eliminated radioactive dose in the urine and in the feces was 6.34% and 11.64% respectively.No sign of particle displacement was found on SPECT imaging.On autopsy three months after the implantation,the size of the radioactive seeds became smaller and fragile.With the radioactive dose used increasing,the area of liver damage at the site of seed implantation became bigger,which was demonstrated on CT scan,macroscopic exam and pathologic study.The local damaged focus of the liver caused by ~(32)P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally.Conclusion The implantation of ~(32)P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general adverse effects.The implanted seeds can slowly release the radioactive dose and will not immigrate to other organs in the body.Besides,the seeds possess excellent stability,targeted orientation and safety.

Objective To analyze the clinical efficacy of the laparoscopic breast-conserving surgery combined with radiofrequency ablation to treat the early-stage breast cancer.Methods We collected 55 patients diagnosed early-stage breast cancer in retrospect,which started from January 2014 to December 2016.Twenty-seven of them were performed the laparoscopic breast-conserving surgery combined with radiofrequency ablation while others went through laparoscopic breast-conserving surgery without radiofrequency ablation.Meanwhile,we adopted the student t-test and the chi-square test to compare results of two groups.More specific,the main indexes of this study are including the post-operative local recurrence,the incidence of fat liquefaction or the incision-infection,operation time,post-operative hospital stay and the hospitalization expense.Results The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had low local-recurrence than the laparoscopic breastconserving surgery group (0 and 7.69％).Additionally,there were no statistical differences between two groups in the incidence of fat liquefaction.However,The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had more hospitalization expense than the laparoscopic breast-conserving surgery group [(4.1 ± 0.7) ten thousand yuan and (2.3 ± 0.6) ten thousand yuan,P ＜ 0.05].Conclusions Although the laparoscopic breast-conserving surgery combined with radiofrequency ablation group remarkably increased the hospitalization expense because of the utility of the radiofrequency ablation related apparatus,it may provide the probability of shaving more residual tumor cell and may low down the recurrence,especially not rising up the incidence of the post-operative fat liquefaction.Therefore,this surgery method might be one of the potential developments in the minimal-invasive of early stage breast cancer.

0.05). Dysphasia resolved significantly after stent placement in both groups.The improvement of dysphasia was more significant in Group A than in Group B after 2 months of stent placement(1.37?0.56 in group A, 1.82?0.50 in group B,P=0.004).The median survival period was longer in Group A than in Group B (7 months vs 4 months).The mean survival period was also longer in Group A than in Group B (8.3 months vs 3.5 months).There was a statistically significant difference in the survival period between the two groups(P

Objective To investigate the failure mode in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery,and to discuss the significance and feasibility of postoperative radiotherapy according to the failure mode.Methods A retrospective analysis was performed on 227 patients with stage pT3N0M0 TESCC who met the inclusion criteria from January 2007 to December 2010.Their postoperative failure mode was analyzed,and,with reference to relevant research,the significance of postoperative radiotherapy and its target patients were explored.The Kaplan-Meier method was used to calculate overall survival (OS),local recurrence (LR),and distant metastasis (DM) rates,and the log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox model was used for multivariate prognostic analysis.Results After surgery,there were 58 patients (25.6％) with LR in the thoracic cavity and 27 patients (11.9％) with DM,and 10 patients had both LR and DM.Twentynine (50％) of the 58 patients had recurrence in the thoracic mediastinal lymph nodes.The results of univariate analysis showed that the 3-and 5-year OS rates of patients with upper thoracic esophageal cancer were significantly lower than those of patients with middle and lower esophageal cancer (P =0.000),and the chest-regional recurrence rate was significantly higher in the former group than in the latter two groups (P=0.047);the 3-and 5-year OS rates of patients with poorly differentiated squamous cell carcinoma were significantly lower than those of patients with moderately and well differentiated squamous cell carcinoma (P =0.005),and the DM rate was significantly higher than in the former group than in the latter two groups (P=0.000).The results of multivariate analysis showed that lesion site and the degree of pathological differentiation were independent prognostic factors for OS (P=0.014 and 0.010);lesion site was the independent prognostic factor for chest-regional recurrence (P=0.046);the degree of pathological differentiation was the independent prognostic factor for DM (P=0.000).Conclusions For patients with stage pT3N0M0 TESCC after two-field esophagectomy,the most common failure mode is chest-regional recurrence,especially in patients with upper thoracic esophageal cancer.Therefore,postoperative radiotherapy is suggested for upper-thoracic TESCC.

Objective To determine the prognostic factors in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TSCC) after esophagectomy, and to compare the effects of different treatment modalities on the prognosis of patients.Methods A retrospective analysis was conducted on 480 patients with stage pT3N0M0 TSCC from 2007 to 2010 to determine the prognostic factors in the patients, and to compare the effects of different treatment modalities on their prognosis.Survival rate was calculated using the Kaplan-Meier estimator, and multivariate analysis of prognostic factors was performed using the Cox model.Results Of the 439, 333, and 278 patients who completed the 1-, 3-, and 5-year follow-up, respectively, the 1-, 3-, and 5-year overall survival (OS) rates were 90.0%, 68.7%, and 57.9%(median 87 months, 95% confidence interval (CI=74.7-99.4), respectively, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 82.3%, 60.4%, and 52.3%(median 71.3 months, 95%CI=55.1-87.5), respectively.In order to account for the different constituent ratios of some clinical and pathological data between the three groups of patients, 55 patients in each group were matched using propensity score matching (PSM)(all P>0.05).It was found that the post-PSM 1-,3-, and 5-year OS and DFS were significantly different between patients who received surgery only, postoperative chemotherapy (POCT), and postoperative chemoradiotherapy/radiotherapy (POCRT/RT)(P=0.000 and 0.006,respectively).Multivariate Cox analysis showed that age, lesion location, and treatment modality were independent prognostic factors for OS and DFS (P=0.029,0.004,0.000 and P=0.009,0.003,0.002), and the length of lesion was also an independent prognostic factor for DFS (P=0.003).Conclusions Although the rate of post-operative treatment failure is still high among patients with stage pT3N0M0 TSCC, POCRT/PORT can improve the prognosis and the 5-year OS and DFS of these patients.However, further large-sample prospective studies will be required to confirm these findings.

Objective To evaluation and comparison the curative effect of different adjuvant therapy and prognostic factors with thoracic esophageal squamous cell carcinoma (ESCC) after surgery,and to find the best treatment for them.Methods A total of 863 patients with thoracic ESCC underwent surgery in the fourth hospital of Hebei Medical University,From January 2007 to December 2010,To analyze the influence factors of the patient′s independent prognosis and the effect of postoperative adjuvant therapy on the prognosis of patients.The 1:1, after the tendency of a total of 261 cases were used PSM method (87 cases/group).The Kaplan-Meier method was used to calculate OS,DFS and log-rank test and monovariable analysis,Cox model was used to multivariable analysis.Results The sample size in 1,3,5 was 123,589,863 cases.The 1-,3-,and 5-year overall survival (OS) and disease-free survival (DFS) of all patients were 89.7%,62.1%,51.7% and 76.8%,52.1%,44.2%,respectively.The 1,3,5-years of OS and DFS were 956%,73.3%,61.1% and 85.6%,61.1%,54.4%,78.9%,38.9%,31.3% and 67.8%,27.8%,20.0%,92.2%,55.6%,44.4% and 67.8%,44.4%,36.7%(all P=0.000) among postoperation chemoradiotherapy (POCRT),postoperation chemotherapy (POCT) and postoperation radiotherapy (PORT) after pairing with PSM.The result of COX analysis showed that the degree of inflammatory adhesion,pTNM stage and the number of positive lymph nodes were the independent prognostic factors in patients with OS (P=0.002,0.000,0.007).The history of drinking,pTNM stage and treatment model were the independent prognostic factors of DFS (P=0.009,0.000,0.012).Conclusions Patients with thoracic esophageal squamous cell carcinoma after surgery to receive adjuvant therapy has a good effect,compared with PORT and POCT,POCRT can significantly improve the OS and DFS,and POCRT was the independent prognostic factors of DFS.

Objective To investigate the failure model of patients with stage pN0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery alone and to discuss the feasibility of postoperative radiotherapy.Methods A retrospective analysis was performed on 473 patients with TESCC who received surgery alone from January 2007 to December 2010.The feasibility of adjuvant radiotherapy for pN0 TESCC patients was investigated through the failure model of postoperative patients.Results Of all patients,there were 57 cases with chest-regional recurrence (12.1％),most of which occurred in the mediastinal lymph nodes(52 case).There were 42 (8.9％) patients were identified as distant metastasis (DM),of which 13 cases were found to have both local recurrence and DM,and the total failure rate was 20.9％.The chest-regional recurrence rate of upper TESCC was statistically significantly higher than middle and lower (x2 =7.469,P ＜ 0.05),but DM rate had no statistically significant difference (P ＞ 0.05).The chest-regional recurrence rate and DM rate of the advanced T stage were significantly higher than those of the early T stage(x2 =10.247,7.886,P ＜ 0.05).The result of univariate analysis showed that disease site,the degree of adhesion,postoperative stump were significant factors of chestregional recurrence rate (x2 =14.232,9.486,7.546,P ＜ 0.05).Gender,smoking and preoperative weight loss ≥5 kg significantly influenced DM (x2 =10.823,10.275,6.065,P ＜ 0.05).In addition,the T stage was the significant influence factor of chest-regional recurrence and DM(x2 =15.994,12.885,P ＜0.05).The result of multivariate analysis showed that T stage and postoperative stump were independent factors of chest-regional recurrence (P ＜ 0.05).Smoking was an independent factor of DM (P ＜ 0.05).Conclusions There was a high rate of chest-regional recurrence in patients with stage pN0 TESCC who received surgery alone.Postoperative radiotherapy was recommended for patients with upper TESCC,advanced T stage,severe local adhesion,positive margin in and postoperative stump.Male,smoking and preoperative weight loss≥5 kg were associated with higher DM rate.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

Traditional Chinese Medicine massage is a kind of physiotherapy which affects on specific parts of the body surface by means of training to regulate the function of the body to achieve the therapeutic effect. In this work,under positive detection model, the chemical fingerprint of exhaled breath from volunteers before and after receiving Traditional Chinese Medicine massage within m/z 50-1000 were detected by extractive electrospray ionization-mass spectrometry (EESI-MS). And through high resolution mass spectrometry analysis, the metabolites such as epinephrine (m/z 184. 0889), 3-(3-hydroxyphenyl) propionic acid (m/z 167.0615) and L-tryptophan (m/z 205. 0933) were successfully identified. Besides, chemical fingerprints of volunteers before and after receiving Traditional Chinese Medicine massage under different health condition were clearly differentiated via partial least squares discrimination analysis (PLS-DA). The results showed that Traditional Chinese Medicine massage could significantly change the metabolic process of volunteers. Moreover, it further indicated that the established method could provide a real time fashion to follow metabolic changes caused by Traditional Chinese Medicine massage.