Biliary tract carcinoma (BTC) is a common malignancy in human digestive system.The lethality of BTC is essentially attributed to the asymptomatic growth of BTC and the lack of effective diagnostic options.The disease is therefore usually detected at an advanced stage and lost the opportunity of surgical therapy.Conventional chemotherapy and radiation therapy have been notably ineffective against BTC.There is now a real and urgent need to focus on developing novel and potent therapeutic strategies against BTC.Human epidermal growth factor receptor 2/neu (HER2/neu) is a member of the ErbB receptor tyrosine kinase family.HER2/neu is associated with tumor proliferation,invasion,and metastasis that would impact in a significant way on clinical outcome.HER/neu may become a new therapy target of BTC.

Objective To evaluate the clinical efficacy of gemcitabine-oxaliplatin (GEMOX) regimen combined with targeted therapy for advanced gallbladder cancer.Methods The retrospective descriptive study was conducted.The clinical data of 21 patients with advanced gallbladder cancer who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January 2016 and December 2017 were collected,including 8 males and 13 females,aged from 28 to 80 years,with the age of (58± 12)years.Patients received GEMOX regimen combined with targeted therapy.According to the results of gene test,patients selected tageted therapy with Cetuximab,Herceptin or Apatinib.Observation indicators:(1) gene test situations;(2) situations of GEMOX regimen combined with targeted therapy;(3) adverse reactions of GEMOX regimen combined with targeted therapy.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were represented as absolute number or percentage.The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method.The survival analysis was done using the Log-rank test.Results (1) Gene test situations:of 21 patients,19 were confirmed as K-ras wild type,including 13 of single K-ras wild type,4 of K-ras wild type combined with human epidermal growth factor receptor 2 (HER2),2 of K-ras wild type combined with vascular endothelial growth factor receptor 2 (VEGFR2);5 were detected positive HER2,including 1 of single positive HER2,4 of positive HER2 combined with K-ras wild type;3 were detected positive VEGFR2,including 1 of single positive VEGFR2,2 of positive VEGFR2 combined with K-ras wild type.Two and 19 patients had 0 and l of Eastern Cooperative Oncology Group score.(2) Situations of GEMOX regimen combined with targeted therapy:all the 21 patients underwent ≥ 2 courses of GEMOX regimen combined with targeted therapy.Among the 21 patients,0,4,9 and 8 were respectively detected in the complete remission (CR),partial remission (PR),stable disease (SD) and disease progression (PD).Fourteen patients (13 of single K-ras wild type and 1 of K-ras wild type combined with positive VEGFR2) received GEMOX regimen combined with Cetuximab therapy,including 0 with CR,4 with PR,5 with SD and 5 with PD;5 patients (1 of single positive HER2 and 4 of positive HER2 combined with K-ras wild type) received GEMOX regimen combined with Herceptin therapy,including 0 with CR,0 with PR,2 with SD and 3 with PD;2 patients (1 of single positive VEGFR2 and 1 of positive VEGFR2 combined with K-ras wild type) received GEMOX regimen combined with Apatinib therapy,including 0 with CR,0 with PR,2 with SD and 0 with PD.The objective response rate was 19.0％ (4/21) and disease control rate was 61.9％(13/21) in the 21 patients.The median onset time was 1.8 months in the 21 patients.The 3-,6-and 9-month progression free survival (PFS) rates and median PFS time were respectively 90.5％,71.4％,58.5％ and 10.7 months.The 6-and 12-month overall survival rates were respectively 90.2％ and 58.6％,and median overall survival (OS) time was 15.5 months in the 21 patients.The PFS and OS time were 8.4 months and 10.4 months in the 7 patients combined with jaundice,10.5 months and 14.8 months in the 14 patients without jaundice,with no statistically significant difference (x2 =0.868,0.774,P＞0.05).(3) Adverse reactions of GEMOX regimen combined with targeted therapy:the most common adverse events were skin rash and digestive tract reactions.No serious adverse event occurred during the therapy.All the adverse events were improved after symptomatic treatments.Conclusion GEMOX regimen combined with targeted therapy for advanced gallbladder cancer has good outcomes,less adverse reactions and higher safety.

OBJECTIVETo prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines(MGC803 and MNK45).

METHODS5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope(SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs.

RESULTSDeep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was(4.54±0.43)%, entrapment rate was(21.56±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a as lowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P<0.05), while the difference was not significant as compared to positive control group (P>0.05).

CONCLUSIONThe 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Delayed-Action Preparations ; Fluorouracil ; pharmacology ; Humans ; Lactic Acid ; pharmacology ; Nanotubes, Carbon ; Polyesters ; Polymers ; pharmacology ; Stomach Neoplasms ; pathology