Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was prepared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-Sc7301 concentration (3-48 nmol/L) and the incubation time (P<0.05). It was concluded that the TAX-Sc7301 immunoconjugate is potentially applicable as a targeted agent against HER2-positive tumor cells.

Objective To evaluate the outcome of surgical treatment of tricuspid valve regurgitation after valve replacement.Methods Twenty one patients with tricuspid valve insufficiency after valve replacement were performed surgical treatment.Tricuspid valve-plasty was performed in 17 patients and tricuspid valve replacement was done in 4 patients.Three patients underwent edge-to-edge tricuspid valveplasty.DeVega procedure was performed in 5 patients.Cosgrove-Edward annuloplasty ring was used in 15 patients.Four patients' valve were replaced by SJM bileallet mechanical prostheses.Results There was 3 patients dead early after operation with a mortality of 14.3％(3/21).The causes of death including multiple organ failure,cardiac arrest and low cardiac output syndrome.The rate of early postoperative complications was 33.3％ (7/21),including pulmonary edema,arrhythmia,acute renal failure and low cardiac output syndrome.The patients were followed up 9-60 months.The rate of readmission was 23.8％ (5/21).Two patients went to hospital again for pleural effusion,1 patient for left ventricular dysfunction and 2 patients for right ventricular dysfunction.The other patients recovered well.Conclusions Surgical therapy is effective on severe tricuspid valve regurgitation after valve replacement.Preoperative aggressive treatment of heart failure,a reasonable grasp of surgical indications and timing of surgery,strict perioperative management are the keys to guarantee patients a smooth recovery.

Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was prepared and its specific binding to tumor cells was investigated in this study.Sc7301 was conjugated to　TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained.After purification and labeling by Cyano-fluorescein isothiocyanate (FITC),the specific binding of TAX-Sc7301to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively.TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2cells.And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-Sc7301concentration (3-48 nmol/L) and the incubation time (P＜0.05).It was concluded that the TAX-Sc7301immunoconjugate is potentially applicable as a targeted agent against HER2-positive tumor cells.

OBJECTIVECellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.

METHODSThe inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.

RESULTSCisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.

CONCLUSIONOur results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cellular Senescence ; Cisplatin ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p19 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Tumor Suppressor Protein p53 ; metabolism ; Up-Regulation