1.Effect of Smad7 gene modified BMSCs to TGF-β signal conduction in hepatic stellate cells
Chinese Journal of Immunology 2016;32(10):1441-1445
Objective:To investigate the mechanism of Smad7 gene modified bone marrow mesenchymal stem cells ( Smad7-BMSCs) to prevent hepatic fibrosis in vitro. Methods:Smad7-EGFP-BMSCs were established by isolating and purifying BMSCs of rats, and transfecting Ad-Smad7-EGFP. HSC-T6 were divided into Group A, Group B, Group C and Group D, which were respectively incubated with Smad7-EGFP-BMSCs, BMSCs, Smad7 plasmid and PBS for 72 hours. The level of Smad7and TGF-β1protein in the culture solution was determined by ELISA. The expression of mRNA and protein of Smad7,TGF-β1,Col Ⅰ and α-SMA in the hepatic stellate cells were respectively determined by Western blot and RT-PCR. Cellular apoptosis was determined by flow cytometry. Results:(1)The results of ELISA showed that the level of TGF-β1 protein decreased(P<0. 01) but the level of Smad7 protein increased (P<0. 01) in Group B,Group C and Group D compared with Group A;the level of TGF-β1 protein decreased(P<0. 01) but the level of Smad7 protein increased (P<0. 01) in Group D compared with Group B and Group C. (2)The results of Western blot and RT-PCR showed that the level of mRNA and protein of Smad7,TGF-β1,Col Ⅰ and α-SMA decreased(P<0. 01) but the level of mRNA and protein of Smad7 protein increased (P<0. 01) in Group B,Group C and Group D compared with Group A;the level of mRNA and protein of Smad7,TGF-β1,ColⅠandα-SMA decreased(P<0. 01) but the level of mRNA and protein of Smad7 protein increased (P<0. 01) in Group D compared with Group B and Group C. (3)The results of flow cytometry showed that the rate of cellular apoptosis de-creased(P<0. 01),but the level of Smad7 protein increased (P<0. 01) in Group B,Group C and Group D compared with Group A;the rate of cellular apoptosis decreased(P<0. 01)in Group D compared with Group B and Group C. Conclusion:Smad7-BMSCs can have the effect of anti-hepatic fibrosis by affecting TGF-β1 signal pathway and promoting cellular apoptosis in hepatic stellate cells.
2.Efficacy observation of irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the second-line treatment of advanced colorectal cancer
Yujie MA ; Yongkun SUN ; Dongna CHEN ; Aiqin MAO ; Aijiang SU ; Kaiping OU
Cancer Research and Clinic 2019;31(6):405-408
Objective To observe the clinical efficacy of irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the second-line treatment of advanced colorectal cancer. Methods The clinical data of 19 patients with advanced colorectal cancer who were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from October 2014 to December 2017 were retrospectively analyzed, and these patients failed the first-line chemotherapy regimen. All patients were treated with irinotecan plus capecitabine or tegafur-gimeracil-oteracil potassium. The patient's short-term efficacy, adverse reactions, progression-free survival, and overall survival were analyzed. Results After treatment, the efficacy in 18 of the 19 patients with advanced colorectal cancer was evaluable, including partial remission in 3 patients, stable disease in 13 patients, and disease progression in 2 patients. The objective remission rate was 16.7% (3/18), the disease control rate was 88.9% (16/18), the median progression-free survival time was 7.6 months, and the median overall survival time was 23.3 months. All of the patients were well tolerated , and the grade 4 adverse reaction was presented as grade 4 neutropenia (1 case), grade 3 leukopenia (2 cases) and thrombocytopenia (1 case), grade 2 diarrhea (1 case), and grade 1 diarrhea (3 cases), and grade 1-2 liver injury (3 cases) and nephrotoxicity (2 cases). Conclusion Irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the treatment of advanced colorectal cancer is effective and safe, which is worthy of clinical promotion.