1.Influence of anti- angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloid
Yunchun MAO ; Xuemei MA ; Shufang SHI ; Yinguang GAO ; Hongjiao QI ; Shuyuan CHEN
International Journal of Surgery 2011;38(7):461-465,506
Objective To investigate the influence of anti-angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloids. Methods Thirty pieces of keloids from a patient were implanted into subcutaneous tissue of the nude mice, 24 pieces of which survived were divided into three groups which were treated with perilesional injection of vascular endothelial growth factor( VEGF) (0.4 mg/0.2 mL) , Endostar(0.125 g/0.2 mL) and physiological saline (0.2 mL)on the 21 d, 23 d, 25 d, 27 d after implantation. Sample were collected on the 10th day after perilesional injection, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining. Results IHC staining indicated that PCNA expression of fibroblasts was significantly increased in keloid tissue after VEGF injection, PCNA expression of fibroblasts was significantly reduced in keloid tissue after Endostar injection,TUNEL assay revealed lower apoptotic cells expression in the keloid tissue after VEGF injection and higher in the Endostar group than control group. The rate of proliferative index (PI) , apoptotic index(AI) and AI/PI of fibroblasts in keloid after VEGF (PI:41.13 ±2.29,AI:5.75 ±1.28,AI/PI: 0.14 ± 0.04)or Endostar injection (PI:27.25 ±2.61,AI:11.00±1.31,AI/PI:0.41 ±0.09)and control group (PI: 34.75 ±3.62,AI:7. 88 ± 1.64,AI/PI:0. 23 ±0.07) showed statistical differences. Conclusion Anti-angiogenesis therapy is shown to induce keloid regression through suppression of keloid fibroblast proliferation,induction of apoptosis, which may be a new approach for the treatment of keloids.
2.The early effects of revision hip arthroplasty for reconstruction of Paprosky type III acetabular defect using Cup-in-Cup technology
Jiacheng ZANG ; Xiuxiang ZHAO ; Xinlong MA ; Yinguang ZHANG
Chinese Journal of Orthopaedics 2022;42(9):579-586
Objective:To investigate the early effects of cup in cup technique in reconstructing paprosky III acetabular bone defect in revision hip arthroplasty.Methods:From January 2017 to December 2019, a total of 20 cases (20 hips) with paprosky III acetabular bone defect were reconstructed by Cup-in-Cup technique, including 9 males and 11 females. The age ranged from 45 to 76 years, with an average of 64.6 years. The causes of revision were aseptic loosening of prosthesis in 17 cases and loosening of prosthesis caused by periprosthetic infection in 3 cases. There were 13 hips with acetabular bone defect of paprosky IIIA and 7 hips with paprosky IIIB. The acetabular side was repaired in 13 cases, and the acetabulum and femoral side were repaired in 7 cases at the same time. Harris hip score was used to evaluate hip function during postoperative follow-up. The occurrence of serious complications such as intraoperative vascular and nerve injury, postoperative prosthesis dislocation, periprosthetic infection and fracture were counted. The height and horizontal position of hip rotation center were measured by X-ray film.Results:The operation duration was 110±25 min (range 80-180 min) and intraoperative bleeding was 700±180 ml. All cases were followed up for 12-36 months, with an average of 18 months. At the last follow-up, the Harris hip score of 16 cases was more than 80, with excellen in 2 cases, good in 14 cases and fair in 4 cases. The Harris score was 84.3±7.5, which was significantly higher than that before operation 40.1±16.6 ( t=15.34, P<0.001). The height of hip joint rotation center on the affected side decreased from 34.2± 3.3 mm before operation to 18.6±2.8 mm after operation with significant difference ( t=15.11, P<0.001). The horizontal distance increased from 18.1±5.5 mm before operation to 26.2±7.3 mm after operation with significant difference ( t=-5.95, P<0.001). After operation, the height of hip joint rotation center on the affected side was slightly higher than that on the opposite side, with a significant difference between the affected side 18.6±2.8 mm and the opposite side 12.2±3.3 mm ( t=6.73, P=0.018). The horizontal position was 26.2±7.3 mm, which had no significant difference compared with the contralateral 30.1±5.5 mm ( t=-3.29, P=0.381). There was no vascular and nerve injury, periprosthetic infection or incision related complications. During the following-up, the prosthesis was in satisfied position without prosthesis or screw loosening and fracture. Conclusion:The reconstruction of paprosky III acetabular bone defect with Cup-in-Cup technique in revision hip arthroplasty can obtain satisfied early effects, with achieving relatively normal hip rotation center and initial stability.
3.Association between TOX gene expression level and radiosensitivity in lower-grade gliomas
Yinguang MA ; Ming SUN ; Chang LIU ; Lu BAI ; Huijun LI ; Zaixiang TANG
Chinese Journal of Radiation Oncology 2023;32(9):836-842
Objective:To investigate the relationship between the expression level of thymocyte selection-associated high mobility group box protein ( TOX) gene and the radiosensitivity of lower-grade glioma (LGG) patients. Methods:Using bioinformatics research methods, 474 LGG patients from The Cancer Genome Atlas (TCGA) database were selected as the test set (TCGA-474 set), and two different genetic data sets ( n=412 and n=171) from the Chinese Glioma Genome Atlas (CGGA) database were selected as the validation set (CGGA-412 set and CGGA-171 set). Patients were stratified based on whether received radiotherapy, and divided into the high and low TOX expression group according to the expression level of TOX gene in LGG. Survival curves of all patients were plotted. The overall survival (OS) and progression-free survival (PFS) of patients in the high and low TOX expression groups were compared and analyzed using log-rank test. Results:Multivariate analysis of OS in the TCGA-474 set showed that high expression of TOX was a protective factor for OS ( HR=0.061, 95% CI: 0.005-0.791, P=0.044). After stratification analysis based on radiotherapy and adjustment for confounding factors, the HR (95% CI) of patients with high TOX expression in the TCGA-474, CGGA-412, and CGGA-171 sets were 0.405 (0.261-0.629), 0.581 (0.418-0.806), and 0.464 (0.269-0.800), respectively, with P values of <0.001, 0.001, and 0.008, respectively. Among patients receiving radiotherapy in the TCGA-474 set, the OS and PFS of patients with high TOX expression were significantly longer than those in the low TOX expression group, and the differences were statistically significant (both P<0.001). The OS benefit of patients with high expression of TOX was significantly prolonged in both the CGGA-412 and CGGA-171 sets compared to those with low TOX expression, and the differences were statistically significant (both P<0.001). Conclusion:The high expression of TOX may be related to the radiosensitivity of LGG, which may be a gene marker of the radiosensitivity of LGG.
4.Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231.
Yinguang GAO ; Zhicheng GE ; Zhongtao ZHANG ; Zhigang BAI ; Xuemei MA ; Yu WANG
Chinese Medical Journal 2014;127(10):1947-1953
BACKGROUNDBreast cancer is one of the most common malignant female diseases worldwide. It is a significant threat to every woman's health. Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells. According to previous literature, overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models, but there has been limited research on the significance of VEGI in the breast cancer.
METHODSIn our study, cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed. The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo. The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting. The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth, invasion, adhesion, and migration assay with subcutaneous tumor-bearing nude mice models. Then the growth curves of the subcutaneous tumors were studied. Expressions of VEGI, CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.
RESULTSInfection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI. As can be seen in the invasion, adhesion and migration assay, the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration, adhesion and invasion. The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups. Immunohistochemistry analysis of the tumor biopsies clearly showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly. In vitro and in vivo, the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.
CONCLUSIONSTaken together, recombinant lentivirus that were successfully constructed, demonstrated up-regulated VEGI gene expression in breast cancer cells. Lentivirus-mediated over-expression of VEGI weakened the ability of the breast cancer cell migration, adhesion and invasion. Over-expression of VEGI diminished the tumorigenic capacity of breast cancer cells in vivo. Up-regulation of VEGI gene expression however inhibited breast cancer MDA-MB-231 cell in the early apoptosis.
Apoptosis ; genetics ; physiology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; Female ; Gene Expression Regulation, Neoplastic ; genetics ; physiology ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; Vascular Endothelial Growth Factors ; genetics ; metabolism