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Objective To study the inhibitory effect of T lymphocytes secreting EphrinAl-Caspase-3 in vivo and on the growth of cancer cells in nude mice with breast cancer. Methods Nude mice (n = 35) were inoculated with breast cancer cells to construct a nude mouse model of breast cancer. When the tumor volume reached 0. 1 cm3, 30 nude mice with average size tumor tissue were randomly divided into PBS group, uninfected adenovirus group, T lymphocyte infected with Ad-EphrinAl-Caspase-3 group, and intratumoral transplantation. Tumor size was measured every day 2 to 3. Three groups of tumor-bearing nude mice were selected. After the above-mentioned cell transplantation, the subcutaneous tumor tissue homogenate was obtained every day 2 to 3, and the content of EphrinAl-Caspase-3 was detected by ELISA. At the end of the experiment, the animals in each group were sacrificed by cervical dissection and sliced. The presence of T lymphocytes expressing green fluorescent protein was observed under a fluorescence microscope, and Caspase-3 and Ki-67 were detected by immunofluorescence. Results After one week of inoculation of breast cancer cells into nude mice, the presence of subcutaneous tumors could be touched by hand, which proved that the tumor-bearing animals of breast cancer cells were successfully modeled. On the 8th day after inoculation, the tumor volume of the nude mice in each group became larger, and the difference between the treatment group and the PBS group/T lymphocyte group was extremely significant ( P<0.05). Although the tumor volume of the T lymphocyte transplantation group was slower than that of the PBS control group, there was no statistically significant difference between the two. The expression of EphrinAl-Caspase-3 was detected in the EphrinAl-Caspase-3 treatment group on the 2nd day, reached the peak on the 8th day, and then the secretion decreased gradually. No expression of EphrinAl-Caspase-3 was detected in the PBS control group and the T lymphocyte group. The presence of dispersed green fluorescent protein-labeled EphrinAl-Caspase-3-T lymphocytes was observed in the tumor tissues of the treatment group, while the presence of green fluorescent protein was not detected in the PBS group and the T lymphocyte groups. In the infected cells of the treatment group, the proportion of Caspase-3 positive cells was up- regulated, and the proportion of Ki-67 positive cells was down-regulated. No expression of EphrinAl-Caspase-3 was detected in the PBS group and the T lymphocyte group. Conclusion EphrinAl-Caspase-3 can significantly inhibit the growth of breast cancer cells, thereby exerting an anti-tumor effect.
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Objective:To investigate the expressions and significance of tyrosine kinase receptor EphA2 and its ligand ephrinA1 in human malignant gliomas and their correlation with tumor angiogenesis. Methods:The expressions of EphA2, ephrinA1, and CD105-stained microvessel density (MVD) were detected via immunohistochemical assay in 62 glioma tissues and 8 normal brain tissues. The correlation between EphA2 and ephrinA1 expression and microvessel counts in the glioma tissues were assessed. Results:Immunohistochemical staining results revealed that variable levels of EphA2 and MVD expression were significantly higher than that of the normal brain samples. Statistical difference was observed in EphA2 and MVD expressions between human gliomas and normal brain samples (P<0.01). The positive rate of EphA2 and MVD expressions was significantly higher in high-grade gliomas (WHO III-IV) than that in low-grade gliomas (WHO I-II) (P<0.01). EphrinA1 was expressed at low levels in most malignant gliomas, and the increased ephrinA1 expression was associated with lower-grade histology. MVD was significantly positively correlated with EphA2 expression (r=0.713, P<0.01) and significantly negatively correlated with ephrinA1 expression (r=-0. 772, P<0.01). EphA2 was significantly negatively correlated with ephrinA1 expression (r=-0.912, P<0.01). Conclusion:Specifically over-expressed EphA2 and its low-expressed ligand ephrinA1 in malignant gliomas may be closely correlated with the invasion and malignant degree of gliomas. Cooperation is involved in the angiogenesis and has an important function in the initiation and progression of gliomas.
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Objective:To detect the effect of EphrinA1-Fc on the phosphorylation of EphA2 and extracellular signal-regulated ki-nase (ERK) in 786-O renal carcinoma cells (RCCs). Methods:The soluble ligand EphrinA1-Fc was used to inhibit the 786-O RCCs in vitro. Western blot analysis was used to examine the phosphorylation of EphA2 and ERK1/2 in the 786-O RCCs at different time points. Results:After the intervention with EphrinA1-Fc for 5, 10, 30, and 60 min, the expression of p-EphA2 increased (F=9.392, P=0.025) as well as that of p-ERK (F=4.428, P=0.041). No p-EphA2 and p-ERK expression was observed in the pre-intervention group. Conclusion:One of the possible mechanisms of the inhibitory effect of EphrinA1-Fc on tumor metastasis and recurrence involves the phosphorylation of EphA2 by EphrinA1-Fc, leading to the degradation of EphA2.
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Objective To investigate the expressions of EphA2 and EphrinA1 in bladder carcinomas and their clinical significance. Method The expressions of EphA2 and EphrinA1 were detected on bladder carcinomas (75 cases ) by immunohistochemistry S-P method. Results ( 1 ) The positive rates of expression of EphA2 and EphrinA1 were 61.3%(46/75) and 46.7%(35/75) respectively. (2) The expression of EphA2 was related to tumor size, lymphatic metastasis and TNM staging(P＜ 0.05),but not to gender,age and pathology type (P ＞ 0.05 ). ( 3 )The expression of EphrinA1 was related to tumor size and lymphatic metastasis (P ＜ 0.05 ), but not to gender, age, pathology type and TNM staging (P ＞ 0.05 ). (4)There was significantly positive correlation between the expression of EphA2 and EphrinA1 (P ＜ 0.05).Conclusions EphA2 and EphrinA1 are related to the occurrence and development of bladder carcinoma.The combined detection of EphA2 and EphrinA1 can help to predict the clinical and pathologic characteristics of bladder carcinoma. It is an important index to assist treatment, they are predictive factors for bladder carcinoma.
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Objective To investigate the expressions of EphA2 and its ligand EphrinA1 and their relationship with angiogenesis in gastric carcinoma. Methods Expressions of EphA2,EphrinA1 and CD34-stained microvessel density (MVD) were detected by immunohistochemical assay in gastric carcinoma tissues,adjacent tissues (1.5 to 2 cm from the mass) and normal gastric mucosa (5 to 10 cm from the mass) from 82 cases. The correlations among EphA2 and EphrinA1 expressions,MVD and clinic pathological features were analyzed. Results EphA2,EphrinA1 expressions and MVD in gastric carcinomas tissues were significantly higher than those in adjacent tissues and normal gastric tissues (P