Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project. MATERIALS AND METHODS: Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. RESULTS: Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells. CONCLUSION: These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

Therapeutic effect compared between three cannulated screws and proximal femoral locking plate in treatment of femoral neck fracture / 中国医师进修杂志

Objective To compare the therapeutic effect between three cannulated screws and proximal femoral locking plate in treatment of femoral neck fracture.Methods A total of 75 patients were included,the three cannulated screws group contained 31 patients,and the proximal femoral locking plate group contained 44 patients.The clinical healing time,hip function score at last follow-up and postoperative complication were compared.Results All patients were followed up for 13-18 (15.3 ± 3.2) months.The excellent and good rate of proximal femoral locking plate group was 95.5％ (42/44),and three cannulated screws group was 83.9％(26/31),there was no statistical difference between the two groups (P ＞ 0.05).The clinical healing time of fracture and hip function score at last follow-up in proximal femoral locking plate group were significantly better than those in three cannulated screws group [(14.6 ± 1.7) weeks vs.(18.1 ± 4.9) weeks,(90.9 ± 3.5) scores vs.(82.3 ± 8.3) scores],there were statistical differences between the two groups (P ＜ 0.05).Conclusions Proximal femoral locking plate provides short clinical healing time of fracture,stable fixation,good biomechanical properties and a low rate of postoperative complication in treatment of femoral neck fracture.It is one of the ideal methods in treatment of femoral neck fracture.