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RISS 인기검색어
- 검색키워드
- 저자 : Xuehua Ding (검색결과 2 건)
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Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells
Jinxiang Huang,Fenglin Zhang,Lei Jiang,Guohan Hu,Wei Sun,Chenran Zhang,Xuehua Ding 대한암학회 2017 Cancer Research and Treatment Vol.49 No.2
Purpose Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogenrelated 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.
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Zheng Cai,Xinjie Hong,Wei Dai,Zhengwei Zhang,Qiang Liang,Xuehua Ding,Wei Sun 대한척추신경외과학회 2023 Neurospine Vol.20 No.3
Objective: Intramedullary spinal cavernous malformations (ISCMs) are rare vascular lesions of the spinal cord with unclear natural history and controversy over treatment. This study aimed to report a series of symptomatic ISCMs underwent microsurgical management to illustrate the natural history, clinical presentation, and surgical outcomes and to evaluate factors associated with hemorrhage events and neurological prognosis. Methods: This single-center retrospective study included 29 consecutive patients with whose demographic, symptomology, imaging, neurological, and surgical data were collected. The risk for hemorrhage events and factors affecting surgical outcomes were retrospectively analyzed. Results: There were 12 female (41.4%) and 17 male patients (58.6%), with an average age of 45.2 years (range, 17–69 years). The mean size of the lesion was 9.7 mm (range, 3–20 mm). Most patients had a bowel or/and bladder dysfunction symptom (n = 11, 37.9%), followed by sensory deficits (n = 5, 17.2%), gait disturbance (n = 5, 17.2%), pain (n = 4, 13.8%), and weakness (n = 4, 13.8%), most (n = 15, 51.7%) with a chronic onset. All patients received total resection without rehemorrhages after surgical resection in follow-up. Sixty-five point five percent patients (n = 19) improved, 13.8% (n = 4) remained stable, 20.7% (n = 6) got worsen. The overall annual hemorrhage risk was 2.1% per patient-year. A total of 27 hemorrhages occurred in the 18 patients, of which rehemorrhage rate increased to 50.0% (n = 9) with a previous history of hemorrhage. Patients with smaller lesion sizes were more likely to have hemorrhage or rehemorrhage events (p = 0.008). Recurrent hemorrhage of the lesions was a risk factor for neurological outcomes (p = 0.016). Conclusion: The risk of rehemorrhage was significantly increased in symptomatic ISCM patients with a previous history of hemorrhage. Rehemorrhage was a risk factor for neurological outcomes. Patients can benefit from microsurgical treatment to avoid rehemorrhage and further neurological deterioration.
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