ABSTRACT
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.
Subject(s)
Humans , Apoptosis , Bromocriptine , Half-Life , Hand , Pituitary Neoplasms , Prolactinoma , Receptors, Dopamine D2 , S-Phase Kinase-Associated ProteinsABSTRACT
Gene ADAM10 (a disintegrin and metalloproteinase 10) is a member of ADAMs gene family. The corresponding membrane protein contains a disintegrin domain and a metalloproteinase domain. It is involved in various biological events such as cell adhesion, cell fusion, cell migration, and membrane protein shedding and proteolysis. ADAM10 protein is overexpressed in many tumors, which interacts with adhesion molecules and critical signaling molecules associated with cancer development and tumor progression, and promotes tumor invasion and metastasis. Regulating the expression of ADAM 10 can inhibit tumor invasion and metastasis , which may become a new strategy for anticancer therapy.
ABSTRACT
Objective To provide anatomical basis for endoscopic endonasal transsphenoidal surgery for excision of sellar tumors. Methods The relationship between ostia of sphenoidal sinus and sellar areas of 25 heads of adult cadavers, and the structure of pituitary fossa and the relationship of the anterior-posterior clinoid processes of 21 heads of adult cadavers were observed and measured. At the same time, structure of 9 fresh heads of adult cadavers were observed with the operating endoscope. Results The distance between the ostia of the sphenoidal sinus to the tuberculum sellae, internal carotid artery, optic nerve and dorsum sellae were 14.6?3.0mm, 13.7?2.2mm, 11.6?1.8mm, and 22.6?3.2mm, respectively. The sagittal diameter of the pituitary fossa was 10.2?1.5mm. The transverse diameter of the pituitary fossa was 1.4?2.4mm. The distance between two anterior clinoid processes was 25.0?3.0mm. The distance between two posterior clinoid processes was 15.8?3.3mm. The distance between anterior clinoid process and ipsilateral posterior clinoid process was 7.8?1.7mm. The distance between anterior clinoid process to contralateral posterior clinoid process was 21.8?2.4mm. Conclusion These results would provide the surgeons a stereoscopic image about sellar areas, so that the operative field could be accurately defined in endoscopic endonasal transsphenoidal surgery for the excision of sellar tumors.
ABSTRACT
This paper reports 17 cases of traumatic bilateral epidural hematomas. The incidence of these cases was 8.7% of all cases of epidural hematoma. The hematomas in 15 cases were across the midline, and in the other 2 cases were at different location on either side. The mechanism and clinical features of bilateral epidural hematomas were discussed. The indications for early diagnosis were stressed.