OBJECTIVEDespite intensive medical treatment, patients with glioblastoma (grade IV glioma [GBM]) have a low 5-year survival rate of 5.5%. In this study, the authors tried to improve currently used therapies by identification of a therapeutic target, IGFBP3, for glioma treatment.METHODSIGFBP3 RNA expression in 135 patients newly diagnosed with glioma was correlated with clinicopathological factors. Immunohistochemical analysis was performed to determine IGFBP3 protein expression in glioma specimens. The effect of IGFBP3 depletion on cell proliferation was examined using IGFBP3 knockdown glioma cells. Intracranial infusion of IGFBP3 siRNAs was performed to evaluate the effect of IGFBP3 depletion in mouse intracranial xenograft models.RESULTSWe demonstrated higher IGFBP3 expression in GBM than in tumor margin and grade II glioma. IGFBP3 expression was not only positively correlated with tumor grades but also associated with tumor histology and IDH1/2 mutation status. Additionally, higher IGFBP3 expression predicted shorter overall survival in glioma and GBM proneural subgroup patients. In vitro cell culture studies suggested IGFBP3 knockdown suppressed cell proliferation and induced cell cycle G2/M arrest as well as apoptosis in glioma cells. Also, accumulation of DNA double-strand breaks and γH2AX was observed in IGFBP3 knockdown cells. IGFBP3 knockdown delayed in vivo tumor growth in mouse subcutaneous xenograft models. Furthermore, convection-enhanced delivery of IGFBP3 siRNA to mouse brain suppressed intracranial tumor growth and prolonged survival of tumor-bearing mice.CONCLUSIONSOur findings suggest IGFBP3 predicts poor outcome of glioma patients and is a potential therapeutic target for which depletion of its expression suppresses tumor growth through inducing apoptosis and accumulation of DNA damage in glioma cells.

COX-2 overexpression is a predictor for poor survival for advanced stage NPC. In vitro, NS-398 radiosensitizes the NPC-BM1 cell line, providing a basis for testing the combination of COX-2 inhibitors with radiation in the treatment of patients with NPC.

No abstract

Low TS expression is significantly associated with female GC patients and responders to 5-FU-based adjuvant chemotherapy. It predicts longer DFS and OS in selected GC patients treated with 5-FU-based adjuvant chemotherapy after curative resection. The results suggest that prospective assessment of TS staining intensity in tissue samples obtained from GC patients undergoing gastrectomy would be useful to predict the patients who would be benefited from 5-FU-based adjuvant chemotherapy after gastrectomy.

Metastatic melanoma to a pituitary oncocytoma is a very rare condition. A 76-year-old man was presented with progressive visual disturbance and falling down with initial loss of consciousness 2 days before admission. He had a subungual acral lentiginous melanoma (T3N1M0) with gangrenous change of left big toe, treated by amputation 15 months ago. Computed tomography and MR imaging demonstrated masses involving inguina, mediastinum and left renal hilum and dumb-bell shaped hyperdense mass, approximately 6.2 x 3.7 mm, that involved pituitary fossa and suprasellar region with adjacent bony destruction. He underwent surgical resection of the tumor. Microscopically, the tumor revealed an admixture of pituitary adenoma and invasive metastatic melanoma with fragments containing both populations in juxtaposition. The adenoma was negative for melanoma markers and pituitary hormone markers. The melanoma was positive for S-100 protein and BMB-45. Ultrastructure of the adenoma revealed abundant mitochondria and sparse secretory granules. The diagnosis was metastatic melanoma to a pituitary oncocytoma. The current literature on metastatic tumors to pituitary adenoma is reviewed.