Matrix metalloproteinases (MMPs) have been implicated to play a critical role in glioma invasiveness. In this study, we aimed to investigate the expression of MMP-2 and MMP-9 in human gliomas of different degrees of malignancy, and evaluated the correlation between MMP-2 and MMP-9 expression in gliomas. The samples from 65 cases of glioma were divided into four groups according to the WHO classification: there were 16 cases of grade I, 17 cases of grade II, 20 cases of grade III, and 12 cases of grade IV. Normal brain samples served as the control group, and biopsy specimens were obtained from 8 glioma patients with a needle placed into the adjacent brain 1 cm from the margin after tumor resection. All the samples were stained with hematoxylin and eosin and immunohistochemistry. A computer-aided image-analysis system was employed to measure the integral optical density (IOD) of positive slides. No positive staining was found in the control group. The positive staining was localized in the cytoplasm of glioma cells, the extracellular matrix (ECM), the basement membrane (BM), and the endothelial cells of blood vessels. Positive staining rates increased significantly when the degree of malignancy of gliomas was elevated. The IOD value of MMP-2 and MMP-9 also indicated that the intensity of MMP-2 and MMP-9 expression was elevated significantly with the degree of malignancy of the gliomas. There was a positive correlation between MMP-2 and MMP-9 expression in gliomas. Glioma invasion and angiogenesis were particularly seen in the biopsied tissues, and MMP-9 immunostaining seemed to be much more intense and extensive than MMP-2 immunostaining in these samples. These results suggest that MMP-2 and MMP-9 staining in gliomas is localized in the cytoplasm of tumor cells, BM, and endothelial cells, and that MMP-2 and MMP-9 together play an important role in the invasiveness of gliomas, mediating the degradation of the ECM and angiogenesis. MMP-2 and MMP-9 could be molecular targets in the treatment of malignant glioma.

Serum copper and zinc concentrations and copper/zinc ratios have been shown to be increased in several types of human malignancies, including human brain tumors. In this study, copper and zinc levels and copper/zinc ratios were determined by atomic absorption analysis in tissue and serum from 29 primary and metastatic brain tumor patients. Metastatic carcinomas and malignant gliomas revealed significantly higher tissue copper concentrations than control tissues and meningiomas. Malignant gliomas demonstrated significantly higher tissue copper/zinc ratios. Both serum copper and copper/zinc ratio were significantly higher in the metastatic carcinoma group than control; however, serum copper levels in malignant glioma patients were not significantly different from control tissues. There were no differences both in the serum and the tissue concentrations of these trace elements in meningiomas and controls. These data suggested that copper, an important angiogenic factors, is accumulated within the malignant tissues of metastatic carcinoma and malignant glioma, but not meningiomas. These findings may have implications regarding angiogenesis in these tumors.

Angiogenesis plays a crucial role in tumor growth. Recently, endocan has emerged as a new marker of vascular endothelial cells from cancers in other organs. In this study, we elucidated the relationship between endocan expression and tumor invasion of pituitary adenoma. Tumor tissues were obtained from 70 patients with pituitary adenoma and were examined using fluorescence immunohistochemistry. Tissue samples included 4 adrenocorticotrophic hormone producing adenomas, 10 growth hormone-producing adenomas, 49 clinically nonfunctioning adenomas, 6 prolactin producing adenomas, and 1 thyroid-stimulating hormone producing adenoma. Endocan was exclusively expressed in CD34-positive vascular endothelial cells, with over 90 % colocalization. The CD34 expression was significantly elevated with endocan expression (linear regression slope, 1.200; r(2) = 0.268, F = 23.08, p < 0.0001). As a percentage of CD34 expression, endocan expression was elevated in a Knosp grading dependent manner (Spearman's r-value, 0.651; p < 0.0001), and was also significantly elevated in macroadenomas compared with microadenomas (p = 0.0133). However, no differences in endocan expression were observed between hormonal subtypes (p = 0.066; Kruskal-Wallis test), age (Spearman's rank correlation test, p = 0.4909), or sex (Mann-Whitney test, p = 0.1701). These data show that endocan is closely related to tumor angiogenesis, and may predict tumor invasion into neighboring cavernous sinuses in pituitary adenomas.

Hypoxia inducible factors (HIF) are transcription factors regulating expression of several genes related to oxygen homeostasis in response to hypoxic stress. Although HIF1-alpha and platelet derived growth factor-B (PDGF-B) are expressed in glioma tissue and closely related to tumor angiogenesis mediating vascular endothelial growth factor (VEGF) activity, their direct relationship has not yet been clarified. The aim of this study is to investigate whether HIF1-alpha regulates PDGF-B expression. The human glioblastoma cell lines, U87MG, U251MG, and A172, were exposed to 1-21% oxygen for 24 h. PDGF-B mRNA expression were quantitatively analyzed by real time RT-PCR, their intracellular protein levels were determined by computerized image analysis supported by flow cytometry to detect intracellular PDGF-B, and the concentration of secreted PDGF-B protein was assayed by ELIA. We also assayed following transfection of the cells with short interference RNA (siRNA) targeting HIF1-alpha mRNA. Relative PDGF-B mRNA and secretion of PDGF-B protein were significantly elevated at 1% oxygen. Following transfection of HIF1-alpha siRNA at 1% oxygen, PDGF-B expression was significantly suppressed at mRNA level. Our findings indicated that HIF1-alpha up-regulated expression of PDGF-B in human glioblastoma cells and showed the feasibility of siRNA technology in glioblastoma cell lines.

Cavernous hemangiomas rarely occur in the calvarium and most commonly present in middle-age. Although a congenital vascular disorder can theoretically cause a diploic lesion in any age group, a calvarial cavernous hemangioma has not been reported in newborn. A 4-month-old male infant presented with a large left parietal mass that had been present since birth. Total resection was performed. Pathological examination revealed a cavernous hemangioma developing within the diploic space adjacent to prior hemorrhages. Surgery was performed in this case because of the size and persistence of the lesion. Removal of tumors of a benign nature from the calvarium can be done safely. Cavernous hemangioma of the skull in a neonate should be considered as one of the differential diagnoses in the case of suspected ossified cephalohematoma.