The TNs extending into multiple fossae can be totally removed using the following single-stage surgical techniques: Type MP by the anterior transpetrosal approach; Type ME by the zygomatic or orbitozygomatic infratemporal approach; and Type MPE by the zygomatic transpetrosal approach. In 12 of 13 cases involving multiple fossae in this series, total tumor removal was achieved using single-stage skull base surgery.

When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.

Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA-binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons. The expression of Musashi1 is downregulated with the successive progression of neurogenesis. In normal adult human tissues, we detected low levels of Musashi1 expression in brain and testis by RT-PCR analysis. In an RNA panel of 32 cancer tissues and cell lines, elevated expression of Musashi1 was seen in all five malignant gliomas studied, in contrast to the slight expression seen in other tumor cells, including those in several melanomas and a prostate cancer. Western blot analysis showed strong Musashi1 expression in malignant gliomas compared with nonneoplastic brain tissue. Glioblastomas, the most malignant form of glioma, showed higher Musashi1 expression than less malignant gliomas by immunohistochemical analysis. Tumors with strong Musashi1 expression tended to have high proliferative activity. Thus, the expression of Musashi1 correlated with the grade of the malignancy and proliferative activity in gliomas. These results suggest that primary CNS tumors may share gene expression patterns with primitive, undifferentiated CNS cells and that Musashi1 may be a useful marker for the diagnosis of CNS tumors.

ADAMs (a disintegrin and metalloproteinases) are multifunctional molecules involved in cell-cell fusion, cell adhesion, membrane protein shedding, and proteolysis. In the present study, we examined the mRNA expression of 13 different ADAM species with putative metalloproteinase activity in human astrocytic tumors, nonneoplastic brain tissues, and other intracranial tumors by reverse transcriptase-polymerase chain reaction, and found that prototype membrane-anchored ADAM12 (ADAM12m) is predominantly expressed in glioblastomas. Real-time quantitative polymerase chain reaction indicated that the expression level of ADAM12m is remarkably at least 5.7-fold higher in glioblastomas (n ‫؍‬ 16) than in nonneoplastic brain tissues (n ‫؍‬ 6), low grade (n ‫؍‬ 7) and anaplastic astrocytic tumors (n ‫؍‬ 9) (P < 0.05 for each group), and intracranial neurinomas (n ‫؍‬ 5) (P < 0.01). In situ hybridization showed that glioblastoma cells are responsible for the gene expression. ADAMs (a disintegrin and metalloproteinases) are a gene family of multidomain membrane-anchored proteins comprising of more than 30 members in various animal species (see http://www.people.virginia.edu/ϳjw7g/Tableof theADAMs.html) and are implicated in pathophysiological conditions, which include neuronal development, 1 cancer development and progression, 2,3 and inflammatory responses 4 through proteolysis, cell adhesion, cell fusion, and cell-matrix interaction. 5,6 They contain several distinct domains with structural homology to the reprolysin/adamalysin family of snake venom metalloproteinases.7 A typical ADAM protein includes an N-terminal signal peptide, and propeptide, metalloproteinase, disintegrin, cysteine-rich, epidermal growth factor-like, transmembrane, and cytoplasmic domains. The metalloproteinase domains of several ADAMs have a catalytic site with the conventional zinc-dependent metalloproteinase sequence (HEXGHXXGXXHD), which is highly homologous to that of the matrix metalloproteinases (MMPs).

The microvasculature and immune cells are major components of the tumor microenvironment (TME). Hypoxia plays a pivotal role in the TME through hypoxia-inducible factor 1-alpha (HIF-1α) which upregulates vascular endothelial growth factor (VEGF). VEGF, an angiogenesis stimulator, suppresses tumor immunity by inhibiting the maturation of dendritic cells, and induces immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells. HIF-1α directly induces immune checkpoint molecules. VEGF/VEGF receptor (VEGFR)-targeted therapy as a cancer treatment has not only anti-angiogenic effects, but also immune-supportive effects. Anti-angiogenic therapy has the potential to change the immunological "cold tumors" into the "hot tumors". Glioblastoma (GB) is a hypervascular tumor with high VEGF expression which leads to development of an immuno suppressive TME. Therefore, in the last decade, several combination immunotherapies with anti-angiogenic agents have been developed for numerous tumors including GBs. In particular, combination therapy with an immune checkpoint inhibitor and VEGF/VEGFR-targeted therapy has been suggested as a synergic treatment strategy that may show favorable changes in the TME. In this article, we discuss the cross talk among immunosuppressive cells exposed to VEGF in the hypoxic TME of GBs. Current efficient combination strategies using VEGF/VEGFR-targeted therapy are reviewed and proposed as novel cancer treatments.