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Justin G. Santarelli, Vahé Sarkissian, Lewis C. Hou, Anand Veeravagu and Victor Tse

✓The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naïve brain and cancer cells is made in advance of any metastatic breach of the blood–brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

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Nika V. Polevaya, M. Yashar S. Kalani, Gary K. Steinberg and Victor C. K. Tse

✓ The description of cerebral aneurysms dates back to antiquity. Little was known, however, about the pathological mechanisms of aneurysm formation and treatment options for this disease until 200 years ago. The modern era of aneurysm treatment began with the hunterian ligation of the proximal artery, followed by clip and coil occlusion. In this article, the authors describe the transition from conservative therapy to internal carotid artery (ICA) ligation and gradual occlusion of the ICA to the direct placement of clips on aneurysms. The driving forces and rationale behind each major advancement are summarized, and the authors attempt to predict what these innovations mean for the future of intracranial aneurysm management.

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M. Yashar S. Kalani, Maziyar A. Kalani, Ryder Gwinn, Bart Keogh and Victor C. K. Tse

The human insular cortex, or the lobus insularis, is considered the developmentally most primitive lobe of the telencephalon. Covered by an overlying cortical lid, the insula has functions that are distinct from yet related to those of the adjacent temporal lobe and deep limbic structures. In the first part of this paper the authors outline the development of the human insula, including the cellular heterogeneity comprising the various parts of the insular lobe. Using the understanding gained from the development of the insula they then address implications of insular development for cortical development and connection as well as for tumorigenesis and tumor spread from the insula to other cortical structures, most notably the temporal lobe. An understanding of cortico-insular development and interconnection allows for both a better understanding of insular pathology and also facilitates planning of resection of cortico-insular gliomas to avoid damage to eloquent structures.

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Jay D. Turner, Richard Williamson, Kaith K. Almefty, Peter Nakaji, Randall Porter, Victor Tse and M. Yashar S. Kalani

MicroRNAs (miRNAs) are now recognized as the primary RNAs involved in the purposeful silencing of the cell's own message. In addition to the established role of miRNAs as developmental regulators of normal cellular function, they have recently been shown to be important players in pathological states such as cancer. The authors review the literature on the role of miRNAs in the formation and propagation of gliomas and medulloblastomas, highlighting the potential of these molecules and their inhibitors as therapeutics.

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Stephen L. Huhn, Yun Yung, Samuel Cheshier, Griffith Harsh, Laurie Ailles, Irving Weissman, Hannes Vogel and Victor Tse

Object

The goal of this study was to illustrate the findings of a significant subpopulation of cells within a pediatric astroblastoma that have the specific cell surface phenotype found on known human neural stem cells.

Methods

Cells with a cell surface marker profile characteristic of human neural stem cells were isolated using fluorescence-activated cell sorting from a mostly nonmitotic astroblastoma removed from the brain of an 11-year-old girl. An unusually high proportion (24%) of the cells were CD133 positive and CD24, CD34, and CD45 negative (CD133+ CD24CD34CD45 cells), the phenotypic antigenic pattern associated with neural stem cells; very few CD133-positive cells were not also CD24, CD34, and CD45 negative. Some cells (12%) were CD34 positive, indicating the presence within the tumor of hematopoietic stem cells. Cells formed cytospheres that resembled neurospheres when seeded into stem cell media and coexpressed β-tubulin and glial fibrillary acidic protein (GFAP) but did not express the oligodendrocyte marker O4. Cell proliferation was demonstrated by incorporation of bromodeoxyuridine. The cells lost their capacity for self-renewal in vitro after four to six passages, although they continued to coexpress β-tubulin and GFAP. The cells did not differentiate into neurons or astrocytes when placed in differentiation medium.

Conclusions

Although this astroblastoma contained a high proportion of phenotypic neural stemlike cells, the cells had limited proliferative capacity and multipotency. Their role in astroblastoma formation and growth is unknown.

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Lewis C. Hou, Anand Veeravagu, Andrew R. Hsu and Victor C. K. Tse

✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.