Kaveh Barami

Relationship of gliomas to the ventricular walls

The role of neural stem cells in gliomagenesis remains controversial. The aim of this study was to determine the anatomic relationship of human gliomas to the lining of the ventricular walls, known as the subventricular zone, an area replete with neural stem cells. We performed a retrospective radiographic analysis of 100 consecutive patients with gliomas and sought to determine the relationship of the lesions to the ventricular walls as seen on their MRI scans. Our results indicated that in 93% of cases the lesions contacted at least one region of the lateral ventricular wall. Contact with the ventricular wall was independent of the glioma size or mass effect. These findings were correlated to cytoarchitectural studies of the human subventricular zone. Our findings lend further support that there is an intimate association between gliomas and the subventricular zone.

Oncomodulatory mechanisms of human cytomegalovirus in gliomas.

Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of high grade gliomas. Although HCMV is not recognized as an oncogenic virus, it might increase the malignancy of the infected cell by disrupting cellular pathways involved in the cell cycle, apoptosis, angiogenesis, cell invasion and the host immune response. This article reviews the recent evidence of the modulatory effects of HCMV infection leading to the malignant progression of gliomas and explores novel therapeutic targets against such lethal tumors.

Relationship of neural stem cells with their vascular niche: implications in the malignant progression of gliomas.

During embryogenesis and in regions of the adult brain undergoing post-natal neurogenesis, neural stem cells and endothelial precursors are found within a vascular niche, where the coordinated interactions between neurogenesis and vasculogenesis dictates development and responses to the environment. Moreover, recent evidence suggests that gliomas may arise from transformed neural stem cells and that angiogenesis is important in the malignant progression of these tumors. Taken together, these findings have led researchers to focus on the dynamic interaction between neural stem cells and their vascular niche so as to find new therapeutic strategies to halt the progression of gliomas. This review summarizes the cellular substrates responsible for the coordinated interactions between the nervous and vascular systems and how this relates to gliomagenesis.

Biology of the subventricular zone in relation to gliomagenesis.

There is recent compelling evidence that gliomas arise from neural stem cells residing in the lining of the lateral ventricles, known as the subventricular zone, that have undergone malignant transformation. This article reviews the operative elements, including cytoskeletal proteins, tumor suppressor genes, cell adhesion molecules, growth factors, transcription factors and developmental pathways that link the subventricular zone to gliomagenesis. It is hoped that with an improved understanding of the putative source of gliomas, new therapeutic strategies will be developed against such deadly tumors.

Incidence, risk factors and management of delayed wound dehiscence after craniotomy for tumor resection.

Dehiscence after a wound has healed is a known complication of craniotomy for tumor resection. We conducted a retrospective analysis of 64 patients who underwent craniotomy for tumor resection followed by radiation or radiosurgery between 2006 and 2010. Five patients (7.8%) were identified who showed wound dehiscence from two to eight months after the craniotomy wound had healed. Four patients had previously undergone additional craniotomies, additional radiosurgery or had been treated with the anti-angiogenic factor, bevacizumab. These treatments may be risk factors for developing delayed dehiscence and, in combination, may potentiate local wound healing problems. Potential mechanisms and management strategies are discussed.

Lipopolysaccharide-induced inflammatory cytokine production by Schwann's cells dependent upon TLR4 expression

Signaling of Toll-like receptor-4 (TLR4) through its cognate ligand endotoxin appears critical in tissue inflammation associated with bacterial infection. We found that anti-GM1 antibody (Ab) enhances TLR4 expression in Schwanns cells (SCs) in vivo and in vitro. The anti-GM1 Ab-treated SC also showed increased release of pro-inflammation cytokines IL-1beta and TNF-alpha after incubation with lipopolysaccharide (LPS). Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in LPS stimulated cultures. These findings suggest that elevation of TLR4 expression increases sensitivity of SC to LPS and production of inflammatory mediators that may be responsible for peripheral nerve dysfunction.

CyberKnife radiosurgery for management of intracranial perineural spread of cutaneous malignancies

Intracranial perineural spread (PNS) is a rare complication of cutaneous malignancies and refers to access of the tumor to the intracranial space typically by tracking along cranial nerves. Patients are usually treated with palliative external-beam radiotherapy or with radiosurgery if there has been prior standard radiotherapy. Two patients are presented, both with cranial neuropathies occurring years after treatment for cutaneous malignancies. Radiographic workup showed recurrent tumor involving multiple cranial nerves. Both patients were treated with CyberKnife radiosurgery. To the authors knowledge, these are the first reported patients with intracranial PNS treated via CyberKnife radiosurgery.