Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific GBM subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients following treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available towards GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.

SummaryThe challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.

This study assesses the efficacy of preoperative lumbar drain (LD) placement prior to elective open cranial and endoscopic anterior skull base (ASB) surgery in reducing postoperative cerebrospinal fluid (CSF) leak. A retrospective review of 93 patients who underwent LD placement at our institution between 2006 and 2011 was performed. Of these patients, 43 underwent elective LD placement prior to ASB surgery; 2 patients had evidence of CSF rhinorrhea prior to surgery, and 41 had no evidence of a preoperative CSF leak. Of those 41 patients, 2 developed CSF rhinorrhea (2/41= 4.9%) as a result of surgery—all in our endoscopic patient population (N = 21; 2/21= 9.5%). No postoperative CSF leaks were noted in our open ASB surgery cohort (N = 20). Other complications were rare, but we encountered two instances of delayed malignant cerebral edema in the open ASB cohort that are discussed in detail. Overall, preoperative LD placement was found to be an effective means of preventing postoperative CSF leaks after ASB approaches, but potential and significant intracranial complications may occur in select patients that merit careful consideration prior to LD placement.