Restoration of p53 function for selective Fas-mediated apoptosis in human and rat glioma cells in vitro and in vivo by a p53 COOH-terminal peptide.

We have shown that a COOH-terminal peptide of p53 (amino acids 361-382, p53p), linked to the truncated homeobox domain of Antennapedia (Ant) as a carrier for transduction, induced rapid apoptosis in human premalignant and malignant cell lines. Here, we report that human and rat glioma lines containing endogenous mutant p53 or wild-type (WT) p53 were induced into apoptosis by exposure to this peptide called p53p-Ant. The peptide was comparatively nontoxic to proliferating nonmalignant human and rat glial cell lines containing WT p53 and proliferating normal human peripheral marrow blood stem cells.

Translational regulation of TRAIL sensitivity.

TNF-related apoptosis-inducing ligand (TRAIL) is a peptide that induces apoptosis to varying degrees in tumor cells. While TRAIL sensitivity in tumors has been linked to c-myc- and MEK/Erk-induced enhancement of caspase activation, our recent study identified a third input controlling TRAIL sensitivity, namely the Akt-mTOR pathway. We showed that instead of enhancing TRAIL sensitivity, Akt expression, acting through mTOR and the mTOR targets S6 kinase and eIF-4E, selectively enhances translation of the anti-apoptotic protein FLIP(S) and confers TRAIL resistance.

Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury.

Object: Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities.

Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults.

Object: The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression.

Methods: Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed.

Changes in transcranial motor evoked potentials during intramedullary spinal cord tumor resection correlate with postoperative motor function.

Objective: Intraoperative monitoring of transcranial motor evoked potentials (TcMEPs) has been investigated recently as a means of preventing motor deficits associated with resection of intramedullary spinal cord tumors (IMSCTs). In this study, we hypothesized that changes in the intraoperative MEPs during tumor resection correlate with postoperative motor function deficits.

Methods: A retrospective record review was conducted for 28 patients who underwent resection of an IMSCT using myogenic or muscle-recorded TcMEPs during a 44-month period.

Cooperative translational control of gene expression by Ras and Akt in cancer.

Ras and Akt are signaling proteins that mediate fundamental aspects of normal growth and development in many organisms. When the Ras and Akt pathways become overly active, malignant transformation of normal tissue can occur. The combined activity of these two proteins has generated the transformation of human cell cultures and tumor formation in mice.

Spinal cord and intradural-extraparenchymal spinal tumors: current best care practices and strategies.

The management of patients with intradural spinal tumors differs in many respects from approaches taken for patients with intracranial tumors. Intramedullary lesions are often completely surrounded by normal spinal cord, displacing vital functional tracts eccentrically. Extramedullary lesions can drastically compress the spinal cord and nerve roots, reducing normal tissue to a ribbon-like consistency.

Stereotactic radiosurgery and interstitial brachytherapy for glial neoplasms.

The application of focal radiation therapies in the management of malignant gliomas has gone through a number of stages. Earlier efforts to improve local control of malignant gliomas involved the use of brachytherapy. Despite some early encouraging results, Phase 3 studies did not prove a significant survival benefit for the addition of brachytherapy for newly diagnosed glioblastoma.

Neuromonitoring during surgery for metastatic tumors to the spine: intraoperative interpretation and management strategies.

Resection of metastatic tumors of the spine poses great technical challenges, with the potential of creating severe neurologic deficits. Several modalities of electrophysiologic monitoring, including SSEPs and MEPs, have evolved to aid in resection of these tumors. This review has presented additional techniques-such as mapping of the dorsal columns with antidromic-elicited SSEPs to plan the myelotomy and direct intra-medullary stimulation-that help to identify the extent of the tumor margin at its interface with functional tracts.

Intraventricular neurocytomas.

The literature to date on the treatment of CNC reflects an evolution of clinical practice in neurooncology. The advent of sophisticated tools, such as MRS and molecular pathology, has facilitated more efficient diagnosis of CNC. Decreased morbidity associated with surgical intervention has resulted in better outcomes in patients undergoing resection of CNC.

Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration.

The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown.

Autologous adjuvant linked fibroblasts induce anti-glioma immunity: implications for development of a glioma vaccine.

Objectives: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe an in vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described.

Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro.

Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro.