An Eighteen Serum Cytokine Signature for Discriminating Glioma from Normal Healthy Individuals.

Glioblastomas (GBM) are largely incurable as they diffusely infiltrate adjacent brain tissues and are difficult to diagnose at early stages. Biomarkers derived from serum, which can be obtained by minimally invasive procedures, may help in early diagnosis, prognosis and treatment monitoring. To develop a serum cytokine signature, we profiled 48 cytokines in sera derived from normal healthy individuals (n = 26) and different grades of glioma patients (n = 194).

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis.

Glioblastoma (grade IV glioma/GBM) is the most common primary adult malignant brain tumor with poor prognosis. To characterize molecular determinants of tumor-stroma interaction in GBM, we profiled 48 serum cytokines and identified macrophage colony-stimulating factor (MCSF) as one of the elevated cytokines in sera from GBM patients. Both MCSF transcript and protein were up-regulated in GBM tissue samples through a spleen tyrosine kinase (SYK)-dependent activation of the PI3K-NFκB pathway.

Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1β in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein.

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n=27) and GBM (n=28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.

Methylation silencing of ULK2, an autophagy gene, is essential for astrocyte transformation and tumor growth.

Glioblastoma (GBM) is the most aggressive type of brain tumor and shows very poor prognosis. Here, using genome-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological processes. One of the hypermethylated genes in GBM, ULK2, an upstream autophagy inducer, was found to be down-regulated in GBM.

STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a strong predictor of poor survival in patients with glioblastoma.

Object: Insulin-like growth factor binding proteins (IGFBPs) have been implicated in the pathogenesis of glioma. In a previous study the authors demonstrated that IGFBP-3 is a novel glioblastoma biomarker associated with poor survival. Since signal transducer and activator of transcription 1 (STAT-1) has been shown to be regulated by IGFBP-3 during chondrogenesis and is a prosurvival and radioresistant molecule in different tumors, the aim in the present study was to explore the functional significance of IGFBP-3 in malignant glioma cells, to determine if STAT-1 is indeed regulated by IGFBP-3, and to study the potential of STAT-1 as a biomarker in glioblastoma.

A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.

Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples.

Outcome of lesionectomy in medically refractory epilepsy due to non-mesial temporal sclerosis (non-MTS) lesions.

Objectives: To analyze the seizure outcome of lesionectomy for refractory epilepsy secondary to non-mesial temporal sclerosis (non-MTS) lesions.

Methods: Sixty-eight patients with non-MTS lesions (M:F=42:26; age at onset: 11.7±9.

A DNA methylation prognostic signature of glioblastoma: identification of NPTX2-PTEN-NF-κB nexus.

Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n = 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients.

miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma.

Glioblastoma is one of the common types of primary brain tumors with a median survival of 12-15 months. The receptor tyrosine kinase (RTK) pathway is known to be deregulated in 88% of the patients with glioblastoma. 45% of GBM patients show amplifications and activating mutations in EGFR gene leading to the upregulation of the pathway.

A fourteen gene GBM prognostic signature identifies association of immune response pathway and mesenchymal subtype with high risk group.

Background: Recent research on glioblastoma (GBM) has focused on deducing gene signatures predicting prognosis. The present study evaluated the mRNA expression of selected genes and correlated with outcome to arrive at a prognostic gene signature.

Methods: Patients with GBM (n = 123) were prospectively recruited, treated with a uniform protocol and followed up.

Traumatic epidural and subdural hematomas and extensive brain infarcts in a patient with pial arteriovenous malformation: Mechanisms underlying clinical and radiological findings.

We report a rare case of a patient with a pial arteriovenous malformation (AVM) who presented in altered sensorium. He was found to have large epidural and subdural hematomas overlying a pial AVM. He underwent evacuation of these hematomas and postop computed tomography showed infarcts deep to the site of hematoma evacuation.

Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients.

Aim: Mild traumatic brain injury (MTBI) is associated with often selective impairment of both working memory (WM) and the executive functions (EFs). Research indicates that one of the commonest deficits present in MTBI patients falls in the domain of WM. We aimed to investigate the role of EFs in WM impairment following MTBI.

IDH1 mutations in diffusely infiltrating astrocytomas: grade specificity, association with protein expression, and clinical relevance.

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization [WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody.

Insulin growth factor-2 binding protein 3 (IGF2BP3) is a glioblastoma-specific marker that activates phosphatidylinositol 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) pathways by modulating IGF-2.

Glioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to be up-regulated in GBMs but not in lower grade astrocytomas (p < 0.0001).

Predictive model for survival among neurosurgical intensive care patients.

Background: Models for prediction of outcome of intensive care patients greatly help the physician to make decisions and are also important for risk stratification in clinical research and quality improvement. At present, there are no major predictive models for neurosurgical intensive care unit (NSICU) patients. This study aimed to develop a predictive model for survival in NSICU patients.

Pathological spectrum of neuronal/glioneuronal tumors from a tertiary referral neurological Institute.

Neuronal/glioneuronal tumors are uncommon neoplasms of the CNS with frequent association with refractory epilepsy. Reports documenting the entire spectrum of neuronal/glioneuronal tumors are scarce in the literature. Zulch et al.

Homozygous 10q23/PTEN deletion and its impact on outcome in glioblastoma: a prospective translational study on a uniformly treated cohort of adult patients.

Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n=73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan-Meier log-rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion.

Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.

Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network.

Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis.

Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM).

Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients.

Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma.

Background: Insulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma.

Methods: The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256).

Histological and immunohistochemical characterization of AT/RT: a report of 15 cases from India.

Atypical teratoid rhabdoid tumor (AT/RT) is a highly malignant embryonal CNS tumor, generally unresponsive to any form of therapy, uniformly fatal within 1 year. We report 15 cases of AT/RT diagnosed at our center over a period of 5 years (2003-08). Tumors were located in different sites of the neuraxis, posterior fossa being the most common (n = 10) followed by cerebral lobes (n = 3).

Reduction of functional brain connectivity in mild traumatic brain injury during working memory.

Working memory deficits are present in patients with mild traumatic brain injury (MTBI). Functional connectivity of different brain regions is required for adequate working memory. Brain injury is associated with disrupted connectivity due to microscopic axonal damage.

Mixed-density extradural hematomas on computed tomography-prognostic significance.

Background: It has been variably reported that patients who acutely present with low- or mixed-density blood on CT scan are associated with poor clinical outcome. The aim of the study was to correlate the presence or absence of mixed density within EDHs on CT scanning with the clinical outcome.

Methods: This is a retrospective study of a total of 109 patients with EDHs who were operated on from August 2001 to August 2002.

Pediatric infratentorial subdural empyema: analysis of 14 cases.

Object: Pediatric cases of infratentorial subdural empyema (SDE) are both rare and associated with high rates of morbidity and mortality. The goal of this study was to report patient characteristics, treatment, and outcome in an exclusively pediatric series of SDE cases.

Methods: A series of 14 pediatric cases of infratentorial SDE was retrospectively analyzed.