Search results for "Glioblast"
showing 10 items of 141 documents
P08.76 Anti-EGFL7 treatment as an add-on for glioma therapy
2016
Glioblastoma multiforme (GBM) is one the most common and malignant forms of brain tumors. The median survival time of patients diagnosed with primary GBM is around 15 months. In spite of multimodal treatments GBMs remain essentially incurable. Therefore, alternative treatments targeting previously unexplored aspects of GBMs are required. However, the molecular mechanisms underlying the formation of brain tumors have only partially been defined. Especially Notch, a conserved developmental pathway, is promising in terms of GBM formation, as components of this signaling cascade are aberrantly expressed in gliomas. Studies reported that the inhibition of Notch decreased glioma cell proliferatio…
OS1.5 Harnessing soluble LRIG1 for pan-RTK targeting in glioblastoma
2018
INTRODUCTION: The role of receptor tyrosine kinases (RTKs) in glioblastoma is widely acknowledged. However, therapies based on RTK targeting have been continuously unsuccessful in GBM patients, highlighting the complexity of RTK signaling and biology. LRIG1 (Leucine-rich Repeats and ImmunoGlobulin domains protein 1) was identified as an endogenous inhibitor of epidermal growth factor receptor (EGFR) and other RTKs, and was confirmed as a tumor suppressor in various cancer types. We previously identified the soluble form of LRIG1 as a potent inhibitor of GBM growth in vivo, irrespective of EGFR status. Here, we aim to shed light on the molecular mechanisms underlying its anti-cancer activity…
Bmi1 and Cell of Origin Determinants of Brain Tumor Phenotype
2007
Glioblastomas frequently express oncogenic EGFR and loss of the Ink4a/Arf locus. Bmi1, a positive regulator of stem cell self renewal, may be critical to drive brain tumor growth. In this issue of Cancer Cell, Bruggeman and colleagues suggest that brain tumors with these molecular alterations can be initiated in both neural precursor and differentiated cell compartments in the absence of Bmi1; however, tumorigenicity is reduced, and tumors contain fewer precursor cells. Surprisingly, tumors appear less malignant when initiated in precursor cells. Bmi1-deficient tumors also had fewer neuronal lineage cells, suggesting a role for Bmi1 in determination of cell lineage and tumor phenotype.
RNA-sequencing and bioinformatic analysis to pre-assess sensitivity to targeted therapeutics in recurrent glioblastoma.
2019
e13533 Background: This study developed molecular guided tools for individualized selection of chemotherapeutics for recurrent glioblastoma (rGB). A consortium involving clinical neurooncologists, molecular biologists and bioinformaticians identified gene expression patterns in rGB and quantitatively analyzed pathways involved in response to FDA approved oncodrugs. Methods: From2016 to 2018 biopsies from GB were collected using a multisampling approach. Biopsy material was used to isolate glioma stem-like cells and examined by RNA-sequencing. RNA-seq results were subjected to differential expression (DE) analysis and Oncobox analysis – a bioinformatic tool for quantitative pathway activati…
MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and …
2010
The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key player in tumor cell resistance. Promoter methylation, MGMT activity and immunohistochemistry are used for determining the MGMT status. However, it is unclear whether MGMT promoter methylation correlates with MGMT activity and whether MGMT promoter methylation of the pretreatment tumor predicts the MGMT status of recurrences. To address these questions, we determined MGMT activity promoter methylation and immunoreactivity in pretreatment and recurrent glioblastomas (GB, WHO Grade IV), and in astrocytomas (WHO Grade III). We show that GB that were promoter methylated display a range of 0-62 fmol/mg MGMT and tumor…
Extent of resection and survival in glioblastoma multiforme
2016
Brown and colleagues1 reported the results of a systematic review of the literature aimed in determining whether greater extent of resection (EOR) is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients affected by glioblastoma multiforme. The analysis revealed 37 studies suitable for inclusion. The authors found that gross total resection (GTR) for glioblastoma multiforme reduces 1- and 2-year mortality, thus supporting GTR over subtotal resection and biopsy.
Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools
2019
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…
The commonly used marker ELAV is transiently expressed in neuroblasts and glial cells in theDrosophilaembryonic CNS
2007
Glial cells in the Drosophila embryonic nervous system can be monitored with the marker Reversed-polarity (Repo), whereas neurons lack Repo and express the RNA-binding protein ELAV (Embryonic Lethal, Abnormal Vision). Since the first description of the ELAV protein distribution in 1991 (Robinow and White), it is believed that ELAV is an exclusive neuronal and postmitotic marker. Looking at ELAV expression, we unexpectedly observed that, in addition to neurons, ELAV is transiently expressed in embryonic glial cells. Furthermore, it is transiently present in the proliferating longitudinal glioblast, and it is transcribed in embryonic neuroblasts. Likewise, elav-Gal4 lines, which are generally…
Counseling Patients with a Glioblastoma Amenable Only for Subtotal Resection: Results of a Multicenter Retrospective Assessment of Survival and Neuro…
2017
Background Patients with a glioblastoma (GB) amenable only for subtotal resection (STR) represent a challenge in patient counseling. Our objective was to assess impact of extent of resection (EoR) on survival and clinical outcome of these patients. Methods We performed a retrospective multicenter assessment. Patients receiving an intended STR in 3 centers with unilocular, primary, highly eloquent GB who received the same adjuvant treatment were included. We assessed EoR, neurologic outcome, and rate of complications. Progression-free survival (PFS) and overall survival (OS) were calculated with Kaplan–Meier estimations. We used 1% EoR and 1-cm3 steps to detect a threshold for a minimal EoR …
Design, synthesis and biological evaluation of new anticancer drugs: FGFR inhibitors
2021
Fibroblast growth factor receptors (FGFRs) constitute a family of tyrosine kinases receptors (RTKs) that exert pivotal physiological functions in human embryonic and adult tissues. Hyperactivated FGFR signaling drives tumorigenesis in multiple cancer types, including lung and brain cancers. Great effort has been laid on the development of new compounds that specifically target the FGFR axis. However, cancer cell- based and microenvironmental resistance mechanisms against FGFR inhibitors often arise and are currently poorly understood. Furthermore, FGFR-targeted therapy often presents different side effects, e due to the broad biological spectrum of the FGFR signaling axis as well as to its …