High grade glioma classification The term malignant or high grade glioma refers to tumors that are classified as: ●WHO Grade 3 glioma: Anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma ● Grade 4 (glioblastoma multiforme) ---------- see Pediatric high grade glioma. Brainstem high grade glioma Cystic high grade glioma Pediatric high grade glioma Recurrent high grade glioma Temporal lobe high grade glioma Thalamic high grade glioma…
Title:Anti-cancer Therapies in High Grade Gliomas. VOLUME: 10 ISSUE: 3. Author(s):Cristiana Pistol Tanase, Ana-Maria Enciu, Simona Mihai, Ana Iulia Neagu, Bogdan Calenic and Maria Linda Cruceru. Affiliation:Victor Babes National Institute of Pathology, Dept. of Biochemistry-Proteomics, no 99-101 Splaiul Independentei, 050096 sect 5 Bucharest, Romania.. Keywords:Antiangiogenic therapy, cancer stem cells, glioma, microRNA, personalized medicine, PI-3K.. Abstract:High grade gliomas represent one of the most aggressive and treatment-resistant types of human cancer, with only 1-2 years median survival rate for patients with grade IV glioma. The treatment of glioblastoma is a considerable therapeutic challenge; combination therapy targeting multiple pathways is becoming a fast growing area of research. This review offers an up-to-date perspective of the literature about current molecular therapy targets in high grade glioma, that include angiogenic signals, tyrosine kinase receptors, nodal signaling ...
PRIMARY OBJECTIVES:. I. To evaluate the feasibility of proton beam radiation therapy in patients with low grade gliomas. (Phase I). SECONDARY OBJECTIVES:. I. To assess late complications from irradiation using proton beam therapy in place of conventional photon beam therapy for the treatment of low grade gliomas. (Phase II) II. To assess acute side effects from irradiation using proton beam therapy in place of conventional photon beam therapy for the treatment of low grade gliomas. (Phase II) III. To compare the dose distribution to tumor and surrounding normal structures using DVHs (Dose Volume Histograms) generated from the proton plan used to treat the patient and the photon plan generated for comparison purposes. (Phase II) IV. To monitor the rates of local control, overall and disease specific survival using proton radiotherapy. (Phase II) V. To evaluate the time to progression of low grade gliomas treated with protons. (Phase II) VI. To evaluate the incidence and severity of fatigue in ...
Malignant glioma is one of the most common types of primary malignancies in the human central nervous system. Temozolomide (TMZ) is the most commonly used drug in clinical therapy of glioma; however, chemoresistance makes glioma difficult to cure and relapse likely. Sirtuin 1 (SIRT1) serves important roles in cell proliferation, differentiation and metabolism, but the role of SIRT1 in human glioma remains largely unexplored. In the present study, SIRT1 expression was assessed in human glioma tissues and cells. RNA interference and SIRT1 inhibitor were used to determine the effect of SIRT1 on glioma growth inhibition and glioma cell chemoresistance in vitro and in vivo. The levels of reactive oxygen species (ROS) in glioma cells were detected with the dihydroethidium probe following SIRT1 inhibition. The results demonstrated that SIRT1 was overexpressed in glioma tissues and cells, and patients with higher SIRT1 expression exhibited poorer prognosis. SIRT1 inhibition inhibited the proliferation ...
Poor chemosensitivity and the development of chemoresistance remain major obstacles to successful chemotherapy of malignant gliomas. Recently, a new goal has been set: changing malignant glioma from a deadly to a chronic disease. To this end a multidisciplinary approach to malignant glioma treatment has been proposed, in which surgery, radiotherapy and chemotherapy are combined in order to most benefit the patients. We identified endoplasmic reticulum (ER) as a novel target and outlined specific pathways within the ER stress response (ESR) that lead to malignant glioma cell death/apoptosis.; First, we report that ER chaperone GRP78 is significantly elevated in malignant glioma. Knockdown of GRP78 using siRNA in glioblastoma cell lines significantly lowers their resistance to temozolomide (TMZ), the chemotherapeutic agent of choice for treatment of malignant gliomas, as established by colony survival assays.; Second, we show that dimethyl celecoxib (DMC), an analog of celecoxib (Cxb) lacking its ...
TY - JOUR. T1 - Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. AU - Tachibana, Issei. AU - Smith, Justin S.. AU - Sato, Kazunari. AU - Hosek, Sandra M.. AU - Kimmel, David W.. AU - Jenkins, Robert B.. PY - 2000/5/15. Y1 - 2000/5/15. N2 - Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the ...
We observed a 42% reduced risk of glioma for individuals with a history of diabetes versus those without (OR = 0.58; 95% CI, 0.40-0.84). Results were similar by sex, study design (case-control vs. nested case-control), and after restricting the outcome to glioblastoma, the most common histological subtype. The risks for other glioma subtypes were also reduced for those with versus without diabetes, albeit nonsignificantly. Diabetes-associated SNPs identified from GWAS were generally not associated with glioma risk, nor did these SNPs explain the inverse association we observed between glioma risk and diabetes history.. A lower risk of glioma associated with diabetes was first reported in a 1965 study, reporting a lower frequency of intracranial gliomas among diabetics versus nondiabetics but no difference in the frequency of meningiomas and pituitary neoplasms (36). Our finding of an inverse association between diabetes and glioma risk is consistent with results from previous case-control ...
Derived from brain glial cells, gliomas are currently the most common primary tumours in the central nervous system and are characterised by a high recurrence rate and poor prognosis. RWDD3 (RWD domain-containing sumoylation enhancer, also termed RSUME), which can be induced by cellular stress, such as CoCl2, heat shock and hypoxia, may play a crucial role in tumour angiogenesis, growth and metastasis. MicroRNAs (miRNAs) have been demonstrated to act as negative regulators of post-transcriptional gene expression and are involved in tumour growth and metastasis. In the present study, we explored the role of RWDD3 in glioma cell proliferation and invasion by the knockdown of RWDD3 with lentiviral shRNA and demonstrated that miRNA hsa-miR-375, regulates RWDD3 and has an important role in glioma progression. We found that expression of RWDD3 in high-grade gliomas was significantly higher than that noted in normal brain tissues and lower-grade gliomas in vivo. Knockdown of RWDD3 effectively led to ...
TY - JOUR. T1 - Prognostic factors and survival patterns in pediatric low-grade gliomas over 4 decades. AU - Youland, Ryan S.. AU - Khwaja, Shariq S.. AU - Schomas, David A.. AU - Keating, Gesina F.. AU - Wetjen, Nicholas M.. AU - Laack, Nadia N.. PY - 2013/4/1. Y1 - 2013/4/1. N2 - BACKGROUND:: This study reports changes in long-term survival after the introduction of modern imaging in pediatric patients with low-grade gliomas (LGGs). METHODS:: Records from 351 consecutive pediatric patients diagnosed with LGG between 1970 and 2009 at Mayo Clinic Rochester were reviewed and divided into diagnosis before (group I: 1970 to 1989) and after (group II: 1990 to 2009) postoperative magnetic resonance imaging became regularly used in pediatric LGG. RESULTS:: Median progression-free survival (PFS) and overall survival (OS) were not reached. Overall, 10-year PFS was 62% and OS was 90%. On multivariate analysis, improved PFS was associated with gross total resection (GTR; P,0.0001) and postoperative ...
HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies. In this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunohistochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells
The June 2012 International Society of Pediatric Neuro Oncology (ISPNO) meeting in Toronto, Canada featuried a Low Grade Glioma (LGG) Symposium. This was the third time the PLGA Foundation had sponsored a targeted session at ISPNO and interest in the low grade glioma field continues to grow amongst scientists and medical experts because of meeting such as these.. The ISPNO meets once every 2 years and attracts an international audience of over 1000 experts in the clinical and research fields. The exposure that this symposium gives to this disease is immense. The LGG session sold out in the first two weeks with over 200 participants registering. This means that more attention will be focused on the most common forms of childrens brain tumors giving hope to the children battling these tumors for more effective treatments and a cure.. The LGG Session was moderated by Dr. Charles Eberhart, Associate Professor of Oncology, Pathology and Opthomology at Johns Hopkins University School of Medicine, and ...
BACKGROUND:. Recurrent glioma patients have very limited treatment options. A major cause of gliomarelated morbidity and mortality is the extensive infiltrative and invasive nature of glioma cells. Thus, inhibition of glioma invasion is a potentially promising strategy.. Work in the Neuro-Oncology Branch laboratory of Dr. Howard Fine has identified TrkA as an important signaling receptor for mediating glioma cell invasion. Both genetic and pharmacological inhibition of Trk potently inhibits glioma invasion and tumor progression in vitro and in vivo. AZD7451 is a first in-class inhibitor of Trk.. OBJECTIVES:. To establish the maximally tolerated dose (MTD) of continuous twice a day AZD7451 dosing in patients with recurrent glioblastoma not on enzyme-inducing anti-epileptic drugs (EIAED).. To generate pharmacokinetic data on continuous twice a day AZD7451 dosing.. ELIGIBILITY:. Patients with histologically proven glioblastoma are eligible for this study. Patients should have failed prior standard ...
Signs of Glioma Susceptibility 5 including medical signs and symptoms of Glioma Susceptibility 5, symptoms, misdiagnosis, tests, common medical issues, duration, and the correct diagnosis for Glioma Susceptibility 5 signs or Glioma Susceptibility 5 symptoms.
The aim of the present analysis was to evaluate the recurrence pattern in patients with recurrent malignant glioma after re-irradiation in combination with bevacizumab as there is limited data on how to optimally choose dose, fractionation and delineation margins. Thirty-one patients with recurrent malignant glioma treated with re-irradiation and bevacizumab after previous chemoradiotherapy (concurrent temozolomide 75 mg/m2/d according to the EORTC/NCIC trial) and [18 F]FET-PET and/or MRI confirmed recurrence were retrospectively analyzed. Bevacizumab was applied twice during fractionated re-irradiation (10 mg/kg, d1 + d15, median 36 Gy, conventionally fractionated). Recurrence patterns were assessed by means of [18 F]FET-PET and/or MRI. Median follow-up was 34.0 months for all patients [95%-CI, 27.7-40.3] and median post-recurrence survival 10.8 months [95%-CI, 9.2-12.4]. Concerning the recurrence patterns, 61.3% of these were located in-field (19 patients), 22.6% were marginal (7 patients) and 16.1%
Brain tumor news: A phase I/II trial of the histone deacetylase inhibitor, romidepsin, for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03.
In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW 7 (hCDC 4/hAGO/SEL 10), its association with survival of patients with glioblastoma and its potential role as a tumor suppressor gene in glioma cells. The F-box protein Fbxw7 is a component of SCFFbxw7, a Skp1-Cul1-F-box E3 ubiquitin ligase complex that tags specific proteins for proteasome degradation. FBXW 7 is mutated in several human cancers and functions as a haploinsufficient tumor suppressor in mice. Any of the identified targets, Cyclin E, c-Myc, c-Jun, Notch1/4 and Aurora-A may have oncogenic properties when accumulated in tumors with FBXW 7 loss. We tested the expression of FBXW 7 in human glioma biopsies by quantitative PCR and compared the transcript levels of grade IV glioma (glioblastoma, G-IV) with those of grade II tumors (G-II). In more than 80% G-IV, expression of FBXW 7 was significantly reduced. In addition, levels of FBXW 7 were correlated with survival indicating a possible
Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years-despite debulking surgery, radiotherapy and cytotoxic chemotherapy-with a median survival of 9-12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma metastases usually involve the regional lymph nodes, lungs and pleural cavity, and
The immunolocalization of type I, III and IV collagens and fibronectin in two rat glioma cell lines in vitro (BT4C and BT4Cn) is described. In addition, antibodies against denatured type I and III collagens were used to study breakdown products of native type I and III collagens. For the BT4C cells, the extracellular matrix expression in monolayer cultures and in multicellular tumor spheroids was compared. Type IV collagen was strongly expressed in BT4C tumor spheroids but was negative in the corresponding monolayer cultures. Denatured type I collagen was found both in monolayers and in spheroids of BT4C, suggesting either a rapid turnover (i.e., synthesis and immediate breakdown) of type I collagen or an altered collagen gene transcription. Both cell lines were negative for native type I and III and denatured type III collagen.. Fibronectin was strongly expressed in both cell lines.. Supporting the immunofluorescence data, the hydroxyproline content in the tumor spheroids was twice the amount ...
Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer ...
INTRODUCTION: Gliomas are most common and fatal primary brain neoplasms, with few known risk factors. High dose ionizing radiation is the only known environmental risk factor. Previous studies show Caucasians having greater rates compared to African Americans, and higher rates of glioblastoma found in areas with higher socio-economic status (SES), suggesting involvement of SES-related factors. We examine spatial distribution of glioma incidence in Caucasians and African Americans to determine geographical disparities related to race, SES, and radon. AIM: To determine whether geospatial clusters of high glioma incidence exist, intending to identify potential environmental risk factors in areas with high glioma risk. METHODS: Data from Surveillance, Epidemiology, and End Results (SEER) Program 2001-2014 were used to generate descriptive statistics for adult glioma. Global Morans I test was performed for glioma rates, radon levels, and SES contextual factors and predicated use of Local Indicator of
Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG
In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in. This review starts with a brief introduction on the pathological and molecular characteristics of gliomas, followed by an overview of the models that have been used in the last decades in glioma research. Next, we will discuss how these models may play a role in better understanding glioma development and especially in how they can aid in the design and optimization of novel therapies. The strengths and weaknesses of the different models will be ...
Previous studies in our laboratory have shown that proliferation of human malignant gliomas in vitro depends in part upon the activation of protein kinase C (PKC) and, conversely, can be blocked by inhibitors of PKC. Here, we examined the effect of tamoxifen, a known PKC inhibitor, on DNA synthesis and proliferation of an established human glioma line (U138) and two low passage cultures of explanted human glioblastomas. Tamoxifen produced a profound, dose-dependent inhibition of both [3H] thymidine incorporation and cell proliferation, with a 50% effective dose of 20 ng/ml under serum-free conditions and 50 to 200 ng/ml in the presence of 10% serum. These tumors were estrogen receptor negative and showed no mitogenic response to estradiol. Furthermore, concentrations of estradiol as high as 10 µg/ml had no effect on the tamoxifen-induced inhibition. This suggests that the mechanism of growth inhibition by tamoxifen in these gliomas did not involve an estrogen receptor-mediated process but may ...
The chemokine GRO-α (CXCL1) has been found to mediate the proliferation of glia progenitor cells during neural development. As malignant gliomas are thought to arise from glia progenitors or their differentiated counterparts, astrocytes or oligodendrocytes, we have investigated whether GRO-α regulates the tumor characteristics of glioma cells. We found first that resected glioma specimens were strongly immunoreactive for GRO-α expression in cells with the morphology of tumor cells. In culture, the U251 glioma line transfected to overexpress GRO-α had elevated levels of motility and invasiveness. GRO-α transfectants increased their expression of several proteins associated with migratory behavior, including matrix metalloproteinase-2, β1-integrin and SPARC. The implantation of GRO-α glioma clones into the brain of nude mice caused the early demise of mice and this was associated with the formation of larger intracerebral tumors when compared with mice implanted with vector control lines. ...
Semaphorins and plexins are implicated in the progression of various types of cancer, although the molecular basis has not been fully elucidated. Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator of RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from the plasma membrane. Glioma cells challenged with Sema5A indeed showed a marked reduction in Rac1-GTP levels by 60%, with a concomitant disruption of lamellipodia. The inactivation of Rac1 was corroborated to contribute to the impediment of glioma cell invasion by Sema5A, as supported by the abolishment of effect upon forced expression of a constitutively active Rac1 mutant. Furthermore, silencing the endogenous expression of RhoGDIα in glioma cells was ...
Treating malignant glioma in Chinese patients: update on temozolomide Liang Chang,1 Jun Su,1 Xiuzhi Jia,2,3 Huan Ren2,3 1Department of Neurosurgery, The Tumor Hospital of Harbin Medical University, 2Department of Immunology, Harbin Medical University, 3Key Lab Infection and Immunity, Heilongjiang Province, Harbin, People's Republic of China Abstract: Malignant glioma, ie, anaplastic astrocytoma and glioblastoma, is the most common type of primary malignant brain tumor in the People's Republic of China, and is particularly aggressive. The median survival of patients with newly diagnosed glioblastoma is only 12–14 months despite advanced therapeutic strategies. Treatment of malignant glioma consists mainly of surgical resection followed by adjuvant radiation and chemotherapy. Temozolomide (TMZ), a second-generation oral alkylating agent, is playing an increasingly important role in the treatment of malignant glioma in Chinese patients. Since the publication of a study by Stupp et al in 2005
The current standard of care for malignant glioma is initial treatment with radiation therapy combined with TMZ; however, malignant gliomas usually recur with a median time to progression of approximately 7 months [1]. Two decades of molecular studies have identified important genetic events such as dysregulation of growth factor signaling via amplification or mutation of receptor tyrosine kinase genes; activation of PI3K pathway; and inactivation of p53 and Rb tumor suppressor pathways [2]. In this study, we tried to identify the potential targets for counteracting the pro-survival signaling implicated in radioresistance of malignant glioma cells and to get insight into potential strategies to improve the therapeutic outcome of radiotherapy and TMZ in the management of GBM.. Inhibition of signal transduction pathways may provide the basis for a new paradigm of GBM therapy, based on the fact that most human gliomas exhibit aberrant activation of a pro-survival/pro-growth signaling network. EGFR ...
TY - JOUR. T1 - Intraoperative tumor segmentation and volume measurement in MRI-guided glioma surgery for tumor resection rate control. AU - Hata, Nobuhiko. AU - Muragaki, Yoshihiro. AU - Inomata, Takashi. AU - Maruyama, Takashi. AU - Iseki, Hiroshi. AU - Hori, Tomokatsu. AU - Dohi, Takeyoshi. PY - 2005/1. Y1 - 2005/1. N2 - Gross-total surgery under intraoperative magnetic resonance imaging (MRI) is a promising method of glioma removal. The purpose of this article is intraoperative measurement of resected tumor volume in MRI-guided glioma surgery using semiautomatic image segmentation to unbiased resection rate control. A newly developed software program based on a fuzzy connectedness (FC) segmentation algorithm was used to achieve fast and semiautomatic tumor segmentation and tumor volume measurement. The program was validated by retrospective study of eight glioma cases and then applied to seven glioma cases. All clinical cases underwent actual MRI-guided surgery using 0.3-T open magnets. The ...
The SUMO-activating enzyme SAE1 is indispensable for protein SUMOylation. A dysregulation of SAE1 expression involves in progression of several human cancers. However, its biological roles of SAE1 in glioma are unclear by now. The differential proteome between human glioma tissues and para-cancerous brain tissues were identified by LC-MS/MS. SAE1 expression was further assessed by immunohistochemistry. The patient overall survival versus SAE1 expression level was evaluated by Kaplan-Meier method. The glioma cell growth and migration were evaluated under SAE1 overexpression or inhibition by the CCK8, transwell assay and wound healing analysis. The SUMO1 modified target proteins were enriched from total cellular or tissue proteins by incubation with the anti-SUMO1 antibody on protein-A beads overnight, then the SUMOylated proteins were detected by Western blot. Cell apoptosis and cell cycle were analyzed by flow cytometry. The nude mouse xenograft was determined glioma growth and tumorigenicity in vivo.
A glioma is a type of tumor that starts in the brain or spine. Gliomas arise from glial cells, which act as a supportive cell in the central nervous system. Gliomas are the second most common type of tumor after meningiomas.. There are three types of normal glial cells that can produce tumors. An astrocyte will produce astrocytomas (including glioblastomas), an oligodendrocyte will produce oligodendrogliomas, and ependymomas come from ependymal cells. Tumors that display a mixture of these different cells are called mixed gliomas. Tumors are also commonly identified by their specific locations (such as brain stem gliomas), not the tissue type from which they originate.. Gliomas are also categorized by grade, determined by pathologic evaluation of the tumor. Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which tumors are graded from I (least advanced disease / best prognosis) to IV (most advanced disease / worst ...
To date, standardized strategies for the treatment of recurrent glioma are lacking. Chemotherapy with the alkylating agent BCNU (1,3-bis (2-chloroethyl)-1-nitroso-urea) is a therapeutic option even though its efficacy and safety, particularly the risk of pulmonary fibrosis, remains controversial. To address these issues, we performed a retrospective analysis on clinical outcome and side effects of BCNU-based chemotherapy in recurrent glioma. Survival data of 34 mostly chemotherapy-naïve glioblastoma patients treated with BCNU at 1st relapse were compared to 29 untreated control patients, employing a multiple Cox regression model which considered known prognostic factors including MGMT promoter hypermethylation. Additionally, medical records of 163 patients treated with BCNU for recurrent glioma WHO grade II to IV were retrospectively evaluated for BCNU-related side effects classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0. In recurrent
TY - JOUR. T1 - Decrease in circulating endothelial progenitor cells in treated glioma patients. AU - Corsini, Elena. AU - Ciusani, Emilio. AU - Gaviani, Paola. AU - Silvani, Antonio. AU - Canazza, Alessandra. AU - Bernardi, Gaetano. AU - Calatozzolo, Chiara. AU - Meco, Francesco Di. AU - Salmaggi, Andrea. PY - 2012/5. Y1 - 2012/5. N2 - High-grade gliomas are highly vascularized tumors, in which the amount of new blood vessels is closely related with the degree of malignancy. The role of endothelial progenitor cells (EPCs) in the neoangiogenesis of gliomas and the effects of post-surgical therapies (i.e., radiotherapy (RT) and chemotherapy) have not yet been fully elucidated. The aim of the present study was to evaluate the effect of surgery and post-surgical treatment on the levels of circulating EPCs in glioma patients and their correlation with vascular endothelial growth factor (VEGF). In this study, we assessed by flow cytometry the number of EPCs in the peripheral blood of 78 high-grade ...
Gliomas (tumors in the brain) are especially aggressive malignant forms of cancer, often resulting in the death of affected patients within one to two years following diagnosis. There is no cure for gliomas and most available treatments provide only minor symptomatic relief.. A review of the modern scientific literature reveals numerous preclinical studies, some case reports, and one controlled clinical study demonstrating cannabinoids ability to act as antineoplastic agents, particularly on glioma cell lines.. Writing in the September 1998 issue of the journal FEBS Letters, investigators at Madrids Complutense University, School of Biology, first reported that delta-9-THC induced apoptosis (programmed cell death) in glioma cells in culture.[1] Investigators followed up their initial findings in 2000, reporting that the administration of both THC and the synthetic cannabinoid agonist WIN 55,212-2 "induced a considerable regression of malignant gliomas" in animals.[2] Researchers again ...
by Vetscite. A new study of the genetic factors underlying glioma formation in dogs may hold clues to how these common and often untreatable tumors form in humans. The genome study, which was conducted across 25 dog breeds, identified three genes associated with the tumor. The results from this research, led by Katarina Truvé of the Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh of Uppsala University, were published on May 12 in PLOS Genetics.. Gliomas are the most common form of malignant primary brain tumors in humans and the second most common in dogs. Several dog breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, while certain related breeds do not, suggesting that a mix of genes may impact glioma formation. Dr Truvé says: "Researchers in the consortium are now continuing the analysis of the genes identified, and their functional roles in development and progression of glioma in both dogs and humans.". To identify genetic ...
Background Recently, CD4+IL-17A+ T helper 17 (Th17) cells were identified and reported in several diseased states, including autoimmunity, infection and various peripheral nervous system tumors. However, the presence of Th17 in glia-derived tumors of the central nervous system has not been studied. Methodology/Principal Findings In this report, we demonstrate that mRNA expression for the Th17 cell cytokine IL-17A, as well as Th17 cells, are present in human glioma. The mRNA expression for IL-17A in glioma was recapitulated in an immunocompetent mouse model of malignant glioma. Furthermore, the presence of Th17 cells was confirmed in both human and mouse glioma. Interestingly, some Th17 cells present in mouse glioma co-expressed the Th1 and Th2 lineage markers, IFN-γ and IL-4, respectively, but predominantly co-expressed the Treg lineage marker FoxP3. Conclusions These data confirm the presence of Th17 cells in glia-derived CNS tumors and provide the rationale for further investigation into the role
2017 Springer International Publishing Switzerland Purpose: To examine the association of age when adult height was attained with glioma risk. Methods: We analyzed data from a US-based case-control study of glioma risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated between age at attainment of adult height and glioma risk. Multivariate models were adjusted for age, race, sex, education, and state of residence. We examined associations overall, and according to glioma grade, sex, and final adult height. Results: The study set included n = 951 controls and n = 776 cases, with a median age of 56 (18-92); the majority was male (53.8%) and identified as Caucasian. Older age at height completion was associated with an increased risk of glioma. A significant positive trend was observed both for glioblastoma (OR 1.10; 95% CI 1.04-1.17 per 1-year increase in age) and lower grade non-glioblastoma subtypes combined (OR 1.18; 95% CI 1.10-1.28 ...
Glioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM) as per histology. LGGs are further divided into isocitrate dehydrogenase (IDH) wild type or mutant, which is further classified into either oligodendroglioma that harbors 1p/19q codeletion or diffuse astrocytoma that has an intact 1p/19q loci but enriched for ATRX loss and TP53 mutation. GBMs are divided into IDH wild type that corresponds to primary or de novo GBMs and IDH mutant that corresponds to secondary or progressive GBMs. To make the 2016 WHO subtypes of diffuse gliomas more robust, we carried out Prediction Analysis of Microarrays (PAM) to develop DNA methylation signatures for these subtypes. In this study, we applied PAM on a
PURPOSE: Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-beta family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiological and pathological conditions. EXPERIMENTAL DESIGN: The expression of GDF-15 in glioma cell lines was assessed by qRT-PCR and immunoblot. GDF-15 levels in situ and in peripheral blood of glioma patients were examined by immunohistochemistry and ELISA, respectively. Effects of shRNA-mediated GDF-15 inhibition on proliferation and immunogenicity of SMA-560 glioma cells were investigated by [methyl-3H]thymidine incorporation and immune-mediated target cell lysis. The impact of GDF-15 on glioma growth in vivo was assessed in syngeneic mice.RESULTS: GDF-15 is expressed by gliomas of different WHO grades as assessed by immunohistochemistry. The high expression of GDF-15 in tumor tissue translates into elevated GDF-15 serum levels in glioblastoma patients compared to healthy controls. ...
Project Description: Grade IV astrocytomas known as glioblastoma multiforme (GBM) are the most aggressive primary brain tumors, with a median survival rate of 15 months after diagnosis. Current methodologies for diagnosis include time-consuming histopathological reviews of biopsied brain tumor tissue to determine malignancy, which can delay early diagnosis and treatment. We propose to use microfluidics in combination with labeled magnetic beads to separate invasive glioma cells from other healthy neural tissue within a few hours. A strategy that combines rapid cell sorting with subsequent cell culture of a pure population of the patients glioma cells could not only speed up time to diagnosis, but also enhance personalized treatment. We hypothesize that incubating magnetic beads labeled with anti-epithelial cell adhesion molecule (epCAM) antibody will allow for the selective separation of glioma cells from other neural tissue cell types from co-culture, as judged by recent evidence that glioma ...
Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats behavior was
Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 - 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 - 165 cc). With a
OBJECT: Angiocentric glioma was recently recognized as a distinct clinicopathological entity in the 2007 World Health Organization Classification of Tumours of the Central Nervous System. The authors present the first 3 pediatric cases of angiocentric glioma encountered at their institution and review the literature of reported cases to elucidate the characteristics and outcomes of pediatric patients with this novel tumor. METHODS: The children in the 3 cases of angiocentric glioma were 10, 10, and 13 years old. Two presented with intractable seizures and 1 with worsening headache and several months of decreasing visual acuity. Twenty-five cases, including the 3 first described in the present paper, were culled from the literature. RESULTS: In all 3 cases, MR imaging demonstrated a superficial, nonenhancing, T2-hyperintense lesion in the left temporal lobe. Histologically, the tumors were composed of monomorphous cells with a strikingly perivascular orientation that were variably reactive for glial
TY - JOUR. T1 - αvβ3 and αvβ5 integrin expression in glioma periphery. AU - Bello, Lorenzo. AU - Francolini, Maura. AU - Marthyn, Paola. AU - Zhang, Jianping. AU - Carroll, Rona S.. AU - Nikas, Demetrios C.. AU - Strasser, Jon F.. AU - Villani, Roberto. AU - Cheresh, David A.. AU - McL. Black, Peter. PY - 2001. Y1 - 2001. N2 - OBJECTIVE: This study analyzed the expression of integrins αvβ3 and αvβ5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS: The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS: Our data on glioma tissues demonstrated that both integrins were expressed in glioma ...
Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with ...
The up-regulation of thioredoxin reductase-1 (TrxR1) is detected in more than half of gliomas, which is significantly associated with increased malignancy grade and recurrence rate. The biological functions of NADPH-dependent TrxR1 are mainly associated with reduced thioredoxin-1 (Trx1) which plays critical roles in cellular redox signaling and tumour radio-resistance. Our previous work has proved that TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown could notably radiosensitize glioma cells. However, whether TrxR1-overexpressing glioma cells could be re-radiosensitized by TIGAR silence is still far from clear. In the present study, TrxR1 was stably over-expressed in U-87MG and T98G glioma cells. Both in vitro and in vivo data demonstrated that the radiosensitivity of glioma cells was considerably diminished by TrxR1 overexpression. TIGAR abrogation was able to radiosensitize TrxR1-overexpressing gliomas by inhibiting IR-induced Trx1 nuclear transport. Post-radiotherapy, TIGAR ...
Malignant gliomas represent a difficult therapeutic challenge due to the invasive nature of the tumor and limited tumoral delivery of therapeutic agents. In this study, novel nano liposome carriers composed of sulfatides were developed for the glioma targeted delivery. Firstly, sulfatides-containing liposomes (SCLs) were found to interact with glioma cells specifically. The specific interactions between sulfatides and tenascin-c (TN-C), a glioma overexpressed protein, may have an important role. Secondly, the mechanism of intracellular delivery of SCLs was studied. SCLs were found to be effectively internalized in glioma cells by both clathrin-dependent and caveolae/lipids rafts pathways. Thirdly, doxorubicin (DOX) was effectively loaded into the SCLs to form a liposomal drug, SCL-DOX. SCL-DOX could effectively accumulate in the nuclei of glioma cells that resulted in superior in vitro cytotoxicity. In a subcutaneous xenografts animal model, SCL-DOX could effectively inhibit tumor growth and ...
The expression of functional GABAA-receptors in glioma cells correlates with low malignancy of tumours and cell lines from glioma lack these receptors. Here we show that contact with neurons induces the expression of functional GABAA-receptors. C6 and F98 glioma cell lines were labelled by recombinant expression of enhanced green fluorescent protein injected into rat brain and studied in acute slices after two to three weeks of tumour growth. The cells responded to GABA or the specific agonist, muscimol with a current typical for GABAA-receptors, as studied with the patch-clamp technique. To get insight into the mechanism of GABAA receptor induction, the C6 or F98 cells were co-cultured with neurons, astrocytes, oligodendrocytes and microglia. Glioma cells expressed functional GABAA receptors within 24 h only in cultures where physical contact to neurons occurred. Activation of GABAA-receptors in the co-cultures attenuated glioma cell metabolism while blockade of the receptors increased ...
TY - JOUR. T1 - Preface. Modern management of high grade glioma, Part I.. AU - Yang, Isaac. AU - Han, Seunggu J.. PY - 2012/4. Y1 - 2012/4. UR - http://www.scopus.com/inward/record.url?scp=84863802507&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84863802507&partnerID=8YFLogxK. M3 - Editorial. C2 - 22440878. AN - SCOPUS:84863802507. VL - 23. SP - xiii. JO - Neurosurgery Clinics of North America. JF - Neurosurgery Clinics of North America. SN - 1042-3680. IS - 2. ER - ...
Patients with a high grade glioma have an increasing overall survival and progression free survival after initial treatment. Because of a better perform
Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Unraveling the molecular and genetic complexity that determines GBMs pronounced migratory property could provide new options for therapeutic targeting that may significantly complement current surgical and chemoradiation therapy and alter the current poor outcome. In this study, we establish stable AJAP1 overexpressing glioma cells in order to examine in vivo tumor growth. We examine AJAP1 localization by confocal microscopy and AJAP1s functional effect on migration and invasion across surfaces coated with laminin. Finally, analysis of AJAP1 expression in murine xenografts and GBM primary tumors revealed its association with tumor growth and survival. Stable overexpression of AJAP1 promotes adherence, decreases invasion of glioma cells through an extracellular-like matrix, and slows migration in the presence of laminin. These observations are reversed by gene knockdown using multiple siRNAs. Additionally, ...