			Home About us Contact

High-grade Gliomas (high-grade + glioma)

Distribution by Scientific Domains

Medical Sciences	82%
Life Sciences	17%

Distribution within Medical Sciences

Oncology & Radiotherapy	58%
Pathology	15%
Neurology	7%

Kinds of High-grade Gliomas

recurrent high-grade glioma

Selected Abstracts

High-Grade Gliomas , Diagnosis and Treatment

EUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2007
K. A. Jellinger
No abstract is available for this article. [source]

High-grade gliomas: Babies are not small adults! (commentary on Sanders et al., pp 888)

PEDIATRIC BLOOD & CANCER, Issue 7 2007
Didier Frappaz
No abstract is available for this article. [source]

A phase I clinical trial of interferon-beta gene therapy for high-grade glioma: novel findings from gene expression profiling and autopsy

THE JOURNAL OF GENE MEDICINE, Issue 4 2008
Toshihiko Wakabayashi
Background High-grade gliomas are highly lethal neoplasms representing approximately 20% of all intracranial tumors. Cationic liposome-mediated interferon-beta (IFN- ,) gene transfer has been found to induce regression of experimental glioma. We have previously performed a pilot clinical trial to evaluate the safety and effectiveness of this IFN- , gene therapy in five patients with high-grade glioma. Two patients showed more than 50% reduction while others had stable disease 10 weeks after treatment initiation. Methods To identify alterations in gene expression in brain tumors 2 weeks after the gene therapy trial, we used a microarray technology and Gene Ontology analysis. The results were validated by patients' clinical course and findings of histology and autopsy. Results and conclusions Using hierarchical clustering and principal component analysis, five series of gene therapy trials were classified according to the response to IFN- , gene therapy. Significant changes in gene expression related to immunoresponse and apoptosis were observed. Moreover, novel patterns of altered gene expression, such as inhibition of neovascularization, were identified, suggesting the involvement of pathways reported previously as not involved. Autopsy and histological examinations revealed dramatic changes in the tumor tissues after therapy in all patients. Many tumor cells showed necrotic changes, and immunohistochemistry identified numerous CD8-positive lymphocytes and macrophages infiltrating the tumor and surrounding tissues; these were probably the effects of therapy. Simultaneously, CD34-immunoreactive vessels were notably decreased in the vector-injected brain. This study facilitates the understanding of the antitumor mechanism and helps identify candidate target molecules for new approaches. However, additional clinical trials are warranted. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Blood oxygenation level-dependent MRI of cerebral gliomas during breath holding

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2004
Yuan-Yu Hsu MD
Abstract Purpose To assess the cerebrovascular responses to short breath holding of cerebral gliomas using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Materials and Methods Six patients with a low-grade glioma and one patient with a high-grade glioma were studied using T2*-weighted echo planar imaging (EPI) during repeated periods of 15-second or 20-second breath-holding. Tumor vascularity was evaluated using dynamic susceptibility contrast perfusion MRI. Results Increases in BOLD signal intensity during repeated breath-holding were consistently identified in patients' normal appearing gray matter, comparable with those in healthy adults. Absence of significant BOLD signal enhancement was noted both in low-grade and high-grade gliomas, which is either due to overwhelming hypoxia in a tumor, inadequacy or absence of hypercapnia-induced vasodilatation of tumor vessels, or both. Breath-hold regulated decreases in BOLD signals occurred only in the high-grade glioma, which is most likely due to the hypercapnia-induced steal effect that redistributes blood flow from tumor regions with unresponsive neovasculature to surrounding normal tissue. Conclusion BOLD MRI during short breath holding can disclose differential cerebrovascular response between normal tissue and cerebral glioma. J. Magn. Reson. Imaging 2004;19:160,167. © 2004 Wiley-Liss, Inc. [source]

Measuring performance status in pediatric patients with brain tumors,experience of the HIT-GBM-C protocol,,

PEDIATRIC BLOOD & CANCER, Issue 3 2010
Johannes E. A. Wolff MD
Abstract Background Measuring the quality of life or performance status in pediatric neurooncology has proven a challenge. Here, we report in a treatment protocol for pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma. Procedure The Fertigkeitenskala Münster,Heidelberg (FMH) is a 56-item quantitative measure of health status. The number of yes answers is transformed to age-dependent percentiles. Physicians were also asked the patients' health status by their own judgment on a 1,5 scale: normal, mild handicap, age-normal activity severely reduced but patient not in bed, in bed, and in ICU. Results Assessments were available from 50 of 97 eligible patients. For 22 patients both questionnaire and the physicians score obtained. At the beginning of the treatment, only 5 patients scored over 40 FMH%, and 4 of these survived. Of 16 patients who initially scored less than 40 FMH%, 15 died. During later assessments, most FMH measures became gradually worse. FMH scores improved in three patients. The physician's judgment was documented at diagnosis and during treatment (n,=,50). Per physician, 22% of the patients were normal before chemotherapy, decreasing to 16% in the middle of the protocol. At diagnosis only 16% of patients had severely reduced activity, which increased to 30.6% in the middle of the protocol. The FMH% correlated well with the physicians' judgments (P,<,0.005). Conclusion The FMH scale is easily obtained and provides a valid assessment of health status. Patients with poor performance at diagnosis had a poorer prognosis. Pediatr Blood Cancer. 2010;55:520,524. © 2010 Wiley-Liss, Inc. [source]

PARP1 expression in pediatric central nervous system tumors,

PEDIATRIC BLOOD & CANCER, Issue 7 2009
Valerie N. Barton BA
Abstract Background Despite advances in therapy, outcome in many high-grade pediatric central nervous system (CNS) tumors remains poor. The focus of neuro-oncology research has thus turned towards identifying novel therapeutic targets. Poly(ADP-ribose) polymerase-1 (PARP1) is a DNA repair protein that has been studied in a variety of malignancies and may interfere with therapy-induced DNA damage, however expression in pediatric CNS tumors is unknown. Procedure We evaluated PARP1 mRNA expression in 81 pediatric CNS tumors using microarray technology. Protein expression was examined by Western blot. Results PARP1 mRNA is highly expressed in high-grade tumors (P,<,0.0001). PARP1 mRNA expression was greater in high-grade glioma than pilocytic astrocytoma (P,=,3.5,×,10,5) and in large cell medulloblastoma over classic medulloblastoma (P,=,0.0053). PARP1 protein was also prominent in high-grade tumors (P,=,0.022). Conclusion These findings indicate that PARP1 is expressed in high-grade pediatric CNS tumors, implicating PARP1 inhibition as a potential therapeutic target. Pediatr Blood Cancer 2009; 53:1227,1230. © 2009 Wiley-Liss, Inc. [source]

A phase I clinical trial of interferon-beta gene therapy for high-grade glioma: novel findings from gene expression profiling and autopsy

Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

APMIS, Issue 8 2010
Benedikte Hasselbalch
Hasselbalch B, Eriksen JG, Broholm H, Christensen IJ, Grunnet K, Horsman MR, Poulsen HS, Stockhausen M-T, Lassen U. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan. APMIS 2010; 118: 585,94. Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan. Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating that they share the same regulatory mechanisms. None of the EGFR-related biomarkers showed any significant correlations with each other. None of the biomarkers tested alone or in combination could identify a patient population likely to benefit from bevacizumab and irinotecan, with or without the addition of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy. [source]

Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol,

CANCER, Issue 3 2010
Johannes E.A. Wolff MD
Abstract BACKGROUND: The authors hypothesized that intensified chemotherapy in protocol HIT-GBM-C would increase survival of pediatric patients with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). METHODS: Pediatric patients with newly diagnosed HGG and DIPG were treated with standard fractionated radiation and simultaneous chemotherapy (cisplatin 20 mg/m2 × 5 days, etoposide 100 mg/m2 × 3 days, and vincristine, and 1 cycle of cisplatin + etoposide + ifosfamide 1.5 g/m × 5 days [PEI] during the last week of radiation). Subsequent maintenance chemotherapy included further cycles of PEI in Weeks 10, 14, 18, 22, 26, and 30, followed by oral valproic acid. RESULTS: Ninety-seven (pons, 37; nonpons, 60) patients (median age, 10 years; grade IV histology, 35) were treated. Resection was complete in 21 patients, partial in 29, biopsy only in 26, and not performed in 21. Overall survival rates were 91% (standard error of the mean [SE] ± 3%), 56%, and 19% at 6, 12, and 60 months after diagnosis, respectively. When compared with previous protocols, there was no significant benefit for patients with residual tumor, but the 5-year overall survival rate for patients with complete resection treated on HIT-GBM-C was 63% ± 12% SE, compared with 17% ± 10% SE for the historical control group (P = .003, log-rank test). CONCLUSIONS: HIT-GBM-C chemotherapy after complete tumor resection was superior to previous protocols. Cancer 2010. © 2009 American Cancer Society. [source]

Phase II investigation of docetaxel in pediatric patients with recurrent solid tumors

CANCER, Issue 8 2006
A report from the Children's Oncology Group
Abstract BACKGROUND Docetaxel, which is an antitubulin agent, has demonstrable activity against murine and human tumors. The current study was designed to determine response rates to docetaxel in various strata of recurrent solid tumors of childhood and to assess toxicity in a group of patients who were assigned to receive it. METHODS Docetaxel was given at a dose of 125 mg/m2 once every 21 days as a 1-hour intravenous infusion for a maximum of 12 courses. From January 1997 to November 2001, 109 male patients and 68 female patients (total, 177 patients) were enrolled, and 173 patients were eligible. The median patient age at entry was 13 years (range, 1-27 yrs). One hundred sixty patients were evaluable for response. RESULTS There were no deaths attributable to study drug. Hematologic toxicity was common during therapy. Dermatologic, neurologic, pulmonary, and infectious side effects as well as edema were significant. One patient each had acute myeloid leukemia, acute lymphoid leukemia, and high-grade glioma reported as secondary malignancies. One patient with osteosarcoma and 1 patient with rhabdomyosarcoma achieved a complete response. Partial responses were observed in patients with Ewing sarcoma (3 patients), osteosarcoma (1 patient), squamous cell carcinoma (1 patient), and medulloblastoma (1 patient). Seventeen patients had stable disease. The 1-year and 5-year overall survival rates for the 160 evaluable patients were 24% (standard error = 4%) and 6% (standard error = 2%), respectively. CONCLUSIONS Docetaxel demonstrated activity in patients with recurrent Ewing sarcoma but was found to be ineffective for treating the other types of recurrent solid tumors that were studied. Cancer 2006. © 2006 American Cancer Society. [source]

Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma

CANCER, Issue 6 2004
Peter Hau M.D.
Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source]

Preradiation chemotherapy for pediatric patients with high-grade glioma,

CANCER, Issue 1 2002
Dr. med. habil, Johannes E. A. Wolff M.D.
Abstract BACKGROUND To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported. METHODS Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. RESULTS The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of , 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of , 90% (P = 0.003), irradiation with , 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006). CONCLUSIONS These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection. Cancer 2002;94:264,71. © 2002 American Cancer Society. [source]

Intensity-modulated radiotherapy with an integrated boost to the macroscopic tumor volume in the treatment of high-grade gliomas

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2001
Christoph Thilmann M.D.
Abstract Integrated boost radiotherapy (IBRT) delivers a higher fraction size to the gross tumor volume and a conventional fraction size to the surrounding tissue of microscopic spread. We compared stereotactic conformal radiotherapy (SCRT) and intensity-modulated radiotherapy (IMRT) with regard to their suitability for IBRT in the treatment of high-grade gliomas. In 20 patients treated with conventional radiotherapy, an additional treatment plan for IBRT [planning target volume (PTV1) defined as contrast-enhancing lesion plus margin due to setup errors 75 Gy, PTV2 defined as edema plus margin due to microscopic spread and setup error 60 Gy] with 7 non-coplanar beams for IMRT and for SCRT was carried out and compared. The part of the PTV2 irradiated with more than 107% of the prescribed dose was 13.9% for IMRT and 30.9% for SCRT (P < 0.001). Dose coverage of PTV2 (volume above 95% of the prescribed dose) was improved with IMRT (88.4% vs. 75.3% with SCRT, P < 0.001). Dose coverage of PTV1 was slightly higher with SCRT (93.7% vs. 87.5% with IMRT), but the conformity to the boost shape was improved by IMRT [conformity index (COIN95) = 0.85 vs. 0.69 with SCRT]. Simultaneously the brain volume irradiated with > 50 Gy was reduced from 60 to 33 cc (P < 0.001). We conclude that IMRT is suitable for local dose escalation in the enhancing lesion and for delivering a homogeneous dose to the PTV2 outside the PTV1 at the same time. Our encouraging results justify application of IMRT for IBRT in the treatment of high-grade gliomas. For clinical evaluation a phase III study has been initiated. © 2001 Wiley-Liss, Inc. [source]

Biomolecular characterization of human glioblastoma cells in primary cultures: Differentiating and antiangiogenic effects of natural and synthetic PPAR, agonists

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008
E. Benedetti
Gliomas are the most commonly diagnosed malignant brain primary tumors. Prognosis of patients with high-grade gliomas is poor and scarcely affected by radiotherapy and chemotherapy. Several studies have reported antiproliferative and/or differentiating activities of some lipophylic molecules on glioblastoma cells. Some of these activities in cell signaling are mediated by a class of transcriptional factors referred to as peroxisome proliferator-activated receptors (PPARs). PPAR, has been identified in transformed neural cells of human origin and it has been demonstrated that PPAR, agonists decrease cell proliferation, stimulate apoptosis and induce morphological changes and expression of markers typical of a more differentiated phenotype in glioblastoma and astrocytoma cell lines. These findings arise from studies mainly performed on long-term cultured transformed cell lines. Such experimental models do not exactly reproduce the in vivo environment since long-term culture often results in the accumulation of further molecular alterations in the cells. To be as close as possible to the in vivo condition, in the present work we investigated the effects of PPAR, natural and synthetic ligands on the biomolecular features of primary cultures of human glioblastoma cells derived from surgical specimens. We provide evidence that PPAR, agonists may interfere with glioblastoma growth and malignancy and might be taken in account as novel antitumoral drugs. J. Cell. Physiol. 217: 93,102, 2008. © 2008 Wiley-Liss, Inc. [source]

Blood oxygenation level-dependent MRI of cerebral gliomas during breath holding

Predicting the Histopathological Grade of Cerebral Gliomas Using High b value MR DW Imaging at 3-Tesla

JOURNAL OF NEUROIMAGING, Issue 3 2008
Juan Alvarez-Linera MD
ABSTRACT BACKGROUND Our aim was to prospectively assess whether magnetic resonance (MR) diffusion-weighted (DW) imaging using high b values can predict better than b value of 1,000 s/mm2 the histopathological grade of cerebral gliomas. METHODS Fifty-four patients with histologically verified brain gliomas (35 high-grade and 19 low-grade gliomas) underwent MR DW imaging. Isotropic DW images and apparent diffusion coefficient (ADC) were obtained with b values of 1,000 and 3,000 s/mm2. Each tumor was evaluated as being hyperintense, iso-intense or hypointense to normal, contralateral-hemisphere white matter. RESULTS Most of the patients with high- and low-grade gliomas showed areas of increased signal intensity on their isotropic images, obtained with a b value of 1,000 s/mm2. However, with a b value of 3,000 s/mm2 the areas of increased signal intensity were seen in 97.1% of the high-grade gliomas, while 94.7% of the low-grade gliomas showed no area of increased signal intensity. The mean area under the ROC curve for ADC ratio, obtained with a b value of 3,000 s/mm2, was significantly higher than that obtained with 1,000 s/mm2 (.932 vs. .856, P= .04). CONCLUSION High b value DW MR might be useful as a complementary tool in preoperative assessment of the histopathological grading of cerebral gliomas. [source]

Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spread

NEUROPATHOLOGY, Issue 2 2009
Julia Snoei
Leptomeningeal spread is a casual but conspicuous finding in both low- and high-grade gliomas. We hypothesized a compromised integrity of the glia limitans-basal lamina complex due to glycosylation defects by loss of protein-o-mannosyltransferase-1 (POMT1) activity, also a well-known feature in developmental brain disorders with leptomeningeal heterotopia. Hypothesizing it as analogous in gliomas, we have performed a comprehensive polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of the POMT1 gene in 41 brain tumor specimens. Each specimen was subjected to laser capture microdissection analyses to dissect: (i) subarachnoid tumor components; (ii) deeply localized tumor areas; and (iii) histologically unaffected CNS fragments. In addition, leukocyte DNA of healthy Caucasians served as controls (n = 100). Sequence alterations were found in exons 7, 9, 15 and 18. Exon 7 bore two sequence alterations, one 751C > T transition with amino acid exchange of arginine by tryptophane (Arg251Trp) (n = 12/41 in Tu vs n = 7/82 in Co) and a 752G > A transition with replacement of arginine by glutamine (Arg251Gln) (n = 3/41 in Tu vs n = 0/82 in Co) that were significantly increased in the tumor specimens compared to controls (P < 0.05). A 979G > A transition in exon 9 resulted in a valine to isoleucine switch (Val327Ile) (n = 6/40 in Tu vs n = 4/84 in Co). Individual specimens revealed a 1565G > A (Arg522Lys) transition in exon 15 and a 1922C > T (Ala641Val) transition in exon 18. Two gangliogliomas only revealed sequence alterations in the superficial area but not in intraparenchymal and adjacent control specimens. We conclude that a significant increase of POMT1 missense mutations may indicate a functional role in neoplastic conditions in individual tumors. Future studies will be important to evaluate a functional impact of POMT1 alterations in human brain tumors. [source]

Quantitative characterization of hemodynamic properties and vasculature dysfunction of high-grade gliomas

NMR IN BIOMEDICINE, Issue 6 2007
Vijaya Nagesh
Abstract Aberrations in tumor and peritumoral vasculature may not be distinguishable by cerebral blood flow (CBF) or cerebral blood volume (CBV) alone. The relationships between CBF and CBV were examined to estimate vasculature-specific hemodynamic characteristics. Twenty glioma patients were studied with dynamic susceptibility T2*-weighted MRI [(dynamic contrast-enhanced magnetic resonance imaging (DSC-MRI)] before and during week 1 and 3 of radiotherapy (RT). CBF and CBV were calculated from DSC-MRI, and relationships between the two were evaluated: the physiological measure of mean transit time (MTT),=,CBV/CBF; empirical fitting using the power law CBV,=,constant,×,(CBF),. Three different tissue types were assessed: the Gd-enhancing tumor volume (GEV); non-enhanced abnormal tissue located beyond GEV but within the abnormal hyperintense region on FLAIR images (NEV); normal tissue in the hemisphere contralateral to the tumor (CNT). The effects of tissue types, CBV magnitudes (low, medium and high), before and during RT, on MTT and , were analyzed by analysis of variance (ANOVA). The MTT and , for the three tissue types were significantly different (p,<,0.009). MTT increased from CNT (1.60,s) to NEV (1.93,s) to GEV (2.28,s) (p,<,0.0005). , was significantly greater in GEV (1.079) and NEV (1.070) than in CNT (1.025). , increased with increasing CBV magnitude while MTT was independent of CBV magnitude. There was a significant decrease in MTT of NEV and GEV during week 3 of RT compared with pre-RT values for all CBV magnitudes. There was a significant increase in , during RT in the tumor and peritumor. Progressive abnormalities in vasculature and hemodynamic characteristics of the vascular bed were delineated, with significant disorder in the tumor but mild abnormality in peritumoral tissue. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Fluorescence Lifetime Spectroscopy of Glioblastoma Multiforme,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2004
Laura Marcu
ABSTRACT Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. We investigated the use of time-resolved, laser-induced fluorescence spectroscopy for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas. The fluorescence of human brain samples (glioblastoma multiforme, cortex and white matter: six patients, 23 sites) was induced ex vivo with a pulsed nitrogen laser (337 nm, 3 ns). The time-resolved spectra were detected in a 360,550 nm wavelength range using a fast digitizer and gated detection. Parameters derived from both the spectral- (intensities from narrow spectral bands) and the time domain (average lifetime) measured at 390 and 460 nm were used for tissue characterization. We determined that high-grade gliomas are characterized by fluorescence lifetimes that varied with the emission wavelength (>3 ns at 390 nm, <1 ns at 460 nm) and their emission is overall longer than that of normal brain tissue. Our study demonstrates that the use of fluorescence lifetime not only improves the specificity of fluorescence measurements but also allows a more robust evaluation of data collected from brain tissue. Combined information from both the spectraland the time domain can enhance the ability of fluorescencebased techniques to diagnose and detect brain tumor margins intraoperatively. [source]

Impact of Morphology, MIB-1, p53 and MGMT on Outcome in Pilocytic Astrocytomas

BRAIN PATHOLOGY, Issue 3 2010
Craig Horbinski MD
Abstract Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population. PAs can exhibit variable behavior that does not always correlate with location, yet at present there is no way to predict which tumors will be more aggressive. To address this problem, an institutional cohort of 147 PAs (118 with outcome data) from both cerebellar and noncerebellar locations (spine, diencephalon, midbrain, brainstem and cortex) was utilized. Parameters included quantification of characteristic morphologic variables as well as genes previously shown to be of relevance in high-grade gliomas, including MIB-1, p53 and MGMT. In this cohort, the classic biphasic appearance was most common in cerebellar tumors, whereas noncerebellar tumors were predominantly microcystic. Associations with outcome suggest that the presence of degenerative atypia may be a favorable factor in PAs. Oligodendroglial morphology and the absence of leptomeningeal invasion are adverse histologic factors, but only in cerebellar tumors. Conversely, MIB-1 proliferation index and p53 and MGMT expression do not correlate with outcome. Morphologic biomarkers thus do exist for PAs, but the utility of each biomarker varies according to location. These results suggest that PAs differ fundamentally according to location; therefore, biological behavior may not simply depend on extent of resection. [source]

Reduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARC

BRAIN PATHOLOGY, Issue 1 2010
Christian Mawrin
Abstract Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion. [source]

The 2007 WHO Classification of Tumors of the Nervous System: Controversies in Surgical Neuropathology

BRAIN PATHOLOGY, Issue 3 2008
Bernd W. Scheithauer MD
Abstract Controversy surrounds the recent 2007 WHO Classification of Tumours of the Nervous System. A number of nosologic issues remain to be resolved, some a reflection of conceptual disagreement, others the result of inadequate data to permit their definitive resolution. Among these and discussed herein are (i) the nosologic place of highly anaplastic oligoastrocytic tumors, (ii) the forms and significance of microvascular changes in high-grade gliomas, (iii) the makeup of the glioneuronal tumors category, (iv) the subclassification of pineal parenchymal tumors of intermediate type, and (v) the classification of principle forms of mesenchymal neoplasms, specifically hemangiopericytoma and solitary fibrous tumor. These issues and others are the substance of this and an upcoming companion article. [source]

Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas,

CANCER, Issue 5 2008
Casilda Balmaceda MD
Abstract BACKGROUND. The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence. METHODS. This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m2 of temozolomide was followed by 9 consecutive doses of 90-mg/m2 every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m2 twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred. RESULTS. For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system). CONCLUSIONS. Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature. Cancer 2008. © 2008 American Cancer Society. [source]

DNA ligase IV is a potential molecular target in ACNU sensitivity

CANCER SCIENCE, Issue 8 2010
Natsuko Kondo
Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy. (Cancer Sci 2010) [source]