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BRAINLIFE NEWSLETTER
Volume 4, Number 39 - 20 September 2005

Volume 4
Archive


1: AJNR Am J Neuroradiol. 2005 Sep;26(8):2157-60.
 
Glioblastoma multiforme of the conus medullaris in a child: description of a case and literature review.

Stecco A, Quirico C, Giampietro A, Sessa G, Boldorini R, Carriero A.

SCDU Radiologia, AO Maggiore della Carita, Novara, Italy.

We describe a case of glioblastoma multiforme of the conus medullaris in a child. MR imaging showed at the T12-L1 level an intramedullary mass with signal alteration, with only two nodules of contrast enhancement. The finding was consistent with astrocytoma. Pathologic evaluation was consistent with glioblastoma multiforme. Nine months after the surgical treatment, the patient showed leptomeningeal recurrence. This case appears to be unusual for both the hysto-type and the nonspecific MR imaging features.

PMID: 16155176 [PubMed - in process]

 
2: AJNR Am J Neuroradiol. 2005 Sep;26(8):2053-6.
 
Primary Intraosseous Meningioma: CT and MRI Appearance.

Tokgoz N, Oner YA, Kaymaz M, Ucar M, Yilmaz G, Tali TE.

Department of Radiology, Division of Neuroradiology, Gazi University School of Medicine, Ankara, Turkey.

Benign primary intraosseous meningioma presenting with osteolytic skull lesion and soft-tissue component is rare. CT and MR imaging of a patient with frontoparietal scalp swelling showed an osteolytic intracalvarial lesion with an extradural soft-tissue component. Following wide surgical resection, the histological examination revealed an intraosseous chordoid meningioma. The clinical and radiological findings of primary intraosseous meningioma are discussed and the relevant literature is reviewed.

PMID: 16155159 [PubMed - in process]

 
3: AJNR Am J Neuroradiol. 2005 Sep;26(8):1980-5.
 
The Effect of Prior Surgery on Blood Oxygen Level-Dependent Functional MR Imaging in the Preoperative Assessment of Brain Tumors.

Kim MJ, Holodny AI, Hou BL, Peck KK, Moskowitz CS, Bogomolny DL, Gutin PH.

Department of Radiology, Functional MRI Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY.

BACKGROUND AND PURPOSE: Blood oxygen level-dependent functional MR imaging (BOLD fMRI) is a clinically useful technique for preoperative mapping of eloquent cortices in patients with brain tumors. The purpose of this study was to determine the effect on BOLD fMRI accuracy of susceptibility artifacts caused by prior surgery by comparing volumes of activation in the primary motor cortex (PMC) of patients with and without prior brain surgery. METHODS: The volumes of fMRI activation of the PMC were measured for the tumor and nontumor sides in patients with (n = 13) and without (n = 30) prior neurosurgery. Statistical comparisons of the volumes were performed by using paired t tests and linear regression analysis. The location and degree of susceptibility artifact were subjectively assessed. RESULTS: No significant difference was found between the mean tumor and nontumor volumes of fMRI activations in patients without prior surgery (P = .51). In patients who had prior surgery, the volume of activation was significantly smaller on the side of the prior operation when compared with the contralateral side (P = .001). The volume of activation on the side of the tumor was also significantly smaller in the patients with prior surgery compared with those without prior surgery (P < .001). Nevertheless, the PMC was identified in all cases, and its location was confirmed intraoperatively. CONCLUSION: Prior surgery is associated with a decrease in the volume of fMRI activation in patients with prior surgery; however, by examining the T2 images, an astute radiologist can recognize this phenomenon, draw the appropriate conclusions, and correctly identify the PMC.

PMID: 16155146 [PubMed - in process]

 
4: AJNR Am J Neuroradiol. 2005 Sep;26(8):1967-72.
 
Radiation Necrosis Versus Glioma Recurrence: Conventional MR Imaging Clues to Diagnosis.

Mullins ME, Barest GD, Schaefer PW, Hochberg FH, Gonzalez RG, Lev MH.

Department of Radiology, Massachusetts General Hospital, Boston, MA.

BACKGROUND AND PURPOSE: Conventional MR imaging findings are considered to be inadequate for reliably distinguishing radiation necrosis from tumor recurrence in patients with glioma. Despite this belief, we hypothesized that certain conventional MR imaging findings, alone or in combination, though not definitive, may favor one or another of these diagnoses in proton beam-treated patients with new enhancing lesions on serial scanning. METHODS: MR imaging findings (axial T1-, T2-, and post-gadolinium T1-weighted) of 27 proton beam radiation therapy patients with high-grade gliomas were retrospectively reviewed. Entry criteria included new MR imaging enhancing lesions after treatment and histologically unequivocal biopsy proof of diagnosis. Readers rated corpus callosum involvement, midline spread, subependymal spread, new discrete multiple enhancing foci, a "spreading wavefront" appearance, and septum pellucidum involvement. Statistical analysis was by the Fisher exact test. RESULTS: Corpus callosum involvement in combination with multiple other findings was highly associated with progressive glioma. These combinations included involvement of the corpus callosum with multiple enhancing foci (P = .02), involvement of the corpus callosum with crossing the midline and multiple enhancing lesions (P = .04), and involvement of the corpus callosum with subependymal spread and multiple enhancing lesions (P = .01). CONCLUSIONS: In proton beam-treated patients with glioma, corpus callosum involvement, in conjunction with multiple enhancing lesions with or without crossing of the midline and subependymal spread, favors predominant glioma progression. Overall, combinations of enhancement patterns were more likely than individual patterns to distinguish necrosis from predominant tumor progression. Together with clinical and functional imaging findings, these results may assist in determining the need for biopsy.

PMID: 16155144 [PubMed - in process]

 
5: AJNR Am J Neuroradiol. 2005 Aug;26(7):1858-61.
 
Posterior pituitary astrocytoma: a rare tumor of the neurohypophysis: a case report.

Shah B, Lipper MH, Laws ER, Lopes MB, Spellman MJ Jr.

Department of Radiology, Division of Neuroradiology, University of Virginia Health Systems, Charlottesville, VA 22908, USA.

Astrocytoma, or pituicytoma, of the posterior pituitary is a relatively rare entity consisting of poorly characterized glial tumor cells. We report two cases of posterior pituitary astrocytomas in middle-aged women presenting as focal lesions of the neurohypophysis. A review of the literature reveals only a few reports of this tumor, and there has been scanty discussion of the imaging findings of posterior pituitary astrocytomas compared with lesions of the anterior pituitary gland. This report reviews the clinical characteristics and imaging findings and discusses the differential diagnosis of these two cases.

Publication Types:
  • Case Reports
  • Review
  • Review of Reported Cases

PMID: 16091544 [PubMed - indexed for MEDLINE]

 
6: Cancer Genet Cytogenet. 2005 Oct 1;162(1):63-7.
 
GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.

Piaskowski S, Rieske P, Szybka M, Wozniak K, Bednarek A, Pluciennik E, Jaskolski D, Sikorska B, Liberski PP.

Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University, Czechoslowacka st. 8/10, 92-216 Lodz, Poland.

Deletions of 1p occur in approximately 30% of meningiomas. Based on loss of heterozygosity (LOH) analysis, two regions on 1p have been suspected to be carriers of tumor suppressor genes. We chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western blotting to find out if changes of the GADD45a protein expression occurred. Nineteen samples with 1p LOH (12 grade I; 7 grade II, WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were also analyzed by means of real-time polymerase chain reaction to find abnormalities in EPB41 mRNA levels in meningioma. LOH analysis was performed using seven microsatellite markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34), D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously described localization of putative tumor suppressor genes on 1p and involvement in meningioma pathogenesis (1p36 and 1p32). The open reading frame of GADD45A and intron splicing sites showed neither mutations nor polymorphisms. GADD45a protein molecular weight and expression level were unaltered in meningiomas with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41 gene expression was unchanged in all analyzed meningiomas. This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered.

PMID: 16157202 [PubMed - in process]

 
7: Cancer Res. 2005 Sep 15;65(18):8359-65.
 
Plasminogen kringle 5-engineered glioma cells block migration of tumor-associated macrophages and suppress tumor vascularization and progression.

Perri SR, Nalbantoglu J, Annabi B, Koty Z, Lejeune L, Francois M, Di Falco MR, Beliveau R, Galipeau J.

Division of Experimental Medicine, Lady Davis Institute for Medical Research.

Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain (K5) of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. In this study, we provide evidence that eukaryotically expressed His-tagged human K5 cDNA (hK5His) is exported extracellularly and maintains predicted disulfide bridging conformation in solution. Functionally, hK5His protein produced by retrovirally engineered human U87MG glioma cells suppresses in vitro migration of both human umbilical vein endothelial cells and human macrophages. Subcutaneous implantation of Matrigel-embedded hK5His-producing glioma cells in nonobese diabetic/severe combined immunodeficient mice reveals that hK5His induces a marked reduction in blood vessel formation and significantly suppresses the recruitment of tumor-infiltrating CD45(+)Mac3(+)Gr1(-) macrophages. Therapeutically, we show in a nude mouse orthotopic brain cancer model that tumor-targeted K5 expression is capable of effectively suppressing glioma growth and promotes significant long-term survival (>120 days) of test animals. These data suggest that plasminogen K5 acts as a novel two-pronged anticancer agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages, resulting in a potent, clinically relevant antitumor effect.

PMID: 16166313 [PubMed - in process]

 
8: Cancer Res. 2005 Sep 15;65(18):8250-5.
 
Essential role for ras signaling in glioblastoma maintenance.

Holmen SL, Williams BO.

Molecular Medicine and Virology Group and Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan.

Malignant gliomas can be induced in mice through the combined expression of activated forms of both KRas and Akt in glial progenitor cells. To determine the reliance of these tumors on continued KRas signaling in vivo, we generated a viral vector that allows the expression of KRas to be controlled post-delivery. Tumor-free survival rates were compared between those animals with continued KRas expression and animals in which KRas expression was suppressed. KRas signaling was found to be required for the maintenance of these tumors in vivo; inhibition of KRas expression resulted in apoptotic tumor regression and increased survival. Subsequent reexpression of KRas reinitiated tumor growth, indicating that a percentage of the progenitor cells survived and retained tumorigenic properties.

PMID: 16166301 [PubMed - in process]

 
9: Cancer Res. 2005 Jul 15;65(14):6178-88.
 
Stromal cell-derived factor-1alpha and CXCR4 expression in hemangioblastoma and clear cell-renal cell carcinoma: von Hippel-Lindau loss-of-function induces expression of a ligand and its receptor.

Zagzag D, Krishnamachary B, Yee H, Okuyama H, Chiriboga L, Ali MA, Melamed J, Semenza GL.

Microvascular and Molecular Neuro-oncology Laboratory, New York, New York, USA. dz4@nyu.edu

The genetic hallmark of hemangioblastomas and clear cell-renal cell carcinomas (CC-RCCs) is loss-of-function of the von Hippel-Lindau (VHL) tumor suppressor protein. VHL is required for oxygen-dependent degradation of hypoxia-inducible factor-1alpha (HIF-1alpha). In hemangioblastomas and CC-RCCs, HIF-1alpha is constitutively overexpressed leading to increased transcription of HIF-1-regulated genes, including vascular endothelial growth factor (VEGF). Because loss of VHL function is associated with increased expression of the chemokine receptor CXCR4 in CC-RCCs, we investigated the expression of HIF-1alpha, CXCR4, and its ligand stromal cell-derived factor-1alpha (SDF-1alpha) in hemangioblastomas and CC-RCCs. Immunohistochemistry revealed overexpression of both CXCR4 and SDF-1alpha within tumor cells and endothelial cells of hemangioblastomas and CC-RCCs. HIF-1alpha was detected in tumor cell nuclei of both hemangioblastomas and CC-RCCs. A specific ELISA showed that hemangioblastomas and CC-RCCs expressed SDF-1alpha protein at levels that were significantly higher than those found in normal tissue. Analysis of the VHL-null RCC line 786-0 revealed that SDF-1alpha mRNA levels were 100-fold higher than in a subclone transfected with the wild-type VHL gene. Expression of CXCR4 and SDF-1alpha mRNA was significantly decreased in HIF-1alpha-null compared with wild-type mouse embryo fibroblasts (MEFs). ELISA and Western blot studies for SDF-1alpha and CXCR4 protein expression confirmed the RNA findings in RCC lines and MEFs. These results suggest that loss-of-function of a single tumor suppressor gene can up-regulate the expression of both a ligand and its receptor, which may establish an autocrine signaling pathway with important roles in the pathogenesis of hemangioblastoma and CC-RCC.

PMID: 16024619 [PubMed - indexed for MEDLINE]

 
10: Childs Nerv Syst. 2005 Sep 10; [Epub ahead of print]
 
Long-term effects of transient cerebellar mutism after cerebellar astrocytoma or medulloblastoma tumor resection in childhood.

Huber JF, Bradley K, Spiegler BJ, Dennis M.

Department of Pediatrics, University of Toronto, Toronto, Canada.

BACKGROUND: Following cerebellar tumor resection, some patients develop transient cerebellar mutism (TCM). Although the mutism resolves, it is not known whether there are long-term motor speech deficits in patients with TCM that are in excess of those in individuals with cerebellar tumors who had not developed postoperative TCM. METHODS: Long-term survivors of cerebellar tumors resected in childhood who developed TCM were matched to survivors without TCM and to controls. Speech samples were formally analyzed by two speech pathologists. RESULTS: Tumor survivors who had TCM had significantly more ataxic dysarthric speech and slower speech than either those without TCM or controls and were more dysfluent than controls. Tumor survivors without TCM did not differ from controls on ataxic dysarthria or speech rate. CONCLUSIONS: Survivors who had TCM showed more speech deficits than controls or survivors without TCM. The data suggest that speech deficits are chronic if not permanent sequelae of TCM.

PMID: 16155765 [PubMed - as supplied by publisher]

 
11: Int J Cancer. 2005 Sep 13; [Epub ahead of print]
 
Maternal medication use and the risk of brain tumors in the offspring: The SEARCH international case-control study.

Cardy AH, Little J, McKean-Cowdin R, Lijinsky W, Choi NW, Cordier S, Filippini G, Holly EA, Lubin F, McCredie M, Mueller BA, Peris-Bonet R, Arslan A, Preston-Martin S.

Department of Public Health, University of Aberdeen, Aberdeen, United Kingdom.

N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (</=5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring. (c) 2005 Wiley-Liss, Inc.

PMID: 16161045 [PubMed - as supplied by publisher]

 
12: J Clin Oncol. 2005 Aug 1;23(22):5198-204.
 
Cognitive and adaptive outcome in low-grade pediatric cerebellar astrocytomas: evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies (CCG 9891/POG 9130).

Beebe DW, Ris MD, Armstrong FD, Fontanesi J, Mulhern R, Holmes E, Wisoff JH.

Cincinnati Children's Hospital Medical Center, The University of Cincinnati School of Medicine, Cincinnati, OH 45229-3039, USA. dean.beebe@cchmc.org

PURPOSE: Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits if they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study (1) assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and (2) examined the effect of tumor location and medical complications on cognitive and adaptive functioning. PATIENTS AND METHODS: The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astrocytomas, who underwent only surgical treatment as part of Children's Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location: vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. RESULTS: The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. CONCLUSION: We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.

PMID: 16051961 [PubMed - indexed for MEDLINE]

 
13: J Clin Oncol. 2005 Aug 1;23(22):5034-43. Epub 2005 Jun 13.
 
Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.

Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O'Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F; International Primary CNS Lymphoma Collaborative Group.

Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. abreyl@mskcc.org

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

PMID: 15955902 [PubMed - indexed for MEDLINE]

 
14: J Neurooncol. 2005 Sep 5; [Epub ahead of print]
 
Prospective study of quality of life in adults with newly diagnosed high-grade gliomas.

Brown PD, Ballman KV, Rummans TA, Maurer MJ, Sloan JA, Boeve BF, Gupta L, Tang-Wai DF, Arusell RM, Clark MM, Buckner JC.

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, brown.paul@mayo.edu, lovejoy.margery@mayo.edu.

OBJECTIVE: To assess baseline quality of life (QOL) and its prognostic importance for adults with newly diagnosed high-grade gliomas, we analyzed QOL and outcome data prospectively collected in three phase II high-grade glioma protocols. METHODS: At study entry, patients completed five self-administered forms to assess overall QOL (linear analogue scale assessment [LASA] and Functional Assessment of Cancer Therapy-Brain [FACT-Br]); fatigue (Symptom Distress Scale [SDS]); excessive daytime somnolence (Epworth Sleepiness Scale [ESS]); and depression (POMS-SF). Folstein Mini-Mental State Examination (MMSE) and Eastern Cooperative Oncology Group (ECOG) performance scores (PS) were obtained by the health care provider. RESULTS: Baseline QOL data were available for 194 of 220 patients (88%) enrolled in the three protocols. Differences in baseline QOL among the three studies were not statistically significant. One-third of patients had clinically significant fatigue at baseline. Increased fatigue (P = 0.003), excessive daytime somnolence (P = 0.01), and lower overall QOL scores (LASA, P = 0.001; FACT-Br, P = 0.0001) correlated with worse ECOG PS. No relation was found between QOL and corticosteroid or anticonvulsant therapy, extent of resection, tumor grade, or sex. Multivariate analyses found worse ECOG PS (PS 2, P = 0.007) associated with increased fatigue. Worse ECOG PS (PS 2, P = 0.002) was also associated with worse overall QOL (LASA). On multivariate analyses of survival, increased fatigue (P = 0.003) predicted poorer overall survival. CONCLUSIONS: Performance status is related to QOL in patients with newly diagnosed high-grade brain tumors. Increased fatigue is an independent predictor of overall survival. Interventional studies directed at improving QOL, especially fatigue, may have important benefits for these patients.

PMID: 16163448 [PubMed - as supplied by publisher]

 
15: J Neurooncol. 2005 Sep 1; [Epub ahead of print]
 
Radiation-induced Spinal Cord Glioma Subsequent to Treatment of Hodgkin's Disease:Case Report and Review.

Riffaud L, Bernard M, Lesimple T, Morandi X.

Departments of Neurosurgery, Rennes University, Rennes, France, laurent.riffaud@chu-rennes.fr.

Radiation-induced neoplasms of the central nervous system generally present as meningioma or sarcoma. Spinal cord glioma after radiation therapy is rare and half of the cases documented occurred after treatment of Hodgkin's disease.A 39-year-old male presented with a 1-month history of gradually worsening neck ache and paraparesis. The patient had been treated for stage IB Hodgkin's disease 9 years previously with combined therapy: MOPP-ABV and a 40-Gray mediastinal radiotherapy from T1 to T10. Magnetic resonance imaging disclosed an intramedullary lesion from C6 to T2 and histopathological examination from biopsy demonstrated a malignant glioma. Despite chemotherapy and additional radiotherapy, the patient's neurological status worsened and he died 11 months after initial presentation.We suggest a strategy aimed solely at obtaining a tissue diagnosis to differentiate myelitis from tumor, and, in the event of tumor, confirming the strong likelihood of a high histopathological grade. The very limited survival associated with these tumors regardless of therapy advocates palliative therapies without attempting complete resection.

PMID: 16158216 [PubMed - as supplied by publisher]

 
16: J Neurooncol. 2005 Sep 2; [Epub ahead of print]
 
Possible pathophysiological role of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in metastatic brain tumor-associated intracerebral hemorrhage.

Jung S, Moon KS, Jung TY, Kim IY, Lee YH, Rhu HH, Sun HS, Jeong YI, Kim KK, Kang SS.

Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.

BACKGROUND: Intratumoral hemorrhage, as one of the cerebrovascular complications in various tumor-related conditions, occurs mainly in malignant brain tumors. Recent studies have shown that the overexpression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) may play a role for the loss of vascular integrity and the subsequent hemorrhage in several instances, in addition to their well-known properties in tumor development and metastasis. METHODS: To investigate the potential role of VEGF and MMP in hemorrhagic complication of metastatic brain tumor, we estimated the expression of VEGF, MMP-2 & -9 by immunohistochemical studies in pathological specimens of metastatic brain tumors obtained from 16 patients, 7 in hemorrhagic and 9 in non-hemorrhagic group. We also examined the expression of collagen type IV, CD34, Factor VIII in order to evaluate the status of tumor vasculature. RESULTS: Patients in hemorrhagic group showed a higher VEGF expression with neovascularization than those in non-hemorrhagic group. The basement membranes of newly formed vessels were disrupted in cases with high expression in both MMP-2 and -9. These results indicate that rapid growing nascent blood vessels, responding vigorously to VEGF, are concentrated around the hemorrhagic tumors. Besides, these results suggest a possibility that the basement membranes of these nascent vessels could be disrupted proteolytically by MMP. CONCLUSION: We conclude that overexpression of VEGF and MMP may play a role in metastatic brain tumor-associated hemorrhage. Presumably, the underlying pathophysiological mechanisms are through rapid growth and breakdown of vessels around the tumors caused by overexpression of VEGF and MMP of tumor cells.

PMID: 16158215 [PubMed - as supplied by publisher]

 
17: J Neurooncol. 2005 Sep 2; [Epub ahead of print]
 
Identification of EGFRvIII-derived CTL Epitopes Restricted by HLA A0201 for Dendritic Cell Based Immunotherapy of Gliomas.

Wu AH, Xiao J, Anker L, Hall WA, Gregerson DS, Cavenee WK, Chen W, Low WC.

Department of Neurosurgery, University of Minnesota Medical School, 2001 Sixth Street, SE, Minneapolis, MN, 55455.

The type III variant of the epidermal growth factor receptor (EGFRvIII) mutation is present in 20-25% of patients with glioblastoma multiforme (GBM). EGFRvIII is not expressed in normal tissue and is therefore a suitable candidate antigen for dendritic cell (DC) based immunotherapy of GBM. To identify the antigenic epitope(s) that may serve as targets for EGFRvIII-specific cytotoxic T lymphocytes (CTLs), the peptide sequence of EGFRvIII was screened with two software programs to predict candidate epitopes restricted by the major histocompatibility complex class I subtype HLA-A0201, which is the predominant subtype in most ethnic groups. Three predicted peptides were constructed and loaded to mature human DCs generated from peripheral blood monocytes. Autologous CD8(+) T cells were stimulated in vitro with the EGFRvIII peptide-pulsed DCs. One of the three peptides was found to induce EGFRvIII-specific CTLs as demonstrated by IFN-gamma production and cytotoxicity against HLA-A0201(+) EGFRvIII transfected U87 glioma cells. These results suggest that vaccination with EGFRvIII peptide-pulsed DCs or adoptive transfer of in vitro elicited EGFRvIII-specific CTLs by EGFRvIII peptide-pulsed DCs are potential approaches to the treatment of glioma patients.

PMID: 16155724 [PubMed - as supplied by publisher]

 
18: J Neurooncol. 2005 Sep 2; [Epub ahead of print]
 
Isolation and Culture of Microvascular Endothelial Cells from Gliomas of Different WHO Grades.

Miebach S, Grau S, Hummel V, Rieckmann P, Tonn JC, Goldbrunner RH.

Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Munich, Germany.

Gliomas are the most common intrinsic brain tumors. The degree of vascularization corresponds to malignancy and is related to prognosis. In order to retrieve information about tumor behavior in situ, the use of primary tissue material for experiments is advantageous. With increasing evidence for the importance of microenvironment and vascularization in tumor biology, we concentrated on the isolation of endothelial cells (EC) from primary tumor material to investigate the role of endothelium within tumor tissue.We developed a method for isolation and purification of tumor-derived endothelial cells. EC were isolated and cultivated from normal brain using tissue digestion and Percoll density gradient centrifugation resulting in a >95% of EC culture. For isolation of EC from gliomas of different malignancy grades a combination of tissue digestion, Percoll gradient centrifugation and magnetic bead sorting by anti-CD31, -VE-Cadherin and -CD 105 was employed. This approach provided a purity of >98%. Cells were classified and characterized by testing expression of CD105, CD31, VE-Cadherin, vWF, UEA-1 and measuring DiI-Ac-LDL-uptake. To exclude contamination, staining and negative selection with anti-SMA, -GFAP, and -CD68 was performed. Tumors were histopathologically diagnosed according to WHO classification. We isolated EC from normal brain (NBEC, n = 11), low-grade gliomas WHO II (LGEC, n = 22), and high-grade gliomas WHO III & IV (HGEC, n = 11). There were no clear differences in EC morphology between the different tumor grades. However, a significantly higher proliferation rate of HGEC compared to LGEC was observed as well as distinctive antigen expression. Already in early passages isolated EC showed a rapid change in antigen expression indicating a phenotypic shift under culture conditions.We could establish a protocol for reliable and reproducible isolation and culture of EC from gliomas with different WHO grading. In first phenotypical and functional analyses, NBEC, LGEC and HGEC show remarkable differences. EC from all tumors could be grown in culture. However, passage related changes of EC phenotype demand very early passages to work with.

PMID: 16155723 [PubMed - as supplied by publisher]

 
19: J Neurosurg. 2005 Mar;102(2 Suppl):224-7.

Atypical external hydrocephalus with visual failure due to occult leptomeningeal dissemination of a pontine glioma. Case report.

Tarnaris A, Edwards RJ, Lowis SP, Pople IK.

Department of Neurosurgery, Frenchay Hospital, Bristol; and Department of Paediatric Oncology, Bristol Royal Hospital for Sick Children, Bristol, United Kingdom.

The authors report on the case of a diffuse pontine glioma in a 5-year-old boy in whom radiologically and cytologically occult leptomeningeal metastases led to the development of an atypical "external" hydrocephalus, associated with grossly elevated intracranial pressure (ICP). Initial neuroimaging demonstrated only mild communicating ventricular dilation associated with a noticeable enlargement of the subarachnoid space, particularly over the surface of the frontal lobes; these features are not usually associated with significantly elevated ICP. Possible pathophysiological mechanisms resulting in this unusual clinical presentation are discussed. Early recognition of the severity of the raised ICP despite the paucity of clinical and radiological signs may have averted the development of blindness due to optic atrophy.

PMID: 16156235 [PubMed - in process]

 
20: J Neurosurg. 2005 Mar;102(2 Suppl):197-206.

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

Misaki K, Marukawa K, Hayashi Y, Fukusato T, Minamoto T, Hasegawa M, Yamashita J, Fujisawa H.

Department of Neurosurgery, Graduate School of Medical Science, Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

PMID: 16156230 [PubMed - in process]

 
21: J Neurosurg. 2005 Mar;102(2 Suppl):179-86.

Neuroimaging-detected late transient treatment-induced lesions in pediatric patients with brain tumors.

Helton KJ, Edwards M, Steen RG, Merchant TE, Sapp MV, Boop FA, Langston J.

Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennesee 38105-2794, USA. kathleen.helton@stjude.org

OBJECT: After the resection of brain tumors in pediatric patients, it can be difficult to differentiate recurrent tumor from treatment effects. Although late-delayed reactions are thought to be permanent, in this study the authors sought to characterize transient brain lesions (TBLs) in the late-delayed period that completely resolved without imaging or neurological sequelae. METHODS: In a retrospective review of an institutional neuroimaging brain tumor database, 11 patients were identified who met the imaging criteria (transient T2-weighted hyperintense enhancing lesions outside of the tumor bed, which occurred after radiation and/or chemotherapy) and had undergone three-dimensional dosimetry; their radiographic, clinical, and radiation-dosimetry results were analyzed. In the 11 patients who had been treated with multiple protocols 17 loci of abnormality, including 43 discrete, asymptomatic TBLs, were detected. The median TBL diameter was 1 cm or smaller, without mass effect or necrosis, and occurred 10 months after radiation therapy, 11 months after chemotherapy, resolved by 3 months, and occurred within the high-dose radiation treatment volume (median 55.8 Gy). The findings from extended follow up revealed the development of additional permanent complications of radiation therapy within the radiation port in five of the 11 patients. CONCLUSIONS: A benign form of treatment-induced brain injury in children, TBLs should be treated using short-interval follow up. When these lesions are identified as a result of their characteristic imaging features, location, and temporal course, TBLs may be clearly distinguished from recurrent tumor or radiation necrosis and do not require biopsy. Further studies are needed to determine whether patients with TBLs are at an increased risk of developing more severe treatment-related brain injury.

PMID: 16156228 [PubMed - in process]

 
22: Neurology. 2004 Nov 9;63(9):1759-60; author reply 1759-60.

Comment on:  
Brainstem involvement in hypertensive encephalopathy: clinical and radiological findings.

Biousse V, Newman NJ, Chang GY.

Publication Types:
  • Case Reports
  • Comment
  • Letter

PMID: 15534284 [PubMed - indexed for MEDLINE]
 
 

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