National Cancer Institute®
Last Modified: February 1, 2002
UI - 11547945
AU - Yoshida T; Nakazato Y
TI - Characterization of refractile eosinophilic granular cells in oligodendroglial tumors.
SO - Acta Neuropathol (Berl) 2001 Jul;102(1):11-9
AD - First Department of Pathology, Gunma University, School of Medicine, Maebashi, Japan. firstname.lastname@example.org
Refractile eosinophilic granular cells (rEGCs), which are distinct from the previously reported eosinophilic granular cells in oligodendroglial tumors, were characterized. The granules of rEGCs showed intense eosinophilia and prominent refractility, and were arranged in clusters or piled up in the perikaryon. The rEGCs tended to distribute in the vicinity of fibrovascular stroma and collagenous areas. They appeared in oligodendroglial tumors with numerous minigemistocytes and gliofibrillary oligodendrocytes. More rEGCs were present in WHO grade III oligodendroglial tumors. Histochemically, the granules stained blue with Kluver-Barrera and vividly red with Masson's trichrome stain, but negative with periodic acid-Schiff reagent. Almost all of the rEGCs were immunopositive for glial fibrillary acidic protein (GFAP) and heat shock protein 27 (HSP27), and some of them showed immunopositivity with alphaB-crystallin. No MIB-1 immunopositivity of rEGCs was found. Ultrastructurally, the rEGCs had many ellipsoidal structures associated with bundles of glial fibers in the cytoplasm. The morphological features of granules of rEGCs were similar to those of Rosenthal fibers except for the size and shape of the structure. We considered that the rEGCs originated from overexpression and accumulation of alphaB-crystallin and HSP27 in GFAP-positive oligodendroglial cells due to various pathological conditions. The presence of the rEGCs in the oligodendrogliomas may suggest more aggressive clinical behavior of tumors.
UI - 11547953
AU - Kraus JA; de Millas W; Sorensen N; Herbold C; Schichor C; Tonn JC;
TI - Wiestler OD; von Deimling A; Pietsch T Indications for a tumor suppressor gene at 22q11 involved in the pathogenesis of ependymal tumors and distinct from hSNF5/INI1.
SO - Acta Neuropathol (Berl) 2001 Jul;102(1):69-74
AD - Department of Neurology, University of Bonn Medical Center, Germany.
Ependymomas account for approximately 9% of all neuroepithelial tumors and represent the most frequent neuroepithelial tumors of the spinal cord. In adults, allelic loss of chromosome arm 22q occurs in up to 60% of the cases studied. Some of these tumors show an altered neurofibromatosis type 2 (NF2) gene; in others, NF2 appears to be unaffected, indicating the involvement of another tumor suppressor gene. Recently, the tumor suppressor gene hSNF5/INI1, located on 22q11.23, has been shown to contribute to the pathogenesis of renal and extrarenal rhabdoid tumors. In addition, this gene may be responsible for a new hereditary syndrome predisposing to a variety of tumors designated "rhabdoid predisposition syndrome." In the present study, we analyzed a series of 53 ependymal tumors of 48 patients [4 myxopapillary ependymomas (WHO grade I), 3 subependymomas (WHO grade I), 18 ependymomas (WHO grade II), 21 anaplastic ependymomas (WHO grade III) and 2 ependymoblastomas (WHO grade IV)] for mutations and homozygous deletions in the coding region of the hSNF5/INI1 gene and for allelic loss of its flanking chromosomal regions in 39 ependymal tumors of 35 patients. Allelic loss was detected in 11 of 35 informative primary ependymal tumors (31%) with a common region of overlap covered by the markers D22S257 and D22S310 on 22q11 including the marker D22S301. However, a detailed molecular analysis of 53 ependymal tumors for mutations and homozygous deletion of the hSNF5/INI1 gene revealed no alterations. We conclude that the hSNF5/INI1 gene is not involved in the pathogenesis of human ependymal tumors with allelic loss on chromosome arm 22q and an intact NF2 locus. In addition, our study localizes a putative ependymoma tumor suppressor gene(s) to a domain of chromosome arm 22q flanked by the microsatellite markers D22S257 and D22S310.
UI - 11731876
AU - Arienti VM; Botturi A; Boiardi A; Broggi G; Collice M; Fariselli L;
TI - Zanni D; Botturi M Adult brain low-grade astrocytomas: survival after surgery and radiotherapy.
SO - Neurol Sci 2001 Jun;22(3):233-8
AD - Niguarda Ca' Granda General Hospital, Piazza Ospedale Maggiore 3, I-20162 Milan, Italy.
In order to identify prognostic factors of survival, twelve elements of disease and treatment have been evaluated for a population of 49 patients with diffuse low-grade astrocytoma treated with surgical resection and radiotherapy. The survival values were inversely correlated with age and major residual portion. On the other hand, KPS, lobar site, grade II Daumas-Duport lesions, protoplasmatic variant, early epilepsy, hyperfractionated radiotherapy and extent of exeresis were prognostic factors correlated with survival. Tumor extent and radiation total dose were not correlated in a meaningful way. Only KPS was statistically significant when compared to all the prognostic factors. We believe that patient selection according to age, lesion site and histological features are not sufficient to generate a homogeneous tumoral population. The most appropriate therapy for treating low-grade astrocytomas is still an open subject. However, recent studies have shown that the prognostic value of a group of factors is useful to plan controlled studies that compare differentiated treatment protocols.
UI - 10918738
AU - Wolansky LJ; Holodny AI; Sheth MP; Axen R; Prasad V
TI - Double-shot magnetic resonance imaging of cerebral lesions: fast spin-echo versus echo planar sequences.
SO - J Neuroimaging 2000 Jul;10(3):131-7
AD - Department of Radiology, New Jersey Medical School/University of Medicine and Dentistry of New Jersey, Newark 07103, USA.
The authors compared two new rapid MRI techniques: double-shot echo-planar imaging (DS-EPI) versus double-shot fast spin-echo (DS-FSE) in the evaluation of cerebral lesions. The authors examined 35 patients with 37 lesions, which were hyperintense on long TR images. Patients were scanned with both DS-EPI and DS-FSE with a time of repetition (TR) of 10,000 milliseconds and an echo time (TE) of 80 milliseconds. Conspicuity was determined from region of interest measurements to calculate contrast to noise ratio (C/N). Visual comparisons between DS-EPI and DS-FSE, and between DS-EPI and T2-weighted conventional spin-echo (CSE) were also performed to evaluate the sequences' ability to depict hemorrhage. The mean C/N for both sequences was comparable: 36.7 for DS-FSE and 35.6 for DS-EPI, with no statistically significant difference (p = 0.77). With regards to depicting blood products, DS-EPI proved far more effective than DS-FSE and comparable to CSE. Also, DS-EPI proved to be more time-efficient, requiring 1.67 seconds per section, while DS-FSE required 3.33 seconds per section. Whereas DS-FSE and DS-EPI are comparable in their ability to depict hyperintense cerebral pathology, DS-EPI is more time-efficient, and therefore appears preferable. Because of the high magnetic susceptibility of DS-EPI, geometric distortion degrades visualization of lesions in the posterior fossa or near the sinuses. On the other hand, the high magnetic susceptibility results in high conspicuity of blood products.
UI - 11585328
AU - Kumar R; Achari G; Banerjee D; Chhabra DK
TI - Uncommon presentation of medulloblastoma.
SO - Childs Nerv Syst 2001 Sep;17(9):538-42; discussion 543
AD - Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India. email@example.com
INTRODUCTION: Medulloblastoma commonly occurs in children as a midline posterior fossa mass arising from the vermis, which appears as a hyperdense, homogeneously enhancing mass on CT scan and is associated with the clinical profile of posterior fossa syndrome. This unique clinico-radiological pattern is considered 'typical', but then medulloblastomas do not follow the typical clinico-radiological pattern in a significant number of cases. PATIENTS: Out of the 42 cases of medulloblastoma operated on at SGPGIMS from 1988 to 1998, 29 cases were retrospectively and 13 cases were prospectively studied to detect the atypical clinico-radiological features. The typical radiological feature of a hyperdense homogeneously enhancing mass was seen in only 23 of the 42 patients, while 5 patients had hypodense nonenhancing masses, 13 had cystic changes, and 6 patients had calcifications in their tumours. Three patients presented with tumours in a very unusual location, i.e. the cerebellopontine angle cistern. RESULTS: During follow-up, which ranged from a minimum period of 1 year to a maximum of 9 years, patients came back with metastases at very unusual sites. There were 5 cases of metastases in the frontal and subfrontal area (developed between 5 months and 5 years following surgery), and 1 patient developed a cervical intramedullary metastasis. Two patients developed abdominal metastases and ascites 2 years after definitive surgery and ventriculo-peritoneal shunting. Each of these 2 patients, however, had received a full course of craniospinal irradiation following surgery. Thus, we had a number of cases with an unusual clinical, radiological and metastatic pattern.
UI - 11733071
AU - Misra A; Chosdol K; Sarkar C; Mahapatra AK; Sinha S
TI - Alteration of a sequence with homology to human endogenous retrovirus (HERV-K) in primary human glioma: implications for viral repeat mediated rearrangement.
SO - Mutat Res 2001 Dec 12;484(1-2):53-9
AD - Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, 110029, New Delhi, India.
We had earlier demonstrated that a comparison of DNA fingerprinting profiles of tumor and corresponding normal DNA from the same patient by random amplified polymorphic DNA (RAPD) analysis can readily demonstrate alterations in tumor DNA [Gene 206 (1998) 45 and J. Neuro Oncol. 48 (2000) 1]. These alterations could be used to identify changes in tumor DNA where the prior identity of the locus was not known. In this study, we report the identification, cloning and characterization of a RAPD amplified fragment which was lost in a glioma, a grade IV glioblastoma multiforme (GBM). Comparison of the RAPD profile of tumor and corresponding leucocyte DNA revealed several differences between the two. These included a band of 443 bases, which was demonstrated in the normal, but not in tumor DNA. On sequencing, this band was found to be homologous with a group of SINE sequences, which are probably derived from the human endogenous retrovirus-K (HERV-K). Homology search also reveals that HERV-K-derived sequences are interspersed, amongst others, in the tumor suppressor gene BRCA2 and the DNA repair gene XRCC1. Of particular interest is the inverted repeat pattern of HERV-derived sequences in the genes. While not demonstrating a cause effect relationship, this highlights the possible role of such virus-derived sequences in gene inactivation by recombination during tumorigenesis.
UI - 11765681
AU - Beall C; Delzell E; Rodu B; Sathiakumar N; Lees PS; Breysse PN; Myers S
TI - Case-control study of intracranial tumors among employees at a petrochemical research facility.
SO - J Occup Environ Med 2001 Dec;43(12):1103-13
AD - Department of Epidemiology and International Health, School of Public Health, University of Alabama, RPHB 527, Ryals Building, 1665 University Boulevard, Birmingham, AL 35294-0022, USA. firstname.lastname@example.org
This case-control study evaluated the relation between potential exposure to chemical and physical agents and the occurrence of intracranial tumors among employees at a petrochemical research facility. Cases were employees with glioma (n = 6) or benign intracranial tumors (n = 6). Controls (n = 119) were individually matched to cases on gender and birth year, and they were alive and did not have an intracranial tumor at the case's diagnosis date. Exposure information came from interviews with subjects or surrogates and from corporate records on agents used in research projects. Analyses computed matched odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for self-reported exposure to 15 agents and project-based estimates of exposure to 29 agents. For gliomas, the OR was elevated for self-reported exposure to ionizing radiation (OR, 15.7; CI, 1.4 to 179.4), n-hexane (OR, infinity; CI, 1.4 to infinity), organometallics (OR, 9.4; CI, 1.5 to 59.7), and amines other than nitrosamines (OR, 6.0; CI, 1.0 to 35.7). The OR also was elevated for project-based potential use of ionizing radiation (OR, 9.6; CI, 1.7 to 55.2) and for potential use of n-hexane lasting at least 4 years (OR, 16.2; CI, 1.1 to 227.6). For benign intracranial tumors, the OR was elevated only for self-reported exposure to ionizing radiation (OR, 5.4; CI, 1.7 to 43.1) and other amines (OR, 5.2; CI, 0.9 to 29.5). Occupational exposure may have contributed to the glioma excess, but the specific causal agents remain unknown. The study indicated that benign intracranial tumors were unlikely to be work-related.
UI - 11748492
AU - Raininko R; Thelin L; Eeg-Olofsson O
TI - Non-neoplastic brain abnormalities on MRI in children and adolescents with neurofibromatosis type 1.
SO - Neuropediatrics 2001 Oct;32(5):225-30
AD - Department of Oncology, Radiology and Clinical Immunology, Section of Radiology, Uppsala University, Uppsala, Sweden. email@example.com
The occurrence, localization and longitudinal course of non-neoplastic MRI abnormalities in children and adolescents with neurofibromatosis type 1 (NF 1) were studied. Thirty-five patients who satisfied the criteria for NF 1 underwent 114 MRI examinations. They were 9 months to 18 years old at their first examination, and 23 were examined more than once (2 - 11 times). The follow-up time varied from 3 months to 10 years (mean 4 years). Thirty-one patients (89%) showed focal high signal intensities on T2-weighted images in the cerebellum, brain stem, deep cerebral gray matter and, less frequently, in the cerebral white matter. Changes were also seen in 80% and 50% of the proton density-weighted and T1-weighted images, respectively. Newly appearing, growing, decreasing and disappearing lesions occurred contemporaneously and in all ages. New lesions still developed in the late teens. Three lesions showed temporary contrast enhancement. Five expansive lesions were found in four individuals without related clinical symptoms. Four of them receded during follow-up. These cases indicate that the differential diagnosis between neoplastic and non-neoplastic lesions is not clear. The results support the view that high T2-signal lesions are so common in NF 1 that they should be included as another criterion for the diagnosis.
UI - 11784850
AU - Choi C; Kutsch O; Park J; Zhou T; Seol DW; Benveniste EN
TI - Tumor necrosis factor-related apoptosis-inducing ligand induces caspase-dependent interleukin-8 expression and apoptosis in human astroglioma cells.
SO - Mol Cell Biol 2002 Feb;22(3):724-36
AD - Department of Cell Biology, University of Alabama at Birmingham, 35294, USA. firstname.lastname@example.org
Among the tumor necrosis factor (TNF) family of cytokines, FasL and TNF-related apoptosis-inducing ligand (TRAIL) are known to induce cell death via caspase activation. Recently, other biological functions of these death ligands have been postulated in vitro and in vivo. It was previously shown that Fas ligation induces chemokine expression in human glioma cells. In this study, we investigated whether the TRAIL-DR5 system transduces signals similar to those induced by other TNF family ligands and receptors. To address this issue, two human glioma cell lines, CRT-MG and U87-MG, were used, and an agonistic antibody against DR5 (TRA-8) and human recombinant TRAIL were used to ligate DR5. We demonstrate that DR5 ligation by either TRAIL or TRA-8 induces two functional outcomes, apoptosis and expression of the chemokine interleukin-8 (IL-8); the nonspecific caspase inhibitor Boc-D-Fmk blocks both TRAIL-mediated cell death and IL-8 production; the caspase 3-specific inhibitor z-DEVD-Fmk suppresses TRAIL-mediated apoptosis but not IL-8 induction; caspase 1- and 8-specific inhibitors block both TRAIL-mediated cell death and IL-8 production; and DR5 ligation by TRAIL mediates AP-1 and NF-kappaB activation, which can be inhibited by caspase 1- and 8-specific inhibitors. These findings collectively indicate that DR5 ligation on human glioma cells leads to apoptosis and that the activation of AP-1 and NF-kappaB leads to the induction of IL-8 expression; these responses are dependent on caspase activation. Therefore, the TRAIL-DR5 system has a role not only as an inducer of apoptotic cell death but also as a transducer for proinflammatory and angiogenic signals in human brain tumors.
UI - 11556747
AU - Korkolopoulou P; Patsouris E; Konstantinidou AE; Christodoulou P;
TI - Thomas-Tsagli E; Kouzelis K; Angelidakis D; Rologis D; Davaris P Mitosin and DNA topoisomerase IIalpha: two novel proliferation markers in the prognostication of diffuse astrocytoma patient survival.
SO - Appl Immunohistochem Mol Morphol 2001 Sep;9(3):207-14
AD - Department of Pathology, National and Kapodistrian University of Athens, Greece. email@example.com
The expression of two novel proliferation-associated markers, mitosin and topoisomerase IIalpha (Topo IIalpha), was evaluated immunohistochemically in consecutive paraffin sections from 60 diffuse astrocytomas (grades 2 to 4) in relation to clinicopathologic parameters, proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1) expression and survival. The percentage of mitosin and Topo IIalpha-positive cells (LI) increased with grade and Ki-67 LI, but could not discriminate between grade 3 on the one hand and grades 2 or 4 on the other hand. In 51% of cases, Ki-67 LI exceeded Topo IIalpha LI, especially within grade 4. Topo IIalpha and mitosin expression was adversely related to overall and disease-free survival in the entire cohort and in grades 2/3. However, only Topo IIalpha LI affected disease-free survival in grade 4 tumors. Multivariate analysis selected only mitosin LI along with the age of the patient, as the independent parameters predicting overall survival, whereas Topo IIalpha emerged as the single independent predictor of disease-free survival. It is concluded that the proliferative potential of astrocytomas, as measured by mitosin and Topo IIalpha immunostaining, conveys useful prognostic information, in addition to that obtained by standard clinicopathologic parameters.
UI - 11714115
AU - Cordier S; Mandereau L; Preston-Martin S; Little J; Lubin F; Mueller B;
TI - Holly E; Filippini G; Peris-Bonet R; McCredie M; Choi NW; Arsla A Parental occupations and childhood brain tumors: results of an international case-control study.
SO - Cancer Causes Control 2001 Nov;12(9):865-74
AD - INSERM, Villejuif, France.
OBJECTIVE: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT). METHODS: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors. RESULTS: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry. CONCLUSION: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder.
UI - 11787095
AU - Aronen HJ; Lundbom N; Haapamaki S; Huttunen J; Korvenoja A; Makela J;
TI - Kaste M; Jaaskelainen J [Functional imaging of brain tumors]
SO - Duodecim 2000;116(4):431-42
AD - KYS:n kliinisen radiologian osasto PL 1777, 70211 Kuopio.
UI - 11814000
AU - Woydt M; Krone A; Soerensen N; Roosen K
TI - Ultrasound-guided neuronavigation of deep-seated cavernous haemangiomas: clinical results and navigation techniques.
SO - Br J Neurosurg 2001 Dec;15(6):485-95
AD - Neurosurgical Department, University of Wuerzburg, Germany. Michael@Woydt.de
The aim of this study was to evaluate guidance techniques and patient outcomes of ultrasound-guided neuronavigation of deep-seated intracerebral cavernous hemangiomas (CAs). Thirty-five patients with deep-seated intracerebral CAs with sizes ranging between 7 and 45 mm were operated upon only with ultrasound-guidance. Twenty-seven were located in or near eloquent regions. In 30 patients dissection to the lesion was performed through sulci and fissures. The best approach to a lesion based on surface anatomy and depth was determined using sonographic information. Navigation was done sonographically. In five patients the shortest approach via a corticotomy was determined sonographically. Twenty-six patients had no neurological deficit postoperatively. Preoperative deficits improved in seven of nine patients. Fifteen of 19 patients suffering epileptic seizures had no seizures postoperatively. Intraoperative sonography revealed residual CA tissue after microsurgical extirpation in two cases. This report shows that intraoperative sonographic navigation provides safe guidance to deep-seated CAs with good clinical outcome independent of size.
UI - 11813172
AU - Yalcin B; Buyukpamukcu M; Akalan N; Cila A; Kutluk MT; Akyuz C
TI - Value of surveillance imaging in the management of medulloblastoma.
SO - Med Pediatr Oncol 2002 Feb;38(2):91-7
AD - Department of Pediatric Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey.
BACKGROUND: To investigate the value of surveillance scanning for the detection of recurrences in medulloblastoma. PROCEDURE: The charts of 95 patients with medulloblastoma were retrospectively reviewed. Information regarding the patient characteristics, treatment modalities, dates, types and results of CT and MRI studies, the frequency with which recurrences were identified on surveillance images, changes in patient management, outcome of the patients following recurrences, and survival data were analyzed. RESULTS: Thirty-one patients had a recurrence of tumor in the central nervous system; none experienced extraneural relapses. Of all recurrences, 21 were symptomatic and 10 were discovered by surveillance scans asymptomatically. None of the patients with a recurrence survived. For all 95 patients, 5-year overall and event-free survival rates were 47.1 and 49.8%, respectively. In patients with symptomatic and asymptomatic recurrences, the mean time to recurrence since initial diagnosis, the mean duration of survival post-recurrence, and the mean duration of overall follow-up were 19.2 and 26.1 months, 3.6 and 8.0 months, and 22.8 and 34.1 months, respectively. For 95 patients, 468 surveillance and 38 symptomatic images were reviewed as 313 CTs and 193 MRIs. Rate of diagnosis of recurrence per surveillance image was 2.1% (10/468). CONCLUSIONS: In our study, surveillance scanning brought no survival advantage since it detected a minority of recurrences. Longer survival achieved by early detection of recurrences might be a reflection of lead-time and length biases. Surveillance procedures will gain more importance as new effective therapeutic options are developed for recurrent medulloblastoma. Copyright 2002 Wiley-Liss, Inc.
UI - 11021607
AU - Morgan RW; Kelsh MA; Zhao K; Exuzides KA; Heringer S; Negrete W
TI - Radiofrequency exposure and mortality from cancer of the brain and lymphatic/hematopoietic systems.
SO - Epidemiology 2000 Mar;11(2):118-27
AD - Exponent Health Group, Menlo Park, CA 94025, USA.
The proliferation of wireless communication technologies has raised public concern regarding potential health effects of radiofrequency (RF) exposures. This is the first report of findings from a large-cohort mortality study among employees of Motorola, a manufacturer of wireless communication products. We examined all major causes of mortality, with brain cancers, lymphomas, and leukemias as a priori outcomes of interest. Using job titles, we classified workers into high, moderate, low, and background RF exposure groups. A total of 195,775 workers contributed 2.7 million person-years during the 1976-1996 period. Using external comparisons, the standardized mortality ratios for RF-exposed workers were 0.53 [95% confidence interval (CI) = 0.21-1.09] and 0.54 (95% CI = 0.33-0.83) for central nervous system/brain cancers and all lymphomas/leukemias. Rate ratios calculated from Poisson regression models based on internal comparisons were near 1.0 for brain cancers and below 1.0 for all lymphomas and leukemias. These findings were consistent across cumulative, peak, and usual exposure classifications. We did not observe higher risk with increased exposure duration or latency. Although this study is limited by the use of a qualitative exposure matrix and the relatively young age of the cohort, our findings do not support an association between occupational RF exposure and brain cancers or lymphoma/leukemia.
UI - 11733826
AU - Serafim A; Vilanova LC; Silva NS
TI - Neurological evaluation of children and adolescents with brain tumor, based on ambulatory-oriented follow-up.
SO - Arq Neuropsiquiatr 2001 Dec;59(4):849-53
AD - Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
Taken as proved that brain tumors are the second most frequent childhood neoplasm - only outnumbered by leukemias - we have undertaken a clinical perspective study with seventy brain tumor patients ranging from one to fifteen years of age, throughout a four-year period (1993-1997), based on ambulatory-oriented follow-up. Forty-one male and twenty-nine female patients were analyzed, in that a slightly higher number of infratentorial tumors was observed (thirty-eight cases), compared to those supratentorially located (thirty-two cases). The most repeatedly observed during the study was the medulloblastoma (twenty-one patients), followed by the astrocytoma (fifteen patients) and the germinoma (eleven patients). It should be pointed out that during the ambulatory follow-up 75,5% of patients developed neurological sequels. A tumor recurrence was noticed in 34,3% of them, while 21,4% eventually died.
UI - 11733839
AU - Martins DC; Stavale JN; Malheiros SM; Santiago LH; Roman LC; Aguiar KC
TI - [Fraction of gemistocytic astrocytes and immunoexpression of p53 protein in astrocytomas grade II and III (WHO)]
SO - Arq Neuropsiquiatr 2001 Dec;59(4):926-31
AD - Departamento de Patologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brasil.
Twenty-two patients with astrocytomas, grade II or III WHO, were studied from 1990 to 1998. In all cases, histopathology showed that the astrocytomas had a gemistocytic component. The aims of this study were to establish the fraction of gemistocytic astrocytes, to investigate p53 protein immunoexpression and to evaluate correlations between these two parameters with the tumour outcome. Tumor cells were quantified at high-power magnification (x400). At least 1000 neoplastic cells (small neoplastic astrocytes plus gemistocytes) were counted in each specimen. The percentage of gemistocytes was defined as the gemistocytic index. Nuclear expression of p53 protein was evaluated in neoplastic astrocytes and gemistocytes. Both the frequency (7/22) as well the p53 immunoexpression indices in gemistocytes, regardless of the grade of the astrocytomas, were inferior from those reported in the literature. No correlation was found between the gemistocytic indices and the p53 immunoexpression.
UI - 11791179
AU - Adachi Y; Chandrasekar N; Kin Y; Lakka SS; Mohanam S; Yanamandra N;
TI - Mohan PM; Fuller GN; Fang B; Fueyo J; Dinh DH; Olivero WC; Tamiya T; Ohmoto T; Kyritsis AP; Rao JS Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense uPAR and sense p16 gene sequences.
SO - Oncogene 2002 Jan 3;21(1):87-95
AD - Department of Neurological Surgery, Okayama University Medical School, 2-5-1 shikata-cho, Okayama, 700-8558, Japan.
Our previous studies showed that the urokinase-type plasminogen activator receptor (uPAR) and the p16 tumor suppressor gene play a significant role in glioma invasion. We expected that downregulation of uPAR and overexpression of p16 using a bicistronic vector might cause a additive and cooperative effect in the suppression of glioma invasion and growth. The bicistronic construct (Ad-uPAR/p16)-infected glioblastoma cell lines had significantly lower levels of uPAR and higher levels of p16 than controls. Cell cycle analysis showed the bicistronic vector caused G0/G1 arrest of the cell cycle. In vitro glioblastoma cell growth and invasiveness were inhibited in Ad-uPAR/p16-infected cells compared with controls. Ad-uPAR/p16 suppressed the tumor growth of glioblastoma cell lines in an ex vivo intracerebral tumor model and an in vivo subcutaneous tumor model. Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.
UI - 11810382
AU - Leonardi MA; Lumenta CB
TI - Oligodendrogliomas in the CT/MR-era.
SO - Acta Neurochir (Wien) 2001 Dec;143(12):1195-203
AD - Department of Neurosurgery, Academic Hospital Munchen-Bogenhausen, Munchen, Germany.
BACKGROUND: The aim of this study was to investigate survival times and 4 prognostic factors of oligodendrogliomas in the CT/MR-era, since most previous studies result from the pre-CT-era, where modern histopathological classification, diagnostic and therapeutic tools were not used. Thus, in the past mixed gliomas were included, and survival times and prognostic factors were not corrected for grades. METHOD: We present a retrospective study of 19 pure low grade (LO) and 21 pure anaplastic (AO) oligodendrogliomas (according to WHO) treated in the CT/MR-era 1987 to 1999. Survival times and rates were calculated in each grade according to the Kaplan-Meier-method. Following factors were analyzed for influence on survival in each grade using uni- and multivariate analysis: KI (karnofski index) equal or greater than 80 at time of diagnosis, contrast medium enhancement and calcification in preoperative CT or MRI, radiation therapy. FINDINGS: In LO median survival time was 114 months and 5 and 10-year survival rates were 78.9 and 44.1%, respectively. For AO median survival time was 21 months and 5- and 10-year survival rates were 23.8% and 0.05%, respectively. This difference reached statistical difference (p=0.0002). In LO none of the factors were statistically associated with better survival. Patients with AO had a significantly better outcome, when presenting with a KI of 80 or higher (uni- and multivariate analysis), than had tumours without contrast medium uptake (univariate) and for those with radiation therapy (univariate and multivariate). INTERPRETATION: In the CT/MR-era we did not observe a longer survival time or rate for patients with pure oligodendrogliomas compared to historical data. Prognostic factors should be evaluated separately in each grade, since grading according to WHO is strongly associated with survival. Patients with AO had a statistically longer survival when presenting with higher KI, without contrast enhancement and after postoperative radiation therapy.
UI - 11832530
AU - Pollack IF; Finkelstein SD; Woods J; Burnham J; Holmes EJ; Hamilton RL;
TI - Yates AJ; Boyett JM; Finlay JL; Sposto R; The Children's Cancer Group Expression of p53 and prognosis in children with malignant gliomas.
SO - N Engl J Med 2002 Feb 7;346(6):420-7
AD - Department of Neurosurgery, University of Pittsburgh Medical Center and Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA. firstname.lastname@example.org
BACKGROUND: The prognosis of children with high-grade gliomas is uncertain, even when clinical and histologic findings are considered. We investigated whether mutations in the TP53 gene or the degree of expression of p53 protein in high-grade gliomas is associated with progression-free survival in children with these tumors. METHODS: Paraffin-embedded specimens of malignant gliomas from children treated in the Children's Cancer Group study CCG-945 were assessed by mutational analysis of TP53 (121 specimens) and immunohistochemical analysis of p53 (115 specimens). For mutational studies, areas of tissue that contained malignant glioma were isolated by microdissection, and the DNA was subjected to polymerase-chain-reaction-based amplification and sequencing of TP53 exons 5, 6, 7, and 8. Immunohistochemical analysis was performed with the use of a microwave-enhanced antigen retrieval and an antibody that bound both wild-type and mutant p53. RESULTS: We found a significant association between overexpression of p53 and outcome; this association was independent of histologic features, age, sex, the extent of resection, and tumor location. The rate ( +/- SE) of progression-free survival at five years was 44 +/- 6 percent in the group of 74 patients whose tumors had low levels of expression of p53 and 17 +/- 6 percent in the group of 41 patients whose tumors had overexpression of p53 (P<0.001). A nonsignificant association was observed between mutations in TP53 and outcome. CONCLUSIONS: Overexpression of p53 in malignant gliomas during childhood is strongly associated with an adverse outcome, independently of clinical prognostic factors and histologic findings.
UI - 11665461
AU - Beall C; Delzell E; Rodu B; Sathiakumar N; Myers S
TI - Cancer and benign tumor incidence among employees in a polymers research complex.
SO - J Occup Environ Med 2001 Oct;43(10):914-24
AD - Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, 220A Royals Building, 1665 University Boulevard, Birmingham, AL 35294-0022, USA. email@example.com
The detection of several intracranial tumors among employees in one building complex (C500) at a petrochemical research facility prompted investigation of a possible workplace cause. This retrospective follow-up study included 1847 subjects, of whom 1735 had worked in C500. Medical records, death certificates, and Illinois State Cancer Registry data confirmed self-reported cancers and tumors. Analyses compared the subjects' cancer and benign intracranial tumor incidence rates with national general population rates. C500 employees had 15% fewer than expected total cancers (92 observed/108 expected; standardized incidence ratio [SIR], 85; 95% confidence interval [95% CI], 69 to 104). An excess of brain cancer (6/2.0; SIR, 302; 95% CI, 111 to 657) was concentrated among white men who had 10 or more years since hire and 5 or more years of C500 employment (4/0.7; SIR, 602; 95% CI, 165 to 1552) and who had worked in a particular building of C500 (5/0.7; SIR, 735; 95% CI, 239 to 1716). An excess of benign intracranial tumors (6/1.6; SIR, 385; 95% CI, 142 to 839) was not restricted to a single type of tumor and was not concentrated in any particular building. Occupational exposure may have caused the increased rate of brain cancer but is a less likely explanation for the elevated rate of benign intracranial tumors.
UI - 11702108
AU - Ohtani T; Kurihara H; Ishiuchi S; Saito N; Oriuchi N; Inoue T; Sasaki T
TI - Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging.
SO - Eur J Nucl Med 2001 Nov;28(11):1664-70
AD - Department of Neurosurgery, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan. firstname.lastname@example.org
The purpose of this study was to assess the clinical potential of methyl-11C-choline (11C-choline) in the diagnosis of brain tumours. To this end, the results of 11C-choline positron emission tomography (PET) in 22 patients suspected of having brain tumours were compared with the findings of contrast-enhanced magnetic resonance (MR) imaging and fluorine-18 fluorodeoxyglucose PET. A histopathological diagnosis was made for each patient during open surgery. The standardised uptake values of brain tumours and the tumour-to-white matter count (T/W) ratios were determined. The degree of 11C-choline accumulation noted in PET images was compared with the gadolinium-enhanced areas of MR images. The mean T/W ratio of 11C-choline in high-grade gliomas was found to be higher than that in low-grade gliomas. This difference was statistically significant (mean+/-SD: 8.7+/-6.2, n=9 versus 1.5+/-0.7, n=5, P<0.03) when data pertaining to the prominent uptake of 11C-choline in a patient with a pilocytic astrocytoma were excluded. 11C-choline PET failed to detect non-neoplastic lesions in two patients. Areas of 11C-choline accumulation in PET scans were larger than areas enhanced on MR images in five cases involving high-grade gliomas. 11C-choline PET differentiated between low-grade gliomas and high-grade gliomas, but did not differentiate between low-grade gliomas and non-neoplastic lesions. The combination of 11C-choline PET and MR imaging may provide investigators with an accurate means by which to identify high-grade gliomas.
UI - 11705870
AU - Bobola MS; Blank A; Berger MS; Stevens BA; Silber JR
TI - Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas.
SO - Clin Cancer Res 2001 Nov;7(11):3510-8
AD - Department of Neurological Surgery, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195, USA.
Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair activity that confers resistance to ionizing radiation and alkylating agents in human cell lines. The major Ap endo in human cells is Ape1, an abundant multi-functional protein also known as Ref-1, Hap-1, and Apex. In this work, we assayed Ap endo activity in human adult gliomas to establish correlates with tumor characteristics, and in histologically normal brain adjacent to tumors to characterize changes in activity accompanying neurocarcinogenesis. To our knowledge, this is the first available analysis of Ap endo activity in human brain tumors. Mean activity in 84 gliomas of different diagnostic types and grades was 0.072 +/- 0.095 fmol abasic sites incised/cell/min, ranging approximately 550-fold from 0.00077 to 0.42. The mean for high-grade gliomas was 3.5-fold greater than for low-grade tumors (P < or = 4.0 x 10(-5)), a difference observed within all diagnostic types. Activity was correlated with the fraction of S-phase cells in diploid gliomas (P < or = 0.02), suggesting that proliferation could be a determinant of activity in these tumors. Activity was also correlated with S-phase fraction in the majority of aneuploid gliomas (P < or = 0.03). Moreover, within the aneuploid tumors, there was a significant relationship between activity and the fraction of aneuploid cells (P < or = 4.0 x 10(-4)). In the 58 cases analyzed, mean activity was 7.3-fold higher in gliomas than in adjacent histologically normal brain (0.070 +/- 0.10 versus 0.0096 +/- 0.012 fmol/cell/min; P < or = 3.0 x 10(-5)). Increased tumor activity was observed in 93% of tumor/normal pairs, indicating that elevation of Ap endo activity is characteristic of human gliomagenesis. The elevation was large within most pairs, being 13-fold on average and > or = 10-fold in 43% of cases. A concomitant increase in Ape1 protein was observed by Western blotting in the subset of tumor/normal pairs examined. A clinically important consequence of the increase in Ap endo activity that accompanies neurocarcinogenesis may be enhanced resistance to the radiotherapy and alkylating agent-based chemotherapy that are mainstays of adjuvant therapy for malignant gliomas.
UI - 11744878
AU - Poussaint TY
TI - Magnetic resonance imaging of pediatric brain tumors: state of the art.
SO - Top Magn Reson Imaging 2001 Dec;12(6):411-33
AD - Department of Radiology, Harvard Medical School, and Children's Hospital, Boston, Massachusetts 02115, USA. email@example.com
Over the past 25 years, magnetic resonance imaging (MRI) has developed into the primary imaging tool for evaluation of the central nervous system. MRI is the essential imaging study in the twenty-first century for the evaluation of the child with a brain tumor for initial preoperative diagnosis, treatment planning and image-guided therapies. This article provides an overview of the locations and MRI features of common pediatric tumors of childhood.
UI - 11746940
AU - Schad LR
TI - Improved target volume characterization in stereotactic treatment planning of brain lesions by using high-resolution BOLD MR-venography.
SO - NMR Biomed 2001 Nov-Dec;14(7-8):478-83
AD - Department of Biophysics and Medical Radiation Physics, German Cancer Research Center, Heidelberg, Germany. firstname.lastname@example.org
In this methodological paper I report the stereotactic correlation of different magnetic resonance imaging (MRI) techniques [MR angiography (MRA), MRI, blood bolus tagging (STAR), functional MRI, and high-resolution BOLD venography (HRBV)] in patients with cerebral arterio-venous malformations (AVM) and brain tumors. The patient's head was fixed in a stereotactic localization system which is usable in both MR-systems and linear accelerator installations. Using phantom measurements global geometric MR image distortions can be 'corrected' (reducing displacements to the size of a pixel) by calculations based on modeling the distortion as a fourth-order two-dimensional polynomial. Further object-induced local distortions can be corrected by additionally measured field maps. Using this method multimodality matching could be performed automatically as long as all images are acquired in the same examination and the patient is sufficiently immobilized to allow precise definition of the target volume. Information about the hemodynamics of the AVM was provided by a dynamic MRA with the STAR technique, leading to an improved definition of the size of the nidus, the origin of the feeding arteries, whereas HRBV imaging yielded detailed and improved information about the venous pattern and drainage. In addition, functional MRI was performed in patients with lesions close to the primary motor cortex area, leading to an improved definition of structures at risk for the high-dose application in radiosurgery. In patients with brain tumors the potential of HRBV to probe tumor angiogenesis and its use in intensity-modulated treatment planning is still hampered by the open question of how to translate a BOLD signal pattern measured in the tumor to a dose distribution, which should be addressed in future studies. Copyright 2001 John Wiley & Sons, Ltd.
UI - 11756757
AU - Brat DJ; Castellano-Sanchez A; Kaur B; Van Meir EG
TI - Genetic and biologic progression in astrocytomas and their relation to angiogenic dysregulation.
SO - Adv Anat Pathol 2002 Jan;9(1):24-36
AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. email@example.com
Infiltrative astrocytic neoplasms are the most common malignancies of the central nervous system. They remain clinically problematic because of their involvement of brain structures critical to proper cognitive, behavioral, and motor function; their widely invasive properties, which make them difficult to resect totally; and their nearly inevitable biologic progression in spite of adjuvant therapy. Glioblastoma multiforme (GBM, World Health Organization grade IV), the most malignant form of infiltrating astrocytoma, can present as a high-grade lesion from the outset (so-called de novo GBM) or can evolve from a lower grade precursor lesion (secondary GBM). Molecular genetic investigations suggest that GBM is best regarded as a clinicopathologic entity composed of multiple molecular genetic subsets. Molecular alterations associated with progression to GBM and that define genetic subsets include epidermal growth factor receptor amplifications, p53 mutations, retinoblastoma pathway alterations [most co