Last Modified: November 1, 2001
Table of Contents
CancerMail from the National Cancer Institute
UI - 21220024
AU - Yoshida S; Fukino K; Harada H; Nagai H; Imoto I; Inazawa J; Takahashi H; Teramoto A; Emi M
TI - The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors.
SO - J Hum Genet 2001;46(4):182-7
AD - Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
By examining 19 human cell lines derived from brain tumors for altered expression of expressed sequence tags (ESTs) in chromosomal band 4q21-22, we detected loss of expression, in 10 cell lines, of two sequences, WI6336 and WI7913. Both corresponded to the c-Jun NH2-terminal kinase (JNK) 3. In the present study, genomic cloning revealed that the JNK3 gene consists of 14 exons interrupted by 13 introns; its transcription-initiation site is within exon 3 and the termination codon lies in exon 14. Fluorescence in situ hybridization (FISH) and radiation-hybrid mapping confirmed the gene to 4q21-22. Together with prior evidence that, in JNK3-deficient mice, the JNK3 signaling pathway mediates apoptosis in central nervous tissue, our results suggest that loss of expression of the JNK3 gene may play an important role in the development of brain tumors in humans.
UI - 21220529
AU - Zheng T; Cantor KP; Zhang Y; Keim S; Lynch CF
TI - Occupational risk factors for brain cancer: a population-based case-control study in Iowa.
SO - J Occup Environ Med 2001 Apr;43(4):317-24
AD - Yale University School of Public Health, New Haven, USA. firstname.lastname@example.org
A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.
UI - 21236156
AU - Remmelinck M; Lopes MB; Nagy N; Rorive S; Rombaut K; Decaestecker C; Kiss R; Salmon I
TI - How could static telepathology improve diagnosis in neuropathology?
SO - Anal Cell Pathol 2000;21(3-4):177-82
AD - Department of Pathology, Cliniques Universitaires de Bruxelles, H pital Erasme, Universite Libre de Bruxelles, Brussels, Belgium.
The present paper reports our experience with, and our opinion of static telepathology as applied to neuropathology by means of the PHAROS acquisition system and conventional telephone data transmission (modem). The classical procedure of expert consultation based on surface mailing of histological slides is routinely performed, especially in highly specialized fields of pathology. Telepathology is an easy means of sharing scientific expertise at international level and could thus improve diagnosis particularly in neuropathology, where certain tumor types are very rare and complex to diagnose. Dynamic telepathology allows the referring pathologist to capture by himself images supporting their diagnosis. Using static telepathology the pathologist could be limited in diagnosis by problems in fields selection. We devoted a whole year to collecting all the technical parameters characterizing the use of digitized neuropathological data files in order to investigate the feasibility of telepathology and the extent to which its use could improve diagnoses. Our results on a series of 38 histological brain examinations illustrate how we successfully established an international connection between two departments of pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35 cases and deferred only 3. Despite a time-consuming procedure for the telepathology session of a few cases, this tool provides easy access to expert diagnosis and real-time discussion, both of which are of considerable interest and offer significant improvements in neuropathology.
UI - 21261631
AU - Harada K; Nishizaki T; Kubota H; Harada K; Suzuki M; Sasaki K
TI - Distinct primary central nervous system lymphoma defined by comparative genomic hybridization and laser scanning cytometry.
SO - Cancer Genet Cytogenet 2001 Mar;125(2):147-50
AD - Department of Neurosurgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, 755-8505, Yamaguchi, Japan. email@example.com
We investigated chromosomal alterations using comparative genomic hybridization (CGH), and DNA ploidy patterns using laser scanning cytometry (LSC) in 8 primary central nervous system lymphomas (PCNSLs). The average number of chromosomal alterations detected by CGH was 6.9 (gain: 4.1, deletion: 2.8). Frequent alterations were gains of chromosomes 12, 18q, and X, and deletion of 6q, which were similar to those seen in non-CNS diffuse large B-cell lymphoma. DNA aneuploidy was detected by LSC in 4 of the 8 cases. The DNA aneuploid lymphomas had more chromosomal alterations than the DNA diploid ones (9.3 vs. 4.5, P <.05). The former had higher MIB-1 indices than the latter. The present investigation indicates that although most of the PCNSL are histologically uniform, they are divided cytogenetically into DNA aneuploid and diploid tumors.
UI - 21371363
AU - Vaquero J; Zurita M; Morales C; Coca S
TI - Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.
SO - Br J Neurosurg 2001 Jun;15(3):247-50
AD - Laboratory of Experimental Neuro-oncology, Neuroscience Research Unit of the Mapfre-Medicine Foundation & Neurosurgical Service, Puerta de Hierro Clinic Hospital, Autonomous University, Madrid, Spain.
The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma.
UI - 21404633
AU - Chen HJ; Cho CL; Liang CL; Chen L; Chang HW; Lu K; Lee TC
TI - Differential telomerase expression and telomere length in primary intracranial tumors.
SO - Chang Gung Med J 2001 Jun;24(6):352-60
AD - Department of Neurosurgery, Chang Gung Memorial Hospital, 123, Tao-Pei Road, Niaosung, Kaohsiung, Taiwan, R.O.C. firstname.lastname@example.org
BACKGROUND: Telomerase activity and telomere length have been shown to be involved in controlling cell proliferation and regulating cell senescence. The authors examined telomerase activity and telomere length in intracranial tumors to determine the clinicopathological behavior of primary intracranial tumors with respect to telomerase expression and alteration of telomere length. METHODS: Telomerase activity was examined in 139 brain tumor samples. Telomere length was examined in 138 of the 139 samples. These tumors included 61 meningiomas, 27 schwannomas, 19 high-grade neuroepithelial tumors, and 32 low-grade neuroepithelial tumors. Telomerase activity was measured with a telomerase polymerase chain reaction, enzyme-linked immunosolvent assay kit. Telomere length was examined by Southern blot analysis for the terminal restriction fragment length. RESULTS: Telomerase activity was detected in 39.2% (20/51) of the neuroepithelial tumors. Detection rates were 47.4% (9/19) for anaplastic astrocytomas and glioblastomas and 34.4% (11/32) for low-grade neuroepithelial tumors. However, detectable telomerase activity was found in 30.8% (4/13) of atypical or malignant meningiomas, but was not detected in any schwannomas. There was a highly significant difference in the telomerase detection rate in neuroepithelial or non-neuroepithelial tumors (p = 0.001). Telomere elongation was found in 11.7% (7/60) of all meningiomas, 46.1% (6/13) of atypical or malignant meningiomas, and 14.8% (4/27) of schwannomas. Elongation of telomere length was detected in 12.6% (11/87) of the cases and 23.5% (12/51) in neuroepithelial tumors. This difference was also significant (p < 0.05). Telomere length was reduced in the majority, (75%, 3/4) of malignant or atypical meningiomas with detectable telomerase activity, but only 45% (9/20) of the neuroepithelial tumors. CONCLUSION: These results indicate that telomerase activation may be a critical step in the pathogenesis of intracranial tumors. Telomere length elongation also indicates a high potential for malignant behavior in these tumors.
UI - 21397940
AU - Fukumura D; Xu L; Chen Y; Gohongi T; Seed B; Jain RK
TI - Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo.
SO - Cancer Res 2001 Aug 15;61(16):6020-4
AD - Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. email@example.com
Hypoxia and acidosis are hallmarks of tumors as well as critical determinants of response to treatments. They can upregulate vascular endothelial growth factor (VEGF) in vitro. However, the relationship between tissue oxygen partial pressure (pO(2))/pH and VEGF transcription in vivo is not known. Thus, we developed a novel in vivo microscopy technique to simultaneously measure VEGF promoter activity, pO(2), and pH. To monitor VEGF expression in vivo, we engineered human glioma cells that express green fluorescent protein (GFP) under the control of the VEGF promoter. These cells were implanted into the cranial windows in severe combined immunodeficient mice, and VEGF promoter activity was assessed by GFP imaging. Tissue pO(2) and pH were determined by phosphorescence quenching microscopy and ratio imaging microscopy, respectively. These techniques have allowed us to show, for the first time, that VEGF transcription in brain tumors is independently regulated by the tissue pO(2) and pH. One week after tumor implantation, significant angiogenesis was observed, with increased GFP fluorescence throughout the tumor. Under hypoxic or neutral pH conditions, VEGF-promoter activity increased, with a decrease in pO(2) and independent of pH. Under low pH or oxygenated conditions, VEGF-promoter activity increased, with a decrease in pH and independent of pO(2). In agreement with the in vivo findings, both hypoxia and acidic pH induced VEGF expression in these cells in vitro and showed no additive effect for combined hypoxia and low pH. These results suggest that VEGF transcription in brain tumors is regulated by both tissue pO(2) and pH via distinct pathways.
UI - 21193585
AU - Anonymous
TI - Nokia, Ericsson and others are happier...
SO - Ann Oncol 2001 Feb;12(2):140-1
UI - 21199020
AU - Sugita Y; Terasaki M; Shigemori M; Sakata K; Morimatsu M
TI - Acute focal demyelinating disease simulating brain tumors: histopathologic guidelines for an accurate diagnosis.
SO - Neuropathology 2001 Mar;21(1):25-31
AD - Department of Pathology, Kurume University School of Medicine, Kurume-shi, Fukuoka-ken, Japan. firstname.lastname@example.org
The object of the present study was to determine the histopathological guidelines for accurate diagnosis of cases of acute focal demyelinating disease that simulates brain tumors. The surgical pathology of three such cases is assessed. Histopathological keys to the diagnosis of such cases are as follows. First, a pattern of sheets of atypical gemistocytic astrocytes in the white matter that show well-formed processes and that are adequately distanced from each other argues against a diagnosis of neoplasm. Second, uniform distribution of foamy macrophages aligned along axons, with occasional focal collections surrounding blood vessels and in the absence of any associated coagulative necrosis argues against the presence of a tumor. Third, perivascular chronic inflammatory infiltration, especially a mixture of lymphocytes and macrophages, favors the diagnosis of demyelination plaque. In such cases the lymphocytes will be predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack of vascular endothelial proliferation should raise the suspicion that the lesion may not be a brain tumor. These diagnostic keys should be followed when diagnosing cases that are suspected to be demyelination processes rather than brain tumors. The presence of demyelination plaque should then be confirmed by imaging modalities such as staining with myelin-and axon-specific stains.
UI - 21232099
AU - Braun V; Dempf S; Tomczak R; Wunderlich A; Weller R; Richter HP
TI - Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.
SO - Neurosurgery 2001 May;48(5):1178-81; discussion 1181-2
AD - Department of Neurosurgery, University of Ulm, Gunzburg, Germany. email@example.com
OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).
UI - 21280980
AU - Nishio S; Morioka T; Takeshita I; Fukui M
TI - Nerve cell tumours of the cerebrum: variable clinical and pathological manifestations.
SO - J Clin Neurosci 2001 May;8(3):225-30
AD - Department of Neurosurgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Nerve cell tumours of the cerebrum tend to display a high degree of morphological variability from case to case, and this leads to poor understanding of these tumours. We retrospectively reviewed the clinical and patho-anatomic features of 16 primary nerve cell tumours of the cerebrum (M:9; F:7; average age at onset: 10.2 years). Intraventricular tumours were not included. In 13 patients epileptic seizures were the only symptoms, while three had headache or hemiparesis. Seven tumours were located in the frontal lobe, four in the parietal lobe, two in the temporal lobe and one each in the fronto-parietal lobes, occipital lobe and the midbrain. Tumours were histologically classified into three groups. In the first group, six tumours had the morphological features of classic gangliocytoma or ganglioglioma. In the second group six cerebral and midbrain tumours were composed of small cells, which showed apparent neuronal differentiation including positive immunoreactivity for synaptophysin and the presence of synaptic structures. These tumours usually involved both the cortex and white matter. In the third group, three tumours were composed of small nerve cells and ganglioid cells. All tumours were relatively well circumscribed, and thus eight tumours were totally removed, five subtotally and three partially. Following surgery, three patients, except one, are alive with stable imaging findings for 4 months - 19.3 years (average 11.6 years) after treatment. While small nerve cell tumours are found throughout the cerebrum and its identification broadens the spectrum of neuronal and mixed neuro-glial tumours, most of these tumours are biologically indolent. Copyright 2001 Harcourt Publishers Ltd.
UI - 21280982
AU - Attar A; Ugur HC; Savas A; Yuceer N; Egemen N
TI - Surgical treatment of intracranial cavernous angiomas.
SO - J Clin Neurosci 2001 May;8(3):235-9
AD - School of Medicine, Department of Neurosurgery, Ankara University, Ankara, Turkey.
We present a surgical series of 35 patients (25 males and 10 females) with histopathologically verified intracranial cavernous angiomas. The 35 malformations were located as follows: 21 were in the cerebral hemispheres; 4 in the lateral ventricles, 4 in the brain stem; and 6 in the cerebellum. Seizures and focal neurological deficits were the main clinical features observed in patients with intracranial cavernous angiomas. A number of these vascular malformations were misdiagnosed by computerized tomography. In the last 10 years, magnetic resonance imaging has been the most sensitive method for detecting these lesions. Thirty-five cavernous angiomas were treated surgically; in 33 patients a complete excision, and in 2 patients subtotal excision were obtained. One of the patients died one year after the operation. The overall outcome was good in all of the 34 remaining patients, resulting in improved seizure control or neurological deficit. The rationale for neurologic differential diagnosis and surgical treatment and follow up results are discussed. Copyright 2001 Harcourt Publishers Ltd.
UI - 21304142
AU - Weltens C; Menten J; Feron M; Bellon E; Demaerel P; Maes F; Van den Bogaert W; van der Schueren E
TI - Interobserver variations in gross tumor volume delineation of brain tumors on computed tomography and impact of magnetic resonance imaging.
SO - Radiother Oncol 2001 Jul;60(1):49-59
AD - Department of Radiotherapy, University Hospital Gasthuisberg, Leuven, Belgium.
PURPOSE: (1) To assess the interobserver variability of brain tumor delineation on computed tomography (CT). (2) To assess the impact of the addition of magnetic resonance imaging (MRI) information. METHODS: Nine physicians were asked to delineate the gross tumor volume (GTV) of five patients with supratentorial inoperable brain tumors on CT scans and 2 weeks (or more) later on MRIs. The delineations were performed on a computer screen. During delineation on MRI, the registered CT images (without delineation) were displayed on the screen (MRI+CT). RESULTS: A high interobserver variability in GTV delineation on CT is found: the ratio of the largest to the smallest defined volumes varies for the five patients by factors of resp. 2.8, 1.8, 1.8, 1.9 and 1.7. The interobserver variability is as large on MRI+CT as on CT alone (ratio largest/smallest volume: 2.4, 1.7, 1.9, 2.7 and 1.5). Volumes delineated on MRI+CT (mean: 69.6 cm(3)) are larger than on CT alone (mean: 59.5 cm(3)). Residual volumes (volume delineated on one image modality but not on the other) are >0 for CT alone and for MRI+CT. CONCLUSIONS: A large interobserver variability in GTV delineation of brain tumors is demonstrated. The addition of MRI to CT does not reduce interobserver variability. GTVs delineated on MRI+CT are larger than on CT alone, but some volumes are delineated on CT and not on MRI. Therefore, a combination of the two image modalities is recommended for brain tumor delineation for treatment planning.
UI - 21359702
AU - De Divitiis O; La Torre D
TI - Inverse correlation of TRF1 expression and cell proliferation in human primary intracranial tumors.
SO - J Neurosurg Sci 2001 Mar;45(1):1-6
AD - Department of Neurosurgery, Polyclinic, University of Messina, Messina, Italy. firstname.lastname@example.org
BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling cellular proliferative potential. TRF1 is involved in a negative feedback mechanism that allows telomere shortening by inhibiting the activity of telomerase. Down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. The goal of the present study was to determine whether routine immunohistochemical (IHC) techniques can characterize TRF1 expression in different human brain tumor specimens and whether it correlates with other indices of brain tumor's proliferative potential. METHODS: A cohort of 20 flash-frozen surgical specimens [14 meningiomas and 6 anaplastic astrocytomas (AA)] were evaluated for TRF1 expression. Results of parallel investigations of tumor's proliferative indices as assessed by Ki67 labeling index (LI) determinations were cross-correlated with TRF1 expression results and histotype. RESULTS: We demonstrated variable levels of TRF1 expression in 12 out of 14 (87.5%) meningioma samples. By contrast, we detected no expression of TRF1 in tissue samples from AA (p=0.008). The Ki67 LI was higher in AA than in meningioma samples (15.21+/-9.34 vs 26.6+/-13.89, p=0.044). Statistical analysis revealed a significant inverse correlation between TRF1 expression, histotype, and LI (c2=14.1; p=0.0008). CONCLUSIONS: We demonstrated for the first time that routine IHC techniques are capable to identifying TRF1 expression in intracranial tumors. The results suggest that TRF1 is heterogeneously expressed in meningiomas, and absent in AA. The TRF1 status in intracranial tumors might be of prognostic value and possibly represent a potential application for biologically targeted therapeutic strategies.
UI - 21370240
AU - Lehnhardt FG; Rohn G; Ernestus RI; Grune M; Hoehn M
TI - 1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components.
SO - NMR Biomed 2001 Aug;14(5):307-17
AD - Max-Planck-Institute for Neurological Research, Cologne, Germany.
In vitro NMR spectroscopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. (31)P- and (1)H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. (31)P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the (1)H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the (31)P- and the (1)H-spectra. Based on the total detectable (31)P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary glioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and -23% (p = 0.0314) change, respectively]. (1)H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the (31)P-spectra, the (1)H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. (1)H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution (1)H- and (31)P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism. Copyright 2001 John Wiley & Sons, Ltd.
UI - 21417651
AU - Fruhwald MC; O'Dorisio MS; Dai Z; Tanner SM; Balster DA; Gao X; Wright FA; Plass C
TI - Aberrant promoter methylation of previously unidentified target genes is a common abnormality in medulloblastomas--implications for tumor biology and potential clinical utility.
SO - Oncogene 2001 Aug 16;20(36):5033-42
AD - Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Columbus, OH 43210, USA. email@example.com
Medulloblastomas exhibit an array of diverse cytogenetic abnormalities. To evaluate the significance of epigenetic rather than genetic lesions in medulloblastomas and other primitive neuroectodermal tumors (PNETs) of the childhood CNS we performed a systematic analysis of gene specific and global methylation. Methylation-specific PCR detected no methylation for p15(INK4B), von Hippel Lindau and TP53 and only limited methylation for E-Cadherin and p16(INK4A) in tumors. The cell lines Daoy and MHH-PNET-5 in which the p16(INK4A) promoter was methylated did not express the gene, but demonstrated abnormalities by SSCP. Immunohistochemistry for p16 was negative in all examined normal cerebella and medulloblastomas. Using the technique of Restriction Landmark Genomic Scanning we detected methylation affecting up to 1% of all CpG islands in primary MB/PNETs and 6% in MB cell lines. Methylation patterns differed between medulloblastomas and PNETs. Examination of several methylated sequences revealed homologies to known genes and expressed sequences. Analysis of survival data identified seven of 30 hypermethylated sequences significantly correlating with poor prognosis. We suggest that DNA hypermethylation has an outstanding potential for the identification of novel tumor suppressors as well as diagnostic and therapeutic targets in MBs and other PNETs of the CNS.
UI - 21213414
AU - Weckesser M; Matheja P; Rickert CH; Strater R; Palkovic S; Lottgen J; Kurlemann G; Paulus W; Wassmann H; Schober O
TI - High uptake of L-3-[123I]iodo-alpha-methyl tyrosine in pilocytic astrocytomas.
SO - Eur J Nucl Med 2001 Mar;28(3):273-81
AD - Department of Nuclear Medicine, Munster University, Albert-Schweitzer-Strasse 33, 48149 Munster, Germany. firstname.lastname@example.org
Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[123I]iodo-alpha-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n = 10, r = 0.87, P < 0.05). Differences in IMT uptake in primaries (1.7 +/- 0.6, n = 10) and in recurrent tumours (2.3 +/- 0.7, n = 6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.
UI - 21230830
AU - Crivellari D; Pagani O; Veronesi A; Lombardi D; Nole F; Thurlimann B; Hess D; Borner M; Bauer J; Martinelli G; Graffeo R; Sessa C; Goldhirsch A; International Breast Cancer Study Group
TI - High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.
SO - Ann Oncol 2001 Mar;12(3):353-6
AD - Divisione di Oncologia Medica, Istituto Nazionale Tumori, Aviano, Italy. email@example.com
BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.
UI - 21382807
AU - Knerr I; Schuster S; Nomikos P; Buchfelder M; Dotsch J; Schoof E; Fahlbusch R; Rascher W
TI - Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans.
SO - Neuropathol Appl Neurobiol 2001 Jun;27(3):215-22
AD - Departments of Paediatrics and Neurosurgery, University of Erlangen-Nuremberg, Germany.
The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.
UI - 21382808
AU - Aronica E; Yankaya B; Jansen GH; Leenstra S; van Veelen CW; Gorter JA; Troost D
TI - Ionotropic and metabotropic glutamate receptor protein expression in glioneuronal tumours from patients with intractable epilepsy.
SO - Neuropathol Appl Neurobiol 2001 Jun;27(3):223-37
AD - Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. firstname.lastname@example.org
Glioneuronal tumours are an increasingly recognized cause of chronic pharmaco-resistant epilepsy. In the present study the immunocytochemical expression of various glutamate receptor (GluR) subtypes was investigated in 41 gangliogliomas (GG) and 16 dysembryoplastic neuroepithelial tumours (DNT) from patients with intractable epilepsy. Immunocytochemistry with antibodies specific for ionotropic NR1, NR2A/B (NMDA) GluR1, GluR2 (AMPA), GluR5-7 (kainate), and metabotropic mGluR1, mGluR2-3, mGluR5, mGluR7a subtypes demonstrated in both GG and DNT the presence of an highly differentiated neuronal population, containing subunits from each receptor class. More than 50% of tumours contained a high percentage of neuronal cells immunolabelled for NMDA, AMPA and kainate receptor subunits. A high percentage of neurones showed strong expression of NR2A-B, which co-localized with NR1. Group I mGluRs (mGluR1 and mGluR5) were highly represented in the neuronal component of the tumours. Immunolabelling for several GluRs was also present in the glial component. Increased expression of mGluR2-3, mGluR5 and GluR5-7 was observed in reactive astrocytes in the perilesional zone compared to normal cortex. The neurochemical profile of glioneuronal tumours, with high expression of specific GluR subtypes, supports the central role of glutamatergic transmission in the mechanisms underlying the intrinsic and high epileptogenicity of these lesions.
UI - 21396267
AU - Smith JS; Tachibana I; Passe SM; Huntley BK; Borell TJ; Iturria N; O'Fallon JR; Schaefer PL; Scheithauer BW; James CD; Buckner JC; Jenkins RB
TI - PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.
SO - J Natl Cancer Inst 2001 Aug 15;93(16):1246-56
AD - Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. METHODS: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.
UI - 21378243
AU - Xu X; Joh HD; Pin S; Schiller NI; Prange C; Burger PC; Schiller MR
TI - Expression of multiple larger-sized transcripts for several genes in oligodendrogliomas: potential markers for glioma subtype.
SO - Cancer Lett 2001 Sep 28;171(1):67-77
AD - Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Astrocytomas and oligodendrogliomas are two brain tumors that follow different clinical courses. Although many of these tumors can be identified based on standard histopathological criteria, a significant percentage present notable problems in diagnosis. To identify markers that might prove useful in distinguishing glioma subtypes, we prepared and analyzed cDNA libraries for differential expression of genes in an astrocytoma (grade II), an oligodendroglioma (grade II), and a meningioma (benign). The tumor libraries were compared by sequencing randomly selected clones and tabulating the expression frequency of each gene. In addition to identifying several genes previously reported or expected to be differentially expressed among these tumors, several potential new brain tumor markers were identified and confirmed by Northern blot analysis of a panel of brain tumors. A surprising result of this analysis was the observation that several larger-sized transcripts for various genes were predominantly expressed in the oligodendroglioma tumors, when compared to the other brain tumors or in non-tumor gray matter. These findings are consistent with different pre-mRNA splicing patterns observed between oligodendrogliomas and astrocytomas. In support of this hypothesis, our screen revealed significantly higher levels of two hnRNP A1 transcripts in oligodendrogliomas. hnRNP A1 is a component of the spliceosome whose expression levels affect splice site selection in vivo. The preferential expression of larger-sized transcripts for several genes in oligodendrogliomas may be useful for distinguishing astrocytic and oligodendroglial gliomas.
UI - 21402852
AU - Caldemeyer KS; Mirowski GW
TI - Tuberous sclerosis. Part I. Clinical and central nervous system findings.
SO - J Am Acad Dermatol 2001 Sep;45(3):448-9
AD - Department of Radiology, Division of Neuroradiology, Indiana University Medical Center, 550 N University Blvd., Indianapolis, IN 46202, USA. email@example.com
UI - 20506396
AU - Greenwald J
TI - Do cell phones need warnings?
SO - Time 2000 Oct 9;156(15):66-7
UI - 20572052
AU - Muscat JE; Malkin MG; Thompson S; Shore RE; Stellman SD; McRee D; Neugut AI; Wynder EL
TI - Handheld cellular telephone use and risk of brain cancer.
SO - JAMA 2000 Dec 20;284(23):3001-7
AD - American Health Foundation, 1 Dana Rd, Valhalla, NY 10595, USA. firstname.lastname@example.org
CONTEXT: A relative paucity of data exist on the possible health effects of using cellular telephones. OBJECTIVE: To test the hypothesis that using handheld cellular telephones is related to the risk of primary brain cancer. DESIGN AND SETTING: Case-control study conducted in 5 US academic medical centers between 1994 and 1998 using a structured questionnaire. PATIENTS: A total of 469 men and women aged 18 to 80 years with primary brain cancer and 422 matched controls without brain cancer. MAIN OUTCOME MEASURE: Risk of brain cancer compared by use of handheld cellular telephones, in hours per month and years of use. RESULTS: The median monthly hours of use were 2.5 for cases and 2.2 for controls. Compared with patients who never used handheld cellular telephones, the multivariate odds ratio (OR) associated with regular past or current use was 0.85 (95% confidence interval [CI], 0.6-1.2). The OR for infrequent users (<0. 72 h/mo) was 1.0 (95% CI, 0.5-2.0) and for frequent users (>10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The mean duration of use was 2.8 years for cases and 2.7 years for controls; no association with brain cancer was observed according to duration of use (P =.54). In cases, cerebral tumors occurred more frequently on the same side of the head where cellular telephones had been used (26 vs 15 cases; P =.06), but in the cases with temporal lobe cancer a greater proportion of tumors occurred in the contralateral than ipsilateral side (9 vs 5 cases; P =.33). The OR was less than 1.0 for all histologic categories of brain cancer except for uncommon neuroepitheliomatous cancers (OR, 2.1; 95% CI, 0.9-4.7). CONCLUSIONS: Our data suggest that use of handheld cellular telephones is not associated with risk of brain cancer, but further studies are needed to account for longer induction periods, especially for slow-growing tumors with neuronal features.
UI - 21206157
AU - Zimmerman SM; Zimmerman RW
TI - Handheld cellular telephones and brain cancer risk.
SO - JAMA 2001 Apr 11;285(14):1838-9
UI - 21206155
AU - Kane RC
TI - Handheld cellular telephones and brain cancer risk.
SO - JAMA 2001 Apr 11;285(14):1838; discussion 1838-9
UI - 21206156
AU - Hardell L; Mild KH
TI - Handheld cellular telephones and brain cancer risk.
SO - JAMA 2001 Apr 11;285(14):1838; discussion 1838-9
UI - 21243852
AU - Son BC; Kim MC; Choi BG; Kim EN; Baik HM; Choe BY; Naruse S; Kang JK
TI - Proton magnetic resonance chemical shift imaging (1H CSI)-directed stereotactic biopsy.
SO - Acta Neurochir (Wien) 2001;143(1):45-9; discussion 49-50
AD - Department of Neurosurgery, Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
INTRODUCTION: To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging (1H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed 1H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results. PATIENTS AND METHOD: The 1H CSI-directed stereotactic biopsy was performed in four patients. 1H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images. RESULTS: 1H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing 1H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis. CONCLUSION: 1H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from 1H CSI. We believe that 1H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.
UI - 21239322
AU - Liu Y; Collins RT; Rothfus WE
TI - Robust midsagittal plane extraction from normal and pathological 3-D neuroradiology images.
SO - IEEE Trans Med Imaging 2001 Mar;20(3):175-92
AD - Robotics Institute, Carnegie Mellon University, Pittsburgh, PA 15213, USA. email@example.com
This paper focuses on extracting the ideal midsagittal plane (iMSP) from three-dimensional (3-D) normal and pathological neuroimages. The main challenges in this work are the structural asymmetry that may exist in pathological brains, and the anisotropic, unevenly sampled image data that is common in clinical practice. We present an edge-based, cross-correlation approach that decomposes the plane fitting problem into discovery of two-dimensional symmetry axes on each slice, followed by a robust estimation of plane parameters. The algorithm's tolerance to brain asymmetries, input image offsets and image noise is quantitatively evaluated. We find that the algorithm can extract the iMSP from input 3-D images with 1) large asymmetrical lesions; 2) arbitrary initial rotation offsets; 3) low signal-to-noise ratio or high bias field. The iMSP algorithm is compared with an approach based on maximization of mutual information registration, and is found to exhibit superior performance under adverse conditions. Finally, no statistically significant difference is found between the midsagittal plane computed by the iMSP algorithm and that estimated by two trained neuroradiologists.
UI - 21239323
AU - Otte M
TI - Elastic registration of fMRI data using Bezier-spline transformations.
SO - IEEE Trans Med Imaging 2001 Mar;20(3):193-206
AD - Neurologische Universitatsklinik, Freiburg, Germany. firstname.lastname@example.org
A three-dimensional (3-D) elastic registration algorithm has been developed to find a veridical transformation that maps activation patterns from functional magnetic resonance imaging (fMRI) experiments onto a 3-D high-resolution anatomical dataset. The proposed algorithm uses trilinear Bezier-splines and a 3-D voxel-based optimization technique to determine the transformation that maps the functional data onto the coordinate system of the anatomical dataset. Simple conditions are presented which guarantee that the data are mapped one-to-one on each other. Two voxel-based similarity measures, the linear correlation coefficient and the entropy correlation coefficient, are used. Their performance with respect to the registration of fMRI data is compared. Tests on simulated and real data have been performed to evaluate the accuracy of the method. Our results demonstrate that subvoxel accuracy can be achieved even for noisy low-resolution multislice datasets with local distortions up to 10 mm. Although the method is optimized for the registration of functional and anatomical MR images, it can also be used for solving other elastic registration problems.
UI - 21241520
AU - Li KC
TI - Beyond "radiologic-pathologic correlation".
SO - Acad Radiol 2001 May;8(5):375-6
UI - 21241522
AU - Roberts HC; Roberts TP; Bollen AW; Ley S; Brasch RC; Dillon WP
TI - Correlation of microvascular permeability derived from dynamic contrast-enhanced MR imaging with histologic grade and tumor labeling index: a study in human brain tumors.
SO - Acad Radiol 2001 May;8(5):384-91
AD - Department of Radiology, University of California, San Francisco 94143, USA.
RATIONALE AND OBJECTIVES: Dynam