National Cancer Institute®
Last Modified: July 1, 2002
UI - 12013686
AU - Lang O; Kondas O; Torok S; Hauser P; Bognar L; Schuler D
TI - [Incidence of pediatric brain tumors in Hungary between 1989 and 1999]
SO - Orv Hetil 2002 Mar 3;143(9):451-4
AD - Altalanos Orvostudomanyi Kar, II. sz. Gyermekgyogyaszati Klinika, Semmelweis Egyetem, Budapest.
INTRODUCTION: The incidence of primary brain tumors in childhood has increased all over the world in the last decades, so it is the second most frequent tumor after leukaemias. AIMS OF THE STUDY: The aim of this study was to examine the incidence and relative frequency of central nervous system tumors diagnosed under 15 years of age in Hungary. METHODS: The data obtained from the Hungarian Pediatric Oncology Group and the National Neurosurgical Institute between 1989 and 1998, and the reports of the head pediatricians of the counties were used. RESULTS: There were 685 reported cases between 1989 and 1998. The prevalence of cerebral tumors has increased during the last decade in Hungary like that in several developed countries. The increase of the incidence of primary central nervous system tumors in the last ten years was 4.2% per year. In 1998 the incidence of central nervous system tumors was 42.9 cases per million children. The most frequent histological categories were: astrocytoma (30%), medulloblastoma/primitive neuroectodermal tumors (21%), ependymoma (9%) and other tumors (40%). CONCLUSION: The results suggest an increase in the incidence of primary brain tumors in Hungary, similar to those reported in several countries.
UI - 12015749
AU - Jeuken JW; Sprenger SH; Gilhuis J; Teepen HL; Grotenhuis AJ; Wesseling P
TI - Correlation between localization, age, and chromosomal imbalances in ependymal tumours as detected by CGH.
SO - J Pathol 2002 Jun;197(2):238-44
AD - Department of Neurology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. firstname.lastname@example.org
Ependymal tumours (ETs) are gliomas that arise from the ependymal lining of the cerebral ventricles and from the remnants of the central canal of the spinal cord. Both clinical and genetic studies suggest that distinct genetic subtypes of ETs exist, the subtypes being correlated with patient age and/or tumour site. In the present study, the tumour genome of 20 ETs (15 adult and five paediatric cases) was screened for chromosomal imbalances by comparative genomic hybridization (CGH). The most frequently detected imbalances were -22q (75%), -10q (65%), -21 (50%), -16p (50%), -1p (45%), +4q (45%), -10p (45%), -2q (40%), -6 (40%), -19 (40%), -2p (35%), -3p (35%), and -16q (35%). Comparison of the chromosomal imbalances detected in ETs with those previously reported in oligodendroglial and astrocytic tumours revealed that in this respect ETs show similarities to these other gliomas. By combining these results with those of a recent study of Zheng et al. and Hirose et al., it was found that although ETs from different sites and from adult and paediatric patients show overlap at the CGH level, some chromosomal imbalances occur predominantly in a certain category. In adult patients, spinal ETs relatively often showed +2, +7, +12, and -14q; infratentorial ETs -22; and supratentorial ETs -9. In addition, in posterior fossa ETs, -6 and +9 were much more frequent in adults than in children. It is concluded that the genetic background of ETs is complex and partly determined by tumour site, histopathological subtype, and age of the patient. Copyright 2002 John Wiley & Sons, Ltd.
UI - 11900859
AU - Zupanska A; Kaminska B
TI - The diversity of p53 mutations among human brain tumors and their functional consequences.
SO - Neurochem Int 2002 Jun;40(7):637-45
AD - Laboratory of Transcription Regulation, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur Str., 02-093 Warsaw, Poland.
The p53 tumor suppressor is implicated in cell cycle control, DNA repair, replicative senescence and programmed cell death. Inactivation of the p53 contributes to the wide range of human tumors, including glial neoplasms. In this review, we describe the regulation and biochemical properties of p53 protein that may explain its ability to activate various genetic programs underlying cellular responses to stress conditions. The overall spectrum of p53 mutations is rather shared between tumor types indicating that these mutations are not tumor type-specific. However, there is one example of germ-line mutation of p53 gene (the deletion of the codon 236) that is associated with a familiar brain tumor syndrome. We compare the frequency and type of most common mutations among various brain tumours (focusing on glioblastomas) and their consequences on protein functions. Furthermore, we discuss the most promising approaches of potential brain tumor therapy, including an adenovirus-mediated p53 gene transfer. Human glioblastomas are highly sensitive to the effects of p53 activity when the wild-type p53 is introduced ectopically. It suggests that the genetic or pharmacological modulation of the p53 pathway is potentially important strategy in the treatment of human cancers.
UI - 12066901
AU - Buatti JM; Friedman WA
TI - Temporary ventricular drainage and emergency radiotherapy in the management of hydrocephalus associated with germinoma.
SO - J Neurosurg 2002 Jun;96(6):1020-2
AD - Department of Radiation Oncology, University of Iowa, Iowa City, USA.
OBJECT: The authors used an alternative strategy to avoid shunt placement for hydrocephalus associated with germinoma, and the ensuing complications. METHODS: Between 1998 and 2000, five patients presenting with germinomas of the pineal area and symptomatic obstructive hydrocephalus were treated with a novel strategy. On arrival, they underwent ventriculostomy placement and one of several surgical procedures to obtain tissue for diagnosis. Within several days of the initial diagnosis, stereotactically guided fractionated radiotherapy was started. All patients experienced rapid tumor shrinkage and resolution of hydrocephalus, allowing discontinuation of external ventricular drainage without the need for permanent shunting of cerebrospinal fluid. To date, follow up reveals 100% radiographically and clinically confirmed tumor control. CONCLUSIONS: Prompt resolution of hydrocephalus and absence of complications make this a potentially valuable therapy for control of germinomas and their symptoms.
UI - 12066902
AU - Tzika AA; Cheng LL; Goumnerova L; Madsen JR; Zurakowski D; Astrakas LG;
TI - Zarifi MK; Scott RM; Anthony DC; Gonzalez RG; Black PM Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy.
SO - J Neurosurg 2002 Jun;96(6):1023-31
AD - Department of Radiology, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Institute, Boston, 02114, USA. email@example.com
OBJECT: Magnetic resonance (MR) spectroscopy provides biochemical information about tumors. The authors sought to determine the relationship between in vivo and ex vivo biochemical characterization of pediatric brain tumors by using MR spectroscopy. Their hypothesis was that ex vivo MR spectroscopy provides a link between in vivo MR spectroscopy and neuropathological analysis. METHODS: In vivo proton MR spectroscopy was performed before surgery in 11 patients with neuroepithelial tumors. During resection, a total of 40 tumor biopsy samples were obtained from within the volume of interest identified on in vivo MR spectroscopy and were frozen immediately in liquid nitrogen. High-Resolution Magic Angle Spinning (HRMAS) was used to perform ex vivo MR spectroscopy in these 40 tumor biopsy samples. Neuropathological analysis was performed using the same biopsy samples, and the tumors were classified as ependymoma, choroid plexus carcinoma, pineoblastoma (one each), and pilocytic astrocytoma, medullobastoma, low-grade glioma, and glioblastoma multiforme (two each). Ex vivo HRMAS MR spectroscopy improved line widths and line shapes in the spectra, compared with in vivo MR spectroscopy. Choline (Cho) detected in vivo corresponded to three different peaks ex vivo (glycerophosphocholine, phosphocholine [PCho], and Cho). Metabolite ratios from in vivo spectra correlated with ratios from ex vivo spectra (Pearson correlation coefficient range r = 0.72-0.91; p < or = 0.01). Metabolite ratios from ex vivo spectra, such as PCho/ total creatine (tCr) and lipid/tCr, correlated with the percentage of cancerous tissue and percentage of tumor necrosis, respectively (r = 0.84; p < 0.001). CONCLUSIONS: Agreement between in vivo and ex vivo MR spectroscopy indicates that ex vivo HRMAS MR spectroscopy can improve resolution of this modality and provide a link between in vivo MR spectroscopy and neuropathological analysis.
UI - 11895926
AU - Yamamoto S; Yoshida Y; Aoyagi M; Ohno K; Hirakawa K; Hamada H
TI - Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro.
SO - Clin Cancer Res 2002 Mar;8(3):913-21
AD - Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, Tokyo 170-8455, Japan. firstname.lastname@example.org
PURPOSE: Recombinant adenoviral vectors are widely used in clinical and experimental studies to treat malignant tumors. Recently, host immune responses have been proposed as a major limitation in using adenoviral vectors for repeated gene delivery. We demonstrate another limitation unrelated to host immunity. EXPERIMENTAL DESIGN: We repeatedly transduced an adenoviral vector expressing the human p53 gene (AxCIhp53) into U373MG, a p53-susceptible cell line, and established the AxCIhp53-resistant cell line U373R. Most U373R cells survived even after AxCIhp53 treatment due to reduced transduction efficiency. Expression levels of adenovirus receptors were estimated to investigate the cause of reduced transduction efficiency. The mutant vector was used to overcome the resistance. RESULTS: The transduction efficiency of an adenoviral vector possessing the reporter LacZ gene (AxCAZ2-F/wt) for U373R cells was 25.4-fold less than that for parent cells. The expression levels of integrins alpha(v)beta(3) and alpha(v)beta(5) were found to be decreased in U373R cells without affecting the expression levels of Coxsackievirus and adenovirus receptor. The mutant vector AxCAZ2-F/K20, with a linker and a stretch of 20 lysine residues at the COOH-terminal of the fiber protein, improved the transduction efficiency of U373R cells to 12.6-fold of that of AxCAZ2-F/wt. A mutant vector carrying the p53 gene, AxCAhp53-F/K20, dramatically induced apoptosis in U373R cells. CONCLUSIONS: Glioma cells expressing low levels of adenovirus receptors might survive and proliferate to recur after repeated adenoviral transduction, even if the adenoviral transduction is effective at first. Changing the tropism of vectors is a potent method to overcome resistance.
UI - 11955328
AU - Li N; Zhou X; Meng K; Ma H; Wu B; Zheng X; Sun G
TI - [A clinicopathological and prognostic study of 22 cases central neurocytoma]
SO - Zhonghua Bing Li Xue Za Zhi 2002 Feb;31(1):12-5
AD - Department of Pathology, Nanjing General Hospital of PLA, Nanjing 210002, China (Email: email@example.com)
OBJECTIVE: To investigate the clinicopathological features and prognosis of 22 cases of central neurocytoma (CNC), representing 0.48% of a series of 4 528 patients undergoing biopsy for central nervous system tumors. METHODS: The histopathological, ultrastructral, immunohistochemical and clinical features of CNC were studied by electron microscopic examination and immunohistochemical stain for Synaptophysin (Syn), neuron special enolase (NSE), Leu-7, glial fibrillary acid protein (GFAP), MBP and proliferating cell nuclear antigen (PCNA). RESULTS: The age of the cases ranged from 4 to 44 (average 27.9 years) with all tumors localized in the ventricles. In the 18 patients followed up, 14 were alive for 8 months to 14 years and 11 months after the operation, and 4 died. The average survival period was 70.7 months. Histologically, the tumor in all 22 cases had the oligodendroglioma-like pattern with honeycomb appearance and cell-free islands of eosinophilic matrix. Cellular anaplasia, mitosis and necrotic areas were rarely seen in the tumors. Immunohistochemical study demonstrated strong positivity for Syn, NSE and Leu-7, and negative for GFAP and MBP. Ultrastructural features showed presence of round tumor cells with abundant cell processes containing microtubules, neurosecretory granules, clear vesicles and lysosome-like structures. CONCLUSIONS: The differential diagnosis between CNC and oligodendroglioma could not be established by routine light microscopy. The importance of immunohistochemical and electron microscopic studies for making a correct diagnosis is emphasized. The prognosis of patients is usually favorable, even if the tumor was resected subtotally. The relationship between the presence of anaplastic histological features in CNC and patient outcome remains unclear.
UI - 11955336
AU - Tian X; Wang J; Zhang J; Du J; Pang CS; Ho-Keung NG
TI - [The effects of wild-type PTEN transfection on gene expressions of glioblastomas]
SO - Zhonghua Bing Li Xue Za Zhi 2002 Feb;31(1):46-9
AD - Department of Pathology, Health Science Center, Beijing University, Beijing 100083, China. firstname.lastname@example.org
OBJECTIVE: To study the effects of wild-type PTEN on gene expressions of glioblastomas. METHODS: Glioblastoma U87MG cells, which express inactivated PTEN, were transfected with wild-type PTEN constructs and stable transfected clones were selected. Then, cDNA microarray analyses were used to identify differentially expressed genes in wild-type PTEN transfected cells and control cells. RESULTS: Transfected wild-type PTEN inhibited the proliferation of U87MG. By cDNA microarray analyses, 89 cDNA clones were identified, which were differentially expressed in wild-type PTEN transfected cells and control cells. Among these genes, 13 genes were unknown and 76 genes were known genes, including glial fibrillary acidic protein, p21/WAF1, human TGF-beta inducible early protein, human DNA fragmentation factor 45 etc. CONCLUSION: Wild-type PTEN can affect the expressions of multiple genes, by which it regulates the proliferation, differentiation and apoptosis of glioblastomas.
UI - 11955327
AU - Fang J; Luo L; Li J; Sun S; Yuan Y
TI - [Pathological and immunohistochemical study of pineal parenchymal tumors]
SO - Zhonghua Bing Li Xue Za Zhi 2002 Feb;31(1):8-11
AD - Department of Neuropathology, Beijing Neurosurgical Institute, Beijing 100050, China (Email: fangjingyi@X263.net)
OBJECTIVE: To investigate the histological typing and differentiation as well as clinical manifestation and prognosis in pineal parenchymal tumors (PPTs). METHODS: The histological typing of 21 PPTs were made by using HE staining. Synaptophysin (Syn), neuron special enolase (NSE), neurofilament (NF), neuroblastoma (NB), glial fibrillary acid protein (GFAP), cytokeratin (CK), desmin (Des) were detected in 20 cases with SP immunohistochemical staining methods. Analysis of the clinical data and follow-up were performed. RESULTS: 9 pineocytomas, 4 pineoblastomas, 8 pineal parenchymal tumors of intermediate differentiation were found in 21 PPTs. Immunoreactivity to Syn, NSE, NF, GFAP, NB were in 20, 20, 14, 15, 2, while Des and CK were negative in all cases. CONCLUSIONS: Pineal parenchymal tumors of intermediate differentiation were characterized by a distinctly biphasic pattern, including areas of pineocytoma and pineoblastoma, or with intermediate differentiation and transitional feature. PPTs expressed neuronic differentiation. Death rate of PPTs were higher inside 1 year after the operation.
UI - 12046517
AU - Derenda M
TI - [Report on the Scientific Conference "On earlier diagnosis of intracranial tumors." Elblag, October 4, 2001]
SO - Neurol Neurochir Pol 2002 Mar-Apr;36(2):416-9
AD - Oddzialu Neurochirurgii Wojewodzkiego Szpitala Zespolonego w Elblagu.
UI - 12015841
AU - Pollack IF; Hamilton RL; Burnham J; Holmes EJ; Finkelstein SD; Sposto R;
TI - Yates AJ; Boyett JM; Finlay JL Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort.
SO - Neurosurgery 2002 Jun;50(6):1238-44; discussion 1244-5
AD - Departments of Neurosurgery, University of Pittsburgh Medical Center and the Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. Ian.Pollack@chp.edu
OBJECTIVE: Prognoses of pediatric high-grade gliomas are unpredictable, even when clinical and histological factors are taken into account. In preliminary studies with an institutional cohort of pediatric high-grade gliomas, we observed a strong association between outcome and proliferation index, as assessed by immunolabeling with the MIB-1 antibody. To determine whether this marker could provide prognostically useful information independent of tumor histology, we examined the prognostic usefulness of this marker in the multi-institutional cohort of Children's Cancer Group Study 945, the largest group of childhood high-grade gliomas analyzed to date. METHODS: The study group consisted of tumors within this cohort that were classified as high-grade gliomas on central review according to contemporary World Health Organization guidelines and that had sufficient histopathological material to permit proliferation index assessment. Paraffin-embedded sections were cut and processed, microwave antigen enhancement was used, and MIB-1 indices were calculated by percent labeling in approximately 2000 cells (5-10 high-power fields) in the areas with greatest labeling. To ensure that the review diagnostic classification and proliferation labeling index were assigned independently for each tumor, these analyses were performed by two different neuropathologists at separate institutions, and each was blinded to the results of the other. RESULTS: Ninety-eight tumors met eligibility criteria for this study. Among these high-grade gliomas, there was a strong association between MIB-1 labeling and patient outcome: 5-year progression-free survival was 33 +/- 7% in 43 patients whose tumors had MIB-1 indices of less than 18%, 22 +/- 8% in the 27 patients whose tumors had indices between 18 and 36%, and 11 +/- 6% in the 28 patients whose tumors had indices greater than 36% (P = 0.003). As anticipated, a strong association was also observed between histology and MIB-1 labeling index in these cases. Mean labeling indices were 19.4 +/- 2.66 for tumors classified as anaplastic astrocytoma versus 32.1 +/- 3.08 for those classified as glioblastoma multiforme (P = 0.0024). Notwithstanding this correlation, a significant association was noted between labeling index and progression-free survival, even after the analysis had been stratified by histology (P = 0.001). Although histology had an independent association with outcome, the prognostic value of MIB-1 labeling transcended histological subgrouping and was apparent both in tumors classified as anaplastic astrocytoma (P = 0.02) and in those classified as glioblastoma multiforme (P = 0.046). Multivariate regression modeling confirmed the strong independent association between MIB-1 labeling index and outcome. As a group, tumors with labeling indices higher than 36% had an almost uniformly poor outcome, regardless of histology. CONCLUSION: MIB-1 labeling index and histological categorization are each prognostically relevant in childhood high-grade gliomas. MIB-1 labeling index can help to refine the accuracy of histologically based prognostic assessments.
UI - 12071633
AU - Prayson RA
TI - Cell proliferation and tumors of the central nervous system. Part 1: Evaluation of mitotic activity.
SO - J Neuropathol Exp Neurol 2002 Jun;61(6):501-9
AD - Department of Anatomic Pathology, Cleveland Clinic Foundation, Ohio 44195, USA.
Evaluation of cell proliferation has been long recognized in pathology as a mainstay of diagnosis and important in the prognostication of a variety of neoplasms. Routine light microscopic evaluation of mitotic activity has long served as a reasonable assessment of cell proliferation. Counting mitotic figures has the advantage of being inexpensive and relatively quick. The main objections leveled against utilization of mitosis counts in diagnostic decision making are related to the instability of mitotic figures due to prefixation and fixation issues and problems with interobserver reproducibility of counts. This paper reviews factors that affect the identification of mitotic figures and the determination of mitosis counts. The role mitosis evaluation plays in the evaluation of certain neoplasms of the central nervous system is discussed.
UI - 12071636
AU - Okada Y; Nishikawa R; Matsutani M; Louis DN
TI - Hypomethylated X chromosome gain and rare isochromosome 12p in diverse intracranial germ cell tumors.
SO - J Neuropathol Exp Neurol 2002 Jun;61(6):531-8
AD - Department of Pathology and Neurosurgical Service, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Twenty-five primary intracranial germ cell tumors (11 germinomas, 5 teratomas, 5 mixed teratomas-germinomas. 1 mixed choriocarcinoma-teratoma, 1 yolk sac tumor, 1 mixed yolk sac tumor-teratoma, and 1embryonal carcinoma; from 24 males and 1 female) were studied by fluorescence in situ hybridization with probes to the X and Y chromosomes, chromosome 12p, the CDKN2A/p16 gene, and chromosome 13q-loci previously noted to be altered in either intracranial or systemic germ cell tumors. An increased number of X chromosomes, typically 1 extra copy, was observed in 23 of 25 cases (92%), with methylation-sensitive PCR demonstrating that the additional X chromosomes were hypomethylated in 13 of 16 (81%) studied tumors. Five cases (20%) had increased copy numbers of 12p (including tumors with isochromosome 12p), and 3 (12%) had 13q loss. No tumors had CDKN2A/p16 deletion or mutation, and 16 of 25 (64%) were positive for p16 expression by immunohistochemistry. Genetic alterations such as isochromosome 12p, 13q loss and CDKN2A/p16 are therefore not common in intracranial germ cell tumors. However, gains of hypomethylated, active X chromosomes occur in nearly all intracranial germ cell tumors, regardless of histological subtype. Along with the observed male predominance of intracranial germ cell tumors and the predisposition in Klinefelter syndrome patients for these lesions, the data argue strongly that sex chromosome aberrations, rather than isochromosome 12p, are integral to intracranial germ cell tumorigenesis
UI - 12019170
AU - Fulci G; Ishii N; Maurici D; Gernert KM; Hainaut P; Kaur B; Van Meir EG
TI - Initiation of human astrocytoma by clonal evolution of cells with progressive loss of p53 functions in a patient with a 283H TP53 germ-line mutation: evidence for a precursor lesion.
SO - Cancer Res 2002 May 15;62(10):2897-905
AD - Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery and Winship Cancer Institute, Emory University School of Medicine, 1365B Clifton Road, Atlanta, GA 30322, USA.
Little is known about the genetic and molecular events leading to the early stages of human astrocytoma formation. To examine this issue, we analyzed the significance of sequential accumulation of two somatic point mutations (R267W and E258D) in the TP53 gene during the initiation of astrocytoma in a patient born with a single germ-line p53 point mutation (R283H). We adapted a p53 transcriptional assay in yeast to establish the temporal occurrence and allelic distribution of the p53 mutations present in the patient and characterized these mutations through functional assays and structural modeling. Our results show that the first somatic mutation occurred at codon 267 on the p53 allele harboring the germ-line mutation R283H, whereas the second somatic mutation occurred in the remaining wild-type (wt) allele at codon 258. These two mutations induced the formation of tumor cells with the genotype p53(267W+283H/258D), which comprised 70% of the cells in the primary WHO grade II astrocytoma. Another 8% of cells within the tumor had the partially mutated genotype p53(267W+283H/WT) and represented the remnants of a clinically undetectable intermediate stage of astrocytic neoplastic transformation. The remaining 22% of cells had the constitutive p53(283H/WT) genotype and likely consisted of nontumor cells. Functional analysis of the p53 alleles present in the patient's tumor indicated that the germ-line p53(R283H) could transactivate the CDKN1A((p21, WAF1, cip1, SDI1)) but not the BAX gene and retained the ability to induce growth arrest of human glioblastoma cells. The p53(R267W+R283H) and p53(E258D) were incapable of transactivating either promoter or inducing growth arrest. Modeling of p53 interaction with DNA suggests that R283H mutation may weaken the sequence-specific interaction of p53 lysine 120 with the BAX gene but not the CDKN1A p53-responsive elements. Taken together, these results have characterized, for the first time, the genetic events defining a clinically undetectable precursor lesion leading to a grade II astrocytoma. They also suggest that astrocytoma initiation in this patient resulted from monoclonal evolution driven by a sequential loss of proapoptotic and growth arrest functions of p53.
UI - 12077919
AU - Novak L; Emri M; Balkay L; Galuska L; Esik O; Molnar P; Csecsei G; Tron
TI - L [The PET scan in neuro-oncology--indications, differential diagnosis and clinical application]
SO - Orv Hetil 2002 May 26;143(21 Suppl 3):1289-94
AD - Debreceni Egyetem, Orvos- es Egeszsegtudomanyi Centrum, Idegsebeszeti Klinika, Debrecen. email@example.com
Results of 157 PET (positron emission tomography) studies in 102 patients with known or presumed intracranial (ic.) tumors are reviewed. In 106 studies [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and in 51 cases [11C]-methionine (MET) was used as the PET tracer. CT and MRI imaging accompanied the PET studies in each case. Results of pre- and/or postoperative studies are compared. PET was concluded to have a fundamental role in the precise differential diagnosis in case of ic. space-occupying pathologies since it is capable of providing information that is not obtainable or may be equivocal based solely on CT and/or MRI investigations. However, it is also mandatory to be aware of the limits of PET.
UI - 12065727
AU - Pannequin J; Oiry C; Morel C; Kucharczak J; Camby I; Kiss R; Gagne D;
TI - Galleyrand JC; Martinez J C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting with a new gastrin binding site.
SO - J Pharmacol Exp Ther 2002 Jul;302(1):274-82
AD - Laboratory of Amino Acids, Peptides and Proteins, Free University of Brussels, Brussels, Belgium.
It is well known that the amidated C-terminal part of gastrin is crucial for its interaction with the classical seven transmembrane domain receptors CCK-1 or CCK-2. Nevertheless, over the past 10 years, several groups have characterized new binding sites using peptides related to gastrin (particularly glycine-extended forms of gastrin) on various tumoral and nontumoral cell lines. In the present study, we focused on the human astrocytic tumoral cell line U373. Although it has been described that gastrin was able to inhibit the motility of these cells, we were unable to detect any classical CCK/gastrin receptor. On the other hand, by using the radiolabeled C-terminal heptapeptide of gastrin ((125)I-G-7), we evidenced a new binding site that possessed a pharmacological profile different from the classical CCK/gastrin receptors. This new gastrin binding site seemed to be coupled to G proteins and be implicated in c-Fos transcription gene. Moreover, we showed that G-7 was able to induce a strong inhibition of U373 cell migration, a crucial biological effect when we know that astrocytoma cells' migration in brain parenchyma constitutes a major feature of malignancy in astrocytic tumors.
UI - 12076945
AU - Barboriak DP; Provenzale JM
TI - Evaluation of software for registration of contrast-enhanced brain MR images in patients with glioblastoma multiforme.
SO - AJR Am J Roentgenol 2002 Jul;179(1):245-50
AD - Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710, USA.
OBJECTIVE: We evaluated commercially available software that rapidly and automatically registers brain MR images on a clinical workstation, and we studied the accuracy of these registrations. SUBJECTS AND METHODS: Ten patients with a diagnosis of glioblastoma multiforme underwent contrast-enhanced inversion recovery prepared three-dimensional (3D) volumetric spoiled gradient-recalled acquisition in the steady state (SPGR) MR imaging (contiguous 1.5-mm slice thickness, 96-104 slices). After this imaging sequence, each patient was brought out of the head coil into a sitting position and then repositioned in the coil. The inversion recovery prepared 3D SPGR sequence was then repeated. A commercially available software program operating on a clinical workstation was used to automatically register the second inversion recovery prepared SPGR series to the first. The speed of registration was recorded. The accuracy of each registration was estimated by recording the coordinates of eight anatomic landmarks on the registered and reference series and by calculating the mean error among matching landmarks. RESULTS: In nine of 10 patients, the registration software produced a visually satisfactory registration. In one patient, a second registration was necessary to produce a satisfactory registration. The processing time for each iteration was 48.3 +/- 3.8 sec (mean +/- SD). The mean error in aligning matching anatomic landmarks ranged from 0.67 to 1.41 mm, with an overall mean of 1.18 mm. The largest error among matching landmarks was 2.3 mm. CONCLUSION: Commercially available registration software can automatically register 3D imaging volumes in less than 1 min. The mean error in registration was approximately equivalent to the dimensions of a single voxel.
UI - 12076946
AU - Bourekas EC; Varakis K; Bruns D; Christoforidis GA; Baujan M; Slone HW;
TI - Kehagias D Lesions of the corpus callosum: MR imaging and differential considerations in adults and children.
SO - AJR Am J Roentgenol 2002 Jul;179(1):251-7
AD - Department of Radiology, Section of Neuroradiology, The Ohio State University, 160 Means Hall, 1654 Upham Dr., Columbus, OH 43210-1250, USA.
UI - 11702135
AU - Essig M; Metzner R; Bonsanto M; Hawighorst H; Debus J; Tronnier V; Knopp
TI - MV; van Kaick G Postoperative fluid-attenuated inversion recovery MR imaging of cerebral gliomas: initial results.
SO - Eur Radiol 2001;11(10):2004-10
AD - Department of Radiology, German Cancer Research Center, University Hospitals, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. firstname.lastname@example.org
Fluid-attenuated inversion-recovery (FLAIR) imaging has shown to be a valuable imaging modality in the assessment of intra-axial brain tumors; however, no data are available about the role of this technique in the clinically important postoperative stage. The purpose of this study was to evaluate the diagnostic potential of FLAIR MR imaging in residual tumor after surgical resection of cerebral gliomas. Fifteen patients with residual cerebral gliomas were examined within the first 18 days after partial surgical resection of cerebral gliomas. The imaging protocol included T1-weighted spin echo, T2- and proton-density-weighted fast spin echo, and FLAIR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media application. Detection and delineation of residual tumor were the primary parameters of the image analysis. Additionally, the influence of image artifacts on the image interpretation was assessed. On FLAIR images residual signal abnormalities at the border of the resection cavities were observed in all patients, whereas T2- and T1-weighted images present residual abnormalities in 13 of 15 and 10 of 15 patients, respectively. The FLAIR imaging was found to be superior to conventional imaging sequences in the delineation of these changes and comparable to contrast enhanced T1-weighted imaging in the delineation of residual enhancing lesions. Because of protein cell components and blood byproducts within the resection cavity, FLAIR imaging was unable to suppress the cerebrospinal fluid (CSF) in 4 patients. After the decomposition of proteins and blood, CSF could again be completely suppressed and residual or recurrent tumors were clearly identified. Our preliminary study has shown that FLAIR may be a valuable diagnostic modality in the early postoperative MR imaging after resection of cerebral gliomas due to its better delineation of residual pathologic signal at the border of the resection cavity. It should therefore be integrated into the early and/or intraoperative MR imaging protocol.
UI - 11706434
AU - Pesudo Martinez JV; Gonzalez-Darder JM; Feliu Tatay R; Belloch Ugarte V;
TI - Vera Roman J; Gil Salu JL [Assessment of the degree of resection of high grade supratentorial gliomas with early postoperative magnetic resonance]
SO - Neurocirugia (Astur) 2001;12(1):43-50
AD - Servicio de Neurocirugia, Hospital General de Castellon, ERESA.
In this paper we report the results of a prospective study in which we evaluate the degree of tumor removal of 25 supratentorial high grade gliomas by means of an MRI performed in the early postoperative period. In all cases, there was preoperative enhancement 8 patients had been previously operated on while the others had their first operation. In all cases the postoperative early MRI was performed within the first week and in 15 within the first 3 days. In order to evaluate the degree of tumor removal the presence or not of enhancement was considered and if it existed, classified as linear or nodular. RESULTS: To avoid postsurgical artifacts it is important to perform the MRI as soon as possible after surgery, especially within the first 3 days. Generally, linear enhancement disappeared on subsequent follow-up examinations, showing that it probably does no represent residual, tumor while nodular enhancement usually does. Survival with the high-grade tumors was slightly higher in the group without postoperative enhancement or linear one than in the group with nodular enhancement but the difference was not significant.
UI - 11813879
AU - Zagzag D; Capo V
TI - Angiogenesis in the central nervous system: a role for vascular endothelial growth factor/vascular permeability factor and tenascin-C. Common molecular effectors in cerebral neoplastic and non-neoplastic "angiogenic diseases".
SO - Histol Histopathol 2002 Jan;17(1):301-21
AD - Department of Pathology, New York University Medical Center, NY, USA. email@example.com
Human pathological conditions of the central nervous system (CNS) associated with angiogenesis (i.e. neovascularization) include neoplastic, as well as infectious, ischemic, and traumatic processes. Upregulation of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and tenascin-C (TN-C) is spatially and temporally related to neovascularization. Spatially, VEGF/VPF and TN-C are both found at the site of neovascularization, but they are not detected in areas of normal brain or in areas without neovascularization. Temporally, VEGF/VPF and TN-C are found at the peak of angiogenesis and are not detected when angiogenesis had ceased.
UI - 11813884
AU - Hasegawa M; Muramatsu N; Tohma Y; Fukaya K; Fujisawa H; Hayashi Y;
TI - Tachibana O; Kida S; Yamashita J; Saito K Expression of E-cadherin-catenin complex in human benign schwannomas.
SO - Histol Histopathol 2002 Jan;17(1):39-44
AD - Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Japan. firstname.lastname@example.org
The Ca2+-dependent cell adhesion molecule E-cadherin has been known to express in normal and reactive Schwann cells in rodents, and to play an important role in Schwann cell-Schwann cell adhesion and maintenance of peripheral nervous tissue architecture. However, little is known about expression of E-cadherin in schwannomas. The aim of the present study was to investigate the cellular expression and localization of E-cadherin, and its associated protein, alpha E-, alpha N- and beta-catenins in human schwannomas, which are supposed to derive from Schwann cells. We tested the hypothesis that these proteins might show an altered expression/distribution in schwannoma cells which correlates with their neoplastic behavior, including sparse cell-cell contact, as seen those in meningiomas and various carcinomas. In human schwannomas, however, E-cadherin, alpha E-catenin, and beta-catenin were detected by western blotting and immunohistochemistry, whereas alpha N-catenin was not. Immunoprecipitation using anti-E-cadherin antibody resulted in alpha E-catenin forming a complex with E-cadherin. SSCP analysis revealed no mutations in the transmembrane domain or in intracellular catenin-binding site of E-cadherin. These data suggest that the E-cadherin-alpha E-catenin complex is well preserved in human schwannoma cells, which is compatible with its benign behavior, and these molecules might be used as additional cell markers of Schwann cell-derived tumors.
UI - 11837741
AU - Carlotti CG Jr; Salhia B; Weitzman S; Greenberg M; Dirks PB; Mason W;
TI - Becker LE; Rutka JT Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children.
SO - Acta Neuropathol (Berl) 2002 Jan;103(1):1-10
AD - Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins.
UI - 11938773
AU - Hu S; Huang C; Chen B
TI - [Enhanced cytotoxicity of VM-26 in human malignant glioma cells by calcium channel blocker nicardipine in vitro]
SO - Hunan Yi Ke Da Xue Xue Bao 1999;24(2):143-6
AD - Department of Neurosurgery, Second Affiliated Hospital, Hunan Medical University, Changsha 410011.
Using the monolay tumor cell culture system and the method or MTT colorimetric analysis, the cytotoxicity of the anticancer drug VM-26 and Nicardipine(NCDP) in human malignant glioma cell line U251 was studied. The results showed that the cytotoxicity of VM-26 in U251 was enhanced by NCDP at a low dose which did not show direct cytotoxicity. The authors considered that VM-26 combined with NCDP can heighten the intracellular anticancer drug concentration, reverse the drug resistance and heterogeneity in human malignant glioma cells. The mechanism of the enhanced effect was also discussed. These findings will provide an alternative chemotherapeutic clue to treat the postoperative malignant gliomas.
UI - 12057111
AU - DeAngelis LM
TI - Primary central nervous system lymphomas.
SO - Curr Treat Options Oncol 2001 Aug;2(4):309-18
AD - Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021-6700, USA. email@example.com
Primary central nervous system lymphoma (PCNSL) is widely regarded as one of the primary brain tumors most amenable to treatment. Although whole brain radiotherapy was the cornerstone of therapy for decades, recent work clearly indicates that chemotherapy has become the primary focus of treatment for this disease. The initial treatment of PCNSL for all patients, including the elderly, should be chemotherapy using a high-dose methotrexate-based regimen. Although cranial irradiation has often been combined with methotrexate, the unacceptably high incidence of late neurotoxicity, particularly in older patients, has caused many to eliminate radiotherapy, especially in those older than age 60 years. Emerging data support the validity of this approach, and the development of more efficacious chemotherapeutic regimens has been the focus of recent research.
UI - 12057095
AU - Stieber VW
TI - Low-grade gliomas.
SO - Curr Treat Options Oncol 2001 Dec;2(6):495-506
AD - Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157-1030, USA. firstname.lastname@example.org
Low-grade gliomas are uncommon primary brain tumors classified as histologic grades I or II in the World Health Organization (WHO) classification. The most common variants are pilocytic and low-grade astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas located in the cerebral hemispheres. Prognostic factors that predict progression-free and overall survival include young age, pilocytic histology, good Karnofsky performance status, gross total resection, lack of enhancement on imaging, and small preoperative tumor volumes. Edema and vasogenic effects are typically managed with corticosteroids. Dexamethasone is given at an initial dosage of 4 mg given four times daily. Anticonvulsants are given prophylactically after resection and for patients who present with seizures. The rationale for open craniotomy depends on the need for immediate palliation of symptoms by reduction of intracranial pressure or focal mass effect, and/or improved oncologic control. Gross total resection of tumor is generally defined as the absence of residual enhancement on contrast-enhanced postoperative MRI scan. Most retrospective studies suggest that patients who have undergone a gross total resection of tumor have improved survival. Depending upon the proximity of the tumor to eloquent brain, gross total resection may or may not be possible. In these cases a stereotactic biopsy is required to provide the histologic diagnosis. Adjuvant radiotherapy is recommended for patients with incompletely resected grade II tumors or for patients older than age 40 regardless of extent of resection. It may be considered for any pilocytic astrocytoma from which a biopsy has been performed. Phase III randomized prospective trials have shown statistically significantly improved progression-free survival at 5 years with the addition of radiotherapy, though overall survival does not appear different. Based on prospective randomized phase III trials, 50.4 Gy to 54 Gy of conventionally fractionated radiotherapy appears to be a safe and effective regimen with minimal neurotoxicity; 45 Gy may be adequate for biopsied pilocytic astrocytomas. Currently, RTOG trial 98-02 is investigating the efficacy of postradiation PCV chemotherapy (procarbazine, CCNU, and vincristine) in the treatment of newly diagnosed unfavorable low-grade gliomas. Other areas of investigation include Temozolomide chemotherapy and the association of 1p and 19q chromosomal deletions with prolonged survival in oligodendrogliomas and sensitivity to PCV chemotherapy. Radiosurgery