National Cancer Institute®
Last Modified: January 1, 2002
UI - 10728683
AU - DiBiase SJ; Zeng ZC; Chen R; Hyslop T; Curran WJ Jr; Iliakis G
TI - DNA-dependent protein kinase stimulates an independently active, nonhomologous, end-joining apparatus.
SO - Cancer Res 2000 Mar 1;60(5):1245-53
AD - Department of Radiation Oncology, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, USA.
Double-strand breaks (DSBs) can be efficiently removed from the DNA of higher eukaryotes by nonhomologous end-joining (NHEJ). Genetic studies implicate the DNA-dependent protein kinase (DNA-PK) in NHEJ, but the exact function of this protein complex in the rejoining reaction remains to be elucidated. We compared rejoining of DNA DSBs in a human glioma cell line, M059-J, lacking the catalytic subunit of DNA-PK (DNA-PKcs), and their isogenic but DNA-PK-proficient counterpart, M059-K. In both cell lines, rejoining of DNA DSBs was biphasic, with a fast and a slow component operating with a half-life of approximately 22 min and 12 h, respectively. Deficiency in DNA-PK activity did not alter the half-times of either of these components of rejoining but increased from 17 to 72% the proportion of DNA DSB rejoining with slow kinetics. DNA DSB rejoining was nearly complete in both cell lines, and there was only a small increase in the number of unrejoined breaks in M059-J as compared with M059-K cells after 30 h of incubation. Wortmannin radiosensitized to killing M059-K cells and strongly inhibited DNA DSB rejoining. Wortmannin did not affect the radiosensitivity to killing and produced only a modest inhibition in DNA DSB rejoining in M059-J cells, suggesting that, for these end points, DNA-PK is the principal target of the drug. These observations demonstrate that DNA-PK deficiency profoundly decreases the proportion of DNA DSB rejoining with fast kinetics but has only a small effect on the fraction remaining unrejoined. We propose that in higher eukaryotes, an evolutionarily conserved, independently active, but inherently slow NHEJ pathway is stimulated 30-fold by DNA-PKcs to rapidly remove DNA DSBs from the genome. The stimulation is expected to be of local nature and the presence of DNA-PKcs in the vicinity of the DNA DSB determines whether rejoining will follow fast or slow kinetics. Structural and regulatory functions of DNA-PKcs may mediate this impressive acceleration of DNA DSB rejoining, and regions of chromatin within a certain range from this large protein may benefit from these activities. We propose the term DNA-PK surveillance domains to describe these regions.
UI - 11104448
AU - Hardell L; Nasman A; Pahlson A; Hallquist A
TI - Case-control study on radiology work, medical x-ray investigations, and use of cellular telephones as risk factors for brain tumors.
SO - MedGenMed 2000 May 4;():E2
AD - Orebro Medical Center, Department of Oncology, Orebro, Sweden. firstname.lastname@example.org
CONTEXT: Ionizing radiation is a well-established risk factor for brain tumors. During recent years, microwave exposure from the use of cellular telephones has been discussed as a potential risk factor. OBJECTIVE: To determine risk factors for brain tumors. DESIGN: A case-control study, with exposure assessed by questionnaires. PARTICIPANTS: A total of 233 currently living men and women, aged 20 to 80 years, were included. The case patients had histopathologically verified brain tumors and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register. MAIN OUTCOME MEASURES: Ionizing radiation and use of cellular telephones as risk factors for brain tumors. RESULTS: A total of 209 cases (90%) and 425 controls (91%) answered the questionnaire. Work as a physician yielded an odds ratio (OR) of 6.00, with a 95% confidence interval (CI) of 0.62 to 57.7. All three case patients had worked with fluoroscopy. Radiotherapy of the head and neck region yielded an OR of 3.61 (95% CI, 0.65-19.9). Medical diagnostic x-ray examination of the same area yielded an OR of 2.10 (95% CI, 1.25-3.53), with a tumor induction period of 5 years or more. Chemical industry work yielded an OR of 4.10 (95% CI, 1.25-13.4), and laboratory work yielded an OR of 3.21 (95% CI, 1.16-8.85). Ipsilateral use of cellular telephones increased the risk for tumors in the temporal, temporoparietal, and occipital lobes (OR, 2.42; 95% CI, 0.97-6.05), ie, the anatomic areas with highest exposure to microwaves from a mobile telephone. The result was further strengthened (OR, 2.62; 95% CI, 1.02-6.71) in a multivariate analysis that included laboratory work and medical diagnostic x-ray investigations of the head and neck. CONCLUSION: Exposure to ionizing radiation, work in laboratories, and work in the chemical industry increased the risk of brain tumors. Use of a cellular telephone was associated with an increased risk in the anatomic area with highest exposure.
UI - 11104486
AU - Carlo GL; Jenrow RS
TI - Scientific progress - wireless phones and brain cancer: current state of the science.
SO - MedGenMed 2000 Jul 11;():E40
AD - Wireless Technology Research, Washington, DC, USA.
CONTEXT: The current science is not definitive about health risks from wireless phones; however, the legitimate questions about safety that have arisen from recent studies make claims of absolute safety no longer supportable. OBJECTIVE: The objective of this paper is to outline for primary care providers the results of the most current research on the possible impact of wireless phone use on human health. Presented are study results from Wireless Technology Research (WTR) program, the 7-year, $27 million effort funded by the wireless industry in the United States, that represents the world's most comprehensive research effort addressing this issue to date. Science-based recommendations for consumer interventions and future research are presented. DATA SOURCES: Original studies performed under the WTR program as well as other relevant research from around the world. STUDY SELECTION: This article presents a synopsis of the peer-reviewed in vitro and in vivo laboratory research, and the peer-reviewed epidemiology studies supported by the WTR, as well as a summary of other relevant work. DATA EXTRACTION: Only peer-reviewed scientific studies are presented, primarily WTR-sponsored research. In addition, results of the WTR literature surveillance program, which identified other relevant toxicology and epidemiology studies on an ongoing basis, are presented. These studies are presented in the context of their usefulness in providing intervention recommendations for consumers. DATA SYNTHESIS: Following a qualitative synthesis of specific relevant non-WTR research and a critical assessment of the WTR results, the following represents the current state of scientific understanding relevant to the public health impact of wireless phones: laboratory studies appear to have confirmed that radio frequency radiation from wireless phone antennas is insufficient to cause DNA breakage; however, this same radiation appears to cause genetic damage in human blood as measured through the formation of micronuclei. An increase in the rate of brain cancer mortality among hand-held cellular phone users as compared to car phone users, though not statistically significant, was observed in the WTR cohort study. A statistically significant increase in the risk of neuro-epithelial brain tumors was observed among cellular phone users in another case-control study. CONCLUSIONS: As new data emerge, our understanding of this complex problem will improve; however, at present there is a critical need for ongoing and open evaluation of the public health impact of new science, and communication of this science and derivative intervention options to those who are potentially affected.
UI - 11148570
AU - Mena H; Morrison AL; Jones RV; Gyure KA
TI - Central neurocytomas express photoreceptor differentiation.
SO - Cancer 2001 Jan 1;91(1):136-43
AD - Department of Neuropathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
BACKGROUND: Central neurocytomas are composed of mature neuronal elements, frequently arranged in rosettes similar to those present in pineocytomas. This suggests the possibility of similar patterns of differentiation, including photoreceptor differentiation. The authors analyzed the immunoreactivity of central neurocytomas for retinal S-antigen, neuronal, glial, and neuroendocrine markers. METHODS: Thirty-three central neurocytomas were analyzed with reference to their clinicopathologic characteristics, immunoreactivity, and the possibility that anaplastic histologic features correlated with aggressive clinical behavior. RESULTS: There were 18 male and 15 female patients. The median age at diagnosis was 30 years (range, 3-69 years). All of the tumors with specified location were related to the ventricles. Thirty-two tumors were diagnosed at surgery and 1 at autopsy. Histologic features included mineralization (20 of 33), foci of necrosis (4 of 33), chronic inflammation (4 of 33), ganglion cell differentiation (1 of 33), and lipomatous differentiation (1 of 33). None of the lesions had significant nuclear pleomorphism, mitotic activity, or vascular endothelial proliferation. Immunohistochemistry included expression of synaptophysin (33 of 33), neuron specific enolase (31 of 33), S-100 protein (25 of 33), retinal S-antigen (14 of 24), somatostatin (8 of 27), glial fibrillary acidic protein (4 of 33), neurofilament protein (3 of 22), and leucine enkephalin (1 of 27). At follow-up, 15 of 23 patients were alive an average of 8.1 years (range, 0.91-35.9 years) after surgery. CONCLUSIONS: Central neurocytomas behave as slowly growing neoplasms that remain confined within one or several supratentorial ventricles and are associated with long survival after surgical excision. Malignant forms with aggressive clinical behavior were not found. The neoplastic cells can express photoreceptor differentiation possibly relating central neurocytomas to pineocytomas. Adipocyte differentiation may be present, and the possibility of a relation between the central neurocytoma and cerebellar liponeurocytoma should be entertained.
UI - 11332080
AU - Nafe R; Glienke W; Schlote W; Schneider B
TI - EGFR gene amplification in glioblastomas. Is there a relationship with morphology of tumor cell nuclei and proliferative activity?
SO - Anal Quant Cytol Histol 2001 Apr;23(2):135-43
AD - Edinger Institute for Neurology and Department of Urology, Clinics of Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
OBJECTIVE: To confirm a relationship between histomorphology of glioblastomas and amplification of the gene for the epidermal growth factor receptor (EGFR) as the most important molecular biologic alteration in these tumors. STUDY DESIGN: In paraffin sections of surgical specimens from 71 primary resected glioblastomas, tumor cell nuclei in the region with the highest proliferative activity (Ki-67 immunostaining) were investigated morphometrically. Shape variables (roundness factor, Fourier amplitudes) and nuclear area were measured. Additionally, the numerical density of Ki-67-positive tumor cell nuclei was estimated. Differential polymerase chain reaction (PCR) was performed from paraffin sections of the same tumor area. The signals for the EGFR gene and IFN gamma reference gene were quantified densitometrically. RESULTS: Cases with distinct EGFR gene amplification (EGFR/IFN ratios > 5) revealed significantly lower mean values for several Fourier amplitudes, indicating a more regular nuclear shape when compared with cases without evidence of EGFR gene amplification (EGFR/IFN-ratios < or = 1). The Ki-67 index and nuclear area showed no significant differences between these groups. Although a large variation in nuclear morphology was observed for cases without evidence of EGFR gene amplification, discriminant analysis based on morphometric variables provided a good separation of these cases from cases with distinct EGFR gene amplification, with a high percentage of statistically correct reclassified cases. CONCLUSION: Our results provide evidence of a relationship between genetic alterations and histomorphology of glioblastomas.
UI - 11417411
AU - Szekessy DP; Stoltenburg-Didinger G
TI - Differentiation, proliferation and apoptosis in primary and recurrent primitive neuroectodermal tumors of childhood.
SO - Childs Nerv Syst 2001 May;17(6):320-7
AD - Department of Neuropathology, Free University Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. email@example.com
Primitive neuroectodermal tumors (PNETs) of the CNS are a group of embryonal tumors composed of small undifferentiated or poorly differentiated cells. Infratentorially located PNETs are a synonym for medulloblastomas. In this study 31 PNETs, including 5 recurrent tumors, were examined. All children underwent neurosurgery and chemotherapy according to the HIT and HIT-SKK protocols. The specimens were investigated both for their expression of nine immunohistochemical markers for neuronal, astrocytic, mesenchymal and epithelial differentiation and for their proliferation. Results regarding cellular differentiation were confirmed ultrastructurally. Apoptosis was detected by labeling the 3'OH ends generated by DNA fragmentation and by electron microscopy. Glial differentiation was shown to have a prognostic relevance, with an elevated (twofold) risk of recurrence. Neuronal differentiation also indicated a tendency to poor prognosis. Those tumors that recurred later showed an increased proliferation rate (69%) compared with nonrecurrent tumors (58%). Apoptosis was identified in all tumors examined. The proportion of apoptotic cells could not be related to the effect of therapy. These results indicate that cellular differentiation may be a useful predicative factor for the prognosis of cerebral PNETs.
UI - 11419622
AU - Latikka J; Kuurne T; Eskola H
TI - Conductivity of living intracranial tissues.
SO - Phys Med Biol 2001 Jun;46(6):1611-6
AD - Ragnar Granit Institute, Tampere University of Technology, Finland. firstname.lastname@example.org
Resistivity values were measured from living human brain tissue in nine patients. A monopolar needle electrode was used with a measurement frequency of 50 kHz. Mean values were 3.51 Ohms m for grey matter and 3.91 Ohms m for white matter. Cerebrospiral fluid had a mean value of 0.80 Ohms m. Values for tumour tissues were dependent on the type of tumour and ranged from 2.30 to 9.70 Ohms m.
UI - 11437285
AU - Zimmermann M; Seifert V; Trantakis C; Raabe A
TI - Open MRI-guided microsurgery of intracranial tumours in or near eloquent brain areas.
SO - Acta Neurochir (Wien) 2001;143(4):327-37
AD - Neurosurgical Clinic, Johann Wolfgang Goethe-University Frankfurt am Main, Germany.
OBJECTIVES: Preservation of brain function while maximizing resection is the main aim of brain tumour surgery. The purpose of this study was to evaluate the efficacy of intra-operative magnetic resonance imaging to preserve brain function in patients with tumours in or near eloquent fifty-eight craniotomies for intracranial tumours or vascular malformations have been performed at the University of Leipzig using a 0.5 T superconducting MR system "SIGNA SP" (General Electric Medical Systems, USA). In 32 of these patients (15 male/17 female) with intracranial tumours, located in or near eloquent brain areas (sensorimotor cortex/speech center), 34 craniotomies were performed using the image guidance of the interventional MRI. RESULTS: Using intra-operative MRI criteria, complete tumour removal could be achieved in 28 (82%) of 34 procedures. In 3 patients only subtotal tumour removal was possible, because the residual tumour was not visible on the intra-operative MR images, but could be identified on early diagnostic follow-up MR-scans. In 3 patients, incomplete tumour resection was performed in order to avoid neurological impairment. In these patients intra-operative MR-images revealed residual tissue abnormalities involving or encroaching on deep brain structures or motor/language cortex. Pre-operative neurological status was unchanged in 24 patients (70%), worsened in 4 patients (12%) and improved in 6 patients (18%). CONCLUSIONS: Intra-operative MRI is helpful for navigation as well as to demonstrate the tumour margins to achieve a complete and safe resection of intracranial lesions located in or near eloquent brain areas. It enables an image based functional monitoring of the brain which is critical for motor, sensory or language function. Complications related to the surgical procedure are reduced and the risk of neurological deterioration due to tumour removal and postoperative complications is minimized.
UI - 11444508
AU - Perry A
TI - Oligodendroglial neoplasms: current concepts, misconceptions, and folklore.
SO - Adv Anat Pathol 2001 Jul;8(4):183-99
AD - Washington University School of Medicine, St Louis, Missouri 63110-1093, USA. email@example.com
Given current prognostic and therapeutic implications, the accurate classification and grading of oligodendroglial neoplasms has become critical. However, the prevalence of morphologically ambiguous gliomas, subjective histologic criteria, personal biases, oligodendroglioma mimics, and the lack of specific oligodendroglioma markers has led to high interobserver variability and created a contentious problem encountered daily in active surgical neuropathology practices. Since histologic assessment is still a powerful prognosticator, it appropriately remains the diagnostic gold standard. However, recent efforts have focused on identifying the most reproducible and clinically relevant criteria, standardizing classification and grading schemes, and searching for useful ancillary biologic and genetic markers capable of further stratifying an otherwise heterogeneous patient population. This paper reviews the morphologic and genetic spectrum of oligodendroglial neoplasms, recent diagnostic and prognostic developments, and potential future directions.
UI - 11451204
AU - Korshunov A; Golanov A
TI - Pleomorphic xanthoastrocytomas: immunohistochemistry, grading and clinico-pathologic correlations. An analysis of 34 cases from a single Institute.
SO - J Neurooncol 2001 Mar;52(1):63-72
AD - Department of Neuropathology, Neurosurgical NN Burdenko Institute, Moscow, Russia. firstname.lastname@example.org
Pleomorphic xanthoastrocytomas (PXAs) are characterized as a well-delineated tumor entity with clear peculiarities in clinico-radiological picture, pathological appearance and biological behavior. Usually the PXAs are associated with relatively good prognosis. Nevertheless, up to 35% of patients die following one and more recurrence with or without tumor malignant transformation. Till now, there is no agreement on what histopathological features constitute to objective and reliable signs of PXAs malignancy and clinical outcome. Thirty-four PXAs were subdivided on three subsets: typical (Grade I) - tumors without mitoses per 20 high power fields, proliferating (Grade II) tumors with mitoses but without necroses, and malignant (Grade III) - tumors with elevated mitotic index and necrotic foci. Also, immunohistochemical investigation with various tumor-associated antigens was performed. All PXAs subtypes showed differences in clinical outcomes. There were no recurrences and death among the tumors Grade I. Five out of 14 (36%) Grade II PXAs have recurred and one of them died. All 5 patients with PXAs Grade III have rapidly recurred and four of them died. Immunohistochemical variables, such as Ki-S1, p27/Kip1, vascular endothelial growth factor expression, p53 immunoreactivity and apoptotic index also exhibited significant differences among the three PXAs grades. The progression-free survival was significantly reduced for PXAs grade and presence of mitoses, whereas overall survival was reduced for mitotic index >or= 3 and presence of necroses. No one from immunohistochemical variables reached significant value. In summary, the three-tiered PXAs subdivision proposed by us is carrying some element of rationality but, undoubtedly, requires further prospective studies.
UI - 11465394
AU - Jukich PJ; McCarthy BJ; Surawicz TS; Freels S; Davis FG
TI - Trends in incidence of primary brain tumors in the United States, 1985-1994.
SO - Neuro-oncol 2001 Jul;3(3):141-51
AD - Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, 60612, USA.
Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they warrant further study.
UI - 11465395
AU - Davis FG; Kupelian V; Freels S; McCarthy B; Surawicz T
TI - Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups.
SO - Neuro-oncol 2001 Jul;3(3):152-8
AD - Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, 60612, USA.
Prevalence rates are used to supplement descriptions of disease and are unavailable for all primary brain tumors in the United States. Data from two population-based tumor registries were obtained from the Central Brain Tumor Registry of the United States and used to compute age-specific incidence rates (1985-1994) and survival curves for further use in a statistical model to estimate prevalence rates. Prevalence rates were then used to estimate the number of individuals living with a brain tumor diagnosis in the U.S. population for the year 2000. The overall incidence rate in these regions is 13.8 per 100,000 with 2-, 5-, and 10-year survival rates of 58%, 49%, and 38%, respectively. The prevalence rate for all primary brain tumors is 130.8 per 100,000 with approximately 350,000 individuals estimated to be living with this diagnosis in the United States in 2000. The prevalence rate for malignant tumors, 29.5 per 100,000, is similar to previous reports. The prevalence rate for benign tumors, 97.5 per 100,000, is new. Unlike incidence data, the proportion (and expected number) of existing benign tumors (75%, 267,000) is considerably greater than that for malignant tumors (23%, 81,000), reflecting the better prognosis of benign tumors diagnosed in individuals younger than 60 years old. These data underscore the impact of primary brain tumors in the U.S. health care system and emphasize the need for quality-of-life considerations, particularly for those long-term survivors of benign tumors.
UI - 11465400
AU - Jackson RJ; Fuller GN; Abi-Said D; Lang FF; Gokaslan ZL; Shi WM;
TI - Wildrick DM; Sawaya R Limitations of stereotactic biopsy in the initial management of gliomas.
SO - Neuro-oncol 2001 Jul;3(3):193-200
AD - Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. At The University of Texas M. D. Anderson Cancer Center, we retrospectively reviewed a consecutive series of 81 patients whose imaging studies suggested glioma and who underwent stereotactic biopsy followed by craniotomy/resection (within 60 days) between 1993 and 1998. All relevant clinical and imaging information was reviewed, including computerized volumetric analysis of the tumors based on pre- and postoperative MRI. Stereotactic biopsy was performed at institutions other than M. D. Anderson in 78 (96%) of 81 patients. The majority of tumors were located either in eloquent brain (36 of 81 = 44%) or near-eloquent brain (41 of 81 = 51%), and this frequently was the rationale cited for performing stereotactic biopsy. Gross total resection (>95%) was achieved in 46 (57%) of 81 patients, with a median extent of resection of 96% for this series. Diagnoses based on biopsy or resection in the same patient differed in 40 (49%) of 82 cases. This discrepancy was reduced to 30 (38%) of 80 cases when the biopsy slides were reviewed preoperatively by each of three neuropathologists at M. D. Anderson. Major neurologic complications occurred in 10 (12.3%) of 81 surgical patients and 3 (3.7%) of 81 patients undergoing biopsy. Surgical morbidity was probably higher in our series than it would be for glioma patients in general because our patients represent a highly selected subset of glioma patients whose tumors present a technical challenge to remove. Stereotactic biopsy is frequently inaccurate in providing a correct diagnosis and is associated with additional risk and cost. If stereotactic biopsy is performed, expert neuropathology consultation should be sought.
UI - 11465401
AU - Visted T; Bjerkvig R; Enger PO
TI - Cell encapsulation technology as a therapeutic strategy for CNS malignancies.
SO - Neuro-oncol 2001 Jul;3(3):201-10
AD - Department of Anatomy and Cell Biology, University of Bergen, Norway.
Gene therapy using viral vectors has to date failed to reveal its definitive clinical usefulness. Cell encapsulation technology represents an alternative, nonviral approach for the delivery of biologically active compounds to tumors. This strategy involves the use of genetically engineered producer cells that secrete a protein with therapeutic potential. The cells are encapsulated in an immunoisolating material that makes them suitable for transplantation. The capsules, or bioreactors, permit the release of recombinant proteins that may assert their effects in the tumor microenvironment. During the last decades, there has been significant progress in the development of encapsulation technologies that comprise devices for both macro- and microencapsulation. The polysaccharide alginate is the most commonly used material for cell encapsulation and is well tolerated by various tissues. A wide spectrum of cells and tissues has been encapsulated and implanted, both in animals and humans, indicating the general applicability of this approach for both research and medical purposes, including CNS malignancies. Gliomas most frequently recur at the resection site. To provide local and sustained drug delivery, the bioreactors can be implanted in the brain parenchyma or in the ventricular system. The development of comprehensive analyses of geno- and phenotypic profiles of a tumor (genomics and proteomics) may provide new and important guidelines for choosing the optimal combination of bioreactors and recombinant proteins for therapeutic use.
UI - 11459086
AU - Kurosaki M; Saeger W; Ludecke DK
TI - Immunohistochemical localisation of cytokeratins in craniopharyngioma.
SO - Acta Neurochir (Wien) 2001;143(2):147-51
AD - Division of Neurosurgery, Institute of Neurological Sciences, Tottori University School of Medicine, Yonago, Japan.
BACKGROUND: Although craniopharyngiomas have been examined in several microscopical studies to date, immunohistochemical analysis has not been sufficient. METHOD: In addition to the routine haematoxylin and eosin staining, 38 cases of intra- and/or supra-sellar craniopharyngioma, including 34 adamatinomatous and 4 squamous papillary types, were studied using immunohistochemistry for expression of four types of cytokeratin. FINDINGS: Histological examination found epithelial cells in 26 of 38 (68.40%) cases. However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining 3 cases without demonstration of epithelial cell nests were supposed to be adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of 34 adamantinomatous craniopharyngioma cases, the epithelium was detected by immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40 kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities. The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that of the high molecular weight cytokeratin (keratin M-903). However, in many cases (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate staining with cytokeratin 7 appeared in the superficial layer, whereas basal or mid-zone epithelial cells were negative for cytokeratin 7. The basal layer stained negatively for KL-1, as well as cytokeratin 7. INTERPRETATION: Immunostaining for cytokeratin is valuable in the investigation of craniopharyngioma, especially when specimens contain only a small or questionable part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable for analyzing these tumours, with special reference to histological subtypes.
UI - 11485231
AU - Ildan F; Tuna M; Gocer IA; Erman T; Cetinalp E
TI - Intracerebral ganglioglioma: clinical and radiological study of eleven surgically treated cases with follow-up.
SO - Neurosurg Rev 2001 Jul;24(2-3):114-8
AD - Cukurova University School of Medicine, Department of Neurosurgery, Balcali, Adana, Turkey. email@example.com
BACKGROUND: Gangliogliomas are rare benign tumors of the CNS consisting of differentiated neural elements and low-grade glial cells. METHODS: We reviewed our experience of 11 patients with histologically proven ganglioglioma who were surgically treated since 1986 at Cukurova University Medical Center. These patients presented at 18 to 45 years of age. Five were women and six were men. The most common initial symptom was seizures (in nine of 11 patients), which had sometimes persisted over long periods of time. At the time of diagnosis, four patients had focal neurological deficits and three had signs or symptoms of increased intracranial pressure. The cystic and well-circumscribed characteristics of these lesions were detected on computed tomography (CT). Despite their appearance on CT, all but one of the lesions were found to be mostly solid at operation. Magnetic resonance imaging (MRI) in six patients revealed abnormally high signal intensity on T2-imaging. The temporal lobe was the main tumor location (seven patients). All cases were diagnosed according to the Russel and Rubinstein histological criteria for ganglioglioma. RESULTS: Ten patients had radical total resection and one had subtotal resection. No patient underwent postoperative radiation or chemotherapy. Except for one, all are still alive and free of progressive disease 1 to 11 years (mean 6.2) after operation. Six are seizure-free and three have improved seizure control under anticonvulsant therapy. CONCLUSIONS: We conclude that ganglioglioma is a distinct histological phenomenon with mildly predictable clinical symptoms (seizures), mildly characteristic radiological features, and long-term survival after surgical resection without the need of adjuvant treatment such as radiotherapy.
UI - 11485247
AU - Rustia A; Wierzbicki V; Marrocco L; Tossini A; Zamponi C; Lista F
TI - Is exon 5 of the PTEN/MMAC1 gene a prognostic marker in anaplastic glioma?
SO - Neurosurg Rev 2001 Jul;24(2-3):97-102
AD - firstname.lastname@example.org
Chromosome 10 deletions are among the most common genetic changes in highly malignant glial tumors. It has been noted that loss of heterozygosity (LOH) at 10q23 is a frequent alteration in a variety of human tumors and occurs in approximately 70% of all glioblastomas. By mapping of homozygous deletions on 10q23, a candidate tumor suppressor gene has been isolated, called PTEN for "phosphatase and tensin homolog deleted on chromosome 10" and MMAC1 for "mutated in multiple advanced cancers-1." Mutations of this tumor suppressor gene PTEN/MMAC1 have been reported in anaplastic glial tumors. The objective of this paper was to individuate a prognostic marker in exons 5, 6, 7, and 8 of the PTEN/MMAC1 gene for the high-grade malignant glioma with the most aggressive clinical behavior. In this study, we undertook sequence analysis of these exons in six selected patients with high-grade malignant gliomas who underwent radical aggressive tumor resection followed by radiotherapy within 3 weeks after surgery and subsequent chemotherapy. In them, the exon 5 sequence of the PTEN/MMAC1 gene is suggestive of a genetic survival marker in gliomas with high-grade malignancy.
UI - 11484819
AU - Weber M; Stockhammer F; Schmitz U; von Deimling A
TI - Mutational analysis of INI1 in sporadic human brain tumors.
SO - Acta Neuropathol (Berl) 2001 May;101(5):479-82
AD - Institute for Neuropathology, Charite, Humboldt University, Berlin, Germany.
The INI1/SMARCB1/hSNF5 gene on chromosome 22 is frequently mutated in rhabdoid tumors. An association of INI1 mutations with allelic losses on chromosome 22 supports a classical tumor suppressor mechanism. Several brain tumor entities including astrocytomas, glioblastomas and ependymomas are characteri