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Nervous System Tumors (nervous + system_tumor)
Kinds of Nervous System Tumors Selected AbstractsMortality in epilepsy in the first 11 to 14 years after diagnosis: Multivariate analysis of a long-term, prospective, population-based cohortANNALS OF NEUROLOGY, Issue 3 2001Samden D. Lhatoo MRCP The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6,11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy. Ann Neurol 2001;49:336,344 [source] Clinical characteristics and outcomes for a modern series of primary gliosarcoma patientsCANCER, Issue 5 2010Seunggu J. Han BS Abstract BACKGROUND: Primary gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide. METHODS: Using a retrospective review, patients with confirmed PGS were identified (1996-2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases. RESULTS: All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2-22.9 months). Patients with gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946). CONCLUSIONS: The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection. Cancer 2010. © 2010 American Cancer Society. [source] Gender-specific polygenic control of ethylnitrosourea-induced oncogenesis in the rat peripheral nervous systemINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Bernd U. Koelsch Abstract The inbred BD rat strains constitute a model system for analysis of the genetic basis of susceptibility or resistance to the development of neural tumors, as they exhibit distinct strain-specific differences regarding the sensitivity to tumor induction by the alkylating carcinogen N -ethyl- N -nitrosourea (EtNU). Among the different BD strains, BDIX and BDIV rats, respectively, are either highly susceptible or entirely resistant to the development of EtNU-induced malignant schwannomas of the peripheral nervous system (PNS), predominantly of the trigeminal nerves. We have previously mapped one locus associated with susceptibility/resistance to schwannoma induction to the telomeric third of chromosome 10 (Mss1) in segregating (BDIX × BDIV) crosses. We report on the genetic mapping of 6 further loci controlling tumor incidence or survival time on chromosomes 1 (Mss2), 3 (Mss3), 6 (Mss4), 13 (Mss5) and 15 (Mss6) as well as on chromosome 10 (Mss7) close to the centromere. Interestingly, most of these loci mediate gender-specific effects of variable strength ranging from minor influences on tumor development to complete tumor resistance. The gender specificity is reflected by the fact that male (BDIX × BDIV) F2 rats exhibit a 2-fold higher incidence of EtNU-induced schwannomas than females as well as a shorter survival time. A number of human nervous system tumors too arise with a marked gender bias. Genes mediating gender-specific predisposition of developing malignant schwannomas in the rat may be relevant for the human individual risk of developing nervous system tumors. © 2005 Wiley-Liss, Inc. [source] Neuroendocrine tumor targeting: Study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor modelINTERNATIONAL JOURNAL OF CANCER, Issue 6 2002Sylvie Froidevaux Abstract Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes 67Ga and 68Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals 111In, 90Y and 67Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to 111In or 90Y, labeling with 67Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. 67Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [67Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors. © 2002 Wiley-Liss, Inc. [source] Liver grafts from donors with central nervous system tumors: A single-center perspectiveLIVER TRANSPLANTATION, Issue 10 2009Randeep Kashyap Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 ± 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 ± 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204,1208, 2009. © 2009 AASLD. [source] PARP1 expression in pediatric central nervous system tumors,PEDIATRIC BLOOD & CANCER, Issue 7 2009Valerie N. Barton BA Abstract Background Despite advances in therapy, outcome in many high-grade pediatric central nervous system (CNS) tumors remains poor. The focus of neuro-oncology research has thus turned towards identifying novel therapeutic targets. Poly(ADP-ribose) polymerase-1 (PARP1) is a DNA repair protein that has been studied in a variety of malignancies and may interfere with therapy-induced DNA damage, however expression in pediatric CNS tumors is unknown. Procedure We evaluated PARP1 mRNA expression in 81 pediatric CNS tumors using microarray technology. Protein expression was examined by Western blot. Results PARP1 mRNA is highly expressed in high-grade tumors (P,<,0.0001). PARP1 mRNA expression was greater in high-grade glioma than pilocytic astrocytoma (P,=,3.5,×,10,5) and in large cell medulloblastoma over classic medulloblastoma (P,=,0.0053). PARP1 protein was also prominent in high-grade tumors (P,=,0.022). Conclusion These findings indicate that PARP1 is expressed in high-grade pediatric CNS tumors, implicating PARP1 inhibition as a potential therapeutic target. Pediatr Blood Cancer 2009; 53:1227,1230. © 2009 Wiley-Liss, Inc. [source] Epidemiology of cancer in adolescents,PEDIATRIC BLOOD & CANCER, Issue 3 2002Charles Stiller MA Abstract In western populations, the annual incidence rate of cancer among adolescents aged 15,19 years is around 150,200 per million, intermediate between the rates for older children and young adults. The most frequent diagnostic groups are acute leukemia, lymphomas, central nervous system tumors, bone and soft tissue sarcomas, germ cell tumors, thyroid carcinoma, and malignant melanoma. While the causes of most cancers in teenagers are still unknown, health education and promotion and public health programs offer some scope for prevention among people of this age group. Reduction in sun exposure should lead to a reduction in incidence of melanoma, and elimination of hepatitis B in regions where it is endemic should result in a decrease in hepatic carcinoma. Five-year survival of patients diagnosed around 1990 exceeded 70% in the USA and UK. Entry to clinical trials appears to be much less frequent for adolescents with cancer than for children. There is some evidence that higher survival is associated with entry to trials or centralized treatment for certain cancers in this age group. Med Pediatr Oncol 2002;39:149,155. © 2002 Wiley-Liss, Inc. [source] Mortality in epilepsy in the first 11 to 14 years after diagnosis: Multivariate analysis of a long-term, prospective, population-based cohortANNALS OF NEUROLOGY, Issue 3 2001Samden D. Lhatoo MRCP The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6,11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy. Ann Neurol 2001;49:336,344 [source] Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomasAPMIS, Issue 9 2009SUHEYLA UYAR BOZKURT Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki-67 (MIB-1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0,3) and intensity (0,3) of immunolabeling of the tumor cells. A high immunohistochemical score (4,6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB-1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow-up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB-1 score were significantly higher in recurrent meningiomas than in non-recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas. [source] The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene productACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2002Beom Sik Kang Neurofibromatosis type 2 is an autosomal dominant disorder characterized by central nervous system tumors. The cause of the disease has been traced to mutations in the gene coding for a protein that is alternately called merlin or schwannomin and is a member of the ERM family (ezrin, radixin and moesin). The ERM proteins link the cytoskeleton to the cell membrane either directly through integral membrane proteins or indirectly through membrane-associated proteins. In this paper, the expression, purification, crystallization and crystal structure of the N-terminal domain of merlin are described. The crystals exhibit the symmetry of space group P212121, with two molecules in the asymmetric unit. The recorded diffraction pattern extends to 1.8,Å resolution. The structure was solved by the molecular-replacement method and the model was refined to a conventional R value of 19.3% (Rfree = 22.7%). The N-terminal domain of merlin closely resembles those described for the corresponding domains in moesin and radixin and exhibits a cloverleaf architecture with three distinct subdomains. The structure allows a better rationalization of the impact of selected disease-causing mutations on the integrity of the protein. [source] Expression and structure of interleukin 4 receptors in primary meningeal tumorsCANCER, Issue 10 2005Sachin Puri M.Sc. Abstract BACKGROUND It was reported previously that malignant human tumors, like glioma and medulloblastoma, express high-density interleukin (IL-4) receptor mRNA and protein. Because IL-4 receptors (R) are sensitive targets for targeted therapeutics, knowledge of the expression of these receptors in other central nervous system tumors is of great interest. In this study, the authors examined the expression and subunit composition of IL-4R complex in primary human meningiomas. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) analysis for IL-13R,1, IL-4R, and IL-2R,c was performed on total RNA extracted from 35 meningiomas and a normal human brain tissue sample. Results were confirmed in nine randomly selected tumors by quantitative real-time PCR and in situ immunofluorescence assay. RESULTS Transcripts for the IL-4R, and IL-13R,1 chains were overexpressed in meningiomas compared with normal brain tissue. The levels of IL-4R, mRNA appeared to be higher compared with the levels of IL-13R,1 mRNA. The results also showed that tumors with higher disease grade tended to have increased mRNA expression for the IL-4R, chain. This IL-4R, mRNA overexpression appeared to be more frequent in younger patients (age < 37 years). The transcripts for IL-2R,c chain were not detected in any of the tumor samples or in normal brain tissue. Quantitative real-time PCR confirmed the results of the RT-PCR analysis. Meningiomas also demonstrated a bright immunofluorescent staining for the IL-4R, and IL-13R,1 chains but no staining for IL-2R,c. CONCLUSIONS Expression of the IL-4R, and IL-13R,1 chains and absence of IL-2,c expression established that meningiomas expressed type II IL-4Rs. These receptors may serve as a target for cytotoxin/immunotoxin therapy in patients with meningioma who are not amenable to surgical resection or for recurrent tumors. Cancer 2005. © 2005 American Cancer Society. [source] | ||||||||||