Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas.
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The PTEN gene, located on 10q23.3, has recently been described as a candidate tumour suppressor gene that may be important in the development of advanced cancers, including gliomas. We have investigated mutation in the PTEN gene by direct sequence analysis of PCR products amplified from samples microdissected from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV) archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in ten tumours have been identified. Eight of these are DNA sequence changes that could affect the encoded protein and were present in 0/2 pilocytic astrocytomas, 0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%) anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found exclusively in high grade gliomas; this finding was statistically significant. Only two of the PTEN genetic variants have been reported in other studies; two of the genetic changes are in codons in which mutations have not been found previously. The results of this study indicate that mutation in the PTEN gene is present only in histologically more aggressive gliomas, may be associated with the transition from low histological grade to anaplasia, but is absent from the majority of high grade gliomas. (+info)
Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children.
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A series of 23 children with primitive neuroectodermal tumours (PNET) were analysed with comparative genomic hybridization (CGH). Multiple chromosomal imbalances have been detected in 20 patients. The most frequently involved chromosome was chromosome 17, with a gain of 17q (11 cases) and loss of 17p (eight cases). Further recurrent copy number changes were detected. Extra copies of chromosome 7 were present in nine patients and gains of 1q were detected in six patients. A moderate genomic amplification was detected in one patient, involving two sites on 3p and the whole 12p. Losses were more frequent, and especially involved the chromosomes 11 (nine cases), 10q (eight cases), 8 (six cases), X (six patients) and 3 (five cases), and part of chromosome 9 (five cases). These recurrent chromosomal changes may highlight locations of novel genes with an important role in the development and/or progression of PNET. (+info)
Supratentorial cavernous haemangiomas and epilepsy: a review of the literature and case series.
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OBJECTIVES: To characterise the clinical features and response to treatment of supratentorial cavernomas associated with epilepsy. METHODS: A systematic review of the literature was carried out and a retrospective case series of patients with cavernoma diagnosed by MRI and/or histology was compiled. Patient selection biases in the literature review were reduced as far as possible by selection of unbiased publications. RESULTS: In the literature, cavernomas were relatively less common in the frontal lobes. There were multiple cavernomas in 23% of cases. The main clinical manifestations were seizures (79%) and haemorrhage (16%). The annual haemorrhage rate was 0.7%. The outcome after excision was good with improvement in seizures in 92% of patients. In the case series the surgical outcome was less favourable, reflecting inclusion of a higher proportion of patients with intractable epilepsy. In both the literature review and the case series, outcome was poorer in cases with a longer duration of seizures at the time of surgery. CONCLUSIONS: The good surgical results, particularly in cases treated earlier, and the significant cumulative haemorrhage rate, suggest that excision is the optimum treatment. However, these factors have not been examined prospectively and, despite the availability of several retrospective studies, the optimum treatment, particularly for non-intractable cases, will only be determined by a prospective study. (+info)
Prognostic factors for supratentorial low grade astrocytomas in adults.
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The principal prognostic factors and effect on survival were retrospectively evaluated in 56 adult patients with supratentorial low grade astrocytomas treated between 1967 and 1993. Fifteen factors were evaluated with uni- and multivariate analysis to investigate their importance in predicting the length of survival. The median patient age at presentation was 42 years and the median survival was 5.0 years. The following characteristics were associated with improved patient survival by univariate analysis (p < 0.01): Age group, preoperative Karnofsky scale, and extent of surgery. Age group and Karnofsky scale were significant by multivariate analysis, but not the extent of surgery. Thus the usefulness of cytoreductive surgery in the management remains unclear, but the extent of surgery is determined by the characteristics of the tumor and the potential of the patient. Since 93% of our patients received postoperative radiotherapy, the effect of adjuvant irradiation could not be determined. (+info)
Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas.
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PURPOSE: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. RESULTS: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. CONCLUSION: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth. (+info)
A comparative survival evaluation and assessment of interclassification concordance in adult supratentorial astrocytic tumors.
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Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults ((3) (3)16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease. (+info)
Effect of pipecuronium and pancuronium on intracranial pressure and cardiovascular parameters in patients with supratentorial tumours.
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A prospective, randomised, single blind study was conducted to evaluate and compare the intracranial pressure (ICP) and cardiovascular effects of pipecuronium (PPC) and pancuronium (PNC) in 20 patients undergoing supratentorial surgery. Patients were randomly divided into two groups. Patients in Group I (n = 10) received pancuronium (0.1 mg kg(-1)) and in Group II (n = 10) pipecuronium (0.07 mg kg(-1)) for intubation. Intracranial pressure (ICP), heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP, MAP), central venous pressure (CVP), nasopharyngeal temperature and arterial blood gases (ABG) were monitored at the following time periods: before induction (0 minutes); 3 minutes after thiopentone and muscle relaxant; immediately after intubation; and 4, 6, 8, 10, 20 and 30 minutes following intubation. The rise in intracranial pressure at intubation was significantly greater in group I (21.10+/-3.97 torr, 122.59%) when compared to group II patients (1.80+/-0.70 torr, 10.04%) (p<0.0 1). Cardiovascular parameters also showed a significantly greater degree of rise in group I when compared to group II patients. Heart rate increased by 29+/-6.32 beats min(-1) (33.52%) and systolic arterial pressure by 11.60+/-7.37 torr (9.47%) in group I. These parameters did not change significantly in group II. No significant alterations were observed in the other measured parameters in either of the two groups. (+info)
Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.
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PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment. PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of (131)I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment. RESULTS: We treated 42 patients with (131)I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively. CONCLUSION: The MTD for administration of (131)I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis. (+info)