Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse xenografts. Human trials of gossypol as a male contraceptive have demonstrated safety of long-term administration. We studied the activity of Gossypol 10 mg PO bid in 27 patients with pathologically confirmed glial tumors which had recurred after radiation therapy. Fifteen patients had glioblastoma, 11 patients anaplastic astrocytoma, 1 patient relapsed low grade glioma. Response was assessed every 8 weeks using CT/MRI scan and clinical criteria including decadron requirement. Treatment was continued until disease progression. Two patients had partial response (PR); 4 had stable disease for 8 weeks or more. One patient maintained a PR with improved KPS for 78 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily pretreated patients had mild thrombocytopenia, 5 patients developed hypokalemia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Gossypol levels measured by HPLC did not correlate with response or toxicity in this study. We conclude that gossypol is well tolerated and has a low, but measurable, response rate in a heavily pretreated, poor-prognosis group of patients with recurrent glioma. The presumed novel mechanism of action, lack of significant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.
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PMID:Gossypol treatment of recurrent adult malignant gliomas. 1044 75

201Tl-SPECT was performed in 25 patients with a pathological diagnosis of glioma. The lesion-to-normal (L/N) ratio of the glioblastoma group (n = 7) was found to be higher than that of the low-grade glioma group (n = 7; Mann-Whitney U-test, p < 0.0167). 201Tl accumulation in the tumor corresponded to contrast enhancement on MRI in 95% of cases. An insufficient blood-brain barrier was considered to be the primary contributor to 201Tl accumulation. In five cases, there was a discrepancy between the extent of 201Tl accumulation and the Gd-DTPA enhanced area. In these cases, the area of 201Tl accumulation was larger than the area of Gd-DTPA enhancement. This may result from damage to the blood-brain barrier that is not severe enough to be detected with Gd-DTPA or from additional factors other than change in the blood-brain barrier. 201Tl-SPECT is able to demonstrate the extent of glioma more accurately than contrast-enhanced MRI.
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PMID:[Comparison of 201Tl-SPECT and MRI using Gd-DTPA for glioma]. 1045 85

The dose intensity of the PCV regimen can be doubled using peripheral blood stem cell (PBSC) support. This study sought to determine the feasibility of giving dose-intensive PCV concurrently with radiation therapy. Twelve patients, age 3.2-22.7 years, median 7.5 years, with newly diagnosed high grade gliomas were enrolled. Diagnoses included diffuse intrinsic brainstem gliomas (BSG) (n = 6), glioblastoma (n = 4), anaplastic astrocytoma (n = 2). PBSCs were harvested prior to chemotherapy with G-CSF priming. Chemotherapy consisted of CCNU 130 mg/m2 and vincristine 1.5 mg/m2 on day 0, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered every 28 days or when blood counts recovered. The first course was administered the week prior to RT, the second course began on week 3 of RT and the third and fourth course were given after RT. Hematologic toxicity was mild and the majority of courses were given on schedule. Five of six patients with diffuse BSG showed clinical improvement and three showed a radiographic response; however, only one remains alive 12+ months from diagnosis. All four patients with non-brainstem large-volume tumors showed clinical deterioration and radiographic progression during or shortly after RT. MRI scans showed massive edema and enhancement. Median time to radiographic progression was five months. Median overall survival was 11 months. We conclude that dose-intensive, time-compressed PCV given concurrently with large-volume RT appears to result in unacceptable toxicity in patients with large residual tumors.
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PMID:Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. 1058 73

Cerebral amyloid angiopathy (CAA) is frequent but often asymptomatic. It can induce lobar haemorrhage, rapidly progressive dementia or recurrent transient neurological symptoms, other presentations being less frequent. We report 3 patients in their sixties presenting with a space occupying lesion which was the first manifestation of CAA. They were operated with a diagnosis of cerebral tumour. In all three cases, macroscopy was similar, the lesions were superficial in the cerebral cortex and the preoperative diagnoses were glioblastoma, meningioma and cavernoma. Histologically, the lesions consisted of a large inflammatory granuloma with numerous lipophages and siderophages surrounding capillaries with prominent endothelial cells. Vessels in the near cortex and meninges and within the granuloma harboured heavy amyloid deposits immunolabelled by anti-P component, anti-protein beta A4 with a A40 predominance and anti-apolipoprotein E. Adjacent cerebral cortex showed reactive gliosis and rare senile plaques. Amyloidosis is rarely considered among diagnoses of space occupying lesions. In our three cases, CT scan and MRI changes were related to the presence of an inflammatory granuloma around foci of haemorrhage and amyloid laden vessels.
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PMID:Cerebral amyloid angiopathy (CAA) with presentation as a brain inflammatory pseudo-tumour. 1081 36

We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. An autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and a secondary glioblastoma.
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PMID:[Radiation induced glioblastoma: a case report]. 1084 10

Neuronavigation, today a routine method in neurosurgery, has not yet been systematically assessed in direct comparison with conventional microsurgical techniques. The aim of the present study was the direct comparison of the impact of neuronavigation on glioblastoma surgery regarding time consumption, extent of tumor removal and survival. For each of 52 patients operated for primary glioblastoma with neuronavigation, a patient operated on without navigation was matched. Completeness of tumor resection, including volumetric analysis, was examined by early post-operative MRI. Operating and survival times were obtained for all patients. At a rate of 86.5%, surgeons' opinions about neuronavigation were positive. Operating times were identical in the two groups, while preparation times were 30.4 min longer with navigation. Radiological radicality was achieved in 31% of navigation cases vs. 19% in conventional operations. The absolute and relative residual tumor volumes were significantly lower with neuronavigation. Radical tumor resection was associated with a highly significant prolongation in survival (median 18.3 vs. 10.3 months, p < 0.0001). Survival was longer in patients operated on using neuronavigation (median 13.4 vs. 11.1 months). Neuronavigation increases radicality in glioblastoma resection without prolonging operating time. Regarding the problem of brain shift, neuronavigation should be optimized by intraoperative real-time imaging.
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PMID:The benefit of neuronavigation for neurosurgery analyzed by its impact on glioblastoma surgery. 1087 84

Although the efficacy of the nitrosourea-based combination chemotherapy procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, and vincristine (PCV) has been previously demonstrated in the setting of anaplastic/intermediate-grade gliomas, the benefit for glioblastoma patients remains unproven. In the current study, we sought to determine whether the addition of alpha-difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, which has shown encouraging results in the setting of recurrent glioma patients, to a nitrosourea-based therapy (PCV) would constitute a more effective adjuvant therapy in the treatment of glioblastoma multiforme patients in the postradiation therapy setting. Following conventional radiation therapy, 272 glioblastoma (GBM) patients were randomized to receive either alpha-difluoromethylornithine-PCV (DFMO-PCV; 134 patients) or PCV alone (138 patients), with survival and time to tumor progression being the primary endpoints. The starting dosage of DFMO was 3.0 g/m2 p.o. q8h for 14 days before and after treatment with N-(2-chloroethyl)-N-cyclohexyl-N-nitrosurea; PCV was administered as previously described1. Clinical and radiological (Gadolinium-enhanced MRI) follow-ups were nominally at the end of each 6 or 8 week cycle (PCV at 6 weeks; DFMO-PCV at 8 weeks). Laboratory evaluations for hematologic and other adverse effects were at 2 week intervals. There was no difference in median survival or median time-to-tumor progression between the two treatment groups, as measured from day of commencement of postradiotherapy chemotherapy [MS (months): DFMO-PCV, 10.5; Overall survival, as measured from time of tumor diagnosis at first surgery, was 13.3 and 14.2 months at the median and 6.2 and 8.7% at 5 years, respectively, for the DFMO-PCV and PCV arms. The treatment effect was unchanged after adjustment for age, performance status (KPS), extent of surgery, and other factors using the multivariate Cox proportional hazard model. Adverse effects associated with DFMO consisted of gastrointestinal (diarrhea nausea/vomiting), cytopenias, and minimal ototoxicity (limited to tinnitus) at the dose range tested. The addition of DFMO to the nitrosourea-based PCV regimen in this phase III study demonstrated no additional benefit in glioblastoma patients, underscoring the resistance of glioblastoma multiforme tumors to alkylating agents. For patients with anaplastic (intermediate grade) gliomas, in which the previously demonstrated benefit of post-radiation chemotherapy is more substantial, the evaluation of DFMO-PCV vs. PCV is still ongoing and hopefully will yield more encouraging results.
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PMID:Phase III randomized study of postradiotherapy chemotherapy with alpha-difluoromethylornithine-procarbazine, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea, vincristine (DFMO-PCV) versus PCV for glioblastoma multiforme. 1105 Dec 33

Thallium-201 (201Tl) chloride scintigraphy is the imaging method use for the detection of various tumors including glioblastoma, but only limited information on 201Tl uptake in gliosarcoma is available. We investigated a patient with gliosarcoma by means of 201Tl single-photon emission computed tomography (SPECT) and MRI. SPECT imaging revealed high 201Tl uptake in the tumor, which was closely correlated with contrast-enhancement on MRI. These results suggest that SPECT with 201Tl may be useful for detecting gliosarcoma and provide physiological information on this tumor.
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PMID:Gliosarcoma with thallium-201 SPECT. 1110 72

MRI has facilitated diagnostic assessment of the corpus callosum. Diagnostic classification of solitary or multiple lesions of the corpus callosum has not attracted much attention, although signal abnormalities are not uncommon. Our aim was to identify characteristic imaging features of lesions frequently encountered in practice. We reviewed the case histories of 59 patients with lesions shown on MRI. The nature of the lesions was based on clinical features and/or long term follow-up (ischaemic 20, Virchow-Robin spaces 3, diffuse axonal injury 7, multiple sclerosis 11, hydrocephalus 5, acute disseminated encephalomyelitis 5, Marchiafava-Bignami disease 4, lymphoma 2, glioblastoma hamartoma each 1). The location in the sagittal plane, the relationship to the borders of the corpus callosum and midline and the size were documented. The 20 ischaemic lesions were asymmetrical but adjacent to the midline; the latter was involved in new or large lesions. Diffuse axonal injury commonly resulted in large lesions, which tended to be asymmetrical; the midline and borders of the corpus callosum were always involved. Lesions in MS were small, at the lower border of the corpus callosum next to the septum pellucidum, and crossed the midline asymmetrically. Acute disseminated encephalomyelitis and the other perivenous inflammatory diseases caused relatively large, asymmetrical lesions. Hydrocephalus resulted in lesions of the upper part of the corpus callosum, and mostly in its posterior two thirds; they were found in the midline. Lesions in Marchiafava-Bignami disease were large, often symmetrically in the midline in the splenium and did not reach the edge of the corpus callosum.
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PMID:Classification of acquired lesions of the corpus callosum with MRI. 1115 83

The aim of the study was to develop objective criteria that might be helpful for the diagnosis of gliomatosis cerebri (GC) with the highest possible probability based on both the neuroradiological and histopathological findings. Imaging findings in 14 patients with diffuse infiltrating brain neoplasms were studied by two neuroradiologists. Computed tomography and MRI scans were compared with each other side by side. The extent and kind of disease were graded on a scale of 1-5. Interexamination agreement between the two methods was calculated using a kappa analysis. Neither of the neuroradiologists performed the examinations and both were blinded to the histopathological findings, which were also available for all patients, based on biopsy as well as follow-up CT and MRI studies. A neuroradiological-neuropathological correlation was performed. A score system helped to differentiate the findings in three categories: 1 = suggestive of GC; 2 = GC cannot be excluded; and 3 = others. Both CT and MRI were performed in 14 patients with clinical signs and symptoms of an intracerebral tumor. All examinations had diagnostic quality and showed the involvement of at least two brain lobes. Stereotactic biopsy was carried out in all patients. In 2 patients the neuropathological diagnosis was suggestive of GC, in 1 patient glioblastoma, in 2 patients astrocytoma, and in 5 patients nonspecific astrogliotic proliferation. In the remaining 4 cases anaplastic tumor infiltration was diagnosed. The neuroradiological findings in 5 cases were suggestive of GC; in 6 cases a GC could not excluded; and in 3 patients only a slight probability of GC was found. In 2 cases was the neuropathological and the neuroradiological diagnosis of GC concordant. Magnetic resonance imaging is significantly more sensitive than CT in the diagnosis of GC. However, even with multiple, MRI-guided stereotactic biopsies in correlation with intraoperative analysis of the sample by smear preparations by a neuropathologist the antemortem diagnosis of GC is still difficult. Discussion of neuropathological and neuroradiological findings in each case in combination with a score system may help to resolve discrepancies.
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PMID:CT and MRI findings in gliomatosis cerebri: a neuroradiologic and neuropathologic review of diffuse infiltrating brain neoplasms. 1121 33


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