1/36. A case history of glioma progression.Low-grade diffuse astrocytomas have an intrinsic tendency for malignant progression but the factors determining the kinetics of this process are still poorly understood. We report here the case of a male patient who developed a fibrillary astrocytoma at the age of 33 years and who underwent six surgical interventions over a period of 17 years without radiotherapy or chemotherapy. The first three biopsies spanned a period of 11 years and led to the diagnosis of low-grade, diffuse astrocytoma (WHO grade II), with a growth fraction (MIB-1 labeling index) of 2.3-3.7%. The fourth to sixth biopsies showed histological features of anaplastic astrocytoma (WHO grade III), with growth fractions between 5.0 and 10.5%. The fraction of gemistocytic neoplastic astrocytes also increased, from 0.3% in the first biopsy to 17.5% in the last biopsy and preceded the increase in proliferative activity and transition to anaplastic astrocytoma. The fraction of tumor cells immunoreactive to BCL-2 increased from 0.3% to 8.2%. A p53 mutation in codon 273 (CGT-->TGT, Arg-->Cys) was identified in the first biopsy and persisted throughout the course of the disease. However, the fraction of cells with p53 protein accumulation increased significantly during progression, from 3.2% in the first biopsy to 13.7% in the last. The absence of additional genetic alterations (PTEN mutations, loss of chromosome 10 and 19q) may be responsible for the slow progression and lack of glioblastoma features even after a 17-year disease duration.- - - - - - - - - - ranking = 1keywords = progression (Clic here for more details about this article) |
2/36. Establishment of two glioma cell lines from two surgical specimens obtained at different times from the same individual.We established two glioma cell lines from two surgical specimens obtained at different times from the same patient. One (No. 9R), which was derived from the recurrent tumor (glioblastoma, grade IV), proliferated more rapidly in vitro than the other (No. 9) from the primary tumor (slightly anaplastic astrocytoma, grade II-III). No. 9R showed heterotransplantability in nude mice, whereas No. 9 did not. These findings indicate that No. 9R has a more aggressive or malignant nature than No. 9. Both cell lines showed homozygous deletion of the representative tumor suppressor p16 and p15 genes, but no p53 gene alteration. However, examination of the overall mRNA expression profile using a commercially available cDNA-spotted membrane revealed much higher expression levels of several mRNAs, at least, in No. 9R than in No. 9, although the relationship between these mRNAs and the growth potentials remained unknown. These two cell lines, derived from the same individual, with different proliferating potentials may be useful for studies on the molecular bases of glioma malignancy and progression.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
3/36. Globular glioma of the tectum.Brainstem gliomas are a heterogeneous group of tumors whose prognosis and treatment depend not only on the histologic features but also on the location within the brainstem. magnetic resonance imaging allows the recognition of a distinct type of brainstem glioma of the tectal region of the midbrain, leading to aqueductal compression and hydrocephalus. The radiologic appearance of these tumors is usually rather uniform, with a characteristic nonenhancing thickening of the tectal plate. Because of its protracted course, no further treatment is necessary beyond cerebrospinal fluid diversion and close clinicoradiologic follow-up. The authors report two children with tectal plate gliomas of unusual but strikingly similar appearance. They present a clinical picture suggestive of intracranial hypertension without localizing signs. Magnetic resonance images reveal hydrocephalus related to the presence of perfectly circular lesions, hypointense on T1 and hyperintense on T2, which could be mistaken for parasitic cysts or represent dilated rostral portions of the sylvian aqueduct. After the cerebrospinal fluid diversion procedures, no further treatment was given, with one of the patients being monitored for 10 years and the other for 8 months, without tumor progression. These patients demonstrate that tectal gliomas, despite sharing a good prognosis, may have various patterns of growth, leading to unusual radiologic appearances that may pose diagnostic difficulties.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
4/36. Intact sensory fusion in a child with divergence paresis caused by a pontine glioma.PURPOSE: To describe a child with divergence paresis esotropia caused by a brain tumor with intact sensory and motor fusion. METHOD: Case report. RESULTS: A 9-year-old boy who had one episode of double vision was initially seen with a small, variably present esophoria at near vision, an intermittent 10 prism diopter esotropia at distance, and stereopsis of 80 arc seconds. A magnetic resonance imaging examination disclosed a 4.0 x 4.5-cm pontine glioma. CONCLUSIONS: Ophthalmologists should recognize that the presence of intact sensory and motor fusion in a child with acute, comitant esotropia of the divergence paresis type does not preclude intracranial abnormality. If immediate neuroimaging is deferred, repeated thorough ocular motility examinations are warranted to detect progression.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
5/36. Effectiveness of spray application of ACNU in the local control of malignant gliomas: report of two cases.Malignant gliomas encompassing the eloquent areas cannot be removed totally and their surgical extirpation is followed by adjuvant therapy for the residual tumor. Recently, we have employed fibrin glue as a vehicle for the sustained release of ACNU (nimustine hydrochloride) by spray application following subtotal tumor removal in two patients with recurrent malignant gliomas. Follow-up MRI at six months demonstrated no neuroradiological evidence of tumor recurrence in the site of operation. We conclude, this novel mode of intra-operative local chemotherapy by spray application of fibrin glue containing antineoplastic agent is effective in the control of residual tumor progression and may also prevent local recurrence and hence suggests its possible role as an adjuvant therapy in the management of malignant gliomas.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
6/36. Antisense-mediated inhibition of the bcl-2 gene induces apoptosis in human malignant glioma.BACKGROUND: The bcl-2 protooncogene represses a number of cellular apoptotic pathways and is known to be expressed in increasing amounts in glial tumors of higher malignancy. We tested whether antisense oligonucleotides to the bcl-2 gene would affect glioma cell viability. methods: Antisense oligonucleotides directed to the first six codons of the human bcl-2 gene, and nonsense oligonucleotides as a control, were transfected into malignant glioma cells. Two human Bcl-2 positive glioblastoma cell lines from our tumor bank (Jon52 and Roc) were both transfected in vitro with bcl-2 antisense (AS) and nonsense (NS) oligonucleotides at 1 microm and 5 microm concentrations for 5 and 24 hr. Cell viability was assessed at 2, 4, 5, and 7 days by using an MTT mitogenic assay and by cell counting via direct visualization using a hemocytometer. RESULTS: There was up to a log-fold decrease in cell growth of the bcl-2 AS treated cells compared to the NS transfected cells for both Roc (p = 0.007 and p = 0.004) and Jon52 (p = 0.02 and p = 0.004) at 5 and 24 hr of transfection. There was as much as 50% cytotoxicity in both glioblastoma cell lines at 1 microm and 5 microm concentrations after 24 hr transfection with AS bcl-2 oligonucleotides (all p < 0.01). Western blot analysis demonstrated a decrease in the expression of the Bcl-2 protein in one cell line, whereas there was a statistically significant increase in the apoptotic index of both cell lines (p < 0.05 by chi square analysis). CONCLUSIONS: Our results suggest that transfection of human glioma cells with antisense bcl-2 results in an increase in apoptotic death. This provides evidence that Bcl-2 plays a role in tumor progression of glioma by acting as an oncogene, and suggests that inhibition of the bcl-2 gene could have a therapeutic effect.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
7/36. telomerase activity in gliomas with the use of non-radioisotopic and semi-quantitative procedure for terminal repeat amplification protocol.To study the role of telomerase in the pathogenesis of different grades and subtype of gliomas, telomerase activity in 31 gliomas was assessed with the use of non-radioisotopic and semi-quantitative procedures for the terminal repeat amplification protocol in this study. Among the samples were 17 glioblastoma multiformes (GBMs); 4 anaplastic astrocytomas (AAs); 5 astrocytomas (ASs); 1 ependymoblastoma (EPB); 2 ependymomas (EPs); 1 oligodendroglioma (OG) and 1 medulloblastoma (MB). Postive telomerase activity was detected in 9 of 17 GBMs (53%), 1 of 4 AAs (25%), 1 of 5 ASs (20%), 1 of 1 EPB (100%), and in positive controls, T 98G and KE-1. Weakly positive activity was detected in 2 of 3 AAs (66%) and 2 of 5 ASs (40%). No telomerase activity was detected in 8 of 17 GBMs (47%), 1 of 4 AAs (25%), 2 of 5 AS (40%), 2 of 2 (100%) EPs, 1 of 1 OG (100%), 1 of 1 MB (100%) and normal brain tissue. We defined telomerase expression as positive and weakly positive cases. The percentage of telomerase activity expression in gliomas tended to correlate with tumour grade in spite of histopathology of tumours. These results indicated that the telomerase activity of gliomas may be used as a tumour marker and that the activation of telomerase should correlate with initiation and malignant progression of gliomas. In addition, non-radioisotopic and semi-quantitative procedure for the terminal repeat amplification protocol appears to be the most suitable to detect telomerase activity expression in small neurosurgical specimens.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
8/36. Combined intraarterial carboplatin, intraarterial etoposide phosphate, and IV Cytoxan chemotherapy for progressive optic-hypothalamic gliomas in young children.BACKGROUND AND PURPOSE: Optic pathway and/or hypothalamic astrocytomas in children are often quiescent, but in some cases, more aggressive tumors may cause progressive visual, endocrine, and neurologic deterioration. The initial treatment of these gliomas includes surgery and IV chemotherapy. radiotherapy is not recommended in young children because of its severe adverse effects on cognitive and neuroendocrine function. This report suggests a new approach using combined intraarterial and IV carboplatin-based chemotherapy for patients for whom first line treatment has already failed. methods: Six children (mean age, 57 months) with the diagnosis of optic pathway hypothalamic gliomas, who had tumor progression after surgery and underwent IV chemotherapy, were treated monthly with intraarterially administered carboplatin, intraarterially administered etoposide phosphate, and IV administered Cytoxan. Four of the children had histologically verified pilocytic astrocytomas, and in two cases, diagnosis was made on the basis of clinical findings. Administration of the intraarterial chemotherapy required catheter placement in both internal carotid arteries at the level of C2-C3 and into one of the vertebral arteries at the level of C6-C7, with the patient under general anesthesia. RESULTS: Four of six patients had partial radiographic response, one had stable disease, and one had progressive disease after one cycle. Three patients showed clinical improvement. There were no serious complications associated with the angiographic procedures. Toxicities included bronchospasm that resolved after 3 to 4 minutes in one patient. One patient showed mild ototoxicity, and four patients needed platelet transfusion because of hematologic toxicity of drugs. CONCLUSION: These results suggest that this modality of chemotherapy (administered after failure of systemic [ie, IV] chemotherapy), of progressive optic-hypothalamic astrocytomas in young children may be an effective treatment prior to radiotherapy.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
9/36. Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in recurrent brain tumors. Eligibility required histologic confirmation of glioma recurrence despite standard radiotherapy and chemotherapy as well as enhancement of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total intratumoral dose of 10 mg of ACNU was administered continuously with a microinfusion pump over an average of 13h. Fifteen infusions were given in nine patients. All patients completed the treatment safely. On MRI, necrotic changes surrounded the infusion area in all patients, and tumor progression was inhibited or performance score was improved in seven of nine patients. No symptomatic systemic toxicity was evident, although one patient developed permanent left oculomotor palsy locally after treatment of a left medial temporal tumor. It is concluded that direct microinfusion of ACNU into recurrent gliomas can induce tumor necrosis and inhibit tumor growth.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
10/36. radiation-induced glioma presenting as diffuse leptomeningeal gliomatosis: a case report.BACKGROUND: Leptomeningeal gliomatosis is a rare and fatal disease. methods: Case report. RESULTS: We report the case of a man who was presented with severe intractable headaches, lymphocytic CSF pleocytosis, and spinal leptomeningeal enhancement on contrast MRI. Meningeal biopsy demonstrated diffuse infiltration by malignant glial cells, and symptom alleviation was achieved by CSF diversion. He later developed an enhancing thalamic tumor arising within the treatment field of a remotely irradiated pituitary adenoma. Subsequent management included chemotherapy and further radiotherapy with transient response, before death from leptomeningeal and parenchymal tumor progression 16 months after diagnosis. CONCLUSION: We report a unique case embodying two rare conditions: radiation induced glioma and leptomeningeal gliomatosis. Our patient's course is novel in that symptomatic relief was achieved with CSF diversion and a combination of chemotherapy and focal radiation allowed prolonged survival.- - - - - - - - - - ranking = 0.14285714285714keywords = progression (Clic here for more details about this article) |
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