Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-clinical data and adult experience suggests that topoisomerase targeted anti-cancer agents may be highly schedule dependent, and efficacy may improve with prolonged exposure. To investigate this hypothesis, 28 children with recurrent brain and solid tumors were enrolled in a phase II study of oral etoposide (ETP). Patients were prescribed ETP at 50 mg/m2/ day for 21 consecutive days. Courses were repeated every 28 days pending bone marrow recovery. Evaluation of response was initially performed after 8 weeks and then every 12 weeks either by CT or MRI. Three of 4 patients with PNET (primitive neuroectodermal tumor)/medulloblastora achieved a partial response (PR). Two of 5 with ependymoma responded, one with a complete response and one with a PR. Toxicity was manageable with only 1 admission for fever and neutropenia in 120 cycles of therapy. Five patients had grade 3 or 4 neutropenia. One had grade 4 thrombocytopenia and one grade 2 mucositis and withdrew as a result. One patient had grade 2 diarrhea. Two patients who achieved a PR had received ETP as part of prior combination chemotherapy regimens. Daily oral etoposide is active in recurrent PNET/medulloblastoma and ependymoma. Toxicity is manageable and rarely requires intervention. Daily oral etoposide in combination with crosslinking agents should be considered in future phase III trials. Determination of activity in glioma and solid tumors is not complete.
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PMID:Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. 914 2

In recent years, there is increasing recognition of polyphenotypic high-grade malignancies in the non-central nervous system (CNS) tumor literature. Some of these tumors have been regarded as variants of primitive neuroectodermal tumor (PNET) or as extrarenal malignant rhabdoid tumors (MRTs). This report concerns two posterior fossa neoplasms, both of which displayed a "polyphenotypic" expression of neural, epithelial, myogenic, and glial markers, including synaptophysin, neurofilament, vimentin, glial fibrillary acidic protein, S-100, neuron-specific enolase, desmin, S antigen, MIC2, cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. One tumor showed complex intercellular junctions, cytoplasmic intermediate filaments, well-developed rough and smooth endoplasmic reticulum and Golgi apparatus, cilia, and neurosecretory granules. The other neoplasm showed pools of glycogen, desmosomes, and tonofilaments. The histological and ultrastructural appearances were inconsistent with glioma, PNET, meningioma, ependymoma, choroid plexus carcinoma, sarcoma, germ cell tumor, and other tumors in the World Health Organization classification. Although the polyphenotype raises the issue that these may represent variants of MRT or the atypical teratoid-rhabdoid tumor, the morphologic findings in the two cases were very dissimilar. Our two cases underscore the problems in nosology and classification of polyphenotypic tumors of the CNS. This is particularly significant, as therapeutic protocols for PNET, MRT, and non-CNS polyphenotypic tumors are different. We review the literature on polyphenotypic tumors and reiterate the difficulties in precise classification of these complex tumors.
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PMID:"Polyphenotypic" tumors in the central nervous system: problems in nosology and classification. 918 18

Alterations of the p53 protein, which is a 53 kD phosphoprotein and gene product of the p53 gene, has been found to play a major role in the genesis of a variety of human malignancies including tumors of the central nervous system. We investigated 50 tumor specimens from primary central nervous system neoplasms. Tissue samples were screened for mutations by the single-strand conformation polymorphism method and detected mutations were sequenced. All tissue specimens were stained immunohistochemically for p53 protein, which when altered accumulates in the nucleus due to prolonged half-life. Mutations were found in six cases, including one pilocytic astrocytoma World Health Organization (WHO) grade I, two astrocytomas WHO grade II, two anaplastic astrocytomas WHO grade III, and one primitive neuroectodermal tumor (PNET). In terms of relative frequency mutations were found mostly in the group of anaplastic astrocytomas WHO grade III. Interestingly, no mutations were found in the group of investigated glioblastomas. P53 immunopositivity did not correlated with the mutations found, whereas the staining index was significantly higher in the cases with detected mutations than in those without. When p53 alterations is seen as an indicator for different pathogenic pathways in glioma formation, this study gives evidence for a difference between anaplastic astrocytoma and glioblastoma. However, since there was a great overlap in p53 immunopositivity and p53 mutation in tumors of different WHO grades and entities, it seems that p53 will not act as a marker molecule neither for tumor entities nor for tumor malignancy.
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PMID:p53 mutation and protein alteration in 50 gliomas. Retrospective study by DNA-sequencing techniques and immunohistochemistry. 922 41

Of 1728 childhood brain tumors treated at the National Institute of Neurosurgery, Budapest during the years from 1954 until 1995, 83 of the affected children were younger than one year of age. Because of the advent of the CT and MRI scans in the last 11 years, 51 out of the 83 are presented, these being patients treated since these technological advances have been available. There was a male predominance, with 30 boys and 21 girls. Five of the 51 infants were diagnosed before two months of age. The ratio of supratentorial to infratentorial tumors was almost 1:1. Vomiting, alteration of psychomotor development, and macrocrania were the most common presenting features. Craniotomy and tumor debulking was performed in 85% of the children and 94% of the infants. The most frequent histological diagnosis was benign glioma, PNET, malignant glioma, and craniopharyngioma. The surgical mortality rate was 5% for the children and 13% for the infant group. All five neonates survived the surgical procedure. Radiation therapy was given in 29% of the children and in 7% of infants.
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PMID:Brain tumors during the first year of life. 938 39

Pediatric central nervous system neoplasms include a spectrum of both glial and nonglial tumors that differ significantly in location and biological behavior from those of adults. Brain tumors in infants and children most often arise from central neuroepithelial tissue, whereas a significant number of adult tumors arise from central nervous system coverings (e.g., meningioma), adjacent tissue (e.g., pituitary adenoma), or metastases. Most adult brain tumors are supratentorial malignant gliomas, whereas the most common malignant pediatric brain tumor is the cerebellar primitive neuroectodermal tumor (medulloblastoma). This article reviews neuropathological characteristics of the more common pediatric brain tumors. Entities, such as the brainstem glioma, and less common neoplasms like the desmoplastic infantile ganglioglioma and the central nervous system atypical teratoid/rhabdoid tumor are reviewed because they occur almost exclusively in children. Known cytogenetic and molecular characteristics of childhood brain tumors are also reviewed.
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PMID:Neuropathology of pediatric brain tumors. 944 21

Advances have recently been made in the use of chemotherapy for pediatric brain tumors. Chemotherapy increases disease-free survival in high-risk primitive neuroectodermal tumor/medulloblastoma patients and enables the reduction of radiation therapy in standard-risk patients. Radiation can be significantly delayed and neurotoxicity ameliorated in many infants using chemotherapy. Chemotherapy can cause reduction in size of low-grade glioma, optic glioma, and oligodendroglioma. High-grade glioma and ependymoma are relatively chemoresistant. Physicians caring for children with brain tumors are encouraged to participate in controlled studies, so that objective information can be gathered and the role of chemotherapy in these tumors can be better defined.
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PMID:Chemotherapy for pediatric brain tumors. 944 24

Brain tumors in infants present special diagnostic and therapeutic challenges. To figure out the clinical features, pathological classification of the tumors and the treatment outcome of infantile brain tumors, 458 children (age<16) with brain tumors were reviewed retrospectively. Among them 21 cases (4.6%) were diagnosed during the first 12 months of life. Two tumors were definitely of congenital origin. The majority of infants with brain tumors presented with increased intracranial pressure. Fourteen tumors were located at the supratentorial area. Sixteen cases had neuroepithelial tumors; astrocytoma (optic pathway), supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma were found in three cases each. There were two treatment-related mortalities. Compared with the outcomes in older children, the treatment outcome was poorer in medulloblastoma and the optic pathway glioma which showed a higher growth potential. Because of the limited application of postoperative adjuvant therapy, radical surgical removal played a more important role in this age group. The prognosis of patients in whom the tumors could not be totally removed, largely depended on the pathological malignancy of the tumors. Though the treatment outcome was not always dismal, immaturity of the brain, higher growth potential, perioperative risks, limitations in adjuvant therapy, and pessimistic attitude on the part of parents made management more challenging.
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PMID:Brain tumor in the first year of life: a single institute study. 953 22

Chemotherapy delivery for the treatment of malignant brain tumors is markedly enhanced when given in conjunction with osmotic opening of the blood-brain barrier. Osmotic opening or disruption of the blood-brain barrier is achieved while the patient is under general anesthesia, by the infusion of mannitol into the internal carotid or vertebral artery circulation. The mannitol infusion is followed by administration of intraarterial chemotherapy. A National Blood-Brain Barrier Program now exists and includes six universities. Within the National Program over 4200 blood-brain barrier disruption procedures have been performed in over 400 patients. Patients with primary central nervous system (CNS) lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and metastatic cancer are eligible for treatment. Results in patients with primary CNS lymphoma, recently reported in the Cancer Journal, include the first example of a durable response in a primary brain tumor without loss of cognitive function and without use of radiotherapy. Results with PNET and germ cell tumors are also very encouraging. Advanced practice nurses coordinate the care of blood-brain barrier disruption patients. Care includes patients selection, education, close neurological observation, maintenance of fluid and electrolyte balance and managing effects of high-dose chemotherapy. Both acute and long-term medical and psychological follow-up are an essential component of the program, as well as patient and family support.
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PMID:Blood-brain barrier disruption for the treatment of malignant brain tumors: The National Program. 964 16

The toxicity and therapeutic effect of the ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convulsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.
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PMID:Ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl-1-nitrosou rea hydrochloride for subarachnoid dissemination of gliomas. 969 73

Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O6-position of guanine in DNA. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.
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PMID:O6-Methylguanine-DNA methyltransferase protein levels in pediatric brain tumors. 981 47


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