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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fact that glioblastoma multiforme possesses antigens differing from those of normal brain has been stressed in early papers from Scheimberg, Mahaley, Eggers, and Brooks. In our work the presence of specific cytoplasmic and nuclear antigens in neoplastic cells has been demonstrated. These specific antigens are present not only in experimental tumours from the rat, but also in human glioblastoma, and are easily demonstrated by immunodiffusion and immunofluorescence techniques. From our work differences between intracellular and membrane antigens are clear, as the latter do not react with IgG immunoglobulin. On the other hand, tumoural antigens in glioblastoma have similar antigenic qualities to those of histocompatible antigens in normal brain. Experimental and human glioblastomas have weak antigens, as demonstrated by frequent tumour recurrence following amputation and the positive cross-reaction of antibody with normal brain in experimental models. Glioblastoma multiforme may have a common antigen as its antibodies easily cross-react positively with different human tumours with similar, histological features. As tumoural membranes did not react as cytoplasm and nuclei, we cannot say that membrane antigens resemble those of intracellular contents. The fact that viral-induced tumours may have common antigens should point to aetiological possibilities in this group of tumours. Delayed cellular response is very useful during the follow-up of these patients. Positive DNCB and intradermal reactions could be elicited in those patients in whom the antigenic overload has been reduced as a consequence of a surgical procedure. On the other hand, patients with extensive and infiltrating tumoural masses exhibited weak or negative delayed cellular responses. Humoral responses from the patient's sera may not have the prognostic value of cellular responses.
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PMID:Tumoural antigens on experimental and human glioblastoma. 699 46

The prognosis, site of occurrence, and histologic type of primary brain tumors are age-dependent phenomena. In general, the incidence of meningiomas, acoustic Schwannomas, and glioblastomas increases with advancing age until the end of the eighth decade. Of 99 patients consecutively admitted to an aggressive multimodality treatment program for glioblastoma multiforme, 18 per cent were in the 61-70 age group and 4 per cent in the 71-80 group; the oldest was 85. The operative mortality was only 4 per cent. In 16 patients over 65, the 6- and 12-month calculated survival probabilities were 0.65 and 0.31, respectively. The Kaplan-Meier survival curve for these patients was significantly different from that for 26 patients under the age of 40. Grade 4 astrocytomas were present in 62 per cent of patients under 40 but in 83 per cent of patients over 61. In all glioblastoma populations, age is the most significant prognostic variable. The incidence of metastic brain tumors also increases with age, and all of the usual primary sites are represented. The prognosis for elderly patients with metastatic brain tumor is uniformly worse than that for younger patients, even though modern diagnostic and operative techniques carry virtually the same morbidity and mortality rates in older patients as in younger ones. It is vitally important, therefore, that the clinical effects of treatable intracranial tumors in the elderly are not ascribed to dementia, the aging process, the systemic effects of cancer, or the side effects of cancer therapy, without suitable diagnostic investigation.
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PMID:Brain tumors and the geriatric patient. 709 52

Transplanted lines of seven F-344 (Fischer) rat malignant gliomas induced transplacentally with ethylnitrosourea (ENU) were surveyed by in vivo immunoprotection assays for the presence of tumour rejection antigens. These gliomas were representative of commonplace histological types of human primary brain tumours and were analyzed in early transplantation passages. The classical tumour ligation method of immunizing animals was attempted with five glioma lines, but was found unusable in four of these because of a high incidence of local tumour recurrences and distant metastases. In most experiments the animals were immunized by repeated inoculations of heavily-irradiated tumour cells. Two gliomas, a glioblastoma multiforms and a mixed astrocytoma-ependymoma, demonstrated weak but statistically significant tumour rejection responses. Immunization with three other tumours, a mixed oligodendroglioma-astrocytoma and two glioblastomas multiforme, led to enhanced outgrowth of the challenge cell inocula. Neither a rejection nor an enhancement response was observed in assays of the remaining two neoplasms, a glioblastoma multiforme and a mixed astrocytoma-oligodendroglioma. Immunization with a 3-methylcholanthrene-induced urinary bladder carcinoma line, used as a control in assays of six gliomas, had no effect on the outgrowth of transplanted glioma cells. These results suggest that ENU-induced malignant rat gliomas do not uniformly elicit strong tumour-rejection responses in vivo.
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PMID:A survey of ethylnitrosourea-induced rat gliomas for the presence of tumour rejection antigens expressed in vivo. 723 38

The clinico-neuropathological report is given of a glioblastoma multiforme with primary site in the cerebellum. The patient presented clinically with Wallenberg's syndrome; morphological investigations revealed the tumor partly invading the dorsolateral region of medulla oblongata. There are some reports of Wallenberg's syndrome not caused by vascular stenosis or occlusion, but by metastatic tumors in the lateral medullary region. The present report is the first of a cerebellar glioblastoma causing the peculiar brainstem syndrome.
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PMID:Cerebellar glioblastoma presenting clinically as Wallenberg's syndrome. 731 32

Extracranial metastasis of glioblastoma is rare. This is an autopsy case report of a patient with glioblastoma multiforme found to have metastasized to the liver. A 42-year-old woman was admitted with a chief complaint of headache. Physical and neurological examinations on admission showed no abnormalities. CT and MRI demonstrated a tumor in the left parietooccipital region with invasion into the subependymal area of the left lateral ventricular trig-one. A cerebral angiogram showed tumor staining in the same area. Subtotal tumor resection was performed uneventfully. The microscopic diagnosis was glioblastoma multiforme. Postoperatively, the patient underwent whole brain and local irradiation, and intra-arterial ACNU infusion therapy. One month later, she developed low back pain, probably due to spinal dissemination. Postmortem examination showed local recurrence of the tumor and subarachnoidal dissemination not only in the base of the skull but in the lower spinal cord. Tumor was also observed in the liver, but no lung or lymph node metastasis was detected. Metastasis to the liver in this patient is believed to have occurred via the anastomosis between the vertebral and portal venous system.
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PMID:[Glioblastoma multiforme with liver metastasis--case report]. 754 23

The familial occurrence of gliomas, in the absence of well-defined neurological tumor syndromes such as the neurofibromatoses, is uncommon. We present a family of ten children in which the four eldest suffered from gliomas. Three of these siblings had histologically verified glioblastoma multiforme, and one patient also had an intestinal non-Hodgkin's lymphoma, but there were no stigmata or family history of a neurological tumor syndrome. Cytogenetic studies of the proband revealed a normal karyotype. Molecular genetic analysis of the proband's glioblastoma revealed two mutations in the p53 tumor suppressor gene, but these were not present in the germline DNA, mutations were not detected in the MTS1 gene in the tumors or in the germline DNA. These findings suggest that a genetic factor may be responsible for the clustering of glial tumors in this family, but it is unlikely that the genetic alteration is mutation of the p53 gene. The data are discussed in light of the literature on familial brain tumors.
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PMID:Glioblastoma multiforme in four siblings: a cytogenetic and molecular genetic study. 759 55

Biopsies and cell culture, respectively, of four human glioblastoma multiforme (WHO 4) have been evaluated for gene amplification using reverse chromosome painting. Three of the tumours showed amplified domains within chromosome bands 12q13-15. The exact localisation and extension of the amplified domains, however, varies within this region. Southern blot analysis revealed amplification of the GLI oncogene in two of the glioblastomas which were found to contain amplified domains within 12q13-15. Reverse chromosome painting also identified amplified domains within bands 7q21 and 9p23-24. Amplification within region 9p23-24 has previously not been reported in glioblastoma. The amplified domain encompassing 9p23-24 was detected in the same glioblastoma which contained an amplification unit within bands 12q13-14. These data, together with previous reports, indicate that amplifications are predominantly found on chromosomes 7, 9 and 12 in glioblastoma. In addition, this study provides further evidence that coamplification is not a rare event in glioblastoma.
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PMID:DNA amplifications on chromosomes 7, 9 and 12 in glioblastoma detected by reverse chromosome painting. 765 43

The prognosis of glioblastoma multiforme remains poor despite advances in treatment by surgery, irradiation, and chemotherapy. Many malignant gliomas overexpress growth factor receptors. The possibility of targeting these receptors with selective cytotoxic molecules constructed by fusing deoxyribonucleic acid (DNA)-encoding mutant forms of Pseudomonas exotoxin A (PE) with complementary DNA-encoding growth factors was investigated. Several recombinant toxins have been produced, including those in which transforming growth factor (TGF)-alpha, insulin-like growth factor (IGF)-I, and acidic fibroblast growth factor (FGF) were fused to mutant forms of PE lacking the native cell-binding domain. These recombinant proteins are cytotoxic to cells that express specific cell-surface receptors. The cytotoxic activity of TGF-alpha, IGF-I, and acidic FGF chimeric toxins was tested in vitro against human glioblastoma cell lines. Each recombinant toxin exhibited potent and specific killing of cells. The TGF-alpha-PE40 construct was cytotoxic to seven of the eight cell lines and was active at concentrations as low as 0.5 ng/ml (1.1 x 10(-11) M). The acidic FGF-PE40 toxin was also active on seven of the eight cell lines but was 50-fold less active than the TGF-alpha-PE40. The IGF-I-PE40 construct was active on only two cell lines. To determine the possible therapeutic effect in animals, TGF-alpha-PE40 was administered to nude mice bearing subcutaneous human glioblastoma xenografts. The animals were treated for 7 days via a continuous infusion pump placed in the peritoneal cavity. A constant serum level of TGF-alpha-PE40 was achieved that was nontoxic to the mice yet caused a reduction in tumor volume and retarded growth beyond the treatment period. The overexpression of the epidermal growth factor receptor in glioblastomas multiforme and the potency and specificity of the TGF-alpha-PE40 construct designed to target this receptor suggests that TGF-alpha-PE40 has the potential to be an effective antitumor agent for the adjuvant therapy of these carcinomas.
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PMID:Cytotoxicity and antitumor effects of growth factor-toxin fusion proteins on human glioblastoma multiforme cells. 769 18

We have recently shown that vascular endothelial growth factor (VEGF) is produced by human malignant glioma cells and acts on tumor endothelial cells, which express VEGF receptors, suggesting that VEGF is a regulator of tumor angiogenesis. To investigate the feasibility of antiangiogenic brain tumor therapy, we developed an intracerebral (i.c.) rat glioma model. We used two transplantable rat glioma cells lines, C6 and GS-9L, to analyze VEGF regulation in vitro and expression of VEGF and its high affinity tyrosine kinase receptors, flt-1 and flk-1, in vivo. Glioma cells were transplanted i.c. or s.c. into syngeneic rats. C6 gliomas exhibit morphological characteristics of human glioblastoma multiforme such as necroses with palisading cells. Immunocytochemistry with von Willebrand factor showed that C6 gliomas are highly vascularized and therefore show another prominent feature of human glioblastoma. GS-9L gliosarcomas were less vascularized. In situ hybridization showed that VEGF is expressed in vivo in rat glioma cells which reside along necrotic areas and therefore closely mimicks the expression pattern of VEGF observed in human glioblastoma. flt-1 and flk-1 are specifically expressed in endothelial cells in the tumor and at the border between tumor and normal brain but are absent from endothelial cells in the normal brain proper. The action of VEGF may therefore be restricted to tumor endothelium. Upregulation of VEGF, but not acid fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor B messenger RNA was observed in hypoxic C6 and GS-9L cells in vitro. These observations are consistent with a role for VEGF in tumor- and hypoxia-induced angiogenesis. Since the expression pattern of VEGF and its receptors in rat glioma appears to be indistinguishable from human glioblastoma multiforme, this model provides an excellent tool to study anti-angiogenic therapy.
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PMID:Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. 769 95

Mutations in the receptor for the epidermal growth factor provide valuable insight into mechanisms of growth control. Oncogenic mutants of this receptor tyrosine kinase cause erythroid leukemia, fibrosarcoma, angiosarcoma, glioblastoma, and melanoma. Mutations in the avian protooncogene occur by retroviral mechanisms. Deletion of the ligand-binding domain results in erythroblastosis, while additional mutations in cytoplasmic structures broaden the disease potential to other cell types. A carboxyl-terminal structure of erbB oncogenes modulates growth responses in a complex, cell-specific manner; this tissue-specificity region appears to promote growth in erythroblasts and to produce trans-dominant inhibition in fibroblasts. Human glioblastoma multiforme frequently contains receptor mutations that are reminiscent of avian oncogenes. In hereditary melanoma of Xiphophorus, aberrant regulation of transcription by a recombinant promoter determines tissue-specific tumorigenesis. The diversity of oncogenic mutations raises important questions concerning the roles of several receptor structures. The extracellular domain inhibits the receptor when unoccupied by ligand, for example, through a mechanism that is unknown. The auto-phosphorylation sites are dispensable for transformation, so their function in neoplastic growth is unclear. The carboxyl-terminal region promotes or blocks transformation in different tissues, suggesting complex regulation by unknown cellular factors. These issues are critical to understanding of the mechanisms of receptor activation and tissue tropism for this family of oncogenes.
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PMID:Tissue-specific transformation by oncogenic mutants of epidermal growth factor receptor. 771 Nov 15


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