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)

The authors report a case of glioblastoma in which MR images with Gd-DTPA enhancement changed rapidly during the early stage. A 61 year-old male presented with sudden right facial spasm and dysarthria. However, both a plain and an enhanced CT failed to demonstrate any abnormal lesions. On the other hand, T2 weighted MR image revealed a well circumscribed high intensity lesion in the left frontal lobe without mass effect. This lesion could not be differentiated from cerebral infarction, since no contrast enhanced lesion was able to be observed in T1 weighted MR image with Gd-DTPA. His symptoms gradually became aggravated and at 3 months from the onset, MR image with Gd-DTPA disclosed a small enhanced lesion in the left frontal lobe near the cortical surface. After 6 months from the onset, he suffered from right hemiparesis and motor aphasia. The MR image with Gd-DTPA at this time showed a large enhanced lesion in the left frontal lobe with mass effect. He was admitted to our hospital, and subtotal removal of the tumor and intraoperative radiation was carried out. The patient did well postoperatively without additional neurological deficit, and then he received additional radiation therapy. It should be noted that Gd-DTPA enhanced MR image might fail to reveal the lesion of glioblastoma in its early stage, while T1 weighted image discloses only the gyral swelling.
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PMID:[A case of glioblastoma in which early diagnosis was difficult by MRI]. 194 85

Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had borderline hypo-immunoglobulin A, died of glioblastoma multiforme in 1977, and at autopsy, had adenomatous colonic polyps. His eldest brother has normal immunoglobulin levels, but developed immune thrombocytopenia in 1973 and had elevated EBV antibody titers in 1980. Another brother had hypo-immunoglobulin A, thymoma in 1965, and adenomas and adenocarcinoma of the colon. Two other brothers succumbed to glioblastoma in 1968 and 1969. The father of the proband had bronchiectasis in 1952, hypo-immunoglobulin M documented in 1972, and elevated EBV antibody titers 5 years preceding development of a malignant lymphoma. The latter contained 10 EBV genome equivalents/cell by EBV viral DNA/DNA reassociation kinetics analysis. The proband's grandmother had died of an immunoglobulin G-secreting myeloma in 1977, and his grandfather had borderline low immunoglobulin M, elevated EBV antibody titers, and hypopharyngeal carcinoma in 1980. Predisposition to oncogenesis in this family was probably inherited.
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PMID:Diverse familial malignant tumors and Epstein-Barr virus. 627 70

The cellular content of mutant p53 and hsp72 proteins following gamma-ray irradiation, UV irradiation, and heat treatment was studied in A-7 cells, a human glioblastoma cell line. A-7 was found to contain a mutant p53 gene in which the arginine codon at position 175 was substituted by a histidine codon. Although the p53 gene was mutant, the phenotype of the p53 protein appeared wild-type since the cellular content of the p53 protein was limited under normal culturing conditions. The quantity of mutant p53 and hsp72 proteins in A-7 was increased by heat treatment as well as gamma-ray and UV irradiation. Furthermore, the mutant p53 protein was coimmunoprecipitated with anti-hsp72/hsc73 antibody. Additionally, hsp72 and hsc73 were coimmunoprecipitated with anti-p53 antibody. These results suggest that in A-7, p53 protein accumulation may be caused as a result of response to stressors, such as gamma-ray, UV and heat and that mutant p53 protein and hsp72/hsc73 may manage biological functions cooperatively after gamma-ray, UV and also heat treatments.
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PMID:Accumulation of mutant p53 and hsp72 by heat treatment, and their association in a human glioblastoma cell line. 759 17

5,8,11,14-eicosatetraynoic acid (ETYA), an isomorphic competitive analogue of arachidonic acid, spontaneously generates a chemiluminescence signal detected with a liquid scintillation spectrometer operated at ambient temperature in the out-of-coincidence mode. The intensity of the signal was 10- or more-fold above background, required oxygen for its generation, was inhibited by antioxidants, and approximately doubled in D2O. Arachidonic acid, which contains 4-alkene rather than alkyne bonds did no more than double the chemiluminescent signal above background. When examined at 37 degrees C in a Berthold AutoLumat 958 luminometer, DBA (lucigenin) was required to detect a signal above background. Catalase or peroxidase, and to a lesser extent mannitol or histidine but not superoxide dismutase, strongly diminished the signal intensity. These observations provide a baseline for interpreting the functional and electron microscopic changes produced by ETYA in PC3 prostate and A172 glioblastoma cell lines, consistent with a contribution from oxidative stress associated with free radicals, and the absence of these morphological changes in U937 monoblastoid cells.
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PMID:Spontaneous chemiluminescence of ETYA (5,8,11,14-eicosatetraynoic acid) is inhibited by catalase or peroxidase. 784 95

A 50 y.o. male presented with a right parietal tumor which was a glioblastoma on stereotactic biopsy. He was treated by radiation and steroids, with clinical improvement. Four months later, he presented with a left preauricular mass and cervical lymphadenopathy. CT scan showed destruction of the left mastoid and filling of the left tympanic cavity. One month later, he suffered progressive dyspnea. Chest X ray showed a mediastinal mass on the right side and numerous bilateral interstitial opacities in the lungs. A bronchial biopsy was inconclusive. His general condition worsened, and he died. Postmortem showed continuous neoplastic infiltration of the left part of the base of skull, extending into the neck. Numerous metastases were present in mediastinal lymph nodes, lung parenchyma, pleura and pleural aspect of the diaphragm. There were no subdiaphragmatic metastases. Neuropathological examination confirmed a poorly differentiated highly malignant glioblastoma with severe necrosis involving the internal part of the parietal lobe extending to the dura mater of the convexity and falx cerebri with invasion of the superior longitudinal sinus which was entirely occluded. The biopsy scar was not infiltrated. Visceral tumors were morphologically identical to the brain tumor. They were strongly GFAP positive and cytokeratin negative. Extraneural metastases of glioblastoma in the absence of surgery are uncommon in adults. Involvement of the dura mater and/or superior longitudinal sinus is an almost constant feature. In our case, this may have led to invasion of the base of skull and secondary regional, lymphatic, and hematogenous spread.
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PMID:[Extracerebral metastases of a glioblastoma, in the absence of surgery]. 872 51

In a series of 46 glioblastomas, 16 anaplastic astrocytomas and eight astrocytomas, all tumours retaining one or both alleles of CDKN2A (48 tumours) and CDKN2B (49 tumours) were subjected to sequence analysis (entire coding region and splice acceptor and donor sites). One glioblastoma with hemizygous deletion of CDKN2A showed a missense mutation in exon 2 (codon 83) that would result in the substitution of tyrosine for histidine in the protein. None of the tumours retaining alleles of CDKN2B showed mutations of this gene. Glioblastomas with retention of both alleles of CDKN2A (14 tumours) and CDKN2B (16 tumours) expressed transcripts for these genes. In contrast, 7/13 glioblastomas with hemizygous deletions of CDKN2A and 8/11 glioblastomas with hemizygous deletions of CDKN2B showed no or weak expression. Anaplastic astrocytomas and astrocytomas showed a considerable variation in the expression of both genes, regardless of whether they retained one or two copies of the genes. The methylation status of the 5' CpG island of the CDKN2A gene was studied in all 15 tumours retaining only one allele of CDKN2A as well as in the six tumours showing no significant expression of transcript despite their retaining both CDKN2A alleles. Three tumours (one of each malignancy grade studied) were found to have partially methylated the 5' CpG island of CDKN2A. It appears that in human astrocytic gliomas point mutations of the CDKN2A and CDKN2B genes are uncommon and hypermethylation of the 5' CpG region of CDKN2A does not appear to be a major mechanism for inhibiting transcription of this gene.
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PMID:Infrequent methylation of CDKN2A(MTS1/p16) and rare mutation of both CDKN2A and CDKN2B(MTS2/p15) in primary astrocytic tumours. 900 May 91

The contributions of Arthur Elvidge (1899-1985), Wilder Penfield's first neurosurgical recruit, to the development of neurosurgery have been relatively neglected, although his work in brain tumors extended the previous work of Percival Bailey and Harvey Cushing. He published rigorous correlations of clinical and histological information and formulated a revised, modern nosology for neuroepithelial tumors, including a modern histological definition of glioblastoma multiforme. Well ahead of his time, he believed that glioblastoma was not strictly localized and was the first to comment that the tumor frequently showed "satellitosis." He was the first neurosurgeon in North America to use angiography as a radiographic aid in the diagnosis of cerebrovascular disease. Having studied with Egas Moniz, he was the first to detail the use of angiographic examinations specifically for demonstrating cerebrovascular disorders, believing that it would make possible routine surgery of the intracranial blood vessels. Seeking to visualize all phases of angiography, he was the impetus behind the design of one of the first semi-automatic film changers. Elvidge and Egas Moniz made the first observations on thrombosis of the carotid vessels independently of each other. Elvidge elucidated the significance of embolic stroke and commented on the ischemic sequelae of subarachnoid hemorrhage. Besides his contributions to neurosurgery, he codiscovered the mode of transmission of poliomyelitis. Elvidge's soft-spoken manner, his dry wit and candor, mastery of the understatement, love of exotic travel, and consummate dedication to neurosurgery made him a favorite of patients, neurosurgery residents, nurses, and other hospital staff. His accomplishments and example as teacher and physician have become part of neurosurgery's growing legacy.
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PMID:Arthur Roland Elvidge (1899-1985): contributions to the diagnosis of brain tumors and cerebrovascular disease. 942 95

Although characterized by a highly variable phenotype and multiple genetic alterations, glioblastomas are considered monoclonal in origin. We here report on a 64-yr-old patient who developed a second glioblastoma in the left frontal lobe 10 yr after surgical resection of a glioblastoma of right frontal lobe. The first tumor contained 2 p53 mutations, in codon 213 (CGA-->TGA, Arg-->stop) and codon 306 (CGA-->TGA, Arg-->stop), further, 1 missense PTEN mutation (codon 257, TTC-->TTA, Phe-->Leu) and a silent PTEN mutation (codon 154, TTC-->TTT, Phe-->Phe). The second glioblastoma also contained multiple, but different mutations: p53 mutations in codons 158 (CGC-->CAC, Arg-->His) and 273 (CGT-->TGT, Arg-->Cys), and a PTEN mutation in codon 233 (CGA-->TGA, Arg-->Stop). Both neoplasms had a homozygous p16 deletion. The discordant pattern of mutations indicates that the second glioblastoma was not a recurrence but an independent second glioblastoma. The presence in these neoplasms of multiple mutations in tumor suppressor genes suggests the involvement of a novel disease mechanism but there was no indication of a DNA mismatch repair deficiency or of an inherited tumor syndrome.
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PMID:Second primary glioblastoma. 1127 8

Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell growth and survival. By using a yeast two-hybrid screen to identify IGFBP-3-interacting proteins, we cloned humanin (HN) as an IGFBP-3-binding partner. HN is a 24-aa peptide that has been shown to specifically inhibit neuronal cell death induced by familial Alzheimer's disease mutant genes and amyloid-beta (Abeta). The physical interaction of HN with IGFBP-3 was determined to be of high affinity and specificity and was confirmed by yeast mating, displaceable pull-down experiments with (His)-6-tagged HN, and ligand blot experiments. Co-immunoprecipitation of IGFBP-3 and HN from mouse testes confirmed the interaction in vivo. In cross-linking experiments, HN bound IGFBP-3 but did not compete with IGF-I-IGFBP-3 binding; competitive ligand dot blot experiments revealed the 18-aa heparin-binding domain of IGFBP-3 as the binding site for HN. Alanine scanning determined that F6A-HN mutant does not bind IGFBP-3. HN but not F6A-HN inhibited IGFBP-3-induced apoptosis in human glioblastoma-A172. In contrast, HN did not suppress IGFBP-3 response in SH-SY5Y neuroblastoma and mouse cortical primary neurons. In primary neurons, IGFBP-3 markedly potentiated HN rescue ability from Abeta1-43 toxicity. In summary, we have identified an interaction between the survival peptide HN and IGFBP-3 that is pleiotrophic in nature and is capable of both synergistic and antagonistic interaction. This interaction may prove to be important in neurological disease processes and could provide important targets for drug development.
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PMID:Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. 1456 95

The growth rate of numerous cancer cell lines is regulated in part by actions of neuropeptides of the vasoactive intestinal peptide (VIP) family, which also includes pituitary adenylate cyclase-activating peptide (PACAP), glucagon, and peptide histidine/isoleucine (PHI). The aim of this work was to investigate the effect of these peptides on the growth of the rat glioblastoma cell line C6 in vitro. We also sought to determine which binding sites were correlated with the effects observed. Proliferation studies performed by means of a CyQuant trade mark assay showed that VIP and PACAP strongly stimulated C6 cell proliferation at most of the concentrations tested, whereas PHI increased cell proliferation only when associated with VIP. Two growth hormone-releasing factor (GRF) derivatives and the VIP antagonist hybrid peptide neurotensin-VIP were able to inhibit VIP-induced cell growth stimulation, even at very low concentrations. Binding experiments carried out on intact cultured C6 cells, using 125I-labeled VIP and PACAP as tracers, revealed that the effects of the peptides on cell growth were correlated with the expression on C6 cells of polyvalent high-affinity VIP-PACAP binding sites and of a second subtype corresponding to very high-affinity VIP-selective binding species. The latter subtype, which interacted poorly with PACAP with a 10,000-fold lower affinity than VIP, might mediate the antagonist effects of neurotensin- VIP and of both GRF derivatives on VIP-induced cell growth stimulation.
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PMID:Effects of the vasoactive intestinal peptide (VIP) and related peptides on glioblastoma cell growth in vitro. 1459 9


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