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

We tested an experimental strategy to decrease the dose-limiting hematotoxicity of carboplatin without compromising its activity against brain tumors. The effect of pretreatment with WR-1065, a chemomodifier that penetrates brain poorly, on carboplatin's cytotoxicity was evaluated in human hematopoietic granulocyte-monocyte progenitor cells and in three human glioblastoma cell lines. WR-1065 reduced bone marrow toxicity without decreasing carboplatin's activity against glioblastoma cells. These results suggest that the therapeutic index of carboplatin might be increased in the treatment of malignant brain tumors.
Cancer Chemother Pharmacol 1991
PMID:Experimental basis for increasing the therapeutic index of carboplatin in brain tumor therapy by pretreatment with WR compounds. 187 48

The immunohistochemical distribution of alpha and beta subunits of S-100 protein (S-100 alpha, S-100 beta, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 alpha (+) and/or S-100 beta (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 alpha (+) and S-100 beta (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 alpha (-) and S-100 beta (+)]; acoustic Schwannoma. Group 4 [S-100 alpha (-) and S-100 beta (-)]; medulloblastoma malignant lymphoma, germinoma. The S-100 beta immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 beta than for S-100 alpha with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 beta immunoreactivity decreased according to degree of malignancy, while that of S-100 alpha varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 alpha and S-100 beta might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.
 ...
PMID:Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in brain tumors. 188 40

Single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis) was used for detection of mutations of the p53 gene in surgical specimens of human brain tumors. Six of 45 brain tumors showed mobility shifts in the analyses. These six tumors also showed loss of a normal allele. The samples were examined further by direct sequencing. Results showed that four of them had single-base substitutions and the other two had deletions of one and eight base pairs. Five of the six mutations detected were clustered in highly conserved regions of the p53 gene. The frequency of p53 gene mutations in primary brain tumors examined was 9.8%. We also found two new polymorphic markers in the p53 gene, one in intron 7 and the other in an Alu repeat in exon 11. Both markers could be detected by SSCP analysis. Using these two markers, we found two cases of loss of heterozygosity in other brain tumor specimens. Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
 ...
PMID:Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products. 188 8

Human glioblastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteoglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma.
Cancer Res 1991 Sep 15
PMID:Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells. 189 86

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder mapped to 17q11.2 and typically characterized by the occurrence of neural crest-derived tumors. The gene has recently been cloned using reverse genetics or "positional cloning" approaches. Its function, however, remains unknown. We have performed cytogenetic and molecular analyses on 9 malignant tumors from NF1 patients to look for loss of alleles or chromosome rearrangements involving chromosome 17 to test the hypothesis that the NF1 gene acts as a recessive "tumor suppressor" gene. Loss of alleles on this chromosome was detected for 3 of 9 malignant tumors. Two peripheral nerve sheath tumors showed allele loss at informative loci on both the long and short arms of chromosome 17. In contrast, a glioblastoma with focal gliosarcoma showed loss of heterozygosity on the short arm of chromosome 17 only, and not at loci on the long arm. One nerve sheath tumor was previously shown by direct sequence analysis to have a point mutation at the TP53 locus at 17p13. These data support a role for the TP53 gene or other genes on the short arm of chromosome 17 in at least some malignancies in NF1. Six other neurofibrosarcomas showed no allele loss at informative loci on chromosome 17. Cytogenetic analysis was performed on 7 tumors, including 2 with allele loss. The two tumors with allele loss showed abnormal karyotypes while all others were normal. Southern blot and pulsed-field gel analysis using probes within or closely linked to the NF1 locus detected no gross deletions or rearrangements in the tumors studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Genes Chromosomes Cancer 1991 Jan
PMID:Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis. 190 41

The role of Neutron Capture Therapy for the treatment of uncontrollable, localised tumours is examined. Several boron carrier biochemicals are already in use for the selective accumulation of boron in cancer cells, and therapeutic boron concentrations have been achieved in glioblastoma and melanoma in animal models and in patients. Local control of glioblastoma and subcutaneous melanoma has been reported after thermal neutron irradiation. Different neutron beam requirements apply for the treatment of these cancers, in the former case a thermal beam is adequate but a more penetrating epithermal beam is needed for the treatment of deep-seated tumours. A thermal facility for small animal irradiations is available in Australia, and the development of a patient thermal/epithermal facility is under active consideration.
 ...
PMID:The potential of neutron capture therapy in the management of uncontrollable localised tumours. 196 83

Ribonucleic acid was isolated from a wide spectrum of central nervous system tumors to examine the expression of platelet-derived growth factors (PDGF) A and B, tumor growth factors (TGF-beta) 1 and 2, and ros messenger ribonucleic acid. Eight glioblastoma cell lines were examined as well as cell cultures from 22 tumor explants. The explants included 6 glioblastomas, 4 anaplastic astrocytomas, 5 astrocytomas, 3 ependymal tumors, 2 meningiomas, 1 medulloblastoma. and 1 ganglioglioma. For comparison, 2 nontumor glial cell cultures were included. The PDGF B-chain was expressed in 5 of 8 glioblastoma cell lines, 2 of 6 glioblastomas, and in 3 of 4 anaplastic astrocytoma explants. There was no PDGF B expression in 4 astrocytomas, 3 ependymomas of varying malignancy, in the remainder of the tumors, or in the nontumor glial cells. The PDGF A-chain was expressed in all of the tumors, with the exception of the malignant ependymoma and in both nontumor glial cell cultures. TGF-beta 1 was expressed in all of the tumors and in nontumor glial cells. The expression of TGF-beta 2 was expressed in many of the benign and malignant tumors and also in both nontumor glial cell cultures. The ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma cell lines and in 2 of 6 glioblastoma cell explants, but in none of the other tumors or in the nontumor glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors. 199 89

We have applied restriction fragment length polymorphism analysis to a 30-member panel of primary glioma DNAs, which had been previously examined for loss of genetic information (C. D. James, E. Carlbom, J. P. Dumanski, M. Hansen, M. Nordenskjold, V. P. Collins, and W. K. Cavenee, Cancer Res., 48:5546-5551, 1988), to determine the frequency and sublocalization of loss of genetic information from chromosome 9. We have also utilized scanning densitometry for dosage determination of the 9p-localized interferon alpha and interferon beta-1 genes among these same tumors. Our results reveal the following: (a) for those cases in which loss has occurred, the region of common loss lies on the short (p) arm of the chromosome; (b) loss of genetic information from the short arm of chromosome 9 occurs frequently in glial tumors of intermediate (anaplastic, grade III) and high (glioblastoma, grade IV) histological malignancy (10 of 20 cases) but not in tumors of low (grade II) histological malignancy (0 of 10 cases); (c) tumors with 9p deletions are hemi- or nullizygous for interferon beta-1 and the interferon alpha gene cluster; (d) cases of interferon nullizygosity occur exclusively among tumors of highest histological malignancy (glioblastoma). These data, especially the determination of a region of nullizygosity, suggest proximity to or residence within a gene(s) whose function(s) is (are) critical to the suppression of the malignant evolution of glial tumors.
Cancer Res 1991 Mar 15
PMID:Chromosome 9 deletion mapping reveals interferon alpha and interferon beta-1 gene deletions in human glial tumors. 199 58

Anomalies of the epidermal growth factor receptor (EGFR) gene, including amplification, rearrangement, and overexpression, have been reported in malignant human gliomas in vivo. In vitro glioma cell lines coexpress EGFR and at least one of its ligands, transforming growth factor alpha, suggesting the existence of an autocrine growth stimulatory loop. We have studied the tumor tissue from 62 human glioma patients and examined the structure and quantity of the EGFR gene and its transcripts, as well as the quantity of the receptor protein. In addition we have examined the genes and transcripts coding for the pre-pro forms of epidermal growth factor and transforming growth factor alpha, the two endogenous EGFR ligands. EGFR gene amplification was detected in 16 of the 32 malignancy grade IV gliomas (glioblastoma) studied (50%), but only in 1 of 30 gliomas of lesser malignancy grade (I-III). All tumors with an amplified gene overexpressed EGFR mRNA. More than one-half (62.5%) of the glioblastomas with amplified EGFR genes also showed coamplification of rearranged EGFR genes and concomitant expression of aberrant mRNA species. Overexpression, without gene amplification, was observed in some of the low grade gliomas, and aberrant EGFR transcripts were also seen in some cases without gene amplification or detected gene rearrangements. mRNA expression for one or both of the pre-pro forms of the ligands was detected in every tumor studied. Thus, several mechanisms for the activation of the EGFR-mediated growth stimulating pathway are possible in human gliomas in vivo: expression of a structurally altered receptor that may have escaped normal control mechanisms; and/or auto-, juxta-, or paracrine stimulating mechanisms involving coexpression of receptor and ligands, with or without overexpression of the receptor.
Cancer Res 1991 Apr 15
PMID:Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. 200 34

Peripheral blood mononuclear cells (PBM) from normal donors and patients with recurrent glioma were activated initially for 48-72 h with phytohemagglutinin-P (PHA) and recombinant human interleukin-2 (IL-2), and then proliferated in vitro for up to 5 months with IL-2. These cells are termed mitogen-stimulated lymphokine-activated T killer (T-LAK) cells. We measured patterns of T-LAK cell growth, in vitro cytolytic activity on a panel of continuous and primary tumor cells, and the phenotypes of the cells in these cultures. Lymphocyte viability declined dramatically over the first 3-5 days; and then the remaining cells in these cultures began to divide and maintained a constant 30-36 h doubling time for long periods in vitro. Phenotyping revealed that cells in the initial few days of culture were heterogeneous, but became almost totally CD3 T cells after 7-10 days in culture. The T-LAK cells from individual normal donors and cancer patients demonstrated a non-genetically restricted cytolytic ability against a panel of both continuous cell lines and primary autologous and allogeneic glioblastoma cells in vitro. This technique provides a method of generating large numbers of autologous cytolytic T cells with non-restricted anti-tumor activity that can be derived from peripheral blood mononuclear cells.
 ...
PMID:Generation of stimulated, lymphokine activated T killer (T-LAK) cells from the peripheral blood of normal donors and adult patients with recurrent glioblastoma. 201 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>