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)

Malignant glioma is the most common brain tumor. The molecular basis of glioma tumorigenicity has not been defined. Cultured glioma cells accumulate high levels of insulin-like growth factor I (IGF-I) transcripts. We asked whether IGF-I expression is coupled to tumorigenicity, using a combined in vivo/in vitro system employing antisense RNA for IGF-I. An antisense IGF-I expression construct in an expression vector that incorporates Epstein-Barr virus replicative signals and the ZnSO4-inducible metallothionein I transcriptional promoter was assembled. Stable glioma transfectants were derived from C6 glioma cells, which constitutively express IGF-I. B-104 neuroblastoma cells, derived originally from the same tumor but not expressing IGF-I, were also transfected as controls. In the absence of ZnSO4, the C6 transfectants expressed high levels of IGF-I mRNA and protein as detected by in situ hybridization and immunocytochemistry, respectively. Addition of ZnSO4 in the culture medium resulted in high levels of antisense transcript accumulation and dramatically decreased levels of endogenous IGF-I mRNA and IGF-I protein. Subcutaneous injection of either nontransfected C6 parental cells or C6 cells transfected with vector without IGF-I sequences into rats resulted in large tumors after 2 weeks, as did transfected and nontransfected B-104 cells. However, the rats injected with transfected C6 cells yielded no tumors after 40 weeks of observation. Two weeks after injection of the transfected C6 cells a small cyst was apparent in six rats. Histologic sections revealed a few glioma cells infiltrated by a large number of mononuclear cells. No infiltration of mononuclear cells was apparent in the glioma tumors resulting from injection of parental (nontransfected) cells, suggesting that the parental cells, but not the antisense IGF-I transfectants, escape the host immune response.
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PMID:Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. 159 87

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary's criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month follow-up examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disabled. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.
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PMID:Direct surgery for brainstem tumours. 180 73

Xenogeneic immunization of freshly-prepared human glioma extracts into goats has yielded a polyclonal antiserum, which after multiple absorptions specifically identifies antigenic entities only in glioma extracts, and not in appropriate controls, both by radioimmunoassays (RIAs) and Western immunoblots. The results from the absorbed polyclonal antiserum have been confirmed by the successful generation of six stable murine monoclonal antibodies (MAbs) which recognize a subset of the same antigens with high specificity on immunoblots and with no apparent cross-reactivities by RIA to normal brain, serum, liver, muscle, kidney, spleen, or melanoma tissues. Moreover, the tested murine MAbs (B12C4) reveal a striking and abundant glial filament protein, possibly related to glial fibrillary acidic protein (GFAP) or other intermediate filament proteins, by frozen-section immunofluorescence. This is seen only in gliomas and is absent, or dramatically reduced, in normal human cortex. Use of potent immortalizing strain (FF41) of Epstein-Barr virus (EBV) to establish antibody-secreting human lymphoblastoid lines, and the generation of mouse-human chimeric fusions, have yielded lines possessing variable supernatant human antibody secretion. Radioimmunoassays using culture supernatants, and sera from glioma patients and an normal individual, have demonstrated surprisingly similar reactivity profiles, even after a sensitive sandwich RIA employing the B6C6 murine MAb. These results suggest that, although human glioma-associated antigens, including possibly the up-regulation of GFAP expression, clearly exist, there seems to be a muted humoral response as evidenced by a paucity of tumor-specific B-cells. This may be due to antigenic shielding by the blood-brain barrier, or due to a form of immunological compromise in patients harboring these malignancies.
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PMID:Paucity of humoral response in patients to glioma-associated antigen(s): antigen localization by immunofluorescence. 180 70

Two monoclonal antibodies (mAb), termed ED6 and LD6, were obtained by immunizing mice with cytotoxic T cell lines expressing the T cell receptor (TcR) gamma/delta. These mAb were selected according to their ability to trigger the cytolytic program of the immunizing cell lines in a redirected killing assay. Both mAb recognized molecule(s) expressed on the surface of most long-term cultured TcR gamma/delta +, TcR alpha/beta + and CD3-CD16+ lymphocytes, while it was absent on resting peripheral blood lymphocytes. In addition both mAb reacted with neoplastic B cell lines, Epstein-Barr virus-transformed B cell lines, small cell lung cancer and glioma cell lines, while no surface reactivity was detected on ovarian, breast, colon and non-small cell lung cancer lines. The functional activity of these mAb was studied by two cytolytic assays. Both mAb were able to trigger the cytolytic program of CD3+TcR gamma/delta + polyclonal cell lines and of a CD3-CD16+ NK cell clone against the murine mastocytoma target cell line P815 (Fc receptor+) in a 4-h 51Cr-release assay. In addition, ED6 and LD6 hybridomas were lysed by TcR gamma/delta + effector cells while other hybridomas (obtained from the same fusion) were not lysed. ED6 and LD6 mAb (in the presence of submitogenic doses of the phorbol 12-myristate 13-acetate) also induced the secretion of interleukin 2 by ED6/LD6+ T cell clones expressing TcR gamma/delta or alpha/beta. mAb-induced surface antigen modulation experiments showed that the antigenic determinant recognized by ED6 and LD6 co-modulated, thus indicating that the two mAb probably recognize the same or closely associated molecules. The molecular characteristics of the antigen recognized by the mAb were investigated by Western blot analysis. The LD6 mAb recognized a major band of approximately 65 kDa, both under nonreducing and reducing conditions. These data indicate that ED6 and LD6 mAb recognize a novel non-lineage-specific activation antigen which is involved in the induction of the functional program of long-term cultured T or natural killer cells.
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PMID:A novel surface molecule expressed by long-term cultured T and natural killer cells is involved in cell activation. 183 83

Peripheral blood B lymphocytes of multiple sclerosis (MS) patients and control persons were transformed with Epstein-Barr virus. Antibody production of transformed cells against isolated human myelin was investigated by enzyme-linked immunosorbent assay (ELISA). Cells producing reactive antibodies were cloned and propagated to produce monoclonal antibodies (mAbs). These mAbs did also react with acetone fixed frozen sections of normal human white matter, as determined by indirect immunofluorescence staining. Some of the mAbs derived from MS patients and a control person with a central nervous system cyst agglutinated liposomes made from lipids of a chloroform/methanol extract of human myelin, whereas mAbs derived from four glioma patients were negative in these tests. The reactive antibodies were investigated further using agglutination tests with liposomes made from pure auxiliary lipids (cholesterol and lecithin) or containing in addition either galactocerebroside, sulfatide or a mixture of bovine brain gangliosides. The great majority of myelin liposome agglutinating antibodies reacted with all types of liposomes, including those made from pure auxiliary lipids. Investigations by ELISA suggest that phospholipids are the reactive components, at least for some of these mAbs. Some antibodies reacted with liposomes containing galactocerebroside or sulfatide, others only with sulfatide containing liposomes. Antibodies showing these specificities were only obtained from MS patients.
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PMID:Monoclonal autoantibodies derived from multiple sclerosis patients and control persons and their reactivities with antigens of the central nervous system. 256 90

Human IgM kappa antibody to a membrane antigen of human tumors of neuroectodermal origin (melanoma, glioma and neuroblastoma) has been detected in the spent culture fluid of an Epstein-Barr virus (EBV)-transformed human B-lymphoblastoid cell line, L72. The chemical nature of the antigen was identified as ganglioside GD2. The antibody was purified by precipitation of L72 culture fluid with ammonia sulfate and hypotonic buffer followed by ultracentrifugation and Sephacryl S-300 super gel filtration. Approximately 27 mg of pure human IgM was obtained from 101 of spent medium. Total IgM and antibody activity recovery efficiency was 60% and 75%, respectively. The monoclonal character of the immunoglobulin produced by the L72 cell line was determined by agarose isoelectric focusing and immunofixation techniques. 1 mg of the purified IgM possessed an antibody titer endpoint to a GD2-positive melanoma cell line of 1:10,000 as assayed by immune adherence and 1:100 titer by complement-dependent cytotoxicity in vitro. The effect of pure anti-GD2 on suppression of melanoma growth in vivo was tested using a nude mouse model. Three-week-old CD-1 nude mice bearing 2-3 mm M14-A subcutaneous melanoma nodules were treated intraperitoneally with anti-GD2 and rabbit complement. Tumor growth was retarded for 25 days when compared to that of control mice receiving non-specific human IgM and complement. On Day 15, treated tumors were 80% smaller than control tumors. These result indicated that the pure human monoclonal antibody to GD2 may have potential for cancer therapy.
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PMID:Human monoclonal antibody to tumor-associated ganglioside GD2. 609 19

We established two long-term human B-lymphoblastoid cell lines (L55 and L72) transformed by Epstein-Barr virus that produced IgM kappa antibodies to the human tumor antigen, OFA-I. Periphral blood lymphocytes obtained from melanoma patients were used as the source of the B lymphocytes. Antibody specificity was determined by the immune adherence assay using various human cancer and noncancer tissues as targets. L55 antibody (designated anti-OFA-I-1) reacted with a variety of human tumor types whereas L72 antibody (designated anti-OFA-I-2) reacted only with tumor cells of neuroectodermal origin (melanoma, glioma, and neuroblastoma). The levels of IgM detected in the spent medium of 1 X 10(6) L55 and L72 cells were 4 and 9 micrograms/ml, respectively, by radioimmunoassay.
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PMID:Human antibody to OFA-I, a tumor antigen, produced in vitro by Epstein-Barr virus-transformed human B-lymphoid cell lines. 629 Oct 57

The majority of brain stem gliomas tend to occur during childhood and arise in the pons. The prognosis of these typical pontine gliomas is almost invariably bad. In contrast, there exists a group of benign brain stem gliomas, mostly arising from the midbrain and are amenable to surgical resection. They are often low-grade astrocytomas and are associated with better prognosis. We summarized nine cases of intrinsic midbrain gliomas and their clinical behavior was analyzed by radioimagings and histopathological examination. They were classified from CT images according to Stroink et al. and from anatomic staging by Epstein. The result showed that 5 in 9 cases were so called, "focal midbrain gliomas". That is to say, the tumor arose from the tectal plate or the tegmentum of the mesencephalon and expanded dorsally, but did not invade the surrounding neural tissues. Three focal midbrain gliomas in childhood were well demarcated and surgically resectable. Histologically, tumors were astrocytomas and were associated with favorable prognosis. However, two focal midbrain gliomas in adulthood were anaplastic astrocytoma and the prognosis was poor, even though they appeared similar shown on radioimaging study. The overall survival rate of patients with midbrain glioma was longer than that of patients with glioma in the cerebral hemisphere. From these results, it was concluded that a specific group of intrinsic, focal midbrain gliomas can be classified into pediatric benign gliomas and adolescent malignant ones. A further number of cases should be studied to clarify this hypothesis.
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PMID:[A clinicopathological study of nine cases of midbrain glioma]. 775 19

We developed an adenovirus vector for transduction of the human CD21 gene (Adv-CD21), the Epstein-Barr virus (EBV)-specific receptor on human B lymphocytes, to overcome the initial barrier of EBV infection in nonprimate mammalian cells. Inoculation of Adv-CD21 followed by exposure to recombinant EBV carrying a selectable marker resulted in the successful entry of EBV into three of seven nonprimate mammalian cell lines as evidenced by expression of EBV-determined nuclear antigen (EBNA). The EBV-susceptible cell lines included rat glioma-derived 9L, rat mammary carcinoma-derived c-SST-2, and canine kidney-derived MDCK. Subsequent selection culture with G418 yielded drug-resistant cell clones. In these cell clones, EBV existed as an episomal form, as evidenced through the Gardella gel technique. Among the known EBV latency-associated gene products, EBV-encoded small RNAs, EBNA1 and transcripts from the BamHI-A rightward reading frame (BARF0), and latent membrane protein 2A were expressed in all EBV-infected cell clones. The viral lytic events could be induced in these cell clones by simultaneous treatment with 12-O-tetradecanoylphorbol-13-acetate and n-butyric acid, but they were abortive, and infectious virus was not produced. These results indicate that once the initial barrier for attachment is overcome artificially, EBV can establish a stable infection in some nonprimate mammalian cells, and they raise the possibility that transgenic animals with the human CD21 gene could provide an animal model for EBV infection.
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PMID:CD21-mediated entry and stable infection by Epstein-Barr virus in canine and rat cells. 1104 19

The authors previously reported statistically significant inverse associations between adult onset glioma and histories of chickenpox and shingles among 462 cases and 443 controls in the San Francisco Bay Area Adult Glioma Study (1991--1995) and a suggestive but nonsignificant inverse association with immunoglobulin G antibodies to varicella-zoster virus in a small subset of these cases. This report considers antibodies to four common herpesviruses (varicella zoster, herpes simplex, cytomegalovirus, and Epstein Barr) among 134 cases and 165 controls that represent all subjects for whom usable blood specimens were available. The prevalences of immunoglobulin G antibodies to varicella-zoster virus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were 90%, 71%, 57%, and 90%, respectively. After adjustment for age, White versus non-White ethnicity, and gender, glioblastoma cases were less likely than controls to have immunoglobulin G antibodies to varicella-zoster virus (odds ratio = 0.4; 95% confidence interval: 0.1, 0.9). They were also somewhat less likely to have antibodies to Epstein-Barr virus but somewhat more likely to have antibodies to herpes simplex virus and cytomegalovirus. Antibody prevalences to all four herpesviruses were similar between cases with other glioma histologies and controls. These results corroborate our previously suggestive findings of an inverse association of varicella-zoster virus antibodies with adult onset glioma.
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PMID:Prevalence of antibodies to four herpesviruses among adults with glioma and controls. 1144 50


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