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)

The intrathecal immune response in neoplastic meningitis (NM) was studied by quantitation of immune parameters such as immunoglobulin G (IgG); IgM; interleukins (IL) 1, 2, 4, and 6; soluble IL-2 receptors (sIL-2R); interferon gamma (IFNy); tumor necrosis factor-alpha (TNF alpha); and three tumor markers, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and fibronectin (FN), in 47 paired cerebrospinal fluid (CSF) and serum samples from patients with NM from different carcinomas, malignant melanoma, and lymphoma. Elevated IgG and IgM indices, CSF oligoclonal Ig bands, and CSF IL-6 indicated an intrathecal immune activation in most patients with NM. Results for IL-1, IL-2, and IL-4 were always negative. sIL-2R and IFNy were detected occasionally but not associated with specific malignant neoplasms. CSF TNF alpha was detected only in NM from cases of malignant melanoma. None of the immune parameters proved useful for the differentiation of NM from autoimmune or inflammatory conditions. Immune parameters were not correlated with tumor markers CEA, AFP, or FN. Results for AFP were positive only in a case of glioblastoma. CEA was a useful and specific diagnostic parameter in carcinomatous NM. CSF FN levels frequently were elevated but are not specific for NM.
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PMID:Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis. 137 13

By fusion of mouse NS1 myeloma cells with splenocytes from a BALB/c mouse immunized with human melanoma cells, an IgG1 monoclonal antibody, designated as 140.72, was produced. By the mixed hemadsorption antibody binding assay, 140.72 was shown to react with 17 of 20 melanoma cell lines and with 5 of 14 carcinoma cell lines. This antibody also reacted with 3 of 3 normal melanocyte cultures in much lower titers. It did not react with any of 35 other normal and malignant lines, including neuroblastoma, glioblastoma, sarcoma, teratoma, fibroblast, and lymphoid cell lines. Absorption with fresh melanoma and carcinoma homogenates confirmed the results of direct tests. Fetal reactivity of antibody 140.72 was determined by positive absorption with 10 of 11 tissue homogenates derived from different fetuses of 10-16 weeks' gestation. The reactivity of this antibody was completely removed by absorption with a highly purified preparation of carcinoembryonic antigen (CEA) derived from a colon carcinoma. The antigenic activity was detected in the culture medium of reactive cell lines. Immunoprecipitation analyses of melanoma and carcinoma cells indicated that the antigenic determinant recognized by antibody 140.72 is on a glycoprotein with an apparent molecular weight of 95,000-150,000 common to both serologically reactive cell types. Additionally, a 200,000-molecular-weight glycoprotein corresponding to the CEA molecule was detected only on the reactive carcinoma cells. These data confirmed previous findings obtained with polyclonal anti-CEA antisera for the existence of shared CEA-related antigenic determinants on human carcinomas and melanomas and provided additional molecular characterization of these glycoproteins. Further characterization of the molecules bearing the antigenic determinant recognized by antibody 140.72 should be performed with a view to exploring its potential in the immunodiagnosis and immunotherapy of patients with melanoma.
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PMID:Monoclonal antibody recognizing human melanoma-carcinoma cross-reacting oncofetal antigen epitopically associated with carcinoembryonic antigen. 258 73

Incidentally CNS tumours may simulate acute bacterial or viral meningitis, cerebral abscess, and tuberculous or luetic basal meningitis. 64 cases from the literature are analysed together with 2 personal observations. This form of presentation is found most frequently in high-grade malignancy, i.e. in glioblastoma, medulloblastoma and ependymoma. In the group of benign CNS neoplasms dermoid and epidermoid cysts are most often associated with the meningeal syndrome. The only criterion facilitating a differentiation between acute bacterial meningitis and CNS malignancy is CSF culture. In individual cases an afebrile course, a normal sedimentation rate, and a normal WBC count may help to differentiate. In the presence of basal meningitic or diencephalic symptoms related to a prolonged course discrimination between brain tumour an tuberculous or luetic meningitis may become extremely difficult. In these cases the determination of creatine kinase BB isoenzyme and carcinoembryonic antigen in CSF may overcome the difficulty.
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PMID:[CNS tumors with the clinical picture of meningitis]. 388 30

We report a case of intracranial chondrosarcoma of the skull base with fatal intra- and peritumoral hemorrhage. A 75-year-old woman complained of right blepharoptosis and diplopia in 1989. An initial diagnosis of Tolosa-Hunt syndrome was made, and the patient was treated with steroid hormone therapy at a local hospital. Because the symptoms had not been relieved, she was admitted to our hospital. Computed tomography (CT) scan and magnetic resonance (MR) images demonstrated a large mass extending from the right side of the clivus to the parasellar region and petrous apex. The mass was partially calcified and had destroyed the base of the middle cranial fossa. The lesion had homogeneous enhancement with contrast medium. Preoperative diagnosis was chordoma or chondroma. A biopsy of the tumor was made. The pathological diagnosis of biopsy specimen was chondroid chordoma. The patient was followed up but no palliative treatment such as radiotherapy was given. On June 25, 1991, she suffered from cerebral infarction. On June 29, 1993, she died of sudden respiratory failure. Autopsy was performed. It revealed intra- and peritumoral hematoma compressing the medulla oblongata, pons and midbrain. Histologically immature chondroid cells proliferated in a myxoid-rich extracellular matrix. The tumor cells were composed of hyperchromatic nuclei and eosinophilic cytoplasm, but there was no evidence of notochordal differentiation. Compared with biopsy findings, the tumor showed high cellular density. Immunohistochemically, the tumor cells reacted positively for S - 100 protein, vimentin and cytokeratin, but negatively for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In view of these histopathological findings, the diagnosis of low-grade myxoid chondrosarcoma was established. Intratumoral hemorrhage often occurs in malignant brain tumors such as glioblastoma and metastatic brain tumor, but chondroid tumors rarely develop a fatal type of intratumoral hemorrhage. Only 8 cases have been reported in detail to date. We discuss the immunohistochemical features and spontaneous intratumoral hemorrhage of chondrosarcoma.
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PMID:[Chondrosarcoma of the skull base associated with fatal intratumoral hemorrhage : report of an autopsy case and review of the literature]. 884 79

Despite the most aggressive medical and surgical treatments, glioblastoma multiforme remains incurable with a median survival of <1 year. We investigated the antitumor potential of a novel viral agent, an attenuated strain of measles virus (MV), derived from the Edmonston vaccine lineage, genetically engineered to produce carcinoembryonic antigen (CEA). CEA production as the virus replicates can serve as a marker of viral gene expression. Infection of a variety of glioblastoma cell lines including U87, U118, and U251 at MOIs 0.1, 1, and 10 resulted in significant cytopathic effect consisting of excessive syncycial formation and massive cell death at 72-96 h from infection. terminal deoxynucleotidyltransferase-mediated nick end labeling assays demonstrated the mechanism of cell death to be predominantly apoptotic. The efficacy of this approach in vivo was examined in BALB/c nude mice by using both s.c. and intracranial orthotopic U87 tumor models. In the s.c. U87 model, mice with established xenografts were treated with a total dose of 8 x 10(7) plaque forming units of MV-CEA, administered i.v. Mice treated with UV light inactivated MV, and untreated mice with established U87 tumors were used as controls. There was statistically significant regression of s.c. tumors (P < 0.001) and prolongation of survival (P = 0.007) in MV-CEA treated animals compared with the two control groups. In the intracranial orthotopic U87 model, there was significant regression of intracranial U87 tumors treated with intratumoral administration of MV-CEA at a total dose of 1.8 x 10(6) plaque forming units as assessed by magnetic resonance image (P = 0.002), and statistically significant prolongation of survival as compared with mice that received UV-inactivated virus and untreated mice (P = 0.02). Histological examination of brains of MV-CEA-treated animals revealed complete regression of the tumor with the presence of a residual glial scar and reactive changes, mainly presence of hemosiderin-laden macrophages. In addition, CEA levels in the peripheral blood in both the s.c. and orthotopic models increased before tumor regression, indicating viral gene expression, and returned to normal when the tumors regressed. Ifnar(ko) CD46 Ge transgenic mice, susceptible to MV infection, were used to assess central nervous system toxicity of MV-CEA. Intracranial administration of MV-CEA into the caudate nucleus of Ifnar(ko) CD46 Ge did not result in clinical neurotoxicity. Pathologic examination demonstrated limited microglial infiltration surrounding the injection site. In summary, MV-CEA has potent antitumor activity against gliomas in vitro, as well as in both s.c. and orthotopic U87 animal models. Monitoring CEA levels in the serum can serve as a low-risk method of detecting viral gene expression during treatment, and could allow dose optimization and individualization of treatment.
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PMID:Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. 1275 Feb 67

Recent studies have suggested that carcinoembryonic antigen (CEA)-promoter sequences are active only in CEA-positive cells, filing in the criteria for tumor specific targeting of suicide genes. However, the present study on gene therapy of colon cancer and cell-specificity of CEA promoter, provide evidence that CEA-positive and CEA-negative cells transfected with E. coli cytosine deaminase (CD) gene under the control of CEA promotor sequence are sensitive to enzyme/pro-drug therapy with 5-fluorocytosine (5-FC). Individual clones derived from the CEA-negative cell lines: melanoma Hs294T and glioblastoma T98G after transfection with CD differed profoundly in their sensitivity to 5-FC. The IC50 values for several clones of the CEA-negative cells were almost the same as for CEA-positive colon cancer cells. Such 5-FC-sensitive clones derived from the population of CEA-negative cells, present even in small number, because of the very effective bystender effect of this enzyme/pro-drug system can cause severe problems during therapy by efficiently killing surrounding normal cells. Safety is the major issue in gene therapy. Our data suggest that the safety of gene-directed enzyme pro-drug therapy (GDEPT) with CEA promoter driven expression of therapeutic genes is not so obvious as it has originally been claimed.
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PMID:CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter. 1544 34

Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor activity against glioma lines and orthotopic xenografts; this compares favorably with the MV strain expressing the human carcinoembryonic antigen, which is currently in clinical testing. Expression of NIS protein in infected cells results in effective concentration of radioactive iodine, which allows for in vivo monitoring of localization of MV-NIS infection by measuring uptake of (123)I or (99m)Tc. In addition, radiovirotherapy with MV-NIS followed by (131)I administration resulted in significant increase of MV-NIS antitumor activity as compared with virus alone in both subcutaneous (p=0.0003) and orthotopic (p=0.004) glioblastoma models. In conclusion, MV-NIS-based radiovirotherapy has significant antitumor activity against glioblastoma multiforme and represents a promising candidate for clinical translation.
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PMID:Effective radiovirotherapy for malignant gliomas by using oncolytic measles virus strains encoding the sodium iodide symporter (MV-NIS). 2218 60