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 presence of dominant transforming genes in human tumor cell lines has been investigated. High molecular weight DNAs isolated from cell lines established from carcinomas and sarcomas of various organs as well as from a glioblastoma and two melanomas were utilized to transfect NIH/3T3 mouse fibroblasts. The DNAs of T24 and A2182, two cell lines derived from a bladder and a lung carcinoma, respectively, and of HT-1080, a cell line established from a fibrosarcoma, were able to transform recipient NIH/3T3 cells. First-cycle transformants exhibited anchorage-independent growth and were tumorigenic in athymic and immunocompetent mice. Moreover, they contained human DNA sequences and were able to transmit their malignant phenotype in additional cycles of transfection. Southern blot analysis of T24-derived transformants showed that a single fragment of human DNA specifically cosegregated with the malignant phenotype, suggesting that it contained the T24 oncogene. Therefore, these human sequences were molecularly cloned with lambda Charon 9A as the cloning vector. The resulting recombinant DNA molecule, designated lambda T24-15A, was shown to contain a 15-kilobase-pair EcoRI insert of human cellular DNA. lambda T24-15A DNA (either intact or EcoRI digested) transformed NIH/3T3 fibroblasts with a specific activity of 20,000 focus-forming units per pmol of cloned DNA. Our results indicate that we have molecularly cloned a biologically active oncogene present in T24 human bladder carcinoma cells.
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PMID:Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells. 695 33

Total cellular RNAs from a variety of fresh and culture-derived human hematopoietic neoplastic cell types at various stages of differentiation and human sarcoma, carcinoma, melanoma, and glioblastoma cell lines were enriched for poly(A)- containing sequences, fractionated by gel electrophoresis, and blot hybridized to a cloned DNA probe containing the transforming sequences (v-amv) of avian myeloblastosis virus (AMV), a virus known to cause myeloid leukemias in chickens. Expression of RNA sequences homologous to AMV was detected in all immature myeloid and lymphoid T cells in addition to the single erythroid cell line examined, but not in mature T cells or in B cells, including lymphoblast cell lines derived from patients with Burkitt lymphoma. In addition, induction of the cell line HL60, a promyelocytic leukemia line, to differentiate with dimethyl sulfoxide or retinoic acid resulted in a reduction of the level of expression of the human cellular gene c-amv homologous to v-amv. There was no detectable c-amv mRNA in any of the solid tumor cell lines examined. Thus, expression of the human c-amv gene could be correlated with the stage of differentiation of different hematopoietic cell types determined by morphologic and marker studies. Expression of c-amv could not be correlated with the extent of methylation in HL60 and in HL60 induced to differentiate with dimethyl sulfoxide.
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PMID:Differential expression of the amv gene in human hematopoietic cells. 695 33

Since May 1978 the hypoxic-cell radiosensitizer, misonidazole (MIS), has been under clinical investigation in a phase III trial with multiple doses of the drug in 11 patients with brain tumours (seven glioblastomas, four recurrent brain tumours) and three patients with oesophageal carcinoma. The doses of MIS administered were usually well tolerated but the principal toxicities observed were peripheral neuropathy as well as nausea and vomiting was completely reversible. The incidence of neuropathy was not related to the pharmacological parameters of plasma level or half-life. Pharmacological assessment by high-pressure liquid chromatography included assays of plasma, urine and cerebrospinal fluid. The demethylated product, Ro-05-9963, was detected as the major metabolite. Peak plasma levels were obtained one to four hours after administration of MIS, with a half-life of five to ten hours. Cerebrospinal fluid levels of MIS correlated well with those of the plasma. MIS was mainly excreted as the demethylated metabolite, but less than 40% of the given dose could be recovered. The results obtained suggest that the present MIS dosage for glioblastoma patients results in a low plasma level with no observable therapeutic effect.
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PMID:Misonidazole as a radiosensitizer in the radiotherapy of glioblastomas and oesophageal cancer. Pharmacokinetic and clinical studies. 701 90

A survey of 56 normal and neoplastic tissues has shown that plasminogen activators were released by cultured human cells in several molecular weights and their susceptibility to inhibition by antibodies to the normal urinary enzyme, urokinase. Melanoma cells characteristically secreted plasminogen activators which were immunochemically distinct from urokinase and which migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a prominent, closely spaced doublet with an apparent molecular weight of approximately 70,000 and a minor molecular weight component of approximately 60,000. Enzymes with similar characteristics have been observed in serum-free harvest fluids collected from other neoplastic tissue (a breast carcinoma, a glioblastoma, a malignant teratoma, a uterine sarcoma, and a carcinoma of the renal pelvis) and from normal tissue (8-week embryo fibroblasts, normal esophageal fibroblasts, and one culture of normal adult bladder epithelium). Plasminogen activators released by cells derived from most normal adult tissues, or from a 26-week-old embryo, and from other tumors of ectodermal or mesenchymal origin were inhibited by anti-urokinase antibody and showed a closely spaced doublet with a molecular weight of 60,000 as the most abundant molecular species with no evidence of the enzyme with a molecular weight of 70,000.
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PMID:Molecular species of plasminogen activators secreted by normal and neoplastic human cells. 719 17

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

Eighty patients older than 65 years underwent craniotomy for primary or secondary brain tumors. Glioblastoma was the most common tumor, followed by metastatic carcinoma and meningioma. Three patients died within 30 days of surgery. Twenty-three patients showed development of postoperative systemic complications, of which pulmonary complications were most common. Thirty-seven (44%) of the patients showed significant improvement, but 13 (21%) became worse after surgery. Most brain tumors in elderly patients are operable. However, the surgical indications should be determined by the nature of the tumor and the condition of the individual patient. Preoperative and postoperative management must be more demanding if systemic complication are to be avoided.
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PMID:Brain tumors in the elderly. 724 29

An immunological study about the lymphocytes of nineteen patients affected by glioblastoma has been executed by using CML and ADCC tests. Eleven healthy subjects and nine ones affected by bladder carcinoma have been studied for control. The CML test has demonstrated an increase of citotoxic activity of lymphocytes in the totality of the patients affected by glioblastoma (37,09 +/- 3,67)% versus (4,00 +/- 1,78)% of controls. The ADCC test has demonstrated diminution of citotoxic activity of lymphocytes of the patients affected by glioblastoma in comparison with controls (20,57 +/- 9,77)% versus (29,18 +/- 6,67)% of the healthy controls versus (27,66 +/- 8,51)% of bearers of bladder carcinomas.
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PMID:[In vitro cytotoxicity in the immunological study of human glioblastomas]. 730 7

Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.
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PMID:Suppression of tumor growth in vivo by local and systemic 90K level increase. 754 66

We have previously reported the tissue specific distribution of four different FGF-1 transcripts containing alternative 5' untranslated exons spliced to the first protein coding exon. The predominant transcript in brain is FGF-1.B and in kidney FGF-1.A. Others have shown, by in situ hybridization and immunohistochemical analysis, that expression of FGF-1 in the brain is exclusively in neural cells but not in glial cells. Here we have examined the distribution of FGF-1.B and FGF-1.A transcripts in glioblastoma and retinal tissues and in kidney carcinoma cell lines. Our results show that FGF-1.B is the predominant transcript in neural derived tissues including both the diabetic retina and normal retina tissues. Surprisingly, FGF-1.B transcript is highly expressed in glioblastoma tissues. In contrast, a normal brain glial cell line, CHII, expresses very low levels of FGF-1 mRNA. These results strongly implicate the role of FGF-1 in the etiology of glioblastoma. We also examined several kidney carcinoma derived cell lines for the expression of FGF-1 mRNA. Most of these kidney cell lines do not express any FGF-1 transcripts. An interpretation by deduction is that kidney adenocarcinomas are derived from cortex but medulla has been reported as the site of FGF-1 synthesis. Of the kidney derived cell lines which are positive for FGF-1 message, only one expressed FGF-1.A transcript. The data may suggest that the establishment of kidney cell lines results in a switch of promoter usage from the 1.A seen in kidney tissue. Similarly, culturing of glioma cell lines may result in a switch from FGF-1.B seen in glioma tissues to FGF-1.D seen in most glioma cell lines. Continued studies of the FGF-1 transcripts, their functional promoters and their tissues distribution will provide insight into the potential role of FGF-1 in cell growth, tissue differentiation and malignant transformation.
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PMID:Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines. 754 53

Human HT1080 fibrosarcoma cells, subclone H4, express little or no Egr-1 (Zif/268, Krox 24), an early growth response gene encoding a transcription factor. Phorbol ester (but not serum) treatment only can elicit a small increase in Egr-1 expression in H4, in contrast to the normally rapid, high transient expression of Egr-1 observed after the addition of a wide range of stimulating agents to normal or immortalized cell lines. Because several human tumor cell lines express little Egr-1, we tested the hypothesis that this loss was causal to transformation. We report here that the expression of exogenous mouse Egr-1 in H4 cells inhibits transformed growth in a dose-dependent manner and significantly suppresses tumorigenicity in athymic mice. By overexpression of the fragment in Egr-1 that is responsible for its DNA-binding activity, the zinc-finger domain, we show that this domain has a similar activity. Moreover, the expression of antisense mRNA encoding the DNA-binding domain increases the transformed character of the H4 cells. One possible conclusion is that endogenous Egr-1-like genes perform growth-regulatory functions. Other human tumor lines are also growth suppressed by Egr-1 overexpression including ZR-75-1 breast carcinoma, U251 glioblastoma, and to a lesser extent, SAOS-2 osteosarcoma cells. These results are surprising in light of the "early growth response" character of Egr-1 but extend our earlier report of suppression of growth in v-sis-transformed NIH3T3 cells.
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PMID:Egr-1 negatively regulates human tumor cell growth via the DNA-binding domain. 758 51


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