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)

To document over-expression of proto-oncogenes in tumors, it is necessary to determine the level of expression in the progenitor normal tissue. These studies compare the levels of nuclear transcription of a series of growth-factor related genes and proto-oncogenes in human glioblastoma cell lines with those in three normal glial cell populations. The unusual finding was that levels in the three normal glial cell populations varied considerably for several genes and thus overexpression of a specific gene in a tumor cell when compared to just one normal glial cell population would not necessarily represent overexpression. In this study, we compared the level of 17 genes in 7 tumors to the highest level of each gene found in any of three normal glial cell populations. Over-expression of PDGF-B in 4/7 glioblastoma cell lines, EGFR in 1/7, neu in 1/7 IGF-2 in 1/7 and ros in 2/7 was observed. The variation observed in the normal glial cell populations emphasizes the possibility that the normal glial cell populations represent different glial cell lineages and/or stages of differentiation and that the tumors could have arisen from different normal glial cells. Matching lineages of normal and tumor cells, probably by monoclonal antibody reactions, may be required to accurately define over-expression.
Cancer Lett 1992 Jul 31
PMID:Transcriptional patterns of growth factors and proto-oncogenes in human glioblastomas and normal glial cells. 132 85

We have associated pharmacological studies to a semi-quantitative evaluation of P-glycoprotein(s) expression, to establish if classical multidrug resistance (MDR) could account for the complete resistance phenotype exhibited by progressively doxorubicin-resistant rat glioblastoma cells. Three resistant variants (C6 0.001, C6 0.1 and C6 0.5) of the C6 glioblastoma cell line (C6 S) were selected by long-term culture in the presence of three concentrations of doxorubicin (0.001, 0.1 and 0.5 microgram.ml-1 respectively). The degree of doxorubicin resistance was respectively 7, 33 and 400, and all the cell variants were cross-resistant to m-AMSA, etoposide and vincristine. Doxorubicin incorporation was reduced similarly in all resistant cells, irrespective of the level of resistance. When exposed to their respective doxorubicin IC50, the 7-fold resistant cells had the same intracellular drug incorporation as the sensitive cells, whereas the 33-fold and 400-fold resistant cells could incorporate respectively 3.7 and 17 times more drug. The ratio of doxorubicin exposures required for 50% DNA synthesis inhibition and 50% growth inhibition was dependent on the degree of resistance; this ratio was 12.8 in C6 S, 11.6 in C6 0.001, 6.3 in C6 0.1 and 1.8 in C6 0.5. P-glycoprotein(s) overexpression was of the same magnitude as the resistance factor in variants C6 0.001 and C6 0.1, but was lower than resistance factor in variant C6 0.5. Reversal of drug incorporation by verapamil was complete in all resistant cell lines; however, reversal of doxorubicin cytotoxicity was complete only in the 7-fold resistant line and was only partial in the most resistant lines, which remained 10-fold and 20-fold resistant to doxorubicin. These results suggest that classical MDR was the first phenotype selected by doxorubicin in C6 0.001, whereas mechanism(s) of doxorubicin resistance other than classical MDR are added in the most resistant lines.
Br J Cancer 1992 Apr
PMID:P-glycoprotein overexpression cannot explain the complete doxorubicin-resistance phenotype in rat glioblastoma cell lines. 134 23

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.
Cancer 1992 Mar 15
PMID:Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis. 137 13

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with 131I. Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (greater than 50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after II months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.
Int J Cancer 1992 Apr 22
PMID:Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I-labelled anti-tenascin monoclonal antibody BC-2. 137 10

In order to evaluate a possible significance of the expression of proliferating cell nuclear antigen (PCNA) as clinically useful prognostic parameter, we retrospectively investigated a series of 40 glioblastomas by means of immunohistochemistry and compared the results to patient survival. All glioblastomas included in the study had been treated by operation, radiotherapy and intraarterial ACNU [3-(4-amino-2-methyl-5-pyrimidinylmethyl)-1-(2-chloroethyl)-1-nitr osourea] chemotherapy. Patient survival ranged from 2 months to 42 months (mean: 14.2 months). PCNA values varied widely, ranging from 0.5% to 75% (mean: 24.9%). Statistical analysis revealed no significant correlation between PCNA index and patient survival. Our study thus indicates that the expression of PCNA appears not to be a useful prognostic parameter for glioblastoma patients.
J Cancer Res Clin Oncol 1992
PMID:Immunohistochemical demonstration of proliferating cell nuclear antigen in glioblastomas: pronounced heterogeneity and lack of prognostic significance. 137 10

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.
Cancer Res 1992 Jun 15
PMID:Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene. 137 70

Tumor cells of a particular tissue may show a pattern of gene expression characteristic of the precursor cells of this tissue. To test this proposition for tumors of the central nervous system (CNS) we have used immunohistochemistry to analyze the expression of nestin in primary human CNS tumors and corresponding nonneoplastic brain tissue. Nestin defines a recently discovered sixth class of intermediate filament proteins and in the rat is expressed predominantly in CNS stem cells. In the adult nonneoplastic human brain we have detected only nestin expression in occasional endothelial cells. In contrast, a variety of primary CNS tumors contained substantially elevated nestin levels. The nestin-positive cells in the tumor tissue were tumor cells and/or endothelial cells. Glioblastomas expressed higher nestin levels than less malignant gliomas. This may indicate a correlation between nestin expression and malignancy within the glioma tumor group. In the primitive neuroectodermal class of tumors we observed both nestin-expressing and nonexpressing tumors, suggesting that nestin expression could be used to further characterize this complex and heterogeneous tumor group. Nine metastatic carcinomas were studied, and none showed nestin immunoreactivity in tumor cells. In conclusion, our data support the notion that primary CNS tumors share gene expression patterns with primitive, undifferentiated CNS cells and that nestin, like other intermediate filaments, may be useful in tumor diagnosis.
Cancer Res 1992 Oct 01
PMID:Expression of the class VI intermediate filament nestin in human central nervous system tumors. 138 41

The effectiveness of boron neutron capture therapy is predicted to be dependent not only on the amount of boron taken up by the target cells but also on the intracellular distribution of boron. Using the isotopic imaging technique ion microscopy, we have quantitatively determined uptake and intracellular distribution of Na2B12H11SH, a promising boron drug for boron neutron capture therapy, in four human cell lines: U87 glioblastoma cells, HeLa epithelioid carcinoma cells, GM 2408b mutant skin fibroblasts, and GM 3348b skin fibroblasts. The boron uptake of all four cell lines, after exposure to 100-500 micrograms/ml Na2B12H11SH, increased as the dosages were increased but showed a tendency toward saturation. Boron was more concentrated in the cytoplasm than in the nucleus but was not strongly localized within cells. There were no significant differences in boron uptake among the four cell lines. A retention experiment identified at least two different intracellular boron pools, and cells lost greater than 60% of intracellular boron within 1 h upon changing to Na2B12H11SH-free medium, indicating a largely low affinity binding.
Cancer Res 1992 Oct 01
PMID:Quantitative imaging of a radiotherapeutic drug, Na2B12H11SH, at subcellular resolution in tissue cultures using ion microscopy. 139 24

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
Cancer Immunol Immunother 1992
PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

Primary CNS lymphomas (PCNSL), until recently representing about 1% of all brain tumors, show dramatically increased incidence both in high-risk groups (immunocompromised, AIDS) and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas, the morphology and classification of which are identical to those of systemic lymphomas, although PCNSL show different biological behavior and diagnosis according to the New Working Formulation and updated Kiel classification may be difficult. The majority are large B cell variants of high-grade malignancy; low-grade subtypes and T cell lymphomas are rare. Sixty per cent occur in the supratentorial space (hemispheres, periventricular) and 12% in the posterior fossa; 30% are multiple (50%-70% in AIDS). PCNSL show a male preponderance with a peak incidence in the 5th-7th decade (3rd-4th in AIDS). The duration of diffuse or focal clinical symptoms averages 1-2 months. Computed tomography and magnetic resonance imaging scans show single or multiple or diffuse, often typical lesions. Diagnosis is achieved by evaluation of stereotactic biopsy material or cerebrospinal fluid cytology using immunocytological markers. Current therapy in immunocompetent patients, radiation plus corticosteroids and pre- or postradiation polychemotherapy, shows response rates of 85% with a median survival of 17-44 months, a prognosis similar to that for glioblastoma. Meningeal PCNSL is treated with intrathecal methotrexate or cytosine arabinoside. Transliquoral seeding of PCNSL is frequent, distant metastases occurring in 6%-8%. Therapy of AIDS-related PCNSL makes use of radiation and corticosteroids, and rarely of chemotherapy. The pathogenesis of PCNSL is unknown, but Epstein-Barr virus may be a contributory factor.
J Cancer Res Clin Oncol 1992
PMID:Primary central nervous system lymphomas--an update. 140 May 70


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