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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The regulation of microvessel formation and the expression of CNS-specific endothelial properties are attributed to perivascular astroglia. Specific proteolytic pathways mediate processes such as tissue remodeling, differentiation, invasion, and metastasis. We used a coculture system in which C6 glial cells induce CNS microvascular endothelial cells to form capillary-like structures to examine the role of plasminogen activators and collagenases in CNS microvessel morphogenesis. Fibrin zymography revealed the presence of high-molecular weight urokinase-type plasminogen activator (uPA), low-molecular weight uPA, and uPA/inhibitor complexes within endothelial cultures and cocultures. Gelatin zymography revealed the presence of 92-, 72-, and 62-kDa type IV collagenases within endothelial cultures and cocultures. uPA activity was confirmed by incubating the extracts with amiloride, an inhibitor of uPA. Collagenase activity was confirmed by incubating the gels with EDTA, an inhibitor of metalloproteinases. Quantitative densitometry showed a six- to eightfold decrease in coculture uPA during capillary-like structure formation. Substantially less change in type IV 72-kDa procollagenase activity was seen in cocultures during capillary-like structure formation, but active type IV 62-kDa collagenase activity was significantly increased during capillary-like structure formation. These findings establish that uPA and activated type IV collagenase activity specifically regulates morphogenic endothelial responses to glial interactions and suggest mechanisms by which microvessels respond within the CNS.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Neurosurgical review 12 (1989), S. 197-203 
    ISSN: 1437-2320
    Keywords: Human gliomas ; in vitro chemosensitivity test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several in vitro chemosensitivity assays have been developed for predicting clinical response to chemotherapeutic and biologic agents, alone and in combinations. The most widely accepted assay is the colony forming assay (CFA) which assesses the clonogenic capability of stem cells. Other methods include growth inhibition assays by evaluating cell number; thymidine incorporation; or amino acid uptake. More recently an automatic colorimetric technique utilizing crystal violet dye or a tetrazolium (MTT) vital dye has been developed for more rapid assessment of cytotoxic or growth inhibitory activity in vitro. Several reports have compared the results of in vitro tests with patients' clinical response. Two major problems affect the predictive value of in vitro chemosensitivity tests. The foremost is cellular heterogeneity which exists within a single tumor as well as between tumors. Artificial selective pressure inherent to tissue culture system is the other problem. In general, in vitro tests predict clinical resistance more consistently than clinical sensitivity. However, chemosensitivity assays remain useful in screening new agents and preclinical modeling of clinical trials.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 15 (1993), S. 265-267 
    ISSN: 1573-7373
    Keywords: neurotoxicity ; interleukin-2 ; neuropsychological testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case is reported of a 40 year old woman treated with intraventricular IL-2 for leptomeningeal disease who developed progressive cognitive dysfunction. This deterioration started 3 months post-treatment and worsened over the ensuing 4 years. MRI revealed white matter abnormalities that were not present on the pretreatment scan. Although free of disease, the patient has a subcortical dementia and is unable to work. The potential for progressive brain injury and subsequent disability related to intraventricular IL-2 therapy is discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7373
    Keywords: brain tumor research ; brain tumor therapy ; polyamines cell kinetics ; radiation necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proceedings of the 9th International Conference on Brain Tumor Research and Therapy: 1. Introduction; 2. Surgery; 3. Radiation therapy; 4. Chemotherapy; 5. Immunotherapy; 6. Growth-regulatory alterations; 7. Molecular genetics; 8. Brain tumor invasion; 9. Normal tissue damage; 10. Polyamines.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 12 (1992), S. 131-135 
    ISSN: 1573-7373
    Keywords: malignant gliomas ; chemotherapy ; carmustine ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-five patients with malignant gliomas were treated after aggressive surgical resection with alternating intravenous carmustine and cisplatin both during and after radiation therapy. Thirty-three patients were considered evaluable for responses, 17 had glioblastoma multiforme (GBM),14 had anaplastic astrocytoma (AA) and 2 had anaplastic oligodendroglioma (AO). The median age of the evaluable patients was 47 years. The median time to tumor progression was 34.5 weeks, and the median survival for the entire group was 76 weeks. Early progression occurred more frequently in patients with glioblastoma than in those with AA or AO. Seventeen patients (55%) were alive at 18 months (6 GBM, 9 AA, 2 AO). Toxicity was mainly hematologic, otic and tolerable. The results suggest that further trial is warranted to assess the efficacy of alternating carmustine and cisplatin in conjunction with radiation therapy postoperatively in patients with malignant gliomas.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7373
    Keywords: malignant glioma ; recurrent ; chemotherapy ; interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recombinant interferon beta (IFN-βser) has been administered by intravenous bolus injection three times weekly at a dose of 90 × 106 IU to 14, patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-βser appears to have activity in human glioma and is well tolerated at this dosage and schedule.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7373
    Keywords: astrocyte progenitors ; medulloblastoma ; differentiation ; differentiation modulators ; glial fibrillary acidic protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Medulloblastomas are cerebellar tumors which are primarily composed of sheets of uniform, small malignant cells and may have astrocytic, neuronal or no features typical of these cell types. The assessment of astrocytic differentiation in medulloblastoma rests largely on the detection in malignant cells of glial fibrillary acidic protein (GFAP), a marker present in the later stages of normal astrocyte differentiation. It is still not known whether cells that do not contain GFAP in medulloblastomas with astrocytic differentiation correspond to highly proliferative astrocyte progenitors in maturation arrest at earlier stages of differentiation. The purpose of the current study was to examine whether cells in short term culture derived from a medulloblastoma tumor specimen with astrocytic differentiation were of the astrocytic lineage and if so, whether they represented proliferative astrocyte progenitors which would morphologically and antigenically mature in response to differentiating agents. A portion of tumor specimen from a 10-month-old child with recurrent posterior fossa medulloblastoma (RB2) that contained GFAP focally in tumor cells was grown in monolayer culture. We examined cellular structure and appearance of western immunoblotting and immunohistochemical studies for GFAP and neuron-specific enolase (NSE) in RB2 cells before and after treatment with retinoic acid (RA) and dibutyryl cyclic AMP (dBcAMP). RB2 in culture consisted of small polygonal cells (93%), large flat cells (3%), and polygonal cells with cytoplasmic processes (4%). In untreated RB2, 30% of cells expressed GFAP and staining for NSE was negative. RA treatment produced flattened cells and decreased GFAP. DBcAMP reversibly induced fine cytoplasmic processes containing GFAP in 85% of cells within 96h. Neither agent induced NSE. The results suggest that cultured cells which are derived from a medulloblastoma with astrocytic differentiation do not spontaneously differentiate but that treatment with dBcAMP suppresses proliferation, enhances cytoplasmic process formation and increases cytoplasmic GFAP. Cells in culture and in medulloblastoma tumor specimens which do not contain GFAP may represent astrocyte progenitors in maturation arrest.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0730-2312
    Keywords: epidermal growth factor ; brain tumors ; cell surface glycoproteins ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The expression of epidermal growth factor (EGF-R) in normal glial and glioma cells grown in culture was examined by using several independent assays. Immunoprecipitation with the monoclonal antibody R1 of extracts from metabolically labeled glial and glioma cells revealed a protein of Mr ∼ 170,000, with a migration in sodium dodecyl sulfate-polyacrylamide gels identical to the EGR-R of A431 epidermal carcinoma cells. Furthermore, in the majority of glioma extracts, a protein of Mr ∼ 190,000 was specifically immunoprecipitated by this antibody. Similar results were obtained by immunoblotting with a second antibody directed against a synthetic peptide in the sequence of the V-erb-B oncogene. In cell lines expressing both proteins, each was specifically phosphorylated on tyrosine in immune complex kinase assays. The majority of glioma cells bound between 40,000 to 80,000 125I-labeled epidermal growth factor molecules per cell. These results suggest that the expression of EGF-R is common in cultured human glioma cells. In addition, a structurally related protein, is expressed in some of these cells.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 42 (1990), S. 83-94 
    ISSN: 0730-2312
    Keywords: growth regulation ; EGF-receptor ; signal transduction ; glycoconjugates ; tyrosine kinase ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The growth inhibitory effects of exogenously added retinoic acid (RA) on various cultured human glioma cells was observed to be heterogenous, with an ID50 ranging from 10-7 M to no response. The protein tyrosine kinase activity of epidermal growth factor receptor (EGF-receptor) appeared to parallel the cell's growth responsiveness to RA. Cells sensitive to RA-induced growth inhibition exhibited a dose-dependent decrease in EGF-receptor activity, whereas RA-resistant cells showed no alterations in EGF-receptor protein tyrosine kinase activity or expression. The modulation of EGF-receptor by RA was further examined with RA-sensitive (LG) and -resistant (NG-1 ) cell lines. Both cell lines were approximately equal in their ability to bind and internalize epidermal growth factor in the presence or absence of RA. Several independent assays suggested that the inhibition of EGF-receptor activity was independent of protein kinase C modulation as mediated by phorbol myristate acetate. However, alterations in associated glycoconjugates of EGF-receptor were observed among the sensitive cells but not the resistant cells. These results suggest RA-induced growth inhibition in sensitive cells may arise, at least in part, through alterations in EGF-receptor activity and structure.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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