Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ACNU on the in vitro viability of a methylnitrosourea-induced gliosarcoma (T9) and two ethylnitrosourea-induced brain tumors, TR-481 (a malignant neurinoma) and EB-679 (a glioma) was studied. T9 was highly sensitive to ACNU, demonstrating loss of cells following a 3 hour exposure time to 5 microgram/ml; TR-481 was sensitive to 40 microgram/ml of ACNU and EB-679 was highly resistant to 40 microgram/ml of ACNU. The in vitro sensitivity of the tumor cell lines to ACNU is: T 9 greater than TR-481 greater than EB-679. This data indicates that variability of response to both concentration and exposure time of ACNU of malignant brain tumor cells must be taken into consideration in planning in vitro and/or in vivo treatment of experimental brain tumors.
 ...
PMID:In vitro sensitivity of nitrosourea-induced neurogenic tumors to ACNU. 695 45

Neovascularization is a prerequisite for glioma growth, so inhibition of angiogenesis may achieve control of glioma growth. We examined whether glioma cells induce angiogenesis and proliferation in microvascular endothelial cells from Fisher 344 rat brains by co-culture in a physical separation system with rat C6 glioma cells or rat T9 gliosarcoma cells. Endothelial cells cultured on type 1 collagen formed capillary-like structures. C6 glioma cells co-cultured with endothelial cells promoted the formation of these capillary-like structures. However, conditioned medium from C6 cells inhibited the proliferation of endothelial cells. T9 cells had little effect on the formation of capillary-like structures and no effect on the proliferation of endothelial cells. We also examined the effects of human tumor necrosis factor (TNF)-alpha on the formation of the capillary-like structures and on the proliferation of endothelial cells. Human TNF-alpha inhibited the formation of capillary-like structures induced by C6 glioma cells at a concentration of 100 U/ml, as well as the proliferation of endothelial cells at a concentration of 1000 U/ml. These results indicate that induction of angiogenesis varies with glioma cell lines and angiogenesis does not correspond with proliferation of endothelial cells. TNF-alpha can inhibit angiogenesis in gliomas in vitro.
 ...
PMID:Angiogenesis in microvascular endothelial cells induced by glioma cells and inhibited by tumor necrosis factor in vitro. 754 Nov 18

Intracranial tumor classification is paralleled by a grading system that empirically compares tumor entities with "progression stages" of supratentorial gliomas of the adult. This grading system is an integral part of the WHO classification. Glioma progression has originally been defined by descriptive morphology. In this respect, morphological key features of high-grade gliomas (WHO grades III and IV) are microvascular proliferation and the formation of tumor necroses. Glioma progression is now more accurately defined on the molecular genetic level by a stepwise accumulation of oncogene activation and/or tumor suppressor gene inactivation. Angiogenesis occurs during development and progression of glial tumors. Pathological vessels are a hallmark of malignant glioma and it has therefore been suggested that malignant glioma cells are able to induce neovascularization. Despite the exuberant neovascularisation, however, vascular supply may not be sufficient for tumor areas with high cell proliferation, and necroses may develop. Malignant transformation of blood vessel itself is a rare event but may be the underlying mechanism of gliosarcoma development. The recently purified vascular endothelial growth factor (VEGF) is at present the only mitogen known to selectively act on endothelial cells. Growing evidence suggests that VEGF is the key regulator of developmental and pathological angiogenesis. In vivo, VEGF mRNA is upregulated in a subpopulation of malignant glioma cells adjacent to necroses. Since VEGF is hypoxia-inducible, hypoxia may be an important regulator of VEGF mRNA expression and tumor angiogenesis in vivo. Two tyrosine kinase receptors for VEGF are expressed in vessels which invade the tumor, suggesting that tumor angiogenesis is regulated by a paracrine mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vascular morphology and angiogenesis in glial tumors. 758 Jan 12

Camptothecin, a naturally occurring inhibitor of the DNA-replicating enzyme topoisomerase I, demonstrated promising anti-tumor activity in pre-clinical testing; however, because of unexpected toxicity and low anti-tumor effects in the initial clinical trials, further testing was discontinued. We hypothesized that local controlled delivery of camptothecin sodium would achieve effective concentrations in brain tumors without the observed systemic side effects, thereby allowing this novel drug to be used to treat patients with malignant gliomas. To test this hypothesis, we evaluated the sensitivity of rat glioma lines and established human glioma lines to camptothecin in vitro. We found that the LD90 for the established rat and human lines was 0.3 to 1.4 microM after a 1 hr exposure and decreased to less than 0.1 microM after continuous exposure for 7 days. We loaded camptothecin into a controlled-release polymer (ethylene-vinyl acetate co-polymer; EVAc) and showed by high-pressure liquid chromatography that controlled release occurred over at least 21 days. We then tested camptothecin against 9L gliosarcoma, implanted into the brain of Fischer 344 rats. Five days after tumor implantation, animals were treated with camptothecin delivered either systemically or locally by release from EVAc. Local controlled delivery by the polymer significantly extended survival: 59% of the treated animals were long-term survivors (> 120 days) compared to 0% of controls. Systemic administration did not extend survival compared to controls. We compared the efficacy of camptothecin delivered locally with a polymer to camptothecin injected directly into the tumor. Camptothecin increased survival only when delivered locally by polymer.
 ...
PMID:Local delivery of the topoisomerase I inhibitor camptothecin sodium prolongs survival in the rat intracranial 9L gliosarcoma model. 766 33

Formalin-fixed, paraffin-embedded surgical specimens from 140 primary human central nervous system tumors, including 51 meningiomas, 26 astrocytomas, 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 5 ependymomas, 2 subependymomas, 9 medulloblastomas, and 3 paragangliomas, were immunostained using a streptavidin/peroxidase method and the PC10 monoclonal antibody, which recognizes an epitope on the proliferating cell nuclear antigen (PCNA). The following PCNA labeling index (LI) mean values were found for the above neoplasms: meningiomas, 3.80 +/- 7.35%; astrocytomas, 0.65 +/- 1.03%; anaplastic astrocytomas, 8.46 +/- 7.95%; glioblastomas, 10.26 +/- 11.21; gliosarcoma, 46.34%; oligodendrogliomas, 2.31 +/- 3.59%; ependymomas, 1.12 +/- 2.10%; medulloblastomas, 23.91 +/- 11.95%; and paragangliomas, 2.07 +/- 1.86%. Collectively, our findings indicate that while benign central nervous system tumors generally have low PCNA LI values, consistent over-expression of PCNA epitopes was noted in some examples, especially in a number of meningiomas. Among the malignant neuroectodermal tumors, medulloblastomas were found to have the highest PCNA LI values, corresponding to their histological grade of malignancy, and malignant glial tumors generally displayed significantly higher PCNA LI values, than their benign counterparts. Although in our study mean PCNA LI values seemed to reflect histological grading, large discrepancies were noted in all tumor groups. Our data, therefore, suggest than PCNA immunoreactivity can not be considered reliable for predicting the prognosis of the disease in individual cases.
 ...
PMID:Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms. 768 17

A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor alpha, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
 ...
PMID:A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. 776 95

The effect of copper (Cu) depletion on the growth of tumors was investigated in a rat brain tumor model. 9L gliosarcoma cells were injected subcutaneously in 5-week-old male Fischer-344 rats. The control group (n = 18) received a normal diet throughout the experiment and the depletion group (n = 18) received a Cu-deficient diet starting 3 weeks prior to tumor implantation, and 2 mg of D-penicillamine orally, once daily, on the 3 days before and after implantation. Six animals from each group were killed at 1, 2, and 3 weeks following the implantation to measure the tumor weights and determine the tissue Cu concentration by atomic absorption spectrophotometry. The tumor weights increased much more rapidly in the control than in the depletion group. The Cu concentrations in tumor tissue of the depletion group were significantly lower than in the control group. There was no statistical significance in Cu concentration in the brain tissues of the control and depletion groups. Our study indicated that a Cu-deficient diet and D-penicillamine treatment can inhibit subcutaneous glioma growth in this rat model.
 ...
PMID:Suppression of tumor growth in experimental 9L gliosarcoma model by copper depletion. 890 16

This study investigated the independent and combined effects of photodynamic therapy (PDT), laser photodynamic hyperthermia (LPDH) and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) in a rat 9L induced gliosarcoma model. The mortality rate (MR60), mean survival time (MST60), and increasing life span (ILS60) within 60 days were determined to evaluate the therapeutic effect in vivo. The MR60 and MST60 of the gliosarcoma tumor control were 100% and 16.2 days. The ILS60s of PDT and ACNU were 72.84% and 49.81%, respectively, but MR60 of both were 86.72%. All combined treatments produced significantly prolonged survival (P < 0.01). The combined effects of LPDH and ACNU, MR60, MST60, and ILS60 were 60%, 43 days, and 165.4%, respectively. The ILS60 of PDT + ACNU (96.48%) and PDT + LPDH (98.58%) also indicated a synergistic or additive effect. The survival fraction and synthetic rate of DNA, RNA, and protein of glioma 9L tumor cells in vitro after single treatment of PDT or combined with antitumor drugs and laser showed that the cytotoxicity of PDT to 9L tumor cell was obvious by using Rh123, HPD, and Pf-II as photosensitizers. Combined treatments of PDT, antitumor drugs, and laser suppressed the synthesis of DNA, RNA, and protein more significantly than single treatment with PDT.
 ...
PMID:Therapeutic effects of photosensitizers in combination with laser and ACNU on an in vivo or in vitro model of cerebral glioma. 777 98

Interphase cytogenetics, i.e., in situ hybridization using probes to chromosome-specific DNA, enables histological identification of cells bearing numerical chromosome aberrations and cytogenetic analysis of composite tumors. We studied routinely processed tissues from seven glioblastomas and three gliosarcomas using biotinylated probes to pericentromeric alpha-satellite sequences on chromosomes 10, 17 and X. By applying various pretreatment protocols, an evaluable compromise between morphology and signal intensity was obtained in most cases. Compared to vascular cells with normal chromosomal counts, a significant subpopulation of glioblastoma cells showed monosomy 10 (four of five cases), monosomy 17 (one of seven cases) and loss of one X chromosome (one of seven cases). All monosomy 10 cases comprised additional areas where two copies of chromosome 10 were retained. Among the gliosarcomas, both the glioma and the sarcoma portion showed monosomy 10 in one case and monosomy 17 in another case. In contrast, in the third case of gliosarcoma, monosomy 10 was found only in the glioma portion, whereas a gain of chromosome X was observed in the sarcoma portion. We conclude that: (1) numerical chromosome aberrations can be detected in routinely processed brain tumor biopsy specimens using interphase cytogenetics, making retrospective studies feasible; (2) glioblastomas show intratumoral cytogenetic heterogeneity with formation of monoclonal cell clusters; and (3) sarcoma and glioma elements in gliosarcomas may exhibit the same or different numerical chromosome aberrations, suggesting various histogenetic pathways of the sarcoma-like portion.
 ...
PMID:Interphase cytogenetics of glioblastoma and gliosarcoma. 784 70

The efficacy of adenovirus (ADV)-mediated gene therapy to treat brain tumors was tested in a syngeneic glioma model. Tumor cells were transduced in situ with a replication-defective ADV carrying the herpes simplex virus thymidine kinase (HSV-tk) gene controlled by the Rous sarcoma virus promoter. Expression of the HSV-tk gene enables the transduced cell to convert the drug ganciclovir to a form that is cytotoxic to dividing cells. Tumors were generated in Fischer 344 rats by stereotaxic implantation of 9L gliosarcoma cells into the caudate nucleus. Eight days later, the tumors were injected either with the ADV carrying the HSV-tk (ADV-tk) gene or a control ADV vector containing the beta-galactosidase (ADV-beta gal) gene and the rats were treated with either ganciclovir or saline. Tumor size was measured 20 days after implantation of 9L cells or at death. Rats treated with ADV-beta gal and ganciclovir or with ADV-tk and saline had large tumors. No tumors were detected in animals treated with ADV-tk and with ganciclovir at doses > or = 80 mg/kg. An infiltrate of macrophages and lymphocytes at the injection site in animals treated with ADV-tk and ganciclovir indicated an active local immune reaction. In survival studies, all animals treated with ADV-tk and ganciclovir have remained alive longer than 80 and up to 120 days after tumor induction whereas all untreated animals died by 22 days. These results demonstrate that ADV-mediated transfer of HSV-tk to glioma cells in vivo confers sensitivity to ganciclovir, and represents a potential method of treatment of brain tumors.
 ...
PMID:Adenovirus-mediated gene therapy of experimental gliomas. 788 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>