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

In 13 Fischer 344 rats transplanted intracerebrally with 9 L gliosarcoma, 13 normal Fischer 344 rats and 4 clinical cases of malignant glioma, a new water-soluble nitrosourea (MCNU) was given and the concentration was measured in blood, tumor tissues, normal brains around the tumors and normal hemispheres by intravenous or intraarterial infusion of MCNU. At 5 min. after administration of MCNU 20 mg/kg (4-5 mg/body) in 9 L gliosarcoma bearing Fischer rats, mean MCNU concentration in the blood was not different between 20 micrograms/ml intravenous and 23 micrograms/ml intraarterial administrations whereas that in the tumor tissues by intracarotid infusion of MCNU was 40 +/- 14.4 micrograms/g which was about two times as much as 22.9 +/- 8.13 micrograms/g by intravenous infusion of MCNU. Mean MCNU concentration of normal brains around tumor tissues was 2.49 micrograms/g in intravenous and 8.95 micrograms/g in intracarotid infusion. MCNU concentration of tumor tissues in 4 cases of malignant gliomas was higher by intracarotid administration than by intravenous administration compared to that in the blood. Maximum tumor/blood ratio of MCNU was 1.94 in intracarotid administration for the malignant glioma. It is suggested that intraarterial administration was more useful than intravenous infusion as an administration route for malignant brain tumors.
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PMID:[MCNU delivery into malignant brain tumor and normal brain tissue by intravenous or intraarterial infusion]. 215 61

An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 mumol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy.
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PMID:L-buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice. 230 73

Although hyperthermia has been shown to increase the effect of some cytotoxic drugs both in vitro and in vivo, there is sparse data on the interaction of the two modalities during fractionated treatment in vivo. In vitro data suggest that, parallel to development of thermotolerance, tumour cell sensitivity to drugs may be modified. Thermotolerance in tumour and surrounding normal tissue and the sensitivity to the alkylating agent BCNU given alone i.p., or as thermochemotherapy, was investigated in the subcutaneously transplanted BT4An rat glioma. Tumours treated by 44 degrees C water bath hyperthermia alone minutes after the priming hyperthermia were initially sensitive to hyperthermia, but decreased heat sensitivity developed during continued heating. Thermotolerance in the skin was greatest at 24 h. When the skin reaction was compared with the effect on tumours, a therapeutic gain using hyperthermia alone was seen at 168 h. Tumours were most sensitive to BCNU just after the priming hyperthermia, least sensitive at 48 h. When thermochemotherapy with BCNU was given at different intervals after priming hyperthermia, an interaction between the modalities was seen, with the greatest tumour effect just after priming (six of 12 tumours controlled). At 24 h the summary effect of priming treatment and subsequent thermochemotherapy was not greater than thermochemotherapy treatment alone. The thermochemotherapy effect on tumours was more dependent on the hyperthermia sensitivity, i.e. thermotolerant state, than the sensitivity to BCNU alone at that time.
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PMID:Fractionated hyperthermia in vivo: thermotolerance, sensitivity to BCNU and thermochemosensitivity in the BT4An rat glioma. 232 67

Cat brain tumors were produced by stereotactical xenotransplantation of rat glioma clone F98 into the internal capsule of the left hemisphere. Two to four weeks after implantation, the tissue content of water, sodium, potassium, calcium, magnesium, serum albumin, serum immunoglobulin, and hemoglobin was measured in samples taken from the tumor, from peritumoral white and gray matter, and from homotopic regions of the opposite hemisphere. Extravasated serum protein content was determined by subtracting intravascular from total tissue protein, using the hemoglobin content as a marker of blood volume. The development of brain tumors was accompanied by severe vasogenic brain edema, which was clearly confined to the ipsilateral white matter. The increase of water was paralleled by an increase of sodium, calcium, and serum proteins. Potassium and magnesium content remained constant. The calculated sodium and calcium content of edema fluid approximated that of blood serum. The content of blood proteins was about 50% lower, but the ratio of albumin/immunoglobulin was the same as in blood. It is concluded that peritumoral edema is a combination of plasma ultrafiltrate and whole plasma extravasation with different modes of formation. Implications for the pathophysiology and therapy of peritumoral edema are discussed.
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PMID:Quantitative analysis of experimental peritumoral edema in cats. 239 38

Vasogenic brain edema was produced by transplantation of rat glioma C6 cells into rat brain. Using this model, we measured neurotransmitter concentrations and water content of regional brain tissue. In the tumor-implanted controls, monoamine neurotransmitters in the hypothalamus, cortex, and striatum significantly decreased. When treated with DEX, these monoamines tended to return to the levels of the sham-operated controls. Additionally, DEX markedly lowered tumoral monoamines. In the nonsurgical animals, DEX significantly increased norepinephrine but not DA. Regardless of treating with DEX or not, water content showed no changes in the hypothalamus and striatum in the tumor-implanted animals. However, the increase in water content in the cortex was significant, and this increase could be reduced by DEX to the levels of controls. Water content of tumor tissue could also be markedly reduced by DEX. In the nonsurgical animals, there were no changes in water content between DEX-treated and nontreated animals. In conclusion, brain edema produced by the brain tumor may reduce noradrenergic and dopaminergic activities. This is more likely due to compression anoxia caused by the tumor mass, glial hydrops, and edema fluid. It is presumed that the effect of DEX is due to reduction of water content of the tumor and peritumoral white matter as well as by increasing noradrenergic activity.
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PMID:Effect of dexamethasone on neurotransmitter amines in a rat glioma model. 239 42

A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl) porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 micrograms/g of glioma and up to 45 micrograms/g of carcinoma were observed when up to 102 micrograms/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by approximately 80% on the average (up to 33 micrograms/g) when correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thrombocytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies.
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PMID:Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice. 240 7

The purpose of this study was to investigate the effects of tumor-localized hyperthermia at 42 degrees C on the tissue distribution of radioiodinated monoclonal antibody F(ab')2 fragments. Paired-label biodistribution measurements were performed in athymic mice bearing D-54 MG human glioma xenografts on one leg. Mice received both the 131I-labeled F(ab')2 fragment of Mel-14, reactive with human gliomas and melanomas, and nonspecific 125I-labeled RPC 5 F(ab')2. Tumor-bearing legs were placed in a 42 degrees C water bath or a 37 degrees C water bath (control) for 2 or 4 h. In mice sacrificed immediately after 2 h of heating, no hyperthermia-induced differences in the distribution of either fragment were observed. In the 4-h groups, tumor uptake of Mel-14 F(ab')2 increased from 7.04 +/- 1.59% injected dose (ID)/g at 37 degrees C to 20.65 +/- 4.53% ID/g at 42 degrees C (P less than 0.0001), and tumor localization of the control fragment rose from 5.23 +/- 1.35% ID/g to 14.51 +/- 1.37% ID/g (P less than 0.0001). In another experiment, F(ab')2 fragments were injected, tumors were heated for 4 h, and groups were sacrificed at 4, 8, and 16 h after injection. Statistically significant 2- to 3-fold higher uptake of both fragments in tumor were observed at all time points. Hyperthermic conditions also resulted in higher tumor:tissue ratios for both fragments. These results suggest that it may be possible to use tumor-localized hyperthermia to increase the therapeutic utility of radiolabeled monoclonal antibodies, particularly when labeled with short lived nuclides such as the 7.2-h alpha-emitter 211At.
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PMID:Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia. 240 44

Many glioma-derived cell lines have the capability of escaping cell-mediated immune attack. One mechanism of escape is the secretion of a hyaluronidase-sensitive mucopolysaccharide coat by these cells. This coat prevents contact and tumor cell killing by specific cytolytic allogeneic lymphocytes. The production of the coat by the tumor cells is stimulated by a macromolecular factor released by peripheral blood mononuclear (PBMC) cells in culture. We have examined the morphologic and ultrastructural features of this extracellular matrix. Three coat-producing lines were studied. Under phase contrast light microscopy, the coat is a clear pericellular 'halo'. To stain this zone, ruthenium red and Alcian Blue 8 G stains, which bind to acid mucopolysaccharides (to a large extent, hyaluronic acid), were used. The two stains produced similar results. With light microscopy, a weblike pattern of stain was evident throughout the halo region. With transmission electron microscopy, staining was found along the plasma membrane of the glioma cells and their microvilli, stretching in long, branching filaments from these surfaces and, in some instances, from one microvillus to the next. Since mucopolysaccharide matrices have a large aqueous component, it was necessary to determine whether dehydration alters the stain pattern. Therefore, undehydrated ruthenium red stained specimens from each culture were embedded in Quetal 651 (Ted Pella, Inc., Tustin, CA), a water soluble plastic. No morphologic differences were noted between the hydrated and dehydrated specimens. This study indicates that numerous long microvilli and a secreted mucopolysaccharide matrix are important structural elements of the lymphocyte-stimulated tumor cell halo in vitro. The mechanism by which the PBMC factor stimulates coat formation and the importance of the coat in in vivo tumor defenses remain to be elucidated.
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PMID:Ultrastructural features of the lymphocyte-stimulated halos produced by human glioma-derived cells in vitro. 242 Sep 43

Neurological improvement in brain-tumor patients treated with dexamethasone (DEX) precedes a reduction in peritumor brain edema. In the study reported here, levels of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT), homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA) and tissue water content were measured in grey and white matter adjacent to a 9L glioma in the cat to study DEX-neurotransmitter interactions as possible mechanisms for the acute neurological effects of DEX. Tumor-bearing and control cats were treated or not treated with DEX (0.25 mg/kg IV, 0.25 mg/kg IM) with 0.25 mg/kg IM repeated once (DEX 1) or 3 times (DEX 2) 6 hr apart. In control animals DEX 1 treatment led to significant decreases in concentration of DOPAC; DEX 2 treatment led to increases in HVA and 5-HIAA. Peritumor grey matter from untreated tumor-bearing animals had decreased levels of NA and DA and the metabolite DOPAC with no changes in 5-HT and 5-HIAA. DEX 2 but not DEX 1 resulted in a normalization (increase) in peritumor levels of DA and DOPAC. Neither dose of DEX reduced white matter edema. These findings suggest that the acute beneficial effect of DEX on neurological status may be due to alleviation of neurotransmitter amine and metabolite depletion.
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PMID:Effect of dexamethasone on monoamine and metabolite levels in a brain-tumor model. 246 98

The effect of vasogenic brain edema on amine neurotransmitter concentrations was studied in rats bearing transplanted glioma C6 brain tumors. In comparison with sham-operated and nonoperated controls, the tumor-implanted animals showed significant decreases in both dopamine (DA) and norepinephrine (NE) in the hypothalamus, cortex, and striatum. Treatment with dexamethasone (DEX) tended to restore these monoamines to the levels measured in sham-operated controls. In the nonoperated controls, DEX significantly increased NE but not DA. In tumor-bearing rats there was no increase in hypothalamic or striatal water content, and DEX had no effect on the water content of these structures. However, there was a significant increase in the cortical water content, which was reduced by DEX to the control levels. The water content within the tumor was also significantly decreased by DEX. In the nonoperated controls, there was no difference in water content between DEX-treated and nontreated animals. These findings suggest that tumor-induced brain edema reduces noradrenergic and dopaminergic activities. DEX administration resulted in normalization of the water content in edematous regions and of the DA and NE concentrations, and brought about marked symptomatic improvement.
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PMID:Neurotransmitter amines in brain edema of a rat glioma model. 247 22


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