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)

Melphalan-induced toxicity in nude mice following pretreatment with a regimen of L-buthionine sulfoximine (BSO), previously shown to enhance the activity of this alkylating agent against rhabdomyosarcoma and glioma xenografts, was examined. Mice were pretreated with i.p. BSO (2.5 mmol/kg x 7 doses at 12-h intervals plus concomitant availability of a 20-mM solution in the drinking water) or vehicle prior to a single i.p. injection of melphalan (35.65 mg/m2). As compared with control animals who received no BSO pretreatment, mice pretreated with BSO lost weight prior to therapy with melphalan (6.9% weight loss vs 0.3% weight gain; P less than 0.005) and showed a greater mean nadir weight loss after melphalan (3.8% vs. 2.1%; P = 0.049). Treatment with melphalan was associated with histologic evidence of reversible gastrointestinal toxicity, reversible myelosuppression, and histologic evidence of acute renal tubular necrosis, with no differences being observed between mice that had been pretreated with BSO and those that had been pretreated with vehicle. No evidence of cardiac, hepatic, or skeletal muscle toxicity was found in melphalan-treated animals. These results suggest that treatment of nude mice with melphalan following BSO-mediated depletion of glutathione does not result in enhanced organ toxicity despite an increase in the antineoplastic activity of this alkylating agent.
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PMID:Melphalan-induced toxicity in nude mice following pretreatment with buthionine sulfoximine. 204 29

In an attempt to modify the cytotoxicity of cisplatin, amphotericin B (AmB) was given as pretreatment to BDIX rats with intracerebral BT4C glioma implants. Ten animals given AmB 5 mg/kg i.p. followed by cisplatin 5 mg/kg i.p. displayed massive haematuria within 24 h after treatment and died a few days later. The antitumoral effect could not, therefore, be evaluated. Histopathological examination of the kidneys showed extensive tubular necrosis. No signs of apoptotic cell death were found using in situ end labelling with biotin-labelled nucleotides or with DNA integrity analysis in agarose gel electrophoresis. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the distribution of cisplatin in brain tumour, normal brain and kidney. Addition of AmB to cisplatin caused increased adduct formation in kidneys, particularly in tubular cells. It seems plausible that the nephrotoxicity, at least in part, was mediated by increased levels of cisplatin-DNA adducts. Pretreatment with AmB did not have any obvious effect on the formation of adducts in the cerebral cortex. The adduct levels in the tumours from animals pretreated with AmB were not significantly increased compared with those treated with cisplatin only. Thus, addition of AmB to cisplatin caused excessive nephrotoxicity suggesting a decrease in the therapeutic ratio of cisplatin.
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PMID:Effects of cisplatin and amphotericin B on DNA adduct formation and toxicity in malignant glioma and normal tissues in rat. 907 15

Narthecium ossifragum, a perennial herb of the lily family, causes toxic renal tubular necrosis in several ruminant species. 3-Methoxy-2(5H)-furanone (3M2F) has been identified as a nephrotoxin present in N. ossifragum extracts. We studied effects of three different 3M2F-containing fractions isolated from N. ossifragum and synthetic 3M2F on the porcine kidney cell line LLC-PK1. In some of the experiments, we included the glioma cell lines U251 and BT4Cn to compare the effects of the toxin on LLC-PK1 cells to the effect on these cell lines. The synthetic 3M2F was shown to be only mildly toxic, and the most purified fraction from N. ossifragum showed the highest degree of toxicity in our studies. When monolayer cultures were exposed to increasing amounts of 3M2F-containing extract, a dose-dependent increase in cell death was observed. Similarly, reduced neutral red uptake and 3H-thymidine uptake (DNA synthesis) was observed. There was increased apoptotic activity in the LLC-PK1 cells with increasing concentration of 3M2F-containing extract. Multicellular three-dimensional spheroids from LLC-PK1 cells stopped fluid transport, showed degenerative changes and collapsed totally 6 h after extract exposure. Our findings indicate junctional damage, reduced cellular endocytosis and DNA-synthesis as well as induction of apoptosis as possible mechanisms for the acute tubular necrosis observed in ruminant species.
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PMID:Effects of 3-methoxy-2(5H)-furanone-containing extracts from Narthecium ossifragum (L.) Huds. on renal tubular cells in vitro. 1714 20