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)

The chemoprotective effect of amifostine (WR2721) was studied in a BDIX rat model with intracerebral BT4C glioma implants. Twenty-one rats were given cisplatin 5 mg/kg i.p., 21 were given amifostine 200 mg/kg i.p. + cisplatin 5 mg/kg i.p. Ten rats served as untreated controls. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the adduct formation in tumor, normal brain and kidney. Tumor volume and serum creatinine level were analysed 10 days after treatment. In animals pretreated with amifostine there was a delayed adduct formation rate in the normal brain, and in the kidney cortex the number of tubular cells with extremely high adduct level was reduced. No difference in adduct formation was seen in tumors. Tumor volume was significantly larger following amifostine + cisplatin (66% of controls) compared to cisplatin alone (38% of controls). Weight loss was, however, severe in rats given cisplatin alone. In the tumor growth study only 3 out of 11 rats treated with cisplatin 5 mg/kg alone survived until time of sacrifice at 10 days, whereas all those pretreated with amifostine survived. Mean serum creatinine was 48 micromol/l (controls), 146 micromol/l (cisplatin) and 59 micromol/l (amifostine + cisplatin). A marked reduction of histopathological renal changes was found when amifostine was added. Amifostine thus significantly reduced general and renal toxicity of cisplatin. The tumor growth retardation was stronger when cisplatin was given alone but this is probably related to general toxicity and malnutrition indirectly supported by the fact that amifostine did not significantly reduce cisplatin-DNA adduct formation in tumors. The results of the present study suggest that amifostine may have a role in increasing the therapeutic ratio of cisplatin, also in the treatment of malignant glioma.
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PMID:Effects of amifostine on cisplatin induced DNA adduct formation and toxicity in malignant glioma and normal tissues in rat. 1036 Apr 75

Amifostine (WR-2721) is a well-known radioprotective drug, selective for normal cells. The purpose of the present study was to define whether amifostine protects the vascular network from the effects of X-rays. We used the in vivo system of chicken embryo chorioallantoic membrane (CAM) as a model of angiogenesis. Amifostine reversed the early X-rays- induced decrease in the number of CAM blood vessels and reversed the early radiation-induced apoptosis of CAM cells. It also inhibited the increase in tyrosine nitration of actin and a-tubulin, which was observed 6 hours after CAM irradiation, when there was a significant decrease in non-protein SH groups. Furthermore, C6 rat glioma cells were inoculated on CAM and tumor growth, as well as tumor-induced angiogenesis, was estimated on haematoxylin-eosin-stained paraffin sections. Amifostine inhibited the post irradiation increase of C6 tumor-induced angiogenesis. These data suggest that amifostine protects CAM cells and blood vessels from the effects of X-rays, through mechanisms that do not depend solely on its free radical scavenging properties.
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PMID:Amifostine protects blood vessels from the effects of ionizing radiation. 1253 3