| pubmed-article:9219512 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0001554 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0025202 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C1520166 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0220825 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0439064 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0879518 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0205195 | lld:lifeskim |
| pubmed-article:9219512 | lifeskim:mentions | umls-concept:C0205171 | lld:lifeskim |
| pubmed-article:9219512 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:9219512 | pubmed:dateCreated | 1997-8-4 | lld:pubmed |
| pubmed-article:9219512 | pubmed:abstractText | The purpose of the present study was to examine the effect of O6-benzylguanine (O6-BG) on the antitumour activity and toxicity of 8-carbamoyl-3-methylimidazo [5, 1-d]-1,2,3,5-tetrazine-4(3H)-one (temozolomide) in a human malignant melanoma xenograft model following single and multiple administration of the combination. O6-BG irreversibly inactivates the DNA-repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which confers resistance to temozolomide. Preadministration of O6-BG (35 mg/kg, i.p.) 1 h prior to temozolomide (i.p.) was examined using single and daily x5 dosing regimens in athymic mice bearing subcutaneous A375P xenografts. The AGT activity of A375P tumors was 95 +/- 8 fmol/mg protein (mean +/- SE, n = 4). O6-BG alone completely suppressed xenograft AGT activity within 1 h of administration but had no effect upon tumor growth. O6-BG did not significantly increase the tumor growth delay induced by a single 200-mg/ kg dose of temozolomide (P > 0.05, two-tailed Mann-Whitney test) but did increase the associated mean body weight loss (P < 0.025). In contrast, when the same dose of temozolomide was divided into five equal fractions (40 mg/kg) and given with O6-BG on 5 consecutive days, a comparable increase in toxicity was accompanied by a very significant increase in tumor growth delay (P < 0.0025), equivalent to that produced by a 3-fold greater dose of temozolomide alone. O6-BG with temozolomide also produced a greater antitumour effect than an equitoxic dose of temozolomide alone on this schedule (P < 0.005). These data indicate that the enhancement of temozolomide antitumour activity by O6-BG preadministration is dependent upon the schedule of drug administration, with multiple dosing of O6-BG + temozolomide producing the greatest effect. The results also suggest that prolonged administration of the combination can lead to an increase in the therapeutic index of temozolomide. | lld:pubmed |
| pubmed-article:9219512 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9219512 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9219512 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9219512 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:9219512 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9219512 | pubmed:issn | 0344-5704 | lld:pubmed |
| pubmed-article:9219512 | pubmed:author | pubmed-author:NewlandsE SES | lld:pubmed |
| pubmed-article:9219512 | pubmed:author | pubmed-author:WedgeS RSR | lld:pubmed |
| pubmed-article:9219512 | pubmed:author | pubmed-author:PorteousJ KJK | lld:pubmed |
| pubmed-article:9219512 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9219512 | pubmed:volume | 40 | lld:pubmed |
| pubmed-article:9219512 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9219512 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9219512 | pubmed:pagination | 266-72 | lld:pubmed |
| pubmed-article:9219512 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:9219512 | pubmed:meshHeading | pubmed-meshheading:9219512-... | lld:pubmed |
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| pubmed-article:9219512 | pubmed:meshHeading | pubmed-meshheading:9219512-... | lld:pubmed |
| pubmed-article:9219512 | pubmed:year | 1997 | lld:pubmed |
| pubmed-article:9219512 | pubmed:articleTitle | Effect of single and multiple administration of an O6-benzylguanine/temozolomide combination: an evaluation in a human melanoma xenograft model. | lld:pubmed |
| pubmed-article:9219512 | pubmed:affiliation | Department of Medical Oncology, Charing Cross Hospital, London, UK. | lld:pubmed |
| pubmed-article:9219512 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:9219512 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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