FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1600352032> ?p ?o ?g. }

• W1600352032 endingPage "10" @default.
• W1600352032 startingPage "2402" @default.
• W1600352032 abstract "Early phase evaluation of anticancer drugs has traditionally used toxicity (usually hematological) rather than efficacy end points to establish appropriate dosing schedules. To establish a biochemical efficacy end point for overcoming alkylguanine DNA alkyltransferase (AGT)-mediated tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, we performed a novel dose escalation clinical trial for the AGT-depleting agent O6-benzylguanine (BG). The dose of BG required to deplete AGT to undetectable levels (BMD(T)) in sequential computed tomography-guided tumor tissue biopsies before BG and 18 h after BG was determined. Thirty patients received doses of BG ranging from 10 to 120 mg/m2. In tumor tissue, AGT depletion >86% of baseline was demonstrated at all doses tested. Residual tumor AGT activity, present 18 h after BG doses of 10-80 mg/m2, was eliminated at the 120 mg/m2 dose and is thus the BMD(T) of BG. BG pharmacokinetics are characterized by the rapid, dose-independent clearance of BG from plasma Metabolism of BG to its biologically active metabolite, 8-oxo-benzylguanine (8-oxo-BG), was found. The t(1/2) of 8-oxo-BG is longer than BG. Plasma concentrations of 8-oxo-BG well above 200 ng/ml 18 h after the end of the BG infusion were observed at the highest dose levels tested and appeared to correlate with depletion of AGT activity to undetectable levels in tumor tissue. AGT activity in peripheral blood mononuclear cells at baseline did not correlate with tumor tissue AGT activity. Depletion of AGT activity to undetectable levels in peripheral blood mononuclear cells occurred at lower doses and was not a reliable predictor for tumor tissue depletion. No serious side effects were observed with administration of BG alone or in combination with 13 mg/m2 1,3-bis(2-chloroethyl)-1-nitrosourea. This is the first clinical study in which biochemical analyses from pre- and posttreatment tumor biopsies have been used as an efficacy end point for the clinical development of an anticancer agent. From our tumor tissue biopsy data, we have established that a BG dose of 120 mg/m2 infused over 1 h should be used in Phase II clinical trials." @default.
• W1600352032 created "2016-06-24" @default.
• W1600352032 creator A5013881064 @default.
• W1600352032 creator A5018406749 @default.
• W1600352032 creator A5019470085 @default.
• W1600352032 creator A5038788263 @default.
• W1600352032 creator A5045151661 @default.
• W1600352032 creator A5055830608 @default.
• W1600352032 creator A5063050485 @default.
• W1600352032 creator A5076771130 @default.
• W1600352032 creator A5090398738 @default.
• W1600352032 date "1999-05-15" @default.
• W1600352032 modified "2023-10-15" @default.
• W1600352032 title "O6-benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair." @default.
• W1600352032 cites W111616551 @default.
• W1600352032 cites W1507466330 @default.
• W1600352032 cites W1520098239 @default.
• W1600352032 cites W1537425172 @default.
• W1600352032 cites W1583605502 @default.
• W1600352032 cites W1593941483 @default.
• W1600352032 cites W1669292210 @default.
• W1600352032 cites W1907545229 @default.
• W1600352032 cites W1967175894 @default.
• W1600352032 cites W1967962338 @default.
• W1600352032 cites W1971331879 @default.
• W1600352032 cites W1980195588 @default.
• W1600352032 cites W1982367855 @default.
• W1600352032 cites W1989581745 @default.
• W1600352032 cites W2009021763 @default.
• W1600352032 cites W2017392779 @default.
• W1600352032 cites W2028834400 @default.
• W1600352032 cites W2049654630 @default.
• W1600352032 cites W2065060474 @default.
• W1600352032 cites W2073968269 @default.
• W1600352032 cites W2075623636 @default.
• W1600352032 cites W2081350269 @default.
• W1600352032 cites W2086790640 @default.
• W1600352032 cites W2089716931 @default.
• W1600352032 cites W2100070997 @default.
• W1600352032 cites W2100843222 @default.
• W1600352032 cites W2108686635 @default.
• W1600352032 cites W2115938423 @default.
• W1600352032 cites W2116661259 @default.
• W1600352032 cites W2136498171 @default.
• W1600352032 cites W2140693914 @default.
• W1600352032 cites W2144322094 @default.
• W1600352032 cites W2153241484 @default.
• W1600352032 cites W2166382251 @default.
• W1600352032 cites W2174123365 @default.
• W1600352032 cites W2469926274 @default.
• W1600352032 cites W1501100609 @default.
• W1600352032 cites W2464348295 @default.
• W1600352032 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10344750" @default.
• W1600352032 hasPublicationYear "1999" @default.
• W1600352032 type Work @default.
• W1600352032 sameAs 1600352032 @default.
• W1600352032 citedByCount "58" @default.
• W1600352032 countsByYear W16003520322012 @default.
• W1600352032 countsByYear W16003520322014 @default.
• W1600352032 countsByYear W16003520322015 @default.
• W1600352032 crossrefType "journal-article" @default.
• W1600352032 hasAuthorship W1600352032A5013881064 @default.
• W1600352032 hasAuthorship W1600352032A5018406749 @default.
• W1600352032 hasAuthorship W1600352032A5019470085 @default.
• W1600352032 hasAuthorship W1600352032A5038788263 @default.
• W1600352032 hasAuthorship W1600352032A5045151661 @default.
• W1600352032 hasAuthorship W1600352032A5055830608 @default.
• W1600352032 hasAuthorship W1600352032A5063050485 @default.
• W1600352032 hasAuthorship W1600352032A5076771130 @default.
• W1600352032 hasAuthorship W1600352032A5090398738 @default.
• W1600352032 hasConcept C112705442 @default.
• W1600352032 hasConcept C126322002 @default.
• W1600352032 hasConcept C149151106 @default.
• W1600352032 hasConcept C185592680 @default.
• W1600352032 hasConcept C2777477808 @default.
• W1600352032 hasConcept C29730261 @default.
• W1600352032 hasConcept C55493867 @default.
• W1600352032 hasConcept C71924100 @default.
• W1600352032 hasConcept C98274493 @default.
• W1600352032 hasConceptScore W1600352032C112705442 @default.
• W1600352032 hasConceptScore W1600352032C126322002 @default.
• W1600352032 hasConceptScore W1600352032C149151106 @default.
• W1600352032 hasConceptScore W1600352032C185592680 @default.
• W1600352032 hasConceptScore W1600352032C2777477808 @default.
• W1600352032 hasConceptScore W1600352032C29730261 @default.
• W1600352032 hasConceptScore W1600352032C55493867 @default.
• W1600352032 hasConceptScore W1600352032C71924100 @default.
• W1600352032 hasConceptScore W1600352032C98274493 @default.
• W1600352032 hasIssue "10" @default.
• W1600352032 hasLocation W16003520321 @default.
• W1600352032 hasOpenAccess W1600352032 @default.
• W1600352032 hasPrimaryLocation W16003520321 @default.
• W1600352032 hasRelatedWork W1870968175 @default.
• W1600352032 hasRelatedWork W1964759623 @default.
• W1600352032 hasRelatedWork W1997401353 @default.
• W1600352032 hasRelatedWork W1998356222 @default.
• W1600352032 hasRelatedWork W2007079254 @default.
• W1600352032 hasRelatedWork W2018753489 @default.

• next