|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0001459,
umls-concept:C0012860,
umls-concept:C0012935,
umls-concept:C0027950,
umls-concept:C0035549,
umls-concept:C0076080,
umls-concept:C0279023,
umls-concept:C0439836,
umls-concept:C0596402,
umls-concept:C1335439,
umls-concept:C1511667,
umls-concept:C1546857,
umls-concept:C1831920,
umls-concept:C1999216
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2008-10-16
|
|
pubmed:abstractText |
Poly(ADP-ribose) polymerase (PARP) senses DNA breaks and facilitates DNA repair via the polyADP-ribosylation of various DNA binding and repair proteins. We explored the mechanism of potentiation of temozolomide cytotoxicity by the PARP inhibitor ABT-888. We showed that cells treated with temozolomide need to be exposed to ABT-888 for at least 17 to 24 hours to achieve maximal cytotoxicity. The extent of cytotoxicity correlates with the level of double-stranded DNA breaks as indicated by gammaH2AX levels. In synchronized cells, damaging DNA with temozolomide in the presence of ABT-888 during the S phase generated high levels of double-stranded breaks, presumably because the single-stranded DNA breaks resulting from the cleavage of the methylated nucleotides were converted into double-stranded breaks through DNA replication. As a result, treatment of temozolomide and ABT-888 during the S phase leads to higher levels of cytotoxicity. ABT-888 inhibits poly(ADP-ribose) formation in vivo and enhances tumor growth inhibition by temozolomide in multiple models. ABT-888 is well tolerated in animal models. ABT-888 is currently in clinical trials in combination with temozolomide.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
1541-7786
|
|
pubmed:author |
pubmed-author:ChuI YIY,
pubmed-author:Colon-LopezMilagrosM,
pubmed-author:CoxBryan FBF,
pubmed-author:DonawhoCherrieC,
pubmed-author:FrostDavidD,
pubmed-author:Ghoreishi-HaackNayerehN,
pubmed-author:GirandaVincent LVL,
pubmed-author:GuanRanR,
pubmed-author:HradilVincent PVP,
pubmed-author:JarvisKenK,
pubmed-author:JohnsonEric FEF,
pubmed-author:KlinghoferVeredV,
pubmed-author:LiuXuesongX,
pubmed-author:LuoYanY,
pubmed-author:LuoYanpingY,
pubmed-author:PalmaJoannJ,
pubmed-author:PenningThomasT,
pubmed-author:RodriguezLuis ELE,
pubmed-author:RosenbergSaul HSH,
pubmed-author:ZhuGui-DongGD
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
6
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1621-9
|
|
pubmed:meshHeading |
pubmed-meshheading:18922977-Animals,
pubmed-meshheading:18922977-Antineoplastic Agents,
pubmed-meshheading:18922977-Benzimidazoles,
pubmed-meshheading:18922977-Cell Death,
pubmed-meshheading:18922977-Cell Line, Tumor,
pubmed-meshheading:18922977-DNA Breaks, Double-Stranded,
pubmed-meshheading:18922977-DNA Breaks, Single-Stranded,
pubmed-meshheading:18922977-DNA Repair,
pubmed-meshheading:18922977-DNA Replication,
pubmed-meshheading:18922977-Dacarbazine,
pubmed-meshheading:18922977-Disease Models, Animal,
pubmed-meshheading:18922977-Drug Screening Assays, Antitumor,
pubmed-meshheading:18922977-Drug Synergism,
pubmed-meshheading:18922977-Humans,
pubmed-meshheading:18922977-Mice,
pubmed-meshheading:18922977-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:18922977-Rats
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Potentiation of temozolomide cytotoxicity by poly(ADP)ribose polymerase inhibitor ABT-888 requires a conversion of single-stranded DNA damages to double-stranded DNA breaks.
|
|
pubmed:affiliation |
Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL, USA.
|
|
pubmed:publicationType |
Journal Article
|
