dc.contributor.author |
Parsels, LA |
en |
dc.contributor.author |
Morgan, MA |
en |
dc.contributor.author |
Tanska, DM |
en |
dc.contributor.author |
Parsels, JD |
en |
dc.contributor.author |
Palmer, Brian |
en |
dc.contributor.author |
Booth, RJ |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Canman, CE |
en |
dc.contributor.author |
Kraker, AJ |
en |
dc.contributor.author |
Lawrence, TS |
en |
dc.contributor.author |
Maybaum, J |
en |
dc.date.accessioned |
2011-11-17T17:21:16Z |
en |
dc.date.issued |
2009 |
en |
dc.identifier.citation |
Molecular Cancer Therapeutics 8:45-54 2009 |
en |
dc.identifier.issn |
1535-7163 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/9241 |
en |
dc.description.abstract |
The protein kinase checkpoint kinase 1 (Chk1) has been implicated as a key regulator of cell cycle progression and DNA repair, and inhibitors of Chk1 (e.g., UCN-01 and EXEL-9844) potentiate the cytotoxic actions of chemotherapeutic drugs in tumor cells. We have examined the ability of PD-321852, a small-molecule Chk1 inhibitor, to potentiate gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD- 321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines. Gemcitabine chemosensitization, however, did not correlate with abrogation of the S-M or G2-M checkpoint; PD-321852 did not induce premature mitotic entry in gemcitabine-treated BxPC3or M-Panc96 |
en |
dc.language |
EN |
en |
dc.publisher |
American Association for Cancer Research |
en |
dc.relation.ispartofseries |
Molecular Cancer Therapeutics |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from
http://www.sherpa.ac.uk/romeo/issn/1535-7163/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
S-PHASE CHECKPOINT |
en |
dc.subject |
RECOMBINATION REPAIR |
en |
dc.subject |
H2AX PHOSPHORYLATION |
en |
dc.subject |
CDC25A PHOSPHATASE |
en |
dc.subject |
PREMATURE MITOSIS |
en |
dc.subject |
CHK1 INHIBITORS |
en |
dc.subject |
HISTONE H2AX |
en |
dc.subject |
REPLICATION |
en |
dc.subject |
ABROGATION |
en |
dc.subject |
PATHWAY |
en |
dc.title |
Gemcitabine sensitization by Chk1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1158/1535-7163.MCT-08-0662 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
45 |
en |
pubs.volume |
8 |
en |
dc.rights.holder |
Copyright: American Association for Cancer Research |
en |
dc.identifier.pmid |
19139112 |
en |
pubs.end-page |
54 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
88893 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
19139112 |
en |