Matches in SemOpenAlex for { <https://semopenalex.org/work/W2941329858> ?p ?o ?g. }
Showing items 1 to 76 of
76
with 100 items per page.
- W2941329858 abstract "Introduction: Though adjuvant chemotherapy improves survival following surgery, pancreatic cancer carries a poor prognosis. Alternatives are required to the current drug regimens consisting of S-phase dependent drugs such as gemcitabine. PLK1 is a passenger protein involved in G2/M phases which presents a novel target to inhibit in combination with current therapies, which may help overcome inate and acquired resistance. Aim: To evaluate the potential role of a novel PLK1 inhibitor, BI 6727 in pancreatic cancer – both as monotherapy and in combination with gemcitabine in vitro. Methods: The IC50 concentrations of both drugs were established in Suit-2, BxPC-3, Panc-1 and MiaPaCa-2 pancreatic cancer cell lines and isobolar analyses undertaken with a variety of combination therapies. Cell cycle analyses were performed with Flow Activated Cell Sorting, with apoptosis and necrosis quantified on the basis of phosphatidylserine cell surface exposure, propidium iodide staining and cleavage of caspase-3. Results: IC50 ranges for BI 6727 and gemcitabine were 53-77nM and 11-34nM respectively across four pancreatic cell lines. Flow cytometry of MiaPaCa-2 cells demonstrated G2 arrest with BI 6727 and S-phase accumulation with gemcitabine monotherapy. Isobolar analyses showed that when added together the combination of drugs was additive, but BI 6727 pretreatment followed by combination was synergistic. Western blotting for cleaved caspase-3 showed evidence of apoptosis with gemcitabine monotherapy but none with BI 6727 treatment. Although membrane inversion was seen with synergistic drug combinations there was no evidence of cleaved-caspase-3, suggesting a modified form of apoptosis. Conclusion: BI 6727 is effective against a variety of pancreatic cancer cells in vitro. Synergy is demonstrated in MiaPaCa-2 cells when BI 6727 is administered prior to combination therapy with gemcitabine, though mode of cell death does not appear to be caspase-dependent. This supports the concept that PLK1 inhibition can overcome gemcitabine resistance in some cells by allowing resistant cells to initiate gemcitabine induced apoptosis, although this is dependent on drug phasing and the full apoptotic pathway may not be achieved." @default.
- W2941329858 created "2019-05-03" @default.
- W2941329858 creator A5014626452 @default.
- W2941329858 date "2018-01-09" @default.
- W2941329858 modified "2023-09-26" @default.
- W2941329858 title "BI 6727 and gemcitabine combination therapy in pancreatic cancer" @default.
- W2941329858 doi "https://doi.org/10.17638/03015706" @default.
- W2941329858 hasPublicationYear "2018" @default.
- W2941329858 type Work @default.
- W2941329858 sameAs 2941329858 @default.
- W2941329858 citedByCount "0" @default.
- W2941329858 crossrefType "dissertation" @default.
- W2941329858 hasAuthorship W2941329858A5014626452 @default.
- W2941329858 hasConcept C121608353 @default.
- W2941329858 hasConcept C126322002 @default.
- W2941329858 hasConcept C143998085 @default.
- W2941329858 hasConcept C185592680 @default.
- W2941329858 hasConcept C190283241 @default.
- W2941329858 hasConcept C203014093 @default.
- W2941329858 hasConcept C2775934118 @default.
- W2941329858 hasConcept C2776694085 @default.
- W2941329858 hasConcept C2776999253 @default.
- W2941329858 hasConcept C2780210213 @default.
- W2941329858 hasConcept C2780258809 @default.
- W2941329858 hasConcept C29537977 @default.
- W2941329858 hasConcept C31573885 @default.
- W2941329858 hasConcept C502942594 @default.
- W2941329858 hasConcept C553184892 @default.
- W2941329858 hasConcept C55493867 @default.
- W2941329858 hasConcept C71924100 @default.
- W2941329858 hasConcept C98274493 @default.
- W2941329858 hasConceptScore W2941329858C121608353 @default.
- W2941329858 hasConceptScore W2941329858C126322002 @default.
- W2941329858 hasConceptScore W2941329858C143998085 @default.
- W2941329858 hasConceptScore W2941329858C185592680 @default.
- W2941329858 hasConceptScore W2941329858C190283241 @default.
- W2941329858 hasConceptScore W2941329858C203014093 @default.
- W2941329858 hasConceptScore W2941329858C2775934118 @default.
- W2941329858 hasConceptScore W2941329858C2776694085 @default.
- W2941329858 hasConceptScore W2941329858C2776999253 @default.
- W2941329858 hasConceptScore W2941329858C2780210213 @default.
- W2941329858 hasConceptScore W2941329858C2780258809 @default.
- W2941329858 hasConceptScore W2941329858C29537977 @default.
- W2941329858 hasConceptScore W2941329858C31573885 @default.
- W2941329858 hasConceptScore W2941329858C502942594 @default.
- W2941329858 hasConceptScore W2941329858C553184892 @default.
- W2941329858 hasConceptScore W2941329858C55493867 @default.
- W2941329858 hasConceptScore W2941329858C71924100 @default.
- W2941329858 hasConceptScore W2941329858C98274493 @default.
- W2941329858 hasLocation W29413298581 @default.
- W2941329858 hasOpenAccess W2941329858 @default.
- W2941329858 hasPrimaryLocation W29413298581 @default.
- W2941329858 hasRelatedWork W1578087924 @default.
- W2941329858 hasRelatedWork W1981258502 @default.
- W2941329858 hasRelatedWork W1981592508 @default.
- W2941329858 hasRelatedWork W2013818326 @default.
- W2941329858 hasRelatedWork W2032500323 @default.
- W2941329858 hasRelatedWork W2041242686 @default.
- W2941329858 hasRelatedWork W2043969249 @default.
- W2941329858 hasRelatedWork W2053170633 @default.
- W2941329858 hasRelatedWork W2068534025 @default.
- W2941329858 hasRelatedWork W2145438808 @default.
- W2941329858 hasRelatedWork W2571476314 @default.
- W2941329858 hasRelatedWork W2657503393 @default.
- W2941329858 hasRelatedWork W2889052898 @default.
- W2941329858 hasRelatedWork W2921948547 @default.
- W2941329858 hasRelatedWork W3035325460 @default.
- W2941329858 hasRelatedWork W3080571096 @default.
- W2941329858 hasRelatedWork W3090959428 @default.
- W2941329858 hasRelatedWork W3192336000 @default.
- W2941329858 hasRelatedWork W3198606793 @default.
- W2941329858 hasRelatedWork W2766366243 @default.
- W2941329858 isParatext "false" @default.
- W2941329858 isRetracted "false" @default.
- W2941329858 magId "2941329858" @default.
- W2941329858 workType "dissertation" @default.