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Bliss and Loewe int...
Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism
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- Kashif, Muhammad (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
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- Andersson, Claes (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Mansoori, Sharmineh (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Larsson, Rolf (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Nygren, Peter (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Gustafsson, Mats G. (författare)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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(creator_code:org_t)
- 2017-10-19
- 2017
- Engelska.
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 103952-103967
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https://uu.diva-port... (primary) (Raw object)
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https://www.oncotarg...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- We analyzed survival effects for 15 different pairs of clinically relevant anticancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair. COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy (TM) II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of significant effect per cell line. In conclusion, the integrated Bliss and Loewe interaction analysis based on non-parametric statistics may provide more robust interaction analyses and reveal complex patterns of synergy and antagonism.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- synergy analysis
- combinations
- iso-genic
- COMBIA
- R package
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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