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  • Tigecycline br d QUANTIFICATION AND STATISTICAL ANALYSIS B

    2019-10-30


    d QUANTIFICATION AND STATISTICAL ANALYSIS B Synergy calculation
    SUPPLEMENTAL INFORMATION
    Supplemental Information can be found with this Tigecycline article online at https://doi.
    ACKNOWLEDGMENTS
    The work was supported by the U.S. Department of Defense (grant OC130322) and the NIH (grant 5R01CA214567). Individual investigator support was as fol-lows: Ann and Sol Schreiber Mentored grant and Liz Tilberis early career OCRA awards, the Marsha Rivkin Ovarian Center pilot award, and a WeRoc research
    (F) Survival studies during 6 months after i.p. inoculation of 1 3 104 FACS-sorted ALDH+ SKOv3 cells. (G) Percentage of mice that were tumor free after 9 weeks of treatments in an LSL-K-rasG12D/+PtenloxP/loxP endometrioid ovarian cancer model.
    (H) Growth curves of platinum-resistant PDX; n = 5 mice/group for two independent PDX models. The 673A was given daily for 21 days at 20 mg/kg; cisplatin or carboplatin were given weekly.
    (I) (i) Combined waterfall plot from four biological replicates (mean R values) of ALDH1A inhibition in SKOv3 tumors in vivo. (ii) Representative of inhibition of ALDH1a1_C303 in two data sets in SKOv3 tumors in vivo.
    AUTHOR CONTRIBUTIONS
    I.C. designed and performed experiments, interpreted data, wrote the paper, and provided funding. E.V.V., R.S., and B.C. performed and interpreted ALDH inhibition in vivo studies. L.H., K.Y., and E.G. performed experiments. B.H., S.B., and S.D.L. identified ALDH1A-I. M.M. and D.K. designed and interpreted radioresistance studies. I.R. and C.Y.C. designed and interpreted KRAS model studies. I.K. and D.B.L. helped with Seahorse studies. E.Y. provided microflui-dic chips. C.L. designed and interpreted PDX in vivo studies. A.B. and G.M. performed breast cancer and sphere combination studies. C.A.M., C.B., M.C., and T.D.H. designed and interpreted enzymology studies. R.J.B. conceptualized the study, designed the experiments, interpreted the data, wrote the paper, and provided tissue specimens and funding.
    DECLARATION OF INTERESTS
    R.J.B., S.D.L., and T.D.H. have patents related to the use of ALDHi as cancer therapy. R.J.B. is a co-founder of Tradewind Bioscience; however, none of the work described in this study is related to, based on, or supported by the com-pany. T.D.H. holds significant financial equity in SAJE Pharma, LLC.; however, none of the work described in this study is related to, based on, or supported by the company.
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