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    Therapeutic efficacy of variable biological effectiveness of proton therapy in u-ch2 and mug-chor1 human chordoma cell death

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    Author
    Singh, Prerna
    Eley, John
    Mahmood, Nayab
    Bhandary, Binny
    Dukic, Tijana
    Tu, Kevin J.
    Polf, Jerimy
    Lamichhane, Narottam
    Mahmood, Javed
    Vujaskovic, Zeljko
    Shukla, Hem D.
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    Date
    2021-12-04
    Journal
    Cancers
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/cancers13236115
    Abstract
    Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP Keywords:caused complexchordoma;DNA damageprotoninbeamcomparisonradiation;to M-EOBPMiddleandof the genesSpread-Outsuch asBraggDNA topoisomerase Peak (M-SOBPof1,theGTSE1,Spread-OutRAD51B wereBraggdownregulatedPeak (E-SOBP);in E-SOBPradiobiologicaltreated cells.effectiveness;Thus, we concludelinear thatenergytheretransfer;seems resistance to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP. © 2021 by the authors.
    Sponsors
    University of Maryland
    Keyword
    Chordoma
    End of the Spread-Out Bragg Peak (E-SOBP)
    Linear energy transfer
    Middle of the Spread-Out Bragg Peak (M-SOBP)
    Proton beam radiation
    Radiobiological effectiveness
    Radioresistance 1. Introduction
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17365
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers13236115
    Scopus Count
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