Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Does Timing Matter in Radiotherapy of Hepatocellular Carcinoma?

Version 1 : Received: 28 January 2021 / Approved: 29 January 2021 / Online: 29 January 2021 (08:15:35 CET)

How to cite: Hassan, S.; Ali, A.; Sohn, D.; Floegel, U.; Jaenicke, R.; Korf, H.W.; von Gall, C. Does Timing Matter in Radiotherapy of Hepatocellular Carcinoma?. Preprints 2021, 2021010603 (doi: 10.20944/preprints202101.0603.v1). Hassan, S.; Ali, A.; Sohn, D.; Floegel, U.; Jaenicke, R.; Korf, H.W.; von Gall, C. Does Timing Matter in Radiotherapy of Hepatocellular Carcinoma?. Preprints 2021, 2021010603 (doi: 10.20944/preprints202101.0603.v1).

Abstract

This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on healthy liver (HL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA-double strand breaks were investigated in irradiated and non-irradiated organotypic slice culture (OSC) and ex vivo samples by detection of Ki67 and γ-H2AX. OSC proved useful to determine dose-dependent effects on proliferation and DNA damage but appeared unsuited to test the chronotherapeutic approach. Irradiation of ex vivo samples was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on HL were minimal at ZT20. Ex vivo samples revealed disruption in daily variation and down-regulation of all investigated clock genes except Per1 in non-irradiated HCC as compared with HL. Irradiation affected rhythmic clock gene expression in HL and HCC at all ZTs except at ZT20. Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

Subject Areas

Clock genes; Hepatocellular carcinoma; Ki67; Radiotherapy; Transgenic Per2::luc mice; γ-H2AX

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.