Cell-cycle-controlled radiation therapy was effective for treating a murine malignant melanoma cell line in vitro and in vivo

Otani, Keisuke; Naito, Yoshiro; Sakaguchi, Yoshiyuki; Seo, Yuji; Takahashi, Yutaka; Kikuta, Junichi; Ogawa, Kazuhiko; Ishii, Masaru

doi:10.1038/srep30689

Cited by 43 publications

(46 citation statements)

References 28 publications

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“…The phase of the tumor cell population can play a big role in radiation therapy as well. A recent study has shown higher radiosensitivity during the S/G2/M phase (Otani et al 2016). Based on the data in Fig.…”

Section: Discussionmentioning

confidence: 93%

Use of a lipid nanoparticle system as a Trojan horse in delivery of gold nanoparticles to human breast cancer cells for improved outcomes in radiation therapy

et al. 2019

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Background: Radiotherapy is commonly used for treating cancer. Novel sensitizers, such as gold nanoparticles (GNPs), are being used to enhance the local radiation dose. It is not known how the uptake and radiation dose enhancement of GNPs vary in synchronized vs unsynchronized (control) tumor cell populations. Successful application of GNPs in radiation therapy requires NPs to be accumulated within individual tumor cells at clinically feasible NP concentrations. Use of small GNPs as a radiation dose enhancer in the past required very high NP concentration, since the driving force for the uptake of smaller GNPs is low. We used a novel lipid-based NP of 50 nm diameter system as a Trojan horse to deliver smaller GNPs of size 5 nm (LNP-GNP) at 0.2 nM concentration. We investigated the changes in GNP uptake and survival fraction with the LNP delivery at different cell stages using human breast cancer as our tumor model and choosing the triple-negative MDA-MB-231 cell line. Results: Using the LNP-GNP system resulted in a 39-and 73-fold enhancement in uptake of 5 nm GNPs in unsynchronized and synchronized tumor cell populations, respectively. The NP uptake per cell increased from 800 to 1200 and from 30,841 to 88,477 for individual 5 nm GNPs and 5 nm GNPs incorporated in LNPs, respectively. After a radiation dose of 2 Gy with 6 MeV photons, synchronized tumor cell populations incorporated with LNP-GNPs produced a 27% enhancement in tumor cell death compared to the control (unsynchronized; no GNPs; 2 Gy). The findings of our experimental results were supported by modeling predictions based on Monte Carlo calculations. Conclusions: This study clearly shows that the cell cycle, GNPs, and radiation therapy can be combined to improve outcome of cancer therapy. Using the experimental data, we estimated the predicted improvement for a clinical treatment plan where 30 fractions of 2 Gy radiation dose were given over a period of time. Enhanced uptake and radiation sensitivity of a synchronous tumor cell population would produce a significant improvement in cell killing. For example, synchronizing cells and the addition of LNP-GNPs into tumor cells produced a 1000-fold enhancement in cell killing. Because the agents used for cell synchronization are in clinical practice, this approach may be a

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Section: Discussionmentioning

confidence: 93%

Use of a lipid nanoparticle system as a Trojan horse in delivery of gold nanoparticles to human breast cancer cells for improved outcomes in radiation therapy

et al. 2019

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“…Previous studies of cell synchronization using FUCCI induce the synchronization using methods including serum starvation, cell cycle-inhibiting drugs, environmental pH or contact inhibition [10][11][12][13][14][15]. Our assays are prepared using a standard method [10] normally thought to produce asynchronous populations, and we take utmost care to ensure that there is no induced synchronization in our cell cultures due to serum starvation, low pH or contact inhibition (electronic supplementary material, S1).…”

Section: Introductionmentioning

confidence: 99%

Mathematical models incorporating a multi-stage cell cycle replicate normally-hidden inherent synchronization in cell proliferation

Vittadello

McCue

Gunasingh

et al. 2019

J. R. Soc. Interface.

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We present a suite of experimental data showing that cell proliferation assays, prepared using standard methods thought to produce asynchronous cell populations, persistently exhibit inherent synchronization. Our experiments use fluorescent cell cycle indicators to reveal the normally hidden cell synchronization, by highlighting oscillatory subpopulations within the total cell population. These oscillatory subpopulations would never be observed without these cell cycle indicators. On the other hand, our experimental data show that the total cell population appears to grow exponentially, as in an asynchronous population. We reconcile these seemingly inconsistent observations by employing a multi-stage mathematical model of cell proliferation that can replicate the oscillatory subpopulations. Our study has important implications for understanding and improving experimental reproducibility. In particular, inherent synchronization may affect the experimental reproducibility of studies aiming to investigate cell cycle-dependent mechanisms, including changes in migration and drug response.

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“…Harada et al introduced an EGFP-53BP1M FP probe to visualize the diversity of the radiation-induced DNA damage responses in real time [165]. Ishii's group reported that B16BL6 cells in the early S phase were the most susceptible to radiotherapy [166]. Live imaging technology using FPs is expected to make significant contributions to the direct visualization and detailed understanding of radiation adverse events.…”

Section: Biomed Research Internationalmentioning

confidence: 99%

Space Radiation Biology for “Living in Space”

Furukawa

Nagamatsu

Nenoi

et al. 2020

BioMed Research International

100

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Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.

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Cell-cycle-controlled radiation therapy was effective for treating a murine malignant melanoma cell line in vitro and in vivo

Cited by 43 publications

References 28 publications

Use of a lipid nanoparticle system as a Trojan horse in delivery of gold nanoparticles to human breast cancer cells for improved outcomes in radiation therapy

Use of a lipid nanoparticle system as a Trojan horse in delivery of gold nanoparticles to human breast cancer cells for improved outcomes in radiation therapy

Mathematical models incorporating a multi-stage cell cycle replicate normally-hidden inherent synchronization in cell proliferation

Space Radiation Biology for “Living in Space”

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