Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction

Masunaga, Shin Ichiro; Sakurai, Y; Tanaka, Hiroki; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Uzawa, Akiko; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Maruhashi, Akira; Ono, Koji

doi:10.1259/bjr.20120302

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…It has been previously reported that hypoxic conditions can trigger tumor cells to become quiescent (i.e. not actively dividing), and that these quiescent cells uptake less 10 B-BPA or 10 B-BSH compared with non-quiescent cells [ 25 ]. This negative effect was reported to be stronger with 10 B-BPA than with 10 B-BSH, an observation thought to be due to the fact that 10 B-BSH largely accumulates in cells via diffusion, while 10 B-BPA is actively taken up via LAT1/2 transporters [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

Wada

Hirose

Harada

et al. 2018

Journal of Radiation Research

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Boron neutron capture therapy (BNCT) can potentially deliver high linear energy transfer particles to tumor cells without causing severe damage to surrounding normal tissue, and may thus be beneficial for cases with characteristics of infiltrative growth, which need a wider irradiation field, such as glioblastoma multiforme. Hypoxia is an important factor contributing to resistance to anticancer therapies such as radiotherapy and chemotherapy. In this study, we investigated the impact of oxygen status on 10B uptake in glioblastoma cells in vitro in order to evaluate the potential impact of local hypoxia on BNCT. T98G and A172 glioblastoma cells were used in the present study, and we examined the influence of oxygen concentration on cell viability, mRNA expression of L-amino acid transporter 1 (LAT1), and the uptake amount of 10B-BPA. T98G and A172 glioblastoma cells became quiescent after 72 h under 1% hypoxia but remained viable. Uptake of 10B-BPA, which is one of the agents for BNCT in clinical use, decreased linearly as oxygen levels were reduced from 20% through to 10%, 3% and 1%. Hypoxia with <10% O2 significantly decreased mRNA expression of LAT1 in both cell lines, indicating that reduced uptake of 10B-BPA in glioblastoma in hypoxic conditions may be due to reduced expression of this important transporter protein. Hypoxia inhibits 10B-BPA uptake in glioblastoma cells in a linear fashion, meaning that approaches to overcoming local tumor hypoxia may be an effective method of improving the success of BNCT treatment.

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Section: Discussionmentioning

confidence: 99%

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

Wada

Hirose

Harada

et al. 2018

Journal of Radiation Research

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“…Equally, previous studies have suggested that the ROS/RAC2/P38 MAPK feedback loop is associated with the radio‐resistance of quiescent cells, to 100 kV X‐rays (Pei et al, 2017). Furthermore, following γ‐ray irradiation, the radio‐sensitivity of pimonidazole‐unlabelled quiescent tumour cells (oxygenated cell fraction) was higher than the total cell fraction (quiescent plus proliferating cells; Masunaga et al, 2013). The difference in radio‐sensitivity between the total and quiescent‐cell populations after γ‐ray irradiation was markedly reduced with carbon‐ion beams (290 MeV), especially with a greater LET value (Masunaga et al, 2008).…”

Section: Factors Affecting Dna Repair Efficienciesmentioning

confidence: 99%

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

Zhang

Gan

et al. 2020

Journal Cellular Physiology

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Radiotherapy is one of the major modalities for malignancy treatment. High linear energy transfer (LET) charged-particle beams, like proton and carbon ions, exhibit favourable depth-dose distributions and radiobiological enhancement over conventional low-LET photon irradiation, thereby marking a new era in high precision medicine. Tumour cells have developed multicomponent signal transduction networks known as DNA damage responses (DDRs), which initiate cell-cycle checkpoints and induce double-strand break (DSB) repairs in the nucleus by nonhomologous end joining or homologous recombination pathways, to manage ionising radiation (IR)-induced DNA lesions. DNA damage induction and DSB repair pathways are reportedly dependent on the quality of radiation delivered. In this review, we summarise various types of DNA lesion and DSB repair mechanisms, upon irradiation with low and high-LET radiation, respectively. We also analyse factors influencing DNA repair efficiency. Inhibition of DNA damage repair pathways and dysfunctional cell-cycle checkpoint sensitises tumour cells to IR.

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“…Interestingly, the very factors that confer radioresistance in cancers cells (i.e. hypoxia and nutrient deprivation) are the very same that promote the growth of CSCs [ 74 - 76 ]. Moreover, it has also been shown that treatment with low dose photons increases the proportion of radioresistant stem cells (radioadaptive resistance) [ 77 , 78 ].…”

Section: Towards the Establishment Of A National Ion Therapy Randd Centmentioning

confidence: 99%

“…Masunaga et al ., showed that a pimonidazole-unlabelled subfraction of quiescent tumor cells, considered the closest representative subpopulation to CSCs, may be a critical target in tumor control [ 76 ]. Treatment with carbon ions were shown to decrease the difference in radiosensitivity between quiescent and non-quiescent cells, as well as, hypoxic and normoxic cells.…”

Section: Towards the Establishment Of A National Ion Therapy Randd Centmentioning

confidence: 99%

Bringing the heavy: carbon ion therapy in the radiobiological and clinical context

et al. 2014

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Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/β ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.

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Radiosensitivity of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction

Cited by 12 publications

References 18 publications

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy

Harnessing the targeting potential of differential radiobiological effects of photon versus particle radiation for cancer treatment

Bringing the heavy: carbon ion therapy in the radiobiological and clinical context

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