• 2018-07
  • 2020-03
  • 2020-07
  • 2020-08
  • br In this study the radioresistance of GBM and GBM


    In this study, the radioresistance of GBM 8401 and GBM 8401 CD133+ were examined through colony assay, with the results as shown in Fig. 4. The circles and the inverted triangles were the mean survival fraction of GBM 8401 and GBM 8401 CD133+ cell line re-spectively and the error bars were the stander deviation of each data point. The survival curves in Fig. 4 were fitted by using a linear-quadratic model, in which α and β represent the linear and quadratic components of the survival curves and D10 and D60 the absorbed doses corresponding to 10% and 60% survival fractions, respectively. The
    Fig. 4. GBM 8401 and GBM 8401 CD133+ cell survival curves from X-ray ir-radiation; data on survival fractions (symbols) are fitted to a linear-quadratic model (curves). 
    For image analysis, the ImageJ foci count macro was used to cal-culate the foci number and average intensity cell by cell, the product of which was then used as an index of the DNA DSB severity. Fig. 6 shows the time-course expression of γ-H2AX histone protein in GBM 8401 and GBM 8401 CD133+ Angeli’s Salt after 1.6-Gy α-particle irradiation and the error bars were the standard deviation of each data point. The results indicating that at 4 h after irradiation γ-H2AX expression in the GBM 8401 CD133+ cell line was approximately twice as high as that of the GBM 8401 cell line. However, at 12 h after irradiation, γ-H2AX ex-pression in the GBM 8401 CD133+ cell line had decreased to the same level as that of the GBM 8401 cell line. This demonstrated that the DNA repair pathway in both the GBM 8401 and GBM 8401 CD133+ cells was not disrupted or destroyed by high-LET α-particle irradiation. More-over, the high γ-H2AX signal expression and Angeli’s Salt dissolving rate in the GBM 8401 CD133+ cell line could indicate that this cell line has a higher DNA repair capability; such a high γ-H2AX expression has also been observed in several stem cell studies. Turinetto et al. reported high basal γ-H2AX expression in mouse embryonic and induced pluripotent stem cells (iPSC), and they also observed that γ-H2AX expression de-creased during embryonic stem cell (ESC) and iPSC differentiation. Moreover, they noted that high γ-H2AX expression maintained the self-renewal properties of ESC and iPSC [24]. Fernando et al. observed that H2AX phosphorylation following GABAA receptor activation could limit neural stem cell proliferation [25]. These results strongly indicate that
    Fig. 5. The fluorescence images of GBM8401 cells after α-particle irradiation. Panel (A) shows the DAPI image; panel (B) the γ-H2AX staining image; panel (C) the overlapping image of (A) and (B).
    the high γ-H2AX expression observed in CSCs in the present study was closely related to their self-renewal characteristics.
    4. Conclusions
    An increasing number of studies have observed that GBM CSCs are resistant to DNA-damaging agents such as ionizing radiation and te-mozolomide [26]. Radio-oncologists firmly believe that high-LET charged-particle therapies such as carbon therapy and boron neutron capture therapy can heighten DNA damage in GBM cancer cells and thus increase tumor necrosis or apoptosis. However, the use of charged-particle cell irradiation platforms is not widespread, and data from radiobiological studies are thus lacking. In this study, we demonstrated the capabilities of a vertical charged-particle irradiation platform in GBM CSC studies. All of the results, such as high survival fraction and high γ-H2AX signal expression and dissolving rate, indicated that DNA repair capability in the GBM CD133+ cell line was upregulated after α-particle irradiation. However, γ-H2AX signal overexpression could in-duce highly phosphorylated cell-cycle checkpoint protein expression as well as self-renewal in CSCs. Therefore, downregulating γ-H2AX ex-pression in CSCs and interrupting their subsequent self-renewal me-chanism is essential in developing GBM treatment options.
    The permanent human brain malignant glioma cell line 8401 was kindly provided by Dr. Wei-Hwa Lee. We also thank the financial support from the Ministry of Science and Technology, Taiwan by grant 
    107-2314-B-182-068-MY2, Chang Gung Memorial Hospital by grant CMRPD1H0471 and the youth visited researcher program by grant 2017TW2JA0003 form the Institute of modern physics, Chinese Academy of Sciences, China. This manuscript was edited by Wallace Academic Editing.
    107 ORIGINAL ARTICLE: Clinical Endoscopy
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    Shanghai, China; Irvine, California, USA