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Li B, Gao YJ, Wu XY, et al. Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response. Oncol Lett. 2017;14(3):3261-3267doi: 10.3892/ol.2017.6504.
Li, B., Gao, Y. J., Wu, X. Y., Cui, J., Long, Y., Xu, J. L., & Ding, D. G. (2017). Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response. Oncology letters, 14(3), 3261-3267. https://doi.org/10.3892/ol.2017.6504
Li, Bo, et al. "Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response." Oncology letters vol. 14,3 (2017): 3261-3267. doi: https://doi.org/10.3892/ol.2017.6504
Li B, Gao YJ, Wu XY, Cui J, Long Y, Xu JL, Ding DG. Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response. Oncol Lett. 2017 Sep;14(3):3261-3267. doi: 10.3892/ol.2017.6504. Epub 2017 Jun 30. PMID: 28927075; PMCID: PMC5588012.
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Oncol Lett. 2017 Sep;14(3):3261-3267. doi: 10.3892/ol.2017.6504. Epub 2017 Jun 30.

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

Oncology letters

Bo Li, Yong-Ju Gao, Xin-Yu Wu, Jing Cui, Ye Long, Jun-Ling Xu, De-Gang Ding

Affiliations

  1. Department of Nuclear Medicine, Henan Provincial People's Hospital and The People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
  2. Department of Urology Surgery, Henan Provincial People's Hospital and The People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.

PMID: 28927075 PMCID: PMC5588012 DOI: 10.3892/ol.2017.6504

Abstract

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

Keywords: DNA damage checkpoint; ionizing radiation; radiation resistance; renal clear cell carcinoma; tumor initiating cells

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