Targeting radiation-resistant hypoxic tumour cells through ATR inhibition
نویسندگان
چکیده
منابع مشابه
Targeting hypoxic cells through the DNA damage response.
Exposure to hypoxia-induced replication arrest initiates a DNA damage response that includes both ATR- and ATM-mediated signaling. DNA fiber analysis was used to show that these conditions lead to a replication arrest during both the initiation and elongation phases, and that this correlated with decreased levels of nucleotides. The DNA damage response induced by hypoxia is distinct from the cl...
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Exposure to hypoxia-induced replication arrest initiates a DNA damage response that includes both ATRand ATM-mediated signaling. DNA fiber analysis was used to show that these conditions lead to a replication arrest during both the initiation and elongation phases, and that this correlated with decreased levels of nucleotides. The DNA damage response induced by hypoxia is distinct from the clas...
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Tumor-initiating cells (TICs) have been shown both experimentally and clinically to be resistant to radiation and chemotherapy, potentially resulting in residual disease that can lead to recurrence. In this study, we demonstrate that TICs isolated from p53 null mouse mammary tumors repair DNA damage following in vivo ionizing radiation more efficiently than the bulk of the tumor cells. Down-reg...
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To target malignant cells residing in hypoxic regions of solid tumors, we have designed and synthesized prodrugs generating the cytotoxic alkylating species 1,2-bis(methylsulfonyl)-1-(2chloroethyl)hydrazine (90CE) after bioreductive activation. We postulate that one of these agents, 1,2-bis(methylsulfonyl)-1(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119), requires enzymat...
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ژورنال
عنوان ژورنال: British Journal of Cancer
سال: 2012
ISSN: 0007-0920,1532-1827
DOI: 10.1038/bjc.2012.265