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HFL FORM 938 PDF

We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. TPK1 knockdown caused significant radiosensitization in cancer but not normal tissue cell lines. Other means of blocking this pathway, knockdown of thiamine transporter-1 THTR1 or treatment with the thiamine analogue pyrithiamine hydrobromide PyrH caused significant tumor specific radiosensitization. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitization target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumor specific radiosensitization. Surrogate markers and viability assays evaluating tumor cell survival following radiation have previously been used in radiation sensitivity screens [ 1 - 3 ] but have several limitations. In particular cell viability assays such as the 3- 4,5-Dimethylthiazolyl -2,5-diphenyl tetrazolium bromide MTT assay, which measure the number of cells in active metabolism are unreliable for radiation studies for several reasons.

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