Diagnostic Microdosing Approach to Study Gemcitabine Resistance [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 615.8 Specific therapies and kinds of therapies

Thông tin xuất bản: Livermore, Calif : Oak Ridge, Tenn. : Lawrence Livermore National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016

Mô tả vật lý: Size: p. 1843-1848 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 260779

 Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. In this paper, we determined whether subtherapeutic ?microdoses? of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of <
 sup>
 14<
 /sup>
 C-labeled gemcitabine for 4?24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. Finally, these results support gemcitabine levels in DNA as a potential biomarker of drug cytotoxicity.
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