Mice (BDF(1)) inoculated with L1210 leukemia survive for a statistically significantly longer span when four courses of arabinosyl cytosine are administered at 4-day intervals-not in courses consisting of eight equal doses at 3-hour intervals, but in sinusoidally increasing and decreasing 24-hour courses, the largest amount being given at previously mapped circadian and circannual times of peak host resistance to the drug. This finding relates to the many therapeutic situations involving rhythmic, and thus predictable, cycles in the host's tolerance of undesired effects from the agent used.
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http://dx.doi.org/10.1126/science.177.4043.80 | DOI Listing |
ACS Appl Mater Interfaces
February 2023
CIB-Interuniversity Consortium for Biotechnologies, University of Catania, Via Flavia, 23/1, 34148Trieste, Italy.
Leuk Res
October 2017
Department of Pediatrics, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan. Electronic address:
Fms-like tyrosine kinase 3 (FLT3) is highly expressed in mixed-lineage leukemia (MLL) gene-rearranged acute lymphoblastic leukemia (MLL+ALL) with a dismal prognosis. We previously reported that FLT3 ligand (FL) stimulation induced cell cycle arrest in MLL+ALL cells leading to resistance against anti-leukemic agents. Given that FL stimulation enhanced transforming growth factor (TGF)β1 mRNA levels in MLL+ALL cells, we extensively examined the effect of TGFβ1 on the cell cycle progression and chemosensitivity in MLL+ALL cells, and found that TGFβ1 stimulation induced MLL+ALL cells into cell cycle arrest resistant to arabinosyl cytosine; its effect was markedly enhanced in synergy with FL.
View Article and Find Full Text PDFMol Cancer Ther
November 2017
Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
2'--cyano-2'-deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes β-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes nonphosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage.
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