Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition.

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🔗 View Article (PMC 2706929)

Published in Cancer Res on June 23, 2009

Authors

Alexandra C Racanelli1, Scott B Rothbart, Cortney L Heyer, Richard G Moran

Author Affiliations

1: Department of Pharmacology and the Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298-0035, USA.

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Mechanism of the cytotoxic synergism of fluoropyrimidines and folinic acid in mouse leukemic cells. J Biol Chem (1988) 0.97

Biochemical determinants of tumor sensitivity to 5-fluorouracil: ultrasensitive methods for the determination of 5-fluoro-2'-deoxyuridylate, 2'-deoxyuridylate, and thymidylate synthetase. Proc Natl Acad Sci U S A (1979) 0.97

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Resistance to methotrexate in thymidylate synthetase-deficient mutants of cultured mouse mammary tumor FM3A cells. Cancer Res (1981) 0.94

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