Cancer Chemotherapy: Concepts, Clinical Investigations and by Neil W. Gibson (auth.), F. M. Muggia (eds.)

By Neil W. Gibson (auth.), F. M. Muggia (eds.)

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72. Priest DG and Mangum M: Relative affinity of 5,1O-methylenetetrahydrofolylpolyglutamates for the Lactobacillus casei thymidylate synthetase-5-fluorodeoxyuridylate binary complex. Arch Biochem Biophys 210:118-123, 1981. 73. Danenberg PV and Lockshin A: Tight-binding complexes of thymidylate synthetase, folate analogs, and deoxyribonudeotides. Adv Enzyme Regul 20:99-110, 1982. 74. Priest DG, Happel KK, Mangum M, Bednarek 1M, Doig MT, and Baugh CM: Tissue folylpolyglutamate chain-length characterization by electrophoresis as thymidylate synthetasefluorodeoxyuridylate ternary complexes.

69. Cheng Y-C, Dutschman GE, Starnes MC, Fisher MH, Nanavathi T, and Nair MG: Activity of the new antifolate N lO-propargyl-5,8-dideazafolate and its polyglutamates against human dihydrofolate reductase, human thymidylate synthetase, and KB cells containing different levels of dihydrofolate reductase. Cancer Res 45:598-600, 1985. 70. Radparvar S, Houghton Pl, and Houghton lA: Characteristics of thymidylate synthase purified from a human colon adenocarcinoma. Arch Biochem Biophys 260:342-350,1988.

Indeed, this is being evaluated in patients with colorectal adenocarcinoma receiving FUraleucovorin using the nucleoside transport inhibitor dipyridamole [111]. However, data are too preliminary at present to ascertain the efficacy of this approach. A second approach is that based upon observations by Scanlon and colleagues [112], who suggested that cis-dichlorodiamminoplatinum II (cis-DDP) 37 inhibited methionine uptake into cells. It was proposed that, in response to decreased methionine levels, cells increased both methionine biosynthesis and the pools of reduced folate cofactors.

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