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Effects of thymidylate synthase inhibition on thymidine kinase activity and nucleoside transporter expression.
Data suggest that TK activity and NT expression have a common regulatory mechanism which is sensitive to endogenous dTTP pools and that the salvage pathway is a complex system of kinases coordinated with transport of nucleosides. Expand
Combination studies with 3'-azido-3'-deoxythymidine (AZT) plus ICI D1694. Cytotoxic and biochemical effects.
It is suggested that AZT plus ICI D1694 may increase antitumor effect with minimal myelosuppression and CFU-GM survival, exposed to drug concentrations as those used in the tumor cell lines, revealed that the therapeutic index was greater for AZTPlusICI D 1694 than for ICID1694 alone. Expand
Modulation of the equilibrative nucleoside transporter by inhibitors of DNA synthesis.
- J. Pressacco, J. Wiley, G. Jamieson, C. Erlichman, D. Hedley
- Biology, Medicine
- British Journal of Cancer
- 1 October 1995
It is found that surface expression of the es nucleoside transporter is regulated by a mechanism which is sensitive to the supply of deoxynucleotides, and this mechanism might be particularly sensitive to dTTP pools. Expand
ICI D1694 and idoxuridine: a synergistic antitumor combination.
It is suggested that IdUrd plus D1694 is a promising new drug combination, which may have a favorable therapeutic index in vivo, and was synergistic in both MGH-U1 and HCT-8 cells as determined by median-effect analysis. Expand
Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells
- B. Mitrovski, J. Pressacco, S. Mandelbaum, C. Erlichman
- Chemistry, Medicine
- Cancer Chemotherapy and Pharmacology
C2-desamino C2-methyl dideazafolates are potent TS inhibitors, survival is correlated with inhibition of TS for the folate-based TS inhibitors and the biochemical consequences of TS inhibition include increased dUMP and dUrd levels. Expand
Biochemical modulation of iododeoxyuridine by N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2,6-diaminobenz[cd]indole glucuronate (AG-331) leading to enhanced cytotoxicity.
- J. Pressacco, B. Mitrovski, D. Hedley, R. Tsang, C. Erlichman
- Biology, Medicine
- Biochemical pharmacology
- 29 June 1995
The combination of IdUrd and AG-331 may enhance antitumor effects with minimal myelosuppression in vivo, and the combination resulted in an enhanced antitumors effect, as compared with the effect of either agent alone. Expand
Interactions of bupranolol with the polymorphic debrisoquine/sparteine monooxygenase (CYP2D6)
Although the methods were not sufficiently sensitive to measure the Km of bupranolol directly, it is undoubtedly the β-adrenoceptor blocker with the highest-known apparent affinity for CYP2D6. Expand
Cytotoxic and biochemical implications of combining AZT and AG-331
These studies support the original premise that TS inhibition favors increased incorporation of AZT into DNA and that the combination causes more cell kill than either drug alone in MGH-U1 cells. Expand