Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Jan 2004
Randomized Controlled Trial Clinical TrialEffects of reduced cigarette smoking on the uptake of a tobacco-specific lung carcinogen.
Limited data are available on carcinogen uptake in smokers who reduce their smoking. To determine whether reducing the number of cigarettes smoked per day would lead to a corresponding reduction in carcinogen uptake, we measured levels of metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the urine of smokers who reduced their smoking for up to 26 weeks. ⋯ Statistically significant reductions in levels of urinary metabolites of a tobacco-specific lung carcinogen were achieved by reduction in smoking, but for most smokers, reductions were modest and transient.
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J. Natl. Cancer Inst. · Jan 2004
Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression.
Alternative treatment options are needed for advanced neuroblastoma patients because their prognosis remains poor after intensive chemotherapy. Neuroblastoma cells express platelet-derived growth factor (PDGF), stem cell factor (SCF), and vascular endothelial growth factor (VEGF) and their respective receptors, PDGFR, c-Kit, and Flk-1. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the tyrosine kinase activities of c-Kit and PDGFR, on the growth of neuroblastoma cells in vivo and in vitro. ⋯ Imatinib inhibited the growth of neuroblastoma cells in vitro and in vivo. This inhibition was associated with suppression of PDGFR and c-Kit phosphorylation and inhibition of VEGF expression.
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J. Natl. Cancer Inst. · Jan 2004
Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361.
Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA strand breaks. Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging chemotherapy and radiation therapy in vitro. Because classical PARP-1 inhibitors have limited clinical utility, we investigated whether AG14361, a novel potent PARP-1 inhibitor (inhibition constant <5 nM), enhances the effects of chemotherapy and radiation therapy in human cancer cell cultures and xenografts. ⋯ AG14361 is, to our knowledge, the first high-potency PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer.