Publications (2)5.23 Total impact
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Article: A cell-based high-throughput assay for the screening of small-molecule inhibitors of p53-MDM2 interaction.
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ABSTRACT: The p53 tumor suppressor is a potent transcription factor that regulates cell growth inhibition and apoptosis. The oncoprotein MDM2 suppresses p53 activity by direct inhibition of its transcriptional activity and enhances the degradation of p53 via the ubiquitin-proteosome pathway. Overexpression of MDM2, found in many human tumors, impairs p53-mediated cell death effectively. Inhibition of the p53-MDM2 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. To search for new inhibitors of the p53-MDM2 interaction, the authors developed a cell-based high-throughput assay system based on mammalian two-hybrid technology. They also used a dual-luciferase reporter system to rule out false- positive hits due to the cytotoxic effect of compounds. Using this assay, they screened a library consisting of 3840 compounds and identified one compound that activates p53 pathway and induces growth arrest in tumor cells.Journal of Biomolecular Screening 04/2011; 16(4):450-6. · 2.05 Impact Factor -
Article: Effects of O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms on cancer: a meta-analysis.
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ABSTRACT: O(6)-methylguanine-DNA methyltransferase is one of the rare proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway. Its two common single-nucleotide polymorphisms, Leu84Phe and Ile143Val, had previously been identified to contribute to susceptibility of cancer. However, there are conflicting results in studies on the association of the two polymorphisms with cancer. Therefore, we conducted a meta-analysis to clarify the paradox with a large collected sample (13,069 cancer patients and 20,290 controls). We found significant association between the T allele (84Phe) and cancer risk, under the recessive genetic model [P = 0.023, odds ratio (OR) = 1.251, 95% confidence interval (CI) 1.031-1.517, P(heterogeneity) = 0.270], TT versus CC comparison (P = 0.035, OR = 1.239, 95% CI 1.015-1.511, P(heterogeneity) = 0.225) and TT versus CT comparison (P = 0.007, OR = 1.292, 95% CI 1.071-1.559, P(heterogeneity) = 0.374), using the random-effect model. In the ethnicity subgroup analysis, a significant association with cancer among Caucasians was found under the recessive genetic model, homozygote comparison and TT versus TC comparison. In the tumour sites subgroup analysis, only the protective effects of Leu84Phe polymorphism were found in colorectal cancer, under CT versus CC comparison. No significant association between the G allele of Ile143Val and cancer risk was found. The G allele showed an increased lung cancer risk under the dominant genetic model and AG versus AA comparison in all Hardy-Weinberg equilibrium subjects, only when the fixed-effect model was used. However, it was insignificant in the random-effect model.Mutagenesis 11/2009; 25(1):83-95. · 3.18 Impact Factor
