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| 1 | Cell sensitivity as- says: the mtt assay显示文摘 | van Meerloo J Kaspers G J Cloos J | 2011 | Methods Mol Biol2011,731,: | 1 |
| 2 | Cell sensitivity assays: the MTT assay显示文摘 | van Meerloo J Kaspers G J Cloos J | 2011 | Methods Mol Biol2011,731,: | 1 |
| 3 | The adaptor protein ARH escorts megalin to and through endosomes显示文摘 | Nagai M Meerloo T Takeda T | 2003 | Molecular Biology of the Cell2003,14,12: | 1 |
| 4 | Cell sensitivity assays: the MTT assay显示文摘 | van Meerloo J Kaspers GJ Cloos J | 2011 | Methods Mol Biol2011,731,: | 1 |
| 5 | Cell sensitivity assays: the MTTassay显示文摘 | Van Meerloo J Kaspers G J Cloos J | 2011 | Methods Mol Biol2011,731,: | 1 |
| 6 | Escrt-Ⅲ:an endosome-associated heterooligomeric protein complex required for mvb sorting显示文摘 | Babst M Katzmann D J Estepa-Sabal E J Meerloo T Emr S D | | 0,,02: | 1 |
| 7 | Cell sensitivity assays:the MTT assay显示文摘 | Van Meerloo J Kaspers GJ Cloos J | | 0,,: | 1 |
| 8 | Cell sensitivity assays: the MTr assay显示文摘 | Van Meerloo J Kaspers G J Cloos J | 2011 | Methods Mol Biol2011,731,3: | 1 |
| 9 | Cell sensitivity assays: the MTT assay 显示文摘 | Van Meerloo J Kaspers GJ Cloos J | 2011 | MethodsMolBiol2011,731,: | 1 |
| 10 | Calnuc, an EF-hand Ca(2+)-binding protein, is stored and processed in the Golgi and secreted by the constitutive-like pathway in AtT20 cells显示文摘 | Lavoie C Meerloo T Lin P | 2002 | Mol Endocrinol2002,16,11: | 1 |
| 11 | Cell sensitivity assays: the MTT assay显示文摘 | van Meerloo J Kaspers GJ Cloos J | 2011 | Methods Mol Biol2011,731,: | 1 |
| 12 | Cell sensitivity assays: the MIT assay显示文摘 | VAN MEERLOO J KASPERS G J CLOOS 1 | 2011 | Methods Mol Bioi2011,731,: | 1 |
| 13 | Statins markedly potentiate aminopeptidase inhibitor activity against(drug-resistant)human acute myeloid leukemia cells显示文摘Aim: This study aimed to decipher the molecular mechanism underlying the synergistic effect of inhibitors of the mevalonate-cholesterol pathway (i.e., statins) and aminopeptidase inhibitors (APis) on APi-sensitive and -resistant acute myeloid leukemia (AML) cells.Methods: U937 cells and their sublines with low and high levels of acquired resistance to (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester (CHR2863), an APi prodrug, served as main AML cell line models. Drug combination effects were assessed with CHR2863 and in vitro non-toxic concentrations of various statins upon cell growth inhibition, cell cycle effects, and apoptosis induction. Mechanistic studies involved analysis of Rheb prenylation required for mTOR activation.Results: A strong synergy of CHR2863 with the statins simvastatin, fluvastatin, lovastatin, and pravastatin was demonstrated in U937 cells and two CHR2863-resistant sublines. This potent synergy between simvastatin and CHR2863 was also observed with a series of other human AML cell lines (e.g., THP1, MV4-11, and KG1), but not with acute lymphocytic leukemia or multiple solid tumor cell lines. This synergistic activity was: (i) specific for APis (e.g., CHR2863 and Bestatin), rather than for other cytotoxic agents;and (ii) corroborated by enhanced induction of apoptosis and cell cycle arrest which increased the sub-G1 fraction. Consistently, statin potentiation of CHR2863 activity was abrogated by co-administration of mevalonate and/or farnesyl pyrophosphate, suggesting the involvement of protein prenylation;this was experimentally confirmed by impaired Rheb prenylation by simvastatin.Conclusion: These novel findings suggest that the combined inhibitory effect of impaired Rheb prenylation and CHR2863-dependent mTOR inhibition instigates a potent synergistic inhibition of statins and APis on human AML cells. | Gerrit Jansen Marjon Al Yehuda G.Assaraf Sarah Kammerer Johan van Meerloo Gert J.Ossenkoppele Jacqueline Cloos Godefridus J.Peters | 2023 | Cancer Drug Resistance2023,6,3: | 0 |