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- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 2. |
- Hu, Minyu, et al.
(författare)
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Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits
- 2008
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Ingår i: Nutrition Journal. - : Elsevier BV. - 1475-2891. ; 24:10, s. 1030-1038
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Tidskriftsartikel (refereegranskat)abstract
- Objective We evaluated the antiatherogenic effect of lycopene in rabbits fed a high-fat diet. Methods Forty adult male rabbits were divided into five groups that were fed a standard diet, a high-fat diet, a high-fat diet plus 4 mg/kg of lycopene, a high-fat diet plus 12 mg/kg of lycopene, and a high-fat diet plus 10 mg/kg of fluvastatin, respectively. Lycopene and fluvastatin were administered intragastrically. The level of serum total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total antioxidant capacity, and malondialdehyde were measured before and after 4 and 8 wk of experimental treatment. In addition, plasma levels of lycopene, oxidized low-density lipoprotein, serum nitric oxide, and interleukin-1 were measured after the experiment. The area of atherosclerotic plaque and pathologic changes of the aorta were evaluated. Results Compared with the control, levels of total cholesterol, total triacylglycerol, low-density lipoprotein cholesterol, malonaldehyde, oxidized low-density lipoprotein, and interleukin-1 were increased and total antioxidant capacity and nitric oxide were decreased in the animals with a high-fat diet (P < 0.05). Intragastric administration of lycopene counteracted the change in these parameters (P < 0.05). In this case, the data showed that lycopene in the used dose was better than the fluvastatin intervention. Morphologic analysis revealed that lycopene and fluvastatin markedly reduced the formation of atherosclerotic plaques in the aorta compared with the situation in rabbits on a high-fat diet alone. Conclusion Lycopene, like fluvastatin, significantly attenuated atherogenesis in rabbits fed a high-fat diet.
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