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- Hua, Kuo-Tai, et al.
(författare)
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N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
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Ingår i: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
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Tidskriftsartikel (refereegranskat)abstract
- N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
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| 2. |
- Lin, Chun-Yu, et al.
(författare)
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Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages
- 2021
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Ingår i: Life. - : MDPI. - 2075-1729. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 mu M TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and other inflammatory diseases.
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| 3. |
- Ning, Yilin, et al.
(författare)
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Handling ties in continuous outcomes for confounder adjustment with rank-ordered logit and its application to ordinal outcomes
- 2020
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Ingår i: Statistical Methods in Medical Research. - : SAGE Publications. - 0962-2802 .- 1477-0334. ; 29:2, s. 437-454
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Tidskriftsartikel (refereegranskat)abstract
- The rank-ordered logit (rologit) model was recently introduced as a robust approach for analysing continuous outcomes, with the linear exposure effect estimated by scaling the rank-based log-odds estimate. Here we extend the application of the rologit model to continuous outcomes with ties and ordinal outcomes treated as imperfectly-observed continuous outcomes. By identifying the functional relationship between survival times and continuous outcomes, we explicitly establish the equivalence between the rologit and Cox models to justify the use of the Breslow, Efron and perturbation methods in the analysis of continuous outcomes with ties. Using simulation, we found all three methods perform well with few ties. Although an increasing extent of ties increased the bias of the log-odds and linear effect estimates and resulted in reduced power, which was somewhat worse when the model was mis-specified, the perturbation method maintained a type I error around 5%, while the Efron method became conservative with heavy ties but outperformed Breslow. In general, the perturbation method had the highest power, followed by the Efron and then the Breslow method. We applied our approach to three real-life datasets, demonstrating a seamless analytical workflow that uses stratification for confounder adjustment in studies of continuous and ordinal outcomes.
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