Ncreased fraction of cells in G0/G1 (55 compared to 48 for JIMT-1 and 66 compared to 62 for MDA-MB-231 at 48 h). Of note, cells have poor viability after T-STAR overexpression and as only cells with intact morphology can be analysed, the differences are less pronounced compared to the proliferation data. However, data from both knock-down and overexpression studies are in agreement with the survival data presented here, where patients with expression of T-STAR showed an increased RFS. It is also supported by previous work where expression is associated with arrested cell growth [18,38]. Further studies are needed to understand the molecular mechanism of T-STAR growth regulation. To get further insight into the function of T-STAR, previous studies on Sam68, one of its closest relatives, are of value. Sam68 is bound and phosphorylated by many different kinases, i.e. Src, PI3K and PLCc1, and the protein seems to have many target mRNAs, among others CD44, Bcl-X, mTOR and cyclin D1 [16,41]. In the TNF receptor pathway, Sam68 is required for both NF-kB activation and apoptosis signaling [42]. T-STAR, on the other hand, has only been found to interact with one kinase; the breast tumor kinase (BRK), and with only one SH3 binding domain it is not likely toserve as a scaffold protein [16,43]. Interestingly, BRK is the only kinase that co-localizes with Sam68 in the nucleus [16,44], suggesting that this kinase, which has been associated to breast cancer motility [44], is closely connected to the function of the RNA binding proteins. Thus, future studies of the relationship between T-STAR and BRK are of importance to Fruquintinib elucidate the molecular function of T-STAR in breast cancer.ConclusionsUsing a novel antibody reagent, IHC analysis revealed an association between the RNA-binding protein T-STAR and RFS of patients afflicted by primary invasive breast cancer. The expression of T-STAR also correlated with positive HER2 status and hormone receptor negativity. This finding is of major interest as it offers potential as a complement to the current biomarkers ER, PgR and HER2 in prognosis of the disease. In agreement with clinical data, functional studies in breast cancer cell lines showed a strong correlation between T-STAR expression and proliferation, indicating that T-STAR regulation is of importance for both clinical outcome and also breast cancer tumor growth.Supporting InformationTable SClinicopathological characteristics of thepatients. (DOCX)AcknowledgmentsWe thank Elise Nilsson for excellent technical assistance.T-STAR Protein Expression in Breast CancerAuthor ContributionsConceived and designed the experiments: SS CB KJ SE. Performed the experiments: SS. Analyzed the data: SS KJ SE. Contributed reagents/ materials/analysis tools: MU. Wrote the paper: SS KJ SE.
Symptomatic obstructive sleep apnea (OSA) is a breathing disorder that affects 6?3 of the adult Western population [1]. In addition to daytime sleepiness, OSA is implicated in the pathogenesis of cardiovascular diseases, including hypertension, coronary artery disease, congestive heart failure, stroke, cardiac arrhythmias, and sudden cardiac death. The mechanisms 23977191 by which OSA affects the cardiovascular SC 66 system may result from excursions in intrathoracic pressure, sympathoexcitation, and intermittent hypoxemia (IH; cycles of oxygen desaturation and re-oxygenation) [2]. Untreated OSA induces oxidative stress, inflammation, and endothelial cell (EC) dysfunction [3], which have been confirm.Ncreased fraction of cells in G0/G1 (55 compared to 48 for JIMT-1 and 66 compared to 62 for MDA-MB-231 at 48 h). Of note, cells have poor viability after T-STAR overexpression and as only cells with intact morphology can be analysed, the differences are less pronounced compared to the proliferation data. However, data from both knock-down and overexpression studies are in agreement with the survival data presented here, where patients with expression of T-STAR showed an increased RFS. It is also supported by previous work where expression is associated with arrested cell growth [18,38]. Further studies are needed to understand the molecular mechanism of T-STAR growth regulation. To get further insight into the function of T-STAR, previous studies on Sam68, one of its closest relatives, are of value. Sam68 is bound and phosphorylated by many different kinases, i.e. Src, PI3K and PLCc1, and the protein seems to have many target mRNAs, among others CD44, Bcl-X, mTOR and cyclin D1 [16,41]. In the TNF receptor pathway, Sam68 is required for both NF-kB activation and apoptosis signaling [42]. T-STAR, on the other hand, has only been found to interact with one kinase; the breast tumor kinase (BRK), and with only one SH3 binding domain it is not likely toserve as a scaffold protein [16,43]. Interestingly, BRK is the only kinase that co-localizes with Sam68 in the nucleus [16,44], suggesting that this kinase, which has been associated to breast cancer motility [44], is closely connected to the function of the RNA binding proteins. Thus, future studies of the relationship between T-STAR and BRK are of importance to elucidate the molecular function of T-STAR in breast cancer.ConclusionsUsing a novel antibody reagent, IHC analysis revealed an association between the RNA-binding protein T-STAR and RFS of patients afflicted by primary invasive breast cancer. The expression of T-STAR also correlated with positive HER2 status and hormone receptor negativity. This finding is of major interest as it offers potential as a complement to the current biomarkers ER, PgR and HER2 in prognosis of the disease. In agreement with clinical data, functional studies in breast cancer cell lines showed a strong correlation between T-STAR expression and proliferation, indicating that T-STAR regulation is of importance for both clinical outcome and also breast cancer tumor growth.Supporting InformationTable SClinicopathological characteristics of thepatients. (DOCX)AcknowledgmentsWe thank Elise Nilsson for excellent technical assistance.T-STAR Protein Expression in Breast CancerAuthor ContributionsConceived and designed the experiments: SS CB KJ SE. Performed the experiments: SS. Analyzed the data: SS KJ SE. Contributed reagents/ materials/analysis tools: MU. Wrote the paper: SS KJ SE.
Symptomatic obstructive sleep apnea (OSA) is a breathing disorder that affects 6?3 of the adult Western population [1]. In addition to daytime sleepiness, OSA is implicated in the pathogenesis of cardiovascular diseases, including hypertension, coronary artery disease, congestive heart failure, stroke, cardiac arrhythmias, and sudden cardiac death. The mechanisms 23977191 by which OSA affects the cardiovascular system may result from excursions in intrathoracic pressure, sympathoexcitation, and intermittent hypoxemia (IH; cycles of oxygen desaturation and re-oxygenation) [2]. Untreated OSA induces oxidative stress, inflammation, and endothelial cell (EC) dysfunction [3], which have been confirm.