Clinical characteristics, risk factors, and outcomes after adjuvant radiotherapy for patients with thymoma in the United States: analysis of the Surveillance, Epidemiology, and End Results (SEER) Registry (1988–2013)

<p><b>Purpose:</b> The surgery with adjuvant radiation for the treatment of thymoma is still debated. The aim of this study was to examine the efficacy of postoperative radiotherapy (PORT) in a population-based registry of patients with thymoma.</p> <p><b>Materials and methods:</b> We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results database to compare the outcomes of patients with thymoma who received surgery with or without PORT.</p> <p><b>Results:</b> Among the 2234 patients of this study, the surgery with PORT group had a longer mean overall survival (OS) and cancer-specific survival (CSS) than did the surgery without PORT group (OS: 172.3 vs. 155.3 months, <i>p</i> = .005; CSS: 247.3 vs. 241.8 months, <i>p</i> = .04). PORT significantly improved OS and CSS of patients with stage III/IV disease, but decreased CSS for those with stage I/IIA disease. Although the surgery with PORT group had a higher rate of secondary cancers, the between-group difference in the disease-free interval was not significant.</p> <p><b>Conclusions:</b> PORT provides a significant benefit for patients with thymoma, particularly those with advanced disease. However, it also increases the risk of a second malignancy. We suggest that treatment guidelines should adopt a more positive stance on the use of PORT.</p

Ingredients and nutrient content of the basal diets.

<p>CP, crude protein.</p><p>^<b>†</b>The premix provided per kilogram of diet: 100 mg of zinc as zinc oxide, 100 mg of iron as iron sulphate, 30 mg of manganese as manganous oxide, 0.3 mg of selenium as sodium selenite, 20 mg of copper as copper sulphate, 0.5 mg of iodine as calcium iodate, 1720 μg retinyl acetate, 8.0 mg DL-α-tocopheryl acetate, 25 μg cholecalciferol, 3.0 mg menadione sodium bisulphite, 3.0 mg pyridoxine hydrochloride, 2.0 mg thiamin mononitrate, 6.0 mg riboflavin, 1.0 mg folic acid, 20 μg cyanocobalamin, 30 mg nicotinic acid, 30 mg calcium pantothenate, 300 mg choline.</p><p>^<b>‡</b>Values for standardized ileal concentrations of AA were calculated using standardized ileal digestible coefficients provided by Xiong et al., [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139393#pone.0139393.ref028" target="_blank">28</a>]</p><p>Ingredients and nutrient content of the basal diets.</p

Protein levels of total (a) and phosphorylated (b) p70S6K1 in skeletal muscle.

<p>β-actin was used to normalize the abundance of total and phosphorylated S6K1. Values are means ± SEM. <i>P<0</i>.<i>05</i> was considered significant difference. Protein levels were analysed with pen as the experimental unit (n = 3). NP, normal protein diet (14% CP); NP+CS, normal protein diet supplemented with cysteamine; LP, low-protein diet (10% CP); LP+CS, low-protein diet supplemented with cysteamine. P, main effect of dietary protein levels; CS, main effect of cysteamine supplementation; P×CS, interaction between main effects of dietary protein levels and cysteamine supplementation.</p

Effects of dietary crude protein levels and cysteamine (CS) supplementation on mRNA abundance of IGF-1 (insulin)/Akt/FOXO signaling and their target genes in skeletal muscle of finishing pigs.

<p>IGF-1, insulin-like growth factor 1; IGF-1R, IGF-1 receptor; IR, insulin receptor; IRS-1, insulin receptor substrate 1. Akt1, protein kinase B, also named PKB; FOXO, Forkhead Box O; MAFbx, muscle atrophy F-box; MuRF1, muscle Ring finger 1. Values are means ± SEM. Values within a row with different letters differ (<i>P</i><0.05). All traits in this table were analysed with pen as the experimental unit (n = 5). P, main effect of dietary protein levels; CS, main effect of cysteamine supplementation; P×CS, interaction between main effects of dietary protein levels and cysteamine supplementation.</p><p>Effects of dietary crude protein levels and cysteamine (CS) supplementation on mRNA abundance of IGF-1 (insulin)/Akt/FOXO signaling and their target genes in skeletal muscle of finishing pigs.</p

Effects of dietary crude protein levels and cysteamine (CS) supplementation on plasma metabolite and hormone concentrations of finishing pigs.

<p>IGF-1, insulin-like growth factor 1; SS, somatostatin; PUN, plasma urea nitrogen. Values are means ± SEM. Values within a row with different letters differ (<i>P</i><0.05). All traits in this table were analysed with pen as the experimental unit (n = 5). P, main effect of dietary protein levels; CS, main effect of cysteamine supplementation; P×CS, interaction between main effects of dietary protein levels and cysteamine supplementation.</p><p>Effects of dietary crude protein levels and cysteamine (CS) supplementation on plasma metabolite and hormone concentrations of finishing pigs.</p

Protein levels of total (a) and phosphorylated (b) mammalian target of rapamycin in skeletal muscle.

<p>β-actin was used to normalize the abundance of total and phosphorylated mTOR. Values are means ± SEM. <i>P<0</i>.<i>05</i> was considered significant difference. Protein levels were analysed with pen as the experimental unit (n = 3). NP, normal protein diet (14% CP); NP+CS, normal protein diet supplemented with cysteamine; LP, low-protein diet (10% CP); LP+CS, low-protein diet supplemented with cysteamine. P, main effect of dietary protein levels; CS, main effect of cysteamine supplementation; P×CS, interaction between main effects of dietary protein levels and cysteamine supplementation.</p

Primer pairs used in the real-time PCR^†.

<p>^<b>†</b>The primer pairs above were reported by Zhang et al., [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139393#pone.0139393.ref017" target="_blank">17</a>].</p><p><i>Akt</i>, protein kinase B, also named PKB; <i>IGF-1</i>, insulin-like growth factor 1; <i>IGF-1R</i>, <i>IGF-1</i> receptor; <i>IR</i>, insulin receptor; <i>IRS-1</i>, insulin receptor substrate 1; <i>FOXO</i>, Forkhead Box O; <i>MAFbx</i>, muscle atrophy F-box; <i>MuRF1</i>, muscle Ring finger 1.</p><p>Primer pairs used in the real-time PCR<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139393#t002fn001" target="_blank">^†</a>.</p

Protein levels of total (a) and phosphorylated (b) eIF4E-binding protein 1 in skeletal muscle.

<p>β-actin was used to normalize the abundance of total and phosphorylated 4E-BP1. Values are means ± SEM. <i>P<0</i>.<i>05</i> was considered significant difference. Protein levels were analysed with pen as the experimental unit (n = 3). NP, normal protein diet (14% CP); NP+CS, normal protein diet supplemented with cysteamine; LP, low-protein diet (10% CP); LP+CS, low-protein diet supplemented with cysteamine. P, main effect of dietary protein levels; CS, main effect of cysteamine supplementation; P×CS, interaction between main effects of dietary protein levels and cysteamine supplementation.</p

Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes

We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (<b>1</b>), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to the synthesis of a series of benzyloxy analogues. Compound <b>28</b> was chosen for further profiling because of its favorable physicochemical properties and excellent GPR119 potency across species. This compound exhibited a clean off-target profile in counterscreens and good <i>in vivo</i> efficacy in mouse oGTT

Discovery of a Potent and Selective ROMK Inhibitor with Pharmacokinetic Properties Suitable for Preclinical Evaluation

A new subseries of ROMK inhibitors exemplified by <b>28</b> has been developed from the initial screening hit <b>1</b>. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of <b>28</b> as a new mechanism diuretic. Robust pharmacodynamic effects in both SD rats and dogs have been demonstrated