Lanehorn5930

Indoleamine 2,3-dioxygenase 1 (IDO1) is closely associated with immune escape in many tumor tissues, and is considered to be a valuable therapeutic target in cancer immunotherapy. In this study, the modification of amino sidechain was performed with the hydroxyamidine core kept intact to optimize lead compound Epacadostat. 19 new compounds with hydrazide, thietane or sulfonamide moiety as polar capping group in sidechain were prepared and their IDO1 inhibitory activities were evaluated. Sulfonamide 3a showed potent IDO1 inhibition in both enzymatic and cellular assays with the IC50 value of 71 nM and EC50 value of 11 nM, respectively. Furthermore, in vivo Lewis lung cancer (LLC) allograft studies of 3a indicated that it handicapped the tumor growth with similar efficacy to Epacadostat. Molecular docking demonstrated that the change of polar capping group affords influence on the orientation of amino ethylene side chain and forms new hydrogen bonding. BACKGROUND The Bismuth-Corlette (BC) classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary tree. As the right hepatic artery crosses just behind the left bile duct, we hypothesized that BC IIIb tumors would have a higher likelihood of local unresectability due to involvement of the contralateral artery. METHODS A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma taken to the operating room for intended curative resection between April 2008 and September 2016. Telaprevir nmr Cases were assigned BC stages based on preoperative imaging. RESULTS Sixty-eight patients were included in the study. All underwent staging laparoscopy after which 16 cases were aborted for metastatic disease. Of the remaining 52 cases, 14 cases were explored and aborted for locally advanced disease. Thirty-eight underwent attempt at curative resection. After excluding cases aborted for metastatic disease, the chance of proceeding with resection was 55.6% for BC IIIb staged lesions compared to 80.0% of BC IIIa lesions and to 82.4% for BC I-IIIa staged lesions (P  less then  0.05). About 44.4% of BC IIIb lesions were aborted for locally advanced disease versus 17.6% of remaining BC stages. CONCLUSIONS When hilar cholangiocarcinoma is preoperatively staged as BC IIIb, surgeons should anticipate higher rates of locally unresectable disease, likely involving the right hepatic artery. Sphingomyelin synthase 2 (SMS2) has attracted attention as a drug target for the treatment of various cardiovascular and metabolic diseases. The modification of a high throughput screening hit, 2-quinolone 10, enhanced SMS2 inhibition at nanomolar concentrations with good selectivity against SMS1. To improve the pharmaceutical properties such as passive membrane permeability and aqueous solubility, adjustment of lipophilicity was attempted and 1,8-naphthyridin-2-one 37 was identified as a potent and selective SMS2 inhibitor. A significant reduction in hepatic sphingomyelin levels following repeated treatment in mice suggested that compound 37 could be an effective in vivo tool for clarifying the role of SMS2 enzyme and developing the treatment for SMS2-related diseases. Histone-lysine N-methyltransferase SET7 emerged as a potential target for multiple cancers. In a virtual screening program used to explore new and potent inhibitors of SET7, compound 16 was discovered as a top hit with an IC50 value of 6.02 μM. A further similarity search afforded a new compound 23, which exhibited better activity against SET7 with an IC50 value of 1.96 μM. Importantly, compound 23 selectively inhibited the proliferation of MV4-11 cells. Comprehensively, compound 23 can serve as a lead for further identification and development of more potent SET7 inhibitors. OBJECTIVE To validate a Spanish-language questionnaire on adolescent eating behavior based on Social Cognitive Theory. DESIGN The validity (reliability and construct validity) of a self-administered questionnaire containing 28 questions with Likert scale-type response options was evaluated. SETTING School located in Tonala, Jalisco, Mexico (a peri-urban area) with approximately 1,400 students enrolled. PARTICIPANTS One hundred fifty-two adolescents enrolled in the second year of a middle school in Tonalá, Jalisco, Mexico (mean age, 13.7 years; SD, 0.5 years; 64% female). The retest was completed by 70 adolescents chosen at random. OUTCOME MEASURES AND ANALYSIS The questionnaire's reliability was measured through internal consistency (Cronbach α) and reproducibility (intraclass correlation coefficient [ICC]). Construct validity was assessed using exploratory factor analysis. RESULTS Five questions were eliminated from the questionnaire because of a lack of temporal stability (ICC ≤0.4). The exploratory factor analysis was satisfactory for 3 factors (41.89% of variance) environmental facilitators and social support, self-efficacy and self-regulation, and outcome expectations and outcome expectations value. The questionnaire had good internal consistency (α = 0.824) and excellent temporal stability (ICC = 0.849). CONCLUSIONS AND IMPLICATIONS The results substantiate the reliability and construct validity of this questionnaire. The questionnaire has the potential to use the assessment of Social Cognitive Theory constructs in clinical practice or in nutrition interventions aimed at modifying the eating habits of Spanish-speaking adolescents. OBJECTIVE To evaluate the association of early involvement in cooking activities with cooking skills in adulthood, the importance of different sources for the acquisition, and the link between cooking skills and healthy eating. DESIGN Cross-sectional survey. PARTICIPANTS A random sample of 3,659 Swiss adults (47% men; average age = 58.8 years). MAIN OUTCOME MEASURE Self-reported cooking skills. ANALYSIS ANOVA, Pearson correlations, t tests, and multiple regressions. RESULTS More frequent involvement in cooking activities during childhood predicted better cooking skills in adulthood in males (β = .13, P less then .001) and females (β = .12, P less then .001). Females were more involved than males in most age groups (P  less then .001). Women learned most about cooking from their mothers, cooking courses, and self-study using different media. Men identified their partners/spouses and mothers as the 2 most important sources. The study found associations between cooking skills and diet quality in men (r = .11; P less then .