A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Melanocortin receptor agonist transiently increases oxygen consumption in rats

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAcute injections of melanocortin (MC) agonist and antagonist are highly effective in reducing or increasing food take, respectively. Much less is known about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the effect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this increase had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreased the food intake during the first days, but then the feeding recovered and the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, even though the weight loss was maintained. The HS024 treated rats were hyperphagic throughout the test period, continuously gaining weight, resulting in increased fat pads and high leptin levels. This is the first study that describes long term effects of MC receptor agonist and antagonist on metabolism and energy balance

Melanocortin receptor agonist transiently increases oxygen consumption in rats

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAcute injections of melanocortin (MC) agonist and antagonist are highly effective in reducing or increasing food take, respectively. Much less is known about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the effect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this increase had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreased the food intake during the first days, but then the feeding recovered and the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, even though the weight loss was maintained. The HS024 treated rats were hyperphagic throughout the test period, continuously gaining weight, resulting in increased fat pads and high leptin levels. This is the first study that describes long term effects of MC receptor agonist and antagonist on metabolism and energy balance

An oxidatively-activated safety catch linker for solid phase synthesis

A N-benzyl-4-amino-2,2-dimethylbutanoic acid-based system has been developed as a new oxidatively activated safety catch linker for reaction monitoring and optimisation on solid support. The CAN promoted oxidative debenzylation of the tertiary N-benzylamine moiety, followed by concomitant cyclisation and release of alcohols and amines has been demonstrated both in solution phase model studies and on the solid phase. The linker system has been applied to the solid phase synthesis of a collection of phenol derivatives, and to the demonstration of the attachment and release of a chiral auxiliary from a solid support