Search

Background: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18 F isotope., Results: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n = 5), 14.7% ±8.58% (n = 3) and 14.92% ±3.9% (n = 3) for 18 F KAM001, 18 F KAM002 and 18 F KAM003 respectively, with radiochemical purity of greater than 99%., Conclusions: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.

The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nodes, while the analysis of directed networks revealed the distinction between networks of different disciplines. The study showed that larger motifs contained the three-node motif as a subgraph. Topological analysis revealed that similar networks have similar small motifs, but as the motif size increases, differences arise. Pearson correlation coefficient showed strong positive relationship between some undirected networks but inverse relationship between some directed networks. The study suggests that the three-node motif is a building block of larger motifs. It also suggests that undirected networks share similar low-level structures. Moreover, similar networks share similar small motifs, but larger motifs define the unique structure of individuals. Pearson correlation coefficient suggests that protein structure networks, dolphin social network, and co-authorships in network science belong to a superfamily. In addition, yeast protein-protein interaction network, primary school contact network, Zachary's karate club network, and co-purchase of political books network can be classified into a superfamily.

Background: Asthmatic patients taking low to moderate doses of inhaled topical corticosteroids have been shown to have lower bone density than those taking bronchodilators only. There is little information on bone density in asthmatic patients taking high dose inhaled corticosteroids., Methods: Bone mass was studied in three age matched groups of asthmatic patients. These comprised: 17 asthmatic patients who had never taken inhaled or systemic corticosteroids (group 1); 20 patients who had taken beclomethasone diproprionate in a dosage of 1000-2000 micrograms daily for at least a year, who had also received courses of systemic corticosteroids in the past (group 2); and 20 patients who were taking both high dose inhaled corticosteroids and regular low dose prednisolone, at a median dose of 7 mg daily (group 3). Vertebral bone density was measured by quantitative computed tomography. Biochemical indices of bone formation and resorption were also measured., Results: Mean bone density in group 2 (127.5(22.6) mg/ml) was similar to that in group 3 (114.5 (36.0) mg/ml). Bone density was significantly lower in both of these groups than in group 1 (160.4 (27.4) mg/ml). There were no significant differences between groups for any of the markers of bone formation and resorption., Conclusions: Asthmatic patients receiving high dose inhaled beclomethasone and intermittent courses of systemic corticosteroids have reduced vertebral bone density. The bone loss is similar in degree to that seen in patients taking high dose inhaled topical corticosteroids and continuous low dose systemic corticosteroids.