We found a higher proportion of reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either drug alone. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of IP when EGFR-TKI is administered in combination with nivolumab, including concomitant and sequential use, and careful monitoring for IP is recommended.

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We created a novel mutated form of human interleukin-13 (IL-13) in which a positively charged arginine (R) at position 112 was substituted to a negatively charged aspartic acid (D). This mutant, termed IL-13R112D, was expressed in Escherichia coli and purified to near homogeneity. IL-13R112D was found to be a potent IL-13 agonist with 5-10-fold improved binding affinity to IL-13 receptors compared with wild-type IL-13 (wtIL-13). The conclusion of IL-13 agonist activity was drawn on the basis of approximately 10-fold improved activity over wtIL-13 in several assays: (a) inhibition of CD14 expression in primary monocytes; (b) proliferation of TF-1 and B9 cell lines; and (c) activation of STAT6 in Epstein-Barr virus-immortalized B cells, primary monocytes, and THP-1 monocytic cell line. Furthermore, mutant IL-13R112D neutralized the cytotoxic activity of a chimeric fusion protein composed of wtIL-13 and a Pseudomonas exotoxin A (IL-13-PE38) approximately 10 times better than wtIL-13. Based on these results, it was concluded that IL-13R112D interacts with much stronger affinity than wtIL-13 on all cell types tested and that Arg-112 plays an important role in the interaction with its receptors (IL-13R). Thus, these results suggest that IL-13R112D may be a useful ligand for the study of IL-13 interaction with its receptors or, alternatively, in designing specific targeted agents for IL-13R-positive malignancies.

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Objective To describe the characteristics of cases with drug-associated rhabdomyolysis reported to the U.S. Food and Drug Administration (FDA). Methods A retrospective analysis of all drug-associated rhabdomyolysis cases reported to FDA between January 2004 and December 2009 was conducted. The analyses included the number of unique cases, age, gender, body weight and proportion of fatal outcome. Time to onset from beginning of the suspected drugs and frequently reported suspected drugs were also tabulated. Results There were 8,610 cases of drug-associated rhabdomyolysis in the database. Both case numbers and proportion of the fatal outcome appeared stable over the study period. Average age was 43.3 years old. The reported ratio of male to female was approximately 5 to 3. More than half of reported cases developed rhabdomyolysis within a month after beginning the suspected drug. Potential high risk groups for fatal outcome, such as age group younger than 10 years old and body weight group less than 50 kg were suggested. Suspected drugs for younger cases and their probable indication appear to be different from adult cases. There has been long standing controversial concern regarding an increased risk when a fibric acid derivative is added to an HMG-CoA reductase inhibitor. This study suggested that concomitant use of these two kinds of agents may be associated with a lower risk for fatal outcome, whereas renal dysfunction appeared to be associated with a higher risk for fatal outcome among the HMG-CoA reductase inhibitor-associated rhabdomyolysis cases. Conclusion The characteristics of cases of drug-associated rhabdomyolysis were described. Because of the various limitations of a spontaneous reporting-system database, the reported number should be interpreted with caution.

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Although a number of genes expressed in most tissues, including the liver, exhibit circadian regulation, gene expression profiles are usually examined only at one scheduled time each day. In this study, we investigated the effects of obese diabetes on the hepatic mRNA levels of various genes at 6-h intervals over a single 24-h period. Microarray analysis revealed that many genes are expressed rhythmically, not only in control KK mice but also in obese diabetic KK-A y mice. Real-time quantitative PCR verified that 19 of 23 putative circadianly expressed genes showed significant 24-h rhythmicity in both strains. However, obese diabetes attenuated these expression rhythms in 10 of 19 genes. More importantly, the effects of obese diabetes were observed throughout the day in only two genes. These results suggest that observation time influences the results of gene expression analyses of genes expressed circadianly.