Renal cell carcinoma (RCC) frequently recurs or metastasizes after surgical resection. Everolimus, an mTOR inhibitor, is used as a second-line treatment, but the response of RCC to everolimus is insufficient. Metformin is an antidiabetic drug; recent reports have indicated its anti-cancer effects in various cancers, and it is known to have synergistic effects with other drugs. We investigated the possibility of coadministering everolimus and metformin as an effective treatment for RCC. RCC cells treated with a combination of the two drugs showed significantly inhibited cell viability, cell migration, and invasion, and increased apoptosis compared to those treated with each drug alone. An anti-cancer synergistic effect was also confirmed in the xenograft model. Transcriptome analysis for identifying the underlying mechanism of the combined treatment showed the downregulation of mitochondrial fusion genes and upregulation of mitochondrial fission genes by the combination treatment. Changes in mitochondrial dynamics following the combination treatment were observed using LysoTracker, LysoSensor, and JC-1 staining. In conclusion, the combination of everolimus and metformin inhibited RCC growth by disrupting mitochondrial dynamics. Therefore, we suggest that a treatment combining metformin and everolimus disrupts mitochondrial dynamics in RCC, and may be a novel strategy for RCC treatment.
Purpose This research was performed to inquire the reliability and validity of internal rotation and external rotation of shoulder joint using smart phone and goniometer to healthy subjects. Methods Universal goniometer and two android application, hysical tools YMED ROM and goniometer developed by Nagomi.aqu was used to collect the data from 30 healthy subjects in age of 20s, 15 male and 15 female, from S University in Busan, Republic of Korea. As a procedure, all subjects were properly stretched before the experiment. The active internal and external rotation of right arm of each subject were measured and 3 raters measured each subject 5 times with 3 different tools, overall 15 times for each subject. And each rater were blindfolded to conceal the results from other raters. SPSS 20.0 software were used to process all statistics, and intraclass correlation coeffienct (2.k) model were used to calculate the reliability and pearson correlation coefficient validity were used to calculate the validity. Results As the result, intrarater reliability of 3 raters showed high reliability (ICC>0.9). Interrater reliability showed high reliability in all measurement (ICC>0.9), validity of measuring tools showed very high correlation in both active internal and external rotation of shoulder joint. Conclusion This research showed the value measured with goniometer application using gyroscope of smartphone is reliable. Peculiarly, the value of both reliability and validity of external rotation was higher than that of internal rotation
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