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Park, Ye‐,Lim,Kim, Hwang‐,Phill,Cho, Young‐,Won,Min, Dong‐,Wook,Cheon, Seul‐,Ki,Lim, Yoo Joo,Song, Sang‐,Hyun,Kim, Sung Jin,Han, Sae‐,Won,Park, Kyu Joo,Kim, T John Wiley Sons, Inc. 2019 International journal of cancer: Journal internati Vol.144 No.2
<P><I>PIK3CA</I> is a frequently mutated gene in cancer, including about ~15 to 20% of colorectal cancers (CRC). <I>PIK3CA</I> mutations lead to activation of the PI3K/AKT/mTOR signaling pathway, which plays pivotal roles in tumorigenesis. Here, we investigated the mechanism of resistance of <I>PIK3CA</I>‐mutant CRC cell lines to gedatolisib, a dual PI3K/mTOR inhibitor. Out of a panel of 29 CRC cell lines, we identified 7 harboring one or more <I>PIK3CA</I> mutations; of these, 5 and 2 were found to be sensitive and resistant to gedatolisib, respectively. Both of the gedatolisib‐resistant cell lines expressed high levels of active glycogen synthase kinase 3‐beta (GSK3β) and harbored the same frameshift mutation (c.465_466insC; H155fs*) in <I>TCF7</I>, which encodes a positive transcriptional regulator of the WNT/β‐catenin signaling pathway. Inhibition of GSK3β activity in gedatolisib‐resistant cells by siRNA‐mediated knockdown or treatment with a GSK3β‐specific inhibitor effectively reduced the activity of molecules downstream of mTOR and also decreased signaling through the WNT/β‐catenin pathway. Notably, GSK3β inhibition rendered the resistant cell lines sensitive to gedatolisib cytotoxicity, both <I>in vitro</I> and in a mouse xenograft model. Taken together, these data demonstrate that aberrant regulation of WNT/β‐catenin signaling and active GSK3β induced by the <I>TCF7</I> frameshift mutation cause resistance to the dual PI3K/mTOR inhibitor gedatolisib. Cotreatment with GSK3β inhibitors may be a strategy to overcome the resistance of <I>PIK3CA</I>‐ and <I>TCF7</I>‐mutant CRC to PI3K/mTOR‐targeted therapies.</P>
Ye-seul Kim,Yeon-soo Park,Gyeong-cheol Cho,Ki-ho Park,Shin-Hyang Kim,Seung Yeon Baik,Cho Long Kim,Soo-yun Jung,Won-Hye Lee,Youn-young Choi,Seung-Hwan Lee,Kee-Hong Choi 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.11
Objective This study evaluated the psychometric properties of the Korean Anxiety Screening Assessment (K-ANX) developed for screening anxiety disorders. Methods Data from 613 participants were analyzed. The K-ANX was evaluated for reliability using Cronbach’s alpha, item-total correlation, and test information curve, and for validity using focus group interviews, factor analysis, correlational analysis, and item characteristics based on item response theory (IRT). The diagnostic sensitivity and specificity of the K-ANX were compared with those of the Beck Anxiety Inventory (BAI) and Generalized Anxiety Disorder 7-item scale (GAD-7). Results The K-ANX showed excellent internal consistency (α=0.97) and item-total coefficients (0.92–0.97), and a one-factor structure was suggested. All items were highly correlated with the total scores of the BAI, GAD-7, and Penn State Worry Questionnaire. IRT analysis indicated the K-ANX was most informative as a screening tool for anxiety disorders at the range between 0.8 and 1.6 (i.e., top 21.2 to 5.5 percentiles). Higher sensitivity (0.795) and specificity (0.937) for identifying anxiety disorders were observed in the K-ANX compared to the BAI and GAD-7. Conclusion The K-ANX is a reliable and valid measure to screen anxiety disorders in a Korean sample, with greater sensitivity and specificity than current measures of anxiety symptoms.
Effect of Ovarian Extract on Oocyte Maturation and Early Embryonic Development in Pigs
Seul-Gi Yang(Seul-Gi Yang),Jae-Hun Choi(Jae-Hun Choi),Young-Seo Jo(Young-Seo Jo),Ye-Won Kim(Ye-Won Kim),Dong-Mok Lee(Dong-Mok Lee),Hyo-Jin Park(Hyo-Jin Park),Deog-Bon Koo(Deog-Bon Koo) 한국동물보건학회 2022 한국동물보건학회지 Vol.1 No.2
Various factors in the ovary are known to regulate oocyte maturation and hormone secretory functions; however, the effect of ovarian extract (OE) on oocyte maturation and embryonic development in pigs remains unknown. In this study, we first evaluated whether OE supplementation in the in vitro maturation (IVM) medium alters the oocyte maturation capacity by affecting glucose/amino acid metabolites, meiotic maturation, cumulus cell (CC) expansion, and antioxidants. Various OE concentrations (50, 100, 200, 500, and 5000 μg/mL) were included in the IVM medium. Only the oocytes treated with 100 μg/mL OE exhibited an improved meiotic maturation rate when compared with that of the other groups (non-treated group, 78.6 ± 3.0% vs. 100 μg/mL OE-treated group, 81.6 ± 4.3%); however, the difference was not significant. To observe the changes in glucose and amino acid metabolism in the OE-treated oocytes, we measured the amounts of diverse constituents (glucose, lactate, glutamine, and ammonia) in the IVM medium containing OE. Lactate and ammonia levels in the OE-treated group after 44 h of IVM were higher (p < 0.01) than those in the non-treated group. In addition, the expression of the CC expansion factors (Has2 and Tnfaip6) significantly increased (p < 0.05), whereas the mRNA expression levels of antioxidative enzymes (Sod1, Cat, and Gpx1) significantly diminished (p < 0.05) in the OE-treated group. Moreover, mature oocytes treated with 100 μg/mL OE demonstrated increased subsequent embryonic development rates after 144 h of IVM. Thus, the addition of OE in IVM mediums may improve oocyte maturation capacity which could enhance antioxidative enzyme activation, energy metabolism, and expression of the CC expansion factors in porcine oocytes.