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Yoon, Jeong,Juhn, Kyoung-Mi,Yoon, San-Hyun,Ko, Yong,Lim, Jin-Ho The Korean Society for Reproductive Medicine 2017 Clinical and Experimental Reproductive Medicine Vol.44 No.1
Objective: The aims of this study were to investigate whether fertilization could induce the resumption of meiosis in mouse oocytes arrested at metaphase I (MI) after in vitro maturation (IVM), and to investigate the effect of $Ca^{2+}$ chelator treatment at the time of fertilization on the transition from MI to metaphase II (MII). Methods: MII-stage and arrested MI-stage mouse oocytes after IVM were fertilized, and then embryonic development was monitored. Blastocysts from each group were transferred into 2.5 days post-coitum pseudo-pregnant ICR mice. MI oocytes after IVM were treated with a $Ca^{2+}$ chelator to investigate the effect of $Ca^{2+}$ oscillations on their maturation. Results: As insemination time increased, the number of oocytes in the MI group that reached the MII stage also increased. The blastocyst rates and total cell numbers in the MII group were significantly higher than in the MI group. No pregnancy occurred in the MI group, but 10 pregnancies were achieved (10 of 12) in the MII group. The proportion of MI oocytes that matured to MII oocytes after fertilization was significantly higher in the non-treated group than in the $Ca^{2+}$ chelator-treated group. Conclusion: The findings that a higher proportion of MI-arrested oocytes progressed to MII after fertilization and that the MI-to-MII transition was blocked by $Ca^{2+}$ chelator treatments before fertilization indicate that the maturation of MI oocytes to MII oocytes is associated with intracellular $Ca^{2+}$ oscillations driven by fertilization.
Yoon, Jeong,Yoon, Hye-Jin,Juhn, Kyoung-Mi,Ko, Jin-Kyung,Yoon, San-Hyun,Ko, Yong,Lim, Jin-Ho The Korean Society for Reproductive Medicine 2011 Clinical and Experimental Reproductive Medicine Vol.38 No.4
Objective: Since IVF program was first established, various types of media and culture systems have been developed either in-house or commercially. The aim of this study was to compare the efficacy of in-house Maria Research Center (MRC) media to that of commercially available Sydney IVF media in human day 3 embryo transfer cycles. Methods: Three hundred sixty nine couples were included in this prospective, randomized, and comparative study. All couples undergoing IVF treatment at the Maria Fertility Hospital were randomly assigned to either Sydney IVF (n=178) or MRC (n=191) media. Results: No difference was observed between the MRC media and Sydney IVF media groups with respect to fertilization rate (74.4% vs. 75.5%). The clinical pregnancy and implantation rates of MRC media (47.1% and 20.0%, respectively) were also similar to those of Sydney IVF media (44.4% and 19.4%, respectively). However, the proportion of embryos with good quality on day 3 was significantly higher in the MRC media group than the Sydney IVF media group (50.2% vs. 43.2%) ($p$ <0.05). Conclusion: MRC media were as effective as Sydney IVF media for sustaining embryo development and pregnancy rates. The present study implies that MRC media can be a suitable alternative to commercially available media for human IVF-ET program.
Yun, Jiyeon,Hong, Min Hee,Kim, Seok-Young,Park, Chae-Won,Kim, Soyoung,Yun, Mi Ran,Kang, Han Na,Pyo, Kyoung-Ho,Lee, Sung Sook,Koh, Jong Sung,Song, Ho-Juhn,Kim, Dong Kyun,Lee, Young-Sung,Oh, Se-Woong,Ch American Association for Cancer Research 2019 Clinical Cancer Research Vol.25 No.8
<P><B>Purpose:</B></P><P>Given that osimertinib is the only approved third-generation EGFR-TKI against <I>EGFR</I> activating and resistant T790M mutated non–small cell lung cancer (NSCLC), additional mutant-selective inhibitors with a higher efficacy, especially for brain metastases, with favorable toxicity profile are still needed. In this study, we investigated the antitumor efficacy of YH25448, an oral, mutant-selective, irreversible third-generation EGFR-TKI in preclinical models.</P><P><B>Experimental Design:</B></P><P>Antitumor activity of YH25448 was investigated <I>in vitro</I> using mutant <I>EGFR</I>-expressing Ba/F3 cells and various lung cancer cell lines. <I>In vivo</I> antitumor efficacy, ability to penetrate the blood–brain barrier (BBB), and skin toxicity of YH25448 were examined and compared with those of osimertinib using cell lines and PDX model.</P><P><B>Results:</B></P><P>Compared with osimertinib, YH25448 showed a higher selectivity and potency in kinase assay and mutant <I>EGFR</I>-expressing Ba/F3 cells. In various cell line models harboring <I>EGFR</I> activating and T790M mutation, YH25448 effectively inhibited EGFR downstream signaling pathways, leading to cellular apoptosis. When compared <I>in vivo</I> at equimolar concentrations, YH25448 produced significantly better tumor regression than osimertinib. Importantly, YH25448 induced profound tumor regression in brain metastasis model with excellent brain/plasma and tumor/brain area under the concentration–time curve value. YH25448 rarely suppressed the levels of p-EGFR in hair follicles, leading to less keratosis than osimertinib in animal model. The potent systemic and intracranial activity of YH25448 has been shown in an ongoing phase I/II clinical trial for advanced <I>EGFR</I> T790M mutated NSCLC (NCT03046992).</P><P><B>Conclusions:</B></P><P>Our findings suggest that YH25448 is a promising third-generation EGFR inhibitor, which may be more effective and better tolerated than the currently approved osimertinib.</P>