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Influence of hormone therapy on platinum-based chemotherapy using ovarian cancer cell line
( Kyungjin Lee ),( Minkyung Lee ),( Taehee Kim ),( Yejeong Kim ),( Sina Jang ),( Banghyun Lee ),( Sung Ook Hwang ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-
Objective: In epithelial ovarian, primary peritoneal, or fallopian tube cancer (EOC), no studies have analyzed impacts of hormone therapy combined with platinum-based chemotherapy according to hormonal receptor expression. This study evaluated influence of hormone therapies (according to hormonal receptor expressions) and their molecular mechanisms on efficacy of platinum-based chemotherapy using a high-grade serous ovarian cancer (HGSC) cell line. Methods: Caov3 cells were stimulated with the following therapeutic agents: paclitaxel (P); carboplatin (C); tamoxifen (T); MPA (M); paclitaxel and tamoxifen (PT); paclitaxel and MPA (PM); carboplatin and tamoxifen (CT); carboplatin and MPA (CM); paclitaxel and carboplatin (PC); paclitaxel, carboplatin, and tamoxifen (PCT); and paclitaxel, carboplatin, and MPA (PCM). MTT assay was performed, and quantitative real-time RT-PCR and methylation assay using estrogen receptor (ER)-, ER-, progesterone receptor (PR)-A, PR-B, and PR-AB were performed. Results: Compared with the non-treated (NT) group, Caov3 cell viability decreased significantly in all groups with the highest decreases in the T and PCT groups (P <0.05). Viability increased significantly in PT and PM groups compared with P group, and in CM group compared with C group (P <0.05). Additionally, compared with PC group, viability decreased significantly in PCT group and increased significantly in PCM group (P <0.05). Expressions of ER-, ER-, and PR-B to PR-AB were not different between the groups. In methylation analyses of ER-, ER-, PR-A, and PR-B genes, methylation of promoters and gene bodies of PCT group were different from the other groups. Conclusion: Combinations of tamoxifen or MPA have influences on platinum-based chemotherapy efficacy in HGSC cells regardless of ER and PR expression. Methylation of ER and/or PR might have influences on HGSC cell proliferation under a combination of platinum-based chemotherapy and tamoxifen.
KyungJin Lee,HyeRyung Jung,JooYoun Cho,HyeYoon Park,DoHyung Kang,InJin Jang,SangGoo Shin,JunSoo Kwon 대한신경정신의학회 2007 PSYCHIATRY INVESTIGATION Vol.4 No.1
Serotonin dysfunction has been implicated in the pathogenesis of obsessive compulsive disorder (OCD). Neurocognitive dysfunction is considered as the core pathology in the OCD. This study aimed to investigate the association of T102C polymorphism of the 5-HT2A receptor gene with the neurocognitive function in OCD. Fifty four patients with OCD were participated in this study. Neurocognitive function tests were administered to the patients with OCD. T102C of the 5-HT2A gene were analyzed by Polymerase Chain Reaction (PCR) amplification and Restriction Fragment Length Polymorphism (RFLP). The distribution of genotypic patterns of T102C was grouped into T/T genotype (n=16), T/C genotype (n=28) and T/T genotype (n=10). The group of patients with T/T genotype demonstrated significant delayed response time in immediate recall (p=0.036) and delayed recall (p=0.038) of Rey-Osterrieth Complex Figure test which was used to evaluate visuospatial construction ability and visuospatial memory. These results showed that T/T genotype of T102C has higher performance deficit in neurocognitive function tests such as RCFT than the other types. We suggest that T102C genotype may contribute to neurocognitive function and neurocognitive function may serve as a good candidate phenotype for association or linkage studies on OCD.
Jang Sangwon,Park Inah,Choi Mijung,Kim Jihoon,Yeo Seungeun,Huh Sung-Oh,Choi Ji-Woong,Moon Cheil,Choe Han Kyoung,Choe Youngshik,Kim Kyungjin 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Social interaction among conspecifics is essential for maintaining adaptive, cooperative, and social behaviors, along with survival among mammals. The 5-hydroxytryptamine (5-HT) neuronal system is an important neurotransmitter system for regulating social behaviors; however, the circadian role of 5-HT in social interaction behaviors is unclear. To investigate whether the circadian nuclear receptor REV-ERBα, a transcriptional repressor of the rate-limiting enzyme tryptophan hydroxylase 2 (Tph2) gene in 5-HT biosynthesis, may affect social interaction behaviors, we generated a conditional knockout (cKO) mouse by targeting Rev-Erbα in dorsal raphe (DR) 5-HT neurons (5-HTDR-specific REV-ERBα cKO) using the CRISPR/Cas9 gene editing system and assayed social behaviors, including social preference and social recognition, with a three-chamber social interaction test at two circadian time (CT) points, i.e., at dawn (CT00) and dusk (CT12). The genetic ablation of Rev-Erbα in DR 5-HTergic neurons caused impaired social interaction behaviors, particularly social preference but not social recognition, with no difference between the two CT points. This deficit of social preference induced by Rev-Erbα in 5-HTDR-specific mice is functionally associated with real-time elevated neuron activity and 5-HT levels at dusk, as determined by fiber-photometry imaging sensors. Moreover, optogenetic inhibition of DR to nucleus accumbens (NAc) 5-HTergic circuit restored the impairment of social preference in 5-HTDR-specific REV-ERBα cKO mice. These results suggest the significance of the circadian regulation of 5-HT levels by REV-ERBα in regulating social interaction behaviors.
Jang, Jaebong,Chung, Sooyoung,Choi, Youjeong,Lim, Hye Young,Son, Yeongeon,Chun, Sung Kook,Son, Gi Hoon,Kim, Kyungjin,Suh, Young-Ger,Jung, Jong-Wha Elsevier 2018 Life sciences Vol.200 No.-
<P><B>Abstract</B></P> <P><B>Aims</B></P> <P>We have previously identified a chemical scaffold possessing 2-ethoxypropanoic acid (designated as KS15) that directly binds to the C-terminal region of cryptochromes (CRYs: CRY1 and CRY2) and enhances E-box-mediated transcription. However, it is still unclear how KS15 impairs the feedback actions of the CRYs and which chemical moieties are functionally important for its actions.</P> <P><B>Main methods</B></P> <P>The E-box-mediated transcriptional activities were mainly used to examine the effects of KS15 and its derivatives. Co-immunoprecipitation assays accompanied by immunoblotting were employed to monitor protein-protein associations. We also examined the effects of KS15 and selected derivatives on circadian molecular rhythms in cultured cells.</P> <P><B>Key findings</B></P> <P>The present study shows that KS15 inhibits the interaction between CRYs and Brain-Muscle-Arnt-Like protein 1 (BMAL1), thereby impairing the feedback actions of CRYs on E-box-dependent transcription by CLOCK:BMAL1 heterodimer, an indispensable transcriptional regulator of the mammalian circadian clock. Subsequent structure-activity relationship analyses using a well-designed panel of derivatives identified the structural requirements for the effects of KS15 on CRY-evoked regulation of E-box-mediated transcription. We found that KS15 and several derivatives significantly reduce the amplitude and delayed the phase of molecular circadian rhythms in fibroblast cultures.</P> <P><B>Significance</B></P> <P>Taken together, our results provide valuable information on the molecular mode-of-action as well as the chemical components of the CRYs inhibitor that pharmacologically impact on the transcriptional activity of the CLOCK:BMAL1 heterodimer.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Kang, Kyungjin,Song, Jeongyong,Kang, Chiho,Sung, Sangjin,Jang, Gunhee IEEE 2017 IEEE transactions on industrial electronics Vol.64 No.9
<P>We developed a real-time method to detect the dynamic eccentricity of a rotor in a permanent-magnet (PM) motor by monitoring a fault detection signal induced in an additional winding, without performing any further postprocessing, even under a nonstationary rotational speed. After deriving a mathematical equation of the back electromotive force (EMF) induced in a tooth-coil winding, we proposed a fault detection signal, which is the back EMF in an additional winding divided by the rotational speed, when the additional winding is wound around the teeth corresponding to an even number of pole pitches. We used the 2-D finite-element model of a three-phase PM motor with eight poles and 12 slots to verify the proposed method. We also developed an experimental setup which can change the dynamic eccentricity of a PM motor and we performed the experiment for PM motors with dynamic eccentricities of 0%, 25%, and 50% to verify the proposed method. Through the mathematical equation, numerical simulation, and experiment, we confirmed that the fault detection signal proposed in this paper can successfully detect the dynamic eccentricity in a PM motor in real time.</P>
Lee, Kyungjin,Sohn, Youngjoo,Lee, Min-Jung,Cho, Hyun-Sam,Jang, Min-Hee,Han, Na-Young,Shin, Kyu-Won,Kim, Sung-Hoon,Cho, Ik-Hyun,Bu, Youngmin,Jung, Hyuk-Sang Informa Healthcare 2012 Immunopharmacology and immunotoxicology Vol.34 No.4
<P>The root of <I>Angelica acutiloba</I> is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of <I>A. acutiloba</I> on allergic reactions in <I>in vitro</I> and <I>in vivo</I> models and its mechanism of action. <I>A. acutiloba</I> was extracted by maceration with 80% ethanol (AAE) and standardized by high-performance liquid chromatography. We investigated the effect of AAE on phorbol-12-myristate-13-acetate plus calcium ionophore A23187 (PMACI)-induced cytokine release; phosphorylation of JNK, ERK, and p38 in human mast cell-1 (HMC-1); and compound 48/80-induced release of histamine in rat peritoneal mast cells (RPMCs). We also investigated the effects on Evans blue (EB) extravasation induced by anti-DNP IgE in rats. Treatment with 1, 10 and 100 μg/ml AAE concentration-dependently inhibited the release of cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-8) and phosphorylation of ERK and JNK induced by PMACI in HMC-1 cells, but it did not inhibit the phosphorylation of p38. It also inhibited compound 48/80-induced histamine release in RPMCs. Oral administration of 271 mg/kg AAE inhibited EB extravasation in a passive cutaneous anaphylaxis rat model. In conclusion, AAE inhibited mast cell-derived allergic reactions by inhibiting the release of histamine, the production of pro-inflammatory cytokines, and the phosphorylation of ERK and JNK.</P>