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Kim, Jee Yeon,Hwang, Junha,Lee, Seo Hyun,Lee, Hyo Jin,Jelinek, Jaroslav,Jeong, Hyeseon,Lim, Jae Sung,Kim, Jin Man,Song, Kyu Sang,Kim, Byung Hoon,Lee, Sukhoon,Kim, Jei BioMed Central 2015 Clinical epigenetics Vol.7 No.-
<P><B>Background</B></P><P>The vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling pathway is involved in cancer-related biological functions and is a therapeutic target in cancer. However, the influence of epigenetic regulation of VEGF-VEGFR signaling-related genes remains unclear. Here, we evaluated the effects of <I>FLT1</I> and <I>KDR</I> promoter hypermethylation combined with drugs targeting VEGF-VEGFR signaling on cancer-related phenotypes in renal cancer cells (RCCs) and examined changes in <I>FLT1</I> and <I>KDR</I> promoter hypermethylation in tissues from patients with renal cancer.</P><P><B>Results</B></P><P>In vitro experiments were performed to evaluate the effects of beavacizumab (an anti-VEGF antibody), an anti-FLT1 peptide, an anti-KDR antibody, and the VEGFR tyrosine kinase inhibitors (TKIs) sunitinib and axitinib in 13 RCC lines with different levels of <I>FLT1</I> and/or <I>KDR</I> promoter methylation and in 2 FLT1 or KDR in vitro knockdown models. The synergistic effects of sunitinib and axitinib treatment were also evaluated in four RCC lines having different levels of <I>FLT1</I> and/or <I>KDR</I> methylation. In our in vitro experiments, bevacizumab and an anti-KDR antibody did not affect the proliferation of RCCs having <I>FLT1</I> and/or <I>KDR</I> hypermethylation. In contrast, in RCCs with <I>FLT1</I> hypermethylation, proliferation inhibition was counteracted by treatment with an anti-FLT1 peptide and both VEGF-TKIs (sunitinib and axitinib). Demethylation with sunitinib or axitinib synergistically increased proliferation inhibition in the RCCs exhibiting <I>FLT1</I> hypermethylation. Using in vitro <I>FLT1</I> or <I>KDR</I> knockdown models, decreased proliferation inhibition following anti-FLT1 peptide, sunitinib, and axitinib treatment was observed only in <I>FLT1</I>-knockdown cells. In patients with renal cancer who received sunitinib, <I>FLT1</I> promoter methylation was higher in renal cancer tissues from eight nonresponders (stable or progressive disease assessed by the Response Evaluation Criteria in Solid Tumors) than in cancer tissues from five responders (complete response or partial response).</P><P><B>Conclusions</B></P><P>The present data showed that hypermethylated <I>FLT1</I> was important for the efficacy of anti-VEGF/VEGFR drugs targeting FLT1 or intracellular VEGFR signaling. <I>FLT1</I> hypermethylation causing alterations of FLT1 function could serve as a useful biomarker for predicting changes in <I>FLT1</I> status in RCCs.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s13148-015-0134-9) contains supplementary material, which is available to authorized users.</P>
( Dain Kim ),( Hyeseon Yoon ),( Sangkyu Kim ),( Jimin Wi ),( Heesu Chae ),( Gyunghee Jo ),( Jun-yeol Yoon ),( Heeyoun Kim ),( Chankyu Lee ),( Se-ho Kim ),( Hyo Jeong Hong ) 한국미생물 · 생명공학회 2018 Journal of microbiology and biotechnology Vol.28 No.12
Cross-reactive material 197 (CRM<sub>197</sub>) is a non-toxic mutant of diphtheria toxin containing a single amino acid substitution of glycine 52 with glutamic acid. CRM<sub>197</sub> has been used as a carrier protein for poorly immunogenic polysaccharide antigens to improve immune responses. In this study, to develop a sandwich ELISA that can detect CRM<sub>197</sub> and CRM<sub>197</sub> conjugate vaccines, we generated a human anti-CRM<sub>197</sub> monoclonal antibody (mAb) 3F9 using a phage-displayed human synthetic Fab library and produced mouse anti-CRM197 polyclonal antibody. The affinity (K<sub>D</sub>) of 3F9 for CRM<sub>197</sub> was 3.55 nM, based on Bio-Layer interferometry, and it bound specifically to the B fragment of CRM<sub>197</sub>. The sandwich ELISA was carried out using 3F9 as a capture antibody and the mouse polyclonal antibody as a detection antibody. The detection limit of the sandwich ELISA was <1 ng/ml CRM<sub>197</sub>. In addition, the 3F9 antibody bound to the CRM<sub>197</sub>-polysaccharide conjugates tested in a dose-dependent manner. This ELISA system will be useful for the quantification and characterization of CRM<sub>197</sub> and CRM<sub>197</sub> conjugate vaccines. To our knowledge, this study is the first to generate a human monoclonal antibody against CRM197 and to develop a sandwich ELISA for CRM<sub>197</sub> conjugate vaccines.
28-day inhalation toxicity of graphene nanoplatelets in Sparague-Dawley rats
Jinkwon Kim(김진권),Jaehoon Shin(신재훈),Miseong Jo(조미성),Younghoon Kim(김영훈),Eungyeong Son(손은경),Hyeseon Park(박혜선),Byeonghak Moon(문병학),Jongseong Lee(이종성),Jinee Baek(백진이),Boowook Kim(김부욱),Jinsik Kim(김진식),Kangh 환경독성보건학회 2016 한국독성학회 심포지움 및 학술발표회 Vol.2016 No.10
Seon Nyo Kim,Seung Hyun Kim,Chan Kim,Hanna Kim,Jieun Hwang,Misun Yang,So Yoon Ahn,Se In Sung,Yun Sil Chang,Hyeseon Kim 대한신생아학회 2024 Neonatal medicine Vol.31 No.2
Purpose: To investigate the risk factors associated with hypospadias in ver y low birth weight (VLBW) infants (VLBW Is). Methods: We retrospectively analyzed 729 infants born at ≥24 weeks of gestational age and weighing <1,500 g from Januar y 2012 to December 2022. We assessed the prevalence of hypospadias by birth weight percentiles and also compared the demo graphics and placental histopatholog y of the infants with hypospadias (n=52) and those without hypospadias (n=677). Results: Of the 729 patients analysed, hypospadias was recorded in 26 (20.3%), 14 (26.9%), and 12 (2.5%) infants in the <3rd, ≥3rd–<10 t h, a nd ≥10 t h–<90th percentiles, respectively. Of all of the patients with hypospadias, 50% had birth weights <3rd percentile (P<0.001). The hypospadias group demonstrated a longer mean gestational age (30.1 weeks vs. 27.9 weeks, P<0.001), lower incidence of maternal pregnancyinduced hypertension (48.1% vs. 17.3%, P<0.001), lower incidence of pre mature rupture of membrane (11.5% vs. 27.1%, P=0.013), lower acute chorioamniotic maternal response (9.1% vs. 35.2%, P<0.001), and higher maternal underperfusion (95.5% vs. 71.9%, P<0.001). Conclusion: The frequency of hypospadias was found to be the highest among VBLW Is <3rd percentile, who were severely small for their gestational age (SGA). Additionally, the incidence increased with a decreasing birth weight. Physical examination is necessar y at birth for VLBW Is classified as SGA. Moreover, the data on the incidence of hypospadias among VLBW Is in neonatal intensive care units can assist in tracking counseling from the prenatal to the postnatal period for patients born <3rd percentile.
Yoon Hee Choo,Moinay Kim,Jae Hyun Kim,Hanwool Jeon,Hee-Won Jung,Eun Jin Ha,Jiwoong Oh,Youngbo Shim,Seung Bin Kim,Han-Gil Jung,So Hee Park,Jung Ook Kim,Junhyung Kim,Hyeseon Kim,Seungjoo Lee 대한신경외과학회 2023 Journal of Korean neurosurgical society Vol.66 No.6
The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.
Activated Rap1A Induces Osteoblastic Differentiation and Cell Adhesion
Hyeseon Kim, Taeck J. Jeon 조선대학교 기초과학연구원 2016 조선자연과학논문집 Vol.9 No.3
Rap1 is a key regulator of cell adhesion and migration. Although increasing evidence indicates that the Rap1 signaling pathway is involved in the process of bone remodeling, the mechanism by which Rap1 regulates osteoblastic differentiation and cell adhesion remains unknown. Here, we investigated the morphological characteristics and osteoblastic differentiation of cells expressing constitutively activated form of Rap1A (Rap1ACA) or Rap1 GTPase activating protein Rap1GAP and found that activated Rap1 induces osteoblastic differentiation and cell adhesion as well as cell spreading. When osteoblastic differentiation was induced, Rap1ACA cells showed considerably higher levels of calcium deposits than the wild-type and Rap1GAP-overexpressing cells did. Rap1ACA cells showed increased spreading and size, as well as strong cell adhesion and significantly decreased growth rates. F-actin staining using phalloidin revealed several thin thread-like filopodia around the protrusions in Rap1ACA cells, which possibly contribute to the increased cell adhesion.
Hyeseon Kim,Jinsup Kim,Rimm Huh,Sung Yoon Cho,진동규 대한소아내분비학회 2015 Annals of Pediatirc Endocrinology & Metabolism Vol.20 No.2
We report a 13-year-old girl with Graves disease, who showed an increased level of serum creatine kinase (CK) accompanied by myalgia after methimazole (MMI) treatment. This patient developed muscular pain two weeks after MMI administration, along with increased CK levels. The level of thyroid hormone was within the normal range when she showed increased CK levels. After the MMI dose was decreased and levo-thyroxine was added, serum CK levels decreased to normal and the myalgia improved. The pathophysiologic mechanism of this effect has not yet been elucidated. An acute relatively hypothyroid state occurs secondary to antithyroid drug (ATD) administration in chronic hyperthyroidism, which may cause changes in the CK levels. In this report, we present a rare pediatric case, along with a literature review of similar cases. In the initial state of MMI treatment, myalgia should be detected and when it occurs, CK levels should be measured. The clinical strategy of monitoring CK levels with the aim of normalizing thyroid hormones is helpful in case of the development of adverse reactions, such as myalgia, during ATD treatment for Graves disease in children.