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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO kim UIJU CHO sook HEE HONG HYUNG SOON PARK IN-HO kim HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG Division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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SUV39H1-driven NFATc1 methylation is essential for the c-Cbl-mediated degradation of NFATc1 in an osteoclast lineage

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Genes & Diseases 2024年第4期11卷 86-89页

作者： Do-Won Jeong Hye-Jin kim Jong-Wan Park Seulbee Lee Hyeryeon Jung Eugene C.Yi Nacksung kime Yang-sook Chun Department of Biomedical Sciences Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Physiology Seoul National University College of MedicineSeoul 03080Republic of Korea Ischemic/Hypoxic Disease Institute Seoul National University College of MedicineSeoul 03080Republic of Korea Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and Technology and College of Medicine Or College of PharmacySeoul National UniversitySeoul 03080Republic of Korea Department of Pharmacology Chonnam National University Medical SchoolGwangju 61469Republic of Korea

Bone undergoes continuous remodeling by tightly-coordinated actions of bone-resorbing osteoclasts and boneforming osteoblasts.1 Recent studies document that the dysregulation of histone methylation profiles is associated with the progression of ***,the specific epigenetic modifiers are incompletely *** this study,we demonstrate an inhibitory role of a variegation 3-9 homolog 1(SUV39H1)in osteoclast formation.

关键词： osteoclast remodeling incomplete

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Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine

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World Journal of Transplantation 2016年第2期6卷 403-410页

作者： Kwi Suk kim Aree Moon Hyoung Jin Kang Hee Young Shin Young Hee Choi hyang sook kim Sang Geon kim Department of Pharmacy Seoul National University Hospital College of Pharmacy Duksung Women’s University Department of Pediatrics Cancer Research InstituteSeoul National University College of Medicine College of Pharmacy Dongguk University College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University

AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease(VOD) in non-adult patients undergoing hematopoietic stem cell transplantation(HSCT) during cyclosporine ***: A total of 123 patients taking cyclosporinewere evaluated using an electronic medical system at the Seoul National University Children's Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions(ADRs) including VOD. RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease(a GVHD) and VOD. Although the incidences of a GVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level(BILmax) of ≥ 1.4 mg/d L correlated with VOD incidence after cyclosporine therapy. CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/d L, suggestive of more sensitive VOD indication in this age group.

关键词： Hematopoietic stem cell transplantation Veno-occlusive disease Cyclosporine Adverse drug reaction Total bilirubin

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Repurposing ibrutinib:therapeutic effects and implications for translational approaches in Alzheimer’s disease

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Neural Regeneration Research 2023年第10期18卷 2194-2195页

作者： Hyun-ju Lee hyang-sook Hoe Department of Neural Development and Disease Korea Brain Research Institute(KBRI)DaeguSouth Korea Department of Brain and Cognitive Sciences Daegu Gyeongbuk Institute of Science&TechnologyDaegu 42988South Korea

Alzheimer’s disease(AD)is the most prevalent neurodegenerative disease,and the number of patients with AD is estimated to double by 2060(Alzheimer’s Association,2022).The AD mortality rate has increased by 145%over the last decade,the largest increase among the ten leading causes of death in the US(Alzheimer’s Association,2022).

关键词： Alzheimer mortality therapeutic

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Prognostic role of plasma level of angiopoietin-1,angiopoietin-2,and vascular endothelial growth factor in hepatocellular carcinoma

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World Journal of Gastroenterology 2021年第27期27卷 4453-4467页

作者： Gwang Hyeon Choi Eun Sun Jang Jin-Wook kim sook-hyang Jeong Department of Internal Medicine Seoul National University Bundang HospitalSeoul National University College of MedicineSeongnam 13620South Korea

BACKGROUND Most hepatocellular carcinomas(HCCs)are hypervascular,with characteristic features of hepatic arterial supply to the *** factors involved in tumor angiogenesis include angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),and vascular endothelial growth factor(VEGF).AIM To investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival(OS)and progression-free survival(PFS).METHODS Plasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1,Ang-2,and *** associations with clinical characteristics,OS,and PFS were *** The median plasma levels of Ang-1,Ang-2,and VEGF were 3216 pg/mL,1684 pg/mL,and 26.5 pg/mL,*** plasma level of Ang-2 showed a significant increase from early stage[Barcelona clinic liver cancer(BCLC)A]to intermediate(BCLC B)and advanced stage HCC(BCLC C/D),whereas Ang-1,VEGF,and alpha-fetoprotein(AFP)levels in the plasma did not show any such *** analysis,propensity score-matched analysis,and timedependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and *** Ang-1 nor VEGF was significantly associated with OS or *** neutrophil-to-lymphocyte ratio was an independent factor for OS and *** The plasma levels of Ang-2 correlated with liver function,tumor stage,and tumor invasiveness,showing better performance in predicting OS and PFS than AFP,Ang-1,or VEGF.

关键词： Hepatocellular carcinoma Angiogenesis Biomarker Prognosis Survival

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Species delimitation in the green algal genus Codium (Bryopsidales) from Korea using DNA barcoding

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Acta Oceanologica Sinica 2015年第4期34卷 114-124页

作者： LEE Hyung Woo kim Myung sook Department of Biology Jeju National University

Codium, one of the largest marine green algal genera, is difficult to delimit species boundary accurately based on morphological identification only. DNA barcoding is a powerful tool for discriminating species of seaweeds. The plastid elongation factor TU （tufA） is considered as maker to perform DNA barcoding of green algal species than rbcL gene due to universality and rapid evolution rate. We conducted DNA barcoding application to Codium specimens from the Jeju Island, Korea to overcome the limit of morphological identification and to confirm the species diversity. As a result of applying tufA marker, we newly generated fifty-five tufA barcodes to resolve eight species. TufA marker exhibited 6.1%–21.8% interspecific divergences, wider than the gap of rbcL exon 1, 3.5%–11.5%. Molecular analysis of rbcL exon 1 sequences of Codium revealed eight distinct species like tufA analysis separated in five phylogenetic groups. DNA barcoding of the genus Codium using tufA marker is more helpful to overcome the limit of morphological identification, and this is more potential to reveal cryptic species and to resolve the relationships among subspecies than rbcL analysis alone. The complement of tufA barcoding and rbcL analyses including morphology for the genus Codium in the northwestern Pacific will give much more reliable achievement for discovering species diversity and resolving the phylogenetic relationships.

关键词： Codium DNA barcoding rbcL Species delimitation tufA

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Stability of Symmetric Solitary Wave Solutions of a Forced Korteweg-de Vries Equation and the Polynomial Chaos

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Advances in Applied Mathematics and Mechanics 2012年第6期4卷 833-847页

作者： Hongjoong kim Kyoung-sook Moon Department of Mathematics Korea UniversitySeoul 136-701Korea Mathematics&Information Gachon UniversityGyeonggi-do 461-701Korea

In this paper,we consider the numerical stability of gravity-capillary waves generated by a localized pressure in water of finite depth based on the forced Korteweg-de Vries(FKdV)framework and the polynomial *** stability studies are focused on the symmetric solitary wave for the subcritical flow with the Bond number greater than one *** its steady symmetric solitarywave-like solutions are randomly perturbed,the evolutions of some waves show stability in time regardless of the randomness while other waves produce unstable *** representing the perturbation with a random variable,the governing FKdV equation is interpreted as a stochastic *** polynomial chaos expansion of the random solution has been used for the study of stability in two *** it allows us to identify the stable solution of the stochastic governing *** it is used to construct upper and lower bounding surfaces for unstable solutions,which encompass the fluctuations of waves.

关键词： Stability solitary waves polynomial chaos forced Korteweg-de Vries equation

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A novel isoxazole compound CM2-II-173 inhibits the invasivephenotype of triple-negative breast cancer cells

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肿瘤学研究(英文) 2023年第6期31卷 867-875页

作者： EUN sook kim SANGHEE kim AREE MOON Duksung Innovative Drug Center College of PharmacyDuksung Women’s UniversitySeoul03169Korea College of Pharmacy Seoul National UniversitySeoul08826Korea

Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient ***-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lackof effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on theinvasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibitedinvasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness ofMCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 *** of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with *** and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibitedinvasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect onthe invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated thatCM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, butalso of liver, prostate, and ovarian cancer cells.

关键词： MMP-9 Cell invasion Breast cells

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Effect of Ca addition on the microstructure and mechanical properties of heat-treated Mg-6.0Zn-1.2Y-0.7Zr alloy

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Journal of Magnesium and Alloys 2021年第5期9卷 1636-1648页

作者： Young Gil Jung Wonseok Yang Yong Joo kim Shae.K.kim Young Ok Yoon Hyunkyu Lim Do hyang kim Advanced Materials and Process R&D Department Korea Institute of Industrial Technology156Gaetbeol-roIncheon 21999Republic of Korea Department of Metallurgical Engineering Yonsei University50Yonsei-roSeoulSeodaemun-gu 03722Republic of Korea

In this study,the effects of Ca addition on the microstructure,thermal properties,and mechanical properties of a Mg-6.0Zn-1.2Y-0.7Zr(ZWK611)alloy at room temperature and 150℃ were *** an increase in the Ca content,the ignition resistance of the ZWK611 alloy improved and the grains became *** as-cast ZWK611 alloy consisted mainly of the dendriticα-Mg matrix and I-phase(Mg_(3)Zn_(6)Y)at the grain *** the other hand,theτ-(Ca_(2)Mg_(6)Zn_(3))and I-phases were formed in the Ca-added ZWK611 *** fraction of theτ-phase increased with an increase in the Ca *** the solid-solution treatment,these phases remained partially at the grain boundaries of the Ca-added ZWK611 alloys and an additional W-phase(Mg_(3)Zn_(3)Y)was *** phases remaining at the grain boundaries restricted the grain growth through the grain boundary pinning *** aging treatment resulted in the formation of MgZn'precipitates in theα-Mg matrix of the *** precipitates were more uniformly distributed in the Ca-added alloys than in the alloys without ***,the heat treatment-induced precipitation improved the tensile and creep properties of the T6-treated *** T6-treated ZWK611+0.7Ca alloy exhibited the best mechanical properties at room temperature and 150℃ among all the tested alloys.

关键词： Mg-Zn-Y alloys Heat-treatment Precipitate Mechanical properties Thermal analysis

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Validation of Sea Level Data in the East Asian Marginal Seas: Comparison between TOPEX/POSEIDON Altimeter and In-Situ Tide Gauges

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Advances in Atmospheric Sciences 2003年第4期20卷 650-660页

作者： Yong-Hoon YOUN Im Sang OH Ki-Hyun kim Young-hyang PARK Jong Woo kim Meteorological Research Institute/Korea Meteorological Administration SeoulKoreaResearch Institute of OceanographySeoul National UniversitySeoulKoreaDepartment of Earth SciencesSejing UniversitySeoulKoreaLaboratoire d'Oceanographie PhysiqueMuseum National d'Histoire NaturelleParisDepartment of Earth SciencesSejong UniversitySeoulKorea

In an effort to assess the reliability of satellite altimeter systems, the authors conduct a comparative analysis of sea level data that were collected from the TOPEX/POSEIDON (T/P) altimeter and 10 tide gauges (TG) near the satellite passing ground tracks. The analysis is made using datasets collected from marginal sea regions surrounding the Korean Peninsula at T/P cycles of 2 to 230, which correspond to October 1992 to December 1998. Proper treatment of tidal errors is a very critical step in data processing because the study area has very strong tide. When the T/P data are processed, the procedures of Park and Gamberoni (1995) are adapted to reduce errors associated with the tide. When the T/P data are processed in this way, the alias periods of M2, S2, and K1 constituents are found to be 62.1, 58.7, and 173 days repectively. The compatibility of the T/P and TG datasets are examined at various filtering periods. The results indicate that the low-frequency signals of the T/P data can be interpreted more safely with longer filtering periods (such as up to the maximum selected value of 200 days). When RMS errors for the 200-day low-pass filter period are compared with all 10 tidal stations, the values span the range of 2.8 to 6.7 cm. The results of a correlation analysis for this filtering period also show a strong agreement between the T/P and TG datasets across all stations investigated (e.g.,p- values consistently less than 0.001). Hence according to the analysis, the conclusion is made that the analysis of surface sea level using satellite altimeter data can be made safely with reasonably extended filtering periods such as 200 days.

关键词： sea level TOPEX/POSEIDON altimeter tide gauge

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