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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

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

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

Cloning,expression in Escherichia coli,and enzymatic properties of laccase from Aeromonas hydrophila WL-11

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Journal of Environmental Sciences 2010年第4期22卷 635-640页

作者： Jing Wu kyoung-sook kim Jai-Heon Lee Young-Choon Lee Department of Biotechnology Dong-A University Busan 604-714 South Korea. Brain Korea 21 Center for Silver-Bio Industrialization Dong-A University Busan 604-714 South Korea

A strain WL-11 with high laccase activity was isolated from activated sludge collected from the effluent treatment plant of a textile and dyeing industry. It was identified as Aeromonas hydrophila by physiological test and 16S rDNA sequence analysis. A gene encoding of laccase from a newly isolated Aeromonas hydrophila WL-11 was cloned and characterized. Nucleotide sequence analysis showed an open reading frame of 1605 bp encoding a polypeptide comprised of 534 amino acids. The primary structure of the enzyme predicted the structural features characteristic of other laccases, including the conserved regions of four histidine-rich copper-binding sites. The predicted amino acid sequence showed a high homology （more than 60%） with bacterial laccases in the genome and protein databases and the highest degree of similarity （61% identity） was observed with the multicopper oxidase of KlebsieUa sp. 601. When expressed in Escherichia coli, the recombinant enzyme was overproduced in the cytoplasm as soluble and active form. The purified enzyme had an optimum pH of 2.6 and 8.0 for ABTS （2,2＇-azino-bis（3-ethylbenzthiazolinesulfonic acid） and DMP （2,6-dimethoxyphenol）, respectively. The kinetic study on ABTS revealed a higher affinity of this enzyme to this substrate than DMP.

关键词： cloning expression enzymatic properties laccase Aeromonas hydrophila

p73 G4C14 to A4T14 polymorphism is associated with colorectal cancer risk and survival

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World Journal of Gastroenterology 2010年第35期16卷 4448-4454页

作者： Kyung-Eun Lee Young-Seoub Hong Byoung-Gwon kim Na-Young kim kyoung-Mu Lee Jong-Young Kwak Mee-sook Roh Department of Clinical Laboratory Science College of Health Sciences Catholic University of Pusan Department of Preventive Medicine Dong-A University College of Medicine Clinical Research Institute Seoul National University College of Medicine Medical Research Center for Cancer Molecular Therapy Dong-A University College of Medicine Department of Pathology Dong-A University College of Medicine

AIM:To analyze the association between the p73 G4C14-to-A4T14 polymorphism(a.k.a.,the GC/AT variation) and colorectal cancer risk and survival in the Korean population,and to evaluate the relationships between p73 polymorphism and the p73 protein expression or clinicopathological characteristics of colorectal ***:Three hundred and eighty-three histologically confirmed cases and 469 healthy controls,recruited at one teaching hospital in Pusan,Korea from 2001 and 2007,were genotyped for p73 G4C14-to-A4T14 by PCR with confronting two-pair primers(PCR-CTPP) and the expression profile of p73 in cancer tissues(n=383) was analyzed by ***:Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated by unconditional logistic regression model adjusted for age and *** with the GC/GC genotypes,the GC/AT and AT/AT genotypes were significantly associated with colorectal cancer risk(GC/AT vs GC/GC:OR = 1.46,95% CI:1.10-1.94;AT/AT vs GC/GC:1.72,0.98-3.03;Ptrend=0.01).When stratified by age and gender,the association was restricted to those less than 60 years of age(GC/AT or AT/AT vs GC/GC:2.22,1.39-3.55) and male(GC/AT or AT/AT vs GC/GC:1.91,1.31-2.77).The expression of p73 was associated with invasion depth(P = 0.003) and advanced Duke's stage(P = 0.06) of colorectal *** patients with the GC/GC genotype were associated with worse survival compared with those with the other genotypes(P = 0.02).However,no signif icant relationship was observed between the p73 G4C14-to-A4T14 polymorphism and p73 protein expression in cancer ***:Our results suggest that the p73 GC/AT polymorphism is associated with an increased colorectal cancer risk and survival in the Korean population.

关键词： p73 G4C14 to A4T14 polymorphism Colorectal cancer

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

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

Sarcomatoid carcinoma of the pancreas—multimodality imaging findings with serial imaging follow-up:A case report and review of literature

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World Journal of Clinical Cases 2021年第13期9卷 3102-3113页

作者： Hyun Jae Lim Hye Seon Kang Jeong Eun Lee Ji Hye Min Kyung sook Shin Sun kyoung You Kyung-Hee kim Department of Radiology Chungnam National University HospitalDaejeon 35015South Korea Department of Radiology Chungnam National University HospitalChungnam National University College of MedicineDaejeon 35015South Korea Department of Radiology and Center for Imaging Science Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Department of Pathology Cancer Research InstituteCollege of MedicineChungnam National UniversityDaejeon 35015South Korea

BACKGROUND Sarcomatoid carcinoma of the pancreas is extremely rare and has an extremely poor *** a few cases of sarcomatoid carcinoma of pancreas have been reported,most are focused on a histopathological *** the best of our knowledge,there are no reports documenting multimodality imaging characteristics and chronological changes with emphasis on radiologic *** SUMMARY A 64-year-old woman was admitted to Chungnam National University Hospital with acute ***-enhanced computed tomography of the abdomen revealed a 2.6 cm×2.8 cm multilobular cystic mass in the pancreatic *** pancreatic lesion showed suspected mural nodules and thin ***,mucinous cystic neoplasm of pancreas was *** 7 mo,the patient was readmitted for repeated epigastric abdominal pain and ***-up contrast-enhanced computed tomography of the abdomen and magnetic resonance imaging revealed a marked enlargement(5.4 cm×4 cm),with a predominant internal solid *** mass showed low signal intensity on a T1-weighted image and heterogeneously intermediate high signal intensity on a T2-weighted image. It showed diffusion restriction and peripheral rimenhancement on an arterial phase image, and progressive enhancement on portalvenous and delayed phase images. Distal pancreatectomy was performed. Basedon the morphology and immunohistochemical staining of the specimen,pancreatic sarcomatoid carcinoma was *** present the computed tomography, magnetic resonance imaging, and positronemission tomography computed tomography findings, pathologic features, andchronological changes for preoperative diagnosis.

关键词： Carcinosarcoma Pancreas Computed tomography Magnetic resonance imaging Pancreatectomy Case report

Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

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World Journal of Gastroenterology 2012年第44期18卷 6420-6426页

作者： Jaeseok Han Eung-Hwi kim Woohyuk Choi Hee-sook Jun Department of Microbiology and Infectious Diseases University of Calgary3330 Hospital Drive N.W.CalgaryAlberta T2N 4N1Canada Del E.Webb Neuroscience Aging and Stem Cell Research CenterSanford Burnham Medical Research InstituteLa JollaCA 92037United States Lee Gil Ya Cancer and Diabetes Institute Gachon University7-45 SondodongYeonsu-kuIncheon 406-840South Korea College of Pharmacy Gachon University7-45 Sondo-dongYeonsu-kuIncheon 406-840South Korea

AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese ***:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level *** intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 *** and insulin tolerance tests were *** staining was performed to investigate islet morphology and insulin ***:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained *** tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected ***:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

关键词： Insulin gene therapy Synthetic promoter Glucose-responsive element Liver-specific promoter Type 2 diabetes