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        SURF4 has oncogenic potential in NIH3T3 cells

        Kim, Jayoung,Hong, Chae Mi,Park, Su Min,Shin, Dong Hoon,Kim, Jee Yeon,Kwon, Sang-Mo,Kim, Jae Ho,Kim, Chi Dae,Lim, Dae-Sik,Lee, Dongjun Elsevier 2018 Biochemical and biophysical research communication Vol.502 No.1

        <P><B>Abstract</B></P> <P>SURF4, which is located in the Surfeit gene cluster, encodes for a conserved integral membrane protein containing multiple putative transmembrane regions. However, the physiological role of SURF4 has not been determined. We found that <I>SURF4</I> demonstrated aberrant amplification and increased expression in the tumor tissues of several human cancer patients. Overexpression of SURF4 led to increased cell proliferation, migration, and maintenance of anchorage-independent growth. In addition, NIH3T3 cells overexpressing SURF4 induced tumor growth in the mice. Collectively, our findings demonstrate that SURF4 has the potential for inducing cellular transformation and cell migration <I>in vitro</I> and has oncogenic transformation ability <I>in vivo</I>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>SURF4</I> was found to be amplified and highly expressed in the tumor tissues of several human cancer patients. </LI> <LI> Patients with tumors exhibiting high <I>SURF4</I> expression had significantly shorter overall survival than low <I>SURF4</I> expression. </LI> <LI> <I>SURF4</I> can induce cellular transformation and cell migration <I>in vitro</I> and promotes oncogenic transformation <I>in vivo.</I> </LI> </UL> </P>

      • Differential disruption of autoinhibition and defect in assembly of cytoskeleton during cell division decide the fate of human <i>DIAPH1</i>-related cytoskeletopathy

        Kim, Bong Jik,Ueyama, Takehiko,Miyoshi, Takushi,Lee, Seungmin,Han, Jin Hee,Park, Hye-Rim,Kim, Ah Reum,Oh, Jayoung,Kim, Min Young,Kang, Yong Seok,Oh, Doo Yi,Yun, Jiwon,Hwang, Sang Mee,Kim, Nayoung K D BMJ Publishing Group Ltd 2019 Journal of medical genetics Vol.56 No.12

        <P><B>Background</B></P><P>Diaphanous-related formin 1 (DIA1), which assembles the unbranched actin microfilament and microtubule cytoskeleton, is encoded by <I>DIAPH1</I>. Constitutive activation by the disruption of autoinhibitory interactions between the N-terminal diaphanous inhibitory domain (DID) and C-terminal diaphanous autoregulatory domain (DAD) dysregulates DIA1, resulting in both hearing loss and blood cell abnormalities.</P><P><B>Methods and results</B></P><P>Here, we report the first constitutively active mutant in the DID (p.A265S) of humans with only hearing loss and not blood cell abnormality through whole exome sequencing. The previously reported DAD mutants and our DID mutant (p.A265S) shared the finding of diminished autoinhibitory interaction, abnormally upregulated actin polymerisation activity and increased localisations at the plasma membrane. However, the obvious defect in the DIA1-driven assembly of cytoskeleton ‘during cell division’ was only from the DAD mutants, not from p.A265S, which did not show any blood cell abnormality. We also evaluated the five DID mutants in the hydrophobic pocket since four of these five additional mutants were predicted to critically disrupt interaction between the DID and DAD. These additional pathogenic DID mutants revealed varying degrees of defect in the DIA1-driven cytoskeleton assembly, including nearly normal phenotype during cell division as well as obvious impaired autoinhibition, again coinciding with our key observation in DIA1 mutant (p.A265S) in the DID.</P><P><B>Conclusion</B></P><P>Here, we report the first mutant in the DID of humans with only hearing loss. The differential cell biological phenotypes of DIA1 during cell division appear to be potential determinants of the clinical severity of <I>DIAPH1-</I>related cytoskeletopathy in humans.</P>

      • SCISCIESCOPUSKCI등재

        Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

        Kim, Won Tae,Yun, Seok Joong,Yan, Chunri,Jeong, Pildu,Kim, Ye Hwan,Lee, Il-Seok,Kang, Ho-Won,Park, Sunghyouk,Moon, Sung-Kwon,Choi, Yung-Hyun,Choi, Young Deuk,Kim, Isaac Yi,Kim, Jayoung,Kim, Wun-Jae Yonsei University College of Medicine 2016 Yonsei medical journal Vol.57 No.4

        <P><B>Purpose</B></P><P>Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome.</P><P><B>Materials and Methods</B></P><P>A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed.</P><P><B>Results</B></P><P>Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (<I>CPT1A, CPT1B, CPT1C, CPT2, SLC25A20</I>, and <I>CRAT</I>) or tryptophan metabolism (<I>TPH1</I> and <I>IDO1</I>) was assessed by RT-PCR in our BCA cohort (n=135). C<I>PT1B, CPT1C, SLC25A20, CRAT, TPH1</I>, and <I>IOD1</I> were significantly downregulated in tumor tissues compared to normal bladder tissues (<I>p</I><0.05 all) of patients with non-muscle invasive BCA, whereas <I>CPT1B, CPT1C, CRAT</I>, and <I>TPH1</I> were downregulated in those with muscle invasive BCA (<I>p</I><0.05), with no changes in <I>IDO1</I> expression.</P><P><B>Conclusion</B></P><P>Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.</P>

      • KCI등재SCOPUS

        Decreased <i>DBC1</i> Expression Is Associated With Poor Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer

        Shim, Ui Jae,Lee, Il-Seok,Kang, Ho Won,Kim, Jayoung,Kim, Won Tae,Kim, Isaac Yi,Ryu, Keun Ho,Choi, Yung Hyun,Moon, Sung-Kwon,Kim, Yong-June,Yun, Seok-Joong,Lee, Sang-Cheol,Kim, Wun-Jae The Korean Urological Association 2013 Korean Journal of Urology Vol.54 No.9

        <P><B>Purpose</B></P><P>The deleted in bladder cancer 1 (<I>DBC1</I>) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of <I>DBC1</I> as a prognostic marker in BC.</P><P><B>Materials and Methods</B></P><P>The expression of <I>DBC1</I> was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of <I>DBC1</I> was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model.</P><P><B>Results</B></P><P><I>DBC1</I> expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower <I>DBC1</I> expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low <I>DBC1</I> expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of <I>DBC1</I> expression in NMIBC (log-rank test, each, p<0.05).</P><P><B>Conclusions</B></P><P>The expression of <I>DBC1</I> was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that <I>DBC1</I> expression can be a useful prognostic marker for patients with NMIBC.</P>

      • SCIESCOPUSKCI등재
      • KCI등재

        Advances in urinary biomarker discovery in urological research

        Jayoung Kim,김원태,김원재 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.-

        A disease-specific biomarker (or biomarkers) is a characteristic reflecting a pathological condition in human body, which can be used as a diagnostic or prognostic tool for the clinical management. A urine-based biomarker(s) may provide a clinical value as attractive tools for clinicians to utilize in the clinical setting in particular to bladder diseases including bladder cancer and other bladder benign dysfunctions. Urine can be easily obtained by patients with no preparation or painful procedures required from patients' side. Currently advanced omics technologies and computational power identified potential omics-based novel biomarkers. An unbiased profiling based on transcriptomics, proteomics, epigenetics, metabolomics approaches et al. found that expression at RNA, protein, and metabolite levels are linked with specific bladder diseases and outcomes. In this review, we will discuss about the urine-based biomarkers reported by many investigators including us and how these biomarkers can be applied as a diagnostic and prognostic tool in clinical trials and patient care to promote bladder health. Furthermore, we will discuss how these promising biomarkers can be developed into a smart medical device and what we should be cautious about toward being used in real clinical setting.

      • KCI등재

        파킨슨병에서 혀 압력과 연하 기능 및 삶의 질의 연관성

        JaYoung Kim,Kyoung Hyo Choi,Young-Jin Song,Sun Ju Chung,Kye Won Park,Kyeong Joo Song,Woo Chul Son,Hye Joon Ahn 대한연하장애학회 2020 대한연하장애학회지 Vol.10 No.1

        Objective: The purpose of this study was to verify the hypothesis, by performing objective measurements, that tonguepressure will have an association with swallowing function in patients with Parkinson’s disease. It was also of interestwhether measures of lingual function were consistent with reports of swallowing related quality of life. Methods: The subjects were 18 patients with Parkinson’s disease. Their tongue pressure was examined by using anIowa oral performance instrument (IOPI). They all underwent video fluoroscopic swallowing study (VFSS) and theycompleted a Korean swallowing-quality of life questionnaire (K-SWAL-QOL). Tongue pressures were measured in theanterior (MTPa: maximal tongue pressure anterior) and posterior (MTPp: maximal tongue pressure posterior). Thecutoff value of MTP was 34 kPa. Results: The average of tongue pressure was decreased in both anterior (MTPa=27.79±13.44 kPa) and posterior(MTPp=19.20±8.88 kPa), and MTPp of all the subjects was less than 34 kPa. For the MTPa, 11 patients were under34 kPa (abnormal group) and 7 patients were above 34 kPa (normal group). The oral transit time (OTT) of the abnormalMTPa group was significantly delayed more than that of the normal group (P=0.006). On the correlationanalysis, the MTPa and OTT, MTPa and penetration aspiration scale (PAS), MTPp and PAS showed significant negativecorrelations with each other. The MTP and the social, sleep and fatigue subscores of K-SWAL-QOL showedsignificant positive correlations. Conclusion: In patients with Parkinson’s disease, lower tongue pressure was related to delayed oral transit time anda higher aspiration tendency. We expect the clinical usage of the easily measured tongue pressure to predict theswallowing function and help plan the correct treatment.

      • Ammonolysis-Induced Solvent Removal : A Facile Approach for Solidifying Emulsion Droplets into PLGA Microspheres

        Kim, Jayoung,Hong, Dasom,Chung, Younglim,Sah, Hongkee 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.18

        An ammonolysis-based microencapsulation technique useful for the preparation of biodegradable microspheres was described in this study. A dispersed phase consisting ot poly-ㅇ,L-lactide-co-glycolide, progesterone, and methyl chloroacetate was emulsified in an aqueous phase. Upon addition of ammonia solution, the emulsion droplets were quickly transformed into poly-D,L-lactide-co-glycolide microspheres laden with progesterone. Rapid solvent removal was accompanied by ammonolysis. The chemical reaction converted water-immiscible methyl chloroacetate to water-iniscible chloroacetaipide and methanol. Chloroacetamide formation was proved by ¹H NMR and ESI-MS studies. Thermogravimetric analysis showed that the microspheres contained only small amounts of residual methyl chloroacetate. Incorporation efficiencies of progesterone ranged from 64.3 ± 1.1 to 72.8 ± 0,3%, depending upon microsphere formulations. X-ray powder diffractometry analysis substantiated that no polymorphic transition of progesterone occurred during microeneapsulation. To evaluate the feasibility of this new method against the commonly used microencapsulation method, microspheres were also prepared by a typical dichloroinethane-based solvent evaporation process. The important attributes of microspheres prepared from both methods were characterized for comparison. The new ammonolysis-hased microencapsulation process showed interesting features distinct from those of the solvent evaporation process. The microencapsulation process reported in this study might he applicable in loading pharmaceuticals into various polymeric microspheres.

      • KCI등재

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