http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Kim, Taekx2010,Keun,Park, Chang Sik,Jang, Jihye,Kim, Mi Ra,Na, Heex2010,Jun,Lee, Kangseung,Kim, Hyun Jung,Heo, Kyun,Yoo, Byong Chul,Kim, Youngx2010,Myeong,Lee, Je‐,Wook,Kim, Su Jin,Kim, Eu John Wiley and Sons Inc. 2018 MOLECULAR ONCOLOGY Vol.12 No.3
<P>The C‐type lectin‐like domain of CLEC14a (CLEC14a‐C‐type lectin‐like domain [CTLD]) is a key domain that mediates endothelial cell–cell contacts in angiogenesis. However, the role of CLEC14a‐CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity‐determining region grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti‐angiogenic human monoclonal antibody that specifically targets CLEC14a‐CTLD and that shows improved stability and homogeneity relative to the parental antibody. We found that this antibody directly inhibits CLEC14a‐CTLD‐mediated endothelial cell–cell contact and simultaneously downregulates expression of CLEC14a on the surface of endothelial cells. Using various <I>in vitro</I> and <I>in vivo</I> functional assays, we demonstrated that this antibody effectively suppresses vascular endothelial growth factor (VEGF)‐dependent angiogenesis and tumor angiogenesis of SNU182 human hepatocellular carcinoma, CFPAC‐1 human pancreatic cancer, and U87 human glioma cells. Furthermore, we also found that this antibody significantly inhibits tumor angiogenesis of HCT116 and bevacizumab‐adapted HCT116 human colorectal cancer cells. These findings suggest that antibody targeting of CLEC14a‐CTLD has the potential to suppress VEGF‐dependent angiogenesis and tumor angiogenesis and that CLEC14a‐CTLD may be a novel anti‐angiogenic target for VEGF‐dependent angiogenesis and tumor angiogenesis.</P>
Kim, Inki,Choi, Yeonx2010,Sook,Song, Jae Hwi,Choi, Eun A,Park, Sojung,Lee, Eun Ji,Rhee, Je‐,Keun,Kim, Song Cheol,Chang, Suhwan John Wiley and Sons Inc. 2018 MOLECULAR ONCOLOGY Vol.12 No.9
<P>Pancreatic cancer is one of the most difficult cancers to cure due to the lack of early diagnostic tools and effective therapeutic agents. In this study, we aimed to isolate new bioactive compounds that effectively kill pancreatic ductal adenocarcinoma (PDAC) cells, but not untransformed, human pancreatic ductal epithelial (HPDE) cells. To this end, we established four primary PDAC cell lines and screened 4141 compounds from four bioactive‐compound libraries. Initial screening yielded 113 primary hit compounds that caused over a 50% viability reduction in all tested PDAC cells. Subsequent triplicate, dose‐dependent analysis revealed three compounds with a tumor cell‐specific cytotoxic effect. We found that these three compounds fall into a single category of thiopurine biogenesis. Among them, 6‐thioguanine (6‐TG) showed an IC<SUB>50</SUB> of 0.39–1.13 μ<SMALL>M</SMALL> toward PDAC cells but had no effect on HPDE cells. We propose that this cancer selectivity is due to differences in thiopurine methyltransferase (TPMT) expression between normal and cancer cells. This enzyme is responsible for methylation of thiopurine, which reduces its cytotoxicity. We found that <I>TPMT</I> levels were lower in all four PDAC cell lines than in HPDE or Panc1 cells, and that knockdown of <I>TPMT</I> in HPDE or Panc1 cells sensitized them to 6‐TG. Lastly, we used a patient‐derived xenograft model to confirm that 6‐TG has a significant antitumor effect in combination with gemcitabine. Overall, our study presents 6‐TG as a strong candidate for use as a therapeutic agent against PDAC with low levels of TPMT.</P>
Kim, Byungx2010,Gyu,Park, Younx2010,Je,Libermann, Towia A.,Cho, Je‐,Yoel Wiley Subscription Services, Inc., A Wiley Company 2011 Journal of cellular biochemistry Vol.112 No.8
<P><B>Abstract</B></P><P>Continuous treatment with parathyroid hormone (PTH) or excess endogenous PTH due to primary hyperparathyroidism causes increased bone resorption and, subsequently, decreased bone volume. Our previous studies showed that myeloid Elf‐1‐like factor (MEF) not only suppresses osteoblast differentiation through inhibition of Runx2 activity and other osteogenesis‐related genes but also specifically increases the expression of Mab21, a potential transcriptional repressor of osteoblast differentiation. Here we show that the JNK1 pathway is involved in the MEF‐mediated up‐regulation of Mab21 expression due to PTH stimulation. PTH increased the transcription level of Mab21 in MG63 human osteoblastic cells, in contrast to the suppressive effect of TGFβ1. PTH phosphorylates serine residues of MEF as well as c‐Jun, a known substrate of JNK1. By <I>in vitro</I> kinase assay, we confirmed that MEF is phosphorylated by JNK1, but not by ERK. Co‐transfection of MEF with both MKK4 and JNK1 increased the promoter activity of Mab21 in CV1 cells significantly more than MEF alone. We also identified the phosphorylation of MEF serine 641 by <I>in vitro</I> and <I>in vivo</I> JNK1 kinase assays combined with a proteomics approach. In conclusion, our findings indicate that MEF is involved in PTH suppression of osteoblasts through activating the MKK4/JNK1 pathway and subsequently up‐regulating Mab21 expression. J. Cell. Biochem. 112: 2051–2061, 2011. © 2011 Wiley‐Liss, Inc.</P>
Ko, Youngx2010,Ho,Kim, Je‐,Hyung,Jin, Lix2010,Hua,Ko, Sukx2010,Min,Kwon, Bongx2010,Joon,Kim, Joosung,Kim, Taek,Cho, Yongx2010,Hoon WILEY‐VCH Verlag 2011 ADVANCED MATERIALS Vol.23 No.45
<P>Electrically driven hybrid light‐emitting diodes (LEDs) consisting of quantum dots, wires, and wells based on the nanometer‐sized pyramid GaN structure are reported by Taek Kim, Yong‐Hoon Cho, and co‐workers on page 5364. The LEDs exhibit mixed emissions from InGaN quantum dots, wires, and wells formed at the tops, edges, and sidewalls of the pyramids, respectively. The hybrid LEDs containing low‐dimensional quantum structures provide a broad‐band, highly efficient visible lighting source. </P>
Leem, Yeax2010,Hyun,Oh, Seikwan,Kang, Hongx2010,Je,Kim, Jungx2010,Hwa,Yoon, Juno,Chang, Jaex2010,Suk John Wiley 2017 Environmental toxicology Vol. No.
<P><B>ABSTRACT</B></P><P>Bisphenol A (BPA), used in the manufacture of products based on polycarbonate plastics and epoxy resins, is well known as an endocrine‐disrupting monomer. In the current study, BPA increased cytotoxicity in hBMSCs in a dose‐ and time‐dependent manner, concomitantly with increased lipid peroxidation. Increased cell death in BPA‐treated cells was markedly blocked by pretreatment with the superoxide dismutase mimetic MnTBAP and MnTMPyP, but not by catalase, glutathione, the glutathione peroxidase mimetic ebselen, the NOS inhibitor NAME, or the xanthine oxidase inhibitor allopurinol. Furthermore, the decline in nuclear β‐catenin and cyclin D1 levels in hBMSCs exposed to BPA was reversed by MnTBAP treatment. Finally, treatment of hBMSCs with the GSK3β inhibitor LiCl<SUB>2</SUB> increased nuclear β‐catenin levels and significantly attenuated cytotoxicity compared with BPA treatment. Our current results in hBMSCs exposed to BPA suggest that BPA causes a disturbance in β‐catenin signaling via a superoxide anion overload. © 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 32: 344–352, 2017.</P>
Park, Sunx2010,Mi,Park, Seungx2010,Ho,Ryu, Kix2010,Jun,Kim, Inx2010,Kyu,Han, Hyeontak,Kim, Hyox2010,Jin,Kim, Seonx2010,Hee,Hong, Keunx2010,Seok,Kim, Hyemin,Kim, Minju,Cho, Bok Im,Heo, Je Elsevier Science B.V. Amsterdam 2019 MOLECULAR ONCOLOGY Vol.13 No.5
<P>The epithelial–mesenchymal transition (EMT) plays a pivotal role in the conversion of early‐stage tumors into invasive malignancies. The transcription factor Snail, an extremely unstable protein whose subcellular levels are regulated by many E3 ubiquitin ligases, promotes EMT as well as associated pathological characteristics including migration, invasion, and metastasis. Through yeast two‐hybrid screening, we identified the carboxyl terminus of Hsc70‐interacting protein (CHIP) as a novel Snail ubiquitin ligase that interacts with Snail to induce ubiquitin‐mediated proteasomal degradation. Inhibition of CHIP expression increases Snail protein levels, induces EMT, and enhances <I>in vitro</I> migration and invasion as well as <I>in vivo</I> metastasis of ovarian cancer cells. In turn, Snail depletion abrogates all phenomena induced by CHIP depletion. Finally, Snail and CHIP expression is inversely correlated in ovarian tumor tissues. These findings establish the CHIP–Snail axis as a post‐translational mechanism of EMT and cancer metastasis regulation.</P>
Lee, Sungx2010,Eun,Min, Changx2010,Ki,Yahng, Seungx2010,Ah,Cho, Byungx2010,Sik,Eom, Kix2010,Seong,Kim, Yoox2010,Jin,Kim, Heex2010,Je,Lee, Seok,Cho, Seokx2010,Goo,Kim, Dongx2010,Wook Blackwell Publishing Ltd 2011 European journal of haematology Vol.86 No.1
<P><B>Abstract</B></P><P>Osteolytic lesions with activated osteoclast (OC) and suppressed osteoblast (OB) activity are characteristics of myeloma bone lesion. Recently, it has been shown that bortezomib treatment enhances OB function. To evaluate the effect of bortezomib on myeloma bone lesions, we performed bone scans, where increased uptake of the radiopharmaceutical by OBs is associated with re‐building activity. Bortezomib treatment markedly enhanced bone metabolic activity and increased alkaline phosphatase levels, and decreased monoclonal protein levels. These findings suggest that bortezomib has potent anti‐myeloma activity and bone‐protecting effects, with enhanced OB function.</P>
Namkung, Jungx2010,Hyun,Lee, Jongx2010,Eun,Kim, Eugene,Kim, Hyunx2010,Je,Seo, Eunx2010,Young,Jang, Hyex2010,Yoon,Shin, Eunx2010,Soon,Cho, Eunx2010,Young,Yang, Junx2010,Mo Blackwell Publishing Ltd 2011 Experimental dermatology Vol.20 No.11
<P><B>Abstract: </B> Th2‐dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL‐4 and IL‐13 are typical pleiotropic Th2 cytokines that play a central role in IgE‐dependent inflammatory reactions. Single‐nucleotide polymorphisms (SNPs) in IL‐4 and IL‐13 have been reported in patients with allergic disease from numerous countries. Gene–gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL‐4, IL‐13, IL‐4R, IL‐13Rα1 and IL‐13Rα2 genes for 1089 case‐control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in these genes. We also searched for gene–gene interactions among these five genes. Our data identified an association between rs3091307 and rs20541 in the IL‐13 gene and between rs2265753 and rs2254672 in the IL‐13Rα1 gene and the AD phenotype. In particular, three of the four SNPs were especially predictive of the allergic type of AD (ADe), and the haplotype TCGG in the IL‐13Rα1 gene showed significant association with AD, especially ADe. Furthermore, the combination of rs3091307 GG/ rs2265753 GG (IL‐13/IL‐13Rα1) conveyed a significantly higher risk for developing ADe. However, we did not identify any SNPs in the IL‐4, IL‐4R and IL‐13Rα2 genes that were associated with AD. As IL‐13Rα1 is most likely expressed in Th17 cells rather than in Th2 cells, these data suggest diversity in the classification of Th cells that needs to be verified in future studies.</P>
Lee, Sungx2010,Eun,Park, Sung Soo,Jeon, Youngx2010,Woo,Yoon, Jaex2010,Ho,Cho, Byungx2010,Sik,Eom, Kix2010,Seong,Kim, Yoox2010,Jin,Lee, Seok,Min, Changx2010,Ki,Kim, Heex2010,Je,Cho, Seo John Wiley Sons, Inc. 2018 American journal of hematology Vol.93 No.11
<P><B>Abstract</B></P><P>This prospective study explored an optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with severe aplastic anemia (SAA) who received haplo‐identical stem cell transplantation from a related mismatched donor (Haplo‐SCT). We explored a safe and sufficient dose of rabbit ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and fludarabine (Flu, 30 mg/m<SUP>2</SUP>/day) for 5 days using step‐by‐step dose de‐escalation. The dose of ATG was de‐escalated from 10 mg/kg (group 1), to 7.5 mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy (group 4) beginning in October 2014. If one patient developed transplant‐related mortality (TRM) with engraftment in a group, we moved to the next lower dose group. Thirty‐four patients were enrolled in groups 1‐3 (<I>n</I> = 10) and 4 (<I>n</I> = 24). All patients achieved primary engraftment. The incidence of acute GVHD (grade ≥ 2) and chronic GVHD (≥ moderate) was 29.4% and 14.7%, respectively. With a median follow‐up of 56.6 and 21.8 months in groups 1‐3 and group 4, respectively, the 2‐year probability of overall survival (91.7% in group 4 vs 70% in groups 1‐3, <I>P</I> = 0.155) and GVHD‐free survival (78.4% in group 4 vs 50% in groups 1‐3, <I>P</I> = 0.115) was shown tended to be better in group 4. This study explored an optimal conditioning with step‐by‐step de‐escalation dosage of ATG and TBI to reduce TRM with sustained graft function. TBI‐600 cGy/Flu/intermediate‐dose ATG resulted in feasible outcomes of Haplo‐SCT for adult patients with SAA.</P>
Lee, Sungx2010,Eun,Kim, Yoox2010,Jin,Yahng, Seungx2010,Ah,Cho, Byungx2010,Sik,Eom, Kix2010,Sung,Lee, Seok,Min, Changx2010,Ki,Kim, Heex2010,Je,Cho, Seokx2010,Goo,Kim, Dongx2010,Wook,L Blackwell Publishing Ltd 2011 European journal of haematology Vol.87 No.6
<P><B>Abstract</B></P><P><I>Objective:</I> The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower‐risk (INT‐1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation‐comorbidity index score ≤3). <I>Methods:</I> Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced‐intensity conditioning (RIC; <I>n</I> = 14), intensified RIC by adding low‐dose total body irradiation (iRIC; <I>n</I> = 15), and myeloablative conditioning (MAC; <I>n</I> = 17). <I>Results:</I> After a median follow‐up of 73.7 months, RIC had a better 4‐yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, <I>P </I>=<I> </I>0.022] because of a lower transplant‐related mortality (TRM) (RR, 0.08, <I>P </I>=<I> </I>0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, <I>P </I>=<I> </I>0.689) because of similarly high TRM (RR of 0.41, <I>P </I>=<I> </I>0.480). Cumulative incidence of acute and chronic graft‐versus‐host disease (GVHD) after RIC was higher, but GVHD‐specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, <I>P </I>=<I> </I>0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients. <I>Conclusion:</I> This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC–SCT should be considered for relative healthy lower‐risk MDS patients.</P>