Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via C/EBPβ and potentiates breast cancer progression

Kim, E-S,Cha, Y,Ham, M,Jung, J,Kim, S G,Hwang, S,Kleemann, R,Moon, A Macmillan Publishers Limited 2014 Oncogene Vol.33 No.27

A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast cancer aggressiveness has been reported. Recent clinical studies have suggested that C-reactive protein (CRP) has a role in breast cancer development. However, limited information is available on the molecular basis for the expression of CRP and its functional significance in breast cell invasion. The present study aimed to elucidate the molecular link between S1P and CRP during the invasive process of breast epithelial cells. This is the first report showing that transcription of CRP was markedly activated by S1P in breast cells. Our data suggest that not only S1P treatment but also the endogenously produced S1P may upregulate CRP in breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta and c-fos were required for S1P-induced CRP expression. Coupling of S1P<SUB>3</SUB> to heterotrimeric G<SUB>αq</SUB> triggered the expression of CRP, utilizing signaling pathways involving reactive oxygen species (ROS), Ca<SUP>2+</SUP> and extracellular signal-related kinases (ERKs). S1P-induced CRP expression was crucial for the transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c-fos, leading to breast cell invasion. Using a xenograft mice tumor model, we demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken together, our findings have revealed a molecular basis for S1P-induced transcriptional activation of CRP and its functional significance in the acquisition of the invasive phenotype of human breast epithelial cells under inflammatory conditions. Our findings may provide useful information on the identification of useful therapeutic targets for inflammatory breast cancer.

Purification and characterization of a novel fibrinolytic α chymotrypsin like serine metalloprotease from the edible mushroom, Lyophyllum shimeji

Moon, S.M.,Kim, J.S.,Kim, H.J.,Choi, M.S.,Park, B.R.,Kim, S.G.,Ahn, H.,Chun, H.S.,Shin, Y.K.,Kim, J.J.,Kim, D.K.,Lee, S.Y.,Seo, Y.W.,Kim, Y.H.,Kim, C.S. Society for Bioscience and Bioengineering, Japan ; 2014 Journal of bioscience and bioengineering Vol.117 No.5

A novel fibrinolytic enzyme was purified from Lyophyllum shimeji, a popular edible mushroom in Asia. The enzyme was purified using combination of anion exchange chromatography on a Mono Q 5/5 column and size exclusion gel filtration chromatography on Superdex 200 100/300 column. This purification protocol resulted 80.9-fold purification of the enzyme and a final yield of 5.7%. The molecular weight of the purified enzyme was estimated to be 21 kDa by SDS-PAGE and size exclusion gel filtration. The N-terminal amino acid sequence was found to be ITFQSASP, which is dissimilar from that of known fibrinolytic enzymes. The purified enzyme was a neutral protease with an optimal reaction pH and temperature of 8.0 and 37<SUP>o</SUP>C, respectively. Enzymatic activity was inhibited by Cu<SUP>2+</SUP> and Co<SUP>2+</SUP>. It was also significantly inhibited by PMSF and TPCK. Furthermore, it was found to exhibit a higher specificity for S-7388, a well-known chymotrypsin chromogenic substrate, indicating chymotrypsin like serine metalloprotease. The relative fibrinolytic activity of 5 μg purified enzyme have two fold more activity than 1 unit/ml of plasmin on fibrin plate. Furthermore, purified enzyme preferentially hydrolyzed the Aα-chain followed by the Bβ- and γ-chain of fibrinogen, which is precursor of fibrin. Therefore, these data suggests that the fibrinolytic enzyme derived from edible mushroom, L. shimeji, might be useful for thrombolytic therapy and preventing thrombotic disease.

난관배양액이 처녀발생유기된 돼지난포란의 체외발달에 미치는 영향

문승주,이경호,김호,김창렬,은대숙,김광현,나진수,김재홍 全南大學校 農業科學技術硏究所 1997 農業科學技術硏究 Vol.32 No.-

본 연구는 난관배양액이 돼지수정란의 체외발달에 미치는 효과를 규명키 위하여 수행하였다. 돼지 미성숙 난포란은 TCM-199, Ham's F-10 그리고 Whitten's 배양액에 10% 난포액과 호르몬(PMSG : 10IU/㎖, HCG : 10IU/㎖)을 첨가 20시간 배양하고 호르몬을 첨가하지 않는 배양액에서 20시간 추가 배양하여 총 40시간동안 배양하여 체외성숙을 유도하였다. 체외성숙후 0.1% hyaluronidase로 난구세포를 제거하고 15% FCS가 함유된 TCM-199으로 3회 세척하고 TCM-199에 15% FCS와 10% ethanol 혼합액에 세척한 난자를 옮겨 10분간 배양 처녀발생을 유기하였다. 처녀발생 6시간후 전핵형성율은 체외성숙배양액으로 TCM-199을 사용했을 때 56.4%, Ham's F-10의 경우 58.3%, Whitten's 배양액의 경우 74.0%를 보였다. 처녀발생 유기 48시간째 난할율은 TCM-199을 사용했을 때 45.7%, Ham's F-10에서 45.4%, Whitten's배양액에서 39.2%를 보였으며 세종류의 배양액에 POCM을 첨가 배양했을 때 TCM-199에 44.8%, Ham's F-10에서 45.4%, Whitten's배양액에서 43.7%로 나타났다. 처녀발생육 난자를 96시간 체외배양시킨 결과 상실배 발달율이 POCM을 첨가 했을 때 첨가하지 않은 시험구에 비하여 유의적으로 높았다(P<0.05) The effect of porcine oviductal conditioned medium(POCM) on in vitro development of chemically activated porcine oocytes was studied. Porcine oocytes were cultured in TCM-199, Ham's F-10 and Whitten's medium with hormonal supplements for 20h and 40h additional culture without hormonal supplements. After in vitro maturation, the denuded oocytes were washed 3 times with TCM-199 contaning 15%(v/v) ethanol to induce pathenogenetic activation. At 6h after activation, pronuclea formation rates were 56.4% in TCM-199, 59.3% in Ham's F-10 and 74.0% in Whitten's maturation medium. At 48h after activation, 45.7%, 45.4% and 39.2% of oocytes claved in TCM-199, Ham's F-10 and Whitten's culture medium, respectively. And 44.8%, 45.5% and 43.7% of oocytes were claved in TCM-199, Ham;s F-10 and Whitten's culture medium supplemented with POCM, respectively. The rates of moular were higher in culture medium with POCM than without POCM at 96h after activation.(P<0.05)

Caspase-3 activation as a key factor for HBx-transformed cell death

Kim, A.,Kwon, O. S.,Kim, S. O.,He, L.,Bae, E. Y.,Lee, M. S.,Jeong, S. J.,Shim, J. H.,Yoon, D. Y.,Kim, C. H.,Moon, A.,Kim, K. E.,Ahn, J. S.,Kim, B. Y. Blackwell Publishing Ltd 2008 Cell proliferation Vol.41 No.5

<P>Abstract. </P><P><I>Objectives</I>: Nuclear factor-kappa B (NF-&kgr;B) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. <I>Materials and methods</I>: NF-&kgr;B activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-&kgr;B, proteasome and DNA topoisomerase. <I>Results</I>: Inhibition of NF-&kgr;B transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3&bgr; (GSK-3&bgr;), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, I&kgr;Bα (S32/36A) mutant plasmid or other NF-&kgr;B inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor. <I>Conclusions</I>: Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.</P>

CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Bae, J.S.,Park, S.H.,Jamiyandorj, U.,Kim, K.M.,Noh, S.J.,Kim, J.R.,Park, H.J.,Kwon, K.S.,Jung, S.H.,Park, H.S.,Park, B.H.,Lee, H.,Moon, W.S.,Sylvester, K.G.,Jang, K.Y. American Association of Pathologists and Bacteriol 2016 The American journal of pathology Vol.186 No.12

<P>Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 alpha 1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, beta-catenin, cyclin D1, and NF-kappa B. Especially, SIRT6 expression was associated with the nuclear localization of B-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.</P>

문학반응이론에 의한 보건의학기술계열 국가시험개선방안에 관한 연구

이창규,이승관,조경진,박종성,정수경,유병서,박상숙,윤효숙,황선철,문경환,김정민,함용운,김지환,임국환,김영순,윤경희,황성준 高麗大學校 倂設 保健大學 保健科學硏究所 1998 保健科學論集 Vol.24 No.1

The nationally-governed examinations for certification of allied health professions in Korea have been continued for thirty three years. During that time, there were a lot of managerial improvements in carrying out the examinations, for example, the looking-over the papers converted from manual method to computerized one. Nevertheless, the overall aspects of item management in the national examinations are still remained as obsolete style. In some developed countries they have already tried or adopted computerized system in making questions, executing item analysis, developing item banking, and in overall management of examinations, looking over papers for their national licensure examinations, and have established good reputations. Since the National Health Personnel Licensing Examination Board was established in 1998, now we can expect there would be a lots of improvements in the managerial systems and organizational structures associated with the national licensing examinations suggesting followings. 1. The contents and scope of the licensing examinations based on job analysis should be announced publicaly. 2. Items should be developed based on the scopes and contents of job characteristics. 3. All the developed items for the licensing examinations should be tested quantitatively prior to banking items. 4. All the parameters of the stored items should be fully estimated through item response theory. 5. All the efforts should be given in order to execute the examinations in individual residential areas on behalf of every examinee. 6. To the licensing examination system the Computerized Adaptive Testing system should be introduced in order to enhance the efficiencies. 7. Security enhancement on the stored items should be reminded in order to prevent leaking out the banking items. 8. Much more improvements should be made for the proper job evaluations. 9. Every efforts should be given to prevent cheatings encountable during the examinations. 10. Make the best of professional volunteers from the various fields in the execution of licensing examinations. 11. Consider a new system in that examinations can be executed twice or more in a year. 12. The current methods of presiding over the examinations should be replaced by a more reasonable one. 13. The results of the examinations should be announced as soon as possible in order not to prolong the examinees' unemployment periods. 14. The National Health Personnel Licensing Examination Board should try to rationalize the management keeping step with the information-oriented society.

Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study

Kim, Moon Young,Baik, Soon Koo,Park, Dong Hun,Lim, Dae Wook,Kim, Jae Woo,Kim, Hyun Soo,Kwon, Sang Ok,Kim, Young Ju,Chang, Sei Jin,Lee, Samuel S. Wiley-Blackwell Publishing 2007 Liver International Vol. No.

<P>Abstract</P><P>Background and Aims</P><P>Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis.</P><P>Material and Methods</P><P>In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies.</P><P>Results</P><P>Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed (<I>P</I><0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07–49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG (<I>P</I><0.01).</P><P>Conclusions</P><P>Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis.</P>

보건소 단위 만성퇴행성질환 예방프로그램 개발에 관한 연구 : 복지기관과의 연계,협동방안 탐색

김택숙,함철호,송순태,문창진,신혜령,김수영,정은경 국립보건연구원 2000 국립보건원보 Vol.37 No.-

Impact of White Matter Changes on Activities of Daily Living in Mild to Moderate Dementia

Moon, So Young,Na, Duk L.,Seo, Sang Won,Lee, Jun-Young,Ku, Bon D.,Kim, Seong Yoon,Park, Kyung Won,Shim, Yong S.,Youn, Young Chul,Chung, Chan-Seung,Cheong, Hae-Kwan,Choi, Seong Hye,Cha, Kyung Ryeol,Kim S. Karger AG 2011 European neurology Vol.65 No.4

<P>The association between white matter changes and activities of daily living (ADL) in a large, well-defined cohort of patients with mild-to-moderate dementia (either Alzheimer’s disease or subcortical vascular dementia) were investigated. A total of 289 patients were divided into three groups (140 mild, 99 moderate, and 50 severe) depending on the degree of white matter changes as indicated on brain magnetic resonance image scans. Further, we analyzed the three groups’ performances on basic and instrumental ADL. The degree of white matter changes was associated with greater age, hypertension, previous history of stroke, higher Hachinski Ischemic Score, worse global cognitive and functional status, and an increased impairment of basic ADL and instrumental ADL. The increased impairment with regard to the severe group’s performance on both the basic and instrumental ADL remained significant after adjustment for age and hypertension. Tasks involving physical activities were most significant. This was the first study investigating the association between white matter changes and ADL in a large, well-defined dementia cohort. The present study suggests that severe white matter changes may be associated with higher impairment on both basic and instrumental ADL.</P><P>Copyright © 2010 S. Karger AG, Basel</P>

난소암 환자에서 2차 및 3차 개복수술

문정일,한구택,이준모,김수평,남궁성은,이헌영,김승조 가톨릭 중앙의료원 가톨릭 암센터 1987 가톨릭 암센터 論集 Vol.1 No.1