DMNQ S-64 Induces Apoptosis via Caspase Activation and Cyclooxygenase-2 Inhibition in Human Nonsmall Lung Cancer Cells

LIM, E.-S.,RHEE, Y.-H.,PARK, M.-K.,SHIM, B.-S.,AHN, K.-S.,KANG, H.,YOO, H.-S.,KIM, S.-H. Wiley (Blackwell Publishing) 2007 Annals of the New York Academy of Sciences Vol.1095 No.1

<P>Shikonin has been reported to induce apoptosis and inhibit angiogenesis in vivo and in vitro. 6-(1-propoxyiminoalkyl)-5,8-dimethoxyoxy 1,4-naphtoquinone S-64 (DMNQ S-64) was synthesized as a shikonin derivative. In this article, the underlying apoptotic mechanism of DMNQ S-64 was examined. DMNQ S-64 exerted cytotoxicity against A549 lung carcinoma cells with IC(50) of 27.3 microM. Apoptotic bodies were observed in DMNQ S-64-treated A549 cells by 4'-6-diamidino-2-phenylindole (DAPI) staining assay. DMNQ S-64 also increased sub-G1 DNA portion in a concentration-dependent manner by flow cytometric analysis. Western blotting has revealed that DMNQ S-64 effectively activates the expression of caspase 8, 9, and 3, cleaves poly (ADP-ribose) polymerase, and increases the ratio of Bax/Bcl-2. Furthermore, cytochrome c was released in a concentration-dependent manner by DMNQ S-64. Similarly, DMNQ S-64 significantly increased caspase 3 activity by enzyme-linked immunosorbent assay (ELISA). It also significantly inhibited the level of prostaglandin E2 (PGE(2)) by ELISA and downregulated the expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner. Taken together, DMNQ S-64 may exhibit cytotoxicity against A549 cells via caspase activation and COX-2 inhibition.</P>

The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance insulin-induced AP-1 activity and cellular transformation

Lee, N. Y.,Choi, H.-K.,Shim, J.-H.,Kang, K.-W.,Dong, Z.,Choi, H. S. Oxford University Press 2009 Carcinogenesis Vol.30 No.4

<P>Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase Pin1 and is a central signaling mechanism in cell proliferation and transformation. Although Pin1 is frequently overexpressed in hepatocellular carcinoma (HCC), the molecular mechanism of Pin1 in HCC has not been completely elucidated. Here, we show that Pin1 interacts with p70S6K in vitro and ex vivo. Overexpression of Pin1 resulted in enhanced p70S6K phosphorylation induced by insulin in SK-HEP-1 cells. In contrast, Pin1(-/-) mouse embryonic fibroblasts (MEFs) exhibited significantly decreased insulin-induced p70S6K phosphorylation compared with Pin1(+/+) MEFs. Furthermore, Pin1 enhanced the insulin-induced extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation through its interaction with p70S6K, whereas the inhibition of p70S6K activity by rapamycin suppressed insulin-induced ERK1/2 phosphorylation in SK-HEP-1 cells. Hence, Pin1 affected activator protein-1 activity through p70S6K-ERK1/2 signaling in SK-HEP-1 cells. Most importantly, Pin1-overexpressing JB6 Cl41 cells enhanced neoplastic cell transformation promoted by insulin much more than green fluorescent protein-overexpressing JB6 Cl41 control cells. These results imply that Pin1 amplifies insulin signaling in hepatocarcinoma cells through its interaction with p70S6K, suggesting that Pin1 plays an important role in insulin-induced tumorigenesis and is a potential therapeutic target in hepatocarcinoma.</P>

S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis

Kim, S Y,S Hong, Y,K Shim, E,Kong, S-Y,Shin, A,Baek, J Y,Jung, K H Nature Publishing Group 2013 The British journal of cancer Vol.109 No.6

<P><B>Background:</B></P><P>S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.</P><P><B>Methods:</B></P><P>Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m<SUP>−2</SUP> followed by oxaliplatin 85 mg m<SUP>−2</SUP> on day 1 and S-1 80 mg m<SUP>−2</SUP> per day from day 1 to 14 every 3 weeks. Polymorphisms in the <I>UGT1A1</I>, <I>UGT1A6</I>, <I>UGT1A7</I> and <I>CYP2A6</I> genes were analysed.</P><P><B>Results:</B></P><P>Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4–81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of <I>UGT1A6*2</I> or <I>UGT1A7*3</I> and an improved tumour response was noted in those without variant alleles of <I>CYP2A6</I> or <I>UGT1A1*60</I>.</P><P><B>Conclusion:</B></P><P>The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.</P>

MSP430 기반 뇌신경자극기 S/W 설계 및 구현

홍상표(S. P. Hong),권성호(C. H. Quan),심현민(H. M. Shim),김규태(K. T. Kim),김규성(K. S. Kim),윤광섭(K. S. Yoon),이상민(S. M. Lee) 한국재활복지공학회 2015 한국재활복지공학회 학술대회논문집 Vol.2015 No.11

This paper presents the results of the neuromodulation S/W Design and Implementation based on MSP430. The MSP430 operating with ultra power is used actively in the development of human implantable devices. In this paper, The neuromodulation S/W that was designed based on MSP430 has a simple architecture. Also, this neuromodulation S/W provides the reliability and scalability of generating neuro signals simultaneously. In order to verify the operation of the neuromodulation S/W, A separate external control device(PC) test program developed. By using the program, The experiments on generating and controling a brain stimulation signals corresponding to the parameter was conducted and shows the results.

煙草赤星病과 施肥量과의 關係에 關한 硏究

南基桓,沈在燮 충북대학교 엽연초연구소 1974 煙草硏究 Vol.2 No.-

This experiment was carried out in order to observe the effects three elements of fertilizer(N.,P.,K.,) on the infection of tobacco brown spot disease. The plots were designed by split plot method with 8 treatment (A: check, B: 50% added applied N., P. and K., C: 50% subatracted applied three elements., D: 50% added applied N., E: 50% added applied P., F: 50% added applied P., G: no applied P., G: an applied P: and H: no applied P.). Check is N 14kg P2O5 21kg and K3O 28kg per 10 are respectively. Y.S.A was employed for sample variety and transplanted on 15 May. The results obtained as follow; 1) There were no differences among the plots (treatments) during the early growing stages. 2) The plot of 1½N, no K. and 1½N.P.K. have shown larger number of lesions than the check respectively. 3) The plot of 1/2 N.P.K.(C), 1½K(F), and no P.(G) have shown almost no differences in the rate of disease occurence as compared with check (A). In conclusion, excess application of N. and defficiency of K. seemed to be related with tobacco brown spot disease infection.

Deoxycorticosterone acetate가 흰 생쥐의 신사구방세포에 미치는 영향

심현,오영,원경희,임정남,홍기숙 이화여자대학교 의과대학 1977 梨花醫學誌 Vol.- No.9

정상 및 부신을 적출한 숫 흰생쥐를 소정의 사료로 사육하면서 deoxycorticosterone acetate (DCA)를 1주간 투여하였다. 신장을 절취하여 Helly씨 용액으로 고정한 후 Wilson씨 방법으로 염색하여 사구방과립세포를 관찰하였으며 동시에 과립세포지수(GCI) 및 과립지수(JGI)를 조사하여 각 실험군을 비교하였다. 1. 정상군에 DCA를 투여한 결과 GCI 및 JGI의 수치는 의의있는 감소를 인정할 수 없었으며 또한 과립세포형의 출현빈도도 제 1형, 제2형, 제3형의 순으로 변화가 없었다. 2. 부신을 적출하면 GCI는 약간의 증가를 하고, JGI는 현저한 증가를 보이고 있었으며 각 세포형의 출현빈도는 제3형, 제2형, 제1형의 순으로 반전되었음을 보여주었다. 3. 부신을 적출한 흰생쥐에 DCA를 투여한 결과는 정상군에 DCA를 투여한 결과와 같이 GCI 및 JGI 양자 모두, 의의있는 감소를 보여주고 있지 않으며 각 과립세포형의 출현빈도에도 변화를 주고 있지 않다. 4. 이상의 결과는 사구방과립세포가 정상상태에 있건 부신을 적출하여 초래된 기능항진된 상태에 있건 간에 DCA 투여는 큰 영향을 주지 않는 것 같다. For the study of the juxtaglomerular granular cells deoxycorticosterone acetate(DCA), 2.5mg/day was administered to the normal and adrenalectomized mice for one week. The sections of renal tissues of all the experimental groups were stained by Wilson's method after the fixation with Helly's fluid, and the juxtaglomerular granular cell index (GCI) and juxtaglomerular granular index (JGI) were calculated at the magnification of 480 under the light microscope. And compared each other. The results observed were as follows. 1. There were not any significant decrease in both the GCI and JGI following the administration of DCA to normal animals, and the frequency of appearance of the various granular cell types in DCA-treated groups was in the order of Type1, Type 2, and type 3 as in the normal. 2. After adrenalectomy, significant increase in JGI was found and the order of the frequency of appearance of the various granular cell types was reversed. The GCI however, showed slight increase in number but is not significant. 3. The administration of DCA to adrenalectomized mice seemed not to show any significant decrease in GCI and JGI as in the DCA-treated normal group and the frequency of appearance of cell types was as same as in the DCA-treated adrenalectomized group. 4. The above results could show that the administration of DCA would not affect to decrease the granulation of juxtaglomerular granular cells in both the normal and adrenalectomized groups.

Increased Serum Levels of Mutant p53 Proteins in Patients with Colorectal Cancer

Shim, K.-S Korean Academy of Medical Science 1998 Journal of Korean medical science Vol.13 No.1

Bi-S 쾌삭강의 칩생성특성

이영문,조삼규,장은실,태원의,심보경 韓國工作機械學會 2000 한국생산제조학회지 Vol.9 No.3

In this study, the characteristics of chip formation of the cold drawn Bi-S free machining steels were assessed. And for comparison, those of the cold drawn Pb-S free machining steel, the hot rolled low carbon steel which has MnS as free machining inclusions and the conventional steels were also investigated. During chip formation, the cold drawn free machining steels show relatively little change in thickness and width of chip compare to those of the conventional carbon steels. And a single parameter which indicates the degree of deformation during chip formation, 'chip cross-section area ratio' is introduced. The chip cross-section area ratio is defined as chip cross-section area is divided by undeformed chip cross-section area. The variational patterns of the chip cross-section area ratio of the materials cut are similar to those of the shear strain values. The shear stress, however, seems to be dependent on the carbon content of the materials. The cold drawn Bi-S and Pb-S steels show nearly the same chip forming behaviors and the energy consumed during chip formation is almost same. A low carbon steel without free machining aids shows poor chip breakability due to its high ductility. By introducing a small amount of free machining inclusions such as MnS, Bi, Pb or merely increasing carbon content the chip breakability improves significantly.

In situ K-doped SWCNTs synthesis by hydrogen arc-discharge method and their field emission properties

K. S. Kim,W. J. Shim,C. J. Lee 한국진공학회 2007 한국진공학회 학술발표회초록집 Vol.16 No.1

Autoanalyzer를 利用한 醫藥品分析硏究 (第3報) : 제제중의 Streptomycin 및 Dihydrostreptomycin의 정량에 대하여 Determination of Streptomycin or Dihydrostreptomycin in Pharmaceutical Preparations.

沈應基,李金貞,崔秉箕,金吉洙,李昌鉉 國立保健硏究院 1971 국립보건연구원보 Vol.8 No.-