• Title/Summary/Keyword: CPT I

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Synergistic antitumor activity of ST1571 and camptothecin in human cancer cells (Camptothecin 에 의한 ST1571 의 항암 활성 증강)

  • Kim, Mi-Ju;Lee, Sang-Min;Bae, Jae-Ho;Chung, Byung-Seon;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.748-755
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    • 2007
  • The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

The Prediction Method of the Small Strain Shear Modulus for Busan Clay Using CPT and DMT (CPT와 DMT를 이용한 부산점토의 최대전단탄성계수 추정방법에 관한 연구)

  • Hong, Sung-Jin;Yoon, Hyung-Ko;Lee, Jong-Sub;Lee, Woo-Jin
    • Journal of the Korean Geotechnical Society
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    • v.25 no.6
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    • pp.5-16
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    • 2009
  • The is study is to evaluate the small strain shear modulus ($G_{max}$) of Busan clay using in-situ penetration tests. A series of dilatometer tests (DMT) and piezocone penetration tests (CPTu) are performed at Busan newport and Noksan sites, and hybrid oedometer tests are also carried out on the specimens obtained from both sites. The $G_{max}$ is evaluated from the shear wave velocity ($V_s$) measured by the bender elements installed at the boundary of oedometer cell. By analyzing these data, the relationship of $G_{max}$ and state variables, such as confined stress and void ratio, is developed. The analysis of lab and in-situ test results reveals that the ratio of $G_{max}$ to $q_t$ is inversely proportional to the plasticity index while the ratio of $G_{max}$ to $E_D$ has a linear relationship with ($I/I_D$)$(p_a/{\sigma}'_v)^{0.5}$. Two correlations suggested in this study, based on CPT and DMT results, appear to provide reasonable predictions of the small strain shear modulus.

Sequential administration of camptothecin sensitizes human colon cancer HCT116 cells to paclitaxel via $p21^{Cip1/WAF1}$

  • Yoo, Jung-Min;Kim, Yun-Jin;Lee, Sung-Jae;Kim, Sang-Hoon
    • Animal cells and systems
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    • v.15 no.1
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    • pp.9-17
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    • 2011
  • Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells

  • Ran, Xiaoli;Zhao, Wenwen;Li, Wenping;Shi, Jingshan;Chen, Xiuping
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.347-355
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    • 2016
  • Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha ($TNF-{\alpha}$) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of $TNF-{\alpha}$ on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe $CM-DCFH_2-DA$. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. $TNF-{\alpha}$ induced LOX-1 expression in a dose- and time- dependent manner in endothelial cells. $TNF-{\alpha}$ induced ROS formation, phosphorylation of $NF-{\kappa}B$ p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. $NF-{\kappa}B$ inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited $TNF-{\alpha}-induced$ LOX-1 expression. CPT and NAC suppressed $TNF-{\alpha}-induced$ LOX-1 expression and phosphorylation of $NF-{\kappa}B$ p65 and ERK in rat aorta. These data suggested that $TNF-{\alpha}$ induced LOX-1 expression via ROS activated $NF-{\kappa}B/ERK$ pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

Effects of Inhibitors on the Function and Activity of Topoisomerase, and Gene Expression in HL-60 Human Leukemia Cells (HL-60 세포의 유전자 발현 및 topoisomerase의 기능 활성에 미치는 억제제의 영향)

  • Jeong, In-Cheol;Cho, Moo-Youn;Park, Jang-Su
    • Journal of Life Science
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    • v.18 no.1
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    • pp.75-83
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    • 2008
  • This studies were designed to elucidate whether inhibitors of topoisomerase regulate function and activity of topoisomerase, and gene expression in HL-60 human leukemia cells. HL-60 cells were treated with 10-hydroxycamptothecin or doxorubicin, total RNA was isolated, and expressed genes were investigated with human oligonucleotide microarray containing 10K gene, respectively. Expression profiles of the human leukemia HL-60 cells treated with 10-hydroxycamptothecin (10-CIT) or doxorubicin associated with signal transduction,. cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription and immune response, especially genes related with transcription and cell growth. In HL-60 cells treated with 10-CPT, the expression of topoisomerase III${\alpha}$, III${\beta}$ and I gene from oligo chip microarray analysis were increased over, but the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were decreased over. In contrast, the expression of topoisomerase II${\alpha}$ and II${\beta}$ gene were increased over in HL-60 cells treated with doxorubicin, whereas the expression of topoisomerase III${\alpha}$ and III${\beta}$ mRNA remained no significant change. These results suggest that these data may be useful for novel therapeutic markers.

A Study on the Ground Improvement Effective Evaluation of Reclaimed Land Using Cone Penetration Test (CPT를 이용한 준설매립지반의 개량효과 평가에 관한 연구)

  • Kim, Jong-Kook;Chae, Young-Su;Kim, Myoung-Mo
    • Proceedings of the Korean Geotechical Society Conference
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    • 2004.03b
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    • pp.910-921
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    • 2004
  • In this study, the pilot tests on the reclaimed land were performed in order to find the suitable construction method with dynamic compaction Type I, Type II at different dynamic energy and hydraulic hammer compaction. The estimation of the compaction through the various pilot tests was performed by the CPT-qc, SPT-N and field density tests. As the result of the pilot tests, it shows that the dynamic compaction method is better than the hydraulic hammer compaction method in the effect of the ground improvement, especially dynamic compaction Type I is much superior to others. When it comes to method for measuring the intensity of the ground, the value of the cone penetration test-resistance(qc) is much suitable for the ground. Besides, the standards for the compaction control, which showed that over 10Mpa at 0 through 5meters in the upper layer and 7Mpa at 5 through 8meters in the lower layer in the CPT-qc, could be found without discrimination of the upper road and lower road on the reclaimed land. And it also found that the intensity of the reclaimed land gets back to the original status in about 10 through 15 days.

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Evaluation on Resistance to Pitting Corrosion of Fe-Cr Alloys via Measurement of the Critical Pitting Temperature (CPT) and Potentiodynamic Polarization According to KS D 0238 (wet, dry), ASTM G 61 and ISO 17475 Standards (Fe-Cr합금의 공식저항성 평가를 위하여 다양한 규격(KS D 0238, ASTM G 61, ISO 17475)에 따라 실시한 동전위 분극 시험과 임계공식온도 측정시험)

  • Kang, Su-Yeon;Lee, Jae-Bong;Kim, Yeong-Ho
    • Korean Journal of Metals and Materials
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    • v.47 no.10
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    • pp.635-643
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    • 2009
  • The resistance to pitting corrosion of Fe-Cr alloys was evaluated by performing potentiodynamic polarization and critical pitting temperature (CPT) tests. For the potentiodynamic polarization tests, various standards were applied, i.e., KS D 0238 (wet, dry), ASTM G 61, and ISO 17475, showing different potentiodynamic polarization results including pitting potentials. ASTM G 61 and ISO 17475 standards presented relatively higher pitting potential while KS D 0238 (dry) indicated lower values than the others. Effects of surface roughness, scan rates, and exposure time to air before tests were also investigated. CPT tests were performed under two different applied potentials, 300 m$V_{SCE}$ and 200 m$V_{SCE}$ in deaerated 1 M NaCl aqueous solution. CPT values and the polarization test results showed a linear relationship.

Effects of Wekyungtang and Kami-Wekyungtang on Pulmonary Tumor Cells and the Changes of Tissues (위경탕(葦莖湯).가미위경탕(加味葦莖湯)의 B16-Fo에 대(對)한 항종양(抗腫瘍) 효과(效果)와 조직(組織) 변화(變化))

  • Kim, Hyeon-Su;Kim, Seong-Hun
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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    • pp.365-385
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    • 1995
  • In order to prove the antitumor effect of Wekyungtang(WKT) that was originated in Bigeubchunkeumyobang(備急千金要方), Wekyungtang with Houttuyniae Herba(WKT-I) and Wekyungtang with Oldenlandiae diffusae Herba(WKT-II) experimentally, the studies were done, We evaluated the cytotoxic activity against B16- Fo as well as the synergistic effects with anticancer drugs such as cyclophophamide (CPM), cisplatin(CPT) and 5-fluorouracil (5-FU) in vitro and measured body weight, survival time, hematological changes, changes of tissues in G57BL/6 implanted with B16-Fo. The results were obtained as follows: 1. In vitro cytotoxic effect against B16-Fo was shown in all groups as compared with control group, but the concentrations showing inhibitory growth rate below 55% of control was recognized in all concentrations of Wekyungtang(WKT) against B16-Fo and also concentration of $10^4$g/ml above in all group with cyclophophamide (CPM), concentration of $10^3$g/ml in Wekyungtang(WKT-l) with cisplatin(CPT) in synergistic effect, 2. In vivo body and tumor weight were significantly suppressed in all groups as compared with control group 3. The number of platelet, WBC, RBC were significantly increased in all groups, platelet aggregation was significantly increased in WKT-I and WKT-II as compared with control group. 4. In changes of tissues heavy infiltration oh cancer was shown in portal vein, pulmonary tissue, vein, peribronchiole, aveoli, while WKT-I was effective in antihepatic metastasis and WKT-II in pulmonary matastasis. From above results it was concluded that wekyungtang(WKT), wekyungtang with Houttuyniae Herba(WKT-I) and wekyungtang with Oldenlandiae diffusae Herba(WKT -II) had antitumor effect, and also wekyungtang combined with Houttuyniae Herba or Oldenlandiae diffusae Herba were more effective than wekyungtang only and also cyclophophamide (CPM), cisplatin(CPT) showed the more synergistic effect which suggests the necessity of continuous study on the mechanism of antitumor action of Houttuyniae Herba or Oldenlandiae diffusae Herba.

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L-Carnitine Reduces Obesity Caused by High-Fat Diet in C57BL/6J Mice

  • Mun, Eun-Gyeng;Soh, Ju-Ryoun;Cha, Youn-Soo
    • Food Science and Biotechnology
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    • v.16 no.2
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    • pp.228-233
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    • 2007
  • This study evaluated the effects of carnitine supplementation on obesity caused by a high-fat diet in C57BL/6J mice. The mice were fed a normal diet (ND), high-fat diet (HD), or carnitine-supplemented (0.5% of diet) high-fat diet (HDC) for 12 weeks. The results showed that body weight, energy intake, and feed intake were lower in the HDC group than the control groups. Acid-soluble acylcarnitine (A SAC), acid-insoluble acylcarnitine (AIAC), and total carnitine (TCNE) in the serum and liver were significantly higher in the HDC group. Hepatic carnitine palmitoyl transferase-I activity was significantly higher in the HDC group than the control groups. Acyl-coA synthetase (ACS) and carnitine palmitoyl transferase-I (CPT-I) mRNA expression in the liver was highest in the HDC group, however hepatic acetyl-coA carboxylase (ACC) mRNA expression in this group was lowest. Serum leptin levels and abdominal fat weight were lowest in the HDC group. We concluded that L-carnitine supplementation diminished the risk of obesity caused by a high-fat diet.

Children's Personality Type, Creative Thinking and Creative Personality (MMTIC에 의한 아동의 성격 유형과 창의성과의 관계)

  • Lee, Myung Hee;Lee, Jeong Dug
    • Korean Journal of Child Studies
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    • v.20 no.4
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    • pp.159-177
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    • 1999
  • This study analyzed children's personality types with the use of the Murphy-Meisgeier Type Indicator for Children(MMTIC: adapted for Korea by Kim, 1993) and examined their relationship to the Torrance Tests of Creative Thinking(TTCT-figural, form A) and the Creative Personality Test(CPT: Yim,1997). Subjects were 210 third- and 218 sixth-grade students. Data were analyzed by one-way ANOVA and t-test. Personality types Sensation/Judgment(SJ), Sensation/Perceiving(SP), iNtuition/Thinking(NT) and iNtuition/Feeling(NF) differentiated the eleboration, originality, and flexibility dimensions of creative thinking. There were gender differences in the relation of personality type NF to elaboration and fluency. There were age differences in personality types SP and NF in relation to elaboration. Personality types differentiated between the independence, openness, attachment and adventurousness dimensions of the CPT. Age differences in personality type SP differentiated independence and type NT differentiated attachment dimensions of creative personality.

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