• 제목/요약/키워드: CPT-I

검색결과 57건 처리시간 0.026초

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

  • 김미주;이상민;배재호;정병선;강치덕;김선희
    • 생명과학회지
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    • 제17권6호통권86호
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    • pp.748-755
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    • 2007
  • 본 연구에서는 전이성 암세포와 항암제 다제내성 세포에 있어서 항암제 내성에 영향을 미치는 것으로 알려진 DNA-dependent protein kinase (DNA-PK) 가 Abl protein-tyrosine kinases저해제인 STl571 내성에도 연관되어 있는지에 대하여 조사하였다. 또한 STl571 과 topoisomerase I 저해제인 camptothecin (CPT) 의 단독 및 병용처리에 의한 항암 활성을 전이성 암세포와 항암제 다제내성 세포를 대상으로 조사하였다. 세포의 전이도와 내성정도에 따라 STl571 의 감수성이 다르게 나타났다. 이와 함께 ST1571의 처리후 농도에 따라 전이도가 낮은 KMl2, PC3 세포와 항암제 감수성인 CEM, MCF-7 세포에서는 DNA-PK 의 발현이 감소하는 반면, 전이도가 높은 KML4a, PC-MM2 세포와 다제내성 CEM/MDR 및 MCR/MDR 세포에서는 그 발현이 증가되어 있음을 알 수 있었다. 이는 DNA-PK 의 발현이 STl571 의 내성에 관여한다는 것을 시사한다. 이와 같은 결과에 근거하여 DNA-PK 의 발현을 감소시키는 CPT를 STl571 내성을 나타내는 암세포에 대하여 STl571 과 병용처리 하였다. 그 결과 DNA-PK의 발현이 감소되고 세포증식이 억제됨으로써 ST1571 의 감수성이 CPT에 의해 증가하는 것을 알 수 있었다. 따라서 본 연구에서는 DNA-PK가 STl571 의 내성을 극복하는데 있어서 새로운 표적이 될 수 있으며, STl571 의 치료내성 극복에 CPT 와의 병용처리가 유효함을 알 수 있었다.

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

  • 홍성진;윤형구;이종섭;이우진
    • 한국지반공학회논문집
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    • 제25권6호
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    • pp.5-16
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    • 2009
  • 본 연구는 콘 관입시험(CTP)과 딜라토미터시험(DMT)을 이용한 부산지역 점토의 최대전단탄성계수 추정($G_{max}$)에 관한 것이다. 이를 위해 부산신항 지역과 녹산지역에서 피에조콘 관입시험(CPT) 및 달라토미터시험(DMT)를 수행하였으며, 비교란 시료를 채취하여 hybrid oedometer 시험을 실시하였다. Oedometer 내벽에 장착된 벤더엘리먼트로 전단파 속도를 측정하여 최대전단탄성계수를 산정하였으며, 이를 바탕으로 부산점토의 최대전단탄성계수와 구속응력, 간극비, 응력이력간의 관계를 파악하였다. 현장시험 및 실내시험을 분석한 결과, $q_t$$G_{max}$의 상관계수 ${\alpha}_G$는 소성지수에 반비례하는 것으로 나타났으며, $E_D$$G_{max}$의 상관계수 $R_G$는 ($I/I_D$)$(p_a/{\sigma}'_v)^{0.5}$와 비례관계를 나타냈다. 이러한 관계를 바탕으로 본 연구에서는 CPT와 DMT 시험으로부터 $G_{max}$를 추정하는 방법을 개발하였으며, 제안된 방법은 부산점토의 최대전단탄성계수를 적절하게 예측하는 것으로 관찰되었다.

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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    • 제15권1호
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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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    • 제20권4호
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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.

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

  • 정인철;조무연;박장수
    • 생명과학회지
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    • 제18권1호
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    • pp.75-83
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    • 2008
  • 인체 DNA topoisomerase는 DNA를 단일 또는 두 가닥을 일시적인 절단을 촉매하여 DNA의 topological 문제를 조절함으로써, DNA 복제, 전사, 재조합과 유사분열 과정 등에 관여한다. 이 효소는 많은 항생, 항암제의 표적효소로서 널리 알려져 있으며, 이들 유도체를 이용한 다양한 억제제의 개발과 임상적 응용에 관한 연구가 활발하게 진행되고 있다. 본 실험에서는 인체 백혈병 HL-60 세포에서 topoisomerase 억제제가 topoisomerase 기능 활성과 유전자 발현을 조절하는지를 규명하기 위하여 본 연구를 수행하였다. 연구 방법은 HL-60세포에 topoisomerase type I과 type II의 대표적 억제제인 10-hydroxycamptothecin (10-CPT)과 doxorubicin을 투여한 후 total RNA를 분리하였고, 10K-oligo-nucleotide microarray 방법으로 분석하여 유전자의 발현 양상을 조사하였다. 연구 결과에 의하면 10-CPT 또는 doxorubicin을 투여한 HL-60세포에서의 유전자 발현 양상은 주로 signal transduction, cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription 및 immune response 등과 관련이 있었다. Topoisomerase type I의 억제제인 10-CPT를 HL-60 세포주에 투여 하였을 때 type I으로 분류되는 topoisomerase III${\alpha}$, III${\beta}$ 및 I의 발현은 증가하였으나 type II인 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현은 감소되었다. 반대로 type II의 억제제인 doxorubicin을 투여하였을 때는 앞의 결과와 상반된 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현이 현저히 증가되었으며, topoisomerase III${\alpha}$와 III${\beta}$의 mRNA의 발현은 약간 감소하는 양상을 보였으나 의미 있는 차이는 없었다. 이 연구 결과는 앞으로 항암제의 기전을 밝히고 약물에 대한 치료 반응을 예측하고 새로운 약제 개발에 기초자료가 될 것으로 여겨진다.

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

  • 김종국;채영수;김명모
    • 한국지반공학회:학술대회논문집
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    • 한국지반공학회 2004년도 춘계학술발표회
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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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Fe-Cr합금의 공식저항성 평가를 위하여 다양한 규격(KS D 0238, ASTM G 61, ISO 17475)에 따라 실시한 동전위 분극 시험과 임계공식온도 측정시험 (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)

  • 강수연;이재봉;김영호
    • 대한금속재료학회지
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    • 제47권10호
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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.

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) (Effects of Wekyungtang and Kami-Wekyungtang on Pulmonary Tumor Cells and the Changes of Tissues)

  • 김현수;김성훈
    • 대한한의학회지
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    • 제16권2호
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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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    • 제16권2호
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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.

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

  • 이명희;이정덕
    • 아동학회지
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    • 제20권4호
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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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