• 약학회지
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• 제43권3호
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• pp.385-390
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• 1999

Camptothecin (CPT) has been known to induce apoptosis in various cancer cell lines. To examine the intracellular apoptotic death signal initiated by CPT, we investigated the possible connection between caspase-3 activation and GSH depletion during CPT-induced apoptosis in HL-60 cells. Treatment of cells with $1{\;}{\mu}M$ CPT induced PARP cleavage accompanied by DNA fragmentation. z-VAD-fmk, a caspase-3 inhibitor, blocked the CPT-induced DNA fragmentation. Pretreatment of cells with N-acetylcysteine, a precursor of GSH biosynthesis, failed to inhibit CPT-induced PARP celavage and DNA gragmenatation. No significant changes in GSH depletion is not essential for caspase activation during CPT-induced apoptosis. We also investigated whether CPT-induced apoptosis is associated with changes of the levels of Bax and Bcl-2, two proteins involved in the control of apoptosis. Bcl-2 levels exhibited a late decrease compared with the kinetics of DNA fragmentation, whereas Bax levels increased more rapidly after CPT treatment. These results suggest that Bax plays more important role than Bcl-2 in inducing DNA fragmentation and may function upsteam of proteolytic activation of caspase-3 pathway in CPT-induced apoptosis.

• 생명과학회지
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• 제10권6호
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• pp.621-629
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• 2000

Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

• Journal of Ginseng Research
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• 제41권3호
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• pp.403-410
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• 2017

Background: Prenyltransferases catalyze the sequential addition of isopentenyl diphosphate units to allylic prenyl diphosphate acceptors and are classified as either trans-prenyltransferases (TPTs) or cis-prenyltransferases (CPTs). The functions of CPTs have been well characterized in bacteria, yeast, and mammals compared to plants. The characterization of CPTs also has been less studied than TPTs. In the present study, molecular cloning and functional characterization of a CPT from a medicinal plant, Panax ginseng Mayer were addressed. Methods: Gene expression patterns of PgCPT1 were analyzed by quantitative reverse transcription polymerase chain reaction. In planta transformation was generated by floral dipping using Agrobacterium tumefaciens. Yeast transformation was performed by lithium acetate and heat-shock for $rer2{\Delta}$ complementation and yeast-two-hybrid assay. Results: The ginseng genome contains at least one family of three putative CPT genes. PgCPT1 is expressed in all organs, but more predominantly in the leaves. Overexpression of PgCPT1 did not show any plant growth defect, and its protein can complement yeast mutant $rer2{\Delta}$ via possible protein-protein interaction with PgCPTL2. Conclusion: Partial complementation of the yeast dolichol biosynthesis mutant $rer2{\Delta}$ suggested that PgCPT1 is involved in dolichol biosynthesis. Direct protein interaction between PgCPT1 and a human Nogo-B receptor homolog suggests that PgCPT1 requires an accessory component for proper function.

• 한국지반공학회논문집
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• 제27권4호
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• pp.21-32
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• 2011

본 연구는 CPT와 DMT를 이용한 부산지역 점토 압축성 추정에 관한 것으로, 이를 위해 부산신항과 녹산점토에 대해 현장시험 및 실내시험을 수행하였다. 압밀시험 결과 부산신항 및 녹산 점토는 정규압밀점토이며, 압축지수는 0.5~1.3로 나타났다. 분석결과에 의하면 콘저항치와 횡방향구속 변형계수의 상관계수인 ${\alpha}_m$과 ${\alpha}_n$은 소성지수에 따라 감소하였으며, 딜라토미터 계수와 횡방향구속 변형계수의 상관계수 $R_M$은 $1/I_D$에 따라 증가하였다. 본 연구에서는 이러한 관계를 이용하여 횡방향구속 변형계수를 추정하는 방법을 제안하였다. 제안된 방법으로 횡방향구속 변형계수를 추정한 결과 CPT 추정방법은 개량 후 지반의 횡방향구속 변형계수를 과소평가한 반면, DMT 추정방법은 개량 전 후 지반 모두 횡방향구속 변형계수를 적절히 추정하였다.

• 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.

• Geomechanics and Engineering
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• 제13권1호
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• pp.119-139
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• 2017

Static Penetration Test (CPT) and Dynamic Penetration Test (DPT) are commonly used in-situ tests in a routine geotechnical investigation. Besides their use for qualitative investigation (lithology, homogeneity and spatial variability), they are used as practical tools of geotechnical characterization (resistance to the penetration, soil rigidity) and modern foundation design as well. The paper aims at presenting the results of an extensive research work on the evaluation of the 1D primary consolidation settlement of saturated clayey soils on the basis of the CPT or DPT tests. The work is based on an analysis of the correlations between the tip resistance to penetration measured in these tests and the parameters of compressibility measured by the compressibility oedometer test, through a local geotechnical database in the northern Algeria. Such an analysis led to the proposal of two methods of calculation of the settlement, one based on the CPT test and the other one on the DPT. The comparison between the predicted settlements and those computed on the basis of the oedometer test showed a good agreement which demonstrate the possbility to use the CPT and DPT tests as reliable tools of computation of foundation settlements in clayey soils.

• Geomechanics and Engineering
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• 제35권1호
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• pp.67-80
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• 2023

Due to the nature of the conjunctive Cone Penetration Test(CPT), which does not verify the actual sample directly, geotechnical engineers commonly classify the underground geomaterials using CPT results with the classification diagrams proposed by various researchers. However, such classification diagrams may fail to reflect local geotechnical characteristics, potentially resulting in misclassification that does not align with the actual stratification in regions with strong local features. To address this, this paper presents an objective method for more accurate local CPT soil classification criteria, which utilizes C4.5 decision tree models trained with the CPT results from the clay-dominant southern coast of Korea and the sand-dominant region in South Carolina, USA. The results and analyses demonstrate that the C4.5 algorithm, in conjunction with oversampling, outlier removal, and pruning methods, can enhance and optimize the decision tree-based CPT soil classification model.

• 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.

• 운동영양학회지
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• 제16권1호
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• pp.1-9
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• 2012

Long chain fatty acids (LCFAs) are transported into cells via plasma transporters, are activated to fatty acyl-CoA by fatty acyl-CoA synthase (ACS), and enter mitochondria via the carnitine system (CPT1/CACT/CPT2). The mitochondrial carnitine system plays an obligatory role in β-oxidation of LCFAs by catalyzing their transport into the mitochondrial matrix. Fatty acyl-CoAs are oxidized via the β-oxidation pathway, which results in the production of acetyl-CoA. The acetyl-CoA can be imported into the tricarboxylic acid (TCA) cycle for oxidation in the mitochondrial matrix or can be used for malonyl-CoA synthesis by acetyl-CoA carboxylase 2 (ACC2) in the cytoplasm. In skeletal muscle, ACC2 catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, which is a potent endogenous inhibitor of carnitine palmitoyltransferase 1 (CPT1). Thus, ACC2 indirectly inhibits the influx of fatty acids into the mitochondria. Fatty acid metabolism can also be regulated by malonyl-CoA-mediated inhibition of CPT1.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제8권2호
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• pp.273-286
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• 1997

본 연구는 주의력결핍 ${\cdot}$ 과잉행동장애 환아에서 사건관련전위와 연속과제수행에 대한 methylphenidate(MPH)의 영향을 평가하고 사건관련전위의 변화와 연속과제수행의 변화 사이의 상관성을 알아보고자 시행되었다. 11명의 주의력결핍 ${\cdot}$ 과잉행동장애 남아에서 MPH(0.5mg/kg)의 급성효과를 알아보기위하여 사건관련전위와 연속과제수행검사를 시행하여 다음과 같은 결과를 얻었다. 약물 투여후, Fz에서 표준자극에 대한 P3 잠복기가 유의하게 감소하였고 Pz, Oz에서 표적자극에 대한 P2 진폭, 그리고 Cz에서 표적자극에 대한 P3 진폭이 유의하게 증가하였다. 또한 CPT-X 파라다임에서 탈락수와 오보수, 그리고 CPT-AX 파라다임에서 오보수가 유의하게 감소하였으며 CPT-X 파라다임의 반응의 정확도(the number of correct responses to targets, Hits)와 민감도(Perceptual sensitivity, d') 그리고 CPT-AX 파라다임의 민감도가 유의하게 증가하였다. 마지막으로 Fz에서 표적자극에 대한 P3 잠복기의 변화와 CPT-AX 파라다임의 민감도의 변화사이에는 음의 상관(p<0.05)이 있었고 Pz에서의 표적자극에 대한 P2 진폭의 변화와 CPT-X 파라다임의 민감도의 변화 사이에는 유의한 양의 상관(p<0.05)이 있었다. 결론적으로 MPH는 주의력결핍 ${\cdot}$ 과잉행동장애 아동에서 변화지향반응, 과제와 연관된 자극에 대한 반응, 정확도, 민감도를 개선시키며 비표적자극으로부터 표적자극을 구별하는 능력의 증가는 큰 기억요소를 요하는 과제에서는 자극 평가시간의 단축을 반영하며 단순과제에서는 변화지향반응의 개선을 반영하는 것으로 나타났다.