• 제목/요약/키워드: Target-sensitivity

검색결과 615건 처리시간 0.029초

Diagnostic Relevance of Overexpressed Serine Threonine Tyrosine Kinase/Novel Oncogene with Kinase Domain (STYK1/NOK) mRNA in Colorectal Cancer

  • Orang, Ayla Valinezhad;Safaralizadeh, Reza;Hosseinpour Feizi, Mohammad Ali;Somi, Mohammad Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권16호
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    • pp.6685-6689
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    • 2014
  • Background: Alterations in gene expression levels or mutations of tyrosine kinases are detected in some human cancers. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with colorectal cancer. We also examined the clinical relevance of STYK1/NOK expression in cancer tissues. Materials and Methods: In tumor samples of patients with colorectal cancer and their matched non-cancerous samples, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitative reverse transcriptase polymerase chain reaction. Associations between the expression levels of STYK1/NOK and clinicopathological characteristics of colorectal cancer were also assessed using Mann-Whitney U and Kruskal-Wallis tests. Results: Upregulation of STYK1/NOK was found in cancer tissues even at early stage of colorectal cancer compared to normal adjacent tissues. The optimal cutoff point of 0.198 the STYK1/NOK expression showed 0.78 sensitivity and 0.75 specificity for diagnosis. Overexpressed STYK1/NOK was correlated with tumor size but had no association with other clinicopathological characteristics of colorectal cancer. Conclusions: These results indicate that STYK1/NOK mRNA is widely expressed in the patients with colorectal cancer and suggest that inhibition of this molecule could potentially serve as a novel therapeutic target.

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

  • Chian, Song;Li, Yin-Yan;Wang, Xiu-Jun;Tang, Xiu-Wen
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권6호
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    • pp.2911-2916
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    • 2014
  • Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

중수로 원전 교류전원 완전상실 사고 시 일차측 열수송 펌프 밀봉 누설 영향에 대한 코드 분석 (Code Analysis of Effect of PHTS Pump Sealing Leakage during Station Blackout at PHWR Plants)

  • 유선오;조민기;이경원;백경록
    • 한국압력기기공학회 논문집
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    • 제16권1호
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    • pp.11-21
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    • 2020
  • This study aims to develop and advance the evaluation technology for assessing PHWR safety. For this purpose, the complete loss of AC power or station blackout (SBO) was selected as a target accident scenario and the analysis model to evaluate the plant responses was envisioned into the MARS-KS input model. The model includes the main features of the primary heat transport system with a simplified model for the horizontal fuel channels, the secondary heat transport system including the shell side of steam generators, feedwater and main steam line, and moderator system. A steady state condition was achieved successfully by running the present model to check out the stable convergence of the key parameters. Subsequently, through the SBO transient analyses two cases with and without the coolant leakage via the PHTS pumps were simulated and the behaviors of the major parameters were compared. The sensitivity analysis on the amount of the coolant leakage by varying its flow area was also performed to investigate the effect on the system responses. It is expected that the results of the present study will contribute to upgrading the evaluation technology of the detailed thermal hydraulic analysis on the SBO transient of the operating PHWRs.

Application of LATE-PCR to Detect Candida and Aspergillus Fungal Pathogens by a DNA Hybridization Assay

  • Gopal, Dhayaalini Bala;Lim, Chua Ang;Khaithir, Tzar Mohd Nizam;Santhanam, Jacinta
    • 한국미생물·생명공학회지
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    • 제45권4호
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    • pp.358-364
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    • 2017
  • Asymmetric PCR preferentially amplifies one DNA strand for use in DNA hybridization studies. Linear-After-The-Exponential-PCR (LATE-PCR) is an advanced asymmetric PCR method which uses innovatively designed primers at different concentrations. This study aimed to optimise LATE-PCR parameters to produce single-stranded DNA of Candida spp. and Aspergillus spp. for detection via probe hybridisation. The internal transcribed spacer (ITS) region was used to design limiting primer and excess primer for LATE-PCR. Primer annealing and melting temperature, difference of melting temperature between limiting and excess primer and concentration of primers were optimized. In order to confirm the presence of single-stranded DNA, the LATE-PCR product was hybridised with digoxigenin labeled complementary oligonucleotide probe specific for each fungal genus and detected using anti-digoxigenin antibody by dot blotting. Important parameters that determine the production of single-stranded DNA in a LATE-PCR reaction are difference of melting temperature between the limiting and excess primer of at least $5^{\circ}C$ and primer concentration ratio of excess primer to limiting primer at 20:1. LATE-PCR products of Candida albicans, Candida parapsilosis, Candida tropicalis and Aspergillus terreus at up to 1:100 dilution and after 1 h hybridization time, successfully hybridised to respective oligonucleotide probes with no cross reactivity observed between each fungal genus probe and non-target products. For Aspergillus fumigatus, LATE-PCR products were detected at 1:10 dilution and after overnight hybridisation. These results indicate high detection sensitivity for single-stranded DNA produced by LATE-PCR. In conclusion, this advancement of PCR may be utilised to detect fungal pathogens which can aid the diagnosis of invasive fungal disease.

Epigenetic modification of α-N-acetylgalactosaminidase enhances cisplatin resistance in ovarian cancer

  • Ha, Ye-Na;Sung, Hye Youn;Yang, San-Duk;Chae, Yun Ju;Ju, Woong;Ahn, Jung-Hyuck
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권1호
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    • pp.43-51
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    • 2018
  • Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified ${\alpha}$-N-acetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly down-regulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

나노 SnO2:CNT를 이용한 가스센서의 제작 및 특성연구 (Characteristics and Preparation of Gas Sensors Using Nano SnO2:CNT)

  • 유일
    • 한국재료학회지
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    • 제26권9호
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    • pp.468-471
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    • 2016
  • $SnO_2:CNT$ thick films for gas sensors were fabricated by screen printing method on alumina substrates and were annealed at $300^{\circ}C$ in air. The nano $SnO_2$ powders were prepared by solution reduction method using tin chloride ($SnCl_2.2H_2O$), hydrazine ($N_2H_4$) and NaOH. Nano $SnO_2:CNT$ sensing materials were prepared by ball-milling for 24h. The weight range of CNT addition on the $SnO_2$ surface was from 0 to 10 %. The structural and morphological properties of these sensing material were investigated using X-ray diffraction and scanning electron microscopy and transmission electron microscope. The structural properties of the $SnO_2:CNT$ sensing materials showed a tetragonal phase with (110), (101), and (211) dominant orientations. No XRD peaks corresponding to CNT were observed in the $SnO_2:CNT$ powders. The particle size of the $SnO_2:CNT$ sensing materials was about 5~10 nm. The sensing characteristics of the $SnO_2:CNT$ thick films for 5 ppm $H_2S$ gas were investigated by comparing the electrical resistance in air with that in the target gases of each sensor in a test box. The results showed that the maximum sensitivity of the $SnO_2:CNT$ gas sensors at room temperature was observed when the CNT concentration was 8wt%.

무인항공기의 근거리 비행체 탐지 및 추적을 위한 영상처리 알고리듬 (An Image Processing Algorithm for Detection and Tracking of Aerial Vehicles in Short-Range)

  • 조성욱;허성식;심현철;최형식
    • 한국항공우주학회지
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    • 제39권12호
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    • pp.1115-1123
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    • 2011
  • 본 논문에서는 무인항공기의 근거리 비행체 탐지 및 추적을 위한 영상처리 알고리듬을 제안한다. 제안된 알고리듬은 연속되는 영상에서 계산되는 호모그래피를 사용하여 움직이는 객체를 검출하고 확률적 다수-가설 추적기법으로 검출된 객체가 접근하는 비행체인지의 여부를 판단한다. 이는 항공기의 저고도 비행 시 영상에 보여지는 지표면과 같이 복잡한 배경 위에서 이동하는 비행체를 검출할 수 있고, 비행체의 동역학적 특성을 고려할 수 있기 때문에 색상기반의 비행체 탐지기법보다 향상된 성능을 보여준다. 또한 외부영향에 대한 임계치의 민감도를 현저히 감소시키므로 소형 무인항공기의 저고도 비행실험수행 시 효과적이다. 제안된 영상처리 알고리듬을 실제 비행실험 영상에 적용하여 성능을 검증하였다.

Pyrimidine 유도체에 의한 완두 Acetolactate Synthase의 저해에 관한 연구 (Inhibition of Acetolactate Synthase from Pea by Pyrimidine Derivatives)

  • 주영아;김대황;장수익;최정도
    • 대한화학회지
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    • 제41권6호
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    • pp.304-312
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    • 1997
  • Acetolactate Synthase(ALS)는 가지를 가진 아미노산 valine, leucine, isoleucine의 생합성 과정에서 공통적으로 작용하는 효소이다. ALS는 서로 구조적 유사성이 없는 최근에 개발된 sulfonylurea, imidazolinone, 그리고 trizolopyrimidine계 제초제들의 공통적인 작용표적이다. 완두로부터 분리한 ALS를 이용하여 새로 합성한 4,6-dimethoxypyrimidine 유도체들의 저해활성을 측정하였다. 가장 우수한 저해활성을 나타내는 유도체는 K11570으로 $IC_{50}$값이 0.2 ${\mu}M$이다. 완두의 ALS에 대한 K11570의 저해활성은 incubation 시간이 증가함에 따라 증가하였으며, 기질 pyruvate에 대해 혼합형 저해유형을 보여주었다. K11570와 sulfonylurea Ally, 그리고 feedback 저해제 leucine에 대한 dual inhibition 실험결과 이들 저해제의 결합부위가 최소한 부분적으로 겹치는 것으로 생각된다. Arg을 변형시킨 효소는 K11570, sulfonylurea Ally, 그리고 leucine의 저해 민감도의 변화가 관찰되었으나, Trp의 변형은 저해 민감도에 영향이 없었다.

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산화주석을 기반으로 한 DMMP 가스센서 제작 (Fabrication of DMMP gas sensor based on $SnO_2$)

  • 최낙진;반태현;백원우;이우석;김재창;허증수;이덕동
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 2003년도 하계학술대회 논문집 Vol.4 No.2
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    • pp.942-945
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    • 2003
  • Nerve gas sensor based on tin oxide was fabricated and its characteristics were examined. Target gas was dimethylmethylphosphonate($C_3H_9O_3P$, DMMP) that is simulant gas of nerve gas. Sensing material was $SnO_2$ added ${\alpha}-Al_2O_3$ with $4{\sim}20wt.%$ and was physically mixed. And then it was deposited by screen printing method on alumina substrate. Sensor device was consisted of sensing electrode with interdigit(IDT) type in front and heater in back side. Total size of device was $7{\times}10{\times}0.6mm^3$. Crystallite size of fabricated $SnO_2$ were characterized by X-ray diffraction(XRD, Rigaku) and morphology of the $SnO_2$ powders was observed by a scanning electron microscope(SEM, Hitachi). Fabricated sensor was measured as flow type and sensor resistance change was monitored real time using LabVIEW program. The best conditions as added $Al_2O_3$ amounts and operating temperature changes were 4wt.% and $300^{\circ}C$ in DMMP 0.5ppm, respectively. The sensitivity was over 75%. Response and recovery times were about 1 and 3 min., respectively. Repetition measurement was very good with ${\pm}3%$ in full scale.

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은하면 제2상한 $^{13}CO(1-0)$ 탐사관측연구 I (A $^{13}CO(1-0)$ Survey of the Second Quadrant of Galactic Plane I)

  • 이영웅;김영식;강현우;정재훈;이창훈;임인성;김봉규;김현구;김광태
    • 천문학회보
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    • 제37권1호
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    • pp.75.1-75.1
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    • 2012
  • We have observed the part of the second quadrant of the Galactic Plane in $^{13}CO(1-0)$ using the multibeam receiver system installed on the 14 m telescope at Taeduk Radio Astronomy Observatory. The target region (L=108 to 112.5) is the part of the $^{12}CO$ Outer Galactic Plane Survey (Heyer et al. 1998), and it is for the exact Galactic plane with the latitude range of +1 and -1 degree. Total of 48,000 spectra (about 9 square degees) were obtained on 50" grid. The selected velocity resolution is 0.63 km/sec and sensitivity per channel is 0.17 K, and the covered velocity is 320 km/sec. We developed a new reduction method, which effectively deals with a relatively noisy 3-dimensional database. The collected $^{13}CO$ database will be manipulated with pre-existing $^{12}CO$ data to get several physical parameters. As it is located in the second quadrant, the kinematic distances of the individual clouds, which will be identified, can be estimated relatively easily without any distance ambiguity. In this meeting we present the reduction method, statistics, and some channel maps, integrated intensity maps, and spatial-velocity maps. We intend to clarify any difference of their characteristics between the clouds in the Outer Galaxy and Inner Galaxy using our data base.

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