• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.1809-1817
• /
• 2012

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권5호
• /
• pp.2207-2212
• /
• 2012

Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of $RAR{\beta}$. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ${\beta}$($RAR{\beta}$). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of $RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of $RAR{\beta}$ in esophageal SCC patients. NNK could induce $RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권5호
• /
• pp.385-393
• /
• 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

• 물과 미래
• /
• 제45권8호
• /
• pp.50-55
• /
• 2012

본 연구는 레이더 반사도를 이용한 RAD-RAR시스템의 개발내용에 대한 설명과 이를 검증하기 위해 2006년 레이더 반사도를 이용한 RAD-RAR시스템의 강우량 추정값과 지상 AWS 강우량관측값을 비교 하였다. 2006년 전체를 보았을 때 RAD-RAR의 일 누적관측값은 지상강우량과 비교하여 약 0.84로 높은 상관계수를 보였다. 또한 본 연구에서 북한 지역 등의 지상 관측 공백지역에 대한 강수량 모니터링의 필요성의 증가 때문에, 2009년 황강댐 부근에서 발생한 강수사례를 분석하여보았다. 북한 지역에 대해서는 GTS 지점에서 황강댐 방류 기간에 대해서 비교 및 검증을 수행하였다. 북한 지역에 대한 사례분석 결과는 상관도가 0.75로 남한 지역(상관도: 0.85)에 비해서 상대적으로 낮게 나타났다. 이는 북한 지역에 대한 검증시 사용된 샘플링의 수가 적었기 때문에 일반화하기 어렵고 또한 북한 지역의 GTS 지점에서 관측된 강수량 자료의 높은 신뢰도를 얻기 어려우므로 더 추가적인 분석이 필요하다.

• 대기
• /
• 제24권3호
• /
• pp.365-378
• /
• 2014

The limits of S-band dual-polarization radars in Korea are not reflected on the recent weather forecasts of Korea Meteorological Administration and furthermore, they are only utilized for rainfall estimations and hydrometeor classification researches. Therefore, this study applied four merging methods [SA (Simple Average), WA (Weighted Average), SSE (Sum of Squared Error), TV (Time-varying mergence)] to the QPE (Quantitative Precipitation Estimation) model [called RAR (Radar-AWS Rainfall) calculation system] using single-polarization radars and S-band dual-polarization radar in order to improve the accuracy of the rainfall estimation of the RAR calculation system. As a result, the merging results of the WA and SSE methods, which are assigned different weights due to the accuracy of the individual model, performed better than the popular merging method, the SA (Simple Average) method. In particular, the results of TVWA (Time-Varying WA) and TVSSE (Time-Varying SSE), which were weighted differently due to the time-varying model error and standard deviation, were superior to the WA and SSE. Among of all the merging methods, the accuracy of the TVWA merging results showed the best performance. Therefore, merging the rainfalls from the RAR calculation system and S-band dual-polarization radar using the merging method proposed by this study enables to improve the accuracy of the quantitative rainfall estimation of the RAR calculation system. Moreover, this study is worthy of the fundamental research on the active utilization of dual-polarization radar for weather forecasts.

• 대한본초학회지
• /
• 제31권3호
• /
• pp.13-22
• /
• 2016

Objectives： Arachidonic acid is control the thromboxane A2 (TXA2) and prostacycline (PGI2) synthesis, TXA2 increase lead to thrombus produced by induces platelet aggregation and vasoconstriction. Angelicae gigantis radix (RAR) is mainly used blood deficiency and stagnation. In previous studies, RAR has been reported that a vasodilating and blood clotting delay effects. In this study, investigate that anti-oxidant and anti-thrombotic effects of RAR by heat-process.Methods： The heated angelicae gigantis radix sample were made by 140, 180, and 220 ℃ and 4, 6, 9 and 12 min using water or 30% ethanol. The anti-oxidant effects were measured by total polyphenol, total flavonoid, DPPH and ABTS radical scavening activation. Anti-thrombotic effect conducted in samples that are determined to be effective through the anti-oxidant experiment such as angelicae gigantis radix roasted 180℃, and 220℃ and angelicae gigantis radix roasted with 30% ethanol 180℃, and 220℃.Results： Anti-oxidant parameters were efficacious in high temperature roasted AR. Also AR and EAR increased a inhibitory activity of FXa compared with RAR. The blood coagulation time of administration groups were significantly increased compare with control group. The TXB2 was significantly decreased in AR and EAR.Conclusions : We confirmed that whether AR and EAR administration has anti-oxidant and anti-thrombotic effect or not. As the results, AR and EAR were improved anti-oxidant effects and blood biochemistry compare with control group. This study provides scientific evidence that AR and EAR are have an anti-oxidant effect and anti-thrombotic effect, it expected that there is no difference between the two.

• Tuberculosis and Respiratory Diseases
• /
• 제73권1호
• /
• pp.11-21
• /
• 2012

Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of $p16^{INK4A}$ immunoexpression. Results: Hypermethylation of CDKN2A, $RAR{\beta}$, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with $p16^{INK4A}$ immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of $p16^{INK4A}$ immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed $p16^{INK4A}$ immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and $p16^{INK4A}$ immunoexpression loss.

• 대한의생명과학회지
• /
• 제26권4호
• /
• pp.256-266
• /
• 2020

Carboxypeptidase D (CPD) is a zinc-dependent protease, which is highly expressed in macrophages, and is thought to participate in inflammatory processes. In the present study, we investigated the possible regulatory effect of all-trans retinoic acid (ATRA), which is an active form of vitamin A and plays a critical regulatory role in both the innate and adaptive immunity, on CPD expression and secretion in human monocytic THP-1 cells. CPD mRNA expression first increased, from a concentration as low as 10 nM ATRA to a maximum level of expression, at 1 μM. ATRA enhanced intracellular CPD expression in a time- and concentration-dependent manner but did not affect cell surface CPD expression. Interestingly, 9-cis-RA did not affect CPD expression. Additionally, an experiment with RAR/RXR selective agonist or antagonists demonstrated that ATRA-induced enhancement of CPD expression was RAR/RXR dependent. ATRA also enhanced CPD secretion from THP-1 cells; however, this enhancement was RAR/RXR-independent. The anti-inflammatory agent dexamethasone reversed ATRA-induced enhancement of CPD expression and secretion. Our results suggest ATRA exerts regulatory effects on expression and secretion of CPD in human monocytes, and ATRA-induced CPD secretion may be associated with inflammatory response.

• 한국수자원학회논문집
• /
• 제53권3호
• /
• pp.155-166
• /
• 2020

본 연구에서는 국내 산지지형을 대표하며, 타 댐 유역에 비해 비교적 수문(수위/유량)관측소와 자료가 많은 용담시험유역에 기상레이더 강수량 추정 값(RAR)을 적용해 산지지형 댐 유역에서 강우의 시공간적 변동성과 이에 따른 홍수량의 정확한 분석을 통해 홍수 시 댐 유입량의 정확한 산정 등에 활용할 목적으로 홍수 유출모의를 수행하였다. 모의에는 최근 5년(2014~2018년) 동안 발생한 비교적 독립적인 총 8개의 홍수사상을 적용하였으며, 모형은 HEC-GeoHMS와 ModClark 방법을 통해 분포형 강우를 적용할 수 있는 비교적 간단한 모형인 HEC-HMS를 활용하였다. 아울러 이 과정에서 레이더 강수량의 모형적용을 위해 NCL 및 Python 기반의 자료처리 스크립트 프로그램을 개발하여 활용하였다. 연구 결과로서 기상레이더 강수량 추정 값(RAR)이 관측에 비해 다소 과소 추정(R² 0.86)된 것을 알 수 있었고, 기존 지점관측 기반 유역평균 강수량을 사용한 방법과의 비교에서는 레이더 강수량을 적용한 모형이 유역의 강우-유출 도달시간 등과 관련된 매개변수 값의 큰 조정 없이도 홍수유출을 효율적으로 (8개모의 평균 E_NS 0.863, R² 0.873, 그리고 PBIAS 7.49%) 잘 모의하는 것을 파악할 수 있었다.

• 한국정보통신학회논문지
• /
• 제13권9호
• /
• pp.1935-1940
• /
• 2009

WSN(Wireless Sensor Network)의 기술 요소 중의 하나는 센서 노드의 위치 관리이다. GPS, 초음파 센서, RSSI 등이 전형적인 노드의 위치 관리 방법이다. 본 논문에서는 센서 노드 위치 측정의 정확성을 향상시키기 위해 RSSI 측정에 회귀분석을 적용한 새로운 위치 관리 방식을 제안한다. 또한 기존 방식의 실험적인 결과와의 비교를 통해 제안된 방식의 성능을 평가한다. 결과에 따르면 우리 의 제안된 방식인 LM-RAR은 RSSI와 Friis 공식을 사용한 기존의 위치 관리 방식보다 향상된 정확성을 보인다.