• 한국발생생물학회지:발생과생식
• /
• 제22권2호
• /
• pp.133-142
• /
• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• 한국수자원학회:학술대회논문집
• /
• 한국수자원학회 2018년도 학술발표회
• /
• pp.291-291
• /
• 2018

하천 및 수자원의 효율적인 관리와 더불어 다양한 수공구조물의 운영 및 관리를 위해서 구조물 주변에서 발생하는 불연속 흐름 및 급변류 등의 현상과 구조물 운영을 반영한 수치해석 기법을 이용한 모델 개발의 중요성이 커지고 있다. 본 연구에서는 하천의 불연속 흐름을 모의하기 위한 1차원 흐름해석 모형(K-River)을 개발하였다. 본 모형은 천이류와 급변류를 수치적으로 안정하게 처리하기 위하여 지배방정식을 보존형 Saint-Venant 방정식으로 선정하고, FVM과 Forward Euler 방법을 이용하여 이산화를 수행하였다. 수치흐름률을 계산하기 위해서 불규칙 단면과 하상의 급경사 등에 신뢰도가 높은 기법으로 판단되는 근사 Riemann해법 중 하나인 HLL flux를 이용하였다. 개발된 K-river 모형의 검증을 위해서 해석해가 존재하는 타원형의 하상융기가 있는 하도에 적용하였으며, 국내에서 하천 설계 및 관리를 위해서 광범위하게 이용되고 있는 1차원 흐름해석 모형인 FDM기반의 HEC-RAS 모의결과와 비교 검토를 수행하였다. 그 결과, FDM기법에서는 모의되지 않는 일부 급변류 패턴을 개발 모형을 통해 모의가능하였으며, 전체적으로 K-River가 기존 모형 보다 해석해에 근사한 결과를 나타내었다. 또한, 배수문을 비롯하여 합류부, 분류부, 펌프장, 암거 등이 설치되어 운영되고 있는 아라뱃길에 적용하여 K-River의 적용성을 평가하였다. K-River를 이용하여 아라뱃길의 흐름분석을 수행한 경우가 HEC-RAS를 이용한 경우보다 수위와 유량의 유동을 시간에 따라 세밀하게 모의하였으며, 이는 배수효과에 의한 파의 전달이 FDM기법 대비 정확히 모의되기 때문으로 판단된다. 추후 연구에서는 현재보다 시간간격을 상세화 하여 수집된 관측수위를 통해 추가적인 검증을 수행하고, 다양한 특성을 가진 타 하천 등에 적용하여 모형의 적용성을 확대하고자 한다.

• BMB Reports
• /
• 제38권3호
• /
• pp.328-333
• /
• 2005

A human homologue of Sar1, named Sara2, was shown to be preferentially expressed during erythropoiesis in a culture stimulated by EPO. Previous studies, in yeast, have shown that secretion-associated and Ras-related protein (Sar1p) plays an essential role in protein transport from the endoplasmic reticulum to the Golgi apparatus. Here, we report the molecular analysis of Sara2 in erythroid cell culture. A 1250 bp long cDNA, encoding a 198 amino-acid protein very similar to Sar1 proteins from other organisms, was obtained. Furthermore, we also report a functional study of Sara2 with Real-time quantitative PCR analysis, demonstrating that expression of Sara2 mRNA increases during the initial stages of erythroid differentiation with EPO and that a two-fold increase in expression occurs following the addition of hydroxyurea (HU). In K562 cells, Sara2 mRNA was observed to have a constant expression and the addition of HU also up-regulated the expression in these cells. Our results suggest that Sara2 is an important gene in processes involving proliferation and differentiation and could be valuable for understanding the vesicular transport system during erythropoiesis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권11호
• /
• pp.5599-5603
• /
• 2012

Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권8호
• /
• pp.3543-3549
• /
• 2015

Background: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Materials and Methods: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Results: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. Conclusions: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

• 한국제4기학회지
• /
• 제22권1호
• /
• pp.28-36
• /
• 2008

The present study has focused on the environmental changes and evidences for sedimentation in the Lake Khuvsgul catchment during the Holocene period, inferred from short core sediment (BO03) from the eastern shore of Borsog Bay, which were analyzed in order to review records of the Holocene climatic evolution and Holocene history in Northern Mongolia. For the purpose of reconstruction of natural phenomenon that occurred in the lake catchment system during the Holocene, physical and chemical properties including HCl-soluble material, biogenic silica, organic matter and grain size distribution of minerals in the core sediments have been analyzed in this study. The vertical variations in composition for these properties show distinctly that five lines of paleoenvironmental evidence occurred in the lake catchment during the Holocene. A modified age model resulting from AMS carbon dating for the BO03 core sediment shows timings of these environmental events at 9.5 Kyr BP, 8.0 Kyr BP, 5.6 Kyr BP and 3.2 Kyr BP, respectively. Paleoenvironmental changes in the Lake Khuvsgul catchment system during the Holocene highlight distinctive features of the hydrological regime and geomorphologic evolution in the lake catchment due to regional landscape and global climatic changes corresponding with the Holocene optimum and thermal optimum. In particular, the change of hydrologic regime based on the sedimentological evidence has been caused by not only overland flow due to melting water, but also base flow due to thick permafrost around Khuvsgul region.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3719-3724
• /
• 2013

Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Results: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. Conclusion: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis.

• BMB Reports
• /
• 제43권7호
• /
• pp.485-490
• /
• 2010

Neurotrophins regulate many aspects of neuronal function through activation of the high affinity Trk receptors. Shc family proteins are implicated in the coupling of RTK to the Ras/mitogen-activated protein kinase signaling cascade. Here we report that the fourth Shc family member, ShcD, associates with TrkB receptor and regulates BDNF-induced MAPK activation. Yeast two-hybrid assay and Co-IP experiments demonstrate ShcD interacts with TrkB in a kinase-activity-dependent manner. Confocal analysis shows ShcD cololizes well with TrkB in transfected 293T cells. Subsequent mapping experiments and mutational analysis indicate that both PTB and SH2 domains are capable of binding to TrkB and PTB domain binds to TrkB NPQY motif. Furthermore, ShcD is involved in BDNF-induced MAPK activation. In summary, we demonstrate that ShcD is a substrate of TrkB and mediates TrkB downstream signaling pathway.

• 한국한의학연구원논문집
• /
• 제12권3호통권18호
• /
• pp.131-141
• /
• 2006

Hominis Placenta has a broad array of clinical applications in Korean medicine, including treatment of inflammatory conditions such as rheumatoid arthritis. The purpose of this study is to explore the global gene expression profiles in human RAW 264.7 cell lines treated with Hominis Placenta herbal-acupuncture solution (HPHAS) using microarray analysis. The RAW 264.7 cells were treated with lipopolysaccharide (LPS), HPHAS, or both. Of the 8,170 genes profiled in this study, with a cut-off level of two-fold change in the expression, 72 genes (CTD1, regulating synaptic membrane exocytosis 2, etc.) were upregulated and 135 genes(splicing factor, arginine/serine-rich 1, actinin, alpha 1, etc.) downregulated following LPS treatment. One gene (acrosin) was upregulated and 12 genes (phospholipase A2, group IB, neurofilament, heavy polypeptide 200kDa, etc.) were downregulated following HPHAS treatment. Eleven genes (RAB27A, member RAS oncogene family, eosinophil peroxidase, etc.) were upregulated and 16 genes (V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (avian), RW1 protein, etc.) were downregulated following co-stimulation of HPHAS and LPS. It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacological actions of HPHAS in the treatment of arthritis. Further studies, however, are required to concretely prove the effectiveness of HPHAS.

• 전자공학회논문지S
• /
• 제36S권9호
• /
• pp.103-112
• /
• 1999

본 논문에서는 차량 항법영 음성 인식을 위한 화자 독립 단독음 인식 시스템을 범용 DSP를 사용하여 구현하였으며, 잡음 처리 기술로 SNR 정규화와 RAS를 결합한 방법을 제안하여 인식 시스템의 성능을 개선시켰다. 인식 알고리즘으로서 반연속 HMM을 사용하였으며, TMS320C31을 이용하여 구현하였다. 실험에서 사용된 인식 단어는 차량 항법 시스템을 위한 명령어 69단어이며, 구현된 인식 시스템은 자동차 환경에서 녹음된 음성 데이터에 의한 인식 결과와 하드웨어 구현에 따르는 제약 조건을 동시에 고려하여 구현되었다. 주행 중에 녹음된 데이터에 대한 컴퓨터 시뮬레이션 상에서 특징 벡터 중 MFCC-CMS를 이용하고, 잡음 처리 방법으로 SNR 정규화와 스펙트럼 차감법을 결합하여 실험한 경우 최고 93.62%의 인식 성능을 보였으며, 89.93%의 인식률을 갖는 기존 방법보다 3.69%의 인식 성능 향상을 가져왔다. 제안된 잡음 처리 방법은 자동차 안에서의 SNR이 5dB이하에서 좋은 인식 성능을 보이는 것으로 나타났다.