• Title/Summary/Keyword: 표적치료

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Endogenous Nitric Oxide Strengthens Doxorubicin-induced Apoptosis in Human Colorectal Cell Lines (Doxorubicin에 의한 내인성 산화질소가 인간 대장암 세포주에서의 세포사멸에 미치는 효과)

  • Im, Soon Jae;Kim, Ji Hye;Kim, Min Young
    • Journal of Life Science
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    • v.24 no.10
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    • pp.1137-1143
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    • 2014
  • Doxorubicin is a general chemotherapy drug widely used for a number of cancers. However, the correlation between endogenous nitric oxide ($NO^{\bullet}$) levels and chemoresistance to doxorubicin remains unclear. In this study, we investigated the effect of endogenous $NO^{\bullet}$ on the anticancer activity of doxorubicin in human colon cancer cell lines HCT116 and HT29 with different p53 status. The cells were treated with either doxorubicin alone or in combination with the $NO^{\bullet}$ synthase (NOS) inhibitor $N^G$-monomethyl-L-arginine (NMA). Doxorubicin differentially inhibited the growth of both the HCT116 (p53-WT) and HT29 (p53-MUT) cells, which was mitigated by cotreatment with NMA. Further studies revealed that inhibition of endogenous $NO^{\bullet}$ mitigated doxorubicin-induced apoptosis in the HCT116 and HT29 cells, as evidenced by apoptotic DNA fragmentation and the sub-G1 peak of apoptotic markers. Apoptosis was delayed in the HT29 cells, and its magnitude was greatly reduced, underscoring the importance of the modulation of p53 in the response. RT-PCR analysis revealed that doxorubicin down-regulated levels of inhibitors of the apoptosis family (cellular IAP-1 and-2). Collectively, these data show that induction of apoptosis by doxorubicin in human colon cancer cells is possibly related to modulation of endogenous $NO^{\bullet}$, the expression of the IAP family of genes, and the status of p53. The underlying mechanisms may represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy for colon cancer.

Discrimination of Flaviviruses with High Frequency of Infection in Asian Countries: Epitope Prediction by Bioinformatic Approaches (아시아 국가 내에서 감염빈도가 높은 플라비바이러스의 구별: 생물정보학적 접근을 통한 항원결정기 예측)

  • Choi, Jae-Won;Jo, Byung-Gwan;Kim, Min Jung;Park, Suji;Kim, Hak Yong
    • The Journal of the Korea Contents Association
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    • v.18 no.4
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    • pp.99-113
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    • 2018
  • Recently, global warming has widened the habitat of mosquitoes and infection chances for mosquito-borne diseases are increasing. Flavivirus is a typical mosquito-borne virus. Flaviviruses with a relatively high frequency of infection in Asian countries include Zika, Dengue, and Japanese encephalitis viruses. Although distinctive diagnosis of flaviviruses is required because the symptoms and therapeutic method differ, there is no diagnostic method that can distinguish them accurately yet. In this study, we propose distinctive diagnosis method of flaviviruses using informations and analysis tools constructed in bioinformatic databases. The envelope protein and non-structural protein 1 which are useful protein for the immuno-diagnostics of three flaviviruses were selected. Their homology was analyzed by multiple sequence alignments and epitope candidates consisting of 10-15 amino acids were selected. Finally two epitopes were suggested to be most useful by immunogenicity analysis and 3D structure prediction. These approaches and results are expected to be great value in the distinctive diagnosis of three flaviviruses with a high frequency of infection in Asian countries.

Antitumor and Immunomodulatory Effects of Chungsangbohahwan on Murine Melanoma-induced Lung Metastasis (청상보하환(淸上補下丸)이 흑색종(黑色腫)의 폐전이(肺轉移) 억제(抑制) 및 면역조절작용(免疫調節作用)에 미치는 영향(影響))

  • Ha, Jee-Yong;You, Byeong-Gil
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.159-175
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    • 1998
  • In order to investigate the antitumor effect by Chungsangbohahwan after B-16 cells were transplanted in C57BL/6 mice, and the immune responses in mice induced by methotrexate, the extract of Chungsangbohahwan was orally administered to the mice for 21 days. Experimental studies were performed for measurance of metastasis, cell cytotoxicity in vitro, natural killer cell activity, productivity of interleukin-2. The results were summarized as follows: 1. Inhibition of metastasis in Chungsangbohahwan-treated group was higher than control group with significance on 7th day and 14th day. 2. On the MTT assay, cell viability was significantly inhibited by $5{\mu}g/well$, $2.5{\mu}g/well$, $1.25{\mu}g/well$, and $0.625{\mu}g/well$ of Chungsangbohahwan concentration inhibited cell viability significantly(P<0.05). $IC_{50}$ for cell viability was $2.17{\mu}g/well$. 3. Natural killer cell activity in Chungsangbohahwan-treated group was significantly increased on 100:1, 50:1 E/T(effect cell/target cell) ratio(P<0.05). 4. Production of interleukin-2 in Chungsangbohahwan-treated group was significantly increased(P<0.05).

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Study on Physiological Summation in Peripheral Retina for Eccentric Viewing Training (중심외주시 훈련용 주변부 망막의 생리적 가중에 관한 연구)

  • Seo, Jae-Myoung;Lee, Ki-Young
    • Journal of Korean Ophthalmic Optics Society
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    • v.18 no.4
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    • pp.489-493
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    • 2013
  • Purpose: This study was to investigate peripheral vision and provide people with macular degeneration with a guideline for eccentric viewing training. Methods: 30 adult subjects with normal vision took part in this study. The lateral area of $20^{\circ}$ eccentricity from the fovea of right eye was only used to measure the physiological summation. The target was sinusoidal vertical gratings within a circular aperture. The critical points in spatial and temporal summation was found to compare each other for 0.7 cpd and 3.0 cpd, respectively. Results: Critical duration and contrast sensitivity for 0.7 cpd were 540 ms and 1.1, and 315 ms and 0.98 for 3.0 cpd respectively. The critical degrees and contrast sensitivity for 0.7 cpd were $11.3^{\circ}$ and 2.8, and $5^{\circ}$ and 2.63 for 3.0 cpd respectively. Conclusions: The critical point in peripheral vision reaches relatively faster than the one in central vision. It is recommended to train the peripheral retina under the lower spatial frequency more frequently for a short time than constantly for a long time.

Functional expression of TREK1 channel in human bone marrow and human umbilical cord vein-derived mesenchymal stem cells (사람의 골수와 제대정맥에서 유래된 중간엽 줄기세포에서 TREK1 통로의 기능적 발현)

  • Park, Kyoung Sun;Kim, Yangmi
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.3
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    • pp.1964-1971
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    • 2015
  • Human bone marrow or human umbilical cord vein derived-mesenchymal stem cells (hBM-MSCs or hUC-MSCs) have known as a potentially useful cell type for clinical therapeutic applications. We investigated two-pore domain potassium (K2P) channels in these cells. K2P channels play a major role in setting the resting membrane potential in many cell types. Among them, TREK1 is targets of hydrogen, hypoxia, polyunsaturated fatty acids, antidepressant, and neurotransmitters. We investigated whether hBM-MSCs and hUC-MSCs express functional TREK1 channel using RT-PCR analysis and patch clamp technique. Potassium channel with a single channel conductance of 100 pS was found in hUC-MSCs and BM-MSCs and the channel was activated by membrane stretch (-5 mmHg ~ -15 mmHg), arachidonic acid ($10{\mu}M$) and intracellular acidosis (pH 6.0). These electrophysiological properties were similar to those of TREK1. Our results suggest that TREK1 is functionally present in hBM-MSCs and hUC-MSCs, where they contribute to its resting membrane potential.

A Localization Method Using RF Transmission Levels in Wireless Sensor Networks (무선 센서 네트워크에서 RF 전송 레벨을 이용한 위치 측정 기법)

  • Yun, Chae-Sang;Hahn, Joo-Sun;Ha, Rhan
    • Proceedings of the Korean Information Science Society Conference
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    • 2007.10d
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    • pp.366-371
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    • 2007
  • 무선 센서 네트워크는 경제적, 환경적 목적으로 다양한 방면에서 활용되고 있다 이 때, 배치된 각 센서의 위치를 파악하는 것은 센서 네트워크에서 가장 기본적이며 가장 중요한 문제 중의 하나이다. 기존 논문에서 제안된 센서 위치 측정 방법은 특별한 장비를 장착하거나 특정한 환경의 지역에 한정시킨 방범으로 제한하고 있는 경우가 대부분이다. 하지만 어떠한 관심 지역의 환경은 언제라도 바뀔 수 있다. 또한, 센서가 위치할 환경의 기온, 풍속 등을 미리 안다는 것은 비현실적인 가정이다. 더구나 각각의 센서에 특별한 장비를 장착한다는 것은 비용 절감을 이유로 센서 네트워크를 운영하는 경우 오히려 그것을 이용하지 않는 경우보다 비용이 더 들 수도 있다. 이에 본 논문에서는 센서 노드의 기본적인 통신 기능은 이용하여, 환경에 순응적으로 센서의 위치를 측정할 수 있는 방법을 제안하고자 한다. 센서 노드에서 기본적으로 제공하는 통신 기능은 RF 전파를 보낼 때 전송 레벨을 달리하여 보낼 수 있다. 이러한 기본적인 기능을 이용하여 위치를 측정하게 되면 전체적인 센서 네트워크의 비용이 절감될 뿐만 아니라 환경에 순응적인 위치 측정이 가능하게 된다. 또한, 각 노드의 위치가 정해진 후 다른 노드와 통신할 때 전파의 세기를 조정함으로써 RF 통신에서 소모되는 전력량을 줄일 수 있다. 따라서 본 논문에서 제안하는 전송 레벨을 이용한 위치 측정 방법은 단순히 위치를 측정한다는 의미뿐 아니라 환경에 순응적으로 작동한다는 장점이 있다. 향후 네트워크 내에서 통신에 소비되는 전력을 줄일 수 있다는 점에서도 중요한 의미를 지닌다.를 집행하는 caspase의 활성 형태인 cleaved caspase-8, -9, -7, -3의 단백질 수준이 목향 헥산추출물의 처리에 의해 증가하였고 caspase-3의 표적 단백질 중 하나인 PARP의 불활성 형태인 cleaved PARP의 단백질 수준도 현저하게 증가하였다. 이 결과들은 목향 헥산 추출물이 LNCaP 세포의 apoptosis를 유도함으로써 전립선 암세포의 증식을 억제함을 보여주는 것이며 목향 헥산추출물에 의한 apoptosis 유도는 caspase 활성 증가와 Bak 및 t-Bid 단백질의 증가에 의한 것임을 제시한다. 따라서 앞으로 항암효과를 나타내는 성분의 동정 및 동물실험을 통하여 좀 더 면밀한 기전 연구가 수행된다면 목향 헥산추출물은 화학적 암예방 물질이나 치료제로 개발될 수 있을 것으로 사료된다.적 분해층과 마모질이가 가장 깊은 것으로 나타났으며 flowable type의 복합레진과 컴포머는 표면 경도와 마모도에서 양호한 결과를 보였다. 이상의 결과 복합레진과 컴포머의 평가요소로서 마모도와 함께 가수분해도 고려되어야 할 것으로 사료된다.증후군 환자에서 대조군에 비해 높은 비율을 보였다.er thinning은 3 군모두에서 관찰되었고 항암 3 일군이 가장 심하게 나타났다. 이상의 실험결과를 보면 술전 항암제투여가 초기에 시행한 경우에는 조직의 치유에 초기 5 일정도까지는 영향을 미치나 7 일이 지나면 정상범주로 회복함을 알수 있었고 실험결과 항암제 투여후 3 일째 피판 형성한 군에서 피판치유가 늦어진 것으로 관찰되어 인체에서 항암 투여후 수술시기는 인체면역계가 회복하는 시기를 3

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Induction of Apoptosis by Sageretia thea Branch Extracts through Activation of NF-κB Signaling Pathway in Human Colorectal Cancer Cells (상동나무(Sageretia thea) 가지추출물의 대장암세포에서 NF-κB 신호전달 활성화를 통한 세포사멸 유도활성)

  • Kim, Jeong Dong;Park, Su Bin;Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.5
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    • pp.428-435
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    • 2020
  • In this study, we evaluated the inhibitory effect against cell growth and potential molecular mechanism of 100% ethanol extracts of branch from Sageretia thea in human colorectal cancer cells, HCT116. Ethanol dose-dependently extracts of STB significantly suppressed the growth of HCT116 cells through apoptosis. STB activated NF-κB signaling pathway through IκB-α proteasomal degradation and inducing p65 accumulation in nucleus. The inhibition of GSK3β by LiCl didn't affect STB mediated degradation IκB-α but STB mediated p65 accumulation in nucleus. In addition, STB phosphorylated GSK3β. Based on these findings, STB may be a potential candidate for the development of anti-cancer agents for human colorectal cancer.

The Effect of 12-O-Tetradecanoylphorbol-13-acetate-induced COX-2 Expression by 3,3'-Diindolylmethane (DIM) on Human Mammary Epithelial Cells (3,3'-Diindolylmethane(DIM)이 Human Mammary Epithelial Cell에서 12-O-tetradecanoylphorbol-13-acetate에 의해 유도된 COX-2 발현에 미치는 영향)

  • Park, So Young;Shim, Jae-Hoon;Kim, Jong-Dae;YoonPark, Jung Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.12
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    • pp.1701-1707
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    • 2012
  • 3,3'-Diindolylmethane (DIM) is a major in vivo derivative of the putative anticancer agent indole-3-carbinol, which is present in cruciferous vegetables and has been reported to have anti-carcinogenic properties. An abnorrmally elevated level of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of carcinogenesis. To investigate the mechanism by which DIM exhibits anti-carcinogenic effects, we investigated the effects of DIM on COX-2 expression in MCF-10A human mammary epithelial cells treated with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). DIM inhibited TPA-induced COX-2 expression and suppressed the synthesis of prostaglandin $E_2$, one of the major products of COX-2. Nuclear factor-kappa B ($NF-{\kappa}B$) is a transcription factor known to play a role in regulation of COX-2 expression. Treatment of MCF-10A cells with TPA increased nuclear translocation of phospho-p65, with the maximal levels being reached at 1 hour, while DIM inhibited the TPA-induced nuclear translocation of phospho-p65. Overall, we demonstrated that DIM suppresses phorbol ester-induced $PGE_2$ production and COX-2 expression in MCF-10A cells. The reduction in COX-2 levels by DIM maybe mediated through inhibition of $NF-{\kappa}B$ signaling.

Effects of Sasa quelpaertensis Extract on mRNA and microRNA Profiles of SNU-16 Human Gastric Cancer Cells (SNU-16 위암 세포의 mRNA 및 miRNA 프로파일에 미치는 제주조릿대 추출물의 영향)

  • Jang, Mi Gyeong;Ko, Hee Chul;Kim, Se-Jae
    • Journal of Life Science
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    • v.30 no.6
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    • pp.501-512
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    • 2020
  • Sasa quelpaertensis Nakai leaf has been used as a folk medicine for the treatment of gastric ulcer, dipsosis, and hematemesis based on its anti-inflammatory, antipyretic, and diuretic characteristics. We have previously reported the procedure for deriving a phytochemical-rich extract (PRE) from S. quelpaertensis and how PRE and its ethyl acetate fraction (EPRE) exhibits an anticancer effect by inducing apoptosis in various gastric cancer cells. To explore the molecular targets involved in this apoptosis, we investigated the mRNA and microRNA profiles of EPRE-treated SNU-16 human gastric cancer cells. In total, 2,875 differentially expressed genes were identified by RNA sequencing, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the EPRE-modulated genes are associated with apoptosis, mitogen-activated protein kinase, inflammatory response, tumor necrosis factor signaling, and cancer pathways. Subsequently, protein-protein interaction network analysis confirmed interactions among genes associated with cell death and apoptosis, and 27 differentially expressed microRNAs were identified by further sequencing. Here, GO and KEGG pathway analysis revealed that EPRE modified the expression of microRNAs associated with the cell cycle and cell death, as well as signaling of tropomyosin-receptor-kinase receptor, transforming growth factor-b, nuclear factor kB, and cancer pathways. Taken together, these results provide insight into the mechanisms underlying the anticancer effect of EPRE.

The Role of Bmi1 in Pilocarpine-induced Status Epilepticus in Mice (Pilocarpine에 의해 유도된 생쥐 경련중첩증에서 Bmi1의 역할)

  • Pyeon, Hae-In;Bak, Jia;Choi, Yun-Sik
    • Journal of Life Science
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    • v.30 no.6
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    • pp.513-521
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    • 2020
  • B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a polycomb group protein and a core component of polycomb repressive complex 1. Initial research into Bmi1 has focused on its role in tumorigenesis, and it is generally accepted that it is important for the proliferation and survival of cancer cells. However, more recent studies have revealed that Bmi1 is downregulated in brains with neurodegenerative disease and that it regulates the function of mitochondria and reactive oxygen species levels. In this study, we tested the therapeutic potential of Bmi1 in pilocarpine-induced seizures in Bmi1-knockout mice. Bmi1 expression transiently increased in the hippocampal CA1 and CA3 and the dentate gyrus following pilocarpine-induced status epilepticus (SE). In terms of seizure behavior, SE induction was 43.14% and 53.57% for Bmi1+/+ and Bmi1+/- mice, respectively. However, there was no significant difference in mortality or hippocampal damage between the two groups. Two months after SE induction, the frequency of epileptic seizures in the Bmi1+/- mice was 50% lower than in the control group, although the difference was not statistically significant. In addition, mossy fiber outgrowth in the Bmi1+/- mice was significantly higher than in their wild-type littermates. Taken together, these data indicate that reduced Bmi1 activity increases pilocarpine-induced seizure probability and mossy fiber outgrowth.