• 제목/요약/키워드: K-Ras

검색결과 605건 처리시간 0.026초

Gamma Irradiation Up-regulates Expression of B Cell Differentiation Molecule CD23 by NF-κB Activation

  • Rho, Hyun-Sook;Park, Soon-Suk;Lee, Choong-Eun
    • BMB Reports
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    • 제37권4호
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    • pp.507-514
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    • 2004
  • Gamma irradiation ($\gamma$-IR) is reported to have diverse effects on immune cell apoptosis, survival and differentiation. In the present study, the immunomodulatory effect of a low dose $\gamma$-IR (5~10 Gy) was investigated, focusing on the role of NF-${\kappa}B$ in the induction of the B cell differentiation molecule, CD23/FceRII. In the human B cell line Ramos, $\gamma$-IR not only induced CD23 expression, but also augmented the IL-4-induced surface CD23 levels. While $\gamma$-IR did not cause STAT6 activation in these cells, it did induce both DNA binding and the transcriptional activity of NF-${\kappa}B$ in the $I{\kappa}B$ degradation-dependent manner. It was subsequently found that different NF-${\kappa}B$ regulating signals modulated the $\gamma$-IR-or IL-4-induced CD23 expression. Inhibitors of NF-${\kappa}B$ activation, such as PDTC and MG132, suppressed the $\gamma$-IR-mediated CD23 expression. In contrast, Ras, which potentiates $\gamma$-IR-induced NF-${\kappa}B$ activity in these cells, further augmented the $\gamma$-IR- or IL-4-induced CD23 levels, The induction of NF-${\kappa}B$ activation and the subsequent up-regulation of CD23 expression by $\gamma$-IR were also observed in monocytic cells. These results suggest that $\gamma$-IR, at specific dosages, can modulate immune cell differentiation through the activation of NF-${\kappa}B$, and this potentially affects the immune inflammatory response that is mediated by cytokines.

Reovirus and Tumor Oncolysis

  • Kim, Man-Bok;Chung, Young-Hwa;Johnston, Randal N.
    • Journal of Microbiology
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    • 제45권3호
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    • pp.187-192
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    • 2007
  • REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

PHABSIM을 이용한 반변천 하천생태유량 산정 - 피라미, 참몰개를 대상으로 - (Estimation of an Optimum Ecological Stream Flow in the Banbyeon Stream Using PHABSIM - Focused on Zacco platypus and Squalidus chankaensis tsuchigae -)

  • 박진석;장성주;송인홍
    • 한국농공학회논문집
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    • 제62권6호
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    • pp.51-62
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    • 2020
  • The objective of this study was to estimate an optimum ecological flow rate in the Banbyeon stream based on the two representative fish species. Hydraulic stream environment was simulated with HEC-RAS for two water flow regimes and used for the PHABSIM hydraulic simulation. A dominant species of Zacco platypus and an endemic species of Squalidus chankaensis tsuchigae were selected as the representative fishes whose habitat conditions were evaluated for the spawning and adult stages. Weighted usable area (WUA) was estimated based on habitat suitability index (HSI) and PHABSIM habitat simulation. Overall deep water zone in the stream demonstrated greater WUA which implies better habitat status. The estimated WUA for Zacco platypus as the dominant species was about five times greater than Squalidus chankaensis tsuchigae at the stream flow of 12 ㎥/s. The optimum ecological flow rates were 15 ㎥/s and 25 ㎥/s for the respective spawning and adult stages of Zacco platypus, while 5 ㎥/s was estimated for both the life cycles of Squalidus chankaensis tsuchigae. Assuming that the dominant species may survive better in wider flow regimes, the optimum ecological flow rate should be determined rater based on the endemic species and flow rate of 5 ㎥/s was suggested for the Banbyeon stream.

기후변화 대응을 위한 경안천 유역의 홍수저감 대안 선정 (Determination of Flood Reduction Alternatives for responding to climate change in Gyeongan Watershed)

  • 한대건;최창현;김덕환;정재원;김정욱;김수전
    • 한국습지학회지
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    • 제18권2호
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    • pp.154-165
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    • 2016
  • 최근 기후변화로 인하여 태풍 및 집중호우로 인한 극한 강우사상의 발생빈도가 증가하고 있으며, 급격한 도시화로 인한 유역 내 불투수 면적이 늘어나고 있다. 이로 인해 재산피해가 증가하고 있어 기후변화를 고려한 미래 하천범람 등 홍수피해를 경감시키기 위한 홍수저감 대안 선정이 필요하다. 따라서 본 연구에서는 기후변화를 고려하여 목표기간별로(기준년도 : 1971~2010년, 목표기간I : 2011~2040년, 목표기간II : 2041~2070년, 목표기간III : 2071~2100년) HEC-HMS모형을 이용하여 기후변화에 따른 홍수량을 산정하였다. 또한, 배수펌프와 저류지를 각각 5개씩 홍수저감 대안으로 설정하여 HEC-RAS모형을 통해 대안별 홍수위를 산정하였다. 지형자료 및 홍수위를 이용하여 홍수범람도를 도시하였으며, 다차원 홍수피해액산정법(Multi dimension - Flood Damage Analysis, MD-FDA)을 이용하여 홍수피해 저감을 위한 대안별 경제성분석을 실시하였다. 홍수저감효과를 분석한 결과 배수펌프를 설치했을 경우 홍수위는 최소0.06m, 최대0.44m 감소하였고, 저류지는 최소0.01m, 최대1.86m 감소하는 것을 확인할 수 있었다. 침수면적은 최소 0.3%, 최대 32.64% 감소하였고, 침수심 역시 낮아지는 것으로 확인되었다. 또한, 경제성분석을 실시하여 대안별 편익 비용비를 비교한 결과 목표기간I에서는 저류지E, 목표기간II, 목표기간III에서는 배수펌프D가 홍수저감을 위한 타당한 대안으로 판단되었다. 본 연구의 결과를 통해 기후변화 적응을 위한 치수사업 시 주요사례로 활용될 수 있을 것으로 기대된다.

3T3-L1 세포의 지방세포형성과정에서 Baicalin에 의한 유전자 발현 프로파일 분석 (Effects of Baicalin on Gene Expression Profiles during Adipogenesis of 3T3-L1 Cells)

  • 이해용;강련화;정상인;조수현;윤유식
    • 한국식품영양과학회지
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    • 제39권1호
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    • pp.54-63
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    • 2010
  • Flavonoid 계열의 한 종류인 baicalin은 항염증, 항암, 항바이러스, 항세균 등의 효능을 가진다. 본 연구진은 선행연구를 통한 이전의 보고에서 baiclain이 adipogenesis pathway(지방세포 형성 경로)의 anti-adipogenic(지방세포 형성억제)과 pro-adipogenic(지방세포 형성 유도) factor들을 조절함으로써 비만 및 adipogenesis를 억제함을 밝혔다. 본 연구에서는, microarray 기술을 이용하여 3T3-L1 세포에서 baiclain이 유도하는 지방세포 형성 억제 효과에 대한 분자적 기작을 보다 상세하게 연구하고자 하였다. 지방세포의 분화 시간(0일, 2일, 4일 및 7일)과 분화 시 baicalin의 처리 유무에 따라 유전자 발현 양상을 분석하기 위해 해당 시료들을 microarray에 적용하였다. Microarray 결과로부터 2배이상의 변화가 있는 3972개의 유전자를 확보하였다. 그 유전자들의 발현 양상을 좀 더 자세히 살펴보기 위해 hierarchical clustering 분석을 진행하였고 그 결과로 20개의 cluster를 분류할 수 있었다. 그들 중 4개의 cluster는 분화의 전반적인 기간에서 baicalin의 첨가에 의해 뚜렷하게 상승(cluster 8과 cluster 10)하거나 반대로 뚜렷하게 감소(cluster 12와 cluster 14)하는 양상을 보였다. Cluster 8과 cluster 10에는 CHOP(CCAAT/enhancer-binding protein homologous protein), INSIG1(insulin induced gene 1), WISP2(WNT1 inducible signaling pathway protein 2), ADM(adrenomedullin), CCND2(cyclin D2), GRN(granulin) 및 TGFB3(transforming growth factor, beta 3)과 같은 세포 증식과 지방세포 형성 억제를 상승시키는 유전자들이 다수 포함되었다. 반대로 cluster 12와 cluster 14에는 세포 증식 억제, 세포 주기 억제 및 세포 성장 억제와 연관되거나 지방세포를 유도하는 유전자인 LTA(lympotoxin A), ACADSB(acyl-Coenzyme A dehydrogenase, short/branched chain), HMGCS2(3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2), IGFBP7(insulin-like growth factor binding protein 7), MERTK(c-merproto-oncogene tyrosine kinase), RASSF2(ras association(RalGDS/AF-6) domain family 2), RHOU(ras homolog gene family, member U) 및 SESN1(sestrin1) 등이 포함되었다. 결론적으로 baicalin은 세포 증식 및 지방세포 형성과 연관된 유전자들을 조절함으로써 지방세포의 분화를 억제하는 것으로 사료된다. 이러한 결과는 baicalin이 유도하는 지방세포 형성 억제 및 비만 억제 효과의 분자적 기작에 대한 중요한 정보를 제시한다.

저염식이를 이용한 cyclosporine 신독성에서 angiotensin converting enzyme Inhibitor의 영향 (The Effect of Angiotensin Converting Enzyme Inhibitor on Chronic Cyclosporine Nephropathy in Salt Depleted Rats)

  • 이은주;이은실;하정희;김용진;박용훈
    • Childhood Kidney Diseases
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    • 제4권2호
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    • pp.127-135
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    • 2000
  • 목 적 : Cyclosporine(CsA)는 면역 억제제로서 중요한 역할을 하고 있지만 가장 중요한 부작용인 신독성 때문에 사용에 제한이 있다. 이에 저염식이를 한 쥐에서 유발되는 만성 CsA 신증에서 angiotensin converting enzyme 억제제(ACEI)가 미치는 영향을 검색하고자 하였다. 대상 및 방법 : 흰 쥐를 대상으로 하여 표준식이(NSD), 저염식이(LSD), NSD+CsA. LSD+CsA, NSD+CsA+ACEI, LSD+CsA+ACEI를 1-6군으로 분류하여 공급하였다. 6주 후 혈중 CsA농도, 혈청 sodium, potassium, GFR을 측정하였고, 신장의 조직검사를 시행하였다. 성 적 : 혈중 CsA농도와 sodium치는 각 군간에 차이가 없었고 potassium치는 CsA 단독 투여시에는 식이군간에 차이가 없었으나, CsA와 ACEI를 병용 투여시에는 NSD군에 비해서 LSD군에서 유의하게 증가하였다. (P<0.05). 사구체 여과율은 CsA만 투여한 경우나 CsA와 ACEI를 병용투여한 경우에서 NSD군에 비해 LSD군에서 유의하게 감소하였고 NSD를 시행한 경우에서는 CsA만 투여한 경우보다 ACEI를 병용투여했을 때 GFR이 더 감소하였다 (P<0.05). 조직학적 소견은 CsA투여에 의한 근위부 세뇨관 위축, 간질의 섬유화와 PAS염색 양성인 과립들이 출현하였고 이는 NSD군보다 LSD군에서 더 저명하였으며 ACEI를 병용시에도 LSD군에서 이러한 변화가 더 저명하게 관찰되었으나 ACEI 투여 전과는 큰 차이를 보이지 않았다. 결 론 : 본 연구에서는 염분 부족은 renin-angiotensin system을 활성화해서 CsA 신증을 더욱 가중시키며, ACEI는 LSD로 유발된 CsA 신증에서 신기능의 화학적 지표와 조직학적으로 더욱 악화시컸다. 이 결과로 LSD로 인해 더욱 조장될 수 있는 간접적인 신허혈 상태에서는 ACEI는 신관류를 개선하지 못하고, 이로 인해 신독성이 더욱 악화될 수 있을 것으로 생각되었다.

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Effects of Buckwheat on the Insulin Sensitivity, Protein Digestibility and Utility in Diabetic Rats

  • Park, Hyun-Ju;Lee, Kyung-Hea
    • Preventive Nutrition and Food Science
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    • 제3권4호
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    • pp.356-361
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    • 1998
  • An experiment was performed to determine if buckwheat intake would improve insulin sensitivity in in normal healthy ras and steptozoticin-induced diabetic Sprague-Dauley rats. For four weeks, rats were fed either corn starch as a cotnrol diet or buckwheat as an experimental diet. As a result, the insulin sensitivity and plasma glucose levels in normal rats were not significantly affected by buckwheat fedding. The insulin sensitivity was lower in diabetic rats than in normal rats(p<0.05). Buckwheat tends to decrease the final plasma glucose level and increase insulin sensitivity in diabetic rats, but there was no sifnificant difference. Another five-week experiment was conducted to determine protein digestibility and protein utility in normal healty rats ad streptozotocin-induced diabetic rats on a control diet or buckwheat diet. The diet composition in this experiment was the same as the preceeding experiment. In the cotnrol diet groups, the protein digestibility in diabetic rats was significantly lower than that in normal rats(p<0.05). Buckwheat reduced protein digestibility in both normal and disbetic rats(p<0.05). Interestingly, in buckwheat diet groups, protei digestibility in diabetic rats was similar to that in normal rats. Protein utility was significantly lower indiabetic rats than in normal rats. This phenomenon was observed as early as the first week of the feeding period. However, protein utility was not sifnificanlty altered in both normal and diabetic rats by buckwheat feeding. It follows that decreased protein digestibility and utility in diabetic rts are not further aggravated by buckwheat feeding, suggesting that buckwheat can be a feasible supplement food for the diabetic therapeutic diet.

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Gas-Phase Technology and Microstructure of Fullerite Films

  • A.S. Berdinsky;Chun, Hui-Gon;Lee, Jing-Hyuk;Song, Yong-Hwa;Yu. V. Shevtsov
    • 한국표면공학회지
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    • 제37권2호
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    • pp.71-75
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    • 2004
  • The technology of $C_{60}$ fullerite films preparation by means of gas-phase deposition and structure of fullerite films are described. A three-channel flow plant was used to obtain fullerite films. The films were deposited in the flow of inert gas under reduced pressure onto a cooled silicon or sapphire substrate placed inside the reaction chamber of the plant. The plant allows one to obtain the films of pure fullerenes and to synthesise the films from fullerene compounds and doped fullerenes. The structure of two types of films were investigated by FE-SEM and SEM techniques: pure fullerite films onto silicon and sapphire substrates as well as compound films were studied by FE-SEM technique. All samples have shown columnar structure with high level of porosity. The synthesis of films composed of fullerene and its compounds for use in electronics is demonstrated to be promising. For example, experiments confirm the possibility to use fullerite films in sensor electronics to produce humidity and thermal sensors. It is also possible to use the sensitivity of these films to isotropic pressure. The experiments with $C_{60}$-Cu-J films have shown quite strong dependence of their resistance on pressure of different sort of medium-gas that could be used in gas-sensitive sensors. The structure and preparation technology of resistive sensor based on fullerite films are described.bed.

인체상피조직 및 타액내 해독효소로서의 glutathione transferase Pi (Pi Class of Glutathione Transferase is the Major Form of Detoxifying Enzyme in the Human Epithelial Tissues and Saliva)

  • 박상철;곽상순;서희명;김옥경;정윤미;최경호;김우호
    • 한국환경성돌연변이발암원학회지
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    • 제11권2호
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    • pp.148-160
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    • 1991
  • 인체의 여리 조직을 대상으로하여 면연조직화학전방법을 통하여 glutathione transferase isoenzyme의 분포를 비교 분석하였다. 상피조직중의 GST-Pi의 다랑분포가 확인되었으며, 특히 외인성 화학물질에 노출되기 쉬운 피부, 유두, 신도 등의 과립층과 췌장, 담도, 타액선, 신세뇨관등의 배설관의 상피 또는 난소의 theca와 granulosa, 고환의 Leydig세포, 부신피 질의 zona reticularis 등의 steroid 생합성이 왕성한 부위에서 높은 GST-Pi 분포가 관찰되었다. 면역조직화학적 분석과 병행하여 Western blot 분석을 시행해본 결과 이러한 GST-Pi 분포가 인체유래 유각상피세포 중에서도 확인되었다. 그러나 K-ras 암유전자로 형질전환하여 암화능을 갖춘 인체상피세포주의 GST-Pi 발현은 유의한 차이를 보이지 않았다. 뿐만아니라 타액중에서도 GST-Pi가 다량 존재함이 Western blot 분석에 의하여 구명되었다. 이러한 결과는 GST-Pi가 인체조직 중 외인성독성물질에 노출되는 부위, 내인성 steroid 합성부위 및 배설능을 갖는 부위의 상피조직에 주로 존재하고 있음을 보여주고 있으며, 이러한 GST-Pi의 조직분포는 동효소가 인체의 해독기능에 주요한 역할을 하고 있음을 시사해주고 있다.

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Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

  • Yoo, Byong Chul;Yeo, Seung-Gu
    • Radiation Oncology Journal
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    • 제35권3호
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    • pp.281-288
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    • 2017
  • Purpose: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. Materials and Methods: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. Results: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. Conclusion: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.