• BMB Reports
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• 제39권5호
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• pp.492-501
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• 2006

Since differentiation therapy is one of the promising strategies for treatment of leukemia, universal efforts have been focused on finding new differentiating agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its effects on K562 cell line. GTP, at concentrations between 25-200 ${\mu}M$, inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive cells after 6-days of treatments of K562 cells. Flow cytometric analyses of glycophorine A (GPA) showed that GTP can induce expression of this marker in more mature erythroid cells in a time- and dose-dependent manner. These effects of GTP were also accompanied with inhibition of DNA synthesis (measured by [$^3H$]-thymidine incorporation) and early S-phase cell cycle arrest by 96 h of exposure. In contrast, no detectable effects were observed when GTP administered to unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL cells. In addition, growth inhibition and differentiating effects of GTP were also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In heat-inactivated medium, where rapid degradation of GTP via extracellular nucleotidases is slow, the anti-proliferative and differentiating effects of all type of guanine nucleotides (except Guo) were significantly decreased. Moreover, adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP effects in K562 cells, suggesting that the extracellulr degradation of GTP or its final conversion to Guo may account for the mechanism of GTP effects. This view is further supported by the fact that GTP and Guo are both capable of impeding the effects of mycophenolic acid. In conclusion, our data will hopefully have important impact on pharmaceutical evaluation of guanine nucleotides for leukemia treatments.

• Molecules and Cells
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• 제41권11호
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• pp.971-978
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• 2018

The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

• Childhood Kidney Diseases
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• 제24권1호
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• pp.1-13
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• 2020

Immunoglobulin (Ig)A vasculitis nephritis (IgAVN), also referred to as Henoch-Schönlein purpura nephritis, is a relatively benign disease in children. However, two 24-year European cohort studies have reported high sustained rates of hypertension, severe proteinuria, and renal dysfunction in patients with IgAVN. Notably, the incidence and exacerbation rates of proteinuria, hypertension, and renal dysfunction during pregnancy were high even in women who recovered from IgAVN before pregnancy. Patients with IgAVN need lifelong care. Trials have been performed to investigate early biomarkers and genes associated with poor prognosis to identify high-risk patients in whom IgAVN may progress to severe renal disease. Urinary IgA/cr, IgM/cr levels, and HLAB35 and angiotensinogen gene expression were shown to be predictors of progression of IgAVN to severe renal dysfunction. The 2019 Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative group published guidelines for pediatric IgAVN, following the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines established in 2012. Compared with the KDIGO guidelines, the SHARE guidelines recommend earlier corticosteroid administration in cases of mild proteinuria (>0.5 g/d). Clinical trials of targeted budesonide delivery to the distal ileum, monoclonal antibody targeting C5, eculizumab and anti-CD20 monoclonal antibody administration, among others are currently underway in patients with IgA nephropathy. It is expected that newer therapeutic agents would become available for IgAVN in the near future. This review summarizes IgAVN with emphasis on recently published literature, including possible preventive strategies, predictive biomarkers for progression of IgAVN, and various treatments.

• 대한수학교육학회지:수학교육학연구
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• 제22권4호
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• pp.477-494
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• 2012

본 연구는 혼합계산 문제에 대한 학생들의 반응 사례 및 오류유형, 혼합계산 지도에 널리 활용되는 기억술, 혼합계산의 핵심인 연산 순서의 규칙에 관한 역사적 논의 및 성격을 고찰하였다. 또한 이를 바탕으로 자연수의 혼합계산 단원의 교과서의 내용구성 및 전개 방식을 비판적으로 분석하고 지도에 관한 개선 방안을 다음과 같이 제시하였다. 첫째, 실생활 문제 상황과 연산 순서의 규칙 사이의 왜곡된 논리적 연결성을 지적하였다. 둘째, 연산 순서의 규약적 성격을 고려하여 교과서를 구성하여야 함을 제시하였다. 셋째, 연산 순서의 문제는 식의 구조에 대한 이해와 결부시켜야 함을 지적하였다. 넷째, 혼합계산식의 이해를 돕는 다양한 교수학적 전략을 참고할 것을 제시하였다. 본 연구는 차후 혼합계산과 관련된 교과서 개발을 위한 시사점을 제공한다는 점에서 의의를 가진다.

• 한국실내디자인학회논문집
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• 제22호
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• pp.61-68
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• 2000

This paper illustrates what the reality of architectural concepts, materials, notions and phenomena are as central questions of contemporay space design. These issues form the goal of modern space design which should attain to the reality of an era when non-real values prevail. Despite the trends of an everchanging and ephemeral dominating quality in architecture for the last ten years, architects still aim to contruct everlasting space on earth. The trends of dematerialization in today's space design can be substantiated in spatial-temporal dimensions as follows. First of all, ephemeral architecture with concepts of hypothetical temporality, everchanging architecture in fluidity, and the transparent architecture with the floating and overlapping image can be analyzed in the dimension of 'time'. In terms of 'space', void quality for the expression of emptiness, neutral space by the simplified and summarized forms, expanded space through ambiguous boundaries and spatial repetition can becharacterized and also be intended strategies for lightness, state of flux, ambiguity, paradox etc., lead modern space design along that path. As this point, we need to pay attention to the so-called 'hypersurface' concept proposed by Stephen Perella. Hypersurface is a sort of cladding sheathing existence independent from the primary structure. With it, the integration between form and image can be achieved. Sometimes hypersurface can be a strategical screen for image projection, a cognitive receptor for surroundings as well as a catalyst for information and communication systems. When the situation dematerializes more and more as the years go on, the concept of hypersurface can be an inclusive method between the phenomenological form in architecture and its self recipient image. Permissive atmospheres created between them in contemporary space design and new paradigms emerged with digital technology will further reinforce the human space's dynamism.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5883-5887
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• 2015

Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-${\gamma}1$. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU-193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5471-5476
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• 2015

2-deoxy-D-Glucose (2DG) causes cytotoxicity in cancer cells by disrupting thiol metabolism. It is an effective component in therapeutic strategies. It targets the metabolism of cancer cells with glycolysis inhibitory activity. On the other hand, MLN4924, a newly discovered investigational small molecule inhibitor of NAE (NEDD8 activating enzyme), inactivates SCF E3 ligase and causes accumulation of its substrates which triggers apoptosis. Combination of these components might provide a more efficient approach to treatment. In this research, 2DG and MLN4924 were co-applied to breast cancer cells (MCF-7 and SKBR-3) and cytotoxic and apoptotic activity were evaluated the by Micro culture tetrazolium test (MTT), TUNEL and ELISA methods. Caspase3 and Bcl2 genes expression were evaluated by real time Q-PCR methods. The results showed that MLN4924 and MLN4924/2DG dose-dependently suppressed the proliferation of MCF7 and SKBR-3 cells. Cell survival of breast cancer cells exposed to the combination of 2DG/MLN4924 was decreased significantly compared to controls (p<0.05), while 2DG and MLN4924 alone had less pronounced effects on the cells. The obtained results suggest that 2DG/MLN4924 is much more efficient in breast cancer cell lines with enhanced cytotoxicity via inducing a apoptosis cell signaling gene, caspase-3.

• 한국콘텐츠학회논문지
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• 제11권10호
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• pp.147-155
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• 2011

글로벌 사회가 도래됨에 따라 국가의 이미지가 이전보다 더 중요시 되었다. 국가경쟁력이 더욱 중요시되는 현시점에서 현대사회의 가장 큰 국제적 행사인 올림픽은 세계인의 평화와 화합의장으로서 뿐만 아니라 개최국의 과학과 기술, 문화 예술의 총체적 역량을 보여줄 수 있는 기회의 장이라는 측면에서 그 중요성이 날로 부각되고 있다. 성공적인 올림픽으로 국가의 이미지를 긍정적으로 확립할 수 있으며 올림픽 엠블럼은 성공적인 올림픽을 만드는 핵심 비주얼아이덴티티 요소이다. 이에 본 연구에서는 엠블럼이 국제사회에서 국가의 아이덴티티를 표현하는 중요한 비주얼매개체라는 점에 근거하여 올림픽 엠블럼에 관하여 연구하고자 한다. 올림픽 엠블럼에 나타난 개최국의 아이덴티티 적용사례를 살펴보고 모티브와 표현에 따른 국가아이덴티티 유형을 도출하였다. 또 도출된 유형을 내부지향과 외부지향의 관점에서 경향을 분석하고 국가아이덴티티를 표현한 엠블럼에서 중요시되는 특성을 파악하였다. 따라서 본 연구의 결과물은 국가브랜드 관점에서 한국가의 존재감을 나타내는 표현수단인 올림픽 엠블럼에 나타난 국가아이덴티티 유형을 이해하고 향후 국가아이덴티티를 반영한 엠블럼 제작 시 효과적인 국가아이덴티티 전략 수립을 위한 기초자료로 활용 될 수 있을 것으로 기대한다.

• 대한본초학회지
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• 제31권4호
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• pp.71-77
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• 2016

Objectives : Adipogenesis was defined as a differentiation process of preadipocytes into the adipocytes. Thus, to control of this process can be one of the most important strategies to prevent obesity. Korean ginseng(Panax ginseng C.A. Meyer) is one of the most widely used medicinal herbs. Although multiple biological activities of Korean ginseng, particularly ginsenosides, have been known, the anti-adipogenic role and function of polysaccharides from Korean ginseng are still unclear. In this study, we examined anti-adipogenic activity of polysaccharides and its molecular basis mechanisms are further investigated.Methods : The cytotoxicity of KGP in 3T3-L1 was evaluated by MTT assay. Anti-adipogenic effect of KGP was examined by Oil Red O (ORO) staining and microscopy observation in 3T3-L1 mature adipocytes. The mRNA expression levels of adipogenic transcriptional factors were analyzed by reverse transcription-polymer chain reaction (RT-PCR). To elucidate the adipogenic molecular mechanism of KGT, SB431542 (TGF-β specific inhibitor) was used.Results : We found that polysaccharides showed no effect on the viability of 3T3-L1 preadipocytes. Dose dependent inhibitory effect of polysaccharides on 3T3-L1 adipogenesis was observed as judged by ORO staining and microscopic image analysis. To obtain further mechanistic insight into anti-adipogenic function of polysaccharides, we then tested the effect of polysaccharides treatment on the adipogenic marker genes. The mRNA expressions level of C/EBPα, PPARγ, C/EBPβ, and fatty acid synthase (FAS) were dose-dependently inhibited by KGP treatment in 3T3-L1 mature adipocytes.Conclusions : In conclusion, these findings suggest that the KGP could be used in treatment of obesity and overweight related diseases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권6호
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• pp.530-543
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• 2006

Adeonoid cystic carcinoma (ACC) is one of the most common malignant tumors of salivary glands. It is characterized by a relentless regrowth especially around nerve tissues and a high rate of hematogenous distant metastasis. Clinically most deaths from salivary ACC are caused by delayed lung metastases that are resistant to conventional chemotherapy. So, knowledge of cellular and molecular properties that influence the dissemination of metastatic tumor cells, is important for new treatment strategies of metastatic lesions. We determined expressions of angiogenic signaling molecules microvessel density (MVD) using surgical specimens of human salivary ACC. Protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, activated VEGFR-2, and human CD31 were assessed in 20 cases of salivary ACC by immunohistochemical staining. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for antibodies of VEGF, VEGFR-2, and activated VEGFR-2. The overall percentages of the 20 specimens expressing VEGF, VEGFR-2, activated VEGFR-2 were 90, 95, and 95%, respectively. Immunoreactivities of the biomarkers in salivary ACC were higher than those in normal salivary gland. Furthermore, immune-related cells as well as tumor cells expressed VEGF/VEGFR-2. Microvessel density of salivary ACC was higher than that of normal salivary gland (P<0.05). Taken together, angiogenic signaling molecules are actively expressed in salivary ACC. And we suggest that these molecules may have critical role in the hematogenous spread of salivay ACC, which has a propensity for delayed lung metastasis. Therefore, these biomarkers can be molecular targets for therapy of metastasis of salivary ACC.