• Title/Summary/Keyword: Synergy Effects

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Multiple Effects of a Novel Epothilone Analog on Cellular Processes and Signaling Pathways Regulated by Rac1 GTPase in the Human Breast Cancer Cells

  • Zhang, Hong;An, Fan;Tang, Li;Qiu, Rongguo
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.2
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    • pp.109-120
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    • 2014
  • The epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. UTD2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. This study investigated the effects of UTD2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in MCF-7 breast cancer cells. Results showed that UTD2 inhibited the cellular functions of actin cytoskeleton, such as wound-closure, migration and invasion, as well as adhesion. Our study further demonstrated that UTD2 suppressed Rac1 GTPase activation and reduced the activity of PAK1, which is a downstream effector of Rac1, while the activity of Cdc42 was not affected. Additionally, the phosphorylation of p38 and ERK were significantly inhibited, but the phosphorylation of JNK remained the same after UTD2 treatment. Moreover, UTD2 inhibited the activity and mRNA expression of MMP-2, which plays a key role in cell motility. UTD2 also reduced the phosphorylation of Akt, which is an important signaling kinase regulating the cell survival through Rac1. Furthermore, UTD2 interrupted the synergy between Rac1 and Raf in focus formation assays. Taken together, these results indicated that UTD2 exerted multiple effects on the actin cytoskeleton and signaling pathways associated with Rac1. This study provided novel insights into the molecular mechanism of the antineoplastic and antimetastatic activities of epothilones. Our findings also suggest that the signaling pathways regulated by Rac1 may be evaluated as biomarkers for the response to therapy in clinical trials of epothilones.

The Impact of Adverse Employment and Working Conditions on the Risk of Workplace Injury in Canada

  • Nadalin, Victoria;Mustard, Cameron;Smith, Peter M.
    • Safety and Health at Work
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    • v.12 no.4
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    • pp.471-478
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    • 2021
  • Background: Employment standards (ES) include having a regular payday, regular breaks, the right to paid sick or vacation time, and paid wages. Inadequate ES contribute to the labour market vulnerability of workers; however, they are not typically considered to be risk factors for workplace injury. In a sample of Canadian workers, we examine the risk of injury associated with inadequate ES, independent of, and combined with inadequate workplace protections from workplace hazards. Methods: Data from 2,803 adults working 15 hours or more/week in workplaces with at least five employees were analysed. We explored associations between exposure to workplace hazards with inadequate protections [termed occupational health and safety (OHS) vulnerability] and inadequate ES on workplace injury (physical or mental injury; injury requiring time off). Additive interaction models were used to examine the independent and combined effects of these exposures. Results: Occupational health and safety vulnerability and inadequate ES were independently associated with increased injury outcomes. Adjusted models showed an additive relationship for all injury outcomes between OHS vulnerability and inadequate ES. Statistically significant superadditive relationships were observed for physical injury risk with policy and procedure vulnerability plus inadequate ES [synergy index (S) 1.50, 95% CI: 1.13-2.00] and for overall OHS vulnerability plus inadequate ES (S 1.53, 95% CI: 1.16-2.02), suggesting a combined effect greater than independent effects. Conclusion: Occupational health and safety vulnerability and inadequate ES are independently associated with workplace injury. For certain injury outcomes, the combined effect of OHS vulnerability and inadequate ES is greater than the independent effects of each individual exposure.

A Novel Monoclonal Antibody Induces Cancer Cell Apoptosis and Enhances the Activity of Chemotherapeutic Drugs

  • Xu, Heng;Tian, Yan-Na;Dun, Bo-Ying;Liu, Hai-Tao;Dong, Guang-Kuo;Wang, Jin-Hua;Lu, Shang-Su;Chen, Bo;She, Jin-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4423-4428
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    • 2014
  • A novel monoclonal antibody (mAb), known as AC10364, was identified from an antibody library generated by immunization of mice with human carcinoma cells. The mAb recognized proteins in lysates from multiple carcinoma cell lines. Cell cytotoxicity assays showed that AC10364 significantly inhibited cell growth and induced apoptosis in multiple carcinoma cell lines, including Bel/fu, KATO-III and A2780. Compared with mAb AC10364 or chemotherapeutic drugs alone, the combination of mAb AC10364 with chemotherapeutic drugs demonstrated enhanced growth inhibitory effects on carcinoma cells. These results suggest that mAb AC10364 is a promising candidate for cancer therapy.

The Green Growth Policy of the Lee Myung-bak Government: Policy Integration Perspectives for System Transition

  • Seong, Jieun
    • STI Policy Review
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    • v.2 no.2
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    • pp.11-24
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    • 2011
  • S&T policy has been traditionally regarded as a sector policy; however, it is now evolving into an infrastructure innovation policy that forms the foundation of diverse types of policies. Simultaneously, environmental and energy policies formerly considered as sector policies are now being expanded and integrated into a higher level policy for sustainable development. With these changes underway, the importance of policy integration has increased. Efforts are being made to minimize contradictions between environmental, social, and innovation policies that emphasize proactive linkage among policies or place the highest priority on environmental policy following the theory of Environmental Policy Integration (EPI). Confronted with these policy changes, the Lee Myung-bak government announced "Low-Carbon Green Growth" in 2008 as national agenda for development that focus attention on environmental and energy issues. Economic policy and environmental policy have been traditionally seen in a conflicting relationship with different paths of policy development. However, the administration of President Lee is now emphasizing the synergy effects between the environment and economic growth with the concept of green growth. The green growth policy of the Korean government has great significance as it has built a momentum for incorporating social goals such as environmental values or sustainable development into economic growth-oriented policies; however, there remain many challenges due to the legacy of the development period that has dominated Korean society. The Korean government says it reflects "EPI" or "environmentalism" in policy goals; however, in reality it prioritizes development over the environment.

A Study on the Analysis of Project Implementations at Public Design - Improving Project for Public Design in Daegu, Dongseong Street - (공공디자인 개선사업의 추진실태 분석에 관한 연구 - 대구시 동성로 공공디자인 개선사업을 중심으로 -)

  • Lee, Jong-Kuk
    • Journal of the Korean housing association
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    • v.25 no.6
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    • pp.67-74
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    • 2014
  • Dongseong-ro public design was reformed for a short time to be short of connection and riffle effect of another project and to have limitation on long term and integrated development, so that systematic plan from beginning of the project was needed to produce synergy effects. The purpose of the study was to investigate reformation of Dongseong-ro public design and to check on existing development project again and to take actions against future projects in advance and to reexamine and make long term plan from point of view of development of downtown. This study investigated reformation of Dongseong-ro public design of Junggucheong office of Daegu that was done from May 2007 to December 2010. The study consisted of purpose of the project, scope, time, the committee of promotion, questionnaire survey, residents' participation and follow up to suggest reformation based on questionnaire survey. This study had limitation of investigation into internal materials of 'Dongseong-ro public design reformation's master planning service' of Junggucheong office of Daegu. Further studies were needed to investigate empirically.

Synergy Effects of Hybrid Catalysts on Syngas Yield of Partial Oxidation of Methane (메탄의 부분산화를 통한 합성가스 제조에서의 hybrid 촉매의 영향)

  • 오영삼;백영순;이재의;목영일
    • Journal of Energy Engineering
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    • v.8 no.1
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    • pp.34-47
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    • 1999
  • 본 연구에서는 촉매상에서 메탄의 산화시 발생되는 반응열을 이용하고 반응생성물과 미반응 메탄과의 개질반응에 의해 합성가스의 수율을 증대시키기 위하여 연소촉매와 개질촉매를 연속적으로 배치한 hybrid 촉매상에서 개질촉매에 따른 메탄의 부분산화반응의 반응 특성과 합성가스 수율에 미치는 영향을 관찰하였다. 메탄의 산화를 위해서 Pt-Rh/cordierite 촉매를 사용하였으며, 개질촉매로는 상업용 개질촉매인 R67, ICI46-1, 수성가스 전환반응촉매인 LX821 촉매와 6 wt% Ni/cordierite 촉매를 사용하였다. 실험결과 연소촉매와 개질촉매를 연속적으로 사용한 경우 메탄의 산화 과정에서 생성된 CO2 및 H2O가 미반응 메탄과의 개질반응 촉진으로 인하여 합성가스이 수율이 증가됨을 확인할 수 있었다. 이때 생성되는 합성가스의 H2/CO 몰비는 온도에 따라 감소하는 것으로 나타났으며, 80$0^{\circ}C$에서 촉매에 따라 2.2~2.8의 값을 가짐을 알 수 있었다. 개질촉매로 R67 및 Ni/cordierite 촉매를 사용하였을 경우 가장 높은 합성가스의 수율을 얻을 수 있었으며, 연소촉매와 개질촉매의 질량비는 1:1~1:2에서 가장 높은 수율의 합성가스를 얻을 수 있었다. 메탄과 산소의 몰비가 2:2에서 메탄의 전환율과 수소 수율이 가장 높게 나타났으며 메탄의 몰비 증가에 따라 감소되는 경향을 보였다.

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The Treatment of Central Pain after Spinal Cord Injury -Case reports- (척수손상 후 발생한 중추성 통증의 치험 -증례 보고-)

  • Lee, Mi-Joung;Kim, Hae-Ja;Lee, Won-Hyung;Shin, Yong-Sup;Choi, Sae-Jin
    • The Korean Journal of Pain
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    • v.13 no.1
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    • pp.105-110
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    • 2000
  • Central neuropathic pain may occur in 10~20% of the patients after spinal cord injury. The central pain syndrome include spontaneous continuing and intermittent pain as well as evoked pain. The pain is evoked by non-noxious stimulation of the region (allodynia) and repeated stimulation (wind-up phenomenon). Four patients were referred suffering from severe pain, allodynia and hyperaesthesia after spinal cord injury. They had received conventional treatment with non-steroidal anti-inflammatory drugs, steroid, anticonvulsant, antidepressant and rehabilitation which failed to provide pain relief. We administered combination of low doses of morphine and ketamine (10 mg) through the epidural catheter with other conventional therapy. Satisfactory pain relief was achieved in each patient. The reduction of pain was not associated with severe side effects. The most bothersome side effect of ketamine was dizziness in one patient, only caused by bolus injection (ketamine 10 mg with normal saline 10 ml). This suggests synergy from this combination that provides an alternative treatment for central pain.

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Atorvastatin: In-Vivo Synergy with Metronidazole as Anti-Blastocystis Therapy

  • Basyoni, Maha M.A.;Fouad, Shawky A.;Amer, Marwa F.;Amer, Ahmed Fathy;Ismail, Dalia Ibrahim
    • Parasites, Hosts and Diseases
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    • v.56 no.2
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    • pp.105-112
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    • 2018
  • Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA were apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with highreduction in Blastocystis shedding (93.4-97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%)were recorded in groups of combination treatments AVA 20-40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.

Efficient Touch Points Study for IMC : (효율적인 IMC를 이루기 위한 접점 분석연구 : MP3 플레이어 사례 연구)

  • Moon, Seung-Jun;Yang, Jung-Gu
    • Archives of design research
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    • v.19 no.5 s.67
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    • pp.303-312
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    • 2006
  • The purpose of this study is to suggest theoretical basis of touch point analysis model in terms of an integrated marketing communications using one specific case study. Results of previous studies have shown several weaknesses. However, this study was carried out to overcome such a weakness. In order to perform this case study, one specific MP3 player was chosen with a market situation analysis. Compared to previous practical situation, the results of this study should be improved in that this model suggested a theoretical basis dealing with synergy effects as well as a correct understanding in consumer's purchase process. Based on the outcome of this study, we hope to see other similar studies which can be of help to the practical efficiency in integrated marketing communication.

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Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer

  • Zhang, Ya-Li;Sun, Feng-Ting;Zhang, Ze;Chen, Xiao-Xu;Liu, Ai-Xiang;Pan, Jing-Jing;Peng, Fei;Zhou, Shuai;Sun, Li-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10475-10481
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    • 2015
  • Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.