• Molecules and Cells
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• 제41권2호
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• pp.83-92
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• 2018

The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal. Here we provide a brief overview of the regulatory mechanisms of the Hippo pathway, its role in cancer stem cell biology, and promising therapeutic interventions.

• 간호행정학회지
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• 제6권1호
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• pp.123-134
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• 2000

This study intended to analyze the effectiveness to obtain by developing the critical pathway presented as the method to improve the quality-betterment and cost effectiveness the through the continuous and consistent patient management for the hysterectomy patient and applying it to the real practice. This study was designed to develop and effect the critical pathway for hysterectomy patients in the way to be possible the intergrated in patient management. It was adopted the process of seven phase to develop a critical pathway. To analyze the application effect of the developed critical pathway, this author offered health care service applying the critical pathway to the hysterectomy patient from July. 20 to Oct. 19. 1999. The study method had been done by investigating the experimental group and control group through the questionnaire on 40 patients who had been inpatient hysterectomy. Dependent variables were measured by modified from satisfaction, and cost and length of hospital stay. The data anlyzed by frequency, x2-test, t-test. The results of this study was as follows; 1. It was decided that the vertical line of the critical pathway was made up of eight items such as monitoring/assessment, treatment, activity, medication, consult. Lab test, diet, patient teaching and horizontal line was 7days from admission to discharge. 2. After the verifying the validity of the expert group about the critical pathway, the horizontal line was amended from hospitalization to five postoperative days and taking their consensus, some contents of the horizontal line was amended and deleted. 3. There was no significant differences in the experimental group and control group in the satisfaction, and significant differences in the cost, the length of hospital stay.

• 한국의료질향상학회지
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• 제7권1호
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• pp.60-70
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• 2000

Background : The aim of this study was to examine the effectiveness of the critical pathway to diabetic patients who were admitted in the hospital. Methods : For establishment of critical pathway for diabetic patients, we organized the multidisciplinary care team. During 5 months, 31 diabetic inpatients were applied the critical pathway and the results were compared with 11 diabetic inpatients who were treated with conventional way. We assessed the patients satisfaction, knowledge on the disease, compliance of medical regimen, length of stay(LOS) and hospital cost. We used the computer program SAS for statistical analysis. Data were summarized with mean, and analyzed using t-test repeated measures ANOVA and Wilcoxon rank sum test. Results : Length of stay(LOS) was remarkably shortened in critical pathway group compared with the conventional treatment group($7.6{\pm}1.23$ vs $12.0{\pm}4.73$, p<0.000). Although LOS was significantly shortened in critical pathway group, patients satisfaction was much higher than conventional treatment group. There were no significant difference of knowledge on the disease, compliance of medical regimen and blood glucose level between two groups at discharge. Hospital cost of each patients also significantly decreased in critical pathway group(890,000 won vs 1,280,000 won, p<0.05). Conclusion : These results showed that establishment of critical pathway for diabetic inpatients with team approach is the one of the way to improve the quality of diabetic patients management and to enhance the efficiency of hospital management.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.95-107
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• 2002

Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.208-213
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• 2007

With the help of a development and popularization of microarray technology that enable to us to simultaneously investigate the expression pattern of thousands of genes, the toxicogenomics experimenters can interpret the genome-scale interaction between genes exposed in toxicant or toxicant-related environment. The ultimate and primary goal of toxicogenomics identifies functional context among the group of genes that are differentially or similarly coexpressed under the specific toxic substance. On the other side, public reference databases with transcriptom, proteom, and biological pathway information are needed for the analysis of these complex omics data. However, due to the heterogeneous and independent nature of these databases, it is hard to individually analyze a large omics annotations and their pathway information. Fortunately, several web sites of the public database provide information linked to other. Nevertheless it involves not only approriate information but also unnecessary information to users. Therefore, the systematically integrated database that is suitable to a demand of experimenters is needed. For these reasons, we propose SOP (Search of Omics Pathway) database system which is constructed as the integrated biological database converting heterogeneous feature of public databases into combined feature. In addition, SOP offers user-friendly web interfaces which enable users to submit gene queries for biological interpretation of gene lists derived from omics experiments. Outputs of SOP web interface are supported as the omics annotation table and the visualized pathway maps of KEGG PATHWAY database. We believe that SOP will appear as a helpful tool to perform biological interpretation of genes or proteins traced to omics experiments, lead to new discoveries from their pathway analysis, and design new hypothesis for a next toxicogenomics experiments.

• Genomics & Informatics
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• 제2권4호
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• pp.191-194
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• 2004

Exponentially increasing biopathway data in recent years provide us with means to elucidate the large-scale modular organization of the cell. Given the existing information on metabolic and regulatory networks, inferring biopathway information through scientific reasoning or data mining of large scale array data or proteomics data get great attention. Naturally, there is a need for a user-friendly system allowing the user to combine large and diverse pathway data sets from different resources. We built a data warehouse - BIOWAY - for analyzing and visualizing biological pathways, by integrating and customizing resources. We have collected many different types of data in regards to pathway information, including metabolic pathway data from KEGG/LIGAND, signaling pathway data from BIND, and protein information data from SWISS-PROT. In addition to providing general data retrieval mechanism, a successful user interface should provide convenient visualization mechanism since biological pathway data is difficult to conceptualize without graphical representations. Still, the visual interface in the previous systems, at best, uses static images only for the specific categorized pathways. Thus, it is difficult to cope with more complex pathways. In the BIOWAY system, all the pathway data can be displayed in computer generated graphical networks, rather than manually drawn image data. Furthermore, it is designed in such a way that all the pathway maps can be expanded or shrinked, by introducing the concept of super node. A subtle graphic layout algorithm has been applied to best display the pathway data.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.493-511
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• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• Journal of Microbiology and Biotechnology
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• 제16권3호
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• pp.391-398
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• 2006

$NF-{\kappa}B$ is a transcription factor involved in the innate immunity against bacterial infection and inflammation. It is also known to render cells resistant to the apoptosis caused by some anticancer drugs. Such a chemoresistance of cancer cells may be related to the activation of $NF-{\kappa}B$ transcription factor; however, the mechanism of activation is not well understood. Here, we demonstrate that a chemotherapeutic agent, etoposide, independently stimulates the $I{\kappa}B{\alpha}$ degradation pathway and PI3-kinase/Akt signaling pathway: The classical $I{\kappa}B{\alpha}$ degradation pathway leads to the nuclear translocation and DNA binding of p65 subunit through $IKK{\beta}$ kinase, whereas the PI3-kinase/Akt pathway plays a distinct role in activating this transcription factor. The PI3-kinase/Akt pathway acts on the p50 subunit of the $NF-{\kappa}B$ transcription factor and enhances the DNA binding affinity of the p50 protein. It may also explain the role of the PI3-kinase/Akt pathway in the anti-apoptotic function of $NF-{\kappa}B$ during chemoresistance of cancer cells.

• 한국식품조리과학회지
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• 제13권5호
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• pp.661-668
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• 1997

By using several solvents, barley extracts containing the anticomplementary activities in classical pathway were prepared (250 $\mu\textrm{g}$/ml): methanol (83.1%), ethanol (71.9%), water extract (25.4%), M-1 (250 $\mu\textrm{g}$/ml), and the soluble part of methanol extract which showed the highest activity (83.4%) and the yield. Anticomplementary activity of methanol extract as well as protease digestion in classical pathway showed 82.4% and 78.4% in the concentration of 250 $\mu\textrm{g}$/ml, respectively. It was found that protein was not involved in anticomplementary activity in the classical pathway and the methanol extract made an impact on classical pathway, but not on alternative pathway. For the immune-stimulating effect, the T cell proliferation effect of the protease digestion displayed little effect irrespective of the dose. In addition, the T cell proliferation effect of methanol extract showed 13-fold higher proliferation effect compared with positive control. It was revealed that the substance containing protein serves as an important factor for the immune proliferation. Therefore, the anticomplementary activity ${\beta}$-glucan in classical pathway and alternative pathway displayed the lowest activity, showing 2.2%, 22.3% respectively. However, the immune-stimulating effect of ${\beta}$-glucan showed the T cell stimulating effect 13 times higher than positive control.

• Mass Spectrometry Letters
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• 제8권3호
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• pp.65-68
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• 2017

Thiamethoxam is one of the main suspect in honeybee colony collapse disorder (CCD). Due to this reason, thiamethoxam including imidacloprid and clothianidin has been banned for two years in some Europe countries. The CCD phenomenon has also been reported in Korea. Regarding this issue and needs, a new project has started to develop the method for the quatitation of thiamethoxam using isotope dilution mass spectrometry (IDMS). In the process of optimization for the IDMS method with thiamethoxam and $thiamethoxam-d_3$, we observed that the fragment peaks did not correspond to the fragmentation pathway as published elsewhere. Here, we proposed a candidate fragmentation pathway. To validate the proposed fragmentation pathway, another isotope analogue, $thiamethoxam-d_4$, was introduced and the MS/MS spectra of both isotope analogues were compared. In addition, the MS/MS/MS spectra of thiamethoxam were inspected for more evidence of the candidate pathway. Those spectra indicated that the proposed fragmentation pathway could be used to assign the fragment peaks of thiamethoxam.