• Molecular Medicine Reports
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• v.20 no.3
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• pp.2476-2483
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• 2019

Atopic dermatitis (AD ) is an inflammatory skin disorder caused by immunological dysregulation and genetic factors. Whether the expression levels of cytokine and skin barrier protein were altered by S100 calcium binding protein A8 (S100A8) and S100A9 in human keratinocytic HaCaT cells was examined in the present study. Alterations of cytokine expression were examined by ELI SA following treatment with S100A8/9 and various signal protein-specific inhibitors. Activation of the mitogen activated protein kinase (MAPK) pathway and nuclear factor (NF)-κB was evaluated by using western blotting and an NF-κB activity test, respectively. The expression levels of interleukin (IL )-6, IL- 8 and monocyte chemoattractant protein-1 increased following treatment with S100A8 and S100A9, and the increase was significantly blocked by specific signaling pathway inhibitors, including toll-like receptor 4 inhibitor (TLR 4i), rottlerin, PD98059, SB203580 and BAY-11-7085. Extracellular signal-regulated kinase (ER K) and p38 MAPK pathways were activated in a time-dependent manner following treatment with S100A8 and S100A9. Phosphorylation of ER K and p38 MAPK were blocked by TLR 4i and rottlerin. S100A8 and S100A9 induced translocation of NF-κB in a time-dependent manner, and the activation of NF-κB was inhibited by TLR 4i, rottlerin, PD98059 and SB203580. In addition, S100A8 and S100A9 decreased the expression of skin barrier proteins, filaggrin and loricrin. These results may help to elucidate the pathogenic mechanisms of AD and develop clinical strategies for controlling AD.

• Clinical and Experimental Pediatrics
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• v.62 no.12
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• pp.444-449
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• 2019

Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. Purpose: HIF-1α deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. Methods: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. Results: HIF-1α protein expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1 overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1 overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. Conclusion: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3431-3436
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• 2016

Background: Carcinogenesis is a multifaceted intricate cellular mechanism of transformation of the normal functions of a cell into neoplastic alterations. Metastasis may result in failure of conventional treatment and death Hence, research on metastatic suppressors in cancer is a high priority. The metastatic suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4 superfamily which was first identified in carcinoma of prostate. Little work has been done on this gene in breast cancer. Herein, we aimed to determine the gene and protein level expression of CD82/KAI1 in breast cancer and its role as a prognosticator. Materials and Methods: In this study, 83 histologically proven cases of breast cancer and a similar number of controls were included. Patient age ranged from 18-70 years. Quantitative Real Time Polymerase Chain Reaction (q-RT PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at gene and protein levels, respectively. Statistical analysis was done to correlate expression of KAI1 and clinicopathological parameters. Results: It was revealed that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast cancer both at the gene and the protein levels (P < .05); (ii) KAI1 expression levels were strongly correlated with TNM staging, histological grade and advanced stage (p<0.001) and no association was found with any other studied parameter; (iii) Lastly, a significant correlation was observed between expression of KAI1 and overall median survival of BC patients (P = 0.04). Conclusions: Our results suggest that lack of expression of the KAI1 might indicate a more aggressive form of breast cancer. Loss of KAI1 may be considered a significant prognostic marker in predicting metastatic manifestation. When evaluated along with the clinical and pathological factors, KAI1 expression may be beneficial to tailor aggressive therapeutic strategies for such patients.

• KIPS Transactions on Software and Data Engineering
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• v.8 no.10
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• pp.397-402
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• 2019

Accurately predicting cancer prognosis to provide appropriate treatment strategies for patients is one of the critical challenges in bioinformatics. Many researches have suggested machine learning models to predict patients' outcomes based on their gene expression data. Gene expression data is high-dimensional numerical data containing about 17,000 genes, so traditional researches used feature selection or dimensionality reduction approaches to elevate the performance of prognostic prediction models. These approaches, however, have an issue of making it difficult for the predictive models to grasp any biological interaction between the selected genes because feature selection and model training stages are performed independently. In this paper, we propose a novel two-dimensional image formatting approach for gene expression data to achieve feature selection and prognostic prediction effectively. Node2Vec is exploited to integrate biological interaction network and gene expression data and a convolutional neural network learns the integrated two-dimensional gene expression image data and predicts cancer prognosis. We evaluated our proposed model through double cross-validation and confirmed superior prognostic prediction accuracy to traditional machine learning models based on raw gene expression data. As our proposed approach is able to improve prediction models without loss of information caused by feature selection steps, we expect this will contribute to development of personalized medicine.

• Genomics & Informatics
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• v.10 no.2
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• pp.69-73
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• 2012

The explosive development of genomics technologies including microarrays and next generation sequencing (NGS) has provided comprehensive maps of cancer genomes, including the expression of mRNAs and microRNAs, DNA copy numbers, sequence variations, and epigenetic changes. These genome-wide profiles of the genetic aberrations could reveal the candidates for diagnostic and/or prognostic biomarkers as well as mechanistic insights into tumor development and progression. Recent efforts to establish the huge cancer genome compendium and integrative omics analyses, so-called "integromics", have extended our understanding on the cancer genome, showing its daunting complexity and heterogeneity. However, the challenges of the structured integration, sharing, and interpretation of the big omics data still remain to be resolved. Here, we review several issues raised in cancer omics data analysis, including NGS, focusing particularly on the study design and analysis strategies. This might be helpful to understand the current trends and strategies of the rapidly evolving cancer genomics research.

• The Journal of Information Technology
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• v.6 no.3
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• pp.45-51
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• 2003

The purposes of this study were to identify Avatar benefits and characteristics of Avatar users. Avatars are imaginary characters that people use to represent themselves in the Cyber. The number of Netizens who want to consume avatars is increasing. It is necessary to understand about the consumption behavior of the Netizens who use Avatars. These data comes from Pollever Research Company in Korea on Oct. 2003. The factor Analysis of the data resulted in five factors that contribute to Avatar Benefits: uniqueness, response, assurance, self-expression, proxy satisfaction and affirmative. And we have found out meaningful themes, showing psychological experiences, purchasing strategies and repurchasing behavior of Avatars in the process of the consumption. The results showed a significant affect on each factor of the benefits and multiful regression analysis. Affirmative response was affected by self-esteem, fashion leadership and conspicuous value. So many Netizens were using unlimited purchasing coupons, exchanging Avatars and buying-selling-buying. Strategies for obtaining involved purchasing Avatars in order to get game points. The reason why Hangame site was No.1 of Avatar site in Korea. We have found out that Netizens needed to repurchase Avatars. Because they wanted to maintain positive psychological experiences in Avatar consumption.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.17-24
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• 2014

Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.

• Molecules and Cells
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• v.40 no.6
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• pp.379-385
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• 2017

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.1-15
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• 2001

Gene therapy has emerged as a new concept of therapeutic strategies to treat diseases which do not respond to the conventional therapies. The principle of gene therapy is to Introduce genetic materials into patient cells to produce therapeutic proteins in these cells. Gene therapy is now at the stage where a number of clinical trials have been carried out to patients with gene-deficiency disease or cancer. Genetic materials for gene therapy are generally composed of gene expression system and gene delivery system. For the clinical application of gene therapy in a way which conventional drugs are used, researches have been focused on the design of gene delivery system which can offer high transfection efficiency with minimal toxicity. Currently, viral delivery systems generally provide higher transfection efficiency compared with non-viral delivery systems while non-viral delivery systems are less toxic, less immunogenic and manufacturable in large scale compared with viral systems. Recently, novel strategies towards the design of new non-viral delivery system, combination of viral and non-viral delivery systems and targeted delivery system have been extensively studied. The continued effort in this area will lead us to develop gene medicine as "gene as a drug" in the near future.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.1-15
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• 2010

Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.