• IMMUNE NETWORK
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• 제7권3호
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• pp.141-148
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• 2007

Background: Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis. Methods: Active systemic anaphylaxis was induced by either penicillin V(Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse Fc ${\gamma}$ RIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry. Results: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in Fc ${\gamma}$ RIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine Fc ${\gamma}$ RIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of Fc ${\gamma}$ RIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). Conclusion: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, Fc ${\gamma}$ RIIb, rather than targeting IgE.

• Journal of Cancer Prevention
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• 제22권4호
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• pp.234-240
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• 2017

Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs. Bioinformatic analysis was performed using various tools. Results: Alterations in several genes were implicated in lung cancer resulting from exposure to radon indoors, namely those in epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox 1 (NKX2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1), and dual specificity phosphatase 27 (putative) (DUSP27). Conclusions: While these genes might regulate the carcinogenic pathways of radioactivity, further analysis is needed to determine whether the genes are indeed completely responsible for causing lung cancer in never smokers exposed to residential radon.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6871-6876
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• 2015

Background: The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis. Materials and Methods: We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6. Results: Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG. Conclusions: MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker.

• 생명과학회지
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• 제30권5호
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• pp.460-467
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• 2020

간암은 전 세계적으로 가장 높게 진단되는 암 중 하나이며, 방사선 및 화학 요법이 일반적으로 사용되는 치료법이지만 다양한 부작용은 치료 효과를 크게 제한한다. 따라서 전통 의학에서 사용되어 온 처방법은 이를 극복할 수 있는 대안이 될 수 있다. 본 연구에서는 동의보감에 기술되어 있는 3가지 한약 처방전(비기환, 대칠기탕 및 목향빈랑환)을 선택하여 인체 간암세포에 대한 항암 효과를 평가하였다. 간암세포에서 3가지 처방전의 에탄올 추출물의 세포 독성을 조사하기 위한 MTT 분석 결과, 비기환 추출물은 대칠기탕 및 목향빈랑환에 비하여 세포 생존력을 현저하게 억제하였다. 그리고, flow cytometry 분석의 결과에서 3가지 처방전 추출물에 의한 간암세포의 증식 억제가 apoptosis 및 autophagy 유도와 관련이 있었다. 특히, 비기환 추출물은 미토콘드리아의 기능을 크게 손상시켰으며 다른 두 처방전과 비교하여 mitophagy 유발 가능성을 보여주었다. 아울러 비기환 추출물은 LC3의 발현을 현저하게 증가시켰으며, 이는 Bcl-2의 발현 감소를 동반하는 반면, Bax의 발현에 영향을 미치지 않았다. PINK1의 발현 또한 비기환 추출물이 처리된 세포에서 매우 증가하였다. 나아가, autophagy 억제제는 3가지 처방전 추출물 처리에 의한 세포 생존율 감소와 apoptosis 유도를 억제하였으며, 이러한 결과는 이들 처방전 추출물 처리에 의한 autophagy가 apoptosis 개시에 관여하고 있음을 보여주는 것이다. 결론적으로, 본 연구 결과는 비기환 추출물이 3가지 처방전 중에서 가장 높은 항암 활성을 보였으며, 비기환 추출물은 autophagy 유도제로서 간암세포의 증식을 억제함을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7645-7652
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• 2014

Neuroblastoma (NB), the most common extracranial solid tumor, accounts for 10% of childhood cancer. To date, scientists have gained quite a lot of knowledge about microRNAs (miRNAs) and their genes in NB. Discovering inner regulation networks, however, still presents problems. Our study was focused on determining differentially-expressed miRNAs, their target genes and transcription factors (TFs) which exert profound influence on the pathogenesis of NB. Here we constructed three regulatory networks: differentially-expressed, related and global. We compared and analyzed the differences between the three networks to distinguish key pathways and significant nodes. Certain pathways demonstrated specific features. The differentially-expressed network consists of already identified differentially-expressed genes, miRNAs and their host genes. With this network, we can clearly see how pathways of differentially expressed genes, differentially expressed miRNAs and TFs affect on the progression of NB. MYCN, for example, which is a mutated gene of NB, is targeted by hsa-miR-29a and hsa-miR-34a, and regulates another eight differentially-expressed miRNAs that target genes VEGFA, BCL2, REL2 and so on. Further related genes and miRNAs were obtained to construct the related network and it was observed that a miRNA and its target gene exhibit special features. Hsa-miR-34a, for example, targets gene MYC, which regulates hsa-miR-34a in turn. This forms a self-adaption association. TFs like MYC and PTEN having six types of adjacent nodes and other classes of TFs investigated really can help to demonstrate that TFs affect pathways through expressions of significant miRNAs involved in the pathogenesis of NB. The present study providing comprehensive data partially reveals the mechanism of NB and should facilitate future studies to gain more significant and related data results for NB.

• 한국작물학회지
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• 제51권5호
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• pp.466-476
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• 2006

한국과 캐나다의 젊은 소비계층인 대학생들을 중심으로 콩에 대한 일반적 인지도, 콩가공식품에 대한 구매 및 소비행태, 수응도 등을 설문문항을 통하여 비교해 보았고, 콩가공식품의 소비시 지적되는 문제점을 알아보았다. 한국 대학생들이 캐나다 대학생들에 비해 콩식품에 대하여 더욱 긍정적인 생각과 올바른 지식을 가지고 있었고, 콩식품에 대한 정보를 얻는 방법으로는 한국 대학생들의 경우 주로 상업적 매체를 통하는 것으로 나타났던 반면, 캐나다 대학생들의 경우는 주로 가족이나 친구 등 인맥을 통하는 비율이 높게 나타났다. 소비행태에 있어서는, 한국의 경우 조사대상자 전체가 구매경험이 있는 것으로 조사되었으나 캐나다의 경우는 조사대상자의 55.4%만이 콩가공식품 구매경험이 있었으며, 친숙하게 느껴지는 콩가공식품, 구매경험이 있는 콩가공식품 그리고 구매빈도가 높은 콩가공식품 등에 대해서는 한국과 캐나다 모두 매우 유사한 경향을 보였는데 두유에 대한 인지도가 가장 높았으며 소비량도 많은 것으로 나타났고 다음으로 콩음료, 마가린 등의 순서로 나타났다. 본 연구결과, 콩가공식품을 포함한 콩식품은 단순한 동양의 전통식품만이 아니라 동서양의 식생활에 일반적인 식품으로 자리매김하고 있는 것으로 나타났다. 단지 콩 유입의 역사가 짧고 낙농업 위주의 식생활이 주를 이루고있는 캐나다에서는 콩식품에 대한 관심이 한국보다 적어 소비경험이 전혀 없는 대학생들이 많았고(44.6%)우유식품을 선호하는 학생들이 많았다. 반면, 한국의 경우는 다양한 콩 가공식품이 일반화되지 않아 두유나 콩음료 등 특정 콩가공식품에 대한 소비율만 높은 것으로 나타났다. 그러나 앞으로 캐나다의 콩가공식품의 소비는 더욱 늘어날 것으로 전망되며, 우리나라 또한 젊은 소비자들의 콩식품 소비 활성화를 위하여 다양한 기호와 욕구를 충족시킬 수 있는 제품개발이 지속적으로 이루어진다면 전통적인 콩식품 및 콩가공식품 소비는 더욱 늘어날 것으로 전망되어 진다.능력이 있었다. 그러므로 $(PPAR{\gamma})$의 활성에 있어 RXR heterodimer가 사람의 백혈병세포에 대한 조절 경로로서 존재하며, PTEN의 upregulation을 통해 백혈병을 조절하기 때문에 백혈병의 예방 및 치료 접근에 $(PPAR{\gamma})$와 RXR ligands가 중요한 역할을 할 것이다.제안 객체 모델에서는 객체의 상태에 따라 사용 가능한 행위가 결정되는 가상 환경을 위해 새로운 인터페이스로 컨텍스트 메뉴(context menu) 인터페이스와 동작 생성 모델을 제시한다. 정의하였다. 객체 모델에서 객체의 상태 정보와 행위 정보를 분석해 아바타가 할 수 있는 행위를 컨텍스트 메뉴로 제공하기 때문에 사용자는 가상 환경의 상태에 상관 없이 직관적으로 명령을 줄 수 있다. 또한 사용자는 기존의 2D 혹은 텍스트기반 스크립트 작성기법을 벗어나 사용자는 제안된 3D 인터페이스 기법을 통하여 실시간으로 아바타의 행위 스크립트를 작성 및 재생 할 수 있다. 본 논문에서 제시한 시스템은 기존의 아바타 중심적인 제어를 객체에 분산함으로써 효율적이고 직관적인 명령을 내릴 수 있고 또한 손쉬운 시나리오 생성을 가능하게 하였다. 본 연구에서는 제안 기법의 활용을 위해 프리젠테이션 도메인 환경의 시스템을 구축하고 아바타-객체 행위제어 및 스크립트 생성 기법을 적용하였다.S는 스크립트 언어를 사용하는 전문가 시스템[7]으로 선언적 룰(Declarative Rule)을 이용하여 지식을 표현 하고 추론을 수행하는 추론 엔진의 한 종류이다. JESS의 지식 표현 방식은 튜닝 원칙을 쉽게 표현하고 수용할 수 있는 구조를 가지고 있으며 작은 크기와 빠른 추론 성능을 가지기 때문에 실시간으로 처리 되는 어플리케이션 튜닝에 적합하다. 지식 기반 모률의 가장 큰 역할은 주어진 데이터베이스 시스템의 모델을 통하여 필요한 새로운 지식을 생성하고 저장하는 것이다.