• 대한소아치과학회지
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• 제27권2호
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• pp.300-308
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• 2000

Fibroblast growth factor(FGF)는 세포의 성장과 이동, 분화와 생존과 관련된 여러가지 과정을 조절하는 것으로 알려져 있다. 이들의 prototype인 FGF-1과 FGF-2는 FGF receptors (FGFRs)를 통해서 세포내로 신호를 전달하는데, 두개봉합부의 조기융합을 보이는 craniosynostosis는 FGFRs중, 특히 FGFR-2의 point mutation에 의해서 야기된다. 최근 여러 보고에서 FGF/FGFR 신호전달은 골아세포의 분화에 있어 필수적인 역할을 한다고 하였으며, bFGF soaked bead를 쥐 두개골의 시상봉합부의 mid-mesenchyme과 osteogenic front부위에 적용하였을 때 osteopontin(OPN) 유전자의 발현을 유도한다고 하였다. 이에 본 연구에서는 ST-2 cell line를 이용한 in vitro실험에서 bFGF가 OPN 유전자 발현에 미치는 영향과 그 기전을 Northern blot analysis를 통해서 연구하고자 하였다. 1 ng/ml bFGF의 투여는 OPN, fibronectin 유전자 발현을 증가시켰으며, type I collagen 유전자 발현은 감소시켰으나 alkaline phosphatase 유전자 발현에는 영향을 미치지 않았다. OPN은 그 발현양상이 bFGF의 농도 증가에 따라 증가하는 양상으로 나타났으며, 시간결과에 따른 발현양상도 bFGF 투여 3시간째부터 bFGF를 투여한 군에서 대조군에 비해 높게 나타났으며 이는 24시간까지 시간의 경과에 따라 증가하는 양상을 보였다. 단백질 합성 억제제인 cycloheximide를 처리한 군에서는 OPN의 증가 양상을 보이지 않았는데 이는 bFGF에 의한 OPN유전자 발현이 새로운 전사조절 단백질 합성 등의 여러 단계를 거쳐서 일어남을 의미한다. 결론적으로 bFGF는 새로운 전사조절 단백질의 합성을 통해서 OPN 유전자 발현을 농도 및 시간 의존적으로 증가시킨다.

• 대한소아치과학회지
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• 제35권3호
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• pp.539-547
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• 2008

Apert syndrome은 관상봉합의 조기유합에 의한 첨두증(acrocephaly)과 합지증(syndactyly)이 함께 나타나는 선천성 유전 질환으로서, 1906년 Apert에 의해 보고된 증후군이다. 약 $65,000{\sim}160,000$ 당 1명꼴로 발생되며, FGFR2(fibroblast growth factor receptor 2)의 돌연변이로 생겨난다고 알려져 있고, 상염색체 우성 유전을 한다. 임상적으로 첨단두증(acrobrachycephaly)을 보이고, 특징적으로 손과 발의 합지증을 보이며, 높은 이마와 평평한 뒤통수, 후퇴된 중안면부, 안구돌출, 시력이상, 양안격리증, 밑으로 쳐진 안검열, 상악골 형성부전, 상대적인 하악 전돌의 양상 등을 보인다. 감소된 비강인두와 좁아진 후비공으로 인한 구호흡과 전방부 개교를 보이며, 이완시에 입술의 모양은 사다리꼴 형태를 보인다. 중이염이 흔하고, 청각장애를 유발하기도 하며, 정신지체가 높은 비율로 나타난다. 특징적인 구내소견으로 연구개열 또는 구개수열과 가성 경구개열, V자 모양의 악궁과 치열의 총생 등이 관찰되며, 전치부 개방교합과 구치부 교차교합을 동반한 Class III 부정교합을 보인다. 본 증례는 강릉대학교 치과병원 소아치과에 내원한 6세 3개월의 남아로 충치 치료를 받고 싶다는 것을 주소로 내원하였다. 이 환자에서 보이는 Apert syndrome의 특징적인 치과적 소견에 대해 보고하는 바이다.

• Journal of Korean Neurosurgical Society
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• 제62권3호
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• pp.313-320
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• 2019

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.

• Asian-Australasian Journal of Animal Sciences
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• 제25권7호
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• pp.950-955
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• 2012

This study was conducted to determine how the isolation method of the porcine preantral follicles influenced the following follicular growth in vitro. Mechanical and enzymatical isolations were used for retrieving the follicles from prepubertal porcine ovaries, and in vitro-growth of the follicles and the expression of folliculogenesis-related genes were subsequently monitored. The enzymatic retrieval with collagenase treatment returned more follicles than the mechanical retrieval, while the percentage of morphologically normal follicles was higher with mechanical retrieval than with enzymatic retrieval. After 4 days of culture, mechanically retrieved, preantral follicles yielded more follicles with normal morphology than enzymatically retrieved follicles, which resulted in improved follicular growth. The mRNA expression of FSHR, LHR Cx43, DNMT1 and FGFR2 genes was significantly higher after culture of the follicles retrieved mechanically. These results suggest that mechanical isolation is a better method of isolating porcine preantral follicles that will develop into competent oocytes in in vitro culture.

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.45-51
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• 2008

Volatile Organic Compounds (VOCs) have been shown to cause nervous system disorders through skin contact or respiration, and also cause foul odors even at low densities in most cases. Also, as a compound itself, VOCs are directly harmful to the environment and to the human body, and may participate in photochemical reactions in air to create secondary pollutants. In this study, HL-60 cells were treated with volatile organic compounds, including ethylbenzene and trichloroethylene, at a value of $IC_50$. Then, the in house-prepared Human HazChem arrayer was utilized in order to compare the gene expression between the two VOCs. After hybridization, 8 upregulated genes and 8 downregulated genes were discovered in the HazChem array. The upregulated genes were identified as SG15, TNFSF10, PRNP, ME1, NCOA4, SRXN1, TXNRD1, and XBP1. The downregulated genes were identified as MME, NRF1, PRARBP, CALCA, CRP, BAX, C7 or f40, and FGFR1. Such results were highly correlated with the quantitative RT-PCR results. The majority of the 16 genes were related with the characteristics of VOCs, including respiratory mechanism, apoptosis, and carcinogenesis-associated genes. Our data showed that our human HazChem array can be used to monitor hazardous materials via gene expression profiling.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제29권2호
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• pp.62-72
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• 2018

Objectives: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. Methods: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. Results: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. Conclusion: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

• BMB Reports
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• 제45권5호
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• pp.287-292
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• 2012

FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti-apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-${\alpha}$. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells.

• 한국동물위생학회지
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• 제42권2호
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• pp.73-83
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• 2019

Foot-and-Mouth Disease (FMD) is a highly contagious trans-boundary viral disease caused by FMD virus, which causes huge economic losses. FMDV infects cloven hoofed (two-toed) mammals such as cattle, sheep, goats, pigs and various wildlife species. To control the FMDV, it is necessary to understand the life cycle and the pathogenesis of FMDV in host. Especially, the protein-protein interaction between FMDV and host will help to understand the survival cycle of viruses in host cell and establish new therapeutic strategies. However, the computational approach for protein-protein interaction between FMDV and pig hosts have not been applied to studies of the onset mechanism of FMDV. In the present work, we have performed the prediction of the pig's proteins which interact with FMDV based on RNA-Seq data, protein sequence, and structure information. After identifying the virus-host interaction, we looked for meaningful pathways and anticipated changes in the host caused by infection with FMDV. A total of 78 proteins of pig were predicted as interacting with FMDV. The 156 interactions include 94 interactions predicted by sequence-based method and the 62 interactions predicted by structure-based method using domain information. The protein interaction network contained integrin as well as STYK1, VTCN1, IDO1, CDH3, SLA-DQB1, FER, and FGFR2 which were related to the up-regulation of inflammation and the down-regulation of cell adhesion and host defense systems such as macrophage and leukocytes. These results provide clues to the knowledge and mechanism of how FMDV affects the host cell.

• Genomics & Informatics
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• 제19권4호
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• pp.38.1-38.7
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• 2021

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18 to 4.41; p = 0.0027-0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89 to 37.3; p = 0.0058- 0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.