• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.776-784
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• 1998

연구목적: 폐암은 생불학적 및 병리학적인 특성에 따라 비소세포폐암과 소세포폐암으로 구분되는데 전체폐암의 약 80%가 비소세포폐암으로 국소적인 폐암인 경우 수술적 치료가 절대적 완치 방법인데 조기에 발견하여 광범위한 절제로 치료된 경우에도 환자의 약 50% 정도만이 5년간 생존한다. 확실히 비소세포폐암에서 비슷한 병기의 환자들도 생존 가망성은 상당한 차이를 보인다. 이러한 상황이 보다 정확히 생존 가망성을 예측하고 각각의 환자에게 보다 효율적인 치료를 제공할 수 있게 도울 수 있는 새로운 예측 인자를 밝혀야 하는 필요성이 제기되었다. 정상적인 세포주기 뿐만 아니라 암종의 세포주기에 중요한 역할을 하는 cyclin D계중 하나인 cyclin D1이 세포주기에서 G1기에서 S기로의 전환을 유도하므로써 세포주기를 진행시키는데 유방암, 식도암 및 방광암에서 이의 과발현이 암발생에 중요한 요인이 되다는 보고가 있다. 이에 본 연구에서는 광범위 절제된 비소세포폐암에서 cyclin D1의 과발현이 예후에 미치는 영향을 알아보기 위해 연구를 시행하였다. 방 법: 1983년 1월부터 1995년 7월까지 한양대학교 부속병원에서 비소세포폐암으로 진단된 술전 병기 IIIa 이하인 환자 총 81예를 대상으로 치료적 목적으로 광범위 폐절제술을 통해 얻어진 술후 조직에서 cyclin D1에 대한 단클론성 향체를 사용하여 면역조직화화적 염색을 시행하고 더불어 병리조직학적 특정과 임상적 특정, 특히 생존률과의 연관성을 알아보았다. 또한 술후 환자의 예후적 인자를 최소한으로 줄이기 위해 술전에 방사선 치료나 항암제 치료를 받은 환자는 제외하였고 혼합형의 조직학적 진단이 이루어진 경우와 술후 l달 이내에 사망한 경우는 본 연구의 대상에서 제외하였다. 조직병리학적 병기 판정은 TNM 병기 판정 기준에 맞추었고 조직학적 특징은 WHO 표준 기준에 맞추었다. 결 과: Cyclin D1의 발현은 총 81예에서 시행하여 26에에서 발현되어 30.9%의 발현율을 보였고 각각의 조직형이나 병기, 암의 크기에는 통계적 차이를 보이지 않았으나 TNM 병기 판정에 따라 NO와 나머지 N1-3의 두군으로 나누어 비교할 때 cyclin D1에 따른 통계적 의의를 보였고(p=0.035) cyclin D1 양성 발현군의 평균생존기간은 $22.76{\pm}3.507$개월, 음성 발현군의 평균생존기간이 $45.3{\pm}5.64$개월 (p=0.0515)로 생존율과외 상당한 통계적인 연관성의 가능성을 나타내었다. 결 론: 본 연구에서는 여러 가지 세포주기를 직, 간접으로 조절하는 인자중 cyclin D1의 과발현은 비소세포폐암에서 상당히 불량한 예후 인자로 작용할 수 있다고 생각되며 앞으로 보다 초기와 진행된 병기에 따른 cyclin D1의 발현이 예후에 미치는 영향 등 보다 세밀하고 대단위적인 연구가 진행되어 비소세포폐암에서 보다 정확한 치료와 예후를 예측활 수 있는 인자로서의 역할을 밝혀야 한다고 생각된다.

• 생명과학회지
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• 제15권3호
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• pp.397-405
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• 2005

브로콜리와 같은 십자화과 식물에서 glucoraphanin의 가수분해를 통해 생성되는 isothiocyanate의 일종인 sulforaphane은 강력한 항암효과를 가지며, 역학적 조사를 포함한 다양한 선행 연구에서 androgen 비 의존적으로 성장하는 전립선 암세포의 증식을 억제하는데 효과가 있었다. 최근 연구 결과에 따르면 sulforaphane은 다양한 인체암세포의 증식을 억제하고 apoptosis를 유발할 수 있는 것으로 알려지고 있으나, 정확한 분자생물학적 기전은 밝혀져 있지 않은 상태이다. 본 연구에서는 sulforaphane의 항암작용 기전을 조사하기 위하여 HeLa 인체자궁경부암세포의 증식에 미치는 sulforaphane의 영향을 조사하였다. Sulforaphane의 처리에 의한 HeLa 세포의 증식억제 및 형태적 변형은 세포주기 C2/M arrest 및 apoptosis 유발과 밀접한 관련이 있음을 알 수 있었다. RT-PCR 및 Western blot 분석 결과, sulforaphane 처리에 의하여 cyclin A 및 cyclin-dependent kinase (Cdk)4 단백질의 발현이 선택적으로 저하되었으며, Cdc2, Cdk inhibitor인 p16 및 p21의 발현은 증가되었다 그러나 sulforaphane은 cyclooxygenases의 발현이나 telomere 조절에 중요한 역할을 하는 인자들의 발현에는 큰 영향을 주지 못하였다. Sulforaphane의 항암 기전을 규명하기 위해서는 더 많은 연구가 부가적으로 필요하겠지만, 본 연구의 결과들에 의하면 sulforaphane은 강력한 인체암세포의 증식 억제 및 항암작용이 있을 것을 시사하여 준다고 할 수 있다.

• 환경생물
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• 제40권4호
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• pp.398-404
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• 2022

본 연구는 플라스틱 가소제인 DEHP가 식물 병원균 중 하나인 P. carotovorum SCC1 균주에 미치는 영향을 조사하였다. DEHP가 균주 생장과 대사에 미치는 영향을 조사한 결과, 개체군 변화에 유의한 영향을 주지 않았으며, 세포막 투과성, ATPase 활성에 유의한 변화가 없었지만 TCA cycle 에서 DEHP 첨가에 따라 Succinyl-CoA synthase 활성이 유의적으로 감소하였다. 병원성 관련 유전자 발현량을 관찰한 결과 pectate lyase 유전자 발현량이 상대적으로 증가한 반면, pectinase 유전자는 상대적으로 발현량이 감소하였다. 따라서 DEHP는 P. carotovorum SCC1의 개체군 변화나 대사에는 유의미한 영향을 미치지 않지만 병원성 관련 유전자 발현에 영향을 미치므로 본 연구 결과는 향후 실제 식물 재배 조건에서 DEHP가 존재할 때 P. carotovorum의 특성에 관한 기초연구 자료로 활용할 수 있을 것이라 사료된다.

• Nutrition Research and Practice
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• 제13권1호
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• pp.58-63
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• 2019

BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS AND METHODS: $CD133^+CD44^+$ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and $40{\mu}g/mL$ for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA ($ddC_t$). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA ($dC_t$). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner ($5.16{\pm}0.13$ at $0{\mu}g/mL$, $4.79{\pm}0.12$ at $10{\mu}g/mL$, $3.24{\pm}0.08$ at $20{\mu}g/mL$ and $3.99{\pm}0.09$ at $40{\mu}g/mL$; P = 0.0276). Telomerase activities concurrently decreased with telomere length ($1.47{\pm}0.04$, $1.09{\pm}0.01$, $0.76{\pm}0.08$, and $0.88{\pm}0.06$; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSION: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

• Journal of Veterinary Science
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• 제23권6호
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• pp.90.01-90.13
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• 2022

Background: Insulin regulates glucose homeostasis and has important effects on metabolism, cell growth, and differentiation. Depending on the cell type and physiological context, insulin signal has specific pathways and biological outcomes in different tissues and cells. For studying the signal pathway of insulin on glycolipid metabolism in porcine embryonic fibroblast (PEF), we used high-throughput sequencing to monitor gene expression patterns regulated by insulin. Objectives: The goal of our research was to see how insulin affected glucose and lipid metabolism in PEFs. Methods: We cultured the PEFs with the addition of insulin and sampled them at 0, 48, and 72 h for RNA-Seq analysis in triplicate for each time point. Results: At 48 and 72 h, 801 and 1,176 genes were differentially expressed, respectively. Of these, 272 up-regulated genes and 264 down-regulated genes were common to both time points. Gene Ontology analysis was used to annotate the functions of the differentially expressed genes (DEGs), the biological processes related to lipid metabolism and cell cycle were dominant. And the DEGs were significantly enriched in interleukin-17 signaling pathway, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, pyruvate metabolism, and others pathways related to lipid metabolism by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Conclusions: These results elucidate the transcriptomic response to insulin in PEF. The genes and pathways involved in the transcriptome mechanisms provide useful information for further research into the complicated molecular processes of insulin in PEF.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.347-350
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• 2012

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

• Asian-Australasian Journal of Animal Sciences
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• 제30권8호
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• pp.1066-1073
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• 2017

Objective: Growth-related traits are important economic traits in the swine industry. However, the genetic mechanism of growth-related traits is little known. The aim of this study was to screen the candidate genes and molecular markers associated with body dimension and body weight traits in pigs. Methods: A genome-wide association study (GWAS) on body dimension and body weight traits was performed in a White $Duroc{\times}Erhualian$ $F_2$ intercross by the illumina PorcineSNP60K Beadchip. A mixed linear model was used to assess the association between single nucleotide polymorphisms (SNPs) and the phenotypes. Results: In total, 611 and 79 SNPs were identified significantly associated with body dimension traits and body weight respectively. All SNPs but 62 were located into 23 genomic regions (quantitative trait loci, QTLs) on 14 autosomal and X chromosomes in Sus scrofa Build 10.2 assembly. Out of the 23 QTLs with the suggestive significance level ($5{\times}10^{-4}$), three QTLs exceeded the genome-wide significance threshold ($1.15{\times}10^{-6}$). Except the one on Sus scrofa chromosome (SSC) 7 which was reported previously all the QTLs are novel. In addition, we identified 5 promising candidate genes, including cell division cycle 7 for abdominal circumference, pleiomorphic adenoma gene 1 and neuropeptides B/W receptor 1 for both body weight and cannon bone circumference on SSC4, phosphoenolpyruvate carboxykinase 1, and bone morphogenetic protein 7 for hip circumference on SSC17. Conclusion: The results have not only demonstrated a number of potential genes/loci associated with the growth-related traits in pigs, but also laid a foundation for studying the genes' role and further identifying causative variants underlying these loci.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.178-178
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• 1994

Hepatitis B Virus (HBV) is a DNA virus with a 3.2kb partially double-stranded genome. The life cycle of the virus involves a reverse transcription of the greater than genome length 3.5kb mRNA. This pegenomic RNA contains all the genetic information encoded by the virus and functions as an intermediate in viral replication. Tumor suppressor p53 has previously been shown to interact with the X-gene product of the HBV, which led us to hypothesize that p53 may act as a negative regulator of HBV replication and the role of the X-gene product is to overcome the p53-mediated restriction. As a first step to prove the above hypothesis, we tested whether p53 represses the propagation of HBV in in vitro replication system. By transient cotransfection of the plasmid containing a complete copy of the HBV genome and/or the plasmid encoding p53, we found that the replication of HBV is specifically blocked by wild-type p53. The levels of HBV DNA, HBs Ag and HBc/e Ag secreted in cell culture media were dramatically reduced upon coexpresion of wild-type p53 but not by the coexpression of the mutants of p53 (G154V and R273L). Furthermore, levels of RNAs originated from HBV genome were repressed more than 10 fold by the cotransfection of the p53 encoding plasmid. These results clearly states that p53 is a nesative regulator of the HBV replication. Next, to addresss the mechanism by which p53 represses the HBV replication, we performed the transient transfection experiments employing the pregenomic/core promoter-CAT(Chloramphenicol Acetyl Transferase) construct as a reporter. Cotransfection of wild-type p53 but not the mutant p53 expression plasmids repressed the CAT activity more than 8 fold. Integrating the above results, we propose that p53 represses the replication of HBV specifically by the down-regulation of the pregenomic/core promoter, which results in the reduced DNA synthesis of HBV. Currently, the mechanism by which HBV overcomes the observed p53-mediated restriction of replication is tinder investigation.

• Molecules and Cells
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• 제28권6호
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• pp.565-573
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• 2009

The pig could be a useful model to characterize molecular aspects determining several delicate phenotypes because they have been bred for those characteristics. The Korean native pig (KNP) is a regional breed in Korea that was characterized by relatively high intramuscular fat content and reddish meat color compared to other western breeds such as Yorkshire (YS). YS grew faster and contained more lean muscle than KNP. We compared the KNP to Yorksire to find molecular clues determining muscle characteristics. The comparison of skeletal gene expression profiles between these two breeds showed molecular differences in muscle. We found 82 differentially expressed genes (DEGs) defined by fold change (more than 1.5 fold difference) and statistical significance (within 5% of false discovery rate). Functional analyses of these DEGs indicated up-regulation of most genes involved in cell cycle arrest, down-regulation of most genes involved in cellular differentiation and its inhibition, down-regulation of most genes encoding component of muscular-structural system, and up-regulation of most genes involved in diverse metabolism in KNP. Especially, DEGs in above-mentioned categories included a large number of genes encoding proteins directly or indirectly involved in p53 pathway. Our results indicated a possible role of p53 to determine muscle characteristics between these two breeds.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7181-7185
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• 2014

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotyping was determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects ($45{\leq}$ years old) and female, in the Turkish population.