• Radiation Oncology Journal
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• 제14권4호
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• pp.265-279
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• 1996

방사선은 DNA손상을 초래하고 세포 성장에 관련된 유전자의 발현 조절 및 apoptosis등을 유발한다고 알려져 있으며 본 연구는 신경계에 있어 방사선 조사 후 종양 발생율과 시간 경과의 관계 및 조사 양과 암 발생의 관계를 구명하기 위해 코발트 60의 전신조사에 따른 흰쥐 뇌 조직의 생체 반응을 연구하고자 하였다. 이를 위하여 상기조직의 jun 및 p53 유전자의 발현도를 1 Gy로 부터 100 Gy 범위의 감마선 용량별 및 1시간에서 6시간까지의 조사 훈 경과 시간 별로 Northern 분석하였다. Jun유전자 발현도는 ley이하에서 1시간 이내에 한계수준에 도달하였으며 30 Gy의 조사 1시간 째에 최대였다. 또한 조사 1시간 이후 1 Gy로부터 10 Gy 범위에서는 조사 5시간 및 6시간까지 점진적으로 증가되었으나 20 Gy로부터 100 Gy 범위에서는 조사 2시간까지 증가 후 감소되는 양상을 나타냈다. p53유전자의 발현도는 1 Gy이하에서 1시간 이내에 한계 수준에 근접했고 1 Gy의 조사 후 6시간 째에 최대였다. 1 Gy로부터 40 Gy까지의 범위에서는 조사 5시간 및 6시간까지 점진적으로 증가되는 반면 50 Gy에서 100 Gy범위에서는 조사 2시간 째까지 증가 후 감소되는 양상을 보였다. 따라서 감마선 조사양이 높을수록 jun 및 p53유전자는 신속하게 최대로 발현되었고 감마선 조사양이 낮을수록 서서히 증가되었다 그러나 jun유전자와 p53유전자의 감마선 조사에 따른 발현 양상에는 상호간의 연관성을 찾을 수 없었다.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.796-805
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• 1997

연구배경 : 세포주기의 활성화, 그 중에서도 특히 $G_1$/S 이행에 관여하는 세포주기관련 단백질들은 암발생에 있어서 매우 중요한 역할을 하는 것으로 알려져 있다. $G_1$ 세포주기 관련 단백질 중의 하나인 cdk4 (cyclin dependent kinase 4)의 억제제로 알려져 있는 p16 유전자는 최근에 밝혀진 종양억제유전자중의 하나로서 MTS1 (multiple tumor suppressor 1)이라고도 불린다. p16 유전자는 지금까지 알려진 어느 종양관련 유전자보다도 유전자변이의 빈도가 높은 암억제유전자인데, 특히 비소세포폐암인 경우는 70% 이상의 세포주에서 p16 단백질의 발현이 없는 것으로 밝혀져 있어 p16 유전자는 비소세포폐암 발생에 매우 중요한 역할을 할 것이라고 알려져 있다. 본 연구에서는 비소세포폐암에서 p16을 이용한 유전자치료의 타당성을 입증하기 위하여 다음과 같은 연구를 시행하였다. 방 법 : p16이 결여된 비소세포폐암 세포주 (NCI-H441)에, 정상섬유아세포에서 총 RNA를 추출하여 역전사효소 및 DNA 중합효소반응으로 증폭된 p16 cDNA를 유핵세포 발현 vector인 pRC-CMV plasmid에 subcloning하여 구축된 pRC-CMV-p16 plasmid vector를 lipofectin을 이용하여 유전자 이입한 후, 단백질을 추출하여 Western blot 분석과 면역침전법으로 $G_1$ 세포주기관련 단백질의 변동을 관찰하고, colony 형성능을 비교함으로써 암억제효과를 확인하였다. 결 과 : p16이 유전자주입된 NCI-H441 세포주에서 p16과 cdk4가 복합체를 형성하고 있고 인산화 Rb가 대조 세포주에 비해 감소되어 있음을 확인할 수 있어, p16이 cdk4와 결합함으로써 cdk4에 의한 Rb의 인산화를 방해하고 이에 따른 $G_1$ 세포주기 정체에 의해 종양억제효과가 나타난다는 설명을 뒷받침할 수 있었다. Clonogenic assay 결과는 p16 유전자주입된 NCI-H441 세포주의 colony 형성능이 대조 세포주에 비하여 현격히 감소함을 관찰하였다. 결 론 : 이상의 결과로 p16(MTS1) 유전자를 p16 단백질을 발현하지 못하는 비소세포폐암 세포주에 주입할 경우, 주입한 유전자에서 생성되는 p16 단백질이 cdk와 결합하여 Rb 단백질의 인산화를 저하시켜 궁극적으로 암억제 효과를 일으킬 수 있음이 확인되었고, 이는 향후 비소세포폐암의 유전자치료에 있어서 p16 유전자의 이용 가능성을 확인한 기초자료가 된다고 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2087-2092
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• 2015

Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

• 미생물학회지
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• 제40권2호
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• pp.121-126
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• 2004

4-chlorobiphenyl (4CB)의 분해균주인 Pseudomonas sp. strain DJ-12의 16S rDNA의 염기서열을 분석한 결과 Comamonas sp. strain DJ-12로 재분류 되었다. Pseudomonas sp. strain DJ-12로부터 4CB의 분해결과 생성되는 2,3-dihydroxybiphenyl을 계속 분해하는데 관여하는 pcbC1Dl 유전자를 이미 보고된 바 있다. 이번 연구에서는 Comamonas sp. strain DJ-12로부터 4CB 분해에 관여하는 pcbABC2D2 유전자를 클로닝하여 염기서열을 분석하였다. PcbAB 및 pcbCD 유전자들의 염기서열은 48, 65％, 추정 아미노산 서열은 33, 42％의 낮은 유사도를 보였다. 본 연구에서 얻어진 pcbC2D2 유전자는 이미 보고만 pcbCIDl 유전자와 염기의 개수와 서열의 유사도가 서로 다름을 보여 주었다. Comamonas sp. strain DJ-12의 두 가지 pcbCD유전자들은 Southern hybridization 결과에서도 유사성을 보이지 않았으며, 서로 다른 위치에 존재함을 보여주었다. 그러나 2,3-dihydroxybiphenyl의 분해 특성은 동일하였다. 이와 같은 결과는 Comamonas sp. strain DJ-12 균주가 2조의 pcbCD 유전자를 가지고 있다는 것을 의미하는 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5303-5306
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• 2012

Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. Methods: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR-restriction fragment-length polymorphism (PCR-RFLP). Results: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57). Conclusion: Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.

• 대한의생명과학회지
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• 제19권3호
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• pp.239-244
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• 2013

Serum liver enzyme levels are widely used in the clinical diagnosis of liver diseases and the assessment of liver status. They also have epidemiological significance to be prospective risk factors for type 2 diabetes, cardiovascular disease. In the previous study, single nucleotide polymorphisms (SNPs) in several genes have been reported to be associated with serum liver enzyme levels in American population. We aimed to confirm whether the genetic variation of C16orf47 (chromosome 16 open reading frame 47) gene also influence the serum liver enzyme levels in Korean population. We genotyped variants in or near C16orf47 in a population-based sample including 994 unrelated Korean adult. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in C16orf47 gene with serum liver enzyme levels. By examining genotype data of a total of 944 subjects in 5 hospital health promotion center, we discovered the C16orf47 gene polymorphisms are associated with serum liver enzyme levels. The common and highest significant polymorphism was rs7203412 (${\beta}$=3.68, P=3.66E-06) with glutamic oxaloacetic transferase (GOT) and rs7203412 (${\beta}$=6.2, P=7.06E-05) with glutamic pyruvate transaminase (GPT) in all group. Furthermore, the SNP rs7203412 was consistently associated with GOT (${\beta}$=6.41, P=6.78E-08) and GPT (${\beta}$=11.53, P=2.81E-06) in men group. Consequently, we found statistically significant SNP in C16orf47 gene that are associated with serum levels of GOT and GPT. In addition, these results suggest that the individuals with the minor alleles of the SNP in the C16orf47 gene may be more elevated serum liver enzyme levels in the Korean population.

• Journal of Microbiology and Biotechnology
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• 제16권1호
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• pp.118-125
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• 2006

The region responsible for replication of the megaplasmid pAtC58 in the nopaline-type Agrobacterium tumefaciens strain C58 was determined. A derivative ofa Co1E1 vector, pBluscript SK-, incapable of autonomous replication in Agrobacterium spp, was cloned with a 7.6-kb Bg1II-HindIII fragment from a cosmid clone of pAtC58, which contains a region adjacent to the operon for the utilization of deoxyfructosyl glutamine (DFG). The resulting plasmid conferred resistance to carbenicillin on the A. tumefaciens strain UIA5 that is a plasmidfree derivative of C58. The plasmid was stably maintained in the strain even after consecutive cultures for generations. Analysis of nested deletions of the 7.6-kb fragment showed that a 4.3-kb BglII-XhoI region sufficiently confers replication of the derivative of the ColE1 vector on UIA5. The region comprises three ORFs, which have high homologies with repA, repB, and repC of plasm ids in virulent Agrobacterium spp. including pTiC58, pTiB6S3, pTi-SAKURA, and pRiA4b as well as those of symbiotic plasmids from Rhizobium spp. Phylogenie analysis showed that rep genes in pAtC58 are more closely related to those in pRiA4 than to pTi plasmids including pTiC58, suggesting that the two inborn plasmids, pTiC58 and pAtC58, harbored in C58 evolved from distinct origins.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.431-436
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• 2008

To identify genes whose expression correlated with biological features of therapy-related AML (t-AML), we analyzed the expression profiles of de novo AML t(9;11) and t-AML t(9;11) bone marrow samples using previously published SAGE data. Three-hundred twenty-nine transcripts that satisfied statistical (P<0.05) and magnitude-of-change ($\geq$ 4-fold) criteria were identified as differentially expressed between de novo AML t(9;11) and t-AML t(9;11) cells. Of these transcripts, 301 (91%) matched known genes or ESTs and were classified according to functional categories (http://david.abcc.ncifcrf.gov/). The majority of differentially expressed genes in t-AML t(9;11) were involved in the regulation of biological and metabolic processes. Especially prominent among these were genes related to immune and drug responses. These results establish a framework for developing new drugs for the treatment of t-AML.

• Animal Bioscience
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• 제34권9호
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• pp.1569-1578
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• 2021

Objective: This study was conducted to investigate the potential effects of prolonged photoperiod on the serum lipids, carcass traits, and meat quality of Jinjiang cattle during winter. Methods: Thirty-four Jinjiang bulls aged between 14 and 16 months were randomly assigned to two groups that were alternatively subjected to either natural daylight +4 h supplemental light (long photoperiod, LP) or natural daylight (natural photoperiod, NP) for 96 days. The potential effects on the levels of serum lipids, carcass traits, meat quality, and genes regulating lipid metabolism in the intramuscular fat (IMF) of the cattle were evaluated. Results: Jinjiang cattle kept under LP showed significant increase in both dry matter intake and backfat thickness. the serum glucose and the plasma leptin levels were significantly reduced, while that of melatonin and insulin were observed to be increased. The crude fat contents of biceps femoris muscle and longissimus dorsi muscle were higher in LP than in NP group. In longissimus dorsi muscle, the proportions of C17:0 and C18:0 were significantly higher but that of the C16:1 was found to be significantly lower in LP group. The relative mRNA expressions in IMF of longissimus dorsi muscle, the lipid synthesis genes (proliferator-activated receptor gamma, fatty acid-binding protein) and the fatty acid synthesis genes (acetyl-coa carboxylase, fatty acid synthetase, 1-acylglycerol-3-phosphate acyltransferase) were significantly up-regulated in LP group (p<0.05); whereas the hormone-sensitive lipase and stearoyl-CoA desaturase 1 were significantly down-regulated in LP than in NP group. Conclusion: Prolonged photoperiod significantly altered the growth performance, hormonal levels, gene expression and fat deposition in Jinjiang cattle. It suggested that the LP improved the fat deposition by regulating the levels of different hormones and genes related to lipid metabolism, thereby improving the fattening of Jinjiang cattle during winter.