• Journal of Photoscience
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• 제9권2호
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• pp.329-331
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• 2002

There is a difference in the inhibitory effects to supplemental UVB (wavelengths 280 to 320 nm) among Japanese rice (Oryza sativa L.), the cultivar Norin I is less resistant while the cultivar Sasanishiki is resistant. UVB induces photodamage in DNA. Cyclobutane pyrimidine dimer (CPD) is a major UV-induced DNA lesion. Photorepair, which is mediated by photolyase, is the major pathway in plants for repairing CPD. We have analyzed CPD induction and repair in Sasanishiki and its close relative Norin I using alkaline agarose gel electrophoresis. Norin I is deficient in CPD photoreactivation and excision, thus UV sensitivity correlates with deficient dimer repair [I]. The photorepair deficiency in Norin I results from a functionally altered photolyase with a photoflash analysis [2]. In this paper, we examined the UVB-sensitivity of several other UV-sensitive and -resistant cultivars and found that the CPD photolyase activity was deficient in UV-sensitive ones. It was also evident that there was a variation in the deduced amino acid sequences of CPD photolyases of the UV-sensitive and -resistant cultivars, whereas each deduced amino acid sequence of the UV-sensitive cultivars and of the UV-resistant ones was the same. These results suggest that the difference in the CPD photolyases of UV-sensitive and -resistant rice might be due to the structural alteration of CPD photolyase.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4095-4099
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• 2014

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1321-1324
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• 2012

Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5311-5317
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• 2015

Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.

• 대한화장품학회지
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• 제24권1호
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• pp.87-99
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• 1998

알킬화제인 MMS에 의한 유전독성의 감소에 미치는 홍삼추출물의 영향을 배양 NIH3T3 세포계에서 분석하였다. 1mM의 MMS를 30분간 처리한 후 정상 배지에서 배양한 시간간격에 따라 세포의 생존률은 증가하였는데 홍삼추출물이 함유된 배지에서 배양한 경우는 약 17%정도 증가한 생존률을 보였다. MMS 처리 후 감소된 DNA 복제가 정상배지 배양시간에 따라 증가하는 정도도 홍삼추출물을 후처리할 경우 현저한 증가를 보였다. MMS 상해를 회복하기 위한 절제회복능은 홍삼추출물을 처리할 경우 유의미한 증가를 보였다. 이러한 절제회복과정 중 효소에 의한 절제단계가 홍삼추출물 처리에 의해 활성화됨을 단사절단 분석을 통하여 규명하였다. 자외선 상해의 경우와 비해서 MMS 상해의 절제단계를 활성화하는 홍삼의 효과는 약간 떨어지는 것으로 보이나, MMS 상해회복의 전과정에 대한 홍삼의 효과는 자외선의 경우와 유사하였으며, MMS 상해에 의한 DNA 복제억제의 완화나 세포생존률은 자외선의 그것들보다 홍삼에 의해 더 증가된 측면을 보였다. 이상의 결과는 홍삼추출물이 MMS 상해의 절제회복에 유의미한 증가를 보이며 따라서 유전독성을 감소시키는 항노화제로써 사용할 수 있음을 시사한다.

• Journal of Trauma and Injury
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• 제21권2호
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• pp.128-135
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• 2008

Purpose: As the care of surgical patients becomes increasingly complex and catheter-based techniques are more frequently applied, the pattern of iatrogenic vascular injuries may be increasing. Major vascular injuries can jeopardize a patient's life or limb survival. The purpose of this study was to examine the current etiology and prognosis for iatrogenic vascular injuries. Methods: We reviewed medical records of 29 cases of iatrogenic vascular injury that were treated Seoul National University Bundang Hospital between October 2003 and October 2008. We studied clinical variables including demographics, cause of injury, clinical presentations, management and prognosis. Results: The mean age was 60.8 years (range: 25-86), and the male to female ratio was 1.9 : 1. The causes of injuries were operation related complication in 18 cases (62.1%), endovascular intervention and diagnostic angiography in 11 cases (37.9%). The types of vascular injury were partial severance in 14 cases, pseudoaneurysm in 8, arteriovenous fistula (AVF) in 3, thrombosis in 2, complete severance in 2. Especially, device related complication including percutaneous closing device were occurred in 9 and the others came from inadvertent physician's procedure. Primary repair were done in 12 cases, end-to-end anastomosis in 5, interposition graft in 4, ligation in 2, patch angioplasty in 1, peudoaneurysm excision and arteriorrhaphy in 1, hematoma evacuation in 1, and endovascular repair in 3. There were 2 cases of mortality, one of them due to hemorrhagic shock and the other due to septic shock. Conclusion: Proper selection of treatment modalities should be important to have better outcome according to the type of injury as well as anatomical location. Each physician should be familiar to new device as well as patient's topographical feature. Immediate referral to vascular specialist is also essential to reduce morbidity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5619-5625
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• 2012

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

• Genomics & Informatics
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• 제15권4호
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• pp.147-155
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• 2017

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

• 한국식품영양과학회지
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• 제25권2호
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• pp.232-239
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• 1996

돌연변이 유발 물질인 mitomycin C(MMC)를 처리하여 배양한 Chinese hamster ovary(CHO) cell에 대한 감잎차 추출액의 항돌연변이 효과를 자매 염색 분체 교환(sister chromatid exchange, SCE) 시험법을 사용하여 측정하여 보았다. 감잎차 추출액 자체는 CHO 세포의 SCE 빈도수를 변화시키지 않았으며, 세포의 분열 주기중 S phase에 S9 mixture 없이 감잎차 추출액이 처리되었을 경우 MMC로 유도된 SCE 빈도수를 감소시키지 않았다. 그러나 S9 mixture 존재하에 $G_{1}$ phase에서 MMC 처리 후 감잎차를 처리하는 후처리 방식으로 감잎차 추출액을 처리하였을 때, 저농도($\leq$40$\mu\textrm{g}$/ml)에서 MMC로 인해 유발된 SCE 빈도수가 낮아지는 것을 볼 수 있었다. 이에 비해 고농도(>40$\mu\textrm{g}$/ml)에서는 SCE 빈도수의 감소 효과가 없었다. 본 연구결과, MMC 처리된 CHO 세포에 대한 감잎차 추출액의 항돌연변이 효과를 볼 수 있었고, 이 효과는 S9 mixture 존재하에서 저농도의 감잎차 추출액이 $G_{1}$ phase에 처리되었을 때 나타났다. 감잎차 추출액의 이러한 항돌연변이의 효과의 기전은 감잎차 추출액의 대사산물이 MMC 처리된 CHO 세포에 대한 DNA-excision repair activity를 촉진시키기 때문인 것으로 생각된다.

• Journal of Chest Surgery
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• 제29권7호
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• pp.780-784
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• 1996

국소성 대동맥하협착은 뚜렷한 막성(discretemembraneous)에서 광범위한 터널형 협착에 이르는다 양한 병변을 보이며 드물지 않게 대동맥팥폐쇄부전이 동반된다. 이러한대동맥하협착과대동맥판폐쇄 부전은 시간이 경과함에 따라 진전되는 것으로 알려져 있으므로 조기수술이 고려되어야 한다. 븐 병 원에서는 중등도의 대동맥 판폐쇄부전이 동반된 국소성 대동맥하협착 환자 1례를 치헙하여 좋은 결과를 얻었다. 수술은 대동맥 판륜 하부의 섬유근성조직 (fibromuscular tissue)을 절제하고 비후된 심실중격에 근절제 및 근절개를 병 행 하였으며, 대동맥 판성 형술 및 교련하부판륜성 형술로 대동맥 판폐 쇄부전을 교정하였 다. 퇴 원 당시의 심장초음파검사에서 좌심실-대동맥간 수축기 압력 차이가 술전에 비 해 현저히 감소하였고 대동맥판폐쇄부전의 소견은 보이지 않았다.