• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3249-3253
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• 2016

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.11
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• pp.1529-1535
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• 2006

Leptin has been investigated as a candidate gene for fat characteristics in beef cattle. Previously, we have reported 57 sequence variants discovered in Korean cattle (Bos Taurus coreanae). In this study, we examined the association between polymorphisms of leptin and carcass traits (cold carcass weight (CWT) and marbling score (Marb)) in Korean cattle. Among 57 polymorphisms, 11 common polymorphic sites were genotyped in our beef cattle (n = 437). Statistical analysis revealed that one single nucleotide polymorphism in coding exon (c.+411T>C (A137A)) showed a significant association with the yield trait, CWT. The C-bearing genotypes (CC or CT) of c.+411T>C (A137A) showed the higher CWT (p = 0.006). c.+150C>G (S50S) also showed a significant association with the quality trait, Marb (p = 0.01). Our findings suggest that polymorphisms in leptin might be one of the important genetic factors that influence carcass yield and quality in beef cattle, especially in CWT and Marb.

• BMB Reports
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• v.49 no.11
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• pp.587-589
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• 2016

The circadian clock system enables organisms to anticipate the rhythmic environmental changes and to manifest behavior and physiology at advantageous times of the day. Transcriptional/translational feedback loop (TTFL) is the basic feature of the eukaryotic circadian clock and is based on the rhythmic association of circadian transcriptional activator and repressor. In Drosophila, repression of dCLOCK/CYCLE (dCLK/CYC) mediated transcription by PERIOD (PER) is critical for inducing circadian rhythms of gene expression. Pacemaker neurons in the brain control specific circadian behaviors upon environmental timing cues such as light and temperature cycle. We show that amino acids 657-707 of dCLK are important for the transcriptional activation and the association with PER both in vitro and in vivo. Flies expressing dCLK lacking AA657-707 in $Clk^{out}$ genetic background, homologous to the mouse Clock allele where exon 19 region is deleted, display pacemaker-neuron-dependent perturbation of the molecular clockwork. The molecular rhythms in light-cycle-sensitive pacemaker neurons such as ventral lateral neurons ($LN_vs$) were significantly disrupted, but those in temperature-cycle-sensitive pacemaker neurons such as dorsal neurons (DNs) were robust. Our results suggest that the dCLK-controlled TTFL diversify in a pacemaker-neuron-dependent manner which may contribute to specific functions such as different sensitivities to entraining cues.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6317-6325
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• 2015

Ginkgo biloba extract (GBE) is a popular phytomedicine and has been used for disorders of the central nervous system, cardiovascular, renal, respiratory, and circulatory diseases. Although GBE is a complex mixture of over 300 compounds, its major components are 24% flavonoids and 6% terpene lactones. In this study, we tested the inhibitory effects of the three major flavonoids (kaempferol, quercetin, and isorhamnetin) from GBE, independently and as mixtures, on aromatase activity using JEG-3 cells (human placental cells) and recombinant proteins (human placental microsome). In both systems, kaempferol showed the strongest inhibitory effects among the three flavonoids; the flavanoid mixtures exerted increased inhibitory effects. The results of exon I.1-driven luciferase reporter gene assays supported the increased inhibitory effects of flavonoid mixtures, accompanied by suppression of estrogen biosynthesis. In the RT-PCR analysis, decreased patterns of aromatase promoter I.1 mRNA expressions were observed, which were similar to the aromatase inhibition patterns of flavonoids and their mixtures. The present study demonstrated that three flavonoids synergistically inhibit estrogen biosynthesis through aromatase inhibition, decrease CYP19 mRNA, and induce transcriptional suppression. Our results support the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing estrogen levels with reduced adverse effects due to estrogen depletion.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.12
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• pp.1706-1710
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• 2006

Leptin receptor (OBR) is a member of the class I cytokine receptor family. It signals mainly via the JAK/STAT pathway and plays an important role in regulating body energy storage and metabolism. This study was designed to investigate the effects of the OBR gene on chicken growth and body composition. Broiler lines selected divergently for or against abdominal fat were used. Primers for the exon9-region in the OBR gene were designed using chicken genomic sequences from the public genome domain. A C/A single nucleotide polymorphism (SNP) was found and its three genotypes (AA, AB and BB) were identified in this population. The results showed that the OBR polymorphism was associated with fatness traits, such as abdominal fat weight and abdominal fat percentage. This research suggests that OBR or a linked gene has effect on fat deposition in the chicken.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.3
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• pp.305-308
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• 2006

A genetic study was conducted to elucidate the effect of alpha-Lactalbumin (${\alpha}$-LA) gene polymorphism on milk production traits involving total milk yield and daily milk yield during first lactation in two breeds of water buffaloes namely, Murrah and Bhadawari. Single strand conformation polymorphism (SSCP) was carried out to explore genetic polymorphism present at this locus. For this study, exon 1 region of ${\alpha}$-LA was analyzed. Finally, polymorphism data was associated with milk production traits by employing least square analysis. In Murrah buffalo, five genotypes such as AB, BB, BC, CC and CD and four alleles A, B, C and D were detected whereas in Bhadawari buffalo two genotypes namely, AB and BC and three alleles namely, A, B and C were found. Genotypes showed significant effects ($p{\leq}0.05$) on total milk yield and daily milk yield in Bhadawari buffalo but had non-significant effects on these traits in Murrah buffalo.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.19-24
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• 2006

Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.

• Journal of Interdisciplinary Genomics
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• v.4 no.1
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• pp.7-10
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• 2022

Purpose:Maturity onset diabetes of the young (MODY) is the most common hereditary form of diabetes mellitus (DM), with similar clinical manifestations to type 1 or type 2 DM, leading to diagnostic ambiguity. Despite increased genetic research on monogenic DM, studies with Asian populations are limited. Therefore, we investigated mutation in possible monogenic DM and MODY in Korean children and aldolescents. Methods: Targeted panel exome sequencing including 32 targets genes was performed for 41 patients with suspected monogenic DM at Kyungpook National University Children's Hospital. Results: Variants were detected in 19 patients, including those in known MODY-associated genes (HNF4A, GCK, HNF1A, CEL, PAX4, INS, and BLK) and monogenic DM-associated genes (WFS1, FRX6, and GLIS3). Conclusion: MODY variants were detected more than expected. Targeted exon sequencing is helpful in diagnosing MODY or possible monogenic DM patients.

• Korean Journal of Biological Psychiatry
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• v.19 no.3
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• pp.128-133
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• 2012

Objectives : Located on chromosome 10q22-q23, the human neuregulin 3 (NRG3) is suggested as a strong positional and functional candidate gene involved in the pathogenesis of schizophrenia. Several case-control studies examining the association between polymorphisms on NRG3 gene with schizophrenia and/or its traits (such as delusion) have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians, white Americans of Western European ancestry and Koreans. Thus, this study aimed to investigate the association of one SNP in exon 9 (rs2295933) of NRG3 gene with the risk of schizophrenia in a Korean population. Methods : Using TaqMan assay, rs2295933 in the exon 9 of NRG3 was genotyped in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. Differences in frequency distributions were analyzed using logistic regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Results : Subsequent analysis revealed that the frequency distribution of rs2295933 of NRG3 was not different between schizophrenia patients and healthy controls of Korean ethnicity. Conclusions : This study does not support the role of NRG3 in schizophrenia in a Korean population.

• Journal of Life Science
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• v.24 no.2
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• pp.181-185
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• 2014

We identified SNPs (single nucleotide polymorphisms) for endothelial nitric oxide synthase (eNOS) genes in the Korean genome. eNOS is present in the vascular endothelium, platelets, and several other cell types that continuously produce modest amounts of NO. Endothelium-derived NO plays a key role in the regulation of vascular tone, and the impaired effects of NO on the cardiovascular system appear to be responsible for coronary atherosclerosis and thrombosis. In recent studies, a missense variant within exon 7 of the eNOS gene in patients with coronary spastic angina-GAG to GAT substitution, which results in the replacement of glutamic acid by aspartic acid (Glu298Asp [G894T])-has been identified and is known to be significantly associated with coronary spasm. We prepared PCR primers based on sequences in Genbank. Primers were prepared for normal and SNPs separately, as reported for other Asian countries, such as G894T. Their sequences were different only at the 3' ends so that primer extension could only by possible when base pairs between templates and primers matched. We also employed ARMS (Amplification Refractory Mutation System) technology to improve the specificity of the PCR reaction. In conclusion, we were able to demonstrate the eNOS G894A polymorphism in Korean gemone. This study should facilitate research on the cause of myocardial infarction and development on further therapy at the genetic level.