• Journal of Medicine and Life Science
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• 제17권2호
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• pp.41-46
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• 2020

Metformin, a predominantly prescribed anti-diabetic drug for decades, has gained new insights for its anti-tumor activity in a variety of cancer cells. Our previous studies also showed the obvious pro-apoptotic activity of metformin and the underlying action mechanisms in hepatocellular carcinoma cells. Together with apoptosis, autophagy is a crucial intracellular process to determine the survival or death of cells under some stressful environments. The present study aimed to determine the role of autophagy in metformin-induced death of H4IIE hepatocellular carcinoma cells. Metformin blocked the formation of autophagosome and the expression of LC3A, generally described as a biomarker of autophagy. Inhibition of AMPK reversed the metformin-induced blockade of autophagy. Antioxidant (NAC) suppressed the metformin-induced cell death but not affected LC3A. The inhibition of protein kinase C totally restored the metformin-suppressed expression of LC3A. In summary, our present study suggests that autophagy is an anti-apoptotic player in metformin-induced apoptosis in H4IIE cells.

• 센서학회지
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• 제16권2호
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• pp.132-141
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• 2007

The purpose this research is to develop QCM (quartz crystal microbalance) biosensor for the determination of haptoglobin. Haptoglobin is an acute-phase protein with a hemoglobin-binding activity and has a potential to be used as a biomarker for infection or cancer. Haptoglobin level in milk has been used for the diagnosis of cow mastitis. In this study, anti-bovine haptoglobin antibody or bovine hemoglobin was chemically immobilized on the surface of the QCM, and the resulting sensor chips were tested for their response to samples containing haptoglobin at different concentrations. Concentration dependent frequency change was observed with both of the sensor chips. Especially, the sensor chip containing anti-bovine haptoglobin antibody showed sufficient sensitivity in the concentrations typically observed in the cows with mastitis.

• Journal of Nutrition and Health
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• 제27권7호
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• pp.740-751
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• 1994

Sister chromatid exchanges(SCE) in peripheral lymphocytes is recently used as a biomarker for increased cytogenetic damage in smokers. The purpose of the investigation was to determine if there were any relationships between dietary factors and their DNA damage as measured by SCE test in a group of 62 male cigarette smokers and 36 non-smokers. As expected, smokers as compared with non-smokers had high SCE levels (10.59$\pm$0.21 versus 9.23$\pm$0.17 SCE/lymphocytes ; p<0.05). No significant relationships were observed between SCEs and age in smokers and non-smokers. In smokers, SCEs were negatively correlated with egg frequency score(r=-0.336) and total food frequency scores(r=-0.283). In non-smokers, SCEs were positively correlated with white vegetable frequency score(r=0.333) and instant food frequency score(r=0.382). There was a positive association between SCEs and the history of coffee intake of smokers(r=0.318). SCE frequency was not influenced by any other dietary factors considered ; dietary diversity and quality scores, alcohol consumption, use of processed foods and intake of burned food. No significant relationships were found between SCEs and serum cholesterol or other hematological parameters of the subjects. These results indicate that increased egg frequency score, total food frequency score which reflects dietary quality, and decreased coffee intake may reduce cancer risk by preventing smoking-induced DNA damage as reflected by sister chromatid exchanges in human lymphocytes.

• 한국환경보건학회지
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• 제28권2호
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• pp.173-182
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• 2002

Exposure to environmental tobacco smoke(ETS) increases the risk of lung cancer and other diverse health effect for nonsmokers. Health risk assessment of nonsmokers related to ETS exposure requires large and exact data of ETS exposure to nonsmokers. This study presented the data of ETS exposure to workers at three category of restaurants(Korean restaurant, coffee shop, wine shop) in Seoul. Markers of ETS exposure measured in this study were area and personal NO$_2$, area and urine nicotine, area respiratory suspended particulate(RSP) and urine cotinine. The mean concentration of RSP and nicotine of all restaurant indoor samples was 177.8$\mu\textrm{g}$/㎥(range:75.3~317.0$\mu\textrm{g}$/㎥) and 7.8$\mu\textrm{g}$/㎥(range:0~57.3$\mu\textrm{g}$/㎥). The mean concentration of urine cotinine measured for the biomarker of ETS exposure was 77.3ng/mL(range:17.3~174.6ng/mL). In all measurements, the concentration of ETS markers at the wine shop was higher than those at other restaurants. The correlation coefficient among the ETS markers measured in the study was significant between area RSP and nicotine concentration and between area NO$_2$and nicotine concentration.

• Molecules and Cells
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• 제28권2호
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• pp.99-103
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• 2009

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

• BMB Reports
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• 제53권12호
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• pp.658-663
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• 2020

The N-myc downstream regulated gene (NDRG) family members are dysregulated in several tumors. Functionally, NDRGs play an important role in the malignant progression of cancer cells. However, little is known about the potential implications of NDRG4 in pancreatic ductal adenocarcinoma (PDAC). The aim of the current study was to elucidate the expression pattern of NDRG4 in PDAC and evaluate its potential cellular biological effects. Here, we firstly report that epigenetic-mediated silencing of NDRG4 promotes PDAC by regulating mitochondrial function. Data mining demonstrated that NDRG4 was significantly down-regulated in PDAC tissues and cells. PDAC patients with low NDRG4 expression showed poor prognosis. Epigenetic regulation by DNA methylation was closely associated with NDRG4 down-regulation. NDRG4 overexpression dramatically suppressed PDAC cell growth and metastasis. Further functional analysis demonstrated that up-regulated NDRG4 in SW1990 and Canpan1 cells resulted in attenuated mitochondrial function, including reduced ATP production, decreased mitochondrial membrane potential, and increased fragmented mitochondria. However, opposite results were obtained for HPNE cells with NDRG4 knockdown. These results indicate that hypermethylation-driven silencing of NDRG4 can promote PDAC by regulating mitochondrial function and that NDRG4 could be as a potential biomarker for PDAC patients.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.122-136
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• 2022

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

• BMB Reports
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• 제51권9호
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• pp.444-449
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• 2018

Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6145-6150
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• 2014

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.