• BMB Reports
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• v.51 no.9
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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.

• Parasites, Hosts and Diseases
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• v.51 no.6
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• pp.689-694
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• 2013

Opisthorchis viverrini and Clonorchis sinensis are parasites known to be carcinogenic and causative agents of cholangiocarcinoma in Asia. The standard method for diagnosis for those parasite infections is stool examination to detect parasite eggs. However, the method has low sensitivity, and eggs of O. viverrini and C. sinensis are difficult to distinguish from each other and from those of some other trematodes. Here, we report a multiplex real-time PCR coupled with high resolution melting (HRM) analysis for the differentiation of O. viverrini and C. sinensis eggs in fecal samples. Using 2 pairs of species-specific primers, DNA sequences from a portion of the mitochondrial NADH dehydrogenase subunit 2 (nad 2) gene, were amplified to generate 209 and 165 bp products for O. viverrini and C. sinensis, respectively. The distinct characteristics of HRM patterns were analyzed, and the melting temperatures peaked at $82.4{\pm}0.09^{\circ}C$ and $85.9{\pm}0.08^{\circ}C$ for O. viverrini and C. sinensis, respectively. This technique was able to detect as few as 1 egg of O. viverrini and 2 eggs of C. sinensis in a 150 mg fecal sample, which is equivalent to 7 and 14 eggs per gram of feces, respectively. The method is species-specific, rapid, simple, and does not require fluorescent probes or post-PCR processing for discrimination of eggs of the 2 species. It offers a new tool for differentiation and detection of Asian liver fluke infections in stool specimens.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• Journal of Life Science
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• v.27 no.6
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• pp.726-737
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• 2017

Carotenoids are isoprenoids with a long polyene chain containing 3 to 15 conjugated double bonds, which determines their absorption spectrum. They typically consist of a $C_{40}$ hydrocarbon backbone often modified by different oxygen-containing functional groups, to yield cyclic or acyclic xanthophylls. Much work has also been focused on the identification, production, and utilization of natural sources of carotenoid (plants, microorganisms and crustacean by-products) as an alternative to the synthetic pigment which currently covers most of the world markets. Nevertheless, only a few carotenoids (${\beta}-carotene$, lycopene, astaxanthin, canthaxanthin, and lutein) can be produced commercially by fermentation or isolation from the small number of abundant natural sources. The market and demand for carotenoids is anticipated to increase dramatically with the discovery that carotenoids exhibit significant anti-carcinogenic activities and play an important role in the prevention of chronic diseases. The increasing importance of carotenoids in the feed, nutraceutical food and pharmaceutical markets has renewed by efforts to find ways of producing additional carotenoid structures in useful quantities. Because microorganisms and plants synthesize hundreds of different complex chemical carotenoid structures and a number of carotenoid biosynthetic pathways have been elucidated on a molecular level, metabolic and genetic engineering of microorganisms can provide a means towards economic production of carotenoid structures that are otherwise inaccessible. The aim of this article is to review our current understanding of carotenoid formation, to explain the perceived benefits of carotenoid in the diet and review the efforts that have been made to increase carotenoid in certain microorganisms.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5915-5920
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• 2013

Aim: Although aberrant miRNA expression has been documented, altered miR-101 expression in cervical cancer and its carcinogenic effects and mechanisms remain unexplored. The aim of our study was to investigate the role of miR-101 alteration in cervical carcinogenesis. Methods: Expression of miR-101 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela cells. After modulating miR-101 expression using miR-101 mimics, cell growth, apoptosis and proliferation, and migration were tested separately by MTT or flow cytometry and cell wound healing assay and protein expression was detected by qRT-PCR. The expression of COX-2 in Hela cell was also examined by immunohistochemical staining and the correlation with miR-101 expression was analysed. Results: The miR-101 demonstrated significantly low expression in Hela cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR-101 expression remarkably influenced cell proliferation, cycling and apoptosis: 1) The expression of microRNA-101 tended to increase after transfection; 2) Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P<0.05); 3) The miR-101 negatively regulates cell migration and invasion, scratch results being lower ($42.7um{\pm}2um$) than that observed pre-transfection ($181.4um{\pm}2um$); 4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX-2 protein, which was negatively correlated with miR-101 expression. Conclusions: Overexpression of miR-101 has obvious inhibitory effects on cell proliferation, migration and invasion. Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis. Our data suggest an important role of miR-101 in the molecular etiology of cancer and indicate potential application of miR-101 in cancer therapy.

• Journal of the Korean Society of Marine Environment & Safety
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• v.14 no.4
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• pp.257-266
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• 2008

PAHs are of mainly anthropogenic origin from urban runoff, oil spill and combustion of fossil fuels. Some PAHs are potentially carcinogenic and mutagenic to aquatic organisms. This study was carried out to survey the contamination of PAHs in the column sediments around Gwangyang bay. Yeosu petrochemical industrial complex, POSCO(Pohang steel compony) and Gwangyang container harbor are located near the bay. The column sediments were collected at 4 stations(A, B, C and D) and fractionated at intervals of two-centimeter depth on July 29, 1999. PAHs in colmn sediment samples were extracted in soxhlet extractor and were identified and quantified by GC-MS. PAHs compounds were analyzed and found to be 13 species. Total PAHs concentrations in the column sediments ranged from 275.04 to 2,838.64${\mu}g/kg$ dry wt. Naphthalene had the highest concentration in the range of 40.60 to 2,294.06${\mu}g/kg$ dry wt. and Anthracene had the lowest concentration in the range of 2.63 to 11.30${\mu}g/kg$ dry wt. The correlation coefficients between individual PAHs and total PAHs in the column sediments were relatively higher in the low molecular compounds such as Naphthalene, Acenaphthylene and Phenanthrene. The relationship between the P/A(Phenanthrene/Anthracene)ratio and F/P(Fluoranthene/Pyrene)ratio showed that P/A ratio was generally above 10 and F/P ratio was above 1 in all sediment samples. These data indicate that PAHs in the column sediments around Gwangyang bay seem to be of both pyrolytic and petrogenic origin The values of PAHs in the column sediments were lower than the biological effect guidelines.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.254-261
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• 2000

The present study has attempted to look into the mechanism of ras-induced carcinogenesis in a human epithelial cell system. Human epithelial cells immortalized with Ad12-SV40 hybrid virus were used to assess carcinogenic potential of the ras-oncogene. Cells transfected with pSV2-ras showed characteristics of cellular transformation. The transformation parameters such as cell density, soft-agar colony formation, and cell aggregation were significantly increased in the cells expressing ras oncoprotein. In addition, the duration required for the appearance of foci was shortened in the ras-transfected cells. Consistent with other reports, our results demonstrated an evidence that the ras-oncogene induced the cellular transformation of human epithelial cell system. When a high concentration of glucocorticoid was added into the media, transformation process was accelerated. It is speculated that glucocorticoid may provide an advantageous environment for the proliferation of the transformed cells. The induction of the intracellular free calcium concentrations following agonist treatment was significantly lower in the transformed cells than in the control cells. These effects were more manifested in the presence of extracellular cacium, indicating that the transformation process may alter the influx pathway of extracellular calcium. The induction of $IP_3$ following agonist treatment was also lower in the transformed cells than in the control cells. Thus, it is suggested that phospholipase C-coupled pathway was down-regulated in the process of the ras-induced transformation. While the levels of $TGF-{\beta}_1$ and PAI-2 mRNAs were decreased, the level of fibronectin mRNA was increased. The results indicate that mechanism of the ras-induced transformation may be associated with the altered expressions of growth regulatory factors. The present study demonstrates an evidence that the ras-induced cellular transformation may be associated with alteration of signal transduction and growth regulatory factors. The study will contribute to improve the understanding of molecular mechanism of epithelium-derived cancers including oral cancer.

• Journal of the Korean Society of Marine Environment & Safety
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• v.13 no.1 s.28
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• pp.9-20
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• 2007

PAHs(Polycyclic Aromatic Hydrocarbons) are widespread contaminants in the marine environment. They are of mainly anthropogenic origin from urban runoff, oil spill and combustion of fossil fuels. Some PAHs are potentially carcinogenic and mutagenic to aquatic organism The contamination of PAHs in the coastal environments has not been well known yet in Korea. This study was carried out to survey the contamination of PAHs in sediments around Gwangyang bay. The Yeosu petrochemical industrial complex, POSCO(Pohang steel company) and Gwangyang container harbor are located around the bay. PAHs in sediment samples were extracted in soxhlet extractor and were identified and quantified by GC-MS(Gas Chromatography-Mass Spectrometry) TOC(Total Organic carbon) and textural parameters in sediment samples were also analyzed 13 species of PAHs were detected at all of the surface sediments. Total PAHs concentrations in the surface sediments ranged from 171.40 to $1013.54{\mu}g/kg$ dry wt.. In most of the surface sediments, Naphthalene was the highest in the range of 14.08 to $691.39{\mu}g/kg$ dry wt. and Anthracene was the lowest in the range of 0.49 to $22.66{\mu}g/kg$ dry wt.. The correlation coefficients between individual PAHs and Total PAHs in the surface sediments were relatively higher in the low molecular compounds such as Naphthalene and Phenanthrene. In the relationship of the P/A(Phenanthrene/Anthracene) ratio and F/P(Fluoranthene/Pyrene) ratio, P/A ratio was generally above 10 and F/P ratio was shown to be above 1 in all sediment samples. These data indicate that PAHs in sediments around Gwangyang bay seem to be of both pyrolytic and petrogenic origin. Total PAHs in the surface sediments were correlated with TOC and textural parameters. The values of PAHs in the surface and core sediments were lower than the biological effect guidelines.