• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.2
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.

• Journal of Embryo Transfer
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• v.30 no.4
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• pp.289-298
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• 2015

Edaravone (Eda) is a potent scavenger of inhibiting free radicals including hydroxyl radicals ($H_2O_2$). Reactive oxygen species (ROS) such as $H_2O_2$ can alter most kinds of cellular molecules such as lipids, proteins and nucleic acids, cellular apoptosis. In addition, oxidative stress from over-production of ROS is involved in the defective embryo development of porcine. Previous study reported that Eda has protective effects against oxidative stress-like cellular damage. However, the effect of Eda on the preimplantation porcine embryos development under oxidative stress is unclear. Therefore, in this study, the effects of Eda on blastocyst development, expression levels of ROS, and apoptotic index were first investigated in preimplantation porcine embryos. After in vitro fertilization, porcine embryos were cultured for 6 days in PZM medium with Eda ($10{\mu}M$), $H_2O_2$ ($200{\mu}M$), and Eda+$H_2O_2$ treated group, respectively. Rate of blastocyst development was significantly increased (P<0.05) in the Eda treated group compared with only $H_2O_2$ treated group. And, we measured intracellular levels of ROS by DCF-DA staining methods and investigated numbers of apoptotic nuclei by TUNEL assay analysis is in porcine blastocyst, respectively. Both intracellular ROS levels and the numbers of apoptotic nucleic were significantly decreased (P<0.05) in porcine blastocysts cultured with Eda ($10{\mu}M$). More over, the total cell number of blastocysts were significantly increased (P<0.05) in the Eda-treated group compared with untreated group and the only $H_2O_2$ treated group. Based on the results, Eda was related to regulate as antioxidant-like function according to the reducing ROS levels during preimplantation periods. Also, Eda is beneficial for developmental competence and preimplantation quality of porcine embryos. Therefore, we concluded that Eda has protective effect to ROS derived apoptotic stress in preimplantation porcine embryos.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.129-136
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• 2015

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

• Journal of Embryo Transfer
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• v.28 no.3
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• pp.251-256
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• 2013

The present study was performed to investigate the effect of Hh-Ag1.5, a small-molecule chemical agonist of SMOothened receptor, on the in vitro maturation and development of in vitro fertilized (IVF) embryos in pigs. Oocytes or fertilized embryos were cultured in a maturation or embryo culture medium supplemented with 0 (control), 25, 50 or 100 nM of Hh-Ag1.5, respectively. Although the maturation rate were not different among treatment groups, the blastocyst formation rate in the group treated with 25 nM Hh-Ag1.5 was significantly increased compared to other groups (P<0.05). While the highest dose of Hh-Ag1.5 (100 nM) did negatively affect to the embryo development and cell number in blastocysts compared to other groups (P<0.05), the apoptotic cell index in blastocysts was significantly lower in 25 and 50 nM groups than in control and 100 nM groups (P<0.05). The mRNA expression of the proapoptotic gene Bax and the ratio of Bax/Bcl-XL decreased in among treatment groups compared to control (P<0.05). The embryo quality related genes, Tert and Zfp42, were significantly decreased in 50 and 100 nM groups compared with control and 25 nM groups (P<0.05). In conclusion, the addition of 25 nM Hh-Ag1.5 to in vitro maturation and culture medium can enhance the developmental potential as well as quality of IVF embryos in pig.

• Journal of Embryo Transfer
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• v.28 no.3
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• pp.243-250
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• 2013

Pyracantha is a genus of thorny evergreen large shrubs in the family of Rosaceae, with common names Firethorn or Pyracantha. It's extract has also been used in cosmetics as a skin-whitening agent and functioning through tyrosinase inhibition. Recent studies have shown that pyracantha extract possesses antioxidant activities and may significantly improve lipoprotein metabolism in rats. Although the mode of action of Pyracantha extract is not fully understood, a strong relationship was observed between antioxidant and apoptosis in some types of cells. Thus, the aim of this study was to evaluated the effect of pyracantha extract on blastocysts formation and their quality of the porcine parthenogenetic embryos. After parthenogenetic activation by chemicals, presumptive porcine parthenogenetic embryos were cultured in PZM-3 medium supplemented with extracts of pyracantha leaf, stalk and root for 6 day (1, 5 and $10{\mu}g/ml$, respectively). In our results, the frequency of blastocyst formation in pyracantha root extract ($5{\mu}g/ml$) treated group had increased that of other groups. Furthermore, blastocysts derived from pyracantha root extract ($5{\mu}g/ml$) treated group had increased the total cell numbers and reduced apoptotic index. Blastocyst development was significantly improved in the pyracantha root extract ($5{\mu}g/ml$) treated group when compared with the $H_2O_2$ treated group (p<0.05). Subsequent evaluation of the intracellular levels of ROS in pyracantha root extract ($5{\mu}g/ml$) treated groups under $H_2O_2$ induced oxidative stress were decreased (p<0.05). In conclusion, our results indicate that treatment of pyracantha root extract may improve in vitro development of porcine parthenogenetic embryos through its antioxidative and antiapoptotic effects.

• The Journal of Korean Obstetrics and Gynecology
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• v.26 no.4
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• pp.191-203
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• 2013

Purpose: This review is to figure out evidence that suggest effectiveness of Korean Medicine treatments against cervical dysplasia. Methods: Studies on cervical cancer and cervical dysplasia were searched through 6 databases: Korean Studies Information Service System(KISS), National Discovery for Science Leaders (NDSL), Korea Institute of Science and Technology Information (Korean TK), Oriental Medicine Advanced Searching Integrated System (OASIS), the Journal of Korean Medicine, and the Journal of Korean Obstetrics & Gynecology. After that, the articles were extracted with reference point of Korean Traditional Medicine. Results: 37 articles were included lastly according to selection criteria. 3 of them were case reports on cervical dysplasia, and 34 were in-vitro studies on Human Papilloma Virus (HPV) positive cancer cell. In case reports, acupuncture, moxibustion, medical herbs and pharmacoacupuncture were used for treatments of cervical dysplasia with about 3 months. Experimental studies on cervical cancer cell showed that several herbs function with clear heat, eliminate stasis (淸熱解毒, 化瘀消腫) have anti-cancer effects inducing apoptosis. Conclusions: The results of articles are not enough to use in practice. Therefore, we indicates more advanced research methodology as follows: development of Korean Medicine treatment protocol with oral and external, in-vivo experimental study, and evaluation immunity index.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4807-4814
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• 2012

Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.

• The Journal of Korean Medicine
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• v.41 no.3
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• pp.22-31
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• 2020

Objectives: The purpose of this study was to investigate the association between sleep status and weight loss among adult women with obesity administered with Gamitaeeumjowee-tang. Methods: We retrospectively reviewed the medical records of 137 patients who were were administered with Gamitaeeumjowee-tang for 3 months for the purpose of weight loss. We divided subjects according to sleep duration and sleep quality. We conducted an independent t-test to compare the differences of weight loss between two groups. Also, a regression analysis was applied to determine which factors affected weight loss. Results: There was no significant difference in weight loss between patients who sleep more than 7 hours regularly and patients who sleep less than 7 hours. There was no significant difference between good sleepers and poor sleepers. Initial body mass index and the number of visits to the clinic were the significant factors in weight loss in 2-4 weeks. Initial weight loss was the significant factor in weight loss in 10-12 weeks. There was no significant correlation of sleep duration and sleep quality in weight loss in 2-4 weeks and 10-12 weeks. Conclusions: This study suggests that weight loss may not be affected by sleep status during Gamitaeeumjowee-tang intervention. ostachys japonicus, THP-1, acute myeloid leukemia, apoptosis, autophagy.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.293-298
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• 2011

Objective : The extracellular matrix (ECM) and cell adhesion molecules play crucial roles in angiogenesis, apoptosis, thrombosis, and inflammation, and also contribute to the pathogenesis of stroke. Integrin, alpha 6 (ITGA6) is a member of ECM adhesion receptors. We investigated whether two single nucleotide polymorphisms (SNPs) (rs11895564, Ala380Thr; rs2293649, Asp694Asp) of ITGA6 were associated with the development and clinical phenotypes of intracerebral hemorrhage (ICH) and ischemic stroke (IS). Methods : We enrolled 199 stroke (78 ICH and 121 IS) and 291 control subjects. Stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ${\geq}6$) and Modified Barthel Index (MBI, <60 and ${\geq}60$). SNPStats, SNPAnalyzer, and Helixtree programs were used to calculate odds ratios, 95% confidence intervals, and p values. Multiple logistic regression models were used to analyze genetic data. Results : A missense SNP rs11895564 was associated with the development of ICH (p=0.026 in codominant2, p=0.013 in recessive, p=0.02 in log-additive models; p=0.041 in allele distributions). The A allele frequency of rs11895564 was higher in the ICH group (13.5%) than in the control group (8.1%). In the clinical phenotypes, rs11895564 and rs2293649 showed significant associations in the MBI scores of IS (p=0.014 in codominant1 model; p=0.02 in allele distributions) and NIHSS scores of ICH (p=0.017 in codominant2, p=0.035 in recessive, p=0.035 in log-additive models), respectively. Conclusion : These results suggest that ITGA6 may be associated with the development and clinical phenotypes of stroke in Korean population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9137-9142
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• 2014

Background: To explore the expression of DcR3 protein and its clinicopathological significance in bladder urothelial carcinomas (BUC). Materials and Methods: Immunohistochemistry was performed to detect the expression of DcR3, caspase-3, Bcl-2, VEGF, Ki-67, PCNA and P53 in 166 BUC and 56 normal bladder tissues. Western blotting was used to detect the expression of DcR3 in the supernatants of cultured BUC cells. Results: Overexpression of DcR3 was found in BUC tissues and cell lines, with significant elevation as compared to normal bladder tissues (p<0.0001). Higher DcR3 expression was related to the status of invasion, lymph node metastasis and recurrence. Furthermore, DcR3 expression was negatively correlated with caspase-3 and positively associated with Bcl-2, VEGF, Ki-67 labeling index (LI), PCNA LI and P53 (all p<0.0001), respectively. Conclusions: DcR3 may play a crucial role as an oncogene in tumorigenesis, deterioration and progress of BUC via influencing related pathways of apoptosis, proliferation and angiogenesis. The detection of DcR3 protein in the formalinfixed and paraffin-embedded samples could assist to predict in prognosis of BUC patients.