• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1583-1587
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• 2015

Bile acids are endogenous metabolites that aid in the digestion and absorption of ingested fat and fat-soluble vitamins. However, high concentrations of deoxycholic acid (DCA) in the colon are associated with high incidence of colorectal cancer. In the present study, the binding of persimmon extracts to DCA in order to decrease inflammatory stress induced by DCA in a small intestinal epithelial cell line, Caco-2, was investigated. Young and ripened persimmons were extracted with distilled water (DW), ethanol, and acidic ethanol. Further, DW extract residue was re-extracted with acidic ethanol. Of the obtained extracts, acidic ethanol extract of young persimmon showed the highest bile-acid binding capacity. Moreover, acidic ethanol extract of young persimmon significantly inhibited nitric oxide production in Caco-2 cells stimulated with DCA and prevented significant reduction of trans-epithelial electric resistance. Based on these results, acidic ethanol extract of young persimmon can be used as a functional ingredient to enhance gastrointestinal health.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.1-9
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• 2006

Human solid tumors exhibit a multicellular resistance (MCR) resulting from limited drug penetration and decreased sensitivity of tumor cells when interacting with their microenvironments. Multicellular cultures represent solid tumor condition in vivo and provide clinically relevant data. There is little data on antitumor effect of paclitaxel (PTX) in multicellular cultures although its MCR has been demonstrated. In the present study, we evaluated antiproliferative effects of PTX in multicellular layers (MCL) of DLD-1 human colorectal carcinoma cells. BrdU labeling index (LI), thickness of MCL, cell cycle distribution and cellular uptake of calcein were measured before and after exposure to PTX at 0.1 to 50 ${\mu}M$ for 24, 48 and 72 hrs. BrdU LI and thickness of MCL showed a concentration- and time-dependent decrease and the changes in both parameters were similar, i.e., 34.2% and 40.6% decrease in BrdU LI and thickness, respectively, when exposed to $50\;{\mu}M$ for 72 hr. The DLD-1 cells grown in MCL showed increase in $%G_{0}/G_{1}$ and resistance to cell cycle arrest and apoptosis compared to monolayers. Calcein uptake in MCL did not change upon PTX exposure, indicating technical problems in multicellular system. Overall, these data indicate that antitumor activity of PTX may be limited in human solid tumors (a multicellular system) and MCL may be an appropriate model to study further pharmacodynamics of PTX.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.155-161
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• 2014

Overexpression of amyloid precursor protein with the Swedish mutation causes abnormal hyperphosphorylation of the microtubule-associated protein tau. Hyperphosphorylated isoforms of tau are major components of neurofibrillary tangles, which are histopathological hallmarks of Alzheimer's disease. Protein phosphatase 2A (PP2A), a major tau protein phosphatase, consists of a structural A subunit, catalytic C subunit, and a variety of regulatory B subunits. The B subunits have been reported to modulate function of the PP2A holoenzyme by regulating substrate binding, enzyme activity, and subcellular localization. In the current study, we characterized regulatory B subunit-specific regulation of tau protein phosphorylation. We showed that the PP2A B subunit PPP2R2A mediated dephosphorylation of tau protein at Ser-199, Ser-202/Thr-205, Thr-231, Ser-262, and Ser-422. Down-regulation of PPP2R5D expression decreased tau phosphorylation at Ser-202/Thr-205, Thr-231, and Ser-422, which indicates activation of the tau kinase glycogen synthase kinase 3 beta ($GSK3{\beta}$) by PP2A with PPP2R5D subunit. The level of activating phosphorylation of the $GSK3{\beta}$ kinase Akt at Thr-308 and Ser-473 were both increased by PPP2R5D knockdown. We also characterized B subunit-specific phosphorylation sites in tau using mass spectrometric analysis. Liquid chromatography-mass spectrometry revealed that the phosphorylation status of the tau protein may be affected by PP2A, depending on the specific B subunits. These studies further our understanding of the function of various B subunits in mediating site-specific regulation of tau protein phosphorylation.

• Journal of Biomedical Engineering Research
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• v.30 no.6
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• pp.482-488
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• 2009

Conventional devices for transanal endoscopic microsurgery that are currently used clinically for intestine or rectal cancer patients have 40 mm external diameter of rectoscope tube - induces anal damage and long-term postoperative pain for small-sized patients. In this paper, we designed rectum and rectoscope models and calculated the changing trends of operation area of the surgical tools in accordance with the step-by-step variation of design parameters of the rectoscope tube - external diameter, axial length, and distal angle. Using the results of computer simulation, we suggested an optimal set of design parameters that minimizes external diameter of the rectoscope tube and at the same time, maintains similar operation area of the surgical tools compared with commercialized devices (${\geq}\;4274.7mm^2$). The results of the simulation showed that the optimal design parameters were 35 mm external diameter, 100 mm axial length, and $45^{\circ}$ distal angle of the rectoscope tube. This result can be applied to the development of endoscopic microsurgery device that can minimize side effects to the intestine or rectal cancer patients.

• Journal of Preventive Medicine and Public Health
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• v.48 no.1
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• pp.1-9
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• 2015

The purpose of the present review is to give an overview of the association between alcohol intake and the risk of developing cancer. Two large-scale expert reports; the World Cancer Research Fund (WCRF)/American Institute of Cancer Research (AICR) report from 2007, including its continuous update project, and the International Agency for Research of Cancer (IARC) monograph from 2012 have extensively reviewed this association in the last decade. We summarize and compare their findings, as well as relate these to the public health impact, with a particular focus on region-specific drinking patterns and disease tendencies. Our findings show that alcohol intake is strongly linked to the risk of developing cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum (in men), and female breast. The two expert reports diverge on the evidence for an association with liver cancer and colorectal cancer in women, which the IARC grades as convincing, but the WCRF/AICR as probable. Despite these discrepancies, there does, however, not seem to be any doubt, that the Population Attributable Fraction of alcohol in relation to cancer is large. As alcohol intake varies largely worldwide, so does, however, also the Population Attributable Fractions, ranging from 10% in Europe to almost 0% in countries where alcohol use is banned. Given the World Health Organization's prediction, that alcohol intake is increasing, especially in low- and middle-income countries, and steadily high in high-income countries, the need for preventive efforts to curb the number of alcohol-related cancers seems growing, as well as the need for taking a region- and gender-specific approach in both future campaigns as well as future research. The review acknowledges the potential beneficial effects of small doses of alcohol in relation to ischaemic heart disease, but a discussion of this lies without the scope of the present study.

• Molecules and Cells
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• v.39 no.12
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• pp.877-887
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• 2016

Tazarotene-induced gene 1 (TIG1) is a retinoic acid-inducible protein that is considered a putative tumor suppressor. The expression of TIG1 is decreased in malignant prostate carcinoma or poorly differentiated colorectal adenocarcinoma, but TIG1 is present in benign or well-differentiated tumors. Ectopic TIG1 expression led to suppression of growth in cancer cells. However, the function of TIG1 in cell differentiation is still unknown. Using a yeast two-hybrid system, we found that transmembrane protein 192 (TMEM192) interacted with TIG1. We also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins, including Beclin-1 and LC-3B. The silencing of TMEM192 reduced the TIG1-mediated upregulation of autophagic activity. Furthermore, silencing of either TIG1 or TMEM192 led to alleviation of the upregulation of autophagy induced by all-trans retinoic acid. Our results demonstrate that the expression of TIG1 leads to cell autophagy through TMEM192. Our study also suggests that TIG1 and TMEM192 play an important role in the all-trans retinoic acid-mediated upregulation of autophagic activity.

• Food Science of Animal Resources
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• v.38 no.3
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• pp.615-628
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• 2018

Preserved egg, a kind of alkaline-fermented food, is a traditional egg product in China. Here, we investigated the nutritional functions of preserved eggs by in vivo and in vitro experiments. The results of in vivo studies showed that the levels of triglycerides (TG), total cholesterol (TCHO) and low-density lipoprotein cholesterol/high density lipoprotein cholesterol (LDL-C/HDL-C) were significantly decreased (p<0.05) in the liver of rats treated with preserved eggs. Meanwhile, the levels of two important cancer markers, interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), were also significantly decreased (p<0.05) in treated rats. In vitro studies were performed on Caco-2 cells, a human epithelial colorectal adenocarcinoma cell line. It demonstrated that the gastrointestinal (GI) digests of preserved eggs significantly accelerated (p<0.05) the apoptosis by upregulating caspase-3 in the Caco-2 cells. Besides, after treated with preserved eggs, the half maximal inhibitory concentration (IC50) of preserved eggs digests to Caco-2 cells was 5.75 mg/mL, indicating the significant inhibition of cell proliferation provided by preserved eggs (p<0.05). The results shown in this study demonstrated that preserved eggs may be a novel functional food involved with antilipemic, anti-inflammatory activity as well as the effect on accelarating the apoptosis of Caco-2 cells.

• Journal of Preventive Medicine and Public Health
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• v.38 no.1
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• pp.9-15
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• 2005

Objectives : To analyze medical expenses by cancer site and survival time among cancer patients in their last year of life. Method : The study subjects were 45,394 people that had died of cancers in 2002, were registered by the Korea Central Cancer Registry and received National Health Insurance benefit in the last year (360 days) of life. Personal identification data, general characteristics, dates of death and cancer incidence, and site of cancer were collected from the National Statistical Office and the Korea Central Cancer Registry, and merged with the data of the individual medical expenses of the Health Insurance Review Agency. Results : Average monthly cost curves were U-shaped with high costs near the time of diagnosis and death, and lower costs in between. Medical expenses in the last year of life were around 30.3, 16.7, 13.0, and 12.1 million won among leukemia, lymphoma, ovarian cancer, and breast cancer patients, respectively. Digestive organ cancers including stomach, esophagus, liver, pancreas, and colorectal cancers had relatively low medical expenses. Medical expenses in the last year of life were inverse U-shaped with high expenses near one year of survival. Average monthly cost in the 12 months before death among the patients who had survived $10{\sim}15$ years were more than two-fold greater than the cost before diagnosis among those who had survived for less than one year. Conclusions : Leukemia was the most expensive cancer. It is possible that once diagnosed as cancer, medical expenses do not return to the level before diagnosis. Further research will be needed to understand the magnitude and change of the medical expenses among cancer patients with long term follow up data.

• Journal of Preventive Medicine and Public Health
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• v.38 no.1
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• pp.38-44
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• 2005

Objective : To compare the mortality rate of Korean medical doctors to that of the general Korean population for the period 1992-2002. Methods : The membership records of the Korean Medical Association were linked to the 1992-2002 death certificate data of Korea s National Statistical Office using 13-digit unique personal identification numbers. The study population consisted of 61,164 medical doctors with a follow-up period of 473,932 person-years. Standardized mortality ratios(SMRs) were calculated to compare cause-specific mortality rates of medical doctors to those of the general population. Results : We confirmed 1,150 deaths at ages from 30 to 75 years from 1 January 1992 to 31 December 2002. The SMR for all-cause of death was 0.47(95% CI : $0.44{\sim}0.50$). The SMRs for smoking-related diseases such as cerebrovascular accidents and chronic obstructive pulmonary disease were smaller than the SMR of all-cause of death. However, the SMRs for colorectal and pancreatic cancers were not significantly lower than those of the general population. Transport accidents and suicides accounted for 72% (94 of 131) of external causes of death. The SMR for suicide was 0.51 (95% CI : $0.38{\sim}0.68$). Conclusions : The mortality rate of South Korean medical doctors was less than 50% that of the general population of South Korea. Cause-specific analysis showed that mortality rates in leading causes of death were lower among medical doctors although differences in mortality rates between medical doctors and the general population varied with the causes of death. These health benefits found among medical doctors may be attributable to the lower level of health damaging behaviors (e.g., lower smoking rates) and better working conditions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.290-295
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• 2008

The cytotoxic characteristics of Vitsin A isolated from Vitis amurensis L. were examined in human colorectal, breast, uterine and renal cancer cells. Vitsin A showed good cytotoxicity against various cancer cells with $IC_{50}$ of $1\;{\sim}\;30\;{\mu}M$. Among them, Vitisin A exhibited strongest cytotoxic effect against MES-SA cells with $IC_{50}$ of 1.11 ${\mu}M$ by SRB assay. To verify whether the cytotoxicity of Vitisin A may be associated with apoptosis, TdT-mediated-dUTP Nick-End Labeling (TUNEL) assay and cell cycle analysis were performed in MES-SA cells. Apoptotic bodies were observed in Vitisin A treated MES-SA cells by TUNEL assay. Also, Vitisin A effectively increased the portion of $sub-G_1$ DNA content by flow cytometric analysis. Taken together, these findings suggest that the cytotoxicity of Vitisin A against MES-SA cells is chiefly mediated by apoptosis.