• Archives of Pharmacal Research
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• v.25 no.5
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• Journal of Korean Medicine for Obesity Research
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• v.19 no.2
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• pp.106-112
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• 2019

Objectives: The aim of this study was to observe the reduction of lipid accumulation by treatment with Akkermansia muciniphila extract on 3T3-L1 adipocytes. Methods: After treating pasteurized Akk. muciniphila strains in HT-29 colorectal cancer cell, the relative expression of interleukin (IL)-8, tumor necrosis factor-α, IL-6, and IL-1β mRNA was analyzed by real time polymerase chain reaction, respectively. 27 strains of Akk. muciniphila which have anti-inflammatory effects were selected. 3T3-L1 pre-adipocytes were treated with Akk. muciniphila for 24 hr and then measured the toxicity using water soluble tetrazolium salt assay. The cells were incubated for 4 days and then differentiated into adipocytes using the medium including adipogenic reagents for 10 days. The Akk. muciniphila was treated when the medium was exchanged for differentiation medium at 4^th day and insulin medium at 6^th day. To observe the lipid accumulation, the cells were stained with Oil red O dye and were measured using a spectrophotometer. Results: In the cytotoxicity test, the cell viability of 3T3-L1 pre-adipocytes was significantly increased compared to the control group which untreated with Akk. muciniphila, and there was no cytotoxicity of Akk. muciniphila at 1×10⁷ CFU/mL. The results on Oil red O staining and absorbance measurements were showed a significant decrease in lipid accumulation in the group which was treated with Akk. muciniphila compared to the control group. Conclusions: In our results, Akk. muciniphila has the inhibitory effect of lipid accumulation in 3T3-L1 adipocytes. This suggests that Akk. muciniphila could be help to improve obesity.

• Journal of Life Science
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• v.25 no.7
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• pp.773-779
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• 2015

This study examined extracts from five different kinds of lees and nuruk and their organic solvent fractions in terms of several biological functions, such as anti-adipogenic, anti-inflammatory, and anti-proliferative activities. The anti-adipogenic activity was investigated by treating mouse pre-adipocyte 3T3-L1 cells with one extract (YE) and four organic solvent fractions (YAc, PAc, RAc, and WPAc) during adipogenesis. Among the treated samples, the ethyl acetate fraction of W-Ju lees (WPAc) showed the strongest anti-adipogenic effect, which was confirmed with oil red O staining and down-regulation of pro-adipogenic genes such as PPAR-gamma and SCD-1. Treatment with WPAc also reduced the expression of PPAR-gamma in a time-dependent manner. The effects of five different extracts were examined on nitric oxide (NO) production in mouse RAW 264.7 cells to determine anti-inflammatory activity. The ethyl acetate fraction of B-Ju lees (PAc) significantly decreased NO production in LPS-stimulated RAW 264.7 cells and it also inhibited NO production in a dose-dependent manner. The PAc fraction also dramatically decreased the viability of human colorectal cancer HCT116 cells in a dose-dependent manner. In addition, PAc increased the expression of NAG-1 and ATF3 genes in a dose dependent manner. Overall, these results indicate that lees and nuruk have several biological functions, including anti-adipogenic, anti-inflammatory, and anti-proliferative activities.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.1007-1021
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• 2018

Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

• Journal of Gastric Cancer
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• v.9 no.1
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• pp.14-17
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• 2009

The clinical significance of hepatic resection for gastric metastases is controversial, even though hepatic resection has been widely accepted as a modality for colorectal metastases. Very few patients with gastric hepatic metastases are good candidates for hepatic resection because of multiple bilateral metastases, extrahepatic disease, or advanced cancer progression, such as peritoneal dissemination or extensive lymph node metastases. Therefore, several authors have reported the clinical significance of hepatic resection for gastric metastases in a small number of patients. Considering the present results with previous reports. The number and distribution of tumors in hepatic metastases from gastric cancer was considered based on the present and previous reports. Several authors have reported significantly better survival in patients with metachronous metastasis than in those with synchronous disease. However, metachronous hepatic resection necessitates the dissection of adhesions between the pancreas, liver, and residual stomach to prepare for Pringle's maneuver. Patients with unilobar liver metastasis, and/or metastatic tumors <4 cm in diameter may be good candidates for hepatic resection. Synchronous metastasis is not a contraindication for hepatic resection. Most of the long-term survivors underwent anatomic hepatic resection with a sufficient resection margin. After hepatic resection, the most frequent site of recurrence was the remaining liver, which was associated with a high frequency of mortality within 2 years. A reasonable strategy for improvement in survival would be to prevent recurrence by means of adjuvant chemotherapy and careful follow-up studies.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.2
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• pp.1292-1303
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• 2015

Jeju province is the highest area about obesity(1st), alcohol consumption(2nd) and male smoking(2nd) among sixteen Korean provinces by the report of Statistics Korea: 2013 community health survey. Therefore, it is assumed that the incidence rate of colon, liver, lung and breast cancer can be high. The purpose of this study is to test these cancer's incidence and mortality trends and compare comparability with national average. The Joinpoint regression model and permutation tests for identifying changes and parallelism in trend were used to test registered data at Jeju Regional Cancer Registry from 1999 to 2012. In male colorectal cancer, Average Age Percent Change(AAPC) of Age-Standardized incidence Rate(ASR) was 8.4% per year(p-value<.000) and the hypothesis of parallelism with Korean male average was rejected because of steep increasing of Jeju male patients' AAPC(p-value=.047). In male liver cancer, AAPC of ASR was -2.98 % per year(p-value<.000) and parallelism with Korean male average was rejected because of sluggish decreasing of Jeju(p-value=.026). In male lung cancer, the ASR parallelism with Korean male average was rejected(p-value=.009) because Jeju patients APC(4.37% per year) was increased during 2006~2012. This study demonstrates that AAPC and Trends of male colon, male lung and male liver were difference from national average. Further studies are needed to understand its causes.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.118-122
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• 2015

Suicidal gene therapy is based on the transduction of tumor cells with "suicide" genes encoding for prodrug-activating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4-ipomeanol (4-IPO) or 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate.In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/2-AA or 4-IPO system were evaluated in HT-29 (human colon cancer cell). pcDNA-CYP4B1 vector was transfected into HT-29 by lipofection and stable transfectant was selected by treatment of hygromycin ($500{\mu}g/mL$) for 3 weeks. Reverse transcription polymerase chain reaction (RT-PCR) analysis was performed for confirmation of CYP4B1 expression in CYP4B1 gene transduced cell. The cytotoxic effects of CYP4B1 transduced cell were determined using dye-exclusion assay after treatment of 2-AA or 4-IPO for 96 hrs. Dye-exclusion assay showed that $IC_{50}$ of HT-29 and CYP4B1 transduced HT-29 was 0.01 mM and 0.003 mM after 4-IPO or 2-AA treatment at 96 hrs exposure, respectively. In conclusion, CYP4B1 based prodrug gene therapy probably have the potential for treatment of colorectal adenocarcinoma.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.555-560
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• 2006

Objectives : The objective of this study is to analyze what quality of life(QOL) scales are frequently used in cancer patients and lay a cornerstone to develop new QOL scales adequate for oriental medical anti-cancer treatment in the future. Methods : We searched 151 articles concerned with 'QOL and scale and cancer' from PubMed and classified them according to periods. nations. cancer types and symptoms. Results: 138 articles(91%) were published after 1996. 65 articles(43%) were published in USA. For breast. lung, prostate. esophageal cancer and melanoma. European Organization for Research and Treatment of Cancer-quiality of life questionaire(EORTC-QLQ) was used most frequently to evaluate quality of life. Functional Assessment of Cancer Treatment(FACT) for bladder cancer. Hospital Anxiety and Depression Scale(HADS) for colorectal cancer and of Washington Quality of Life questionnaire(UW-QOL) for Head & Neck cancer were used repeatedly. And for the patients with the symptoms such as bone marrow depression. depression. pain. dyspnea. nausea & vomiting and voice change. the investigators used EORTC-QLQ mainly to evaluate QOL. FACT-An(anemia) for anemia. FACT-BMT(bone marrow transplant) for bone marrow depression were applicated generally. Conclusions It is anticipated that further investigations will be performed to develop adequate QOL scales for oriental medical anti-cancer therapy.

• Journal of Preventive Medicine and Public Health
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• v.40 no.2
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• pp.150-154
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• 2007

Objectives : The aim of this study is to identify factors determining the purchase of private health insurance under the mandatory National Health Insurance(NHI) system in Korea. Methods : The data were collected by the National Cancer Center in Korea. It includes cancer patients who were newly diagnosed with stomach (ICD code, C16), lung(C33-C34), liver (C22), colorectal cancer(C18-C20) or breast(C50) cancer. Data were gathered from the hospital Order Communication System (OCS), medical records, and face-to-face interviews, using a structured questionnaire. Clinical, socio-demographic and private health insurance related factors were also gathered. Results : Overall, 43.9% of patients had purchased one or more private health insurance schemes related to cancer, with an average monthly premium of \65,311 and an average benefit amount of \19million. Females, younger aged, high income earners, national health insurers and metropolitan citizens were more likely to purchase private health insurance than their counterparts. Conclusions : About half of Korean people have supple-mentary private health insurance and their benefits are sufficient to cover the out-of-pocket fees required for cancer treatment, but inequality remains in the purchase of private health insurance. Further studies are needed to investigate the impacts of private health insurance on NHI, and the relationship between cancer patients' burden and benefits.

• Journal of Life Science
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• v.26 no.2
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• pp.241-246
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• 2016

In the present study, ethanol extracts and their subsequent organic solvent fractions were extracted from the lees of Ehwa Makgeolli containing oriental herbs, a commercialized traditional Korean rice wine, and the prepared lees samples were designated as from KSD-E3-1 to KSD-E3-5. First, their effects on cell viability and on the expression of pro-apoptotic ATF3 and NAG-1 genes in human colorectal HCT116 cells were investigated. Among the treated lees samples, the hexane fraction (KSD-E3-2) and the ethyl acetate fraction (KSD-E3-3) of lees extracts from Ehwa Makgeolli significantly reduced cell viabilities, in a dose dependent manner. The treatment with KSD-E3-2 and KSD-E3-3 also increased the expression of pro-apoptotic NAG-1 and ATF-3 genes and their proteins, which were detected with RT-PCR and Western blot analysis, respectively. In addition, poly-(ADP-ribose) polymerase (PARP) cleavage was detected by treatment with the fraction KSD-E3-3, indicating that KSD-E3-3 could induce apoptosis in HCT116 cells. Interestingly, this PARP cleavage was recovered by transfection of NAG-1 small interfering RNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by the fraction KSD-E3-3 from Ehwa Makgeolli. Overall, the findings may help in understanding the molecular mechanisms of the anti-proliferative and pro-apoptotic activities mediated by the lees of Ehwa Makgeolli.