• 한국식품영양학회지
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• 제32권5호
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• pp.565-570
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• 2019

Proteasome inhibitors can improve the efficiency of cancer treatments by inhibiting nuclear factor ${\kappa}B$($NF-{\kappa}B$) activation in cancer cells. Lentils are a type of beans of which consumption of such beans is increasing. The purpose of this study was to investigate the effects of lentils extract (LE) on the proteasomal activities, $NF-{\kappa}B$ activation, and cell cycle in HepG2 human liver cancer cells. LE treatments inhibited proteasomal activities at concentrations of 10, 50, and $100{\mu}g/mL$ respectively, and repressed $NF-{\kappa}B$ activation at concentrations of 1, 10, and $100{\mu}g/mL$ respectively, in HepG2 cells. LE treatments at concentrations of 1, 10, and $100{\mu}g/mL$ respectively, increased sub-G1 cell population in HepG2 cells, which may be the result of apoptosis. The results suggest that LE inhibited $NF-{\kappa}B$ activation partially with its proteasome inhibitory activities, and the increase of sub-G1 cell population was induced partially, by inhibition of $NF-{\kappa}B$ activation in HepG2 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.201-205
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• 2016

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

• 대한피부과학회지
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• 제56권10호
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• pp.603-608
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• 2018

Background: It is well known that skin cancer and precancerous disease develop more frequently in patients undergoing solid organ transplantation than normal populations in the normal population in Western countries. However, to date, the clinical and demographic features of skin cancer and precancerous disease after solid organ transplantation are not established in Asian countries. We evaluated the clinical and demographic features of primary skin cancer and precancerous lesions after solid organ transplantation and compared these with the trends observed in Western countries. Methods: We retrospectively reviewed the medical records of patients who underwent kidney, liver, heart, and lung transplantation between January 1995 and April 2017 and who developed skin cancer or precancerous lesions after transplantation. The various lesions observed were squamous and basal cell carcinoma, malignant melanoma, Kaposi sarcoma, Bowen's disease, and actinic keratosis. Results: We identified 4604 patients who received organ transplant. The mean age of patients was 44.8 years (male, 64.6%; female, 35.4%), and the sum of the person-year of observation time was 31,024 person-years. The incidence rate per 100,000 person-years was 29.01 for squamous cell carcinoma, 19.34 for basal cell carcinoma, 6.45 for malignant melanoma 3.22 for Kaposi sarcoma, and 74.17 for Bowen's disease and actinic keratosis. The incidence rate per 100,000 person-years was the highest in patients undergoing heart transplantation (610.50), followed by those who underwent kidney transplantation (136.54) and liver transplantation (90.15). Koreans showed lower incidence rates than those observed in Westerners. Conclusion: The incidence of primary skin cancer and precancerous lesions after solid organ transplantation in Koreans was lower than that in Westerners. Squamous cell carcinoma was the most common skin cancer in patients undergoing solid organ transplantation and the incidence rate of skin cancer and precancerous lesions was the highest in patients undergoing heart transplantation.

• Archives of Pharmacal Research
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• 제20권1호
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• pp.29-33
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• 1997

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (ie., cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.

• 한국임상수의학회지
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• 제38권4호
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• pp.179-183
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• 2021

A 12-year-old male American Cocker Spaniel was diagnosed with a type of chronic hepatits (CH) called cholangioheaptits. Routine supportive medication was administered to the patient, and ex vivo boosted immune cell (EBI-C) therapy was used for the treatment. A histopathologic examination of the liver 19 months later revealed that the cholangiohepatitis had progressed to cholangiocarcinoma. The medication and immune cell therapy was maintained. Two months after the new diagnosis, the patient's state worsened, and the dog died 635 days after the first visit. EBI-C therapy is a type of immunotherapy, where immune cells are isolated from the patient's peripheral blood mononuclear cells, expanded ex vivo, and then infused into the patient intravenously every two weeks. EBI-Cs (mean: 2.78 × 10⁸ cells) were obtained 38 times and infused every two weeks. Most EBI-C were T-lymphocytes (99.24% of total EBI cells). T-lymphocytes produce large interferon (IFN)-γ, and IFN-γ inhibits liver fibrosis in dogs with CH. Moreover, in bile duct cancer, an increase in T-lymphocytes correlates with decreasing tumor invasion and metastasis. Thus, we propose that EBI-C therapy is applicable as a new supportive therapy for canine liver disease if other treatments like drug medication, surgery, or radiation are unavailable.

• Preventive Nutrition and Food Science
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• 제5권1호
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• pp.48-53
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• 2000

Inhibitory effects of the methanol extract, hexane extract, methanol soluble fraction (MSF) and juice from 3 weeks fermented Kimchi on the tumor formation in sarcoma-180 cell transplanted mice were studied. Effects of the solvent extracts and juice of the Kimchi on the levels of lipid peroxide, glutathione, and the enzyme activities of the liver were also investigated in normal and sarcoma-180 cell transplanted mice. At 32 days following trans-plantation, MSF reduced the tumor formation by 54% compared with the control group, resulting in the smallest tumor weight. Lipid peroxided content in liver increased by the transplantation of sarcoma-180 cells. However, it decreased when MSF of Kimchi was treated to the mice. MSF also suppressed xanthine oxidase activity in cytosol of the liver cells in mice transplanted by sarcoma-180 cells. Kimchi extracts had no inhibitory effect on hepatic aminopyrine-N-demethylase activity in sarcoma-180 cell transplanted or normal mice. Methanol extract and hexane extract of Kimchi slightly increased hepatic glutathione contents in sarcoma-180 treated mice. The injection of MSF from Kimchi markedly increased glutathione levels in the liver of sarcoma-180 treated mice. The injection of MSF from Kimchi markedly increased glutathione levels in the liver of sarcoma-180 treated mice compared to the controls. The MSF recovered the activities of hepatic glutathione reductase and glutathione S-transferase that decreased by the injection of sarcoma-180 cells. These results showed that MSF of Kimchi could suppress the growth of tumors, inhibiting lipid peroxide production and xanthine oxidase activity, in mice. We also suggested that Kimchi extract might play an important role in the prevention of cancer by enhancement of the glutathione level itself as well as via glutathione reductase and glutathione S-transferase.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1833-1837
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• 2015

An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam-III (10-amino-2,3,4,6-tetramethoxyphenanthrene-1-carboxylic acid lactam). It is cytotoxic to various human and murine cancer cell lines; however, the molecular mechanisms remain unclear. The aims of this study were to investigate cytotoxic effects on and mechanism (s) of human cancer cell death in human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay to determine $IC_{10}$, $IC_{20}$ and $IC_{50}$ levels, reactive oxygen species (ROS) production with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9 activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates, viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader. Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'-dihexyloxacarbocyanine iodide ($DiOC_6$) and using flow cytometry. The compound was cytotoxic to HepG2 and MDA-MB-231 cells with the $IC_{50}$ levels of $26.0{\pm}4.45$ and $51.3{\pm}2.05{\mu}M$, respectively. For murine normal fibroblast NIH3T3 cells, the $IC_{50}$ concentration was $81.3{\pm}10.1{\mu}M$. ROS production was reduced in a dose-response manner in HepG2 cells. The caspase-9 and -3 activities increased in a concentration-dependent manner, whereas caspase-8 activity did not alter, indicating the intrinsic pathway activation. Enterocarpam-III decreased the mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells, suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell proliferation and induced human HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway and induction of caspase-9 activity.

• Journal of Acupuncture Research
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• 제17권1호
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• pp.189-219
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• 2000

To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of aqua-acupuncture with Rubi Fructus infusion solution, we used Rubi Fructus infusion solution(taken by water-alcohol method) put into Chung-wan (CV12) and Chok-Samni(ST36) of BALB/c or C57BL/6 which are corresponding to humanbody. We observed the cytotoxicity, the effect on the expression of MMP-9 gene, the ability to control cancer cell proliferation, change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen, number of pulmonary colony, histological analysis on tissue metastasis of lung and liver, splenic cell proliferation, the expression of cytokine gene, the number of $CD4^+$, $CD8^+$, $CD19^+$ and NK cell, and concluded like this. The results were obtained as follows : 1. Effects of Anti-cancer 1) The cytotoxicity about B16-F10 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-5}$, $2^{-6}$, $2^{-7}$, $2^{-8}$ diluent groups in Rubi Fructus infusion solution treatment was inhibited significantly, compared with control group. 2) The cytotoxicity about HT1080 cell line of $2^0{\sim}2^{-8}$ diluent groups in Rubi Fructus infusion solution treatment was inhibited significantly, compared with control group. 3) The effect on expression of MMP-9 gene was inhibited significantly in all the sample groups, compared with control group. 4) The effect on the control-ability on the cancer cell proliferation showed cytotoxicity significantly in $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-4}$, $2^{-5}$, $2^{-6}$, $2^{-7}$, diluent groups. 2. Effects of Anti-metastasis 1) S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight increase in all the sample groups, compared with control group. The surviving number increased in almost sample groups, except one group put into Chok-Samni(ST36) with 20% Rubi Fructus infusion solution treatment group that showed same number of the control group. 2) S-180 cancer cell line transplants in BALB/c mice showed high MST significantly in almost sample groups, compared with control group. But one group put into Chok-Samni(ST36) with 20% Rubi Fructus infusion solution showed low MST than control group. 3) The group injected in vein with B16-F10 cancer cell line in C57BL/6 mice showed increased ILS than control group significantly in anti-metastasis test. 3. Effects of Immune response improvement 1) The group injected in vein with B16-F10 cancer cell line in C57BL/6 mice were increased significantly in the number of leukocyte and glucose, and decreased significantly in the amount of platelet and LDH, compared with control group. However, there's no significant increase or decrease in number of erythrocyte, total protein and creatinine. 2) We couldn't find any significant relation in spleen weight of the sample group. 3) In pulmonary colony, sample group was decreased significantly, compared with control group. 4) Histological analysis of sample group inhivited compared with that of control group in both of lung and liver. 5) In immune system, all the sample groups showed having more relevancy to the effect on splenic cell proliferation than normal group. 6) Cytokine gene increased in almost sample groups, except one group treated with $50{\mu}g/m{\ell}$ Rubi Fructus infusion solution on IL-12. 7) In flow cytometry there's no significant relation in number of $CD8^+$ cell, however, the number of $CD4^+$, $CD19^+$ cell and NK cell in sample group had more relation than in control group. Above the results showed that aqua-acupuncture of Rubi Fructus solution has effects of anti-cancer, and-metastasis and immune response improvement.

• 대한예방한의학회지
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• 제18권1호
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• pp.11-21
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• 2014

Objective : This study set out to combine the treatment efficacy of Taraxacum with Dongchimi fermentation and investigate Taraxacum's effects on protection of liver cell and controlling nitric oxide(NO) through experiments, thus checking whether it had values as a physiological active matter. The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anticancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Method : The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anti-cancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Results : As shown in the chromatogram results, each valid component content increased in Taraxacum fermented by Dongchimi (TDF) for each time section. Of them, the valid component content at 36.80 minutes was approximately 2.7 times higher in TDF at 21.8% than in Taraxacum Dongchimi (TD) at 8.28%. TDF generated more excellent protection effects against the toxicity that caused oxidative damage to the liver cell(HepG2) with t-BHP than TD. The survival rate was low in TD of $100{\mu}g/m{\ell}$ and $300{\mu}g/m{\ell}$ and increased to 23.3% in TDF of $100{\mu}g/m{\ell}$. The survival rate was the highest at $300{\mu}M$ with a significant difference of 68.1%(P<0.05). Both TD and TDF showed effects of controlling nitric oxide production according to concentration with TDF recording a higher rate of controlling nitric oxide production than TD. There were significant differences(P<0.05) in the effects of controlling nitric oxide production at 200 ug/ml, 400 ug/ml in both groups. Especially the result TDF of $400{\mu}g/m{\ell}$ was thus similar to those of butein, the positive control group. Conclusion : The result of this studies is that Taraxacum fermented by Dongchimi (TDF) increased the valid component content compared with the simple mixture(TD). The findings clearly show that it is a material with the effects of improving immunity and liver cell protection. If fermentation methods are further developed to use it as a functional material, it will be subject to more opportunities of being used in other functional foods and make a contribution to integrated medicinal food development.

• Toxicological Research
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• 제26권1호
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• pp.29-35
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• 2010

The present study was conducted to investigate the antimutagenic potential of the methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The anticarcinogenic effects were also studied by calculation of the $IC_{50}$ on human cancer cell lines and investigating the function of gap junction in rat liver epithelial cells. The IB extract inhibited dose-dependently the ${\beta}$-galactosidase activity induced spontaneously at concentration of more than 200 mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01) the ${\beta}$-galactosidase activities induced by mutagen 6-chloro-9-[3-(2-chloroethylamino)proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous reversions of S. typhimurium TA 98 and 100 but benzo(${\alpha}$)pyrene (BaP)-stimulated reversions were decreased dose-dependently (p < 0.01) at the concentration of more than 100 mg/ml. The $IC_{50}$ value of stomach cancer cells was lower than that of normal rat liver epithelial cells, but the values of colon and uterine cancer cell lines were similar to those of normal rat liver epithelial cells. The transfer of dye through gap junctions was not affected by treatment of the IB extracts at any concentration during treatment periods. The simultaneously treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA) effectively prevented the inhibition of dye transfer induced by TPA 1 hour after treatment at all exposed concentrations. The number of gap junctions was significantly (p < 0.01) increased by the treatment with IB extract at concentrations of more than 40 ${\mu}g$/ml. The inhibition of the expression of gap junction proteins by TPA (0.01 ${\mu}g$/ml) was recovered dose dependently by the simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has antimutagenic and anticarcionogenic activity in vitro.