• Journal of Life Science
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• v.25 no.9
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• pp.1051-1058
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• 2015

Citrus mutant fruits were induced by irradiation of citrus budsticks with 120 Gy of cobalt (⁶⁰CO) gamma irradiation. The citrus mutant inhibited the growth and induced apoptosis in various human cancer cells, including A549, HepG2, HCT116, MCF-7, and Hela. The results of a trypan blue exclusion assay showed that citrus mutant fruits exhibited excellent antiproliferation activity in various human cancer cells and low cytotoxicity in normal 16HBE140- and CHANG cells. In addition, the cell death induced by the citrus mutant fruits was associated with an increased population of cells in sub-G1 phase, and it caused DNA fragmentation in human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells. It also up-regulated the amount of cellular nitric oxide (NO^•) produced as a result of nitric oxide synthase (NOS) activation and suppressed the inhibitor of apoptosis protein (IAP) family in A549 and HepG2 cells. These findings indicate that the citrus mutant fruits activates the NO^•-mediated apoptotic pathway in A549 and HepG2 cells. It may merit further investigation as a potential chemotherapeutic and chemopreventive agent for the treatment of various types of cancer cells. The results provide important major new insights into the mechanisms of the anticancer activity of citrus mutant fruits.

• Molecules and Cells
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• v.43 no.5
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• pp.469-478
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• 2020

Hepatitis C virus (HCV) propagation is highly dependent on cellular proteins. To identify the host factors involved in HCV propagation, we previously performed protein microarray assays and identified the LIM and SH3 domain protein 1 (LASP-1) as an HCV NS5A-interacting partner. LASP-1 plays an important role in the regulation of cell proliferation, migration, and protein-protein interactions. Alteration of LASP-1 expression has been implicated in hepatocellular carcinoma. However, the functional involvement of LASP-1 in HCV propagation and HCV-induced pathogenesis has not been elucidated. Here, we first verified the protein interaction of NS5A and LASP-1 by both in vitro pulldown and coimmunoprecipitation assays. We further showed that NS5A and LASP-1 were colocalized in the cytoplasm of HCV infected cells. NS5A interacted with LASP-1 through the proline motif in domain I of NS5A and the tryptophan residue in the SH3 domain of LASP-1. Knockdown of LASP1 increased HCV replication in both HCV-infected cells and HCV subgenomic replicon cells. LASP-1 negatively regulated viral propagation and thereby overexpression of LASP-1 decreased HCV replication. Moreover, HCV propagation was decreased by wild-type LASP-1 but not by an NS5A binding-defective mutant of LASP-1. We further demonstrated that LASP-1 was involved in the replication stage of the HCV life cycle. Importantly, LASP-1 expression levels were increased in persistently infected cells with HCV. These data suggest that HCV modulates LASP-1 via NS5A in order to regulate virion levels and maintain a persistent infection.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.100-106
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• 1995

Antibodies to hepatitis C drew attention because of high morbidity to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV was known to be transmitted by transfusion, sexual behavior and parenteral drug use. However, some kind of autoimmune mechanism was suggested to be involved in the genesis of HCV-induced liver diseases. We hypothesized the prevalence of having anti-HCV might be higher in psychiatric patients rather than general population because of the characteristic route of transmission. Using Abbott HCV BA kit, anti-HCV was detected in the sera of 113 psychiatric inpatients from early December in 1992 to late May in 1994. The Positivity of anti-HCY was significantly(P<0.05) higher among psychiatric inpatients(10.6%) than in healthy controls(3.0%). There were no disease specificity among psychiatric inpatients who had anti-HCV, though alcoholics tended to have more anti-HCV. We couldn't find any significant correlation of anti-HCV with age, seasons of birth, lymphocytes (%) and liver function.

• Journal of radiological science and technology
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• v.38 no.2
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• pp.115-120
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• 2015

To study the differences of focal liver lesion image detection at 3 minute, 10 minute and 15 minute time points on gadoxetic acid (GA)'s enhanced MR imaging with a flip angle (FA) of $30^{\circ}$ compared with a $11^{\circ}$. The subjects were 69 patients evaluated with GA enhanced MR imaging with 3.0T MR scanner. The patients are total 35(23 men and 7 women at the mean age of 60.4 years), hepatocellular carcinoma(23) and metastsis(12) except for normal, cyst and hemangioma. After GA was injected, FA $11^{\circ}$ and $30^{\circ}$ images were obtained at 3 minute, 10 minute and 15 minute time points respectively. After quantitative and qualitative assessment of each image was done, statistical analysis was performed by using the independent sample T-test. From both quantitative and qualitative assessment of 3 minute and 10 minute MR images after the injection of GA, FA $30^{\circ}$ images was found to be superior than FA $11^{\circ}$, but there were no statistical significance. However, at 15 minute time point, Statistically significant FA $30^{\circ}$ image(p<0.05) was better than FA $11^{\circ}$ therefore, the FA $30^{\circ}$ improves the focal liver lesion detection. FA $30^{\circ}$ of MR image can detect liver lesion more sensitively than the existing $FA11^{\circ}$ image after GA contrast enhancement at 15 minute time point.

• Journal of Nutrition and Health
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• v.53 no.2
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• pp.111-120
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• 2020

Purpose: Corosolic acid (CA), also known as 2α-hydroxyursolic acid, is present in numerous plants, and is reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells such as osteosarcoma, hepatocellular carcinoma, lung adenocarcinoma, and colon cancer. However, the anti-cancer activity of CA on human breast cancer cells and the underlying mechanisms remain to be elucidated. The present study aimed to investigate the anticancer effects of CA in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, apoptosis marker protein expression, migration, invasion rate, and vascular endothelial growth factor (VEGF) levels were assessed by treating MDA-MB-231 cells to increasing concentrations of CA. Results: The results showed that CA significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. To assess the effect of CA on apoptosis, nuclei of MDA-MB-231 cells were stained with DAPI solution. Chromatin condensation, which indicates apoptosis, was observed to increase dose-dependently. In addition, western-blot analysis revealed elevated levels of the apoptosis marker proteins (Bax and cleaved caspase 3) subsequent to MDA-MB-231 exposure to CA. ROS production was also increased in the CA-induced apoptosis in MDA-MB-231 treated cells. Interestingly, CA exposure resulted in significantly decreased migration and invasion rates in the MDA-MB-231 cells. Data further revealed that exposure to CA markedly decreased the VEGF concentration, thereby contributing to a reduction in angiogenesis. Conclusion: Our results determined that exposure to CA induces anti-proliferation, apoptosis, and ROS production, and suppresses cell migration and invasion rate in MDA-MB-231 cells. Taken together, these results indicate the potential of CA to be applied as an effective chemotherapeutic agent for treating breast cancer.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.142-147
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• 1997

Purpose: To compare the effectiveness of the in-phase (IP) sequence and the opposed-phase (Op) sequence in the detection of focal hepatic lesions in the single breath-hold hepatic MR imaging with fast gradient T1-weighted pulse sequences. Materials and Methods: IP and OP T1-weighted breath-hold imaging was performed using fast gradient echo sequences in 45 patients referred for known focal hepatic lesions, in which 78 lesions were detected. Three blind readers independently reviewed the images for lesion detectability. The signal-to-noise ratio (SNR) of the liver, the lesion-to-liver contrast-to-noise ratio (CNR) and the liver-to-spleen CNR were also compared. A consensus was reached by three readers to determine which sequence is better in image quality. Results: On OP images, 61(78%), 61(78%), and 63(89%) lesions were correctly identified for reader 1, 2 and 3, respectively. On IP images, 66(85%), 65(83%), and 65(93%) lesions were detected for each reader, respectively. When two image sets were combined, 71(91 %), 69(88 %), and 76(97%) lesions respectively were detected for each reader. In cases of hepatocellular carcinoma, liver-to-Iesion CNR was greater on the OP images(p (0.05), but in other lesions significant difference was not demonstrated. Liver-to-spleen CNR was higher on OP images(p ( 0.1), but the SNR of the liver was higher on the IP images. Conclusion: Use of both IP and OP imaging can be helpful to avoid erroneous missing of some focal hepatic lesions.

• Journal of the Korean Society for Nondestructive Testing
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• v.31 no.5
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• pp.487-493
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• 2011

Alpha fetoprotein(AFP), which is serological marker for hepatocellular carcinoma, was quantitatively measured by its normal concentration, 10 ng/ml, with a label-free piezoelectric microcantilever mass sensor. The principle of detection is based on changes in the resonant frequency of the piezoelectric microcantilever before and after target molecules are attached to it, and its resonant frequency is measured electrically using a conductance spectrum. The resonant frequency of the developed sensor is approximately 1.34 MHz and the mass sensitivity is approximately 175 Hz/pg. The sensor has high reliability as mass sensor by reducing the effect of surface stress on resonant frequency due to attached proteins. 'Dip and dry' technique was used to react the sensor with reagents for immobilizing AFP antibody on the sensor and detecting AFP antigen. The measured mass of the detected AFP antigen was 6.02 pg at the concentration of 10 ng/ml, and 10.67 pg at 50 ng/ml when the immunoreaction time was 10 min.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.388-392
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• 2006

To verify the solitary nodular hepatocellular tumor model induced by intraparenchymal VX2 tumor cell injection and assess the diagnostic imaging character by computed tomography in rabbits. The tumor cell fragment ($1{\sim}2mm^3$) was loaded in Seldinger needle and directly implanted into the livers of 80 New Zealand white rabbits. The tumor size and patterns of tumor growth were evaluated using spiral computed tomography (CT) at 1, 2, and 3 weeks after tumor implantation. A solitary nodular tumor was successfully created in 82.5% (66/80). The mortality rate was 5% (4/80). The tumor sizes measured were 7.46.3, 14.210.8, 16.212.6 cm at 1, 2, and 3 weeks after tumor implantation on arterial phase CT images. The tumors were round to oval shape with peripheral enhancement and central hypoattenuation on arterial phase, and hypoatteuated wash-out pattern on portal phase. It is considered that inoculation of tumor fragment loaded in Seldinger needle is useful and practical method for creating a solitary hepatic tumor. And CT scanning are valuable to investigate the hepatic tumor and compatible to the observations on macro-and microscopic findings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4633-4639
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• 2015

Background: Previous studies suggested that the H63D and C282Y polymorphisms in the HFE genes were susceptible to many cancer types, nevertheless, the present results were inconclusive. Thus, the present study was aimed to evaluate the association between the HFE polymorphisms (H63D and C282Y) and cancer risk via meta-analysis. Materials and Methods: We retrieved PubMed, Google Scholar, Embase and Web of Science databases for all eligible studies up to April 1, 2015. All the statistical analysis was conducted by STATA 12.0. Results: Finally, a total of 20 publications including 24 case-control studies, comprising 6,524 cases and 31,080 controls for HFE-C282Y polymorphism and 19 publications including 21 case control studies, comprising 5,648 cases and 14,257 controls for HFE-H63D polymorphism were enrolled in our analysis. An increased risk for overall cancer risk was identified in HFE-H63D polymorphism under allele contrast (D vs H: OR=1.153; 95%CI=1.031-1.289, Pheterogeneity=0.002), homozygotes vs wide type (DD vs HH: OR=1.449; 95%CI=1.182-1.777, Pheterogeneity=0.391), dominant model (DD+HD vs HH: OR=1.145; 95%CI=1.007-1.301, Pheterogeneity=0.002) and recessive model (DD vs HD+HH: OR=1.416 ; 95%CI=1.156-1.735, Pheterogeneity=0.549), as well as HFE-C282Y under homozygotes vs wide type (YY vs CC: OR=1.428, 95%CI=1.017-2.006, Pheterogeneity=0.220). In addition, in the stratified analysis by cancer type, an increased risk was identified in hepatocellular carcinoma and breast cancer in C282Y polymorphism, as well as pancreatic cancer in H63D polymorphism, whereas a decreased risk of colorectal cancer was identified in C282Y polymorphism. Conclusions: Present study suggested that H63D and C282Y polymorphisms associated with an increased risk of overall cancer. Nevertheless, well-designed study with large sample size will be continued on this issue of interest.