• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2021-2026
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• 2014

Aim: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. Methods: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. Results: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). Conclusion: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2851-2857
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• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5361-5365
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• 2013

The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR=2.22, 95% CI 1.51-3.27, ${\chi}^2$=16.90, P<0.001), dominant model (AA/GA vs. GG: OR=1.25, 95% CI 1.00-1.55, ${\chi}^2$=3.98, P=0.046), recessive model (AA vs. GA/GG: OR=2.14, 95% CI 1.47-3.09, ${\chi}^2$=16.68, P<0.001) and allele comparison (A vs. G: OR=1.33, 95% CI 1.13-1.57, ${\chi}^2$=11.66, P=0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility.

• Toxicological Research
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• v.8 no.2
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• pp.171-177
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• 1992

To investigate a short term screening method for carcinogenic quinone compounds, 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage, was determined in the kidney and liver DNA isolated from Sprague-Dawley rats after i.p.injection of 7 mg/kg adriamycin (AM), 7mg/kg tetrahydropyranyladriamycin (THP), and 10mg/kg daunomycin (DM) by HPLC-electrochemical detector system. 8-OHdG was also determined from rat hepatocvtes and calf thymus DNA exposed to AM, DM and THP. When rats were treated with DM and THP, 8-OHdG was significantly increased in the kidney compared to control group, and remained at high level (7.9~9.0, 8-OHdG/dG${\times}10^4$)at the end of experiments (48hr after treatment). 8-OHdG level in cultured hepatocyte exposed to AM, DM and THP was 1.5~2 fold higher than control at all time points. (1,2,3,4hr after treatment). From calf thymus DNA exposed to AM, DM and THP, 8-OHdG was 2.5 fold higher than of control. These results suggest that quantitation of 8-OHdG may provide a useful marker for identifying target organ in oxidative chemical carcinogenesis and for short term screening of free radical generating carcinogens.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2003.10a
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• pp.152-152
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• 2003

As utilization of radiation in medicine, industry and biochemical research increases, the protection against radiation damage has become an important issue. Natural products such as herbal medicines are beginning to receive attention as modifiers on the radiation response. In the present study, the protective effect of a herb, Menthae Herba, against radiation-induced DNA damage was evaluated using alkaline single-cell gel electrophoresis (SCGE; comet assay) in the mouse peripheral blood Iymphocytes and the micronucleus formation test in the Chinese hamster ovary (CHO) cells. The tail moment, which was a marker of DNA damage in the SCGE, and the frequency of micronuclei was decreased in groups treated with Mentae Herba extract before exposure to 200 cGy of gamma-ray. We also confirmed its activities to scavenge DPPH and hydroxyl radicals. These experiments demonstrated that Menthae Herba was effective at reducing the radiation-induced damage of DNA and scavenging free radicals. It is plausible that scavenging of free radicals by Menthae Herba may have played an important role in providing the protection against the radiation-induced damage to the DNA. These results indicated that Menthae Herba might be a useful radioprotector and that radical scavenging appears to be one of the mechanisms of radiation protection.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.143-151
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• 2010

Pluripotency of human embryonic stem cell (hESC) is one of the most valuable ability of hESCs for applying cell therapy field, but also showing side effect, for example teratoma formation. When transplant multipotent stem cell, such as mesnchymal stem cell (MSC) which retains similar differentiation ability, they do not form teratoma in vivo, but there exist limitation of cellular source supply. Accordingly, differentiation of hESC into MSC will be promising cellular source with strong points of both hESC and MSC line. In this study, we described the derivation of MSC like cell population from feeder free cultured hESC (hESC-MSC) using direct differentiation system. Cells population, hESC-MSC and bone marrow derived MSC (BM-MSC) retained similar characteristics in vitro, such as morphology, MSC specific marker expression and differentiation capacity. At the point of differentiation of both cell populations, differentiation rate was slower in hESC-MSC than BM-MSC. As these reason, to verify differentially expressed molecular condition of both cell population which bring out different differentiation rate, we compare the molecular condition of hESC-MSC and BM-MSC using 2-D proteomic analysis tool. In the proteomic analysis, we identified 49 differentially expressed proteins in hESC-MSC and BM-MSC, and they involved in different biological process such as positive regulation of molecular function, biological process, cellular metabolic process, nitrogen compound metabolic process, macromolecule metabolic process, metabolic process, molecular function, and positive regulation of molecular function and regulation of ubiquitin protein ligase activity during mitotic cell cycle, cellular response to stress, and RNA localization. As the related function of differentially expressed proteins, we sought to these proteins were key regulators which contribute to their differentiation rate, developmental process and cell proliferation. Our results suggest that the expressions of these proteins between the hESC-MSC and BM-MSC, could give to us further evidence for hESC differentiation into the mesenchymal stem cell is associated with a differentiation factor. As the initial step to understand fundamental difference of hESC-MSC and BM-MSC, we sought to investigate different protein expression profile. And the grafting of hESC differentiation into MSC and their comparative proteomic analysis will be positively contribute to cell therapy without cellular source limitation, also with exact background of their molecular condition.

• Journal of Plant Biotechnology
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• v.7 no.4
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• pp.241-246
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• 2005

Factors affecting regeneration of different Rubus varieties (blackberry, raspberry and their hybrid) were examined and a reliable regeneration system was established. Media for stock plant maintenance were tested; different explants and media were investigated to find the best circumstances for the regeneration. The effect of the commonly used antibiotics was studied to determine the most suitable one for selection of the transformants. We found that both MS and LS media supplemented by $20\;gL^{-1}$ sucrose are suitable for the stock plant maintenance. The optimal hormone content for the stock plants is $0.125\;mgL^{-1}$ 6-benzylaminopurine (BAP) with $0.01\;mgL^{-1}$ indole-3- butyric acid (IBA). The highest regeneration rate was observed on medium containing MS salts with B5 vitamins complemented with glucose, sucrose, maltose, $10\;gL^{-1}$ each, supplemented with benzylaminopurine riboside (BAR) ($2\;mgL^{-1}$) and indole-3-acetic acid (IAA) ($0.1\;mgL^{-1}$). The regenerated shoots appeared directly from the cut edges, without callus phase. Hygromycin and geneticin proved to be good selection agents for the Rubus explants, but due to their severe effect on the tissues we propose to use marker-free constructions for the transformation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7193-7196
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• 2013

Ovarian cancer patients need a surveillance program for the detection of tumor progression after completion of treatment. The methods generally consist of history taking, physical examination, tumor marker monitoring and imaging. However, the details of recurrence detection with each method are not well defined. To clarify this issue, ovarian cancer patients who achieved complete or partial responses and developed tumor progression at the follow up time between January 2004 and December 2010 in University Hospital Chiang Mai, Thailand, were reviewed. Clinical data, CA 125 level and imaging results at the tumor progression time were recorded and analyzed. There were 144 ovarian cancer patients meeting the inclusion criteria with the mean age of 51 years and 62.5% of them were in an advanced stage. Complete response was achieved in 89 patients (61.8%) after primary treatment. The median progression free survival and overall survival were 15.5 months and 37.5 months, respectively. Abnormal symptoms presented in 49.3% of the studied patients and 59.7% developed physical examination abnormalities. In addition, CA 125 was elevated in 89.6% while in 74.3% of tumor progression was identified by CT-scan. Short treatment time period and a high level of CA 125 were significant independent prognostic factors in these patients. In conclusion, careful history taking, physical examination and monitoring of CA 125 levels are important methods for tumor progression detection in a surveillance program for epithelial ovarian cancer patients.

• BMB Reports
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• v.48 no.11
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• pp.597-598
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• 2015

Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca⁺⁺-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

• 한국전산유체공학회:학술대회논문집
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• 1996.05a
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• pp.85-92
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• 1996

Numerical simulations are made for the three-dimensional flow around a wing in ground effect craft haying the complex geometry. A numerical tool is developed for the primary design of hull and wing shape of practical Wing-In-Ground effect(WIG) stop. The finite-difference method is utilized to descretize the governing equations and pressure field is obtained by using Marker-And-Cell(MAC) method. The air and water flows are simultaneously simulated in the time-marching solution procedure for the Navier-Stokes equation. The porosity technique and the density function are devised for the implementation of the three-dimensional body-boundary and the free-surface conditions, respectively. In this paper, a craft is modeled simply by three blocks containing a wing mounted on a main body horizontally, with the endplate. The numerical calculations of a WIG advancing in a calm water are performed and the WIG-generated wave profiles are also obtained. In the final paper, details of the numerical methods employed for the present study and calculated results are discussed.