• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.60-71
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• 2000

Backgrounds : Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. Method : Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). Results : Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung canær (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T -factor, nodal involvement, differentiation Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with prognosis showed that nodal involvement was the only independent prognostic factor in all patients. Conclusion : Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.5
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• pp.515-520
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• 2007

This study was peformed to determine the antioxidative, antimutagenic and cytotoxic effects of the natural seasoning using Lentinus edodes powder (NSLP) by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical donating method, Ames test, and cytotoxicity, respectively. The scavenging effect on DPPH radical in ethyl acetate fraction of NSLP showed $155{\mu}g\;of\;RC_{50}$. The direct antimutagenic effects of ethanol extract and its solvent fractions of NSLP were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, ethanol extract of NSLP alone did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitroso guanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Ethyl acetate fraction of NSLP ($200{\mu}g/plate$) showed approximately 82% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 84% and 80% inhibitions were observed on the mutagenesis induced by 4NQO and MNNG against TA100 strain. In anticancer effects of ethanol extract and its solvent fractions of NSLP against cancer cell lines including human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), human hepatocellular carcinoma (Hep3B), human cervical adenocarcinoma (HeLa) and human gastric carcinoma (AGS) were investigated. The treatment of 1 mg/mL ethyl acetate fraction of NSLP showed strong cytotoxicity of 56.7%, 84.9%, 64.6%, 85.1% and 71.5% against A549, MCF-7, Hep3B, HeLa and AGS, respectively. In contrast 1 mg/mL treatment of NSLP extract and its solvent fractions had only $4{\sim}40%$ cytotoxicity on human transfomed primary embryonal kidney cell (293). From this result, it is suggested that NSLP is believed to have possible antioxidative, antimutagenic and anticancer capacities.

• Food Science and Preservation
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• v.11 no.4
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• pp.550-556
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• 2004

In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.416-421
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• 2008

This study was performed to determine the antimutagenic and anticytotoxic effects of soybean paste (doenjang) added deep sea water salt and see tangle in Salmonella Typhimurium TA98, TA100 and human cancer cell lines. In the Ames test, methanol extract of doenjang did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The methanol extracts of doenjang ($200{\mu}g$/plate) added deep sea salt and see tangle (doenjang C) showed approximately 89.1% and 70% inhibitory effect on the mutagenesis induced by MNNG and 4NQO against TA100 strain, whereas 84.4% inhibitions were observed on the mutagenesis induced by 4NQO against TA98 strain. The cytotoxic effects of doenjang methanol extracts against the cell lines with human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human gastric carcinoma (AGS), human lung carcinoma (A549) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL doenjang C of methanol extracts showed strong cytotoxicities of 71%, 74.4%, 66.2%, 77.3%, and 71.2% against HeLa, Hep3B, AGS, A549, and MCF-7, respectively. In contrast 1 mg/mL treatment of doenjang C methanol extracts had only $10{\sim}40%$ cytotoxicity on normal human embryonal kidney cell (293). Doenjang methanol extract inhibited significantly the tumor growth in mice injected sarcoma-180 cells. Especially, doenjang C methanol extract showed an inhibition of tumor cell activity of 33% by the administration of 25 mg/kg methanol extracts.

• Food Science and Preservation
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• v.14 no.2
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• pp.220-225
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• 2007

This study was performed to measure the antioxidative, antimutagenic, and cytotoxic properties of Prunus armeniaca using the DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical donating method, the Ames test, and cytotoxicity measurements, respectively. Electron-donating abilities were 48.3, 43.9, 14.8 and 12.9 per g dry matter of P. armeniaca seed (PAS), P. armeniaca flesh(PAF), butylated hydroxytoluene, and ${\alpha}-tocopherol$, respectively. The direct antimutagenic effects of an ethanol extract of P. armeniaca were examined in Ames tests using Salmonella typhimurium TA98 and TA100 as reporter organisms. In the Ames test, the ethanol extract of P. armenicaca alone did not exhibit any mutagenicity but the extract did show substantial inhibitory effects against mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide(4NQO). The ethanol extract of PAS(200g dry matter/plate) inhibited strain TA98 mutagenesis induced by 4NQO by ca. 37.9%, and mutation inhibition values of 42.1% and 69.4%, respectively, were observed when 4NQO and MNNG acted on the TA100 strain. The cytotoxic effects of ethanol extracts of P. armeniaca against cell lines of human lung carcinoma(A549), human breast adenocarcinoma(MCF-7), human hepatocellular carcinoma(Hep3B), human cervical adenocarcinoma(HeLa), and human gastric carcinoma(AGS) rose with increases in extract concentration. An ethanol extract(4mg/mL dry matter) of PAF showed strong cytotoxicities of 88.2%, 58%, 72.8%, 89.4%, and 91.9% against A549, AGS, MCF-7, HeLa, and Hep3B cells, respectively. In contrast, the same extract showed only 13 37% cytotoxicity for a nomal human kiney cell line(293). It is suggested that P. armeniaca possesses useful antioxidative, antimutagenic, and anticancer properties.

• Journal of Life Science
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• v.19 no.11
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• pp.1581-1590
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• 2009

Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest pacific, including Korea, Japan and China, and has been widely used as a health food for hundreds of years. Recently, H. fusiforme has been known to exert pharmacological activities including antioxidant, antimutagenic and anticoagulant activities. However, the molecular mechanisms of H. fusiforme in malignant cells have not been clearly elucidated yet. In this study, the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells were investigated. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells, which could be proved by MTT assay, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF treatment correlated with up-regulation of pro-apoptotic Bax expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase, $\beta$-catenin, phospholipase-${\gamma}1$ protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.1
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• pp.29-38
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• 2008

Purpose: The aim of this study was to investigate the feasibility of 3 ' -[F-18]fluoro-3 ' -deoxythymidine positron emission tomography(FLT-PET) for the detection of locally advanced breast cancer and to compare the degree of FLT and 2' -deoxy-2 ' -[F-18]fluoro-d-glucose(FDG) uptake in primary tumor, lymph nodes and other normal organs. Material & Methods: The study subjects consisted of 22 female patients (mean age; $42{\pm}6$ years) with biopsy-confirmed infiltrating ductal carcinoma between Aug 2005 and Nov 2006. We performed conventional imaging workup, FDG-PET and FLT PET/CT. Average tumor size measured by MRI was $7.2{\pm}3.4$ cm. With visual analysis, Tumor and Lymph node uptakes of FLT and FDG were determined by calculation of standardized uptake value (SUV) and tumor to background (TB) ratio. We compared FLT tumor uptake with FDG tumor uptake. We also investigated the correlation between FLT tumor uptake and FDG tumor uptake and the concordant rate with lymph node uptakes of FLT and FDG. FLT and FDG uptakes of bone marrow and liver were measured to compare the biodistribution of each other. Results: All tumor lesions were visually detected in both FLT-PET and FDG-PET. There was no significant correlation between maximal tumor size by MRI and SUVmax of FLT-PET or FDG-PET (p>0.05). SUVmax and $$SUV_{75} (average SUV within volume of interest using 75% isocontour) of FLT-PET were significantly lower than those of FDG-PET in primary tumor (SUVmax; $6.3{\pm}5.2\;vs\;8.3{\pm}4.9$, p=0.02 /$SUV_{75};\;5.3{\pm}4.3\;vs\;6.9{\pm}4.2$, p=0.02). There is significant moderate correlation between uptake of FLT and FDG in primary tumor (SUVmax; rho=0.450, p=0.04 / SUV75; rho=0.472, p=0.03). But, TB ratio of FLT-PET was higher than that of FDG-PET($11.7{\pm}7.7\;vs\;6.3{\pm}3.8$, p=0.001). The concordant rate between FLT and FDG uptake of lymph node was reasonably good (33/34). The FLT SUVs of liver and bone marrow were $4.2{\pm}1.2\;and\;8.3{\pm}4.9$. The FDG SUVs of liver and bone marrow were $1.8{\pm}0.4\;and\;1.6{\pm}0.4$. Conclusion: The uptakes of FLT were lower than those of FDG, but all patients of this study revealed good FLT uptakes of tumor and lymph node. Because FLT-PET revealed high TB ratio and concordant rate with lymph node uptakes of FDG-PET, FLT-PET could be a useful diagnostic tool in locally advanced breast cancer. But, physiological uptake and individual variation of FLT in bone marrow and liver will limit the diagnosis of bone and liver metastases.

• BMB Reports
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• v.40 no.5
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• pp.731-739
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• 2007

The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Journal of Food Hygiene and Safety
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• v.20 no.1
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• pp.53-57
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• 2005

This study was performed to observe the components, antioxidative, antimutagenic and cytotoxic effects of the mineral water using AOAC method, DPPH free radical donating method, Ames test and SRB assay. Mineral water contained eleven kinds of minerals among the total seventeen components and sodium and potassium ion were main components. Mineral water showed electron donating activities ($175.9{\mu}g$). The inhibition rate of mineral water ($200{\mu}g/plate$) in the Sallmonella typhimurium TA98 strain showed $54\%$ against the mutagenesis induced by Trp-P-1. In addition, same concentration of mineral water the Sallmonella typhimurium TA100 strain showed highest $67\%,\;65.8\%\;and\;63\%$ inhibition against $B({\alpha})P$, 4NQO and Trp-P-1, respectively. The cytotoxic effects of mineral water against the cell lines with Human lung carcinoma (A549), Human breast adenocarcinoma (MCF-7), Human stomach adenocarcinoma (AGS) and Human cervical adenocarcinoma (Hela) were inhibited with the increase of the mineral water. The treatment of $50{\mu}g/well$ of mineral water showed cytotoxicities of $66\%,\;47.6\%,\;37.7\%\;and\;45.6\%$ against A549, MCF-7, AGS and Hela.