• Korean Journal of Food Science and Technology
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• v.32 no.6
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• pp.1371-1378
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• 2000

This study was performed to determine the antimutagenic and cytotoxic effect of Agaricus blazei Murill methanol extract on Salmonella typhimurium TA98, TA100 and human cancer cell lines using Ames test and cytotoxicity assay, respectively. In Ames test, methanol extract from A. blazei Murill did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), 4-nitroquinoline-1-oxide(4NQO), 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indol(Trp-P-1) and $benzo({\alpha})pyrene(B({\alpha})P)$. The methanol extracts of A. blazei Murill$(200\;{\mu}g/plate)$ showed approximately 92.4%, 81.9% and 83.4% inhibitory effect on the mutagenesis induced by 4NQO, Trp-P-1 and $B({\alpha})P$ against TA98 strain, whereas 87.3%, 94.7%. 92.3% and 89.9% inhibitions were observed on the mutagenesis induced by MNNG, 4NQO, Trp-P-1 and $B({\alpha})P$ against TA100 strain. The solvent fractions of methanol extracts from A. blazei Murill except water fraction showed high antimutagenic effects of $70{\sim}90%$ against mutation induced by MNNG, 4NQO. Trp-P-1 and $B({\alpha})P$. In anticancer effects of A. blazei Murill extract and fraction against cancer cell lines including human breast adenocarcinoma(MCF7), human lung carcinoma(A549), human fibrosarcoma(HT1080), human hepatocellular carcinoma(Hep3B), human epitheloid carcinoma(HeLa), human gastric carcinoma(KATO III) and human chronic myelogenous leukemia(K562) were investigated. The treatment of 1 mg/mL A. blazei Murill extracts had the highest cytotoxicity with 91.9% against HeLa, followed by KATO III(88.7%), A549(86.5%) and Hpe3B(84.3%). Whereas 1 mg/mL treatment of A. blazei Murill extracts had only $10{\sim}40%$ cytotoxicity on human normal liver cell (WRL68).

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.5
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• pp.921-927
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• 2001

This study was performed to investigated the effects on the cytotoxicity and antigenotoxicity of Cordyceps militaris extracts on the human cancer cell lines. The ethanol extract and five fractions which were hexane, chloroform, ethylacetate, butanol and aqueous were screened for crytotoxicity on human lung carcinoma(A549). human breast adenocarcinoma (MCF-7) human epitheloid carcinoma(HeLa), human fibrosarcoma(HT1080) human hepatocellular carcinoma(Hep3B), human gastric carcinoma(KATOIII) and chronic myelogenous leukemia(K562) cell by SRB and MTT assays. The results showed that growth inhibition rates of the human cancer cell in the presence of Cordyceps militaris were inhibited with increasing concentration of the extract. The ethanol extract from Cordyceps militaris had strong inhibitory effects in1 mg/mL treatment by SRB assay , showing 89.4%, 85.7%, 72.9% and 65.5% inhibition in HT1080, HeLa, Hep3B and A549, respectively. The treatment of 1 mg/mL hexane fraction by SRB assay had the strongest cytotoxicity with 97.0% on HT1080 followed by MCF-7(92.9%) and HeLA(90.3%). The inhibition ration on KATOIII by MTT assay was much higher in the butanol (83.7%) and aqueous (80.4%) than in the ethanol extract (61.5%) And also, K562 showed similar tendency with KATOIII. The effects of Cordyceps militaris extracts on the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) induced by N-methyl-N-nitro-N-nitrosoguanidime(MNNG) were investigated in the bone-marrow cells of ICR male mice. The amount of 10, 20, 40 and 80 mg/kg of each extract were administered to animals immediately after injection of MNNG, and the exposure time was 36 hours. Significant reductions(p<0.05) with 39.7%, 52.7%, 71.4% and 83.9% were observed in the frequencies of MNPCE when 10, 20, 40 and 80 mg/kg of the hexane fraction of Coryceps militarus extracts were given to the mice.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.157-165
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• 2012

Purpose: We evaluated usefulness of abdominal compressor for stereotactic body radiotherapy (SBRT) with unresectable hepatocellular carcinoma (HCC) patients and hepato-biliary cancer and metastatic liver cancer patients. Materials and Methods: From November 2011 to March 2012, we selected HCC patients who gained reduction of diaphragm movement >1 cm through abdominal compressor (diaphragm control, elekta, sweden) for HT (Hi-Art Tomotherapy, USA). We got planning computed tomography (CT) images and 4 dimensional (4D) images through 4D CT (somatom sensation, siemens, germany). The gross tumor volume (GTV) included a gross tumor and margins considering tumor movement. The planning target volume (PTV) included a 5 to 7 mm safety margin around GTV. We classified patients into two groups according to distance between tumor and organs at risk (OAR, stomach, duodenum, bowel). Patients with the distance more than 1 cm are classified as the 1st group and they received SBRT of 4 or 5 fractions. Patients with the distance less than 1 cm are classified as the 2nd group and they received tomotherapy of 20 fractions. Megavoltage computed tomography (MVCT) were performed 4 or 10 fractions. When we verify a MVCT fusion considering priority to liver than bone-technique. We sent MVCT images to Mim_vista (Mimsoftware, ver .5.4. USA) and we re-delineated stomach, duodenum and bowel to bowel_organ and delineated liver. First, we analyzed MVCT images to check the setup variation. Second we compared dose difference between tumor and OAR based on adaptive dose through adaptive planning station and Mim_vista. Results: Average setup variation from MVCT was $-0.66{\pm}1.53$ mm (left-right) $0.39{\pm}4.17$ mm (superior-inferior), $0.71{\pm}1.74$ mm (anterior-posterior), $-0.18{\pm}0.30$ degrees (roll). 1st group ($d{\geq}1$) and 2nd group (d<1) were similar to setup variation. 1st group ($d{\geq}1$) of $V_{diff3%}$ (volume of 3% difference of dose) of GTV through adaptive planing station was $0.78{\pm}0.05%$, PTV was $9.97{\pm}3.62%$, $V_{diff5%}$ was GTV 0.0%, PTV was $2.9{\pm}0.95%$, maximum dose difference rate of bowel_organ was $-6.85{\pm}1.11%$. 2nd Group (d<1) GTV of $V_{diff3%}$ was $1.62{\pm}0.55%$, PTV was $8.61{\pm}2.01%$, $V_{diff5%}$ of GTV was 0.0%, PTV was $5.33{\pm}2.32%$, maximum dose difference rate of bowel_organ was $28.33{\pm}24.41%$. Conclusion: Despite we saw diaphragm movement more than 5 mm with flouroscopy after use an abdominal compressor, average setup_variation from MVCT was less than 5 mm. Therefore, we could estimate the range of setup_error within a 5 mm. Target's dose difference rate of 1st group ($d{\geq}1$) and 2nd group (d<1) were similar, while 1st group ($d{\geq}1$) and 2nd group (d<1)'s bowel_organ's maximum dose difference rate's maximum difference was more than 35%, 1st group ($d{\geq}1$)'s bowel_organ's maximum dose difference rate was smaller than 2nd group (d<1). When applicating SBRT to HCC, abdominal compressor is useful to control diaphragm movement in selected patients with more than 1 cm bowel_organ distance.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.1
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• pp.25-31
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• 2009

This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

• 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.

• Microbiology and Biotechnology Letters
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• v.29 no.3
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• pp.181-185
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• 2001

The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.