• Food Science and Preservation
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• v.11 no.2
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• pp.214-220
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• 2004

This study was carried out to determine the antioxidative, antimutagenic, and anticancer effects of functional food manufactured from fermented soybean(FFMFS) using DPPH free radical donating method, Ames test and cytotoxicity, respectively. FFMFS extracted with ethanol and then further fractionated to n-hexane, chloroform, ethyl acetate(EtOAc), butanol and water, stepwise. Among five fractions, the EtOAc fractions showed highest electron donating activities (31.6 $\mu\textrm{g}$/mL). The inhibition rate of ethanol extract(200 $\mu\textrm{g}$/plate) of FFMFS in the S. typhimurium TA100 strain showed 84.8% against the mutagenesis induced by MNNG. In addition, the suppression of EtOAc fractions with same concentration of FFMFS the S. typhimurium TA98 and TA100 strains showed 88.7% and 92.8% inhibition against Trp-P-l, respectively. The cytotoxic effects of FFMFS against the cell lines with human lung carcinoma(A549), human gastric carcinoma(AGS) and human breast adenocarcinoma(MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL FFMFS of EtOAc fraction showed strong cytotoxicities of 84.5%, 88.7% and 85.6% against A549, AGS and MCF-7, respectively.

• Korean Journal of Medicinal Crop Science
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• v.10 no.2
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• pp.139-143
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• 2002

Ixeris dentate was used to extract the natural compounds with methanol and then the extracts were further fractionated using n-hexane, ethyl acetate, butanol and aqueous fraction. The methanol extract of Ixeris dentate had strong antimutagenic effect in Ames mutagenicity test. Among the extracts fractioned from the methanol extract, the butanol fraction exhibited the greatest antimutagenic effect suppressing the mutagenicity of Salmonella typhimurium TA100 with inhibition rate of 88.93%. Cancer cell lines include human lung carcinoma(A549), human breast adenocarcinoma(MCF-7) and human hepatocellular carcinoma(Hep3B). Hexane fraction showed the strongest effect against A549, MCF-7 and Hep3B at the same concentration compared to those of other fractions.

• Toxicological Research
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• v.35 no.2
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• pp.167-179
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• 2019

Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ${\alpha}$-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ${\alpha}$-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ${\alpha}$-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ${\alpha}$-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ${\alpha}$-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ${\alpha}$-mangostin and apigenin arrested the cell cycle at the $G_2/M$ phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ${\alpha}$-mangostin-treated SKOV-3 cells, respectively. ${\alpha}$-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ${\alpha}$-mangostin likely being involved with inflammation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.5
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• pp.675-681
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• 2013

Home-made broccoli Kochujang (HMBK) was prepared with the addition of 5% broccoli leaf powder. Its physicochemical and functional properties were measured in extracts (80% methanol, 80% ethanol, and distilled water) and compared with home-made Kochujang (HMK) and factory-produced Kochujang (FPK). Total phenolic content (TPC) was 22% higher in methanol extract from HMBK (524.2 GAE/100 g) compared to HMK (431.0 GAE/100 g). TPC was 8% higher in ethanol extract from HMBK (541.9 GAE/100 g) compared to HMK (499.9 GAE/100 g). DPPH radical scavenging activity was 1.6 times higher in the methanol extracts from HMBK than HMK. In contrast there was no difference in DPPH radical scavenging activity between HMBK and HMK. Oxygen radical absorbance capacities in methanol and ethanol extracts from HMBK were similar to HMK, but both were higher than extracts from FPK (55% and 23% higher, respectively). Inhibition of angiotensin I converting enzyme activity in methanol extracts from HMBK was similar to HMK, but it was 2.6 times higher than inhibition activities from FPK. Interestingly, only ethanol extract from HMBK showed a 10.7% and 18.3% inhibition on cell growth of the human colon adenocarcinoma grade II cell line (HT-29) and human lung carcinoma cell line (NCI-H1229), respectively. These results indicate home-made Kochujang with broccoli leaf powder contains high total phenolics, antioxidant activities, and cancer cell growth inhibition activities.

• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.983-994
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• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.1
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• pp.38-44
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• 1995

Metastatic bone tumor is the most common bone tumor and 32.5% of all primary malignant tumors are eventually metastasize to bone. Metastatic bone tumor has been more frequently encountered disease in the orthopedic fields due to the greater longevity of life of the patients with primary visceral cancers by major advances in early detection, diagnosis, and surgical/radiotherapeutic/chemotherapeutic treatment of primary and metastatic lesions. Therefore, the epidemiologic data about the incidences and the patterns of bone metastasis is important. We reviewed 417 patients who were diagnosed and treated for metastatic bone tumor at Kosin University Medical Center from 1985 to 1993 to analyse the primary lesion, age and sex distributions, location of bone metastasis, patterns of metastasis according to the primary. The results were as follows : 1. The common origin of bone metastasis were lung(29.5%), stomach(15.3%), breast(11.3%), unknown(7.7%), cervix(5.3%), liver(4.8%) in order of frequency. 2. There were 251 men and 166 women and their mean age was 54.8 years and the peak age incidence was in 6th decades. Most cases(85.3%) were occured beyond 5th decades. 3. The preferred sites of metastatic deposits were spine(64.0%), pelvis(40.5%), rib(38.8%), femur(36.7%), skull(21.1%), humerus(13.9%), scapula(13.0%) in order of frequency. In the spine, thoracic(42.1%), lumbar(39.1%), cervical(13.2%), sacral(5.6%) vertebrae were involved in order of frequency. 4. Multiple bone metastases were more common(73.1%) than single metastasis(26.9%). 5. In the lung cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, pelvis, femur. 6. In the stomach cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, femur, pelvis. 7. In the breast cancer, the peak age incidence was 5th decades, and the preferred sites of bone metastasis were spine, rib, pelvis. 8. In the bone metastasis with unknown primary site, the peak age incidence was 7th decades, the preferred sites of bone metastasis were spine, femur, pelvis, and the common histologic types were adenocarcinoma and squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Journal of Life Science
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• v.29 no.6
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• pp.679-687
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• 2019

Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• Journal of Life Science
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• v.31 no.2
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• pp.199-208
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• 2021

Euonymus porphyreus, a species of plant in the Celastraceae family, is widely distributed in East Asia, especially in Southern China. The botanical characteristics of E. porphyreus have been reported, but its antioxidative and anticancer activities remain unclear. In this study, we evaluated the antioxidative and anticancer effects of ethanol extracts of E. porphyreus (EEEP) and the molecular mechanism of its anticancer activity in human lung adenocarcinoma A549 cells. The total polyphenol and flavonoid compound contents from EEEP were 115.42 mg/g and 23.07 mg/g, respectively. EEEP showed significant antioxidative effects with a concentration at 50% of the inhibition (IC50) value of 11.09 ㎍/ml, as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. EEEP showed cytotoxic activity by increasing the SubG1 cell population of A549 cells in a dose-dependent manner. Apoptosis in A549 cells treated with EEEP was evident due to increased apoptotic cells and apoptotic bodies, as detected by Annexin V and 4,6-diamidino-2-phenylindole (DAPI) staining, respectively. EEEP-induced apoptosis resulted in increased expression of the First apoptosis signal (Fas), p53, and Bax, with decreased expression of Bcl-2 and subsequent activation of caspase-8, -9, and caspase-3, leading to cleavage of poly (ADP-ribose) polymerase (PARP). Collectively, these results suggest that EEEP may exert an anticancer effect by inducing apoptosis in A549 cells through both intrinsic and extrinsic pathways.