• Journal of Gastric Cancer
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• v.21 no.2
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• pp.191-202
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• 2021

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K_D=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K_D=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.

• Journal of Environmental Health Sciences
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• v.34 no.1
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• pp.55-61
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• 2008

This study was carried out to investigate the antioxidative and antitumor activities of Saussurea lappa for the purpose of developing a functional food. The methanol extract of Saussurea lappa was fractionated with five solvents (hexane, chloroform, EtOAc, BuOH, water) and examined for antioxidative activities and xanthine oxidase inhibitory activity in addition to growth inhibitory activity of human cancer cell (HT-29, SNU-1, HeLa). Total phenol compound contents were higher in EtOAC fraction than other fractions. Also, electron donating ability was over 90% at $500{\mu}g/ml$ (93.1 %) and $1000{\mu}g/ml$ (94.3%). The hexane fraction revealed stronger nitrite scavenging ability than the positive control (ascorbic acid) and its abilities were 22.4% and 42.8% at $500{\mu}g/ml$ and $1000{\mu}g/ml$, respectively. Xanthine oxidase inhibitory activity had similar tendency to electron donating ability. The EtOAc fraction showed high inhibition to xanthien oxidase activities at $500{\mu}g/ml$(81.9%) and $1000{\mu}g/ml$(90.4%). In the antitumor activity test, the hexane fraction exhibited potent growth inhibition activity against HT-29, SNU-1 and HeLa cells. Therefore, we believe that Saussurea lappa can be developed into a functional food with antioxidant activity. Additional studies are required for the hexane and chloroform fractions of Saussurea lappa to develop them into therapeutic supplements for stomach cancer, colon cancer, and cervical cancer.

• Korean Journal of Medicinal Crop Science
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• v.18 no.3
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• pp.135-142
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• 2010

Low quality fresh ginseng was fermented by Pheliuus linteus mycelium at $22^{\circ}C$ for 30 days, then extracted by water solvent at $100^{\circ}C$ for 180 min. On human normal cell lines (HEK293), cytotoxicity was about 10% lower in adding extracts of the fermentation ginseng than that from low quality ginseng. The fermented extracts also inhibited the growth of several human cancer cells. Among them, respectively, digestive organs related cancer cells, such as human stomach adenocarcnioma and human epithelial adenocarcinoma were most effectively inhibited up to 85% and 90%, respectively. Then, selectivities were in the ranges of 3 to 5, compared to 2 to 3 from low quality fresh ginseng. Generally, fermented ginseng extract showed higher anticancer activities as well as higher DPPH radical sacavening activity, possibly due to high contents of total phenolic components as 6.96 mg/g. It was very interesting that the fermented ginseng contained very higher contents of ginsenoside-Rc+$Rb_2$, compared to others in low quality fresh ginseng because of partition digestion of mycelium growth. The results can tell that low quality fresh ginseng can be utilized by the fermentation with Pheliuus linteus mycelium.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.399-409
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• 2009

Objectives : The aim of this study was to experiment the antitumor activity of Agrimonia pilosa Ledebour (APL) in human stomach cancer (AGS) cell lines (in vitro) and male C57BL/6J mouse (in vivo). Methods : The effects of the ethanol extract from the plant on several transplantable rodent tumors were investigated in vitro by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. DNA content analysis and Western blot analysis. Agrimonia pilosa Ledebour (APL) was given to rats with Lewis Lung Carcinoma (LLC) cells. The experimental rats were divided into 3 groups in vivo. Saline was injected into the abdominal cavity in the first group, 50 mg/kg APL was injected into the abdominal cavity in the second group and 100 mg/kg was injected into the abdominal cavity in the third group. After that, we checked their tumor volume periodically. Results : At first, human gastric cancer (AGS) cell lines (in vitro) showed decreased cell viability, and increased $sub-G_1$ contents. When we experimented rat intestinal epithelial (RIE)l as same condition, this result didn't show. With this, compared to normal cells, Agrimonia pilosa Ledebour (APL) led selectively to the extinction of cells only in human gastric cancer. Moreover, we showed that the traditional herbal medicine APL induced caspase-dependent apoptosis in AGS cells. Next, APL inhibited the growth of LLC-bearing mouse tumor. However, we could not verify APL induced caspase-dependent apoptosis in LLC-bearing mouse tumor. Conclusions : The roots of Agrimonia pilosa Ledebour (APL) contain some antitumor constituents.

• Journal of Korean Society of Forest Science
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• v.100 no.1
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• pp.14-24
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• 2011

Anticancer activity of Acer mono aqueous extracts was enhanced by nano-encapsulation process of gelatin. The cytotoxicity on human normal lung cell (HEL299) of the extracts from WE (water extract at 100) showed 23.51%, lower than that from NE (nano-encapsulatioin of water extract of Acer mono) in adding the maximum concentration of 1.0 mg/mL. NE showed more potent scavenging effect as 73.15% than the WE. On SOD-like test, the NE showed highest activity as 32.33% at 1.0 mg/mL concentration. Human stomach adenocarcinoma, liver adenocarcinoma, breast adenocarcinoma and lung adenocarcinoma cell growth were inhibited up to about 59-73%, in adding 1.0 mg/mL of NE. NE was 15% higher than conventional water extraction. Among several cancer cell lines (stomach adenocarcinoma, liver adenocarcinoma), the growth of digestive related cancer cells were most effectively inhibited as about 71-73%. The size of nano particles was in the ranges of 100-200 nm, which can effectively the penetrate into the cells, it was observed by real time confocal microscope. It tells that the aqueous extracts of Acer mono bark could be definitely enhanced by nano-encapsulation process.

• Journal of Gastric Cancer
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• v.16 no.4
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• pp.221-229
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• 2016

Purpose: Dysregulated microRNAs (miRNAs) can contribute to cancer development by leading to abnormal proliferation of cells, apoptosis, and differentiation. Although several miRNAs that are related to gastric cancer have been identified, the reported results have been inconsistent. The aim of this study was to determine miRNA expression profiles and validate miRNAs up- and down-regulated in gastric cancer. Materials and Methods: We evaluated 34 primary gastric cancer tissues and paired adjacent nontumorous gastric tissues. Total RNA was extracted, and low-molecular-weight RNAs (<200 nucleotides) were isolated for further analysis. Two pairs of tissues were processed for GeneChip microarray analysis, and the identified up- and down-regulated miRNAs were validated by real-time quantitative polymerase chain reaction (qPCR). Results: In the set of differentially expressed miRNAs, 5 were overexpressed by more than 2 fold, and 5 were reduced by 2 fold or less in gastric cancer tissues compared with normal gastric tissues. Four of these miRNAs (miR-196b-5p, miR-375, miR-483-5p, and miR-486-5p) were then validated by qPCR, and the relative expression levels of 2 miRNAs (miR-196b-5p and miR-375) were significantly different between cancer and normal tissues. Conclusions: Our results revealed that the expression of miR-196b-5p and miR-375 significantly correlates with gastric cancer. These miRNAs could therefore serve as diagnostic biomarkers of gastric cancer.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.55-61
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• 1992

Background: The lung is the most common site of metastasis and usually it manifests as a single or multiple nodules in chest X-ray. But less commonly the cancer spreads through the lymphatics and X-ray shows diffuse reticulonodular densities. Sometimes, patient is presented with respiratory symptoms only with interstitial lung infiltration before the signs of primary tumor and in that cases, the differential diagnosis with other interstitial lung disease is required. We have experienced 5 such cases, who were diagnosed as lymphangitic carcinomatosis by transbronchial lung biopsy. Methods: Clinical manifestation, pulmonary function test, modified thin section CT, bronchoalveolar lavage and transbronchial lung biopsy were done. Results: The primary tumor was gastric cancer in 3, lung cancer in 2. Pulmonary function test showed restrictive pattern with low DLco in 2 patients and obstructive pattern in one. Bronchoalveolar lavage showed lymphocytosis in 4 patients and malignant cells were found in one patient. Transbronchial lung biopsy revealed malignant cells localized to the lymphatics (peribronchial, perivascular and perialveolar). Cell type was adenocarcinoma in 4 and squamous cell carcinoma in one. Conclusion: Rarely lymphangitic carcinomatosis can be presented as diffuse interstitial lung disease and easily diagnosed by transbronchial lung biopsy.

• Korean Journal of Medicinal Crop Science
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• v.12 no.2
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• pp.141-148
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• 2004

Two compounds from Gomisin N and Gomisin A were isolated from the fruits of Schizandra chinensis Baillon. The highest extraction yield as 21.36% was observed in the ethanol extract, compared to the yield obtained form the water extract. The extraction yields of the single compounds were measured to be 0.13 and 0.014 Gomisin A and Gomisin N, respectively. Approximately, 90% of the growth of human stomach adenocarcinoma cancer cells was inhibited after adding 1.0 g/l of the ethanol extract. The growth of the human normal lung cell was limited to 24% after adding the ethanol extract. The water extract lowered the specific secretion of $TNF-\acute{a}$ and IL-6 from T cells, $10.3{\times}10^{-4}\;pg/cell\;and\;12.1{\times}10^{-4}\;pg/cell$, respectively, compared to the ethanol extracts. On the other hand, a treatment with the ethanol extract increased the specific secretion of $TNF-\acute{a}$ and IL-6 from human T cells, to $11{\times}10^{-4}\;pg/cell\;and\;14.3{\times}10^{-4}\;pg/cell$, respectively. The crude ethanol extract had the highest effect on the differentiation of human promyelocytic leukemia cells compared to the other extracts and Gomisin A and N. In general, the biological activities of the extracts gradually decreased as the purification process proceeded, which suggests that higher immunostimulatory activities can be maintained by adding the crude extracts of the fruits rather than by adding a single compound.

• Korean Journal of Pharmacognosy
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• v.37 no.2 s.145
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• pp.110-115
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• 2006

Melittia inouei (Yuri Nabang) larvae are used as a crude drug in East Asia for treating stomach cancer and inflammation, and currently reared as a pharmaceutical insect in Jejudo, Korea. This study evaluated the immuno-modulating activity of these extracts, by determining the level of, cytokine production from mouse splenocytes stimulated with the extracts. The Melittia inouei larvae extracts did not induce the splenocyte proliferation. On the other hand, they stimulated the splenocytes to produce cytokines such as $TNF-{\alpha}$, whereas they did not stimulate IL10, IL12 or $IFN-{\gamma}$. The aqueous portion of its plant (Tri-chosanthis kirilowii) extract (sap) was found to be a potent inducer of NO production from the CPAE cells. However, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production from splenocytes. These data suggests that a Melittia inouei larvae extract immune modulatory activity in cytokine prodcutions such as $TNF-{\alpha}$ and VEGF which might be related its anticancer effect.

• Journal of Gastric Cancer
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• v.3 no.1
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• pp.38-43
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• 2003

Purpose: Caspase 2, a member of the family of ICE-like proteases, is activated by the Fas pathway and induces apoptosis by triggering the caspase cascade. The purpose of this study was to determine whether the expression pattern of caspase 2 might be associated with gastric cancer development and if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 78 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of caspase 2 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: Caspase 2 was expressed on superficial and foveolar epithelial cells and lymphocytes in the gastric mucosa, mainly in cytoplasm. We found loss of caspase 2 expression in 41 ($52.6\%$) of the 78 gastric cancer tissues. Statistically, histologic type and other pathologic parameters were not related with loss of caspase 2 expression Conclusion: Our findings provide enough evidence that loss of caspase 2 expression may contribute to the development of Korean gastric cancer and that it might be one of the possible escape mechanisms from apoptosis in gastric cancer.