• Journal of Gastric Cancer
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• v.17 no.3
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• pp.212-219
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• 2017

Purpose: The aims of this study were to compare the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manuals on tumor, node, and metastasis (TNM) staging systems and to evaluate whether the 8th edition represents a better refinement of the 7th staging system, when applied for the classification of gastric cancers. Materials and Methods: A total of 5,507 gastric cancer patients, who underwent treatment from January 1989 to December 2013 at a single institute, were included. We compared patient survival rates across the disease groups classified according to the 7th and 8th editions of the AJCC TNM staging systems. Results: Stage migration was observed in 6.4% (n=355) of the patients. Of these, 3.5% (n=192) and 2.9% (n=158) of patients showed a higher stage and lower stage, respectively. According to the 8th edition of the AJCC TNM staging criteria, the 5-year overall survival rates of the patients with stage IIIB and IIIC showed a significant difference (40.8% vs. 20.2%, P<0.001) whereas no significant differences in the 5-year overall survival rates were observed according to the 7th edition criteria (37.6% vs. 33.2%, P=0.381). Conclusions: Restaging stage III cancers according to the 8th edition of the AJCC TNM classification criteria improved survival rate discrimination, particularly, in institutes where the stage III patients were not distinctly categorized.

• Journal of Life Science
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• v.19 no.7
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• pp.866-870
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• 2009

Fascin, a cytoskeleton actin binding protein, functions in cell adhesion and cell migration. Fascin is also known as a candidate biomarker for various cancers, however, regulatory mechanisms of fascin expression remains little understood. In this study, we found an abnormal bristle phenotype, which is similar to that of the Drosophila fascin mutant, in Drafmutant flies. Hence, we investigated whether fascin expression is regulated by Raf signaling. RT-PCR and Western blot analysis showed that Drosophila fascin expression was down-regulated in Draf mutant flies and the level was increased in larvae expressing the oncogenic form of Draf (Draf$^{got}$) under the GAL4-UAS system. Immunostaining analysis showed increased fascin in the hemocytes over-expressing Draf$^{got}$. Our results indicate that fascin expression is regulated by Raf signaling and suggest that Raf signaling may play an important role in the actin cytoskeleton-associated developmental process and tumor progression via regulation of fascin gene.

• Journal of Life Science
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• v.27 no.9
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• pp.1059-1063
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• 2017

Angiogenesis is an essential step in tumoral growth and metastasis and is regulated by a balance between stimulators and inhibitors. Recently, antiangiogenic target therapy has shown promise as a new type of chemotherapy. Natural products have attracted widespread attention worldwide as a useful source of novel therapeutic compounds. The balloon-flower has long been used as a traditional medicinal material and food in Asia. In this study, we investigated whether extract of balloon-flower would inhibit in vitro angiogenesis and vascular-like network formation in human umbilical vein endothelial cells (HUVECs). The extract of Balloon-flower did not affect the viability of HUVECs. However, treatment with the Balloon-flower extract suppressed tube formation of HUVECs. In addition, after treatment with the Balloon-flower extract, cell migration decreased about 80%, and cell invasion was almost completely inhibited. Taken together, these results suggest that extract of Balloon-flower may have potential as an angiogenic inhibitor and that it could be developed as an anticancer agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1305-1313
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• 2009

Saengjihwangeum-ja (SJHEJ) was recorded in DongEuiBoGam as being able to be used for treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM). Modification of proteins by long term circulation of glucose leads to the formation of advanced glycation end product(AGE). Recent immunological studies demonstrated that ligation of AGE play an important role in the development of diabetic complications including atherosclerosis, which includes activation, adhesion, and migration of monocytes. Also, AGE and Maillard reaction product(MRP) could augment monocyte inflammatory responses via ligation of AGE receptor. In this study, the effects of SJHEJ extracts on the expression of inflammatory response-related genes such as tumor necrosis factor-$\alpha$, monocyte chemoattractant protein-1, interferon-g-inducible protein-10, and cyclooxygenase-2 in the human monocyte cell line, THP-1 cells. Reverse transcriptase-polymerase chain reaction revealed that SJHEJ had inhibitory effects on the expression of the TNF-a, MCP-1, IP-10, COX2, IL-1b genes in MRP-induced THP-1 cells. Treatment with SJHEJ had reduced reactive oxygen production in THP-1 cells stimulated by MRP. These inhibitory effects might be exerted via prevention of oxidative stress in activated monocytes. In addition, radical scavenging activity of SJHEJ was increased. These results suggest that SJHEJ has a beneficial effects for improve diabetic vascular complication.

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.205-213
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• 2003

Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

• Molecules and Cells
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• v.37 no.1
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• pp.17-23
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• 2014

We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or ${\beta}$-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. We demonstrated that Sp1 protein or mRNA expression is induced by Bcl-w using Western blotting or RT-PCR, respectively, and markedly elevated in high-grade glioma specimens compared with low-grade glioma tissues using tissue array. However, relationship between Bcl-w-related signaling and aggressive characteristic of GBM is poorly characterized. This study suggested that Bcl-w-induced Sp1 activation promoted expression of glioma stem-like cell markers, such as Musashi, Nanog, Oct4 and sox-2, as well as neurosphere formation and invasiveness, using western blotting, neurosphere formation assay, or invasion assay, culminating in their aggressive behavior. Therefore, Bcl-w-induced Sp1 activation is proposed as a putative marker for aggressiveness of GBM.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.82-89
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• 2006

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

• BMB Reports
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• v.52 no.7
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• pp.457-462
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• 2019

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

• Journal of Gastric Cancer
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• v.19 no.3
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• pp.315-328
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• 2019

Purpose: To investigate the clinical value of serum miR-221-3p and miR-122-5p expression levels in the diagnosis and prognosis of gastric cancer. Materials and Methods: Serum samples from 141 gastric cancer cases (gastric cancer group), 110 gastric polyps (gastric polyp group), and 75 healthy people (healthy control) were used to detect miR-221-3p and miR-122-5p expression using real-time reverse transcription polymerase chain reaction. Results: Serum miR-221-3p expression was significantly higher in the gastric cancer group than in the gastric polyp group, and it was significantly lower than that before operation. The miR-221-3p expression was significantly higher in the death group than in the survival group. The proliferation and migration ability significantly increased and the apoptosis rate significantly decreased by miR-221-3p transfection in gastric cancer cells. In contrast, the function of miR-122-5p in gastric cancer cells was opposite of miR-221-3p. Serum miR-221-3p expression was negatively correlated with that of miR-122-5p in gastric cancer. Serum miR-221-3p and miR-122-5p expressions were significantly correlated with the degree of differentiation, tumor, node, metastasis stage, lymph node metastasis, and invasion depth. miR-221-3p and miR-122-5p expression levels were independent prognostic factors for postoperative gastric cancer. In the diagnosis and predicting prognosis of gastric cancer, receiver operating characteristic analysis revealed that the area under curve of combined detection of serum miR-221-3p and miR-122-5p expression had a greater diagnostic effect than either single maker. Conclusions: The miR-221-3p and miR-122-5p are involved in the development of gastric cancer, and they have important clinical values in gastric cancer diagnosis and prognosis.

• Ocean and Polar Research
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• v.41 no.2
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• pp.79-88
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• 2019

In this study, the inhibitory effect of Atriplex gmelinii C. A. Mey. against the activity of MMP-2 and MMP-9 secreted from phorbol-12-myristate-13-acetate (PMA)-stimulated HT-1080 cells was evaluated by gelatin zymography and enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase-chain reaction (RT-PCR), and Western blot assay. Specimens of the halophyte A. gmelinii were extracted twice for 24 hr with methylene chloride ($CH_2Cl_2$), and then twice with methanol (MeOH), in turn. Each extract significantly inhibited the enzymatic activities in gelatin zymography and MMP ELISA kit, and expression of MMP-2 and 9 in mRNA and protein levels. Two crude extracts were combined and then the combined crude extracts were fractionated into n-hexane, 85% aqueous methanol (85% aq.MeOH), n-butanol (n-BuOH), and water ($H_2O$) fractions, according to solvent polarity. Among solvent-partitioned fractions, the 85% aq.MeOH fraction showed the strongest inhibitory effect against MMP-2 and -9 in gelatin zymography and MMP ELISA kit. In RT-PCR, all solvent-partitioned fractions significantly suppressed mRNA expression of MMP-2 and -9. On the other hand, in Western blot assay, all solvent-partitioned fractions except $H_2O$ significantly reduced expression levels of protein. HT 1080 cell migration was most significantly inhibited by the n-BuOH fraction followed by the 85% aq.MeOH and $H_2O$ fractions. These results suggest that A. gmelinii could be used as a potential source to inhibit tumor cell metastasis.