• Journal of Ginseng Research
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• v.35 no.3
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• pp.315-324
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• 2011

This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without $100{\mu}g/L$ PMA in the absence or presence of various concentrations (100, 200, or $300{\mu}g/mL$) of red ginseng extract. Red ginseng extract treatment caused signifi cant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were signifi cantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity signifi cantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.68-76
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• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Korean Journal of Head & Neck Oncology
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• v.26 no.1
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• pp.3-8
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• 2010

Background : Though papillary microcarcinoma(PMC) of thyroid gland is known to have very favorable long-term prognosis, the recurrence in the neck and distant metastasis have been often reported. The predictive factors of node metastasis and tumor recurrence in clinical course were investigated to define surgical decision or guidelines in surgery of papillary microcarcinoma. Methods : The authors conducted a retrospective analysis of 216 patients of PMC treated with surgery at Department of Surgery, Busan Paik Hospital for the period from 1997 to 2007. Of these patients, 58 cases showing cervical lymph node metastasis at initial surgery were studied. Results : In overall 216 patients, the sex ratio of male to female was 1 : 9.3(male 21, female 195 cases), the mean age at the time of diagnosis was 44.7 years and the median tumor size was 6.61mm. Neck lymph node metastasis was found in 58 patients(26.9%), thyroid capsular invasion was 56 cases(25.9%), multifocality and bilaterality were found in 32(14.8%) and 29 cases(13.4%), respectively. Through statistical analysis, sex, capsular invasion, ETE, and tumor size(>5mm) were considered to be predictive factors of cervical lymph nodes metastasis. Of them, capsular invasion was the most predictive indicator of cervical lymph node metastasis on multivariate analysis. Nodal recurrence was observed in 6 of 58 patients of node positive at initial surgery. Conclusion : The cervical lymph node metastasis is known to be a risk factor of prognosis in PMC of thyroid gland. The results of this study showed four statistically significant independent predictive factors of cervical lymph node metastasis in PMC : capsular invasion, tumor size(>5mm), ETE, and sex. On multivariate analysis, capsular invasion was a great influencing factor in prediction of lymph node metastasis. Basically, patients who has predictive factors of cervical lymph node metastasis should have a thorough investigation, and close surveillance for nodal status is required in follow-up.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.113-118
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• 2001

Purpose: The common features of brain metastases from gastric cancer are unknown because brain metastasis is an uncommon pattern of metastasis. The purpose of this study was to investigate the clinical features of and the prognosis for patients with brain metastases after a curative resection for gastric cancer. Materials and Methods: Twenty-one (21) cases of patients with brain metastases of gastric cancer, who had been treated at the Department of Surgery, Yonsei University College of Medicine, were assessed retrospectively. Results: The mean age was $55.8\pm9.6$ years (range: $34\~70$ years), and the male-to-female ratio was 2.5 : .1. The most common neurologic symptom was headache ($38.5\%$), and no patient was free from the neurologic symptoms. The incidence of parenchymal metastasis (PM: $76.2\%$) was higher than that of leptomeningeal metastasis (LM: $19.0\%$). Patients with gastric cancer and brain metastasis showed high rates of blood and lymphatic vessel invasion (lymphatic vessel invasion: $85.7\%$; blood vessel invasion: $80.9\%$). According to Lauren's classification, the incidence of intestinal types was 14/21 ($66.7\%$), that of diffuse types was 3/21 ($14.3\%$) and that of mixed types was 4/21 ($19.0\%$). The mean interval between the gastrectomy and the diagnosis of brain metastasis was $24.7\pm4.0$ months (PM: 26.8 months; LM: 20.3 months). The median period of survival after diagnosis of brain metastasis was 2 months for paren chymal metastasis and 0 months for leptomeningeal metastasis. Conclusion:.. During a follow-up period, patients with neurologic symptoms should be suspected of having brain metastasis. Early diagnosis and treatment is the only hope to prolong survival in such patients.

• Nutritional Sciences
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• v.7 no.3
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• pp.144-150
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• 2004

We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.119-123
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• 2001

Purpose: The prognosis of operated early gastric cancer is quite excellent and the 5-year survival rate shows to be over $90\%$. The less extensive treatment has been considered to be attractive. However, lymph node metastasis remains a main risk factor for recurrence of early gastric cancer. The author performed this study in order to determine which clinicopathologic factors of early gastric cancer influence lymph node metastasis and recurrence. Materials and Methods: A retrospective study was conducted on 222 patients with early gastric cancer who had been treated by gastrectomy combined with D2 or more extended lymph node dissection between January 1991 and December 1997 at the Department of Surgery, Kyunghee University Hospital. Results: Lymph node metastasis was observed in 26 patients ($11.7\%$), and the depth of tumor invasion and tumor size among clinicopathologic factors affected lymph node metastasis. The 5-year recurrence rate was $4.4\%$, and it was revealed that lymph node metastasis and depth of tumor invasion had a greater effect on recurrence than other clinicopathologic factors. Conclusion: The high risk factors of early gastric cancer in recurrence were submucosal tumor invasion, tumor size more than 2 cm, and lymph node metastasis. Patients of early gastric cancer with such high risk factors should undergo radical gastric resection than limited surgery. (J Korean Gastric Cancer Assoc 2001;1:119-123)

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3507-3511
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• 2012

Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. Conclusion: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).

• Toxicological Research
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• v.26 no.4
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• pp.245-252
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• 2010

Epithelial-mesenchymal transition (EMT) is a complex process in which epithelial cells acquire the characteristics of invasive mesenchymal cells. EMT has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs during development. Epithelial cells undergoing EMT lose cell-cell adhesion structures and polarity, and rearrange their cytoskeletons. Several oncogenic pathways such as transforming growth factor (TGF)-$\beta$, Wnt, and Notch signaling pathways, have been shown to induce EMT. These pathways have activated transcription factors including Snail, Slug, and the ZEB family which work as transcriptional repressors of E-cadherin, thereby making epithelial cells motile and resistant to apoptosis. Mounting evidence shows that EMT is associated with cell invasion and tumor progression. In this review, we summarize the characteristic features of EMT, pathways leading to EMT, and the role of EMT in cell invasion. Three topics are addressed in this review: (1) Definition of EMT, (2) Signaling pathways leading to EMT, (3) Role of EMT in cell invasion. Understanding the role of EMT in cell invasion will provide valuable information for establishing strategies to develop anti-metastatic therapeutics which modulate malignant cellular processes mediated by EMT.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3183-3186
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• 2013

Purpose: The 7th edition of the American Joint Committee on Cancer Staging Manual for esophageal cancer (EC) categorizes N stage according to the number of metastatic lymph nodes (LNs), irrespective of the site. The aim of this study was to determine the prognostic value of subcarinal LN metastasis in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis of 507 consecutive patients with ESCC was conducted. Potential clinicopathological factors that could influence subcarinal LN metastasis were statistically analyzed. Univariate and multivariate analyses were also performed to evaluate the prognostic parameters for survival. Results: The frequency of subcarinal LN metastasis was 22.9% (116/507). Logistic regression analysis showed that tumor length (>3cm vs ${\leq}3cm$; P=0.027), tumor location (lower vs upper/middle; P=0.009), vessel involvement (Yes vs No; P=0.001) and depth of invasion (T3-4a vs T1-2; P=0.012) were associated with 2.085-, 1.810-, 2.535- and 2.201- fold increases, respectively, for risk of subcarinal LN metastasis. Multivariate analyses showed that differentiation (poor vs well/moderate; P=0.001), subcarinal LN metastasis (yes vs no; P=0.033), depth of invasion (T3-4a vs T1-2; P=0.014) and N staging (N1-3 vs N0; P=0.001) were independent prognostic factors. In addition, patients with subcarinal LN metastasis had a significantly lower 5-year cumulative survival rate than those without (26.7% vs 60.9%; P<0.001). Conclusions: Subcarinal LN metastasis is a predictive factor for long-term survival in patients with ESCC.