• Biomolecules & Therapeutics
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• 제18권4호
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• pp.363-374
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• 2010

Growing evidence suggests a prominent role for leptin in human cancer progression. The intricate pattern of leptin cross-talk with other associated signaling pathways is a critical area of research that will ultimately contribute to comprehending the role of leptin in cancer progression. This review summarizes a portion of the current understanding of leptin signaling, with a critical focus on its contribution to tumor cell invasion and metastasis. Five topics are addressed in this review: (1) Leptin receptor, (2) Leptin signaling, (3) Leptin and cancer, and (4) Leptin and tumor invasion. Due to the complex cellular effects of leptin, a more precise understanding of leptin signaling pathways must still be elucidated. Leptin is clearly a major factor for stimulating tumor progression through a complex spectrum of interplay and cross-talk among various signaling molecules. An understanding of the role of leptin in invasion and metastasis will provide valuable information for establishing strategies to modulate leptin signaling, which should be a high priority for the development of anti-cancer therapeutics.

• Journal of Gastric Cancer
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• 제4권2호
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• pp.82-88
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• 2004

Purpose: E-cadherin and CD44H have been shown to play a role in the progression and the metastasis of tumors. This study evaluated the clinical correlations between expression of E-cadherin and CD44H and various clinicopathologic factors and the value of expressions of E-cadherin and CD44H as prognostic factors in Borrmann type IV gastric cancer. Materials and Methods: In 122 patients with Borrmann type IV gastric cancer, we performed the immunohistochemical stainings for E-cadherin and CD44H. We analyzed the correlation between the expressions of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, stage, and peritoneal dissemination, and survival. Results: There were no correlations between reduced expression of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, and stage. However, there was a significant correlation between lymph node metastasis and the lymphatic invasion (P=0.022). There was also a significant correlation between the peritoneal dissemination and CD44H expression (P=0.005). The 5-year survival rate was correlated with CD44H expression expression (P=0.026), peritoneal dissemination (P<0.01), depth of invasion (P<0.01), lymph node metastasis (P<0.01), stage of tumor (P<0.01), and lymphatic invasion (P<0.01). There was no correlation between expression of E-cadherin and survival rate. Conclusion: The expression of CD44H and peritoneal dissemination was correlated. The expression of CD44H was an independent prognostic factor in Borrmann type IV gastric cancer. Further prospective studies with a large number of cases are required.

• 대한두경부종양학회지
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• 제26권1호
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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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• 제1권2호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권2호
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• pp.155-160
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• 2002

Oral squamous cell carcinoma (OSCC), the most common head and neck cancer, shows poor prognosis as a result of frequent local invasion and lymph node metastasis that is mediated by multiple proteolytic enzymes and angiogenesis. In recent reports, angiogenesis is known to play an important role in tumor invasion and metastasis. The purpose of this study was to determine the role of angiogenesis in OSCCs, particularly with respect to the invasive and the metastatic potential. The microvessel density (CD31) in 34 human OSCC cases were investigated by immunohistochemistry, and reviewed with respect to the invasiveness and the presence of lymph node metastasis and following results were obtained. The blood vessel density $(28.8{\pm}7.9)$ in the strong invasive cases were significantly higher than those $(23.3{\pm}6.9)$ in the weak invasive cases. (p<0.05) In the 14 cases with lymph node metastasis, the average blood vessel density was $28.5{\pm}9.6$. On the other hand, in the 20 cases without lymph node metastasis, the blood vessel density was $25.2{\pm}6.4$. The blood vessel density was not statistically related to lymph node metastasis. (p>0.05) These results suggest that angiogenesis may be related to the local invasion of OSCC and further research will be needed to investigate the possibility that antiangiogenic agent can be used as an anticancer agent for OSCC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3831-3836
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• 2013

Background: S100A14 has recently been implicated in the progress of several types of cancers. This study aimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion and metastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA and protein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigated using MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14 was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner grade and vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant and independent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidence interval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro and in vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.

• Nutritional Sciences
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• 제7권3호
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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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• 제1권3호
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• pp.155-160
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• 2001

Purpose: Submucosal gastric carcinomas metastasize to lymph nodes more often than the intramucosal gastric carcinomas. The objectives of this study are to clarify the characteristics of submucosal gastric carcinomas, especially in reference to the status of lymph node metastasis, and to explore the possibility of a minimally invasive operation. Materials and Methods: The clinicopathologic features of 88 patients with submucosal gastric carcinoma, all of whom were treated with a $D_{2}+\alpha$ gastrectomy between January 1994 and December 1999, were examined retrospectively with respect to the status of lymph nodes. The size, depth of submucosal invasion, histologic differentiation, location,and macroscopic finding of the tumor were investigated in association with the presence or the absence of lymph node metastasis. Results: Among the 88 patients, 15 ($17.05\%$) had lymph node metastasis, and the status of metastasis was significantly correlated with tumor size and depth of submucosal invasion. The frequency of metastasis was $0\%$ (0/7) of up to 1.0 cm and $18.5\%$ (15/81) over 1.0 cm in size (p=0.034) and $6.1\%$ (2/33) of up to 1.0mm and $23.6\%$ (13/55) over 1.0 mm in depth of submucosal invasion (p=0.042). Conclusion: The tumor size and depth of submucosal invasion are useful indicators of lymph node metastasis in submucosal gastric carcinoma. A minimally invasive operation can be applied for submucosal gastric carcinoma up to 1.0 cm in size Further studies are needed to limited surgery for depth of submucosal invasion.

• BMB Reports
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• 제53권9호
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• pp.458-465
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• 2020

Metastasis is the main culprit of the great majority of cancerrelated deaths. However, the complicated process of the invasion-metastasis cascade remains the least understood aspect of cancer biology. Telomerase plays a pivotal role in bypassing cellular senescence and sustaining the cancer progression by maintaining telomere homeostasis and genomic integrity. Telomerase reverse transcriptase (TERT) exerts a series of fundamental functions that are independent of its enzymatic cellular activity, including proliferation, inflammation, epithelia-mesenchymal transition (EMT), angiogenesis, DNA repair, and gene expression. Accumulating evidence indicates that TERT may facilitate most steps of the invasion-metastasis cascade. In this review, we summarize important advances that have revealed some of the mechanisms by which TERT facilitates tumor metastasis, providing an update on the non-canonical functions of telomerase beyond telomere maintaining.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.339-347
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• 2022

Purpose: Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology. Materials and Methods: A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47). Results: The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349). Conclusions: Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.