• BMB Reports
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• v.40 no.2
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• Biomolecules & Therapeutics
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• v.18 no.4
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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.

• Korean Journal of Head & Neck Oncology
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• v.21 no.1
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• pp.3-9
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• 2005

Purpose: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracelluar matrix and neovascularization are related to tumor infiltration mechanism. By studying the the tissues of early stage oral tongue cancer patients, we are intend to clarify the invasion related factors in oral tongue cancer. Material and Methods: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction related molecules(MMP2, MMP9) and neovascularization related molecule(VEGF) were observed by immunohistochemical study. Also, immunohistochemical staining of CD31 was done for quantification of neovascularization. With the experiment showed above, we analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates and cervical lymph node metastasis rate in early T-stage oral tongue cancer. Results: The expression rates of MMP2, MMP9, VEGF in 38 early oral cancer patients were 52.6%, 78.9% 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining(p<0.001). VEGF expressions were significantly related with tumor invasion depth(p=0.002). The tumor free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors(p=0.019). Conclusion: This results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer and could be used as a beneficial factors in defining operative field and prognosis.

• Journal of Gastric Cancer
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• v.12 no.4
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• pp.210-216
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• 2012

Purpose: To assess independent prognostic factors for lymph node-negative metastatic gastric cancer patients following curative resection is valuable for more effective follow-up strategies. Materials and Methods: Among 1,874 gastric cancer patients who received curative resection, 967 patients were lymph node-negative. Independent prognostic factors for overall survival in lymph node-negative gastric cancer patients grouped by tumor invasion depth (early gastric cancer versus advanced gastric cancer) were explored with univariate and multivariate analyses. Results: There was a significant difference in the distribution of recurrence pattern between lymph node-negative and lymph nodepositive group. In the lymph node-negative group, the recurrence pattern differed by the depth of tumor invasion. In univariate analysis for overall survival of the early gastric cancer group, age, macroscopic appearance, histologic type, venous invasion, lymphatic invasion, and carcinoembryonic antigen level were significant prognostic factors. Multivariate analysis for these factors showed that venous invasion (hazard ratio, 6.695), age (${\geq}59$, hazard ratio, 2.882), and carcinoembryonic antigen level (${\geq}5$ ng/dl, hazard ratio, 3.938) were significant prognostic factors. Multivariate analysis of advanced gastric cancer group showed that depth of tumor invasion (T2 versus T3, hazard ratio, 2.809), and age (hazard ratio, 2.319) were prognostic factors on overall survival. Conclusions: Based on our results, independent prognostic factors such as venous permeation, carcinoembryonic antigen level, and age, depth of tumor invasion on overall survival were different between early gastric cancer and advanced gastric cancer group in lymph node-negative gastric cancer patients. Therefore, we are confident that our results will contribute to planning follow-up strategies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7049-7054
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• 2014

Background: Almost half of the breast cancer patients with positive sentinel lymph nodes have no additional disease in the remaining axillary lymph nodes. This group of patients do not benefit from complete axillary lymph node dissection. This study was designed to assess the clinicopathologic factors that predict non-sentinel lymph node metastasis in Iranian breast cancer patients with positive sentinel lymph nodes. Materials and Methods: The records of patients who underwent sentinel lymph node biopsy, between 2003 and 2012, were reviewed. Patients with at least one positive sentinel lymph node who underwent completion axillary lymph node dissection were enrolled in the present study. Demographic and clinicopathologic characteristics including age, primary tumor size, histological and nuclear grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and number of harvested lymph nodes, were evaluated. Results: The data of 167 patients were analyzed. A total of 92 (55.1%) had non-sentinel lymph node metastasis. Univariate analysis of data revealed that age, primary tumor size, histological grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio, were associated with non-sentinel lymph node metastasis. After logistic regression analysis, age (OR=0.13; 95% CI, 0.02-0.8), primary tumor size (OR=7.7; 95% CI, 1.4-42.2), lymphovascular invasion (OR=19.4; 95% CI, 1.4-268.6), extracapsular invasion (OR=13.3; 95% CI, 2.3-76), and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio (OR=20.2; 95% CI, 3.4-121.9), were significantly associated with non-sentinel lymph node metastasis. Conclusions: According to this study, age, primary tumor size, lymphovascular invasion, extracapsular invasion, and the ratio of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes, were found to be independent predictors of non-sentinel lymph node metastasis.

• Journal of the Chungcheong Mathematical Society
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• v.28 no.1
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• pp.161-172
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• 2015

In this paper, we consider the chemotaxis-haptotaxis model of tumor invasion with the proliferation and tissue re-establishment term in dimensions one and two. We show the global in time existence of a unique classical solution for the the model in two dimensional spatial domain without any restrictions on the coefficients.

• Journal of Korean Neurosurgical Society
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• v.30 no.11
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• pp.1278-1283
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• 2001

Objective : Transsphenoidal approach(TSA) has been used as useful operative method for pituitary tumor but is still controversal in case of cavernous sinus invasion or severe suprasellar extension. This study was performed to evaluate the surgical result, recurrence, effect of adjuvant treatment, especially in cases of suprasellar extension or cavernous sinus invasion. Material and Methods : We studied 56 cases of surgically treated pituitary adenoma that we were able to follow up, treated by TSA from 1993 to 1998. There were 24 cases of suprasellar extension and 11 cases of cavernous sinus invasion. The medical records and radiological findings were reviewed. Surgical results including hormonal function and recurrence rates were analyzed according to extent of tumor invasion. Mean follow-up period was 19.1 months. Results : Tumors with suprasellar extension were removed totally in 54%, whereas total tumor removal was possible only in 38% with cavernous sinus invasion. Overall of recurrence rate was 14% and recurrence rate was 25% in suprasellar extension and 9% in cavernous sinus invasion. In cases of both suprasellar extension and cavernous sinus invasion, tumors that were treated by TSA and radiation showed recurrence rate of 7%, whereas those treated by surgery alone showed 28% of recurrence. Conclusion : Transsphenoidal approach is safe and useful operative method for pituitary adenoma and adjuvant therapy including radiation therapy is effective means to decrease the recurrence in cases of suprasellar extension or cavernous sinus invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4147-4151
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• 2012

The current study was conducted to explore the inhibitory effects of a small interfering RNA (siRNA) on 3-phosphoinositide-dependent protein kinase 1 (PDK1) expression in esophageal cancer 9706 (EC9706) cells and the influence on their biological behavior. After transfection of a synthesized PDK1 siRNA, PDK1 mRNA and protein expression and the phosphorylation level of the downstream Akt protein were assessed using RT-PCR and Western blot analysis. Proliferation, apoptosis, cell invasion and in vivo tumor formation capacity were also investigated using MTT, flow cytometry, Transwell invasion trials, and nude mouse tumor transplantion, respectively. PDK1 siRNA effectively suppressed PDK1 mRNA and protein expression, and down-regulated the phosphorylation level of the Akt protein in the EC9706 cells (P < 0.05). It also inhibited cell proliferation and invasion, and promoted apoptosis; such effects were particularly obvious at 48 h and 72 h after transfection (P < 0.05). Growth of transplanted tumors was inhibited in nude mice, with decreased PDK1 expression in tumor tissues. PDK1 may be closely correlated with proliferation, apoptosis and invasion of esophageal cancer cells and thus may serve as an effective target for gene therapy.

• Journal of Gastric Cancer
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• v.16 no.4
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• pp.215-220
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• 2016

Purpose: This study aimed to evaluate the rate, patterns, and risk factors associated with tumor recurrence in patients with T1N0 gastric cancer. Materials and Methods: The medical records of 8,753 patients with pathological T1N0M0 gastric cancer who underwent gastrectomy between 1994 and 2014 at Sungkyunkwan University School of Medicine were examined. Results: Among the 8,753 patients, 95 patients (1.1%) experienced tumor recurrence; this included 31 remnant, 27 hematogenous, 9 lymph nodal, 5 peritoneal, and 23 multiple-site recurrences. When patients were divided into two groups according to the presence of tumor recurrence, the following characteristics were higher in the recurrence group than in the non-recurrence group: older age (${\geq}65years$), male gender, undifferentiated histology, submucosal invasion, and venous invasion. In multivariate analysis, older age, male gender, tumor depth (sm2 and sm3 invasion), and venous invasion were independent risk factors for tumor recurrence. The recurrence rates were 0.7% in patients with less than two risk factors, 1.7% in those with two risk factors, 3.0% in those with three risk factors, and 6.3% in those with four risk factors (P<0.001). Conclusions: Although tumor recurrence is rare in pT1N0M0 gastric cancer, some patients with certain risk factors demonstrate an increased rate of tumor recurrence. Careful follow-up is required for patients with three or four risk factors.

• BMB Reports
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• v.47 no.8
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• pp.445-450
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• 2014

Glucose regulated protein 78 (GRP78) is frequently highly expressed in tumor cells, contributing to the acquisition of several phenotypic cancer hallmarks. GRP78 expression is also positively correlated with tumor metastasis, and promotes hepatocellular carcinoma cell invasion via increasing cell motility, however, other mechanisms involving the prometastatic roles of GRP78 remain to be elucidated. Here we report that forced GRP78 expression promotes colon cancer cell migration and invasion through upregulating MMP-2, MMP-9 and especially uPA production. These effects of GRP78 are mediated by enhancing the activation of ${\beta}$-catenin signaling. Interestingly, we identify that GRP78 interacts with uPA both in the cells and in the culture medium, suggesting that GRP78 protein is likely to directly facilitate uPA secretion via protein-protein interaction. Taken together, our findings demonstrate for the first time that besides stimulation of cell motility, GRP78 can act by increasing proteases production to promote tumor cell invasion.