• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5371-5375
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• 2014

Background: An accurate assessment of potential lymph node metastasis is important for the appropriate treatment of early gastric cancers. Therefore, this study analyzed predictive factors associated with lymph node metastasis and identified differences between mucosal and submucosal gastric cancers. Materials and Methods: A total of 518 early gastric cancer patients who underwent radical gastrectomy were reviewed in this study. Clinicopathological features were analyzed to identify predictive factors for lymph node metastasis. Results: The rate of lymph node metastasis in early gastric cancer was 15.3% overall, 3.3% for mucosal cancer, and 23.5% for submucosal cancer. Using univariate analysis, risk factors for lymph node metastasis were identified as tumor location, tumor size, depth of tumor invasion, histological type and lymphovascular invasion. Multivariate analysis revealed that tumor size >2 cm, submucosal invasion, undifferentiated tumors and lymphovascular invasion were independent risk factors for lymph node metastasis. When the carcinomas were confined to the mucosal layer, tumor size showed a significant correlation with lymph node metastasis. On the other hand, histological type and lymphovascular invasion were associated with lymph node metastasis in submucosal carcinomas. Conclusions: Tumor size >2 cm, submucosal tumor, undifferentiated tumor and lymphovascular invasion are predictive factors for lymph node metastasis in early gastric cancer. Risk factors are quite different depending on depth of tumor invasion. Endoscopic treatment might be possible in highly selective cases.

• Toxicological Research
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• 제23권3호
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• pp.197-205
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• 2007

Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for $TGF-{\beta}$ in human cancer progression. The complex pattern on cross-talk of $TGF-{\beta}$ and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of $TGF-{\beta}$ in cancer progression. This review summarizes some of the current understanding of $TGF-{\beta}$ signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) $TGF-{\beta}$ signaling, (2) $TGF-{\beta}$ and EMT, (3) $TGF-{\beta}$ and MMP, (4) $TGF-{\beta}$ and Ras, and (5) Role of $TGF-{\beta}$ in invasion and metastasis. Due to the bifunctional cellular effects of $TGF-{\beta}$, as a tumor promoter and a tumor suppressor, more precisely defined $TGF-{\beta}$ signaling pathways need to be elucidated. According to the current literature, $TGF-{\beta}$ is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of $TGF-{\beta}$ in invasion and metastasis will provide valuable information on establishing strategies to manipulate $TGF-{\beta}$ signaling which should be a high priority for the development of anti-metastatic therapeutics.

• 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 the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권2호
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• pp.81-93
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• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6511-6517
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• 2014

Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, > $400{\times}1000/{\mu}L$) and a control group (1,476 patients, ${\leq}400{\times}1000/{\mu}L$). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권3호
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• pp.133-138
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• 2016

Objectives: To assess the association between muscle invasion by oral squamous cell carcinoma of the posterior mandibular alveolar ridge and cervical lymph node metastasis on the basis of preoperative magnetic resonance imaging (MRI). Materials and Methods: Twenty-six patients with oral squamous cell carcinoma of the posterior mandibular alveolar ridge were evaluated by MRI. The associations between cervical lymph node metastasis and independent factors evaluated by MRI were analyzed. Overall survival was also analyzed in this manner. Representative biopsy specimens were stained with anti-podoplanin and anti-CD34 antibodies. Results: Mylohyoid muscle invasion was associated with cervical lymph node metastasis. A combinational factor of mylohyoid and/or buccinator muscle invasion was also associated with cervical lymph node metastasis. Cervical lymph node metastasis and masticator space invasion had a negative effect on overall survival. No lymphatic vessels were identified near the tumor invasion front within the mandible. In contrast, lymphatic vessels were identified near the front of tumor invasion in the muscles. Conclusion: This study demonstrates an association between muscular invasion by oral squamous cell carcinoma of the posterior mandibular alveolar ridge and cervical lymph node metastasis.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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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 Gastric Cancer
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• 제1권2호
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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)

• Archives of Plastic Surgery
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• 제43권6호
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• pp.538-543
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• 2016

Background Cutaneous squamous cell carcinoma (SCC), which occurs in keratinocytes of the epidermis and is the second most common skin cancer, has a more invasive growth pattern and higher potential to metastasize than basal cell carcinoma. Total excision of the primary tumor is the treatment of choice. For clear excision of the tumor, invasion depth is one of the most important factors. This study was conducted to clarify the relationship between the size and the invasion depth of cutaneous SCC. Methods Twenty-six cases were collected for this prospective study. Frozen biopsies were examined after complete resection of the tumor, followed by histological confirmation by pathological examination. The major and minor axis lengths of the tumor, the invasion depth, and the level of invasion were measured. Recurrence or metastasis was recorded through regular follow-up. Results The Pearson correlation coefficient was used for statistical analysis. Significant results were observed for the relationship between the major and minor axis lengths and the invasion depth of the tumor (0.747, 0.773). No cases of recurrence or metastasis were observed. Conclusions In head and neck cutaneous SCC, the invasion depth of the tumor is closely related to the major and minor axis lengths of the tumor. Therefore, the invasion depth of the tumor can be estimated by measuring the size of the tumor, and a standard vertical safety margin for head and neck cutaneous SCC can be established, which could be helpful in the development of a preoperative reconstruction plan.