• Journal of Gastric Cancer
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• v.3 no.1
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• pp.33-37
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• 2003

Purpose: Alpha-fetoprotein (AFP) is widely accepted as a useful tumor marker for diagnosis of hepatocellular carcinomas. On rare occasions, however, an abnormal elevation of serum AFP also has been reported in an adenocarcinoma of the gastrointestinal tract. We evaluated the influence of preoperative abnormal elevation of serum AFP (AFP positivity) on the prognosis of resectable gastric cancers. Materials and Methods: 812 gastric cancer patients, who were investigated for serum AFP before their operations and who underwent gastric resections with D2 or more extended lymph node dissection, were enrolled in the study. The survival rates were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. Results: Fifty patients ($6.2\%$) were AFP positive (10.1. 4322.6 ng/ml). The survival rate of the AFP positive group was significantly lower than that of the AFP negative group ( $46.6\%\;vs.\;67.0\%$; P=0.0002). The depth of tumor invasion, the degree of regional lymph node metastasis, distant metastases, the TNM stage, the gross type, differentiation, the extent of gastric resection, and the curability of the surgery also significantly influenced survival. Multivariate analysis revealed that the depth of tumor invasion, the degree of regional lymph node metastasis, the curability of the surgery, and AFP positivity were independent prognostic indicators. Conclusion: Preoperative serum AFP can be used as an independent prognostic factor of resectable gastric cancer.

• Journal of Gastric Cancer
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• v.5 no.2
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• pp.113-119
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• 2005

Purpose: Some controversies exist over the prognostic values of lymphatic, venous, and neural invasion in patients with gastric cancer. This study was conducted to confirm the prognostic values of these histopathologic factors in gastric cancer patients who received a gastrectomy. Materials and Methods: Data for clinicopathologic factors and clinical outcomes were collected retrospectively from the medical records of 1,018 gastric cancer patients who received a gastrectomy at Yeungnam University Medical Center between January 1995 and December 1999. A statistical analysis was done using the SPSS program for Windows (Version 10.0, SPSS Inc., USA). The Kaplan-Meier method was used for the survival analysis. Prognostic factors were analyzed by using a multivariate analysis with Cox proportional hazard regression model. Results: Ages ranged from 21 to 79 (median age, 56). A univariate analysis revealed that age, tumor size, location, gross type, depth of invasion, extent of gastrectomy or lymph node dissection, lymph node metastasis, distant metastasis, lymphatic invasion, venous invasion, neural invasion, pathologic stage, histologic type, and curability of surgery had statistical significance. Among these factors, lymph node metastasis, curability of surgery, neural invasion, lymphatic invasion, and depth of invasion were found to be independent prognostic factors by using a multivariate analysis. Venous invasion showed no prognostic value in the multivariate analysis. Conclusion: Neural invasion and lymphatic invasion are useful parameters in determining a prognosis for gastric cancer patients.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.212-224
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• 2020

Purpose: miR-205 is a tumor suppressor and plays an important role in tumor invasiveness. However, the role of miR-205 in human gastric cancer (GC) epithelial-mesenchymal transition (EMT) remains unclear. The aim of this study was to investigate the molecular mechanism of miR-205 in the regulation of EMT in GC invasion. Materials and Methods: Quantitative polymerase chain reaction (qPCR) was used to detect the expression of miR-205 in GC. Further, the correlation between the pathological parameters and prognosis of GC was statistically analyzed. A transwell model was used to evaluate the effect of miR-205-3p on the invasion and migration of GC cells. qPCR, western blotting, and luciferase assay were performed to analyze the relationship and target effects between miR-205-3p and the expression of zinc finger electron box binding homologous box 1 (ZEB1) and 2 (ZEB2). Results: We found that the levels of miR-205-3p were significantly lower (P<0.05) in GC tissues than in matched normal tissues. Additionally, the expression of miR-205-3p was related to the tumor invasion depth, lymph node metastasis, lymph node invasion, and tumor, node, metastasis stage. Patients with lower miR-205-3p expression levels in the tumors had a poorer prognosis. The in vitro assays indicated that miR-205-3p could affect the invasion ability and EMT of GC cells by targeting the expression of both ZEB1 and ZEB2. Conclusions: miR-205-3p promotes GC progression and affects the prognosis of patients by targeting both ZEB1 and ZEB2 to directly influence EMT.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.89-94
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• 2004

Purpose: There is no established treatment-related prognostic factor for gastric cancer except a curative tumor resection. This study was done to clarify the prognostic value of early postoperative intraperitoneal chemotherapy (EPIC) in patients with serosa-positive gastric cancer. Materials and Methods: We analyzed retrospectively the postoperative survival data of 209 patients with serosapositive gastric cancer treated by surgery and chemotherapy. The survival period for patients was calculated from the date of resection until cancer-related death or the last date of follow-up; Kaplan-Meier survival curves were plotted and compared by using the log-rank test. A multivariate analysis was done by using the Cox proportional hazards model. Results: Statistically significant differences in survival rates were noted based on gender, depth of invasion, lymph node metastasis, distant metastasis, stage, location of tumor, macroscopic type, extent of gastric resection, curability of surgery, and adjuvant chemotherapy. Five-year survival rates of patients who received EPIC and systemic chemotherapy were 49 per cent and 25 per cent, respectively (P=0.009). A multivariate analysis revealed that invasion of an adjacent organ, lymph node metastasis, total gastrectomy, and palliative surgery were poor independent prognostic factors. Also, EPIC had a marginal prognostic value (P=0.056). Conclusion: Perioperative intraperitoneal chemotherapy can possibly be one of the independent prognostic indicators in case of serosa-positive gastric cancer. (J Korean Gastric Cancer Assoc 2004;4:89-94)

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2781-2785
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• 2016

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients. Materials and Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test. Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%). Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.24-31
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• 2001

Purpose: Despite knowledge of the adverse effects of resection-line disease, surgeons continue to perform inadequate resections. This demonstrates the need for a more aggressive approach to assessment of resection margins at operation. Materials and Methods: Seven hundred fifteen gastric cancer patients who were operated on at our hospital from 1992 to 1998 were included in this analysis. Various clinicopathological factors, including resection-line involvement, were ascertained from the surgical and histopathological records. Results: Of the 715 evaluable patients, 27 patients ($3.8\%$) had involvement of one or both resection lines; in 10 patients the proximal resection line only, in 16 the distal resection line only, and 1 both resection lines were involved. Presence of resection-line involvement was significantly associated with T3 and T4 stage, N (+) stage, M (+) stage, type of operation (total gastrectomy), tumor location (entire stomach), size$\geq$11 cm), and gross type of tumor (Borrmann 4 type). When performing a distal subtotal gastrectomy, no involvement was found when the cranial and caudal distances between the lesion and the line of transection was equal to or greater than 2 cm and 3 cm, respectively, for early cancer and 7 cm and 3 cm, respectively, for advanced cancer. When performing a total gastrectomy for upper 1/3 or middle 1/3 gastric cancer, no involvement was found when the cranial distances between the lesion and the line of transection were equal to or greater than 3 cm and 4 cm, respectively, without distinction of the presence of serosal invasion. Conclusions: The difference in survival between positive and negative margin patients is limited to the group of patients with curative surgery. An important principle of treatment is that the entire tumor must be removed with a 3 cm distal margin and a 2- to 7 cm margin depending on the location and the depth of wall invasion of the tumor, to provide histologically negative margins.

• Journal of Gastric Cancer
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• v.12 no.3
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• pp.140-148
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• 2012

Purpose: Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. Materials and Methods: The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. Results: In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). Conclusions: Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.93-97
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• 2013

Purpose: Endoscopic submucosal dissection has recently been practiced on a differentiated type of early gastric cancer. However, there is no clear evidence for endoscopic treatments of signet ring cell carcinoma. The aim of this study is to identify the predictive clinicopathological factors for lymph node metastasis in signet ring cell carcinoma for assisting endoscopic submucosal dissection trials. Materials and Methods: A total of 186 patients with early signet ring cell carcinoma who underwent radical curative gastrectomy between January 2001 and September 2009 were enrolled in this study. Retrospective reviews of their medical records are being conducted. Several clinicopathologic factors were being investigated in order to identify predictive factors for lymph nodes metastasis: age, gender, tumor size, type of operation, tumor location, gross type, ulceration, Lauren's classification, depth of invasion, and lymphatic invasion. Results: The lymph node metastasis rate for signet ring cell carcinoma was 4.3% (n=8). Of the 186 lesions with early signet ring cell carcinoma, 91 (48.9%) tumors were larger than 15 mm in size and 40 (21.5%) showed submucosal invasions in the resection specimens. In multivariate analysis, only the lymphatic invasion (P<0.0001) showed an association with lymph node metastasis. To evaluate cutoff values for tumor sizes in the presence of lymph node metastasis, early signet ring cell carcinomas with lymphatic invasions were excluded. In the absence of lymphatic invasion, mucosal cancer with tumor sizes <15 mm had no lymph node metastasis. Conclusions: Endoscopic submucosal dissection can be performed on patients with early signet ring cell carcinoma limited to the mucosa and less than 15 mm.

• Journal of Gastric Cancer
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• v.12 no.2
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• pp.81-87
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• 2012

Purpose: The aim of the present study was to assess the association between the pre-operative plasma fibrinogen level and the adjacent organ involvement in advanced gastric cancer. Materials and Methods: A total of 923 pre-operative plasma samples were obtained from 923 patients diagnosed clinically as having advanced gastric cancer, and fibrinogen levels were measured by immunoassay. Associations between fibrinogen levels and clinicopathologic findings (depth of tumor, adjacent organ involvement, and lymph node metastasis), along with survival were examined by univariate and multivariate analyses. Results: Tumor size, tumor depth, and the presence of lymph node metastasis were found to be positively correlated with the preoperative plasma fibrinogen levels (P<0.001). Fifty (5.4%) patients had adjacent organ involvement. Lymphatic invasion (P<0.001), tumor size (P<0.001), clinical T (depth of invasion) stage (P<0.001), and clinical nodal stage (P=0.018) were found to be associated with adjacent organ involvement. Univariate and multivariate regression analyses showed that a preoperatively elevated plasma fibrinogen level was associated with adjacent organ involvement (P<0.001, 0.028), and Kaplan-Meier analysis showed that it was associated with poorer survival (P<0.001). Conclusions: Plasma fibrinogen was found to be a clinically useful marker of adjacent organ involvement and overall survival. When a high fibrinogen level is encountered, preoperatively, adjacent organ involvement should be suspected in clinically advanced gastric cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.6
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• pp.528-534
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• 2005

Angiogenesis is important for the growth and metastasis of solid tumors. Some growth factors, inflammatory cytokines, and angiogenin are known to promote tumor angiogenesis. Among them, Vascular endothelial growth factor (VEGF) is the most intriguing factor in regard to tumor angiogenesis. Inhibition of VEGF activity by neutralizing antibodies or by the introduction of dominant negative VEGF receptors into endothelial cells of tumor-associated blood vessels resulted in the inhibition of tumor growth and in tumor regression, indicating that VEGF is a major initiator of tumor angiogenesis. VEGF promotes angiogenesis through their receptors, Flt-1 and Flk-1/KDR. on vascular endothelial cells. These two receptors were usually believed to be expressed specifically on vascular endothelial cell. Several reports have now shown that VEGF is not only significantly associated with microvessel density but also has prognostic value in both node-negative and node-positive oral squamous cell carcinoma. For many years several histologic features of the neoplasms are being considered when assessing the influence of malignancy grading on recurrence and prognosis. Among the characteristics investigated, degree of keratinization, nuclear pleomorphism, mode of invasion, microscopic depth of invasion, intravascular invasion, lymphocyte infiltration, and number of mitoses have been considered as important prognostic factors. So, this study was conducted to evaluate the correlation of vascular endothelial growth factor expression with malignancy in paraffin-embedded biopsy specimens from 11 patients with tongue cancers. Our results showed that high immunoreactivity specimens of VEGF expression were significantly lower keratinization degree and more pronounced nuclear pleomorphism than in low immunoreactivity specimens. Thus, VEGF expression could be used as a prognostic marker in tongue cancer.