• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Investigative Magnetic Resonance Imaging
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• v.17 no.1
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• pp.8-18
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• 2013

Purpose : The purpose of this study was to find and categorize the various magnetic resonance imaging (MRI) findings of spinal metastases that correlate with the type of primary cancer. Materials and Methods: We retrospectively reviewed gadolinium-enhanced magnetic resonance images of 30 patients with 169 spinal metastatic lesions from lung cancer (n = 56), breast cancer (n = 29), colorectal cancer (n = 20), hepatocellular carcinoma (HCC) (n = 17), and stomach cancer (n = 47). The size, location, extent of invasion, signal intensity, margin, enhancement pattern, and osteoblastic or osteolytic characteristics of each metastatic tumor were analyzed. Results: The metastatic lesions from HCC were larger than those from the other primary tumors (P < 0.05) except for colorectal cancer (P = 0.268). Well-defined metastatic tumor margins were more frequently seen in lung cancer and breast cancer (P < 0.01). All but HCC showed a tendency to invade the vertebral body rather than the posterior elements (P < 0.02). Colorectal cancer and HCC showed a tendency toward extraosseous invasion without statistical significance. HCC showed a characteristic enhancement pattern of 'worms-in-a-bag'. Rim enhancement with a sclerotic center was only seen in spinal metastases from stomach cancer. Conclusion: Despite many overlapping imaging features, spinal metastases of various primary tumors display some characteristic MRI findings that can help identify the primary cancer.

• Journal of Gastric Cancer
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• v.15 no.4
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• pp.238-245
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• 2015

Purpose: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). Materials and Methods: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. Results: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). Conclusions: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2935-2940
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• 2016

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

• Journal of Gastric Cancer
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• v.11 no.3
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• pp.162-166
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• 2011

Purpose: Endoscopic resection is widely accepted as standard treatment for early gastric cancer (EGC) without lymph node metastasis. The procedure is minimally invasive, safe, and convenient. However, surgery is sometimes needed after endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) due to perforation, bleeding, or incomplete resection. We evaluated the role of surgery after incomplete resection. Materials and Methods: We retrospectively studied 29 patients with gastric cancer who underwent a gastrectomy after incomplete EMR/ESD from 2006 to 2010 at Korea University Hospital. Results: There were 13 incomplete resection cases, seven bleeding cases, three metachronous lesion cases, three recurrence cases, two perforation cases, and one lymphatic invasion case. Among the incomplete resection cases, a positive vertical margin was found in 10, a positive lateral margin in two, and a positive vertical and lateral margin in one case. Most cases (9/13) were diagnosed as mucosal tumors by endoscopic ultrasonography, but only three cases were confirmed as mucosal tumors on final pathology. The positive residual tumor rate was two of 13. The lymph node metastasis rate was three of 13. All lymph node metastasis cases were submucosal tumors with positive lymphatic invasion and no residual tumor in the gastrectomy specimen. No cases of recurrence were observed after curative resection. Conclusions: A gastrectomy is required for patients with incomplete resection following EMR/ESD due to the risk of residual tumor and lymph node metastasis.

• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.43-51
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• 1999

The aim of present study was to elucidate whether the expression of nm23 protein might be of clinical value as a prognostic factor in gastric cancer. The expression of nm23 protein was analyzed using an immunohistochemical method with formalin-fixed and paraffin embedded tissue samples from 76 gastric carcinoma patients. The cytoplasmic immunoreactivity of nm23 protein were detected in 53.9% of the sample tissues(41/76). When the immunoreactivity of nm23 protein with TNM status and other histopathologic findings were compared by using Chi-Square test, nm23 was found to have correlations with lymph node metastasis(p=0.04), a number of metastatic lymph node, and the invasion of lymphatic vessels(p=0.007); however, it had no correlation with TNM status. The conventional prognostic factors such as the depth of invasion, the degree of lymph node metastasis and the presence of distant metastasis, a Borrmann type, size of tumor, and the curability with operation were found to have a strong correlation with the survival time(p<0.003). However, the expression of nm23 protein was not significantly correlated with survival time in survival analysis. These results showed that the expression of nm23 protein is not a useful prognostic indicator in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2971-2977
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• 2014

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4823-4827
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• 2013

Objective: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. Methods: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. Results: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. Conclusion: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2151-2157
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• 2016

Scabraside D, a sulfated triterpene glycoside, was extracted from the sea cucumber Holothuria scabra. It shows anti-proliferation in many of cancer cell lines, but the function and mechanisms of action of scabraside D in human cholangiocarcinoma (HuCCA) have not previously determined. In this study, we investigated the activity of scabraside D on HuCCA cell apoptosis, lymphangiogenesis and metastasis in a nude mouse model. Scabraside D induced signs of apoptosis, such as cell shrinkage, nuclear condensation, nuclear fragmentation and DNA fragmentation on TUNEL assays, while effectively decreasing expression of BCl-2 but increasing caspase-3 gene level expression. Immunohistochemistry revealed that scabraside D significantly reduced lymphatic vessel density (LVD). Moreover, scabraside D treatment significantly decreased VEGF-C, MMP-9 and uPA gene expression, which play important roles in the lymphangiogenesis and invasion of cancer cells in metastasis processes. Quantitative real-time PCR showed that scabraside D significantly decreased iNOS and STAT-3 gene expression. This study demonstrated that scabraside D plays a role in activation of HuCCA tumor apoptosis and inhibition of lymphangiogenesis, invasion and metastasis through decreasing BCl-2, MMP-9, uPA and VEGF-C and increasing caspase-3 expression by suppression of iNOS and STAT-3 expression. Therefore, scabraside D could be a promising candidate for cholangiocarcinoma treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4257-4260
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• 2015

Background: Uterine papillary serous tumors are rarely seen and behave aggressively. Our aim was to evaluate uterine papillary serous tumors arising from polyps. Materials and Methods: Clinicopathological data of patients with uterine serous cancer arising from a polyp at the Gynecological Oncology Department of Zekai Tahir Burak Women's Health Education and Research Hospital were reviewed retrospectively. Results: We analyzed patients according to FIGO 2009 staging system as stage 1A and higher than stage 1A (3 and 6, respectively). All the patients were postmenopausal. Mean CA-125, CA-19.9 and CA15.3 levels were elevated in higher than stage 1A group. However we did not find a statistical difference between age, parity, polyp size, CA-125, CA-15.3, CA-19.9 and CEA levels. Lympho-vascular space invasion (LVSI) showed predictivity for advanced disease (p=0.025). Conclusions: The histopathologic nature of uterine serous carcinoma is a unique entity. LVSI is a prognosticator for defining an advanced stage uterine papillary tumor.