• BMB Reports
• /
• 제48권11호
• /
• pp.630-635
• /
• 2015

Downregulation of olfactomedin-4 (OLFM4) is associated with tumor progression, lymph node invasion and metastases. However, whether or not downregulation of OLFM4 is associated with epigenetic silencing remains unknown. In this study, we investigate the role of OLFM4 in gastric cancer cell invasion. We confirm the previous result that OLFM4 expression is increased in gastric cancer tissues and decreases with an increasing number of metastatic lymph nodes, which are associated with OLFM4 promoter hypermethylation. Overexpression of OLFM4 in gastric cancer cells had an inhibitory effect on cell invasion. Furthermore, we found that focal adhesion kinase (FAK) was negatively correlated with OLFM4 in regards to lymph node metastasis in gastric cancer tissues. Also, inhibition of FAK induced by OLFM4 knockdown resulted in a decrease in cell invasion. Thus, our study demonstrates that epigenetic silencing of OLFM4 enhances gastric cancer cell invasion via activation of FAK signaling.

• Biomolecules & Therapeutics
• /
• 제22권6호
• /
• pp.540-546
• /
• 2014

The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

• Journal of Gastric Cancer
• /
• 제12권4호
• /
• pp.210-216
• /
• 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.

• Journal of Gastric Cancer
• /
• 제6권2호
• /
• pp.84-90
• /
• 2006

Purpose: The macroscopic findings of tumors are not always identical with the microscopic findings. This study investigated the oncologic implications of macroscopic serosal invasion in advanced gastric cancer to find out how to improve the accuracy for the depth of invasion assessed by the surgeon during an operation. Materials and Methods: The medical records of 789 patients with advanced gastric cancer who underwent a gastrectomy at Kyungpook National University Hospital between 1995 and 1999 were reviewed. The prognoses and the recurrence patterns were analyzed according to macroscopic serosal invasion and microscopic serosal invasion, and the clinico-pathological factors of cT3/ss cancers were compared with those of cT3/se cancers. Results: Difference of survival rates according to macroscopic serosal invasion and microscopic serosal invasion revealed statistically significant. Recurrence rates were similar in patients with macroscopic and microscopic serosal invasion (42.2% and 41.4%, respectively). Peritoneal recurrence rates were also similar (19.8% and 21.9%, respectively). The sensitivity and the specificity of macroscopic assessment of serosal invasion were 70.3% and 77.8%, respectively, On univariate and multivariate analyses, Borrmann type I/II cancers and the absence of distant metastases revealed the risk factors for overestimating of serosal invasion. Conclusion: Macroscopic serosal invasion assessed by a surgeon intraoperatively can be used to give a prognosis and to predict the recurrence pattern precisely, although there is a risk for overestimation when the tumor is a Borrmann type I/II cancer or the tumor has no distant metastases. (J Korean Gastric Cancer Assoc 2006;6:84-90)

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권24호
• /
• pp.10713-10718
• /
• 2015

Purpose: To investigate the prognostic value of serum amyloid A (SAA) in patients with hepatocellular carcinoma (HCC) undergoing surgery. Materials and Methods: Preoperative serum samples of 328 patients with HCC who underwent curative resection and of 47 patients with benign liver lesion were assayed. Serum levels of SAA were measured by enzyme-linked immunosorbent assay and its correlations with clinicopathological characteristics and survival were explored. Results: Levels of SAA were significantly higher in patients with HCC than those with benign liver lesion. There were strong correlations between preoperative serum SAA level and tumor size and more advanced BCLC stage. On univariate analysis, elevated SAA was associated with reduced disease-free survival and overall survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that serum SAA level was an independent prognostic factor for overall survival (hazard ratio 2.80, p=0.01). Conclusions: High SAA serum level is a novel biomarker for the prognosis of HCC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권2호
• /
• pp.497-501
• /
• 2016

Aim: To evaluate the relationship between pre-operative CA-125 levels and myometrial invasion in patients with early-stage endometrioid-type endometrial cancer. Materials and Methods: Two-hundred and sixty patients were diagnosed with endometrial cancer between January 2007 and December 2012. Of these, 136 patients with stage 1 endometrioid histologic-type and documented pre-operative serum CA-125 levels were included in the study. Age, preoperative CA-125 level, histologic grade, surgical grade, and presence of deep myometrial invasion were recorded. Additionally, 16, 20, and 35 IU/ml cutoff values were used and compared to evaluate the relationship between pre-operative CA-125 levels and myometrial invasion. Results: The average serum CA-125 level was $35.4{\pm}36.7$ in patients with deep myometrial invasion, and $21.5{\pm}35.8$ in cases without deep myometrial invasion. The relationship between the presence of deep myometrial invasion and CA-125 cut-off values (16, 20, 35 IU/ml) was statistically significant, although the correlation was weak (p<0.05). When the relationship between 16, 20 and 35 IU/ml CA-125 cut-off values and the presence of deep myometrial invasion was studied, specifity and sensitivity values were identified as: 0.60-0.68 for 16 IU/ml; 0.73-0.48 for 20 IU/ml; and 0.89-0.33 for 35 IU/ml. The sensitivity of 16 IU/ml cut-off value was higher when compared to other values. Conclusions: This study demonstrates that preoperative serum CA-125 values maybe used as a predictive test in patients with early stage endometrioid-type endometrium cancer, and as a prognostic factor alone. Further studies should be conducted to identify different CA-125 cut-off values in patients with low risk endometrial cancer.

• Journal of dental hygiene science
• /
• 제18권3호
• /
• pp.188-193
• /
• 2018

The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor $1{\alpha}$ and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7241-7244
• /
• 2014

Background: To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Materials and Methods: Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopic finding, CT imaging and final pathological reports were analyzed. Results: This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imaging were gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. Conclusions: The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1097-1104
• /
• 2012

Background/Aim: Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown. Methods: The impacts of pristimerin on the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling 4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion were determined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively. Results: We found that pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependent manner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition of breast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implanted breast tumors in mice. Conclusion: Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7061-7064
• /
• 2014

Background: To assess the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of intraoperative gross examination (IGE) of uterine specimens in determining deep myometrial invasion and cervical invasion compared to final histology. Materials and Methods: The clinical, surgical and histological data of all FIGO stage I-II endometrial cancer (EC) patients who had primary surgery were reviewed. Results of the IGE for myometrial invasion and cervical invasion were compared to the final histology. The sensitivity, specificity, PPV, NPV, and accuracy of the IGE in determining deep myometrial invasion and cervical invasion were calculated. Association between clinico-pathological factors and discrepancy between IGE and final histology in the determination of myometrial invasion was also assessed. A p-value of <0.05 was considered significant. Results: From January 2007 to December 2012, 179 patients diagnosed with clinical stage I-II endometrial cancer underwent surgical staging. The sensitivity and specificity of IGE in detecting deep myometrial invasion were 42.4% and 90.0%, respectively, and the PPV and NPV were 67.6% and 76.1%. The overall accuracy of IGE was 74.3%. The sensitivity and specificity of IGE in identifying cervical invasion were 28.6% and 97.5%, respectively, while the PPV and NPV were 60.0% and 91.1%. The overall accuracy of IGE was 89.4%. Conclusions: The sensitivity of IGE for detecting deep myometrial invasion and cervical invasion in early-stage EC is too low to be used alone. Alternative methods including intraoperative frozen section analysis, preoperative three dimensional ultrasound, and preoperative magnetic resonance imaging should be strongly considered.