• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2003-2007
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• 2015

Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameter is used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the other rare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, we evaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastric cancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, including all consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFP level. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis were evaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization was the gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in 13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA) response of the patients with their radiologic responses was evaluated, it was found that the radiologic response was compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5 (29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Follow-up of AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of early treatment response and could be more useful than the CEA marker for follow-up in response evaluation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1349-1353
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• 2012

Increasing evidence has revealed that thy-1 was a potential stem cell marker of liver cancer, but no data have been shown on how thy-1 regulates the pathophysiology of liver cancer, such as proliferation, apoptosis, invasion and migration. We previously demonstrated that thy-1 was expressed in about 1% of hepg2 cells, thy-1+hepg2 cells, but not thy-1-, demonstrating high tumorigenesis on inoculation $0.5{\times}10^5$ cells per BACA/LA mouse after 2 months. In the present study, our results showed that higher expression of thy-1 occurs in 72% (36/50 cases) of neoplastic hepatic tissues as compared to 40% (20/50 cases) of control tissues, and the expression of thy-1 is higher in poorly differentiated liver tumors than in the well-differentiated ones. In addition, thy-1 expression was detected in 85% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis or hepatitis. There was a significant negative correlation between thy-1expression and E-cadherin expression (a marker of invasion and migraton), but not between thy-1 expression and AFP expression in all the liver cancer and blood samples. We further investigated the relationship between thy-1 and E-cadherin in liver cancer hepg2 cell line which was transfected with pReceiver-M29/thy-1 eukaryotic expression vector followed by aspirin treatment. Lower expression of E-cadherin but higher expressions of thy-1 were detected in hepg2 cells transfected with pReceiver-M29/thy-1. Taken together, our study suggested that thy-1 probably regulates liver cancer invasion and migration.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.775-780
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• 2012

8-isoprostane (8-$isoPGF_{2{\alpha}}$) is a reliable marker and considered a gold standard for lipid peroxidation. There are very few reports of 8-isoprostane levels in cancer patients, and in patients undergoing chemotherapy. Oxidative stress is however expected and has been observed in patients with cancer. This study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of treatment. It considers the creatinine clearance of the patients, and correction of 8-isoprostane levels by creatinine clearance, and overnight urine volume methods. The average 8-isoprostane levels in urine increased more than 6 to 12 fold on chemotherapy treatment, from $532{\pm}587$ pg/mL at cycle $1,6181{\pm}4334$ at cycle 2, and $5511{\pm}2055$ at cycle 3. Similar results were obtained if 8-isoprostane levels were corrected for overnight urine volume, giving averages of $285{\pm}244{\mu}g$ at cycle $1,4122{\pm}3349$ at cycle 2, and $3266{\pm}1200$ at cycle 3. No significant difference was seen in average total overnight urine volume or number of urinations between chemotherapy cycles except for a large variation in urine volume between cycle 2 and 3. Creatinine levels were significantly different only between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown to induce high levels of lipid peroxidation in lung cancer patients and can be assessed from the 8-isoprostane marker in overnight urine, with or without urine volume correction.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3437-3442
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• 2013

The high incidence of gastric cancer and consequent mortality pose severe threats to human health. Early screening, diagnosis and treatment are the key to improve the prognosis of the patients with gastric cancer. Gastroscopy with biopsy is an efficient method for the diagnosis of early gastric cancer, but the associated discomfort and high cost make it difficult to be a routine method for screening gastric cancer. Serum tumor marker assay is a simple and practical method for detection of gastric cancer, but it is limited by poor sensitivity and specificity. Therefore, people have been looking for novel serum markers of gastric cancer in recent years. Here we review the novel serum tumor markers of gastric cancer and their diagnostic significance, focusing on the discoveries from serum proteomics analyses and epigenetics researches.

• BMB Reports
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• v.51 no.2
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• pp.57-58
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• 2018

An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6545-6548
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• 2015

Background: Synovial sarcoma is a mesenchymal neoplasm that accounts for around 10% of all soft tissue sarcomas. The diagnosis of synovial sarcoma can be a challenging task, particularly with small biopsy specimens. Aim: We investigated transducer-like enhancer of split 1 (TLE1), monoclonal antibody, expression by immunohistochemical analysis in a group of 74 synovial sarcoma cases, 20 cases of MPNST, 12 cases of neurofibroma, 15 cases of schwannoma, 5 cases of MFH, 10 cases of lieomyosarcoma and 10 cases of solitary fibrous tumor. Materials and Methods: Whole tissue sections were examined: (39 biphasic and 35 monophasic). Nuclear immunoreactivity was scored as negative (<5% of cells positive), 1+(mild /5-25%), 2+ (moderate/25-50%), and 3+ (strong >50%). Results: Overall, 71 (96%) of 74 synovial sarcomas were positive for TLE1, including 37 biphasic (95%) and 34 monophasic (97%) tumors. Other spindle cell tumors showed very low or absent staining of TLE1. Conclusions: We conclude that TLE1 is a sensitive marker and can be a useful diagnostic marker for synovial sarcoma, particularly the monophasic forms.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2341-2344
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• 2014

Background: p53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and its significance as a diagnostic marker. Materials and Methods: We compared and evaluated 93 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significance and 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC), 5 follicular adenomas (FA), 5 Hashimoto's thyroiditis (HT) and 12 nodular hyperplasias (NH) for significance as a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffinembedded tissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versus other benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively. Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlation between p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis, extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC from other BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.

• Korean Journal of Clinical Laboratory Science
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• v.46 no.2
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• pp.59-63
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• 2014

The death toll of Colorectal Carcinoma in Korea was 1,826 and 7,721 in the years 1992 and 2011, respectively. This rate of increase was shown to be more than 4.23 times higher than that of any other form of cancer. Therefore, Colorectal Carcinoma requires various diagnostic methods, and Microsatellite Instability (MSI) was applied as a new diagnostic tool. From this study with several microsatellite markers, only marker #13 was detected and observed D13S160 13% (4/30), D13S292 13% (4/30), D13S153 10% (3/30) in order. From the results of amplication with microsatellite marker, D13S292 37% (11/30), D13S153 33% (10/30), D13S160 33% (10/30) in order were shown. The appearance of a genetic mutation, which depends on the loci of Colorectal Carcinoma, was shown amplication from rectal cancer (3.77) which was higher than that of right Colorectal Carcinoma (2.08) (p<0.018). The genetic mutation with lymph node (4.13) appeared higher than normal (1.93) (p<0.001). There were no great differences in the genetic mutation dependent on disease, histological classification and increased group of serum CEA. Accordingly, it is suggested that the correct primers, which can evaluate MSI well from colorectal carcinoma, should be chosen and that MSI be considered a good prognosis and quality control tool.

• Journal of Nutrition and Health
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• v.53 no.2
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• pp.111-120
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• 2020

Purpose: Corosolic acid (CA), also known as 2α-hydroxyursolic acid, is present in numerous plants, and is reported to exhibit anti-cancer and anti-proliferative activities in various cancer cells such as osteosarcoma, hepatocellular carcinoma, lung adenocarcinoma, and colon cancer. However, the anti-cancer activity of CA on human breast cancer cells and the underlying mechanisms remain to be elucidated. The present study aimed to investigate the anticancer effects of CA in the human breast cancer cell line, MDA-MB-231. Methods: Cell viability, reactive oxygen species (ROS) production, apoptosis marker protein expression, migration, invasion rate, and vascular endothelial growth factor (VEGF) levels were assessed by treating MDA-MB-231 cells to increasing concentrations of CA. Results: The results showed that CA significantly inhibited the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. To assess the effect of CA on apoptosis, nuclei of MDA-MB-231 cells were stained with DAPI solution. Chromatin condensation, which indicates apoptosis, was observed to increase dose-dependently. In addition, western-blot analysis revealed elevated levels of the apoptosis marker proteins (Bax and cleaved caspase 3) subsequent to MDA-MB-231 exposure to CA. ROS production was also increased in the CA-induced apoptosis in MDA-MB-231 treated cells. Interestingly, CA exposure resulted in significantly decreased migration and invasion rates in the MDA-MB-231 cells. Data further revealed that exposure to CA markedly decreased the VEGF concentration, thereby contributing to a reduction in angiogenesis. Conclusion: Our results determined that exposure to CA induces anti-proliferation, apoptosis, and ROS production, and suppresses cell migration and invasion rate in MDA-MB-231 cells. Taken together, these results indicate the potential of CA to be applied as an effective chemotherapeutic agent for treating breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.179-183
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• 2016

Breast cancer is the most prevalent type of cancer among women around the world, and mortality is primarily caused by micro-metastatic disease. The complex mechanisms of breast cancer invasion and metastasis are intrinsically related to the malignant cell type so that early detection of micro-metastases can help prolongation of survival for patient. The aim of the present research work was evaluation of the expression status of mammoglobin protein as a candidate molecular marker in the negative sentinel lymph node (SLN). Fifty tumor specimens, and 50 normal adjacent breast tissue samples from the same patients were selected on the basis of having more than 10% tumor content for RNA extraction from SLNs. Tumor samples and normal adjacent breast tissue were archived in the form of frozen fresh tissue in liquid nitrogen. Real-time PCR was performed on a Bioner life express gradient thermal cycler system. Mammoglobin gene overexpression in breast cancer metastasis was investigated. Single marker results were mammaglobin 66.7% and CK19 50.0%, with 58.3% for the two in combination. Due to improved outcome with at least 3 genes (83.3%), it seems, triple marker evaluation will be most likely useful for detecting micro-metastases instead of studying separate genes.