• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1563-1567
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• 2012

To investigate the relationship between serum miRNA-21 (miR-21) expression in esophageal squamous cell carcinomas (ESCCs) and its clinicopathologic features, a 1:1 matched case-control study including 21 patients with ESCC and 21 age- and gender-matched healthy controls was carried out. Serum specimens were taken from all subjects. Total RNA was extracted and the stem-loop real time polymerase chain reaction was used to measure serum miR-21 in both groups. Clinical parameters were assessed to determine associations with serum miR-21 concentrations. Serum miR-21 expression in ESCC samples was significantly higher than in paired cancer-free samples (P<0.05). Metastasis was associated with mir-21 expression in serum (P<0.05), ESCC patients with metastasis having 8.4-fold higher serum miR-21 concentrations than healthy controls. There were no statistically significant associations between miR-21 expression and clinicopathologic parameters, such as gender (P>0.05), age (P>0.05), tumor location (P>0.05), cell differentiation (P>0.05), TNM staging (P>0.05), whether chemo/radiotherapy had been administered (P>0.05), or whether surgery had been performed (P>0.05). These findings suggest that the detection of microRNA-21 in serum might serve as a new tumor biomarker in diagnosis and assessment of prognosis of ESCCs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6557-6562
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• 2013

Objective: Specific promoters could improve efficiency and ensure the safety of gene therapy. The aim of our study was to screen examples for lung cancer. Methods: The firefly luciferase gene was used as a reporter, and promoters based on serum markers of lung cancer were cloned. The activity and specificity of seven promoters, comprising CEACAM5 (carcinoembryonic antigen, CEA), GRP (Gastrin-Releasing Peptide), KRT19 (cytokeratin 19, KRT), SFTPB (surfactant protein B, SP-B), SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA), SELP (Selectin P, Granule Membrane Protein 140kDa, Antigen CD62, GMP) and DKK1 (Dickkopf-1) promoters were compared in lung cancer cells to obtain cancer-specific examples with strong activity. Results: The CEACAM5, DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB promoters were cloned. Furthermore, we successfully constructed recombinant vector pGL-CEACAM5 (DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB) contained the target gene. After cells were transfectedwith recombinant plasmids, we found that the order of promoter activity from high to low was SERPINB3, DKK1, SFTPB, KRT19, CEACAM5, SELP and GRP and the order for promoters regarding specificity and high potential were SERPINB3, DKK1, SELP, SFTPB, CEACAM5, KRT19 and GRP. Conclusion: The approach adopted is feasible to screen for new tumour specific promoters with biomarkers. In addition, the screened lung-specific promoters might have potential for use in lung cancer targeted gene therapy research.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1789-1795
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• 2016

Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2711-2715
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• 2013

Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. Materials and Methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5257-5261
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• 2013

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia ($7.15{\pm}2.18$) and solid tumor groups ($7.11{\pm}1.47$), but both were higher than in the MDS group ($5.12{\pm}1.29$) and benign blood diseases group ($3.08{\pm}1.08$). Taking 7.15‰, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group ($MNF{\geq}7.15$‰) and low MNF group (MNF<7.15‰). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.135-140
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• 2008

Loss of E-cadherin (E-cad) expression has been found in multiple cancers and is postulated to facilitate tumor cell dissociation and metastais. Promotor methylation may provides an alternative pathway for loss of gene function. This study evaluated the role of hypermethylation in the down-regulation of E-cad in oral squamous cell carcinoma (OSCC). We examined the E-cad expression by immunohistochemical staining and detected methylation status by methylation-specific polymerase chain reaction (MSP) in 20 OSCC tissues. Overally, 12 (60%) cases of hypermethylation of E-cad were detected and we found there were no correlation between methylation and age, histologic grade, lympn node metastasis, tumor size and clinical stage. However, Eleven (73.3%) of 15 samples which was negative for E-cad staining showed hypermethylation of E-cad promotor region. On the other hand, only one (20%) of 5 E-cad positive sample was observed with methylated status. The underexpression of E-cad was found to be related to promotor hypermethylation (p=0.035). In conclusion, we suggest that hypermethylation play a role in inactivation of E-cad gene and may be a appreciable biomarker for diagnosis and treatment of OSCC.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.273-286
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• 2021

Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

• Journal of Veterinary Science
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• v.21 no.2
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• pp.23.1-23.10
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• 2020

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.

• Biomedical Science Letters
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• v.28 no.3
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• pp.200-205
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• 2022

Established cancer cell lines are widely used for developing biomarkers for the patient-specific treatment of colorectal cancer and predicting prognoses. However, cancer cell lines may exhibit different drug responses depending upon the characteristics of the cell line. Therefore, it is necessary to select a tumor cell line suitable for the purpose of the study by considering the cell characteristics. This study investigated the levels of CXCL10, which were recently been reported to play an important role in the outcome of tumor treatment, secreted by colon cancer cells. 2 × 10⁵ cells/mL of each colorectal cancer cell was seeded into a 35 mm cell culture dish. After 24 h incubation, culture supernatant was used to determine the secreted CXCL10 levels. Among six colorectal cancer cell lines (HT-29, HCT116, CaCo-2, SW620, SW480, and CT26), Caco-2 cells showed the highest level of CXCL10 secretion. HT-29 cells showed the second-highest level of CXCL10 secretion. No significantly measurable level of CXCL10 secretion was detected in HCT116 cells. These results will be helpful in investigating the molecular basis of colorectal cancer.