• 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.7
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• pp.4261-4265
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• 2013

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4487-4490
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• 2016

Background: Methylation at cg 16941656 of FRY is exclusively found in normal pancreatic tissue and has been proven to be specific for pancreatic-in-origin among several adenocarcinomas. Here, we investigated methylated DNA in the bile as a biomarker to differentiate the cause of obstruction between pancreatic cancer and benign causes. Materials and Methods: Bile samples of 45 patients with obstructive jaundice who underwent ERCP were collected and classified into pancreatic cancer (group 1) and benign causes (group 2) in 24 and 21 patients, respectively. DNA was extracted from bile and bisulfite modification was performed. After, methylation in cg 16941656 of FRY was identified by real-time PCR, with beta-actin used as a positive control. Results: Methylated DNA was identified in 10/24 (41.67%) and 1/21 (4.8%) of cases in groups 1 and 2, respectively (P= 0.012). The sensitivity, specificity, positive predictive value and negative predictive value to differentiate pancreatic cancer from benign causes were 42%, 95%, 91%, and 59%, respectively. Conclusions: Detecting a methylation at cg 16941656 of FRY in bile has high specificity, with an acceptable positive likelihood rate, and may therefore be helpful in distinguish pancreatic cancer from benign strictures.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5059-5062
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• 2015

Background: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. Aim and objectives: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. Materials and Methods: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione-s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. Results: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Conclusions: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4439-4445
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• 2015

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3223-3228
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• 2013

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10917-10922
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• 2015

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$), alpha-fetoprotein (${\geq}100ng/ml$), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

• 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.

• Mass Spectrometry Letters
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• v.5 no.1
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• pp.16-23
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• 2014

Liquid chromatography based mass spectrometry (LC-MS) is a key technology for analyzing highly complex and dynamic proteome samples. With highly accurate and sensitive LC-MS analysis of complex proteome samples, efficient data processing is another critical issue to obtain more information from LC-MS data. A typical proteomic data processing starts with protein database search engine which assigns peptide sequences to MS/MS spectra and finds proteins. Although several search engines, such as SEQUEST and MASCOT, have been widely used, there is no unique standard way to interpret MS/MS spectra of peptides. Each search engine has pros and cons depending on types of mass spectrometers and physicochemical properties of peptides. In this study, we describe a novel data process pipeline which identifies more peptides and proteins by correcting precursor ion mass numbers and unifying multi search engines results. The pipeline utilizes two open-source software, iPE-MMR for mass number correction, and iProphet to combine several search results. The integrated pipeline identified 25% more proteins in mouse epididymal adipose tissue compared with the conventional method. Also the pipeline was validated using control and colitis induced colon tissue. The results of the present study shows that the integrated pipeline can efficiently identify increased number of proteins compared to the conventional method which can be a breakthrough in identification of a potential biomarker candidate.

• Journal of fish pathology
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• v.29 no.1
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• pp.25-33
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• 2016

In human medicine, circulating microRNAs have been successfully utilized as early biomarkers for various abnormalities and disease states. Vertebrate miR-122 is a liver-specific microRNA which is expressed almost solely in hepatocytes and plays an important role in the regulation of hepatocyte function. In this study, to evaluate the potential utility of circulating miR-122 as a biomarker for liver injury in olive flounder (Paralichthys olivaceus), fish were orally intubated with two doses of acetaminophen (500 mg/kg or 1.000 mg/kg of body weight), and the expression of miR-122 in serum was quantified using real time-PCR. Histological change in liver, and the enzymatic activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also analyzed. The results showed that miR-122 was higher in acetaminophen administered groups compared to control group. The histopathological effect of acetaminophen on olive flounder liver was not distinct. The serum level of GPT and GOT was increased within 2 folds compared to control group by acetaminophen administration. However, the serum miR-122 level was increased more than 3 or 4 folds compared to the control group by administration of 1000 mg/kg of acetaminophen. These results suggest the possible use of miR-122 as an indicator of liver injury in olive flounder, even when histopathological effects are not distinctive.