• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4813-4820
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• 2015

Gastric cancer (GC) is one of the most common cancers, with high incidences in East Asia countries. Most GC patients have been reported with low early diagnosis rate and show extremely poor prognosis. Therefore, it is necessary to develop novel and more sensitive biomarkers to improve early diagnosis and therapy in order to provide longer survival and better quality of life for gastric cancer patients. MicroRNAs (miRNAs) play crucial roles in GC development and progression. miRNAs have emerged as a novel molecular biomarker for cancer diagnosis, prognosis and therapy with surprising stability in tissues, serum or other body fluids. This review summarizes major advances in our current knowledge about potential miRNA biomarkers for GC that have been reported in the past two years.

• BMB Reports
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• v.53 no.4
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• pp.173-180
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• 2020

Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.293-299
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• 2008

To screen the differentially expressed genes in cadmuim-exposed marine medaka fish (Oryzias javanicus), a candidate marine test fish for ecological toxicity, the differential display polymerase chain reaction (DD-PCR) was carried out, since the genome-wide gene expression data are not available in this fish species yet. A total of 35 clones were isolated from cadmium-exposed fish and their nucleotide sequences were analyzed. The differentially expressed gene candidates were categorized to response to stimulus (3); ion binding (3); DNA binding (1); protein binding (6); carbohydrate binding (1); metabolic process (4); biological regulation (3); cellular process (2); protein synthesis (2); catalytic activity (2); sense of sight (1); immune (1); neurohormone (1); signaling activity (1); electron carrier activity (1) and others (3). For real-time quantitative RT-PCR, we selected catalase, glucose-6-phosphate dehydrogenase, heat shock protein 70, and metallothionein and confirmed that cadmium exposure enhanced induction of these four genes.

• Journal of Preventive Medicine and Public Health
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• v.42 no.6
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• pp.371-376
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• 2009

In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.36-47
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• 2019

Hypoxia-inducible factor-1 ($HIF-1{\alpha}$) is a transcription factor activated in response to low oxygen level, and is highly expressed in many solid tumors. Moreover, $HIF-1{\alpha}$ is a representative biomarker of hypoxia and also helps to maintain cell homeostasis under hypoxic condition. Most solid tumors show hypoxia, which induces poor prognosis and resistance to conventional cancer therapies. Thus, early diagnosis of hypoxia with positron emission tomography (PET) radiotracer would be highly beneficial for management of malignant solid tumors with effective cancer therapy. YC-1 is a most promising candidate among several $HIF-1{\alpha}$ inhibitors. As an effort to develop a hypoxia imaging tool as a PET radiotracer, we designed and synthesized [$^{18}F$]DFYC based on potent derivative of YC-1 and performed preliminary in vitro cell uptake study. [$^{18}F$]DFYC showed a significant accumulation in SKBR-3 cells among other cancer cells, proving as a good lead to develop a hypoxic solid tumor such as breast cancer.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.3-8
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• 2022

Alteration of the mGluR5 density is closely related to various brain diseases including schizophrenia, depression, Parkinson's disease, and Alzheimer's disease. Therefore, mGluR5 is considered as a valuable imaging biomarker for brain disease and many radiopharmaceuticals have been developed so far. Among them, [¹⁸F]FPEB has favorable pharmacokinetic characteristics, and this is the most frequently used radiopharmaceutical for preclinical and clinical studies. In the present study, we want to introduce the optimized radiosynthetic method for the routine production of [¹⁸F]FPEB using a GE TRACERlabTM FXFN pro module. In addition, the entire process was monitored with a webcam to solve the problems arising from the synthetic process. As a result, [¹⁸F]FPEB was prepared by nucleophilic substitution from its nitro- precursor at 120℃ for 20 min in dimethyl sulfoxide. Radiochemical yield was 13.7 ± 5.1% (decay-corrected, n = 91) with the molar activity of 84 ± 17 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 96%. The manufactured [¹⁸F]FPEB injection for quality controls were carried out in accordance with an KIRAMS approved protocol, as per ICH and USP guidelines.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.149-156
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• 2005

Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.197-204
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• 2012

Purpose: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Materials and Methods: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were reevaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and ${\beta}$-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. Results: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and ${\beta}$-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. Conclusion: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and ${\beta}$-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2725-2729
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• 2015

Background: Transitional cell carcinoma (TCC) and prostate cancer are the most frequent cancers in the male genitourinary tract. Measurement of biological biomarkers may facilitate clinical monitoring and aid early diagnosis of TCC. The aim of the present investigation was to detect the mRNA levels of S100A12 and RAGE (receptor for advanced glycation end products) in patients suffering from bladder TCC. Materials and Methods: To explore the involvement of S100A12 and RAGE genes, total RNA was harvested from cancer tissues and samples obtained from normal non-tumorized urothelium of the same patients. Quantitative PCR (qPCR) was subsequently employed to determine the mRNA levels of S100A12 and RAGE. Results: The results showed that mRNA expression of S100A12 and RAGE was significantly up-regulated in the cancer tissue. Conclusions: According to the results presented in the current study, mRNA expression of S100A12 and RAGE might be as a useful biomarker for TCC. Therefore, this ligand-receptor axis possibly plays important roles in the development of TCC and may serve either as an early diagnostic marker or as a key factor in monitoring of response to treatment. More research is required concerning inhibition of the S100A12-RAGE axis in different cancer models.

• Journal of Environmental Health Sciences
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• v.37 no.5
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• pp.358-368
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• 2011

Objectives: In order to evaluate the association between occupational exposure to chloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL), we conducted a meta-analysis of retrospective cohort studies and casecontrol studies and attempted to summarize the evidence of the association from molecular-epidemiological studies and experiments with human cells. Methods: In the meta-analysis, we restricted the analysis to those studies with data for chlorinated solvents, degreasers, or TCE. Studies involving dry cleaners or launderers were excluded from the analysis because use of TCE as a dry cleaning fluid has been rare since the 1960s. The data were combined using a random-effects model to estimate the summary risks (OR and RR) and 95% confidence intervals (CIs). Molecular evidence of the effect of TCE on human immune system were also reviewed and summarized. Results: Occupational exposure to TCE was strongly associated with NHL among cohort studies (number of studies=13, summary RR=1.33, 95% CI=1.04-1.70) whereas the association was not statistically significant among case-control studies (number of studies=15, summary OR=1.10, 0.98-1.23). When exposure level was considered, it became statistically significant for the highest exposure level (number of studies=5, summary OR=1.70, 1.25-2.32). Molecular evidences showed that TCE exposure in human or cultured human cells may cause a significant decrease immune cell subsets and changes in hormone levels related to immune response. Conclusions: Our results from meta-analysis and additional molecular evidence suggest that occupational exposure to TCE may cause NHL. However, unmeasured potential confounding and unclear dose-response relationships warrant further study on the role of TCE exposure in NHL carcinogenesis.