• BMB Reports
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• v.41 no.10
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• pp.685-692
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• 2008

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

• Toxicological Research
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• v.32 no.1
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• pp.47-56
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• 2016

The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.75-90
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• 2010

Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7575-7581
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• 2014

MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.72-72
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• 2001

• Biomedical Science Letters
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• v.21 no.1
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• pp.1-8
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• 2015

Alzheimer's disease is a common form of dementia occurring among the elderly population and can be identified by symptoms such as cognition impairments, memory loss and neuronal dysfunction. Alzheimer's disease was found to be caused by the deposition of $\beta$-amyloid plaques and neurofibrillary tangles. In addition, mutation in the APP (Amyloid precursor protein), Presenilin 1 (PSEN1) and Presenilin 2 (PSEN2) genes were also found to contribute to Alzheimer's disease. Since the potential conformational diagnosis of Alzheimer's disease requires histopathological tests on brain through autopsy, potential early diagnosis still remains challenging. In recent years, several researches have proposed the use of biomarkers for early diagnosis. In cerebrospinal fluid (CSF), $\beta$-amyloid(1-42), phosphorylated-tau and total tau were suggested to be effective biomarkers for Alzheimer's disease diagnosis. However, a single biomarker might not be sufficient for potential diagnosis of Alzheimer's disease. Thus, the use of RNA interference (RNAi) through microRNAs (miRNAs) has been proposed by several researchers for simultaneous analysis of several biomarkers using microarray technology. These miRNA based biomarkers can be analysed from both blood and CSF, but miRNAs from blood are advantageous over CSF as they are non-invasive and simple for collection. Moreover, the RNAi based therapeutics by siRNA (short interference RNA) or shRNA (short hairpin RNA) have also been proposed to be effective in the treatment of Alzheimer's disease. This review describes the promising application of RNAi technology in therapeutics and as a biomarker for both Alzheimer's disease diagnosis and treatment.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.229-235
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• 2006

Volatile organic compounds (VOCs) are a major component of urban air pollution. It is documented that low exposure levels of VOCs induce alterations in immune reactivity resulting in a subsequent higher risk for the development of allergic reactivity and asthma. Despite these facts, there are few reports on the affected primary target and the underlying effective causal mechanisms. So in this study, to better understand the risk of BTX (benzene, toluene and o-xylene) which are the major VOCs and to identify novel biomarkers on immune response to these VOCs exposure in human T lymphocytes, we performed the toxicogenomic study by analyzing of gene expression profiles using 35 k human oligo-microarray. BTX generated specific gene expression patterns in Jurkat cell line. By clustering analysis, we identified some genes as potential markers on immuno-modulating effects of BTX. Four genes of these, HLA-DOA, ITGB2, HMGA2 and 5TAT4 were the most significantly affected by BTX exposure. Thus, this study suggests that these differentially expressed immune genes may play an important role in the pathogenesis on BTX exposure and have significant potential as novel biomarkers of exposure, susceptibility and response to BTC.

• Journal of Veterinary Clinics
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• v.40 no.2
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• pp.164-174
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• 2023

Canine splenic tumors (STs) are commonly diagnosed during imaging examinations, such as in X-ray and ultrasonography examinations, suggesting their higher prevalence, especially in older dogs. Despite this high prevalence, there are no effective treatment options for STs because of the difficulties in determining therapeutic targets. However, recently, the importance of microRNAs (miRNAs) has evolved owing to their ambivalent characteristics. Biomarkers and novel therapies using miRNAs have been well-studied in human cancer research compared to canine research, except for mammary gland tumors. Therefore, this study aimed to comparatively analyze miRNA expression profiles according to malignancy and biopsy sites to identify novel therapeutic and diagnostic targets. Tissue samples were collected directly from splenic tumor masses and immersed in RNAlater solution for further analysis. To investigate differentially expressed genes (DEGs) between tumor and normal tissues, we used RNA-seq and miRNA microarray analysis. Then, functional analysis based on DEGs was conducted to sort tumor-related DEGs. We found that cfa-miR-150 was upregulated in benign tumors, whereas cfa-miR-134 was upregulated in malignant tumors. Despite limited information on canine miRNAs, we identified two potential biomarkers for the differential diagnosis of STs.

• Molecules and Cells
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• v.43 no.4
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• pp.384-396
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• 2020

Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.