• Title/Summary/Keyword: molecular biomarker

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Molecular Characterization and Expression Analysis of Creatine Kinase Muscle (CK-M) Gene in Horse

  • Do, Kyong-Tak;Cho, Hyun-Woo;Badrinath, Narayanasamy;Park, Jeong-Woong;Choi, Jae-Young;Chung, Young-Hwa;Lee, Hak-Kyo;Song, Ki-Duk;Cho, Byung-Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.12
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    • pp.1680-1685
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    • 2015
  • Since ancient days, domestic horses have been closely associated with human civilization. Today, horse racing is an important industry. Various genes involved in energy production and muscle contraction are differentially regulated during a race. Among them, creatine kinase (CK) is well known for its regulation of energy preservation in animal cells. CK is an iso-enzyme, encoded by different genes and expressed in skeletal muscle, heart, brain and leucocytes. We confirmed that the expression of CK-M significantly increased in the blood after a 30 minute exercise period, while no considerable change was observed in skeletal muscle. Analysis of various tissues showed an ubiquitous expression of the CK-M gene in the horse; CK-M mRNA expression was predominant in the skeletal muscle and the cardiac muscle compared to other tissues. An evolutionary study by synonymous and non-synonymous single nucleotide polymorphism ratio of CK-M gene revealed a positive selection that was conserved in the horse. More studies are warranted in order to develop the expression of CK-M gene as a biomarker in blood of thoroughbred horses.

New Haplotypes of the ATP Synthase Subunit 6 Gene of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia in Saudi Arabia

  • Yacoub, Haitham Ahmed;Mahmoud, Wael Mahmoud;El-Baz, Hatim Alaa-Eldeen El-Din;Eid, Ola Mohamed;El-Fayoumi, Refaat Ibrahim;Mahmoud, Maged Mostafa;Harakeh, Steve;Abuzinadah, Osama H.A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10433-10438
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    • 2015
  • Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

Benzo(a)pyrene-Triglyceride Adduct: a Potential Molecular Biomarker for Carcinogen Exposure

  • Lee, Byung-Mu
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05b
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    • pp.20-45
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    • 2002
  • In this study, we demonstrated the in vitro and in vivo formation of carcinogen-lipid adduct and its correlation with DNA or protein adducts. The lipids from serum or hepatocyte membranes of Spragu-Dawley rats. human serum, and standard major lipids were in vitro reacted with benzo[a]pyrene(BP) and BP metabolites. 7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene(BPDE-I), an ultimate carcinogenic form of BP, was covalently bound to triglyceride(TG). BPDE-I-TG adducts isolated by thin-layer chromatography (TLC) were further detected by high performance liquid chromatography(HPLC). TGs, including triolein, tripalmitin and tristearin, showed positive reactions with BPDE-I. However, cholesterol, phospholipids(Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidyl-inositol and sphingomyelin) and nonesterified fatty acids(palmitic acid, oleic acid, linoleic acid and stearic acid) did not react with BPDE-I. In addition, other BP metabolites (BP-phenols and -diols) did not react with TG, which TG appeared to be the most reactive lipid yet studied with respect to its ability to form an adduct with BPDE-I. There was a clear-cut dose-respect to its ability to form an adduct with BPDE-I-lipid adduct in vitro between TG and [1,3-3H]BPDE-I. In an animal study, BPDE-I-TG was also formed in the serum of rats orally treated with BP(25 mg/rat). Also, obvious correlations between [3H]BP related-biomolecule adducts (DNA, protein) or lipid damage and the BPDE-I-TG adduct were obtained in various tissues of mice i.p. treated with [3H]BP. These data suggest that TG can form an adduct with BPDE-I, as do other macromolecules (DNA, RNA, and protein). Therefore, a carcinogen-lipid adduct would be a useful biomarker for chemical carcinogenesis research and cancer risk assessment.

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Altered Proteome of Extracellular Vesicles Derived from Bladder Cancer Patients Urine

  • Lee, Jingyun;McKinney, Kimberly Q.;Pavlopoulos, Antonis J.;Niu, Meng;Kang, Jung Won;Oh, Jae Won;Kim, Kwang Pyo;Hwang, Sunil
    • Molecules and Cells
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    • v.41 no.3
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    • pp.179-187
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    • 2018
  • Proteomic analysis of extracellular vesicles (EVs) from biological fluid is a powerful approach to discover potential biomarkers for human diseases including cancers, as EV secreted to biological fluids are originated from the affected tissue. In order to investigate significant molecules related to the pathogenesis of bladder cancer, EVs were isolated from patient urine which was analyzed by mass spectrometry based proteomics. Comparison of the EV proteome to the whole urine proteome demonstrated an increased number of protein identification in EV. Comparative MS analyses of urinary EV from control subjects and bladder cancer patients identified a total of 1,222 proteins. Statistical analyses provided 56 proteins significantly increased in bladder cancer urine, including proteins for which expression levels varied by cancer stage (P-value < 0.05). While urine represents a valuable, non-invasive specimen for biomarker discovery in urologic cancers, there is a high degree of intra- and inter-individual variability in urine samples. The enrichment of urinary EV demonstrated its capability and applicability of providing a focused identification of biologically relevant proteins in urological diseases.

Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical Applications

  • Kang, Man-Man;Shan, Shun-Lin;Wen, Xu-Yang;Shan, Hu-Sheng;Wang, Zheng-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6215-6223
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    • 2015
  • Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

Immunosignature: Serum Antibody Profiling for Cancer Diagnostics

  • Chapoval, Andrei I;Legutki, J Bart;Stafford, Philip;Trebukhov, Andrey V;Johnston, Stephen A;Shoikhet, Yakov N;Lazarev, Alexander F
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4833-4837
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    • 2015
  • Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

From genome sequencing to the discovery of potential biomarkers in liver disease

  • Oh, Sumin;Jo, Yeeun;Jung, Sungju;Yoon, Sumin;Yoo, Kyung Hyun
    • BMB Reports
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    • v.53 no.6
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    • pp.299-310
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    • 2020
  • Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers.

Research Trend of Biochip Sensors for Biomarkers Specific to Diagnostics of Lung Cancer Diseases (폐암 질환 진단에 활용 가능한 바이오마커 검출용 바이오칩 센서 연구 동향)

  • Lee, Sang Hyuk;Goh, Eunseo;Lee, Hye Jin
    • Applied Chemistry for Engineering
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    • v.29 no.6
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    • pp.645-651
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    • 2018
  • Lung cancer has the highest death rate of any cancer diseases in Koreans. However, patients often feel difficult to recognize their disease before facing the terminal diagnosis due to the absence of any significant symptoms. Furthermore, the clear detection of an early cancer stage is usually obscure with existing diagnostic methods. For this reason, extensive research efforts have been made on introducing a wide range of biochemical diagnostic tools for the molecular level analysis of biological fluids for lung cancer diagnoses. A chip-based biosensor, one type of the analytical devices, can be a great potential for the diagnosis, which can be used without any further expensive analytical equipments nor skilled analysts. In this mini review, we highlight recent research trends on searching biomarker candidates and bio-chip sensors for lung cancer diagnosis in addition to discussing their future aspects.

Elevated plasma α1-antichymotrypsin is a biomarker candidate for malaria patients

  • Young Yil, Bahk;Sang Bong, Lee;Jong Bo, Kim;Tong-Soo, Kim;Sung-Jong, Hong;Dong Min, Kim;Sungkeun, Lee
    • BMB Reports
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    • v.55 no.11
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    • pp.571-576
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    • 2022
  • Advancements in the field of proteomics have provided opportunities to develop diagnostic and therapeutic strategies against various diseases. About half of the world's population remains at risk of malaria. Caused by protozoan parasites of the genus Plasmodium, malaria is one of the oldest and largest risk factors responsible for the global burden of infectious diseases with an estimated 3.2 billion persons at risk of infection. For epidemiological surveillance and appropriate treatment of individuals infected with Plasmodium spp., timely detection is critical. In this study, we used combinations of depletion of abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, LC-MS/MS and western blot analysis on the plasma of healthy donors (100 individuals) and vivax and falciparum malaria patients (100 vivax malaria patients and 8 falciparum malaria patients). These analyses revealed that α1-antichymotrypsin (AACT) protein levels were elevated in vivax malaria patient plasma samples (mean fold-change ± standard error: 2.83 ± 0.11, based on band intensities), but not in plasma from patients with other mosquito-borne infectious diseases. The results of AACT immunoblot analyses showed that AACT protein was significantly elevated in vivax and falciparum malaria patient plasma samples (≥ 2-fold) compared to healthy control donor plasma samples, which has not been previously reported.

MicroRNA super-resolution imaging in blood for Alzheimer's disease

  • Mirae Lee;Jiwon Woo;Sang Tae Kim;Minho Moon;Sang Yun Kim;Hanna Cho;Sujin Kim;Han-Kyeol Kim;Jeong-Yoon Park
    • BMB Reports
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    • v.56 no.3
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    • pp.190-195
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    • 2023
  • We propose a novel blood biomarker detection method that uses miRNA super-resolution imaging to enable the early diagnosis of Alzheimer's disease (AD). Here, we report a single-molecule detection method for visualizing disease-specific miRNA in tissue from an AD mice model, and peripheral blood mononuclear cells (PBMCs) from AD patients. Using optimized Magnified Analysis of Proteome (MAPs), we confirmed that five miRNAs contribute to neurodegenerative disease in the brain hippocampi of 5XFAD and wild-type mice. We also assessed PBMCs isolated from the whole blood of AD patients and a healthy control group, and subsequently analyzed those samples using miRNA super-resolution imaging. We detected more miR-200a-3p expression in the cornu ammonis 1 and dentate gyrus regions of 3 month-old 5XFAD mice than in wild-type mice. Additionally, miRNA super-resolution imaging of blood provides AD diagnosis platform for studying miRNA regulation inside cells at the single molecule level. Our results present a potential liquid biopsy method that could improve the diagnosis of early stage AD and other diseases.