• Title/Summary/Keyword: molecular biomarkers

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Clinical Efficacy and Possible Applications of Genomics in Lung Cancer

  • Alharbi, Khalid Khalaf
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1693-1698
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    • 2015
  • The heterogeneous nature of lung cancer has become increasingly apparent since introduction of molecular classification. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations. In light of the tsunami of new biomarkers and targeted agents, next generation sequencing testing strategies will be more appropriate in identifying the patients for each therapy and enabling personalized patients care. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices. In genomic era of cancer treatment, the traditional one-size-fits-all paradigm is being replaced with more effective, personalized oncologic care. This review provides an overview of lung cancer genomics and personalized treatment.

Caenorhabditis elegans as a Biological Model for Multilevel Biomarker Analysis in Environmental Toxicology and Risk Assessment

  • Choi, Jin-Hee
    • Toxicological Research
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    • v.24 no.4
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    • pp.235-243
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    • 2008
  • While in some instances, loss of diversity results from acute toxicity (e.g. major pollution incidents), in most cases it results from long-term sub-lethal effects that alter the relative competitive ability and fitness of certain organisms. In such cases the sub-lethal effects will cause a physiological response in the organism that ultimately leads to community level changes. Very sensitive tools are now available to study sub-lethal responses at the molecular level. However, relating such laboratory measurements to ecological effects represents a substantial challenge that can only be met by investigation at all scales (molecular, individual organism and community level) with an appropriate group of organisms. Among the various in vertebrates which can be used as model organisms in such a way, the soil nematode, Caenorhabditis elegans appear to be a promising biological model to diagnose environmental quality. This paper reviews the current status of multilevel biomarkers in environmental toxicology, and C. elegans as promising organisms for this approach.

Mass Spectrometry-based Hair Metabolomics for Biomarker Discovery

  • Lee, Yu Ra;Hong, Jongki;Chung, Bong Chul
    • Mass Spectrometry Letters
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    • v.13 no.1
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    • pp.2-10
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    • 2022
  • Metabolomics makes it possible to analyze the interrelationships between various signaling molecules based on the metabolic pathways involved by using high-resolution devices. This approach can also be used to obtain large-scale metabolic information to identify the relevant pathways for disease diagnosis and prognosis and search for potential biomarkers. In the fields of medicine and forensics, hair analysis is used to detect various metabolites in the body. Hair can be harvested readily in a noninvasive manner and is easier to transport and store than blood and urine. Another advantage from a forensic viewpoint is that hair reflects all the components of body fluids. In addition, because of the unique coating structure of hair, it can be used for measurements without changing or destroying its adsorbed components. In this review, the pretreatments for hair analysis, instrumental conditions and clinical applications are discussed. Especially, the clinical use of hair metabolomics in the diagnosis of various diseases and the limitations of the technique are described.

Current research status for imaging neuroinflammation by PET

  • Namhun Lee;Jae Yong Choi
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.6 no.2
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    • pp.116-130
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    • 2020
  • The aging society is globally one of biggest issue because it is related with various degenerative brain disease such as dementia, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and cerebrovascular disease. These diseases are characterized by misfolded-protein aggregation; another pathological trait is "neuroinflammation". In physiological state, the resting microglia cells are activated and it removes abnormal synapses and cell membrane debris to maintain the homeostasis. In pathological state, however, microglia undergo morphological change form 'resting' to 'activated amoeboid phenotype' and the microglia cells are accumulated by neuronal damage, the inflammatory reactions induced nerve metamorphosis with a variety of neurotoxic factors including cytokines, chemokines, and reactive oxygen species. Thus, the activated microglia cell with various receptors (TSPO, COX, CR, P2XR, etc.) was perceived as important biomarkers for imaging the inflammatory progression. In this review, we would like to introduce the current status of the development of radiotracers that can image activated microglia.

Host-Pathogen Interactions Operative during Mycobacteroides abscessus Infection

  • Eun-Jin Park;Prashanta Silwal;Eun-Kyeong Jo
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.40.1-40.20
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    • 2021
  • Mycobacteroides abscessus (previously Mycobacterium abscessus; Mabc), one of rapidly growing nontuberculous mycobacteria (NTM), is an important pathogen of NTM pulmonary diseases (NTM-PDs) in both immunocompetent and immunocompromised individuals. Mabc infection is chronic and often challenging to treat due to drug resistance, motivating the development of new therapeutics. Despite this, there is a lack of understanding of the relationship between Mabc and the immune system. This review highlights recent progress in the molecular architecture of Mabc and host interactions. We discuss several microbial components that take advantage of host immune defenses, host defense pathways that can overcome Mabc pathogenesis, and how host-pathogen interactions determine the outcomes of Mabc infection. Understanding the molecular mechanisms underlying host-pathogen interactions during Mabc infection will enable the identification of biomarkers and/or drugs to control immune pathogenesis and protect against NTM infection.

What Single Cell RNA Sequencing Has Taught Us about Chronic Obstructive Pulmonary Disease

  • Don D. Sin
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.3
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    • pp.252-260
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    • 2024
  • Chronic obstructive pulmonary disease (COPD) affects close to 400 million people worldwide and is the 3rd leading cause of mortality. It is a heterogeneous disorder with multiple endophenotypes, each driven by specific molecular networks and processes. Therapeutic discovery in COPD has lagged behind other disease areas owing to a lack of understanding of its pathobiology and scarcity of biomarkers to guide therapies. Single cell RNA sequencing (scRNA-seq) is a powerful new tool to identify important cellular and molecular networks that play a crucial role in disease pathogenesis. This paper provides an overview of the scRNA-seq technology and its application in COPD and the lessons learned to date from scRNA-seq experiments in COPD.

Opportunities and Challenges in Nutrigenomics and Health Promotion

  • Milner John A.
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2004.11a
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    • pp.17-23
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    • 2004
  • Not all individuals respond identically, or at times in the same direction, to dietary interventions. These inconsistencies likely arise because of diet and genomic interactions (nutrigenomics effects). A host of factors may influence the response to bioactive food components including specific polymorphisms (nutrigenetic effect), DNA methylation patterns and other epigenomic factors (nutritional epigenomic effects), capacity to induce anuo. suppress specific mRNA expression and patterns (nutritional transcriptomics), the occurrence and activity of proteins (proteomic effects), and/or the dose and temporal changes in cellular small molecular weight compounds will not only provide clues about specificity in response to food components, but assist in the identification of surrogate tissues and biomarkers that can predict a response. While this 'discovery' phase is critical for defining mechanisms and targets, and thus those who will benefit most from intervention, its true usefulness depends on moving this understanding into 'development' (interventions for better prevention, detection, diagnosis, and treatment) and a 'delivery' phase where information is provided to those most in need. It is incumbent on those involved with food and nutrition to embrace the 'omics' that relate to nutrition when considering not only the nutritional value of foods and their food components, but also when addressing acceptability and safety. The future of 'Nutrigenomics and Health Promotion' depends on the ability of the scientific community to identity appropriate biomarkers and susceptibility variants, effective communications about the merits of such undertakings with the health care community and with consumers, and doing all of this within a responsible bioethical framework.

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Self-renewal and circulating capacities of metastatic hepatocarcinoma cells required for collaboration between TM4SF5 and CD44

  • Lee, Doohyung;Lee, Jung Weon
    • BMB Reports
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    • v.48 no.3
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    • pp.127-128
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    • 2015
  • Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

Antioxidant enzymes as redox-based biomarkers: a brief review

  • Yang, Hee-Young;Lee, Tae-Hoon
    • BMB Reports
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    • v.48 no.4
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    • pp.200-208
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    • 2015
  • The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208]

Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectives

  • Hernandez, Rosa;Sanchez-Jimenez, Ester;Melguizo, Consolacion;Prados, Jose;Rama, Ana Rosa
    • BMB Reports
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    • v.51 no.11
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    • pp.563-571
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    • 2018
  • Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.