• 제목/요약/키워드: molecular biomarker

검색결과 261건 처리시간 0.026초

Identification of a novel PARP4 gene promoter CpG locus associated with cisplatin chemoresistance

  • Hye Youn Sung;Jihye Han;Yun Ju Chae;Woong Ju;Jihee Lee Kang;Ae Kyung Park;Jung-Hyuck Ahn
    • BMB Reports
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    • 제56권6호
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    • pp.347-352
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    • 2023
  • The protein family of poly (ADP-ribose) polymerases (PARPs) is comprised of multifunctional nuclear enzymes. Several PARP inhibitors have been developed as new anticancer drugs to combat resistance to chemotherapy. Herein, we characterized PARP4 mRNA expression profiles in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. PARP4 mRNA expression was significantly upregulated in cisplatin-resistant ovarian cancer cell lines, and this upregulation was associated with the hypomethylation of specific cytosine-phosphate-guanine (CpG) sites (cg18582260 and cg17117459) on its promoter. Reduced PARP4 expression was restored by treating cisplatin-sensitive cell lines with a demethylation agent, implicating the epigenetic regulation of PARP4 expression by promoter methylation. Depletion of PARP4 expression in cisplatin-resistant cell lines reduced cisplatin chemoresistance and promoted cisplatin-induced DNA fragmentation. The differential mRNA expression and DNA methylation status at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) according to cisplatin responses, was further validated in primary ovarian tumor tissues. The results showed significantly increased PARP4 mRNA expressions and decreased DNA methylation levels at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) in cisplatin-resistant patients. Additionally, the DNA methylation status at cg18582260 CpG sites in ovarian tumor tissues showed fairly clear discrimination between cisplatin-resistant patients and cisplatin-sensitive patients, with high accuracy (area under the curve = 0.86, P = 0.003845). Our findings suggest that the DNA methylation status of PARP4 at the specific promoter site (cg18582260) may be a useful diagnostic biomarker for predicting the response to cisplatin in ovarian cancer patients.

비소세포폐암 환자의 표적 치료 (Targeted Therapy of Advanced Non-Small Cell Lung Cancer)

  • 이윤규;길현일;김수정;이현주;남희림;함수연;강두영
    • The Korean Journal of Medicine
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    • 제99권2호
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    • pp.96-103
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    • 2024
  • Lung cancer is the leading cause of cancer death in Republic of Korea. After their initial diagnosis, only 10-20% of patients with advanced non-small cell lung cancer (NSCLC) survive for 5 years of longer. Given enormous advances in therapeutics such as novel targeted therapies and immunotherapies, survival rates are improving for advanced patients with NSCLC; 5-year survival rates range from 15% to 50%, contingent upon the biomarker. Detection of the specific molecular alteration as biomarker is thus crucial for identifying subgroups of NSCLC that contain therpapeutically targetable oncogenic drivers. This review examines the process of diagnosing lung adenocarcinoma with dominant biomarkers in order to customize treatment with appropriate targeted therapy.

DNA methylation: a cause and consequence of type 2 diabetes

  • Kim, Mirang
    • Genomics & Informatics
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    • 제17권4호
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    • pp.38.1-38.6
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    • 2019
  • DNA methylation is a relatively stable epigenetic modification that can regulate and stabilize gene expression patterns and hence establish cell identity. Because metabolic intermediates are key factors of DNA methylation and demethylation, perturbations in metabolic homeostasis can trigger alterations in cell-specific patterns of DNA methylation and contribute to disease development, including type 2 diabetes (T2D). During the past decade, genome-wide DNA methylation studies of T2D have expanded our knowledge of the molecular mechanisms underlying T2D. This review summarizes case-control studies of the DNA methylome of T2D and discusses DNA methylation as both a cause and consequence of T2D. Therefore, DNA methylation has potential as a promising T2D biomarker that can be applied to the development of therapeutic strategies for T2D.

MicroRNAs: promising biomarkers for diagnosis and therapeutic targets in human colorectal cancer metastasis

  • Hur, Keun
    • BMB Reports
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    • 제48권4호
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    • pp.217-222
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    • 2015
  • Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Distant metastasis is a major cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. Many miRNAs are aberrantly expressed in cancer and influence tumor progression. Accumulating studies suggest that multiple miRNAs are actively involved in the CRC metastasis process. Thus, we aim to introduce the role of miRNAs in multi-steps of CRC metastasis, including cancer cell invasion, intravasation, circulation, extravasation, colonization, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential application of miRNAs as biomarkers for CRC patients with metastasis. [BMB Reports 2015; 48(4): 217-222]

Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications

  • Cho, Kyung-Hyun
    • BMB Reports
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    • 제42권7호
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    • pp.393-400
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    • 2009
  • High-density lipoprotein (HDL) is a proven biomarker for the monitoring of changes in antioxidant and anti-inflammation capability of body fluids. The beneficial virtues of HDL are highly dependent on its lipids and protein compositions, and their ratios. In normal state, the HDL particle is enriched with lipids and several HDL-associated enzymes, which are responsible for its antioxidant activity. Lower HDL-cholesterol levels (<40 mg/dL) have been recognized as an independent risk factor for coronary artery disease, as well as being a known component of metabolic syndrome. Functional and structural changes of HDL have been recognized as factors pivotal to the evaluation of HDL-quality. In this review, I have elected to focus on the functional and structural correlations of HDL and the roles of HDL-associated apolipoproteins and enzymes. Recent clinical applications of HDL have also been reviewed, particularly the therapeutic targeting of HDL metabolism and reconstituted HDL; these techniques represent promising emerging strategies for the treatment of cardiovascular disease, for drug or gene therapy.

Screening of Potential Stress-Responsive and Immune-Related Genes by Expressed Sequence Tags in Mud Loach (Misgurnus mizolepis)

  • Nam, Yoon-Kwon;Kim, Dong-Soo
    • 한국어병학회지
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    • 제15권2호
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    • pp.83-92
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    • 2002
  • EST analysis was performed to identify stress-responsive and immune-related genes from mud loach (Misgurnus mizolepis), cDNA libraries were constructed with liver, intestine and kidney tissues and randomly chosen clones (216 for liver, 198 for intestine and 224 for kidney) were subjected to automated sequence analysis. Of 638 clones sequenced in totlal, approximalely 25% of ESTs was novel sequences (no match to GenBank) or sequences with high homology to hypothrtical/unknown genes. Several potential stress-responsive biomarker and/or immure-related genes were identified in all the tissues examined. It included lectin, MHC class I/II proteins, proteinase inhibitors, superoxide dismulase, catalase, glutathionc-S. transferase, heat-shock protein, warm temperature acclimation protein, complements, methylrransferasc, zinc finger proteins, macrophage maturation associated protein, and others. This information will offer new possibilities as fundamental baseline data for the molecular genetics and breeding of this species with an emphasis on the development of stress. (and disease)-resistsnt fish.

마이크로패턴된 전극을 이용한 실시간 생체물질 감지 랩칩 시스템 (Interdigitated Microelectrode Lab-on-a-chip sensing system for Biomoelcule Detection)

  • 유용경;황교선;이정훈
    • 대한전기학회:학술대회논문집
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    • 대한전기학회 2015년도 제46회 하계학술대회
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    • pp.1223-1224
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    • 2015
  • Recently, Alzheimer's Disease (AD) is one of the biggest threats to healthy society. Current medical AD diagnosis depends on interviews and the molecular neuroimaging. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. Amyloid ${\beta}$ and Tau-meditated neuronal injury and dysfunction are candidates of biomarker for AD diagnosis using blood. For highly sensitive and selective biosensor platform, interdigitated microelectrodes (IMEs) sensor was prepared with micro fabrication process and Amyloid ${\beta}$ antibody. Amyloid ${\beta}$ concentration of 1, 10, 100, and 1000 pg/mL was injected in reaction chamber with IME sensors, impedance and conductance of IMEs changed respectively. These results show our newly proposed IMEs sensor can be usefully utilized for AD early diagnosis.

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이상운동질환에서의 도파민 신경계 영상 (Imaging of Dopaminergic System in Movement Disorders)

  • 김유경;김상은
    • Nuclear Medicine and Molecular Imaging
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    • 제41권2호
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    • pp.132-140
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    • 2007
  • Parkinson's disease is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several radiopharmaceutics have been developed to evaluate the integrity of dopaminergic neuronal system. In vivo PET and SPECT imaging of presynaptic dopamine imaing are already applied to Parkinson's disease and other parkinsonism, and can demonstrate the dopaminergic dysfunction. This review summarized the use of the presynaptic dopaminergic imaging in PD as biomarkers in evaluation of disease progression as well as in diagnosis of PD.

Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu
    • Toxicological Research
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    • 제33권4호
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    • pp.273-282
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    • 2017
  • Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

Cadmium Toxicity Monitoring Using Stress Related Gene Expressions in Caenorhabditis elegans

  • Roh, Ji-Yeon;Park, Sun-Young;Choi, Jin-Hee
    • Molecular & Cellular Toxicology
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    • 제2권1호
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    • pp.54-59
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    • 2006
  • The toxicity of cadmium on Caenorhabditis elegans was investigated to identify sensitive biomarkers for environmental monitoring and risk assessment. Stress-related gene expression were estimated as toxic endpoints Cadmium exposure led to an increase in the expression of most of the genes tested. The degree of increase was more significant in heat shock protein-16.1, metallothionein-2, cytochrome p450 family protein 35A2, glutathione S-transferase-4, superoxide dismutase-1, catalase-2, C. elegans p53-like protein-1, and apoptosis enhancer-1 than in other genes. The overall results indicate that the stress-related gene expressions of C. elegans have considerable potential as sensitive biomarkers for cadmium toxicity monitoring and risk assessment.