• BMB Reports
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• v.51 no.11
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• pp.545-546
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• 2018

With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient's environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as $TGF-{\beta}$ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of $TGF-{\beta}1$ and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.

• BMB Reports
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• v.48 no.8
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• pp.427-428
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• 2015

Despite high interests on microenvironmental regulation of leukemic cells, little is known for bone marrow (BM) niche in leukemia patients. Our recent study on BMs of acute myeloid leukemia (AML) patients showed that the mesenchymal stromal cells (MSCs) are altered during leukemic conditions in a clinical course-dependent manner. Leukemic blasts caused reprogramming of transcriptomes in MSCs and remodeling of niche cross-talk, selectively suppressing normal primitive hematopoietic cells while supporting leukemogenesis and chemo-resistance. Notably, differences in BM stromal remodeling were correlated to heterogeneity in subsequent clinical courses of AML, i.e., low numbers of mesenchymal progenitors at initial diagnosis were correlated to complete remission for 5-8 years, and high contents of mesenchymal progenitor or MSCs correlated to early or late relapse, respectively. Thus, stromal remodeling by leukemic cell is an intrinsic part of leukemogenesis that can contribute to the clonal dominance of leukemic cells over normal hematopoietic cells, and can serve as a biomarker for prediction of prognosis. [BMB Reports 2015; 48(8): 427-428]

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.106-110
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• 2005

N-ethyl-N-nitrosourea (ENU), which is a toxin and a carcinogen, as well as a mutagen, has a variety of effects on mice. ENU induces point mutation in male germ cell. Number of mutant animals are developed with ENU treatment. However, potentiality ot ENU as a carcinogen is not fully understood, even though, mutagenicity of ENU is broadly studied, In the present study, the gene expression profiling and histopathological investigation of ENU treated mouse's liver and brain were investigated. Also, the expression patterns of cancer related genes in ENU-treated mouse were analyzed.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.185-189
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• 2007

Gene expression levels of choriogenin, vitellogenin and estrogen receptor were determined using Reverse transcription (RT)-PCR technique after exposure to estrogenic chemical bisphenol A in the Korean wild medaka (Oryzias sinensis). These genes have been known to be induced in male test fish when the fish are exposed to estrogenic chemicals. Therefore they can be suggested as a possible biomarker of endocrine disruption in fish, however, relatively little has been known about these genes expression by estrogenic chemicals in Korean wild fish. Mature male Oryzias sinensis were treated with bisphenol A at nominal concentrations of 0.02, 0.2 and 2 mg/L for 6 days and total RNA was extracted from the livers of treated fish for RT-PCR. When the five biomarker genes were amplified by RT-PCR in the same condition, mRNA induction level of each gene was elevated with different sensitivities. Conclusively, the results of this work indicated that measurement of vitellogenin and choriogenin using RT-PCR is effective as a simple tool for the screening of estrogenic chemicals and suggested that O. sinensis would be a suitable model fish for the environmental risk assessment of potential endocrine disruptors.

• Environmental Analysis Health and Toxicology
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• v.19 no.3
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• pp.321-326
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• 2004

The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

• BMB Reports
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• v.53 no.12
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• pp.664-669
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• 2020

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.

• BMB Reports
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• v.54 no.12
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• pp.601-607
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• 2021

Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.

• Korean Journal of Veterinary Service
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• v.46 no.3
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• pp.181-192
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• 2023

Cystatin C, a low-molecular-weight protein synthesized by cells, is being explored as a valuable biomarker for assessing renal function in veterinary medicine. Although the relationship between cystatin C and heart disease remains unclear, some studies suggest a possible association. This retrospective case-control study aimed to investigate the role of cystatin C as a biomarker for heart disease and its correlation with diuretic use in veterinary clinical practice. A total of 39 dogs were included in this study, comprising 9 control dogs without a predisposition to heart disease and 30 dogs in the study group diagnosed with heart disease. Among the 30 dogs with heart disease, 18 exhibited symptoms indicative of heart failure. Results showed significantly higher cystatin C levels in the heart disease group compared to the control group (P<0.05). However, no significant differences were observed among different stages of heart disease severity in the control group. Furthermore, cystatin-C showed statistically positive correlations with BUN (r=0.478, P<0.01), creatinine (r=0.506, P<0.01), and furosemide (r=0.338, P<0.05). Diuretics are essential for managing congestive heart failure, and the observed associations between cystatin C and furosemide suggest potential impacts of diuretic use on renal function in dogs with heart failure. Monitoring renal function markers, such as cystatin C, can aid in predicting and managing potential renal complications, ultimately improving the overall health and quality of life of dogs with heart disease.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.48 no.1
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• pp.3-12
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• 2022

Selection of potential disease-specific biomarkers from saliva or epithelial tissues through next generation sequencing (NGS)-based protein studies has recently become possible. The early diagnosis of oral squamous cell carcinoma (OSCC) has been difficult, if not impossible, until now due to the lack of an effective OSCC biomarker and efficient molecular validation method. The aim of this study was to summarize the advances in the application of NGS in cancer research and to propose potential proteomic and genomic saliva biomarkers for NGS-based study in OSCC screening and diagnosis programs. We have reviewed four categories including definitions and use of NGS, salivary biomarkers and OSCC, current biomarkers using the NGS-based technique, and potential salivary biomarker candidates in OSCC using NGS.

• BMB Reports
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• v.57 no.4
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• pp.194-199
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• 2024

Overexpression of mitofusin-2 (MFN2), a mitochondrial fusion protein, is frequently associated with poor prognosis in cervical cancer patients. Here, I aimed to investigate the involvement of MFN2 in cervical cancer progression and determine the effect of MFN2 on prognosis in cervical cancer patients. After generating MFN2-knockdown SiHa cells derived from squamous cell carcinoma, I investigated the effect of MFN2 on SiHa cell proliferation using the Cell Counting Kit-8 assay and determined the mRNA levels of proliferation markers. Colony-forming ability and tumorigenesis were evaluated using a colony-formation assay and tumor xenograft mouse models. The migratory and invasive abilities associated with MFN2 were measured using wound-healing and invasion assays. Wnt/β-catenin-mediated epithelial-mesenchymal transition (EMT) markers related to MFN2 were assessed through quantitative RT-PCR. MFN2-knockdown SiHa cells exhibited reduced proliferation, colony formation, migration, invasion, and tumor formation in vivo. The motility of SiHa cells with MFN2 knockdown was reduced through Wnt/β-catenin-mediated EMT inhibition. MFN2 promoted cancer progression and tumorigenesis in SiHa cells. Overall, MFN2 could serve as a therapeutic target and a novel biomarker for cervical cancer.