• Annals of Clinical Neurophysiology
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• v.23 no.1
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• pp.46-52
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• 2021

Background: We aimed to investigate candidates for serological biomarkers of neuropathic pain in individuals with neuromyelitis optica spectrum disorder (NMOSD). Methods: We analyzed 38 sera samples from 38 participants with NMOSD in National Cancer Center. Neuropathic pain was evaluated using the painDETECT questionnaire. Pain with neuropathic components (painDETECT score ≥ 13) was observed in 22 participants, among whom 17 had definite neuropathic pain (painDETECT score ≥ 19). The remaining 16 participants had non-neuropathic pain (painDETECT score < 13). Serum glial fibrillary acidic protein (GFAP) levels were assessed using a single-molecule array assay. Several cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, and IL-17A, were measured by a multiplex bead-based immunoassay. Results: In comparison of NMOSD participants with neuropathic pain components (or definite neuropathic pain) and those with non-neuropathic pain, the absolute values of serum GFAP, TNF-α, IL-6, and IL-10 levels were higher in participants with neuropathic pain components (or definite neuropathic pain), but these findings did not reach statistical significance. Conclusions: Further larger-scale investigations to find reliable serological biomarkers for neuropathic pain in NMOSD are warranted.

• Journal of Veterinary Clinics
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• v.40 no.6
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• pp.399-407
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• 2023

Chronic kidney disease (CKD) occurs in more than 15% of the dogs over 10 years of age and causes irreversible renal function deterioration. Therefore, it is important to diagnose CKD early and treat the disease properly. The purpose of this study aimed to to evaluate the clinical utility of urine albumin/creatinine ratio (ACR) using POC (point-of-care) device as an early detection urinary biomarker in CKD dogs and to confirm the correlation between ACR and other known CKD biomarkers. Urine and serum samples were obtained from 50 healthy dogs and 50 dogs with CKD. Serum blood urea nitrogen (BUN), creatinine, and symmetric dimethylarginine (SDMA) concentrations, and urine protein creatinine ratio (UPC) were measured. Urine specific gravity (USG) was evaluated using refractometer, and ACR was measured using an i-SENS A1Care analyzer. The ACR values of dogs with CKD were significantly different from those of healthy dogs (p < 0.001), as with other renal biomarkers. ACR showed significant differences between healthy dogs and dogs with CKD at every IRIS stage (p < 0.005), whereas no significant differences were observed between dogs with CKD IRIS stage I and healthy dogs with UPC. There are significant positive correlation between ACR and BUN (r = 0.611, p < 0.001), creatinine (r = 0.788, p < 0.001), SDMA (r = 0.747, p < 0.001), and UPC (r = 0.784, p < 0.001), and significant negative correlation between ACR and USG (r = -0.700, p < 0.001). In receiver operator characteristic curve analysis, the area under the curve (AUC) was 0.982 (95% CI 0.963-1.000, p < 0.001), with an optimal cut-off value of 64.20 mg/g (94% sensitivity and 94% specificity). Thus, ACR is a useful urinary biomarker for the early diagnosis of proteinuria in CKD and combined use of ACR and other renal biomarkers may be helpful for early diagnosis and prevention of CKD in dogs.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.249-255
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• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4595-4598
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• 2013

We conducted a comprehensive study to investigate the role of genes involved in transport pathways in response to chemotherapy and clinical outcome of osteosarcoma cases. Genotyping of six SNPs was performed in a 384-well plate format on the Sequenom MassARRAY platform for 208 osteosarcoma patients to reveal any correlations of the six SNPs with response to chemotherapy and clinical outcome. Individuals with the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes had a higher probability of responding poorly to chemotherapy, indicated by odds ratios (ORs) of 2.46 (95%CI, 1.21-5.74) and 3.78 (95% CI, 1.20-13.85), respectively. Moreover, the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes were significantly associated with shorter diseasefree survival (DFS) and overall survival (OS). Our study found the two SNPs in two transporter genes and one phase II metabolism enzyme to be associated with response to chemotherapy and overall survival in osteosarcoma patients, suggesting potential prognostic biomarker applications of the two SNPs.

• Clinical and Experimental Pediatrics
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• v.61 no.5
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• pp.156-159
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• 2018

Purpose: Sepsis is a major cause of neonatal morbidity and mortality. Early diagnosis is a major problem because of the lack of specific clinical signs. Therefore, a reliable diagnostic marker is needed to guide the use of antimicrobial agents. The objective of our study was to assess the value of proadrenomedullin (pro-ADM) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Methods: This study enrolled 60 newborn infants with sepsis proven with positive blood cultures and 30 healthy neonates. Complete blood count, C-reactive protein levels, and pro-ADM levels were obtained from all neonates. Results: The pro-ADM levels were significantly higher ($14.39{\pm}0.75nmol/L$) in the sepsis group than in the control group ($3.12{\pm}0.23nmol/L$). The optimal cutoff value for pro-ADM was 4.3 nmol/L, with a sensitivity of 93.3% and a specificity of 86.7%. The pro-ADM levels were also higher in nonsurvivors (P=0.001). Conclusion: Pro-ADM can be used as a reliable biomarker for neonatal sepsis. High pro-ADM levels were associated with mortality and could be an early indicator of disease outcome.

• Journal of Preventive Medicine and Public Health
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• v.42 no.6
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• pp.349-355
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• 2009

Biomarkers are characteristic biological properties that can be detected and measured in a variety of biological matrices in the human body, including the blood and tissue, to give an indication of whether there is a threat of disease, if a disease already exists, or how such a disease may develop in an individual case. Along the continuum from exposure to clinical disease and progression, exposure, internal dose, biologically effective dose, early biological effect, altered structure and/or function, clinical disease, and disease progression can potentially be observed and quantified using biomarkers. While the traditional discovery of biomarkers has been a slow process, the advent of molecular and genomic medicine has resulted in explosive growth in the discovery of new biomarkers. In this review, issues in evaluating biomarkers will be discussed and the biomarkers of environmental exposure, early biologic effect, and susceptibility identified and validated in epidemiological studies will be summarized. The spectrum of genomic approaches currently used to identify and apply biomarkers and strategies to validate genomic biomarkers will also be discussed.

• Journal of Digestive Cancer Research
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• v.10 no.1
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• pp.22-30
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• 2022

Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

• Investigative Magnetic Resonance Imaging
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• v.23 no.3
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• pp.241-250
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• 2019

Purpose: The purpose of this study was to determine the relation between quantitative magnetic resonance imaging biomarkers, and clinical performances in chronic phase of carbon monoxide intoxication. Materials and Methods: Eighteen magnetic resonance scans and cognitive evaluations were performed, on patients with carbon monoxide intoxication in chronic phase. Apparent diffusion coefficient (ADC) ratios of affected versus unaffected centrum semiovale, and corpus callosum were obtained. Signal intensity (SI) ratios between affected centrum semiovale, and normal pons in T2-FLAIR (fluid-attenuated inversion recovery) images were obtained. The Mini-Mental State Exam, and clinical outcome scores were assessed. Correlation coefficients were calculated, between MRI and clinical markers. Patients were further classified into poor-outcome and good-outcome groups based on clinical performance, and imaging parameters were compared. T2-SI ratio of centrum semiovale was compared, with that of 18 sex-matched and age-matched controls. Results: T2-SI ratio of centrum semiovale was significantly higher in the poor-outcome group, than that in the good-outcome group and was strongly inversely correlated, with results from the Mini-Mental State Exam. ADC ratios of centrum semiovale were significantly lower in the poor outcome group than in the good outcome group, and were moderately correlated with the Mini-Mental State Exam score. Conclusion: A higher T2-SI and a lower ratio of ADC values in the centrum semiovale, may indicate presence of more severe white matter injury and clinical impairment. T2-SI ratio and ADC values in the centrum semiovale, are useful quantitative imaging biomarkers for correlation with clinical performance in individuals with carbon monoxide intoxication.

• Tuberculosis and Respiratory Diseases
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• v.70 no.4
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• pp.301-306
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• 2011

Background: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. Methods: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. Results: The pre chemotherapy values (Response group $41.36{\pm}1.72$ vs. Non-response group $41.33{\pm}1.54$, p=0.78) and post chemotherapy values (Response group $39.92{\pm}1.81$ vs. Non-response group $40.41{\pm}1.47$, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). Conclusion: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.