• Clinical and Experimental Pediatrics
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• 제63권4호
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• pp.151-156
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• 2020

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases.

• Journal of Korean Neurosurgical Society
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• 제58권2호
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• pp.93-100
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• 2015

Objective : Optimal treatment decision and estimation of the prognosis in traumatic brain injury (TBI) is currently based on demographic and clinical predictors. But sometimes, there are limitations in these factors. In this study, we analyzed three central nervous system biomarkers in TBI patients, will discuss the roles and clinical applications of biomarkers in TBI. Methods : From July on 2013 to August on 2014, a total of 45 patients were included. The serum was obtained at the time of hospital admission, and biomarkers were extracted with centrifugal process. It was analyzed for the level of S-100 beta (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1). Results : This study included 33 males and 12 females with a mean age of 58.5 (19-84) years. TBI patients were classified into two groups. Group A was severe TBI with Glasgow Coma Scale (GCS) score 3-5 and Group B was mild TBI with GCS score 13-15. The median serum concentration of S100B, GFAP, and UCH-L1 in severe TBI were raised 5.1 fold, 5.5 fold, and 439.1 fold compared to mild injury, respectively. The serum levels of these markers correlated significantly with the injury severity and clinical outcome (p<0.001). Increased level of markers was strongly predicted poor outcomes. Conclusion : S100B, GFAP, and UCH-L1 serum level of were significantly increased in TBI according to severity and associated clinical outcomes. Biomarkers have potential utility as diagnostic, prognostic, and therapeutic adjuncts in the setting of TBI.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.548-558
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• 2018

Objective : Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether $S100{\beta}$, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods : Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma $S100{\beta}$, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results : The average infarction volume was $12.32{\pm}2.31mm^3$ and $46.9{\pm}7.43mm^3$ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was $1.6{\pm}0.55$ and $3.2{\pm}0.70$, respectively. $S100{\beta}$, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, $S100{\beta}$ and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and $S100{\beta}$ (AUC=0.98). Conclusion : $S100{\beta}$, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

• Journal of Periodontal and Implant Science
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• 제50권5호
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• pp.281-290
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• 2020

Purpose: The aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients. Methods: PCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB. Results: Four downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function. Conclusions: This study is the first analysis of miRNAs in the saliva of patients with AP. Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3735-3740
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• 2015

Context: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). Objective: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. Materials and Methods: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. Results: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. Conclusions: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4161-4165
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• 2013

Objective: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. Methods: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. Results: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. Conclusion: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.

• Journal of Periodontal and Implant Science
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• 제42권1호
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• pp.3-12
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• 2012

Purpose: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis. Methods: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria. Results: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-${\alpha}$ therapy in RA subjects with periodontitis have yielded inconsistent results. Conclusions: There are limited data, however, to suggest that anti-TNF-${\alpha}$ agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1361-1365
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• 2015

Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4317-4321
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• 2015

Background: Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression. Materials and Methods: 60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples Results: 48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was statistically significant. On the other hand, 70% of the cases showed concordant Her2 results between the primary tumors and the nodal deposits, 30% showed discordant results and the difference was significant. Conclusions: The study indicated that the discordance in ER and PR receptor expression between the primary breast tumor and their nodal metastasis may be significant. The possible switch in the biomarker status during the disease progression is worth noting and may change the patient therapeutic planning. So, whether the treatment selection should be based on biomarkers in the lymph node is a topic for further studies and future clinical trials.