• Journal of Veterinary Science
• /
• v.21 no.6
• /
• pp.81.1-81.10
• /
• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Journal of Society of Preventive Korean Medicine
• /
• v.27 no.2
• /
• pp.35-48
• /
• 2023

Objective : We studied prognostic biomarkers discovery for lung cancer based on the pattern identification for the personalized Korean medicine. Methods : Using 30 tissue samples, we performed a whole exome sequencing to examine the genetic differences among three groups. Results : The exome sequencing identified among 23,490 SNPs germline variants, 12 variants showed significant frequency differences between Xu and Stasis groups (P<0.0005). As similar, 18 and 10 variants were identified in analysis for Xu vs. Gentleness group and Stasis vs. Gentleness group, respectively (P<0.001). Our exome sequencing also found 8,792 lung cancer specific variants and among the groups identified 6, 34, and 12 variants which showed significant allele frequency differences in the comparison groups; Xu vs. Stasis, Xu vs. Gentleness group, and Stasis vs. Gentleness group. As a result of PCA analysis, in germline data set, Xu group was divided from other groups. Analysis using somatic variants also showed similar result. And in gene ontology analysis using pattern identification variants, we found genes like as FUT3, MYCBPAP, and ST5 were related to tumorigenicity, and tumor metastasis in comparison between Xu and Stasis. Other significant SNPs for two were responsible for eye morphogenesis and olfactory receptor activity. Classification of somatic pattern identification variants showed close relationship in multicellular organism reproduction, anion-anion antiporter activity, and GTPase regulator activity. Conclusions : Taken together, our study identified 40 variants in 29 genes in association with germline difference of pattern identification groups and 52 variants in 47 genes in somatic cancer tissues.

• Journal of Gastric Cancer
• /
• v.23 no.2
• /
• pp.340-354
• /
• 2023

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

• Biomolecules & Therapeutics
• /
• v.32 no.3
• /
• pp.379-389
• /
• 2024

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q Exactive^TM Focus Hybrid Quadrupole-Orbitrap^TM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 ㎛) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40℃. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

• Dementia and Neurocognitive Disorders
• /
• v.23 no.2
• /
• pp.95-106
• /
• 2024

Background and Purpose: Ventricle enlargement has been implicated in the pathophysiology of Alzheimer's disease (AD). We studied the relationship between ventricular size and cognitive function in patients with AD. We focused on the effect of the initial ventricle size on the rate of cognitive decline in patients with AD. Methods: A retrospective analysis of probable clinical AD participants with more than 2 magnetic resonance imaging images was performed. To measure ventricle size, we used visual rating scales of (1) Cardiovascular Health Study (CHS) score and (2) conventional linear measurement method. Results: Increased clinical dementia rating (CDR) was correlated with a decreased Mini-Mental Status Examination (MMSE) score, and increased medial temporal lobe atrophy (MTLA) and global ventricle size (p<0.001, p<0.001, p=0.021, respectively). There was a significant correlation between the change in cognitive function in the group (70%-100%ile) with a large initial ventricle size (p=0.021 for ∆CDR, p=0.01 for ∆MMSE), while the median ventricle size (30%-70%ile) showed correlation with other brain structural changes (MTLA, frontal atrophy [FA], and white matter) (p=0.036 for initial MTLA, p=0.034 for FA). Conclusions: In this study, the initial ventricle size may be a potential new imaging biomarker for initial cognitive function and clinical progression in AD. We found a relationship between the initial ventricle size and initial AD-related brain structural biomarkers.

• Korean Journal of Radiology
• /
• v.23 no.1
• /
• pp.77-88
• /
• 2022

Objective: Our study aimed to evaluate the quality of radiomics studies on brain metastases based on the radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guidelines. Materials and Methods: PubMed MEDLINE, and EMBASE were searched for articles on radiomics for evaluating brain metastases, published until February 2021. Of the 572 articles, 29 relevant original research articles were included and evaluated according to the RQS, TRIPOD checklist, and IBSI guidelines. Results: External validation was performed in only three studies (10.3%). The median RQS was 3.0 (range, -6 to 12), with a low basic adherence rate of 50.0%. The adherence rate was low in comparison to the "gold standard" (10.3%), stating the potential clinical utility (10.3%), performing the cut-off analysis (3.4%), reporting calibration statistics (6.9%), and providing open science and data (3.4%). None of the studies involved test-retest or phantom studies, prospective studies, or cost-effectiveness analyses. The overall rate of adherence to the TRIPOD checklist was 60.3% and low for reporting title (3.4%), blind assessment of outcome (0%), description of the handling of missing data (0%), and presentation of the full prediction model (0%). The majority of studies lacked pre-processing steps, with bias-field correction, isovoxel resampling, skull stripping, and gray-level discretization performed in only six (20.7%), nine (31.0%), four (3.8%), and four (13.8%) studies, respectively. Conclusion: The overall scientific and reporting quality of radiomics studies on brain metastases published during the study period was insufficient. Radiomics studies should adhere to the RQS, TRIPOD, and IBSI guidelines to facilitate the translation of radiomics into the clinical field.

• Tuberculosis and Respiratory Diseases
• /
• v.66 no.6
• /
• pp.444-450
• /
• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Childhood Kidney Diseases
• /
• v.19 no.2
• /
• pp.71-78
• /
• 2015

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensin-aldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended.

• Korean Journal of Biological Psychiatry
• /
• v.23 no.2
• /
• pp.37-40
• /
• 2016

Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.381-384
• /
• 2014

Background: Evidence indicates that Dickkopf-1 (DKK-1) levels may be a biomarker for cancer risk. The aim of this study was to assess DKK-1 and its correlation with clinic-pathological features in patients with bladder cancer. Materials and Methods: DKK-1 levels were determined in serum samples from 90 patients with bladder cancer before transurethral tumor resection. The concentrations of DKK-1 were determined by using enzyme linked immune-sorbent assay (ELISA). Results: Elevated preoperative DKK-1 levels were associated with tumor stage (p<0.001), grade (p<0.001) and histological grade (p<0.001). Conclusions: The results of our study demonstrated that the level of serum DKK-1 is correlated with both disease progression and increase in the tumor grade. Preoperative serum DKK-1 elevation may thus represent a novel marker for the determination of bladder cancer and the detection of patients with a likely poor clinical outcome.