• Biomedical Science Letters
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• v.3 no.2
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• pp.151-160
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• 1997

This study was planned to evaluate the urinary ascorbic acid as a new biological marker for the intoxication of cadmium, which could possibly be driven by its increased utilization and environmental pollution. In order to meet this goal, we have peformed measurement of urinary ascorbic acid concentration, histopathological examination of the kidney, and biochemical test for the liver function using cadmium-intoxicated rats by oral administration. The average concentrations of urinary ascorbic acid in the $CdCl_2$-treated rats were 214.0 mg/dl for 100 ppm group and 254.3 mg/dl for 200 ppm group during experimental period of 50 days. These levels are 24 and 28 times higher than one in the control group (9.0 mg/dl), respectively. Ultrastructural study showed the eosinophilic hyaline cast and focal effacement, fusion in the renal tubules, as well as loss of foot processes on the glomerular epithelial cells. These results suggested that cadmium may be responsible for renal glomerular injury. The blood levels of AST, ALT and LDH in the treated groups (199 IU/I, 88 IU/I, 1190 U/I for the 100 ppm group and 270 IU/I, 226 IU/I, 760 U/I for the 200 ppm group) were higher than ones in the control group(143 IU/I, 50 IU/I, 334 U/I). These results indicated the cadmium induced the damage of liver function. In conclusion, the administration of cadmium showed a remarkable increase of urinary ascorbic acid with renal and hepatic damage. Therefore, it is expected that measurement of urinary ascorbic acid would be an powerful method as a noninvasive biomarker for cadmium intoxication.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.4
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• pp.236-245
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• 2024

Purpose: The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH. Methods: A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated. Results: Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid. Conclusion: Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

• BMB Reports
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• v.41 no.10
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• pp.685-692
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• 2008

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

• Mass Spectrometry Letters
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• v.13 no.1
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• pp.2-10
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• 2022

Metabolomics makes it possible to analyze the interrelationships between various signaling molecules based on the metabolic pathways involved by using high-resolution devices. This approach can also be used to obtain large-scale metabolic information to identify the relevant pathways for disease diagnosis and prognosis and search for potential biomarkers. In the fields of medicine and forensics, hair analysis is used to detect various metabolites in the body. Hair can be harvested readily in a noninvasive manner and is easier to transport and store than blood and urine. Another advantage from a forensic viewpoint is that hair reflects all the components of body fluids. In addition, because of the unique coating structure of hair, it can be used for measurements without changing or destroying its adsorbed components. In this review, the pretreatments for hair analysis, instrumental conditions and clinical applications are discussed. Especially, the clinical use of hair metabolomics in the diagnosis of various diseases and the limitations of the technique are described.

• Toxicological Research
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• v.32 no.1
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• pp.47-56
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• 2016

The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7315-7319
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• 2013

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.2
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• pp.79-87
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• 2024

Purpose: Recently, the prevalence of eosinophilic gastrointestinal disease (EGID) has shown an increasing trend worldwide. As the diagnosis of EGID requires invasive endoscopy with biopsy, noninvasive markers for detecting EGID in suspected patients, particularly children, are urgently needed. Therefore, this study aimed to evaluate the diagnostic accuracy of serum eosinophil cationic protein (ECP) beyond peripheral eosinophil counts in pediatric patients with EGID. Methods: Overall, 156 children diagnosed with EGID were enrolled and 150 children with functional abdominal pain disorder (FAPD) were recruited as controls. All participants underwent endoscopic biopsy in each segment of the gastrointestinal (GI) tract and serum ECP measurement, as well as peripheral eosinophil percent and absolute eosinophil count. Results: Comparing EGID (n=156) with FAPD (n=150) patients, serum ECP levels were significantly higher in pediatric patients with EGID than in those with FAPD (25.8±28.6 ㎍/L vs. 19.5±21.0 ㎍/L, p=0.007), while there was no significant difference in peripheral eosinophil percent and absolute eosinophil counts between the two groups. Serum ECP levels were correlated with peripheral eosinophil percent (r=0.593, p<0.001) and the absolute eosinophil count (r=0.660, p<0.001). The optimal cutoff value of serum ECP for pediatric EGID was 10.5 ㎍/mL, with a sensitivity of 69.9% and a specificity of 43.4% with an area under the receiver operating characteristic curve of 0.562. Conclusion: The combination of serum ECP levels and peripheral eosinophil counts, when employed with appropriated thresholds, could serve as a valuable noninvasive biomarker to distinguish between EGID and FAPD in pediatric patients manifesting GI symptoms.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.25-32
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• 2022

Malignant melanoma has an aggressive nature and high metastatic potential that result in one of the highest cancer mortality rates. Over the past three decades, primary and metastatic melanoma incidence has rapidly increased. The recent advances in diagnostic technology have shown promise, but there is still an enormous need for specific detection methods to diagnose malignant melanoma. Positron emission tomography can visualize a particular biomarker of malignant melanoma and promise a noninvasive image of micrometastases. However, the development of PET radiopharmaceuticals remains necessary for diagnosing malignant melanoma by using positron emission tomography. In this review, the history and a general overview of PET radionuclide labeled benzamide derivatives, including their radiosynthesis, in vivo characterization, and evaluation, are provided as imaging agents for malignant melanoma.

• Journal of Animal Science and Technology
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• v.63 no.2
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• pp.319-331
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• 2021

Heat stress (HS) causes adverse impacts on pig production and health. A potential biomarker of HS is required to predict its occurrence and thereby better manage pigs under HS. Information about the saliva metabolome in heat-stressed pigs is limited. Therefore, this study was aimed to investigate the effects of acute HS on the saliva metabolome and identify metabolites that could be used as potential biomarkers. Growing pigs (n = 6, 3 boars, and 3 gilts) were raised in a thermal neutral (TN; 25℃) environment for a 5-d adaptation period (CON). After adaptation, the pigs were first exposed to HS (30℃; HS30) and then exposed to higher HS (33℃; HS33) for 24 h. Saliva was collected after adaptation, first HS, and second HS, respectively, for metabolomic analysis using 1H-nuclear magnetic resonance spectroscopy. Four metabolites had significantly variable importance in the projection (VIP > 1; p < 0.05) different levels in TN compared to HS groups from all genders (boars and gilts). However, sex-specific characteristics affected metabolites (glutamate and leucine) by showing the opposite results, indicating that HS was less severe in females than in males. A decrease in creatine levels in males and an increase in creatine phosphate levels in females would have contributed to a protective effect from protein degradation by muscle damage. The results showed that HS led to an alteration in metabolites related to energy and protein. Protection from muscle damage may be attributed to the alteration in protein-related metabolites. However, energy-related metabolites showed opposing results according to sex-specific characteristics, such as sex hormone levels and subcutaneous fat layer. This study had shown that saliva samples could be used as a noninvasive method to evaluate heat-stressed pigs. And the results in this study could be contributed to the development of a diagnostic tool as a noninvasive biomarker for managing heat-stressed pigs.

• Investigative Magnetic Resonance Imaging
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• v.23 no.4
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• pp.351-360
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• 2019

Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.