• Journal of Gastric Cancer
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• v.19 no.3
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• pp.254-277
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• 2019

Inflammation can be a causative factor for carcinogenesis or can result from a consequence of cancer progression. Moreover, cancer therapeutic interventions can also induce an inflammatory response. Various inflammatory parameters are used to assess the inflammatory status during cancer treatment. It is important to select the most optimal biomarker among these parameters. Additionally, suitable biomarkers must be examined if there are no known parameters. We briefly reviewed the published literature for the use of inflammatory parameters in the treatment of patients with cancer. Most studies on inflammation evaluated the correlation between host characteristics, effect of interventions, and clinical outcomes. Additionally, the levels of C-reactive protein, albumin, lymphocytes, and platelets were the most commonly used laboratory parameters, either independently or in combination with other laboratory parameters and clinical characteristics. Furthermore, the immune parameters are classically examined using flow cytometry, immunohistochemical staining, and enzyme-linked immunosorbent assay techniques. However, gene expression profiling can aid in assessing the overall peri-interventional immune status. The checklists of guidelines, such as STAndards for Reporting of Diagnostic accuracy and REporting recommendations for tumor MARKer prognostic studies should be considered when designing studies to investigate the inflammatory parameters. Finally, the data should be interpreted after adjusting for clinically important variables, such as age and cancer stage.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.71.1-71.12
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• 2023

With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNAsequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare. Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also noncoding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.

• Journal of Veterinary Science
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• v.22 no.5
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• pp.75.1-75.10
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• 2021

Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. Objectives: This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. Methods: Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2-3.7] ng/mL; median [IQR] and 2.4 [1.4-4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9-3.0] ng/mL; p = 0.012 and 1.4 [0.9-2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9-3.0] ng/mL and 3.1 [2.6-4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9-2.1] ng/mL and 2.7 [1.6-5.8] ng/mL, respectively; p < 0.001). Conclusion: This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.

• Journal of Life Science
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• v.34 no.6
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• pp.434-441
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• 2024

Mammary gland tumors are the most common tumors detected in non-spayed female dogs and pose a significant clinical challenge. Due to the strong similarity between canine mammary tumors (CMT) and human breast cancer (HBC), biomarkers identified in HBC can also be detected in CMT. These biomarkers have been shown to offer valuable insights into early diagnosis, prognosis, and treatment strategies. The purpose of this article is to provide a concise overview of CMT biomarkers based on the current literature. Traditional treatments for CMT in dogs typically begin with surgery, followed by chemotherapy, radiotherapy, or hormonal therapy. However, these treatments alone are not always fully effective. A diagnostic biomarker can detect the presence of a disease or the characteristics of a disease and classify an individual's status. Prognostic biomarkers focus on predicting the expected progression, recurrence, or survival of the disease in patients. By utilizing advances in understanding the mechanism of canine-specific mammary gland tumors, the estimation of biomarkers offers hope for improved outcomes in cancer patients. Novel technologies, such as single-cell RNA sequencing analysis, could provide a valuable resource for deciphering intra- and inter-tumoral heterogeneity. This review paper explores current research on CMT biomarkers and suggests directions for their development.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.79-88
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• 2015

Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as one of the most promising biomarkers of renal epithelial injury. Numerous studies have presented the diagnostic and prognostic utility of urinary and plasma NGAL in patients with acute kidney injury, chronic kidney disease, renal injury after kidney transplantation, and other renal diseases. NGAL is a member of the lipocalin family that is abundantly expressed in neutrophils and monocytes/macrophages and is a mediator of the innate immune response. The biological significance of NGAL to hamper bacterial growth by sequestering iron-binding siderophores has been studied in a knock-out mouse model. Besides neutrophils, NGAL is detectable in most tissues normally encountered by microorganisms, and its expression is upregulated in epithelial cells during inflammation. A growing number of studies have supported the clinical utility of NAGL for detecting invasive bacterial infections. Several investigators including our group have reported that measuring NGAL can be used to help predict and manage urinary tract infections and acute pyelonephritis. This article summarizes the biology and pathophysiology of NGAL and reviews studies on the implications of NGAL in various renal diseases from acute kidney injury to acute pyelonephritis.

• Clinical and Experimental Pediatrics
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• v.56 no.2
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• pp.45-51
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• 2013

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2009.04a
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• pp.137-150
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• 2009

Background: Heart failure can develop secondary to various heart diseases (e.g. mitral valvular insufficiency, congenital heart defects, heart worm infection). The clinical signs of heart failure can be confused with those of other conditions, such as respiratory disease. Therefore, specific, sensitive, rapid and inexpensive blood tests for heart failure are desirable. Cardiac troponins, natriuretic peptides and cytokines have been more recently used as indicators of heart disease in humans and animals. These peptides are sensitive to changes in vasoconstriction and dilation within the heart and are used for the diagnosis and prognosis of heart failure. Methods: Previously developed and newly developed cardiac biomarkers will be discussed for understating clinical implications and diagnostic values in heart diseases in small animals

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.5
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• pp.341-347
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• 2020

Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck cancer. MicroRNAs, as new biomarkers, are recommended for diagnosis and treatment of different types of cancers. Bevacizumab, sold under the trade name Avastin, is a humanized whole monoclonal antibody that targets and blocks VEGF-A (vascular endothelial growth factor A; angiogenesis) and oncogenic signaling pathways. Materials and Methods: This study comprised 50 cases suffering from OSCC and 50 healthy participants. Peripheral blood samples were collected in glass test tubes, and RNA extraction was started immediately. Expression levels of miR-155, miR-191, and miR-494 biomarkers in the peripheral blood of OSCC-affected individuals and healthy volunteers in vivo were evaluated using real-time PCR. The influence of Avastin on the expression levels of the aforementioned biomarkers in vitro and in the HN5 cell line was also investigated. Results: Expression levels of miR-155, miR-191, and miR-494 in the peripheral blood of individuals affected by OSCC were higher than in those who were healthy. Moreover, Avastin at a concentration of 400 μM caused a decrease in the expression levels of the three biomarkers and a 1.5-fold, 3.5-fold, and 4-fold increase in apoptosis in the test samples compared to the controls in the HN5 cell line after 24, 48, and 72 hours, respectively. Conclusion: The findings of this study demonstrate that overexpression of miR-155, miR-191, and miR-494 is associated with OSCC, and Avastin is able to regulate and downregulate the expression of those biomarkers and increase apoptosis in cancerous cells in the HN5 cell line.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.26-33
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• 2019

Recently, the rapid growth of the companion animal market has led to the development of animal disease diagnosis kits. Therefore, the utility of the introduction of biomarkers for the development of animal molecular diagnostics is being reevaluated. A good biomarker should be precise and reliable, distinguish between normal and diseased states, and differentiate between different diseases. Recently reported genetic markers, tumor markers (cell free DNA, circulating tumor cells, granzyme, and skin tumors), and others (brucellosis, programmed death recovery-1, symmetric dimethylarginine, periostin, and cysteinyl leukotrien) have been developed. The biomarkers are used for risk prediction or for the screening, diagnosis, and monitoring of disease progression. The most important criteria for related biomarkers are disease specificity. Many potential biomarkers have emerged from laboratory and test studies, but they have not been validated in independent or large-scale clinical studies. Candidate biomarkers evaluate disease associations, verify the effectiveness of biomarkers for early detection and disease progression, and incorporate them into humans and animals. In the future, it will be necessary to reevaluate the utility of well-structured biomarker-based research and study the development of kits that can be used in on-site tests in accordance with the trends introduced in the diagnosis of animal diseases.

• Clinical and Experimental Pediatrics
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• v.63 no.4
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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.