• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5779-5785
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• 2015

The present study was designed to investigate cholangiocarcinoma (CCA) antibodies in hamster serum. Hamster CCA cell lines were processed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A candidate biomarker was confirmed by immunoprecipitation and western blot, and was further analyzed using ELISA and sera from normal control hamsters, hamsters with opisthorchiasis and hamsters with various stages of CCA, as well as from CCA patients and healthy individuals. One candidate marker was identified as $HSP90{\alpha}$, as indicated by a high level of anti-$HSP90{\alpha}$ in hamster CCA sera. It was found that the levels of anti-$HSP90{\alpha}$ were specifically elevated in the sera of hamsters with CCA compared with other groups and progressively increased with the clinical stage. At the cut-off point of 0.4850 on the receiver operating characteristic curve, anti-$HSP90{\alpha}$ could discriminate CCA from healthy control groups with a sensitivity of 76.2%, specificity of 71.4% and total accuracy 75.5%. In the present study, we have shown that anti-$HSP90{\alpha}$ may be a potential useful serum biomarker to discriminate CCA cases from healthy persons.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2167-2172
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• 2013

Lung cancer remains a major cause of morbidity and mortality worldwide, accounting for more deaths than any other cause. All the clinical practice guidelines recommended against routine screening for lung cancer have cited lack of robust evidence, at least until a few years back. However, the potential to screen lung cancers has received renewed interest due to superior performance of low dose CT (LD-CT) in detecting early stage cancers. The incremental costs and risks involved due to the invasive procedures in the screened population due to a high false positivity rate questions the use of LD-CT scan as a reliable community based screening tool. There is therefore an urgent need to find a less invasive and a more reliable biomarker that is crucial to increase the probability of early lung cancer detection. This can truly make a difference in lung cancer survival and at the same time be more cost and resource utilization effective. Sampling blood serum being minimally invasive, low risk and providing an easy to obtain biofluid, needs to be explored for potential biomarkers. This review discusses the use of circulatory miRNAs that have been able to discriminate lung cancer patients from disease free controls. Several studies conducted recently suggest that circulating miRNAs may have promising future applications for screening and early detection of lung cancer.

• Laboratory Medicine Online
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• 제6권1호
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• pp.25-30
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• 2016

배경: Thymidine kinase 1 (TK1)은 세포 주기의 중요한 조절 효소로 암세포의 증식 시에 증가하는 것으로 알려져 있으며, 현재까지 혈액종양과 다양한 고형암에서 진단 또는 치료 후 모니터링과 예후 예측에 중요한 표지자로 보고되고 있다. 본 연구에서는 한국인에서 혈청 TK1 정량분석을 통하여 건강인의 혈청 TK1 참고치를 설정하고자 하였으며 B세포림프종 환자를 대상으로 임상적 악성도 표지자로서 혈청 TK1 검사의 유용성을 평가하고자 하였다. 방법: 72명의 B세포림프종 환자와 143명의 건강대조군의 혈청검체에서 화학발광면역측정법으로 혈청 TK1 농도를 측정하였다. 건강대조군에서 혈청 TK1의 참고치를 설정하였고, 환자군과 건강대조군에서 측정된 혈청 TK1 결과를 이용해 ROC 분석을 통한 기준치를 구하여 상대적으로 높은 혈청 TK1 정량값과 B세포림프종의 임상 지표들과의 상관성을 비교하였다. 결과: 전체 건강대조군의 혈청 TK1의 95 percentile에 따른 참고범위는 5.4-21.8 U/L였다. B세포림프종 환자군과 건강대조군의 혈청 TK1 수치 비교에서 평균${\pm}$표준편차는 각각 $40.6{\pm}68.5U/L$와 $11.8{\pm}4.4U/L$로 나타났으며 두 그룹 간에 유의한 차이를 보였다(P<0.001). ROC 분석 후, 혈청 TK1 수치 15.2 U/L를 이용하였을 때 민감도 59.7%, 특이도 83.2%, AUC 0.73을 보여 B세포림프종 환자를 선별할 수 있는 기준치로 설정하였다. 상대적으로 높은 혈청 TK1 수치(${\geq}15.2U/L$)는 병기, 골수침범, IPI 점수, LD 수치, 낮은 Hb (<12 g/dL), 림프구 수와 상관성이 있는 것으로 나타났다. 결론: B세포림프종 환자에서 측정되는 혈청 TK1 수치는 B세포림프종의 임상적 악성도 표지자로서 유용하게 사용될 수 있을 것이다.

• Journal of Veterinary Science
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• 제23권4호
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• pp.51.1-51.10
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• 2022

Background: Due to the unavailability of an effective vaccine or antiviral drug against the African swine fever virus (ASFV), rapid diagnosis methods are needed to prevent highly contagious African swine fever. Objectives: The objective of this study was to establish the ladder-shape melting temperature isothermal amplification (LMTIA) assay for the detection of ASFV. Methods: LMTIA primers were designed with the p72 gene of ASFV as the target, and plasmid pUC57 was used to clone the gene. The LMTIA reaction system was optimized with the plasmid as the positive control, and the performance of the LMTIA assay was compared with that of the commercial real-time polymerase chain reaction (PCR) kit in terms of sensitivity and detection rate using 200 serum samples. Results: Our results showed that the LMTIA assay could detect the 10⁴ dilution of DNA extracted from the positive reference serum sample, which was the same as that of the commercial real-time PCR kit. The coincidence rate between the two assays was 100%. Conclusions: The LMTIA assay had high sensitivity, good detection, and simple operation. Thus, it is suitable for facilitating preliminary and cost-effective surveillance for the prevention and control of ASFV.

• Toxicological Research
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• 제32권1호
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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.

• Journal of Ginseng Research
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• 제37권2호
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• pp.194-200
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• 2013

Korean red ginseng (KRG) is prepared by the process of steaming the roots of Panax ginseng. In this study, the feeding effects of KRG-water extract (KRGE) on ethanol-induced liver damage were elucidated by measuring serum biomarkers in rats. Serum ${\gamma}$-glutamyltranspeptidase (g-GT) activity and the concentration of malondialdehyde (MDA) were significantly increased by short-term and long-term ethanol treatment in rats, whereas the activities of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) did not respond. Pretreatment with KRGE maintained the activity of serum GPT, and the MDA concentration induced by short-term ethanol ingestion remained within the normal range. However, co-feeding of KRGE to rats decreased the concentration of MDA but failed to modulate the serum ${\gamma}$-GT activity induced by long-term ethanol treatment. Our studies suggest that in rats, it appears that KRGE does not sufficiently reverse the physiological response evoked by long-term ethanol ingestion to maintain normal conditions, in view of the serum biomarker ${\gamma}$-GT, regardless of KRGE's favorable antioxidant activity.

• 대한의생명과학회지
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• 제11권4호
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9367-9373
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• 2014

In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

• Clinical and Experimental Pediatrics
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• 제56권1호
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• pp.8-12
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• 2013

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

• BMB Reports
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• 제41권9호
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• pp.615-625
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• 2008

Over a last decade, intense interest has been focused on biomarker discovery and their clinical uses. This interest is accelerated by the completion of human genome project and the progress of techniques in proteomics. Especially, cancer biomarker discovery is eminent in this field due to its anticipated critical role in early diagnosis, therapy guidance, and prognosis monitoring of cancers. Among cancers, lung cancer, one of the top three major cancers, is the one showing the highest mortality because of failure in early diagnosis. Numerous potential DNA biomarkers such as hypermethylations of the promoters and mutations in K-ras, p53, and protein biomarkers; carcinoembryonic antigen (CEA), CYFRA21-1, plasma kallikrein B1 (KLKB1), Neuron-specific enolase, etc. have been discovered as lung cancer biomarkers. Despite extensive studies thus far, few are turned out to be useful in clinic. Even those used in clinic do not show enough sensitivity, specificity and reproducibility for general use. This review describes what the cancer biomarkers are for, various types of lung cancer biomarkers discovered at present and predicted future advance in lung cancer biomarker discovery with proteomics technology.