• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.1008-1018
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• 1996

Primary mediastinal nonseminomatous germ cell tumor is extremely rare. Apart from rarity and large size, mediastinal germ cell tumors show striking similarity to testicular tumors in age, incidence, and tumor type. The symptoms associated with these tumors are related mainly to size, invasion of neighboring structures, and distant metastases. Tissue diagnosis is obtained by biopsy of the primary lesion or by biopsy of metastatic sites. Tumors often present with advanced bulky disease, which are unresectable. So these tumors require an aggressive multidisciplinary approach to management. Optimal management includes aggressive surgical debulking and early use of cisplatin-bleomycin-based combination chemotherapy. Serial biomarker measurements permit early recognition of recwrence and improved timing of surgical intervention. The prognosis for mediastinal germ cell tumors is poor, not only because they are far advanced at the time of diagnosis but also because some of the tumors-such as embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors-are very aggressive. In these cases, we present three young male patients with large mass on anterior mediastinum. Tissue diagnosis was obtained by primary lesion biopsy. All patients received surgical debulking and combination chemotherapy and experienced a brief response and eventually had relapses. We report these cases with a review of literatures.

• Journal of Preventive Medicine and Public Health
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• v.39 no.4
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• pp.353-358
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• 2006

Objectives: An increase in the serum gamma-glutamyltransferase (GGT) concentration has been regarded as a marker of alcohol drinking or liver disease. Some reports, however, have suggested that the serum GGT may be a sensitive and early biomarker for the development of prediabetes and diabetes. In this study we investigated whether serum GGT is a reliable predictor of the incident impaired fasting glucose (IFG), including diabetes. Methods: We performed a prospective study for two years (2002-2004). We analyzed the periodic health examination data from a total of 4,711 men. The examinations were done in the years 2002 and 2004. The analyzed data included a self-questionnaire, a physical examination and the laboratory results. Both IFG and diabetes were defined as a serum fasting glucose concentration of more than 100 mg/dL and 126 mg/dL, respectively. Results: A total of 738 cases (15.7%) of incident IFG and 13 cases (0.3%) of diabetes occurred. The mean serum GGT concentrations were quite different between the normal (38.0 IU) and incident IFG groups (50.3 IU), and the incident diabetes group (66.0 IU) (p<0.001). After multivariable adjustment, the relative risks for incident IFG or diabetes across the baseline GGT categories (<10th, 10th-20th, 30th-40th, 50th-60th, 70th-80th and >90th percentile) were 1.0, 1.172 (0.769-1.785), 1.107 (0.725-1.689), 1.444 (0.934-2.232), 2.061 (1.401-3.031) and 2.545 (1.784-3.631) (p-value for trend: <0.001). The risks significantly increased with increasing levels of GGT for 2 years; when comparing the increased groups (<10%, 10-20%, >20%) versus the decreased over 20% group of GGT, the risks for IFG or diabetes were 1.334 (1.002-1.776), 1.613 (1.183-2.199) and 1.399 (1.092-1.794). Conclusions: Our findings suggest that serum GGT concentrations within its normal range may be an early predictor of the development of IFG and diabetes. As serum GGT is a relatively inexpensive test and a reliable marker, it might have important implications in public health promotion.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.

• Journal of Korean Neurosurgical Society
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• v.60 no.1
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• pp.21-29
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• 2017

Objective : The purpose of this study was to analyze outcomes and identify prognostic factors in patients with cerebral metastases from non-small cell lung cancer (NSCLC) treated with gamma knife radiosurgery (GKS) particularly, focusing on associations of biomarkers and systemic treatments. Methods : We retrospectively reviewed the medical records of 134 patients who underwent GKS for brain metastases due to NSCLC between January 2002 and December 2012. Representative biomarkers including epidermal growth factor receptor (EGFR) mutation, K-ras mutation, and anaplastic lymphoma kinase (ALK) mutation status were investigated. Results : The median overall survival after GKS was 22.0 months (95% confidence interval [CI], 8.8-35.1 months). During follow-up, 63 patients underwent salvage treatment after GKS. The median salvage treatment-free survival was 7.9 months (95% CI, 5.2-10.6 months). Multivariate analysis revealed that lower recursive partition analysis (RPA) class, small number of brain lesions, EGFR mutation (+), and ALK mutation (+) were independent positive prognostic factors associated with longer overall survival. Patients who received target agents 30 days after GKS experienced significant improvements in overall survival and salvage treatment-free survival than patients who never received target agents and patients who received target agents before GKS or within 30 days (median overall survival: 5.0 months vs. 18.2 months, and 48.0 months with p-value=0.026; median salvage treatment-free survival: 4.3 months vs. 6.1 months and 16.6 months with p-value=0.006, respectively). To assess the influence of target agents on the pattern of progression, cases that showed local recurrence and new lesion formation were analyzed according to target agents, but no significant effects were identified. Conclusion : The prognosis of patients with brain metastases of NSCLC after GKS significantly differed according to specific biomarkers (EGFR and ALK mutations). Our results show that target agents combined with GKS was related to significantly longer overall survival, and salvage treatment-free survival. However, target agents were not specifically associated with improved local control of the lesion treated by GKS either development of new lesions. Therefore, it seems that currently popular target agents do not affect brain lesions themselves, and can prolong survival by controlling systemic disease status.

• Allergy, Asthma & Respiratory Disease
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• v.5 no.6
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• pp.307-311
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• 2017

Induced sputum and sputum cell count analysis is a test for the diagnosis of various respiratory diseases. In particular, it has long been used as an important biomarker in the diagnosis or characterization of asthma or eosinophilic bronchitis. Despite a relatively long history of this test, there has been no consensus report for conducting and interpreting the analyses in Korea. Based on this awareness and necessity, the Korean Academy of Asthma, Allergy and Clinical Immunology launched the Standardization Committee to review the international guidelines and the literature and to develop a consensus report on the diagnostic procedure and interpretation of the sputum induction test.

• Journal of Veterinary Clinics
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• v.40 no.2
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• pp.130-134
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• 2023

A 12-year-old Standard Poodle presented with intermittent weakness and occasional dyspnea at the Veterinary Medicine Teaching Hospital of Kangwon National University. A grade of 4 out of 6 systolic murmur with an irregular tachycardic rhythm was auscultated on both sides of the chest. Systolic blood pressure was 140 mmHg. Panting was noticed in the hospital, but there was no crackle sound. Blood analysis revealed mild increases in liver panel levels (alanine aminotransferase 149 [reference interval, 19-70] U/L; and alkaline phosphatase, 185 [reference interval, 15-127] U/L) and severe increases in cardiac biomarker levels (n-terminal pro-brain natriuretic peptide, 4169 [reference interval, 50-900] pmol/L; and cardiac troponin I, 0.22 [reference interval, 0.03-0.12] ng/mL). On electrocardiography, irregularly irregular supraventricular tachycardic rhythm with an f-wave and no distinct p-wave was observed. Generalized cardiomegaly with an enlarged right atrium and left ventricle was confirmed on thoracic radiography. Moreover, hepatomegaly and an enlarged caudal vena cava were observed. Echocardiographic evaluation revealed a fibromuscular diaphragm in the right ventricle. Because of the obstructive lesion in the right ventricle, the right atrium and ventricle were enlarged (right atrial area index, 38.82 cm²/m² [reference interval, 4.2-10.2 cm²/m²]; right ventricle end-diastolic area index, 14.152 cm²/m² [reference interval, 4.9-10.92 cm²/m²]). Accordingly, the patient was diagnosed with double-chambered right ventricle (DCRV). Pimobendan, furosemide, enalapril, diltiazem, and S-adenosylmethionine (SAMe) were prescribed, and all symptoms were relieved. DCRV is a right-sided congenital heart defect resembling pulmonic valve stenosis. If symptoms are not severe, medical therapy can be facilitated without surgery or the balloon dilation.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.105-112
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• 2023

Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.

• Journal of the Korean Society of Radiology
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• v.81 no.2
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• pp.324-336
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• 2020

Cardiovascular calcifications can occur in various cardiovascular diseases and can serve as a biomarker for cardiovascular event prediction. Advances in CT have enabled evaluation of calcifications in cardiovascular structures not only on ECG-gated CT but also on non-ECG-gated CT. Therefore, many studies have been conducted on the clinical relevance of cardiovascular calcifications in patients. In this study, we divided cardiovascular calcifications into three classes, i.e., coronary artery, thoracic aorta, and cardiac valve calcifications, which are closely associated with cardiovascular events. Further, we briefly described pericardial calcifications, which can be found incidentally. Since the start of lung cancer screening in Korea in the second half of 2019, the number of non-enhanced, non-ECG-gated, low-dose chest CT has been increasing, and the number of incidentally found cardiovascular calcifications has also been increasing. Therefore, understanding the relevance of cardiovascular calcifications on non-enhanced, non-ECG-gated, low-dose chest CT and their proper reporting are important for radiologists.

• Journal of Life Science
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• v.34 no.4
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• pp.227-235
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• 2024

Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.43-53
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• 2007

[ $\underline{Purpose}$ ]: To evaluate the relationship between the expression of EGFR, p53, Cox-2, Bcl-2 and the clinical parameters of NPC (nasopharyngeal carcinoma) patients treated with radiotherapy with/without chemotherapy, and to determine if these could be used as a biologic marker. $\underline{Materials\;and\;Methods}$: This study retrospectively examined 75 NPC patients who were pathologically diagnosed at St. Mary's Hospital and Kangnam St Mary's Hospital from March 1988 to August 2002 and treated with radiotherapy with/without chemotherapy. The levels of EGFR, p53, Cox-2, and Bcl-2 expression were determined immunohistochemically. The relationship between the levels of EGFR, p53, Cox-2 and Bcl-2 expression and the H- E staining findings including the WHO classification, TNM stage, tumor response to chemotherapy and radiotherapy, disease free survival (DFS), and overall survival (OS) was analyzed. $\underline{Results}$: At a median follow up of 50.8 months (range: $5.5{\sim}201$ months), the 3 years OS rate and PFS rate were 68.7% and 68.2%, respectively. The five year OS rate and PFS rate were 53.5% and 51.1%, respectively. The median OS duration and PFS duration were 85.5 months and 61.1 months, respectively. The WHO classification correlated with the complete response rate, lymph node metastasis and distant metastasis. The expression of p53 was associated with increased mitosis and poor overall survival. The expression of Bcl-2 correlated with the DFS and WHO classification. The expression of Cox-2 correlated with a poor overall survival and response rate in the lymph node. However, EGFR was not correlated with any factors. $\underline{Conclusion}$: These results suggest that the expression of p53, Cox-2, Bcl-2 plays role in predicting prognostic factors for NPC treated with radiotherapy with/without chemotherapy. However, further study on a larger number of patients will be needed to identify more useful biomarkers of NPC.