• Asian Pacific Journal of Cancer Prevention
• /
• 제16권4호
• /
• pp.1403-1407
• /
• 2015

Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권4호
• /
• pp.1657-1663
• /
• 2015

Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권3호
• /
• pp.1051-1056
• /
• 2015

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

• Clinical and Experimental Reproductive Medicine
• /
• 제47권2호
• /
• pp.114-121
• /
• 2020

Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation. Methods: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells. Results: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency. Conclusion: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

• 한국식품위생안전성학회지
• /
• 제29권2호
• /
• pp.85-91
• /
• 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.

• Molecules and Cells
• /
• 제44권7호
• /
• pp.468-480
• /
• 2021

Ubiquitin D (UBD) is highly upregulated in many cancers, and plays a pivotal role in the pathophysiological processes of cancers. However, its roles and underlying mechanisms in oral squamous cell carcinoma (OSCC) are still unclear. In the present study, we investigated the role of UBD in patients with OSCC. Quantitative real-time polymerase chain reaction and Western blot were used to measure the expression of UBD in OSCC tissues. Immunohistochemistry assay was used to detect the differential expressions of UBD in 244 OSCC patients and 32 cases of normal oral mucosae. In addition, CCK-8, colony formation, wound healing and Transwell assays were performed to evaluate the effect of UBD on the cell proliferation, migration, and invasion in OSCC. Furthermore, a xenograft tumor model was established to verify the role of UBD on tumor formation in vivo. We found that UBD was upregulated in human OSCC tissues and cell lines and was associated with clinical and pathological features of patients. Moreover, the overexpression of UBD promoted the proliferation, migration and invasion of OSCC cells; however, the knockdown of UBD exerted the opposite effects. In this study, our results also suggested that UBD promoted OSCC progression through NF-κB signaling. Our findings indicated that UBD played a critical role in OSCC and may serve as a prognostic biomarker and potential therapeutic target for OSCC treatment.

• Nutrition Research and Practice
• /
• 제13권5호
• /
• pp.393-398
• /
• 2019

BACKGROUND/OBJECTIVES: The association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults. SUBJECTS/METHODS: In this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD. RESULTS: There were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (P < 0.05). We found tea consumption reduced CHD risk in female participants (adjusted odds ratio (OR) = 0.484, 95% CI: 0.242-0.968, P = 0.0403). Regarding the type of tea consumed, the risk of CHD was reduced in women who drank partially fermented tea (adjusted OR = 0.210, 95% CI: 0.084-0.522, P = 0.0008). Analytic results for the amount of tea consumed per unit time showed CHD risk was reduced in women who consumed 1-2 cups of tea per day (adjusted OR = 0.291, 95% CI: 0.131-0.643, P = 0.0023). A tea-drinking frequency of > 6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049-0.679, P = 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10-20 years (adjusted OR = 0.360, 95% CI: 0.137-0.946, P = 0.0382). CONCLUSIONS: Tea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

• Journal of Chest Surgery
• /
• 제55권2호
• /
• pp.143-150
• /
• 2022

Background: The effectiveness of extracorporeal membrane oxygenation (ECMO) for patients with refractory cardiogenic shock or cardiac arrest is being established, and serum lactate is well known as a biomarker of end-organ perfusion. We evaluated the efficacy of pre-ECMO lactate for predicting 6-month survival in patients with acute coronary syndrome (ACS) undergoing ECMO. Methods: We reviewed the medical records of 148 patients who underwent veno-arterial (VA) ECMO for ACS between January 2015 and June 2020. These patients were divided into survivors and non-survivors based on 6-month survival. All clinical data before and during ECMO were compared between the 2 groups. Results: Patients' mean age was 66.0±10.5 years, and 116 (78.4%) were men. The total survival rate was 45.9% (n=68). Cox regression analysis showed that the pre-ECMO lactate level was an independent predictor of 6-month mortality (hazard ratio, 1.210; 95% confidence interval [CI], 1.064-1.376; p=0.004). The area under the receiver operating characteristic curve of pre-ECMO lactate was 0.64 (95% CI, 0.56-0.72; p=0.002; cut-off value=9.8 mmol/L). Kaplan-Meier survival analysis showed that the cumulative survival rate at 6 months was significantly higher among patients with a pre-ECMO lactate level of 9.8 mmol/L or less than among those with a level exceeding 9.8 mmol/L (57.3% vs. 31.8%, p=0.0008). Conclusion: A pre-ECMO lactate of 9.8 mmol/L or less may predict a favorable outcome at 6 months in ACS patients undergoing VA-ECMO. Further research aiming to improve the accuracy of predictions of reversibility in patients with high pre-ECMO lactate levels is essential.

• 생명과학회지
• /
• 제34권6호
• /
• pp.434-441
• /
• 2024

유선 종양은 중성화되지 않은 암컷 반려견에서 가장 빈번하게 발견되는 종양으로, 중요한 임상 문제로 대두되고 있다. 반려견 유선 종양(CMT)과 인간 유방암(HBC)의 강한 유사성으로 인해, 인간 유방암에서 확인된 바이오 마커는 반려견 유선종양에서도 검출될 수 있다. 이러한 바이오 마커는 조기 진단, 예후 및 치료 전략에 유용한 통찰력을 제공하는 것으로 나타났다. 본 논문은 연구되어진 반려견 유선종양 바이오 마커에 대한 간략한 개요를 제공하고자 한다. 반려견 유선 종양의 전통적인 치료는 외과적 수술로 시작하여 화학요법, 방사선 요법, 또는 호르몬 요법이 뒤따르지만, 이러한 치료법만으로는 항상 충분하지 않을 수 있다. 반려견 유선 종양 특이적 발암 기전 이해의 바탕으로 개발된 바이오 마커는 환견에게 더 나은 결과를 제공할 희망을 준다. 단일 세포 RNA 시퀀싱 분석은 종양 내 및 종양 간 이질성에 대한 유익한 정보를 제공할 수 있다. 본 리뷰 논문은 반려견 유선 종양 바이오 마커에 대한 현재 연구를 탐구하고 그 발전 방향을 제안한다.

• Radiation Oncology Journal
• /
• 제25권1호
• /
• pp.43-53
• /
• 2007

목 적: 비인강암종 환자들의 종양조직으로부터 EGFR, p53, Cox-2, Bcl-2 단백발현정도를 측정하고 임상양상, 치료성적과의 관련성을 조사하여 이들 단백이 치료에 대한 반응 및 예후를 예측할 수 있는 생물학적 표지자(biomarker)로 이용할 수 있는지 알아보고자 하였다. 대상 및 방법: 1988년 3월 1일부터 2002년 8월 15일까지 성모병원과 강남성모병원에서 비인강암으로 진단받고 근치적 방사선치료와 항암치료를 받았던 환자 104명 중 파라핀 블록이 보존되어 있는 75명을 대상으로 하여 후향적 분석을 시행하였다. 병기는 2002년에 개정된 AJCC로 재분류하였으며, 대상환자의 Hematoxylin-Eosin 염색 슬라이드를 두경부 병리 전문의사가 재검토하여 WHO 분류에 맞게 환자군을 분류하였으며 역형성(anaplasia) 유무, 유사분열(mitosis) 빈도 측정 등 병리조직학적 소견을 확인하였다. EGFR, p53, Cox-2, Bcl-2 단백발현 정도를 면역조직 화학염색을 통해 측정하였으며 이들 단백의 발현정도와 임상병기, 치료성적과의 관련성을 조사하였다. 결 과: 전체 104명 환자의 추적기간은 $5.5{\sim}201$개월이었고 3년 생존율은 68.7%, 5년 생존율은 53.5%, 중앙생존기간은 85.5개월이었으며 3년 무병생존율은 68.2%, 5년 무병생존율은 51.5%, 중앙무병생존기간은 61.1개월이었다. WHO 분류 2와 3 종양은 완전관해율이 높아 항암방사선치료(chemoradiotherapy)에 대한 반응성이 높은 경향을 보였으며(p=0.075), 상대적으로 진단당시 림프절전이율이 높았고, 원격전이할 확률이 높았다. p53은 발현 정도가 증가함에 따라 생존율이 떨어지고 유사분열은 증가하였다. Bcl-2 발현이 증가함에 따라 재발률이 떨어지는 경향을 보였으며, WHO 분류와 연관성을 보였다. Cox-2의 발현이 증가함에 따라 생존율이 떨어지고, 림프절치료율도 낮은 것으로 나타났다. 그러나 EGFR은 어떤 인자와도 상관관계를 보이지 않았다. 결 론: 비인강암에서 치료 후 예후를 예측할 수 있는 생물학적 표지자의 가능성을 가진 것으로 보고되고 있는 Cox-2, p53, Bcl-2, EGFR에 대한 연구결과 Cox-2, p53, Bcl-2의 발현정도는 항암방사선치료후 반응률, 생존율, 재발률과 연관을 보여 향후 치료결과를 예측할 수 있는 예후인자로서의 이용가능성이 있음을 알 수 있었으며 보다 실용적인 생물학적 표지자의 규명을 위해서 향후 보다 많은 환자를 대상으로 한 전향적 연구가 필요할 것으로 생각된다.