• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4241-4246
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• 2016

Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre- and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p=0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

• 생명과학회지
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• 제26권6호
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• pp.705-710
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• 2016

대장암은 세계적으로 3번째로 흔한 암종이며, 암으로 인한 사망의 주요 원인이 되고 있다. 비록 다양한 진단방법이나 치료 방법이 이용되고는 있으나 병의 진행에 관여하는 분자메커니즘 이해의 부족 때문에 여전히 완전한 치료는 어려운 실정이다. 마이크로알엔에이는 단백질 정보를 코딩하고 있지 않은 작은 알엔에이 단편이다. 이러한 마이크로알엔에이는 특정 유전자의 전사과정 또는 번역과정을 조절하는 강력한 유전자 조절자로서의 기능을 가진다. 암의 발생과정에서 중요한 세포신호 전달 과정의 손상이 빈번하게 발생 하는데, 다양한 마이크로알엔에이의 이상발현이 그 원인이 되고 있다. 마이크로알엔에이-31은 암유전자의 역할을 하며 발암과정에 관여하는 다양한 유전자를 조절한다고 알려져 있다. 따라서, 본 연구에서는 대장암에서 마이크로알엔에이-31 발현의 임상적의의를 규명하고자 하였다. 175례의 대장암 조직과 16례의 정상 대장조직에서 실시간 유전자 증폭장치를 이용하여 마이크로알엔에이-31의 발현을 분석하고, 임상병리적 요인들과의 상관관계를 분석하고 임상적 유용성을 연구해 보았다. 마이크로알엔에이-31은 정상조직에 비해 대장암 조직에서 과발현이 되어 있었다. 175례 대장암 조직을 이용한 분석에서 마이크로알엔에이-31의 발현은 병기의 진행 정도에 따라 발현이 증가 되고 있었으며, 실제 마이크로알엔에이-31의 발현이 높은 대장암 환자군의 생존률이 그렇지 않은 환자군에 비해 통계적으로 유의하게 나쁜 것으로 확인 되었다. Cox 비례위험 모형과 로지스틱 회귀 모형을 이용한 분석에서 마이크로알엔에이-31의 과발현이 직접적으로 대장암 환자의 예후 및 원발전이와 연관성이 있는 것이 확인 되었다. 따라서, 이상의 연구결과를 종합해볼 때 대장암에서 과발현 된 마이크로알엔에이-31은 대장암 환자의 예후예측 및 전이예측 바이오마커로서의 활용 가능성이 높다고 볼 수 있다.

• Clinical and Experimental Reproductive Medicine
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• 제44권2호
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• pp.63-72
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• 2017

Objective: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. Methods: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. Results: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. Conclusion: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

• 한국임상수의학회지
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• 제28권1호
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1887-1893
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• 2012

The aim of this study was to detail characteristics of mammary Paget's disease (PD) representing the whole population in China. A total of 4211 female breast cancer inpatients at seven tertiary hospitals from seven representative geographical regions of China were collected randomly during 1999 to 2008. Data for demography, risk factors, diagnostic imaging test, physical examination and pathologic characters were surveyed and biomarker status was tested by immunohistochemistry. The differences of demography and risk factors between PD with breast cancer and other lesions were compared using Chi-square test or t-test, with attention to physical examination and pathological characters. The percentage of PD was 1.6% (68/4211) in all breast cancers. The mean age at diagnosis was 48.1, and 63.2% (43/68) patients were premenopausal. There is no difference in demography and risk factors between PD with breast cancer and other breast cancer (P > 0.05). The main pattern of PD in physical exam and pathologic pattern were patients presenting with a palpable mass in breast (65/68, 95.6%) and PD with underlying invasive cancer (82.4%, 56/68) respectively. The rate of multifocal disease was 7.4% (5/68). PD with invasive breast cancer showed larger tumor size, more multifocal disease, lower ER and PR expression and higher HER2 overexpression than those in other invasive breast cancer (P < 0.05). These results suggested that PD in China is a concomitant disease of breast cancer, and that PD with underlying invasive cancer has more multiple foci and more aggressive behavior compared with other breast invasive cancer. We address the urgent needs for establishing diagnostic and therapeutic guidelines for mammary PD in China.

• Korean Journal of Radiology
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• 제22권10호
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• pp.1719-1729
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• 2021

Objective: Emphysema and small-airway disease are the two major components of chronic obstructive pulmonary disease (COPD). We propose a novel method of quantitative computed tomography (CT) emphysema air-trapping composite (EAtC) mapping to assess each COPD component. We analyzed the potential use of this method for assessing lung function in patients with COPD. Materials and Methods: A total of 584 patients with COPD underwent inspiration and expiration CTs. Using pairwise analysis of inspiration and expiration CTs with non-rigid registration, EAtC mapping classified lung parenchyma into three areas: Normal, functional air trapping (fAT), and emphysema (Emph). We defined fAT as the area with a density change of less than 60 Hounsfield units (HU) between inspiration and expiration CTs among areas with a density less than -856 HU on inspiration CT. The volume fraction of each area was compared with clinical parameters and pulmonary function tests (PFTs). The results were compared with those of parametric response mapping (PRM) analysis. Results: The relative volumes of the EAtC classes differed according to the Global Initiative for Chronic Obstructive Lung Disease stages (p < 0.001). Each class showed moderate correlations with forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC) (r = -0.659-0.674, p < 0.001). Both fAT and Emph were significant predictors of FEV₁ and FEV₁/FVC (R² = 0.352 and 0.488, respectively; p < 0.001). fAT was a significant predictor of mean forced expiratory flow between 25% and 75% and residual volume/total vital capacity (R² = 0.264 and 0.233, respectively; p < 0.001), while Emph and age were significant predictors of carbon monoxide diffusing capacity (R² = 0.303; p < 0.001). fAT showed better correlations with PFTs than with small-airway disease on PRM. Conclusion: The proposed quantitative CT EAtC mapping provides comprehensive lung functional information on each disease component of COPD, which may serve as an imaging biomarker of lung function.

• Clinical and Experimental Pediatrics
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• 제57권8호
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• pp.357-362
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• 2014

Purpose: The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. Methods: We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Results: Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was $1.36{\pm}1.0$ days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was $2.8{\pm}1.4$. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were $4,159{\pm}3,714pg/mL$ and $957{\pm}902pg/mL$, respectively, which decreased significantly in the convalescent phase. Conclusion: Incomplete KD was observed in 87.5% patients. Serum NT- proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

• Investigative Magnetic Resonance Imaging
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• 제21권3호
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• pp.125-130
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• 2017

Purpose: To evaluate the clinical significance of T1 high signal intensity on the globus pallidus as a predictor of severe hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), which is a distinct syndrome characterized by multi-organ dysfunction including cerebral failure. Materials and Methods: From January 2002 to April 2014, we retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical and magnetic resonance (MR) features of 74 consecutive patients (44 men and 30 women; mean age, 59.5 years) with liver cirrhosis. The chronic liver failure-sequential organ failure assessment score was used to diagnose ACLF. The pallidal index (PI), calculated by dividing the mean signal intensity of the globus pallidus by that of the subcortical frontal white matter were compared according to ACLF. The PI was compared with the Model for End-Stage Liver Disease (MELD) score in predicting the development of ACLF. Results: Fifteen patients who were diagnosed with ACLF had higher hepatic encephalopathy grades (initial, P = 0.024; follow-up, P = 0.002), MELD scores (P < 0.001), and PI (P = 0.048). In the ACLF group, the mean PI in patients with cerebral failure was significantly higher than that in the patients without cerebral failure (1.33 vs. 1.20, P = 0.039). In patients with ACLF, the area under the curve (AUC) for PI was 0.680 (95% confidence intervals [CI], 0.52-0.85), which was significantly lower than that for the MELD score (AUC, 0.88; 95% CI, 0.77-0.99) (P = 0.04). Conclusion: The PI can be an ancillary biomarker for predicting the development of ACLF and severe hepatic encephalopathy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1839-1843
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• 2015

Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.