Disease Markers - Volume 34, issue 4

Authors: Malaguarnera, Giulia | Paladina, Isabella | Giordano, Maria | Malaguarnera, Michele | Bertino, Gaetano | Berretta, Massimiliano

Article Type: Research Article

Abstract: Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of …serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers_{2} pyruvate-Kinase (TuM_{2-} PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value. Show more

Keywords: Cholangiocarcinoma, tumor markers, CA 19-9, CEA

DOI: 10.3233/DMA-130964

Citation: Disease Markers, vol. 34, no. 4, pp. 219-228, 2013

Authors: Lee, Chien-Te | Chua, Sarah | Hsu, Chung-Yao | Tsai, Yu-Che | Ng, Hwee-Yeong | Kuo, Chien-Chun | Wu, Chien-Hsing | Chen, Te-Chun | Chiu, Terry Ting-Yu | Lee, Yueh-Ting

Article Type: Research Article

Abstract: BACKGROUND: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients. METHODS: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels …of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared. RESULTS: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC. CONCLUSIONS: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients. Show more

Keywords: Vascular calcification, valvular calcification, hemodialysis, biomarker

DOI: 10.3233/DMA-130965

Citation: Disease Markers, vol. 34, no. 4, pp. 229-235, 2013

Authors: Aydoğdu, Müge | Gürsel, Gül | Sancak, Banu | Yeni, Serpil | Sarı, Gülçin | Taşyürek, Seçil | Türk , Murat | Yüksel, Seher | Senes, Mehmet | Özis, Türkan Nadir

Article Type: Research Article

Abstract: AIM: To assess and compare the roles of plasma and urine concentrations of neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C for early diagnosis of septic acute kidney injury (AKI) in adult critically ill patients. METHODS: Patients were divided into three groups as sepsis-non AKI, sepsis-AKI and non sepsis-non AKI. Plasma samples for NGAL and Cystatin C were determined on admission and on alternate days and urinary samples were collected for every day until …ICU discharge. RESULTS: One hundred fifty one patients were studied; 66 in sepsis-non AKI, 63 in sepsis-AKI, 22 in non-sepsis-non-AKI groups. Although plasma NGAL performed less well (AUC 0.44), urinary NGAL showed significant discrimination for AKI diagnosis (AUC 0.80) with a threshold value of 29.5 ng/ml (88% sensitivity, 73% specificity). Both plasma and urine Cystatin C worked well for the diagnosis of AKI (AUC 0.82 and 0.86, thresholds 1.5 and 0.106 mg/L respectively). CONCLUSION: Plasma and urinary Cystatin C and urinary NGAL are useful markers in predicting AKI in septic critically ill patients. Plasma NGAL raises in patients with sepsis in the absence of AKI and should be used with caution as a marker of AKI in septic ICU patients. Show more

Keywords: NGAL protein, human, Cystatin C, Acute kidney injury, biomarkers, sepsis, Intensive Care Units, predictive value of tests

DOI: 10.3233/DMA-130966

Citation: Disease Markers, vol. 34, no. 4, pp. 237-246, 2013

Authors: Li, Yu-Fen | Sung, Fung-Chang | Tsai, Ming-Hsui | Hua, Chun-Hung | Liu, Chiu-Shong | Huang, Yao-Te | Yeh, Chih-Ching

Article Type: Research Article

Abstract: BACKGROUND: This case-control study investigates the role of xenobiotic-metabolizing genes, including glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), in the susceptibility to oral potentially malignant disorders (OPMDs). METHODS: The genotypes of GSTM1, GSTT1, GSTP1, CYP1A1*2C, and CYP2E1 PstI/RsaI polymorphisms were determined for 217 OPMD cases and 492 age- and sex-matched controls from a Taiwanese penitentiary. RESULTS: Compared to the GSTM1-present genotype, the GSTM1-null genotype was significantly associated with increased risk …of leukoplakia (odds ratio [OR]=1.46, 95% confidence interval [CI]=1.01–2.10). Similarly, compared to the CYP1A1*2C A/G+G/G genotype, the CYP1A1*2C A/A genotype was significantly associated with increased risk of leukoplakia (OR=1.64, 95% CI=1.12–2.40), particularly for smokers consuming > 13 pack-years of cigarettes (OR=2.40, 95% CI=1.40–4.11) (Interaction P=0.039). In addition, participants with 4–5 risk genotypes (OR > 1) experienced higher risks for leukoplakia than those with 0-1 risk genotypes (OR=3.19, 95% CI=1.65–6.15) (Trend test P=0.001). CONCLUSIONS: Our findings suggest that the CYP1A1*2C A/A genotype may increase the risk of leukoplakia, especially for heavy smokers. Xenobiotic-metabolizing genes may simultaneously modulate this disease risk. These observations require further confirmation with larger samples. Show more

Keywords: Glutathione S-transferases, cytochrome P450 1A1, cytochrome P450 2E1, polymorphisms, oral potentially malignant disorders, cigarette smoking

DOI: 10.3233/DMA-130967

Citation: Disease Markers, vol. 34, no. 4, pp. 247-255, 2013

Authors: Bressan, Alessandro | Bozzo, Francesca | Maggi, Carlo Alberto | Binaschi, Monica

Article Type: Research Article

Abstract: The human cancer antigen 125 (CA125) is over-expressed in epithelial ovarian cancer cells and it plays a role in the pathogenesis of ovarian cancer. This protein presents a repeat region containing up to sixty tandem repeat units. The anti-CA125 monoclonal antibodies have been previously classified into three groups: two major families, the OC125-like antibodies and M11-like antibodies, and a third group, the OV197-like antibodies. A model in which a single repeat unit contains all the epitopes …for these antibodies has been also proposed, even if their exact position is still undetermined. In the present work, the affinities of the monoclonal antibodies, representative of the three families, have been investigated for different CA125-recombinant repeats through Western blot analysis. Different patterns of antibody recognition for the recombinant repeats show that CA125 epitopes are not uniformly distributed in the tandem repeat region of the protein. The minimal region for the recognition of these antibodies has been also individuated in the SEA domain through the subcloning of deleted sequences of the highly recognized repeat-25 (R-25), their expression as recombinant fragments in E. coli and Western blot analysis. Obtained data have been further confirmed by ELISA using the entire R-25 as coating antigen. Show more

Keywords: CA125, ovarian carcinoma, epitope type, SEA domain, monoclonal antibodies

DOI: 10.3233/DMA-130968

Citation: Disease Markers, vol. 34, no. 4, pp. 257-267, 2013

Authors: Agostini, M. | Bedin, C. | Enzo, M.V. | Molin, L. | Traldi, P. | D'Angelo, E. | Maschietto, E. | Serraglia, R. | Ragazzi, E. | Prevedello, L. | Foletto, M. | Nitti, D.

Article Type: Research Article

Abstract: BACKGROUND: Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. Mass spectrometry, in particular matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) is currently used for detecting different pattern of expressed protein. This study investigated the differences in low molecular weight (LMW) peptide profiles between obese and normal-weight subjects in combination with multivariate statistical analysis. MATERIALS: Serum samples of 60 obese patients and 10 healthy …subjects were treated by cut-off membrane (30000 Da) to remove the most abundant proteins. The filtrates containing the LMW protein/peptides were analyzed by MALDI-TOF mass spectrometry. Dataset was elaborated to align and normalize the spectra. We performed cluster analysis and principal component analysis to detect some ionic species that could characterize and classify the subject groups. RESULTS: We observed a down-expression of ionic species at m/z 655.94 and an over-expression of species at m/z 1518.78, 1536.77, 1537.78 and 1537.81 in obese patients. Furthermore we found some ionic species that can distinguish obese patients with diabetes from those with normal glucose level. CONCLUSION: Serum peptide profile of LMW associate with multivariate statistical approach was revealed as a promising tool to discriminate and characterize obese patients and it was able to stratify them in relation to comorbidity that usually are associated with this disease. Further research involving a larger sample will be required to validate these findings. Show more

Keywords: Obesity, MALDI-TOF, serum profile, principal component analysis, cluster analysis

DOI: 10.3233/DMA-130971

Citation: Disease Markers, vol. 34, no. 4, pp. 269-278, 2013

Authors: Wu, Sheng-Hui | Shu, Xiao-Ou | Chow, Wong-Ho | Xiang, Yong-Bing | Zhang, Xianglan | Cai, Qiuyin | Li, Hong-Lan | Milne, Ginger | Wen, Wanqing | Ji, Bu-Tian | Rothman, Nathaniel | Gao, Yu-Tang | Zheng, Wei | Yang, Gong

Article Type: Research Article

Abstract: OBJECTIVES: This study evaluated associations of various anthropometric measures of adiposity with a panel of inflammatory and oxidative stress markers in a relatively lean population of Chinese women. METHODS: This analysis included 1,005 Chinese women aged 40–70 years. Plasma concentrations of inflammatory and oxidative stress markers were measured. Anthropometric measurements were taken by trained interviewers. RESULTS: Body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were all positively and linearly associated with …the inflammatory markers, CRP, TNF-α, soluble TNF-receptor 1 (sTNF-R1), and IL-6. A significant positive association of these measures of adiposity with the oxidative stress marker F_2 -IsoP-M, a metabolite of F_2 -IsoPs, but with not F_2 -IsoPs was found. Differences in biomarkers between extreme quartiles of anthropometric measurements varied widely, ranging from 9.7% for sTNF-R1 to 162.0% for CRP. For each specific biomarker, various anthropometric measurements exhibited similar ability to explain variations in the biomarker, with the biggest partial r^{2} (11%) observed for CRP. CONCLUSIONS: This study suggests that both general adiposity (measured by BMI) and central adiposity (measured by WC and WHtR) are positively and similarly associated with various markers of inflammation and oxidative stress in relatively lean Chinese women. The metabolite F_2 -IsoP-M of F_2 -IsoPs may be a better marker of in vivo oxidative stress than its parent compounds. Show more

Keywords: Adiposity, inflammation, oxidative stress, biomarker

DOI: 10.3233/DMA-130969

Citation: Disease Markers, vol. 34, no. 4, pp. 279-293, 2013