Plasma Levels and Diagnostic Utility of VEGF in a Three-Year Follow-Up of Patients with Breast Cancer.

Breast cancer is the most common malignancy in women globally. The increasing worldwide incidence of this type of cancer illustrates the challenge it represents for healthcare providers. Therefore, new tumor markers are constantly being sought. The aim of this study was to assess plasma concentrations and the diagnostic power of VEGF in 100 patients with early-stage breast cancer, both before and after surgical treatment and during a three-year follow-up. The control groups included 50 subjects with benign breast tumors (fibroadenoma) and 50 healthy women. The VEGF concentration was determined using enzyme-linked immunosorbent assay (ELISA) and the CA 15-3 concentration was determined by chemiluminescent microparticle immunoassay (CMIA). We observed significantly higher preoperative plasma concentrations of VEGF and CA 15-3 in patients with breast cancer. VEGF, similar to CA 15-3, demonstrated high diagnostic utility in the assessment of the long-term efficacy of surgical removal of the tumor. Determinations of VEGF had the highest diagnostic usefulness in the detection of breast cancer recurrence (SE 40%, SP 92%, PPV 67%, NPV 79%). Additionally, the highest values of SE, NPV and AUC were observed during the combined analysis with CA 15-3 (60%; 84%; 0.7074, respectively). Our study suggests a promising diagnostic utility of VEGF in the early stages of breast cancer and in the evaluation of the efficacy of the surgical treatment of breast cancer as well as the detection of breast cancer recurrence, particularly in a combined analysis with CA 15-3 as a new diagnostic panel.

Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer.

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.

Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer.

BACKGROUND: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). METHODS: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. RESULTS: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). CONCLUSIONS: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.

Possible Diagnostic Application of CXCL12 and CXCR4 as Tumor Markers in Breast Cancer Patients.

BACKGROUND/AIM: Chemokines are cytokines involved not only in inflammatory but also in inappropriate response of the immune system in breast cancer (BC) progression. We examined the diagnostic usefulness of CXCL12, CXCR4 and CA 15-3 in BC patients, based on ROC curve analysis. MATERIALS AND METHODS: The study group consisted of 100 patients with BC; the control group consisted of 35 women with benign breast disease and 35 healthy patients. The median concentration of chemokines was measured by ELISA and that of CA 15-3 by chemiluminescent microparticle immunoassay. RESULTS: The concentrations of CXCL12 and CXCR4 in the BC group were significantly higher than those in the control groups. The AUC value of CXCL12 (0.7502) was the highest of all the chemokines measured in the BC patients. CONCLUSION: There may be a link between CXCL12, CXCR4 and BC that can assist in the diagnosis, markedly when combined with CA 15-3.

Can VEGFR-3 be a better tumor marker for breast cancer than CA 15-3?

Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is a very important factor which promotes lymphangiogenesis not only in physiological but also in pathological processes in which we can include neoplasia. The aim of this study was to analyze the plasma concentrations and diagnostic utility of this parameter in comparison and in combination with CA 15-3 in breast cancer (BC) patients and in relation to the control groups. The study included 120 breast cancer and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of VEGFR-3 were determined by an Enzyme-Linked Immunosorbent Assay (ELISA), and those of CA 15-3 by a Chemiluminescent Microparticle Immuno Assay (CMIA). Differences in concentrations of both of the tested parameters were statistically significant when breast cancer patients were compared to the control groups. VEGFR-3 had higher values of sensitivity (SE), specificity (SP), predictive value of a positive (PPV) and negative test result (NPV) in the whole BC group (90%; 98.33%; 99.08%; 83.10%, respectively) and, more importantly, in the early stages of BC, than CA 15-3. VEGFR-3 was also a better parameter in terms of statistically significant Area Under Curve (0.9656) in the whole group and at all BC stages (I-IV), but a maximum range was obtained for the combination of VEGFR-3 and CA 15-3 (0.9710). The combined analysis of VEGFR-3 and CA 15-3 provides hope that a new BC diagnostic panel may be developed in the future.

Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis.

Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitor (TIMP-2) may play an important role in the pathogenesis of cancer disease. We investigated the plasma levels and diagnostic power (ROC curve analysis) of M-CSF, MMP-2, TIMP-2 and tumor markers CA 125 and SCC-Ag in cervical cancer (CC) patients as compared to control group. The study included 89 patients with cervical cancer. The control group consisted of 50 healthy, untreated women. The plasma levels of M-CSF, MMP-2 and TIMP-2 were determined using ELISA, CA 125 and SCC-Ag - by CMIA method. The median levels of M-CSF, TIMP-2, SCC-Ag and CA 125 in the entire group of CC were significantly different than compared to the healthy women group. MMP-2 showed the highest value of sensitivity from all examined parameters (in stage I of CC - 93.10%, II - 82.76%, III and IV - 96.88%, total group - 92.05%). The highest specificity was obtained by M-CSF (86%). The area under the ROC curve (AUC) of M-CSF (0.8051) was the largest of all the tested parameters (even higher than commonly used tumor markers) in the group of cervical cancer. The combination of M-CSF, MMP-2 or TIMP-2 with SCC antigen resulted in an increase AUCs in all cases (0.8760;0.7880;0.8081;respectively). The findings of this study suggest the usefulness of all examined parameters in the diagnostics of CC patients. Out of the tested substances, M-CSF also appears to be the best candidate for cancer diagnostics in all stages of the disease, based on ROC analysis.

Plasma levels of M-CSF and VEGF in laboratory diagnostics and differentiation of selected histological types of cervical cancers.

BACKGROUND: The search of useful serum biomarkers for the early detection of cervical cancers has been of a high priority. The activation of Macrophage-Colony Stimulating Factor (M-CSF) and Vascular Endothelial Growth Factor (VEGF) is likely involved in the pathogenesis and spread of cancer. We compared the plasma levels of M-CSF and VEGF to the ones of commonly accepted tumor markers CA 125and SCC-Ag in three groups of patients: 1. the cervical cancer group (patients with either squamous cell carcinoma or adenocarcinoma); 2. the cervical dysplasia group; 3. the control group. METHODS: This cohort study included 100 patients with cervical cancer and 55 patients with cervical dysplasia. The control group consisted of 50 healthy volunteers. The plasma levels of VEGF and M-CSF were determined using ELISA, while CA 125 and SCC-Ag concentrations were obtained by the chemiluminescent microparticle immunoassay (CMIA). RESULTS: The median levels of M-CSF and VEGF as well as CA 125 and SCC-Ag in the entire group of cervical cancer patients, were significantly different compared to the healthy women group. In case of both the squamous cell carcinoma and the adenocarcinoma groups, plasma levels of M-CSF and VEGF were higher compared to the control group. No significant differences in the studied parameters between the squamous cell carcinoma and the adenocarcinoma group were observed. The highest sensitivity and specificity were obtained for VEGF (81.18 and 76.00%, respectively) and SCC-Ag (81.18%; 74.00%) in the squamous cell carcinoma group and for VEGF (86.67%; 76.00%) in the adenocarcinoma group. The area under the ROC curve for VEGF was the largest in the adenocarcinoma group followed by the squamous cell carcinoma group (0.9082 and 0.8566 respectively). CONCLUSIONS: Obtained results indicate a possible clinical applicability and a high diagnostic power for the combination of MSC-F, VEGF, CA 125 and SCC-Ag in the diagnosis of both studied types of cervical cancer.

Diagnostic Power of Selected Cytokines, MMPs and TIMPs in Ovarian Cancer Patients - ROC Analysis.

BACKGROUND/AIM: The aim of the study was to identify new non-invasive ovarian cancer (OC) tumor markers. MATERIALS AND METHODS: In postmenopausal ovarian cancer patients and in a control group (benign ovarian lesions and healthy subjects), preoperative plasma levels of cytokines, metalloproteinases and their tissue inhibitors were determined using ELISA while those of CA125 and HE4 by chemiluminescent microparticle immunoassay methods. RESULTS: The diagnostic sensitivity (SE) value was the highest for HE4 and MMP-7 (78.0%). The diagnostic specificity (SP) for M-CSF, VEGF and MMP-9 was 95.2%, 95.2% and 95.7%, respectively. The highest positive predictive value (PPV) for M-CSF and MMP-9 was ~84.6% and negative predictive value (NPV) for MMP-7 and HE4 was ~87.6%. The biggest areas under the ROC curve were obtained for the combination of VEGF, MMP-7 or MMP-9 with HE4+CA125 (0.9130-0.9234), but not for CA125+HE4 (0.8260). CONCLUSION: Our research confirms the validity of combining classic markers with new markers to improve the diagnostic power of CA125 and HE4.

Diagnostic effectiveness of soluble triggering receptor expressed on myeloid cells-1 in sepsis, severe sepsis and septic shock.

INTRODUCTION: Sensitivities and specificities of clinical signs and biochemical tests in sepsis diagnosis are not satisfactory. The aim of the study was to assess the diagnostic usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in sepsis, severe sepsis and septic shock against interleukin-6 (IL-6), C-reactive protein (CRP) and procalcitonin (PCT). MATERIAL AND METHODS: A prospective, observational study was conducted in 85 adults with sepsis, severe sepsis or septic shock and 22 with non-infective systemic inflammatory response syndrome (NI-SIRS). Serum levels of sTREM-1, CRP, PCT and IL-6 were measured on admission. RESULTS: Median serum sTREM-1 concentrations were higher in severe sepsis (540 pg/ml) and septic shock (536 pg/ml) in comparison with NI-SIRS patients (p < 0.05). There were no differences in sTREM-1 levels between NI-SIRS and sepsis. Similarly, CRP, PCT and IL-6 were significantly elevated in patients with severe sepsis and septic shock in comparison with NI-SIRS. The receiver operating characteristic curve analysis for diagnosis of severe sepsis showed higher discriminative value for CRP and IL-6 (AUC = 0.909, 95% CI: 0.829-0.99 and AUC = 0.854, 95% CI: 0.728-0.980, respectively) than sTREM-1 (AUC = 0.733, 95% CI: 0.596-0.870). In septic shock the highest AUC was found for CRP (AUC = 0.938, 95% CI: 0.872-1.0), lower for IL-6 (AUC = 0.869, 95% CI: 0.751-0.987), PCT (AUC = 0.828, 95% CI: 0.71-0.945) and sTREM-1 (AUC = 0.705, 95% CI: 0.553-0.856). CONCLUSIONS: Serum level of sTREM-1 has lower effectiveness as a diagnostic biomarker in severe sepsis and septic shock, in comparison with CRP and IL-6.

Concentration of Selected Elements and Antioxidative Potential in a Group of Males Working in the Metal Industry: Elements And Antioxidative Potential In Men.

The purpose of this study was to show that some elements have a proven antioxidative effect and are essential for the proper development and functioning of the human body. The study also assessed the concentration of selected elements and total antioxidant status (TAS) in a group of male inhabitants of Bialystok, Poland, who are professionally active in the metal industry. The study group comprised 163 men aged 55-64 years. The concentration of the analyzed elements was determined using flame (Zn and Cu) and electrothermal (Se, Cd, and Pb) atomic absorption spectrometry. Spectrophotometric test kits were used to assay the TAS and glutathione reductase (GR) activity in serum. The results suggested the mean concentration of Se in serum was 54.04 ± 12.10 µg/L, which was below the reference range. A significant negative correlation was observed between the concentration of Se in the serum and Pb and Cd concentrations in the whole blood of the studied men. The concentrations of the other elements, antioxidant potential, and GR activity were within the reference range. A statistically significant positive correlation was observed between Pb and Cd, indicating combined exposure and a considerable negative correlation between lead and selenium as well as between lead and TAS. Selenium and TAS are likely to modify the adverse effects of Pb in the bodies of the studied men. The results indicate that it is necessary to constantly monitor men who are occupationally exposed to heavy metals, maintain a healthy lifestyle, and introduce effective preventive measures at a local level.

Matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor 2 (TIMP-2) in pancreatic cancer (PC).

OBJECTIVES: The incidence rate of pancreatic cancer (PC) is similar to mortality rate, thus searching specific tumor biomarkers of PC is sorely needed. Matrix metalloproteinase-2 (MMP-2) and the imbalance between MMP-2 and its tissue inhibitor (TIMP-2) play a critical role in tumor progression. We aim to assess the diagnostic and prognostic usefulness of serum MMP-2 and TIMP-2 as potential biomarkers in comparison to well-established tumor markers of PC (CA 19-9, carbohydrate antigen 19-9 and CEA, carcinoembryonic antigen). RESULTS: We indicated the significant differences between serum TIMP-2 concentrations in PC patients, CP individuals and control group. The diagnostic sensitivity of TIMP-2 was the highest among all proteins tested and increased up to 96% in combined measurement with MMP-2. The area under ROC curve (AUC) for TIMP-2 was larger than for MMP-2, but lower than for classical tumor markers. METHODS: Presented study comprised on 226 subjects, including 92 PC patients, 43 chronic pancreatitis (CP) patients and 91 healthy volunteers. The serum concentrations of these proteins were measured using immunological methods. CONCLUSIONS: Presented findings suggest higher usefulness of TIMP-2 than MMP-2 as potential biomarker in the diagnosis of PC patients, however more studies on large population are needed to support our results.

Diagnostic power of VEGF, MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve.

PURPOSE: Vascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group. MATERIALS/METHODS: The study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay. RESULTS: Tissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II-75%, III-85%, IV-70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: 'vascular endothelial growth factor + CA15-3'. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases. CONCLUSIONS: The combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.

Human Plasma Levels of VEGF-A, VEGF-C, VEGF-D, their Soluble Receptor - VEGFR-2 and Applicability of these Parameters as Tumor Markers in the Diagnostics of Breast Cancer.

VEGF family members are important factors in promoting angio- and lymphangiogenesis. The aim of this study was to investigate concentrations, diagnostic utility and power of VEGF-A, VEGF-C, VEGF-D and VEGFR-2 in comparison to CA15-3 in breast cancer (BC) patients. The study included 120 BC patients and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of tested parameters were determined by ELISA, CA15-3 by CMIA. Concentrations of all parameters showed statistical significance when compared BC patients to controls. VEGF-D showed the highest SE (82.50%) in total BC group. Highest SP and PPV in total BC group showed VEGF-A(76.67%;84.78%,respectively), but lower than CA15-3. Highest NPV showed VEGF-C(52.33%), but it was lower than CA15-3. VEGF-C was also the best parameter which had statistically significant AUC in total cancer group (0.7672), but also stages I(0.7684) and II(0.7772). In the total group of BC almost all tested parameters showed statistically significant AUC, but a maximum range was obtained for the combination of VEGF-C + CA15-3(0.8476). The combined analysis of tested parameters and CA15-3 resulted in increase in SE and AUC values, which provides hope for developing a new panel of biomarkers that may be used in the diagnosis of BC in the future.

The relationships among monocyte subsets, miRNAs and inflammatory cytokines in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI. METHODS: In eighteen consecutive AMI patients (mean age 56.78 ± 12.4 years, mean left ventricle ejection fraction - LVEF: 41.9 ± 9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice - on admission and after 19.2 ± 5.9 weeks of follow-up. Measurements were also performed among healthy volunteers. RESULTS: AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4-79.04] vs. 84.35% [IQR: 81.2-86.7], p = 0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14-16.64] vs. 5.87% [IQR: 4.48-8.6], p = 0.37 and median 5.99% [IQR: 3.39-11.5] vs. 5.26% [IQR: 3.62-6.2], p = 0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4-11.27] vs. 1.84 [IQR: 0.87-2.53], p = 0.003; miR-155: median 25.35 [IQR: 8.17-43.15] vs. 8.4 [IQR: 0.08-16.9], p = 0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p = 0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines - IL-6 and TNF-α. CONCLUSIONS: These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium.

Plasma levels of VEGF-A, VEGF B, and VEGFR-1 and applicability of these parameters as tumor markers in diagnosis of breast cancer.

The VEGF family members are important factors in promoting angiogenesis and lymphangiogenesis in malignant processes. The aim of this study was to investigate plasma concentrations of VEGF-A, VEGF-B and their soluble VEGFR-1 receptor and their diagnostic utility and potency as compared to CA 15-3 in breast cancer patients and in relation to the control group. The study included 120 breast cancer patients and 60 control patients. Plasma levels of tested parameters were determined with ELISA and CA 15-3 levels were determined with CMIA. Concentrations of all tested parameters in breast cancer patients showed statistically significant difference when compared to the control groups (benign breast tumor patients and/or healthy women). VEGF-B showed the highest values of sensitivity (Sn) and predictive value of a negative test result (NPV) in total BC group (90% and 66.7%, respectively) and, more importantly, in stages I-II of BC (SE: 86.8%; 92.7%, NPV: 82.8%; 88.9%, respectively). Among all parameters tested, VEGF-A showed the highest specificity (Sf) (76.7%) and predictive value of a positive test result (PPV) (84.8%), yet they were lower than for CA 15-3. VEGF-A was also the best parameter that had statistically significant Area Under Curve (AUC) in stages I (0.678) and II (0.768). In the whole group of BC patients all parameters tested showed statistically significant AUC, but the maximum range was obtained for the combination of VEGF-A and CA 15-3 (0.817). The combined analysis of the studied parameters and CA 15-3 resulted in an increase in sensitivity and AUC values, which provides hope for developing a new panel of biomarkers that may be used in BC diagnosis in the future.

Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase Activity in the Serum of Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND/AIM: Non-alcoholic liver disease (NAFLD) is one of the most common causes of chronic liver disease, and its prevalence and medical importance is increasing worldwide. Changes in enzyme activity in liver cells in various liver diseases are reflected by an increase in serum enzymatic activity. For example, alcohol dehydrogenase activity (ADH) and aldehyde dehydrogenase (ALDH), that occur in the liver in large quantities, correlate with disease severity during cirrhosis. In the current study, the activity of ADH isoenzymes and ALDH in the serum of patients with NAFLD was investigated. MATERIALS AND METHODS: Serum samples were collected for routine biochemical studies from 55 patients with NAFLD patients and from 50 healthy individuals. Class I and II ADH and ALDH activity were measured by spectrofluorometric method. Photometric methods were used to measure ADH class III, IV and total ADH activity. RESULTS: Total ADH activity was significantly higher in non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) than in healthy individuals (44 and 48.5% activity, respectively). The median total activity of ADH was 1,164 mU/l in patients with NAFLD, 1,258 mU/l in NASH and 648 mU/l in the control group. The increase in ADH class I and II isoenzyme in serum of patients with NAFL and NASH was statistically significant. The activity of ADH I, ADH II, and total ADH significantly increased with increasing disease progression. CONCLUSION: The activity of isozymes of class I and II alcohol dehydrogenase in patients with NAFLD is enhanced and appears to be due to the release of these isoenzymes from damaged hepatocytes.

Plasma levels and diagnostic utility of macrophage-colony stimulating factor, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 as tumor markers in cervical cancer patients.

Macrophage-colony stimulating factor, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play an important role in malignant processes. The aim of this study was to investigate the diagnostic power of those parameters (serological biomarkers) in comparison to cancer antigen 125 and squamous cell carcinoma antigen in cervical cancer patients and in relation to the control groups. The study included 100 cervical cancer patients, 50 patients with cervical ectropion and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, cancer antigen 125, and squamous cell carcinoma antigen by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases p < 0.05). In stage I of cancer only medial supraclavicular fossa and tissue inhibitor of metalloproteinase-1, in stage II all the tested parameters and cancer antigen 125, and in stage III + IV macrophage-colony stimulating factor, matrix metalloproteinase-9, and cancer antigen 125 showed statistical significance when compared to the healthy volunteers group. Macrophage-colony stimulating factor showed the highest value of sensitivity from all tested parameters (I: 56.25%, II: 72.73%, III + IV: 77.14% and 69% in total cervical cancer group). The highest specificity was obtained by matrix metalloproteinase-9 (94%). Positive predictive values were highest also for matrix metalloproteinase-9 (I: 82.35%, II: 84.21%, III + IV: 88% and 94.55% in total cervical cancer group), negative predictive values for macrophage-colony stimulating factor (I: 75.44%, II: 82.69%, III + IV: 87.5% and 58.11% in total cervical cancer group) and tumor markers. In the total cervical cancer group, all tested parameters showed statistically significant areas under receiver operating characteristic curve, but maximum range was obtained for the combination macrophage-colony stimulating factor + squamous cell carcinoma antigen (0.8723). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and areas under receiver operating characteristic curve values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of cervical cancer in the future.

Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis.

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.

ROC analysis of selected matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in psoriatic patients.

INTRODUCTION: Psoriasis is a common, chronic inflammatory disease characterised by typical scaly skin lesions. The role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis and development of this condition have been repeatedly emphasised in available literature. AIM: ROC analysis of selected MMPs (MMP-2, MMP-3, MMP-9, MMP-12, TIMP-2) and TIMPs (TIMP-2, TIMP-3) in psoriasis patients. The area under the ROC curve (AUC) indicates the clinical usefulness of a biomarker and its diagnostic power. MATERIAL AND METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMPs and TIMPs were determined using the enzyme-linked immunosorbent assay (ELISA) while Psoriasis Area and Severity Index (PASI) was used to define disease advancement. RESULTS: In the total psoriasis patients group, the largest area under the ROC curve was obtained for TIMP-3. After the division of the total group based on disease severity, the highest AUC of all tested parameters was observed for patients with mild disease severity and subgroup Ia for TIMP-3, for subgroup Ib for MMP-12, and for individuals with moderate disease severity for MMP-2. The combined analysis of all tested parameters showed an increase in AUC values in the total group examined as well as in all groups of disease severity. CONCLUSIONS: These results indicate the usefulness and high diagnostic power of TIMP-3 in early detection of psoriasis. Additionally, the combination of all tested parameters appeared to be a valuable biomarker panel for the analysed disease.

The Activity of Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in the Sera of Patients with Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a progressive inflammatory hepatopathy and an important cause of end-stage liver. The liver cells' destruction is reflected by increased activity of different enzymes in the serum. These enzymes include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and exist mainly in the liver. In this study we investigated the activity of alcohol dehydrogenase and its isoenzymes and the total activity of ALDH in the sera of patients with autoimmune hepatitis. METHODS: Serum samples were taken for routine biochemical investigation from 32 patients with autoimmune hepatitis and from 40 healthy subjects. Class I and II of ADH and ALDH activity was measured by the spectrofluorometric method. For measurement of class III ADH and total ADH activity we employed the photometric methods. RESULTS: The activity of the class I ADH isoenzyme was significantly higher in the sera of patients with autoimmune hepatitis. The median activity of this isoenzyme in the patients group was approximately 63% (3.94 mU/L) higher than the control level (1.46 mU/L). For this reason, the total ADH activity was also significantly increased. The activities of other ADH isoenzymes and ALDH tested were unchanged. CONCLUSIONS: The activity of total ADH and class I isoenzymes in the sera of patients with autoimmune hepatitis is increased, and it seems to be caused by the release of alcohol dehydrogenase from damaged liver cells.