Plasma levels and diagnostic utility of VEGF, MMP-2 and TIMP-2 in the diagnostics of breast cancer patients.

OBJECTIVE: We investigated plasma levels and diagnostic utility of vascular endothelial growth factor VEGF, matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2) in comparison to cancer antigen 15-3 (CA 15-3). METHODS: Plasma levels of tested parameters were determined using enzyme-linked immunosorbent assay (ELISA) while CA 15-3 with chemiluminescent microparticle immunoassay (CMIA). RESULTS: The plasma levels of VEGF, TIMP-2 showed significantly higher than CA 15-3 values of the diagnostic sensitivity, the predictive values of positive and negative test results (PPV, NPV) and the area under the receiver-operating characteristics (ROC) curve (AUC) in early stages of breast cancer (BC). The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, NPV and AUC, especially in the combination with VEGF (83%; 72%; 0.888) and TIMP-2 (83%; 72%; 0.894). The highest values were obtained for combination of all three parameters (93%; 85%; 0.923). CONCLUSIONS: These findings suggest the usefulness of the tested parameters in the diagnosis of BC, especially VEGF and TIMP-2 with CA 15-3 in early stages of BC, which could be a new diagnostic panel.

[The plasma levels and diagnostic utility of matrix metalloproteinase-9 and CA 125 in cervical cancer patients]. / Ocena stezenia i przydatnosci diagnostycznej metaloproteinazy-9 i CA 125 w osoczu chorych na raka szyjki macicy.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, involved in the degradation of extracellular matrix components. The physiological function of MMP-9 is associated with regulation of immune processes, embryogenesis, reproduction and wound healing. MMP-9 also plays a critical role in tumor invasion, degrading the basement membrane, what is observed in different types of cancers: breast, gastrointestinal, and gynecological. AIM: The aim of this study was to investigate the plasma levels and diagnostic utility of MMP-9 and CA 125 in cervical cancer patients. MATERIALS AND METHODS: The study included 72 patients with cervical cancer and 24 healthy women. Plasma levels of the MMP- 9 was determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 - by chemiluminescent microparticle immunoassay (CMIA). RESULTS: This studies have shown increase levels of MMP-9 and CA 125 in cervical cancer patients compared to health control group. In addition, the MMP-9 concentration increased with the clinical stage of tumor. The sensitivity and specificity of MMP-9, positive and negative predictive value, were higher or equal than CA 125, but this parameter can not be used as a single marker. Our studies of MMP-9 have shown a high utility to the exclusion of cancer, similarly to CA 125. The combined analysis of MMP-9 and CA 125 significantly increased the ability to diagnose a cervical cancer and the possibility exclusion of cancer. CONCLUSIONS: MMP-9 has shown the usefulness in the diagnosis of cervical cancer, but only in the combined analysis with CA 125, as a new diagnostic panel.

Diagnostic Power of Vascular Endothelial Growth Factor and Macrophage Colony-Stimulating Factor in Breast Cancer Patients Based on ROC Analysis.

Breast cancer (BC) is the most common malignancy in women. Vascular endothelial growth factor (VEGF) has been described as an important regulator of angiogenesis which plays a vital role in the progression of tumor. Macrophage colony-stimulating factor (M-CSF) is a cytokine whose functions include regulation of hematopoietic lineages cells growth, proliferation, and differentiation. We investigated the diagnostic significance of these parameters in comparison to CA15-3 in BC patients and in relation to the control group (benign breast tumor and healthy women). Plasma levels of the tested parameters were determined by ELISA and CA15-3 was determined by CMIA. VEGF was shown to be comparable to CA15-3 values of sensitivity in BC group and, what is more important, higher values in early stages of BC. VEGF was also the only parameter which has statistically significant AUC in all stages of cancer. M-CSF has been shown to be comparable to CA15-3 and VEGF, specificity, and AUC values only in stages III and IV of BC. These results indicate the usefulness and high diagnostic power of VEGF in the detection of BC. Also, it occurred to be the best candidate for cancer diagnostics in stages I and II of BC and in the differentiation between BC and benign cases.

Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3, MMP-9 and TIMP-3 in psoriatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be associated with the pathogenesis and spread of psoriatic disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9 and TIMP-3 in plaque psoriasis patients prior to and following a course of ultraviolet B narrowband treatment with respect to disease advancement. METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index was used to define disease advancement. RESULTS: Plasma levels of MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients compared to healthy individuals. A course of ultraviolet B narrowband treatment resulted in a significant decline in the studied metalloproteinases. Furthermore, the concentration of selected tissue inhibitors was negatively correlated with baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

AIM: The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. MATERIALS AND METHODS: Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. RESULTS: Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. CONCLUSION: This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

Plasma levels of MMP-7 and TIMP-1 in laboratory diagnostics and differentiation of selected histological types of epithelial ovarian cancers.

BACKGROUND: MMP-7 and TIMP-1 may play a role in the pathogenesis of cancer disease. In this study we investigated plasma levels of selected metalloproteinase and its tissue inhibitor in comparison to plasma levels of the commonly accepted tumor markers (CA 125 and HE4) in selected histological types of epithelial ovarian cancer patients as compared to control groups: patients with a benign ovarian tumor and healthy subjects. Plasma levels of MMP-7 and TIMP-1 were determined using ELISA, CA 125 and HE4 - by CMIA methods. RESULTS: Plasma levels of all biomarkers studied were significantly higher in ovarian cancer patients as compared to both control groups. MMP-7 demonstrated comparable to HE4 or CA125 values of diagnostic sensitivity (SE: 61%; 68%; 58%, respectively), specificity (SP: 95%; 95%; 98%, respectively), positive (PPV: 93%; 96%; 98%, respectively) and negative predictive values (NPV: 61%; 66%; 60%, respectively) in the groups tested. The combined use of the aforementioned biomarkers resulted in a further increase in diagnostic criteria and AUC, especially in the early stages of the disease. CONCLUSIONS: These findings suggest the usefulness of combining MMP-7 with CA 125 and HE4 in the diagnosis of epithelial ovarian cancer as a new tumor marker panel.

Plasma levels and diagnostic utility of VEGF, MMP-9, and TIMP-1 in the diagnosis of patients with breast cancer.

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play a role in the pathogenesis of cancer disease. We investigated their levels and utility in comparison to cancer antigen (CA) 15-3 in patients with breast cancer (BC) and in relation to the control groups. The study included 100 women with BC, 50 patients with benign breast tumor, and 50 healthy women. The plasma levels of the tested parameters were determined using enzyme-linked immunosorbent assay, while CA 15-3 with chemiluminescent microparticle immunoassay. The results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between groups of patients with BC and healthy patients or patients with benign breast tumor. The plasma levels of VEGF and tissue inhibitor of metalloproteinase-1 were significantly higher in advanced tumor stages. The tested parameters were comparable to CA 15-3 values of the diagnostic sensitivity, specificity, the predictive values of positive and negative test results, and the area under the receiver-operating characteristic curve. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, negative predictive value, and area under the receiver-operating characteristic curve, especially in the combination of VEGF with tumor marker (84%, 73%, 0.888, respectively). These findings suggest the usefulness of the tested parameters in the diagnosis of BC. VEGF, especially in combination with CA 15-3, showed the highest usefulness in the diagnosis of early BC.

Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer.

BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

Therapy of psoriasis with narrowband ultraviolet-B light influences plasma concentrations of MMP-2 and TIMP-2 in patients.

BACKGROUND: Matrix metalloproteinases (MMPs), which show a significant ability to cleave the components of extracellular matrix, and tissue inhibitors of metalloproteinases (TIMPs), which slow down the activity of those enzymes, may be implicated in the pathogenesis and spread of psoriatic disease. This study aims to analyze plasma levels of MMP-2 and TIMP-2 in plaque psoriasis patients before and after the course of narrowband ultraviolet-B (NBUVB) therapy with respect to disease advancement. PATIENTS AND METHODS: A total of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were enrolled into the study. Plasma levels of MMP-2 and TIMP-2 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index (PASI) was used to define the disease advancement. RESULTS: The results showed increased plasma levels of MMP-2 and TIMP-2, but this change was significant only in case of MMP-2 in total psoriatic group compared to healthy subjects. Moreover, there was an increase in the concentrations of chosen factors with an increase in the severity of the disease. The NBUVB therapy causes a decline in the concentration of the analyzed enzyme and its inhibitor, although this change was statistically significant in the total psoriatic group only in case of MMP-2. There was also a positive correlation between MMP-2, TIMP-2, and PASI score value. CONCLUSION: Our study highlights a possible important role of MMP-2 in the activity of psoriasis and clearance of disease symptoms. Moreover, plasma MMP-2 seems to be a valuable psoriasis biomarker.