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 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.

Improvements in the perception of facial attractiveness following surgical aesthetic treatment; study based on online before and after photos.

BACKGROUND: Aesthetic surgery procedures such as lip augmentation, eyelid correction, face-lifting, or Botox treatment for lines and wrinkles are an important part of cosmetic surgery. OBJECTIVES: The aim of the study was to estimate improvement in appearance following plastic surgery using modern collective intelligence methods of validation. METHODS: A total of 108 photographs showing 54 patients prior to and following cosmetic surgery were downloaded from Internet web presentations of several unnamed plastic surgeons. The same number of photographs depicted each of the four investigated areas of treatment-26 lip enhancement, 26 blepharoplasty, 26 face-lift, 26 botulinum toxin injection. Attractiveness of depicted individuals was assessed by 167 observers. Each photograph was judged separately. RESULTS: Blepharoplasty produced the most remarkable improvement in attractiveness amounting to 32.79 (SD ± 26.35). Improvement following Botox treatment stood at 30.29 (SD ± 24.55), whereas face-lifting produces improvement of 28.70 (SD ± 22.76). Improvement following lip augmentation was estimated at 12.70 (SD ± 29.8). Highest Spearman's rank correlation coefficient was obtained for face-lift and Botox (0.24 and 0.22, respectively). CONCLUSIONS: Blepharoplasty, face-lifting, and Botox deliver a significant improvement in facial attractiveness. Additionally, face-lifting and Botox are distinguished by a high level of reproducibility. Our results indicate that lip augmentation is a treatment with a statistically significant, but less marked improvement in attractiveness.

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.

Impact of face proportions on face attractiveness.

BACKGROUND: Proportions of face components appear to play a role in facial attractiveness. AIMS: The aim of the study was to establish the best proportions of face components in relation to whole face shape for facial attractiveness. METHODS: Only one face component (eye, nose, or lips) of a model in a series of photographs was altered using a computer program. Alterations consisted of size reduction or augmentation by 5% or 10%. Each photograph depicted a particular face component altered to either 90%, 95%, 100%, 105%, or 110% of its original size. Collages of photographs were shown to 167 individuals (male and female) for a fixed period of 7 seconds. Their task was to indicate the most attractive photograph of a model in a presented collage. RESULTS: In total, 48.1% of individuals preferred enhanced eyes both in males and females. We found that the preferred mean eye size in women was statistically significantly higher than that in men. In total, 64.8% of respondents preferred reduced nose proportions in women (27.5% found a reduction to 90% of the original size more attractive while 37.3% preferred a reduction to 95%). It was demonstrated that the preferred mean nose size was statistically significantly lower in females in comparison with males. Respondents expressed a greater preference for nose reduction in women in comparison with men. 38.4% of respondents (in regard to both male and female mouth) preferred reduced mouth. 40.7% of respondents preferred reduced mouth in the female model. CONCLUSIONS: Our work delivers statistically significant evidence that facial attractiveness increases together with the enlargement of the uncovered eye surface as well as the reduction in nose and lip size. Data were obtained using modern collective intelligence methods of validation. Written consent was obtained from all study participants.

Plasma Chemokine CCL2 and Its Receptor CCR2 Concentrations as Diagnostic Biomarkers for Breast Cancer Patients.

The aim of this study was to investigate plasma levels and applicability of CCL2, CCR2, and tumor marker CA 15-3 in breast cancer (BC) patients and in relation to the control groups: patients with benign breast tumor and healthy subjects. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 by Chemiluminescent Microparticle Immunoassay (CMIA). The median levels of CCL2 in entire group of BC were significantly higher compared to the control groups, similarly as median levels of CA 15-3. CCR2 is a negative marker whose levels were significantly lower in BC group compared to healthy women. The concentration of CCL2 in BC increases with advancing tumor stage, while a median level of CCR2 decreases with advancing stage. CCL2 showed the highest value of sensitivity (SE) (64.95%) in entire BC group and also in early stages of disease. The highest specificity (SP) was obtained by CA 15-3 (85.71%). The area under the ROC curve (AUC) of CCR2 (0.7304) was the largest of all the tested parameters (slightly lower than CA 15-3) in the entire BC group, but a maximum range was obtained for the combination of all tested parameters with CA 15-3 (0.8271). In early stages of BC the highest AUC of all tested parameters was observed in CCL2 or CCR2 (stage I: 0.6604 and 0.6564; respectively; stage II: 0.7768, respectively, for CCR2). The findings of this study suggest that there may be applicability of CCL2, CCR2 in diagnosis of BC patients, particularly in conjunction with CA 15-3.

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.

Immunohistochemical expression of Fascin-1 in colorectal cancer in relation to clinical and pathological parameters.

INTRODUCTION: Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 ex-pression and clinical-pathological parameters. MATERIAL AND METHODS: The study material included postoperative samples (tumor and unchanged colon tissue) ob-tained from 51 CRC patients. Fascin-1 expression was assessed in the paraffin sections by immunohistochemistry. RESULTS: A statistically significant correlation was found between the histological type of cancer and the expres-sion of Fascin-1 (p = 0.012). Increased expression of Fascin-1 in CRC was more frequent in adenocarcinoma type without the mucosal component with a better prognosis and decreased expression of this protein correlated with infiltration of cancer cells to blood and lymphatic vessels (p = 0.038). CONCLUSIONS: Our findings indicate a potential role of Fascin-1 in the pathogenesis of colon cancer; however, further studies will show whether this protein plays a role in the infiltration of colorectal cancer cells.

[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.