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Context: Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis., Objective: This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity, total antioxidant capacity [TAC], and sortilin), as potential indicators of angioinvasion in PTC., Design: A cross-sectional study involving 50 angioinvasive patients with PTC (study group) and 30 patients with PTC with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion., Setting: Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context., Patients or Other Participants: Participants included patients with PTC, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded., Intervention(s): Serum biomarkers were measured to evaluate their association with PTC angioinvasion., Main Outcome Measure(s): Primary outcome measures included serum levels of 8-OHdG, total oxidative capacity, TAC, and sortilin., Results: Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, whereas TAC showed a notable decrease (all P < .01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high area under the curve value (0.963) for angioinvasion discernment., Conclusion: Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients' survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients.

The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients' plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I - 0.7089; stage II - 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC., Competing Interests: The authors declare no conflict of interest.

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing., Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation-C-reactive protein (CRP)., Patients and Methods: The study comprised 64 subjects - 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods., Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV -ve ) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk., Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk.

Precision medicine (PM) means the customization of healthcare with decisions and practices adjusted to the individual patient. It includes personalized diagnostics, patients' sub-classification, individual treatment selection and the monitoring of its effectiveness. Currently, in oncology, PM is based on the molecular and cellular features of a tumor, its microenvironment and the patient's genetics and lifestyle. Surprisingly, the available targeted therapies were found effective only in a subset of patients. An in-depth understanding of tumor biology is crucial to improve their effectiveness and develop new therapeutic targets. Completion of genetic information with proteomics and metabolomics can give broader knowledge about tumor biology which consequently provides novel biomarkers and indicates new therapeutic targets. Recently, metabolomics and proteomics have extensively been applied in the field of oncology. In the context of PM, human studies, with the use of mass spectrometry (MS) which allows the detection of thousands of molecules in a large number of samples, are the most valuable. Such studies, focused on cancer biomarkers discovery or patients' stratification, are presented in this review. Moreover, the technical aspects of MS-based clinical proteomics and metabolomics are described., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal-Wallis test and confirmed by the post hoc Dwass-Steele-Critchlow-Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve-ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.

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.

This study is the first to assess the diagnostic utility of redox biomarkers in patients with colorectal cancer (CRC). Antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), uric acid (UA), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS), ferric reducing ability (FRAP)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were measured in serum/plasma samples of 50 CRC patients. The activity of SOD was significantly higher whereas the activity of CAT, GPx and GR was considerably lower in CRC patients compared to the control group (p < 0.0001). Levels of UA, TOS, and OSI and concentrations of AGE, AOPP, and MDA were significantly higher, and the levels of GSH, TAC, and FRAP were considerably lower in CRC patients compared to the healthy controls (p < 0.0001). AUC for CAT with respect to presence of lymph node metastasis was 0.7450 (p = 0.0036), whereas AUC for MDA according to the depth of tumour invasion was 0.7457 (p = 0.0118). CRC is associated with enzymatic/non-enzymatic redox imbalance as well as increased oxidative damage to proteins and lipids. Redox biomarkers can be potential diagnostic indicators of CRC advancement., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article.

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.

Background: It is estimated that in developed countries the incidence rate of pancreatic cancer (PC) will continue to rise and by 2020 will be the second most fatal cancer. The mortality of PC patients closely parallels the incidence rate, as this malignancy remains asymptomatic until it reaches an advanced stage of disease. Thus, novel biochemical markers that improve the management of PC patients are necessary. The aim of the work that follows is to investigate whether selected inflammatory mediators might be used in the diagnosis of PC, with the aim of improving the prognosis for PC patients., Methods: We performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database., Results: It has been proved that certain inflammatory mediators might be involved in tumor progression, such as growth, proliferation, migration and angiogenesis of tumor cells. In the present review, we summarized and referred to a number of original papers concerning the clinical significance of selected cytokines and specific inflammatory proteins such as C-reactive protein, as well as of various matrix metalloproteinases and their tissue inhibitors, as potential biomarkers for PC in comparison to well-established tumor markers for this malignancy., Conclusion: Presented proteins might be potential biomarkers in the diagnosis and progression of PC., (Copyright © 2019 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Thyroid cancer (TC) is a common malignancy of the endocrine system. The global incidence of TC has increased dramatically in recent years. The available tumor biomarkers are not specific to TC and therefore finding new markers which could be helpful in the diagnostic process, prognosis and treatment of TC patients is a great challenge facing present and future researchers. Chemokines are small chemotactic proteins which play a significant role in the migration of leukocytes to many sites of the inflammatory process. It has been suggested that these molecules are able to promote cancer development by mediating inflammation. This paper presents the general structure of chemokines and their receptors as well as their potential significance in TC. The final aspect of this review is a summary of current knowledge and research results concerning the potential significance of selected chemokines and their specific receptors as candidates for novel tumor markers of TC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Glucocorticosteroids, including dexamethasone (Dex), are commonly used to control tumor-induced edema in the brain tumor patients. There are increasing evidences that immunosuppressive action of Dex interferes with immune surveillance resulting in lower patients overall survival; however, the mechanisms underlying these actions remain unclear. Changes in the expression of sialic acids are critical features of many cancers that reduce their immunogenicity and increase viability. Sialoglycans can be recognized by CD33-related Siglecs that negatively regulate the immune response and thereby impair immune surveillance. In this study, we analysed the effect of Dex on cell surface sialylation pattern and recognition of these structures by Siglec-F receptor in poorly immunogenic GL261 and immunogenic SMA560 glioma cells. Relative amount of α2.3-, α2.6- and α2.8-linked sialic acids were detected by Western blot with MAA (Maackia amurensis) and SNA (Sambucus nigra) lectins, and flow cytometry using monoclonal antibody anti-PSA-NCAM. In response to Dex, α2.8 sialylation in both, GL261 and SMA560 was increased, whereas the level of α2.3-linked sialic acids remained unchanged. Moreover, we found the opposite effects of Dex on α2.6 sialylation in poorly immunogenic and immunogenic glioma cells. Furthermore, changes in sialylation pattern were accompanied by dose-dependent effects of Dex on Siglec-F binding to glioma cell membranes as well as decreased α-neuraminidase activity. These results suggest that glucocorticosteroid-induced alterations in cell surface sialylation and Siglecs recognition may dampen anti-tumor immunity, and participate in glioma-promoting process by immune cells. Our study gives new view on corticosteroid therapy in glioma patients.

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.

The aim of this study was to assess the expression of MMP-9 and TIMP-1 in cancerous tissue as well as in the serum and plasma concentrations of these proteins in patients with laryngeal cancer and compare the results to the inflammatory reaction in healthy subjects. Twenty-seven patients who were diagnosed with laryngeal carcinoma and selected for total laryngectomy were included in the study group. MMP-9 and TIMP-1 expression in tissues was assessed using immunohistochemical assays. Immunoenzymatic ELISA methods were used to measure MMP-9 and TIMP-1 concentrations in serum and plasma. MMP-9 and TIMP-1 were identified in tumor cells and in the tumor stroma compartment, as well as in macroscopically healthy mucous membrane. MMP-9 expression was more significant in tumor stroma than in the perimatrix of the mucous membrane ( p = 0.047). TIMP-1 expression was significantly higher in the matrix and perimatrix of the mucous membrane than in cancer tissue ( p = 0.0093) and the tumor stroma compartment ( p < 0.0001). Expression of TIMP-1 was observed more frequently in tumors without infiltrated lymph nodes ( p = 0.009). Serum concentrations of MMP-9 and TIMP-1 as well as plasma TIMP-1 concentration were significantly higher in the study group than in the control group ( p = 0.0004, p = 0.002, and p = 0.0001, respectively). A significantly higher TIMP-1 level in plasma was found in patients with poorly differentiated tumors compared to G1 and G2 ( p = 0.046). MMP-9/TIMP-1 rate in serum was significantly higher in the study group than in the control group. The balance between the level of MMP-9 and TIMP-1 is disrupted in laryngeal cancer. The significant correlation between TIMP-1 expression and the presence of lymph node metastases, as well as that between TIMP-1 plasma concentration and stage of cancer histological differentiation, might indicate the importance of this molecule as a prognostic factor during carcinogenesis.

Background: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals., Methods: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method., Results: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration., Conclusions: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.

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.

Pancreatic carcinoma is a highly malignant disease associated with an extremely poor prognosis, which is caused by late presentation, aggressive invasion and metastases, as well as the detection of pancreatic carcinoma in its advanced stages. Thus, better understanding of the tumour biology of this malignancy is sorely needed to improve the clinical outcome. A great challenge for the medical practice is finding a new biomarker of pancreatic carcinoma that will be helpful in diagnosis, in prognosis and in making clinical decisions, including the assessment of patients' response to therapy. It is suggested that selected chemokines and their specific receptors play an important role in tumour progression, such as tumour growth, angiogenesis, proliferation and development of metastasis. In the present review, general characteristics of chemokines and their specific receptors as well as the significance of these molecules in tumour development are described. The crucial issue of this review is to summarise the importance of various chemokines and their specific receptors in pancreatic carcinoma. Understanding the role of chemokines in the pathogenesis of pancreatic carcinoma is extremely important since these proteins may be used as a potential tool in the diagnosis and prognosis of pancreatic carcinoma patients.

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.

Context: Selectins probably participate in the interactions between platelets and other inflammatory cells in cancer invasion and metastasis formation. We assessed a potential relationship of P-, L- and E-selectin in colorectal cancer (CRC) patients in relation to tumour advancement according to TNM classification, and tumour location., Materials and Methods: The study group was composed of 53 CRC patients and 25 healthy subjects. Plasma levels of soluble P-, L- and E-selectins were measured using the immunoenzymatic method with Quantikine kits (R&D Systems, Minneapolis, MN)., Results: The mean levels of all selectins were significantly higher in CRC patients compared to healthy controls. The highest level of sP-selectin was observed in patients with metastases to the liver (stage IV), and was significantly higher than in patients without metastases (stage I/II) and with lymph node metastases (stage III), p = .02. The highest levels of sL- and sE-selectin were observed in patients with lymph node metastasis. We also found sP-selectin to be the best predictor of CRC., Conclusion: Our finding show possible involvement of tested selectins in CRC advancement and forming metastasis. Among sL- and E- selectins, P-selectin plays an important role in the progression of CRC and could be an attractive biomarker with clinical significance.

Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background/aim: The aim of this study was to investigate a potential role of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as tumor markers for prostate cancer (PCa)., Materials and Methods: Serum samples were obtained from 52 patients with PCa, 34 patients with benign prostatic hyperplasia (BPH) and 60 healthy subjects. Class III and IV of ADH and total ADH activity were measured by the photometric method. For measurement of class I and II ADH and ALDH activity, the fluorometric method was employed., Results: Significantly higher total activity of ADH, ADH III and ADH IV were found in the sera of both, PCa and BPH patients compared with healthy individuals. The diagnostic sensitivity for ADH III activity was 94.2%, specificity 100%, PPV (positive predictive value) and NPV (negative predictive value) were 100% and 95.2% respectively. Area under receiver-operating characteristics (ROC) curve for ADH III activity was 0.993., Conclusion: The results suggest a potential role of ADH III activity as a parameter included in the panel of markers for PCa., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Since angiogenesis plays an important role in the pathogenesis of ovarian cancer the aim of the study was to compare the expression of the most relevant angiogenesis-related genes in serous ovarian cancer samples. Genes were divided into 5 subgroups according to their angiogenic potential: growth factors and their receptors; cytokines/chemokines; adhesion molecules and other matrix related proteins; transcriptions factors and signaling molecules; morphogenic factors, and angiogenesis inhibitors., Materials/methods: Twenty-nine patients were involved in the study: 20 with serous ovarian cancer and 9 healthy controls. All neoplasms were confirmed by histopathological examination. Healthy ovarian control samples were obtained from women diagnosed with fibroids and had previously scheduled operations. Real-time PCR gene arrays were used to examine the expression of 84 human angiogenesis-related genes and expression of selected proteins was assessed with ELISA., Results: Significantly higher expressions of 46 genes were found in the ovarian cancer group compared to the healthy control group. By the use of ELISA we confirmed the expression of three proteins i.e.: angiopoietin-2, angiopoietin-like protein 3, and angiopoietin receptor 2. Only angiopoietin-2 and angiopoietin receptor 2 showed significant differences between ovarian cancer and healthy controls., Conclusions: Changes in the expression of selected genes associated with angiogenesis may add new information to the pathogenesis of ovarian cancer. Although the angiopoietin-2 signaling pathway may play an important role in neovascularization in ovarian cancer, the role of angiopoietin-like protein 3 is yet to be established., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer., Competing Interests: The authors have declared that no competing interest exists.

A new method for the selective determination of laminin-5 concentration using a biosensor and surface plasmon resonance imaging (SPRI) technique is presented. A biosensor based on the specific interaction of laminin-5 with rabbit polyclonal antibody was constructed. The analytically useful dynamic response range of the biosensor is between 0.014 and 0.1 ng mL(-1). The detection limit is 4 pg mL(-1). The potential influence of interferences on the SPRI signal was investigated, and the high selectivity of the biosensor was confirmed. In order to demonstrate the potential application of the biosensor, laminin-5 concentration in blood plasma was determined. The results were compared with the laminin-5 concentration obtained by the commercial enzyme-linked immunosorbent assay (ELISA) kit. A comparison of results from healthy donors obtained by SPRI measurement and ELISA indicates that they are close and shows good agreement with the data reported in the literature. The plasma samples of bladder cancer patients gave higher concentration measured with specific biosensor than by ELISA assay. The study shows the clear difference in concentration of laminin-5 in healthy humans and patients with bladder cancer. Extensive clinical studies using the newly developed method can result in an increase in the use of laminin-5 as a potential cancer marker.

In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples with an independent analytical technique. Linoleamide (p = 0.002) in addition to various acylcarnitines (p = 0.001-0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p = 0.05) and hexannoylcarnitine (p = 0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a potentially highly specific and sensitive diagnostic approach (AUC = 0.766)., Competing Interests: Authors declare no conflicts of interest.

Aim: Colorectal cancer is characterized by high morbidity and mortality in developed countries. The lack of low-cost, easy-to-use screening diagnostic methods is one of the causes of late diagnosis of colorectal cancer. Beta-glucuronidase (GLU) is a lysosomal exoglycosidase involved in degradation of glycosaminoglycans of the cell membranes and extracellular matrix of normal and cancerous colon tissues. The aim of our research was to evaluate the activity of GLU in the serum of colorectal cancer and estimate its potential value in the diagnosis of colorectal cancer., Material and Methods: Blood samples were collected from 21 patients with colorectal adenocarcinoma and 17 healthy subjects. GLU activity was determined by the colorimetric method of Marciniak et al. by measuring the amount of p-nitrophenol released from 4-nitrophenyl-beta-D-glucuronide, at λ = 405 nm., Results: We found significantly greater activity of GLU (p<0.0001) in the serum of patients with colorectal cancer, as compared to the healthy subjects. The serum GLU activity significantly differentiates patients with colorectal cancer from healthy individuals., Conclusions: Serum GLU activity has diagnostic value and may be used in the diagnosis of colon adenocarcinoma.

Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas.

Lung cancer is associated with poor prognosis. The aim of this study was to evaluate the clinical usefulness of HMGB-1 (high-mobility group protein B1) and TGF-β (transforming growth factor beta) in patients with advanced non-small cell lung cancer (NSCLC). We studied 45 patients with NSCLC prior to chemotherapy, 23 patients with Besnier-Boeck-Schaumann (BBS) disease (sarcoidosis), and 15 healthy volunteers. HMGB-1 and TGF-β levels were measured in serum and BALF samples using ELISA method. A higher serum HMGB-1 and TGF-β levels were in NSCLC patients compared with the other groups. TGF-β concentration in BALF was significantly higher in NSCLC than in healthy controls (p=0.047) but lower than in BBS (p=0.016). Serum HMGB-1 in NSCLC correlated with age and gender while its level in BALF was associated with distant metastasis. A higher levels of HMGB-1 in the serum of NSCLC patients with progressive disease was linked with shorter overall survival and disease-free survival. We found a positive correlation between HMGB-1 and TGF-β in BALF of IIIB NSCLC group and overall survival (p=0.04; p=0.003). Our findings confirmed that the measurement of HMGB-1 and TGF-β levels in serum and BALF of patients with NSCLC prior to treatment may have clinical usefulness and predict poor prognosis.

In the last decade, proteomic analysis has become an integral tool for investigation of tumor biology, complementing the genetic analysis. The idea of proteomics is to characterize proteins by evaluation of their expressions, functions, and interactions. Proteomics may also provide information about post-translational modifications of proteins and evaluate their value as specific disease biomarkers. The major purpose of clinical proteomics studies is to improve diagnostic procedures including the precise evaluation of biological features of tumor cells and to understand the molecular pathogenesis of cancers to invent novel therapeutic strategies and targets. This review briefly describes the latest reports in proteomic studies of NSCLC. It contains a summary of the methods used to detect proteomic markers in different types of biological material and their clinical application as diagnostic, prognostic, and predictive biomarkers compiled on the basis of the most recent literature and our own experience., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the ability of cancer cells to metastasize, but it can also stimulate cancer development. The aim of this study was to assess the level of TIMP-1 in serum and its expression in patients with colorectal cancer (CRC). The study group consisted of 43 patients diagnosed with colorectal cancer and 24 healthy volunteers. The level of TIMP-1 was assessed by the ELISA method while the expression of this protein was performed immunohistochemically. The concentration of TIMP-1 in the sera of colorectal cancer patients was significantly higher than in the healthy control group (p = 0.004). Higher level of TIMP-1 in the sera correlated with female gender (p = 0.045), tumor location in colon (p = 0.016), poorly differentiated tumor (p = 0.034) and higher platelet count in whole blood (p < 0.004). A positive reaction of the protein in cancer cells was observed in 31 cases and was found to correlate negatively with its reaction in peritumoral stroma (p < 0.001). According to this study, TIMP-1 protein may play an important role in cancer development. The assessment of this molecule in serum and tissue can be useful at the time of diagnosis and can help us to understand the nature of colorectal pathogenesis.

Platelet activation observed in cancer patients is associated with the release of various cytokines, including P-selectin and CD40 ligand (CD40L). We analyzed the plasma levels of sCD40L in association with adhesion molecules (sP-selectin and sVCAM-1) to check the hypothesis of a possible involvement in cancer progression.Blood samples were obtained from 59 patients with different stages of colorectal cancer (CRC) and 29 age and gender-matched control subjects. Plasma sCD40L, sP-selectin, and sVCAM-1 concentrations were measured with quantitative sandwich enzyme-linked immunoassay.All patients with CRC had significantly higher levels of sCD40L (p<0.001), sP-selectin (p<0.02), and sVCAM-1 (p<0.03), as compared to healthy subjects. The level of sCD40L significantly correlated with sP-selectin (p<0.05) in patients with distant metastases to the liver. We also observed a high negative correlation between sP-selectin and platelets count (p<0.02) in patients with lymph node metastasis. The receiver-operator curve for CRC patients indicated that the area under the curve for sCD40L was 0.915, which may indicate its high efficiency as an inflammatory marker.In our study, the sCD40L correlated with sP-selectin in patients with advanced stage of CRC, which might indicate its possible participation in metastasis formation.

Most patients with gastric cancer are diagnosed at advanced clinical stages with a high frequency of lymph node metastasis. It is very important to find novel factors for the early diagnostic and prognostic evaluation of gastric cancer. It has been shown that IGF-1R activates mitotic division and inhibits apoptosis of cancer cells through the activation of signaling MAP/ERK and PI3K/Akt-1 pathways. IGF-1R plays a role in cell transformation and maintenance of the phenotype in modified cells. Moreover, an IGF-1 receptor effect influences the processes of adhesion, migration, invasion and metastasis of tumor cells. The aim of the study was to assess the expression of IGF-1R in gastric carcinoma in correlation with selected anatomo-clinical parameters. The study enrolled a group of 49 patients treated surgically for gastric cancer. 28 patients had no lymph node metastases. The expression of the studied proteins was assessed using the immunohistochemical method. We found that the expression of IGF-1R in gastric cancer is associated with lymph node metastasis (p < 0.001), is correlated with worse prognosis and high histological malignancy grade, and is an independent predictor of survival in patients with gastric cancer (p < 0.001). IGF-1R may play an important role in tumor growth and metastasis via the lymphatic pathway.

Purpose: The aim of this study was to evaluate the correlation of the expression of Fas and Fas-L proteins in gastric carcinoma cells on the occurrence of metastases to regional lymph nodes., Material/methods: The study included 89 patients treated surgically for gastric carcinoma. The evaluated clinicomorphological parameters were verified based on both histopathological material collected at surgery and intraoperative image. Fas and Fas-L expression was evaluated immunohistochemically in the neoplastic tissue of the removed gastric tumors., Results: A statistically significant positive correlation between Fas expression in gastric carcinoma cells and the number of regional lymph nodes affected by metastases was observed (p<0.05). No such correlation was noticed with respect to Fas-L. A statistically significant correlation between the depth of neoplastic infiltration of the stomach wall (T feature) and the number of affected lymph nodes was observed (p<0.05). No statistically significant correlations in the other examined clinicomorphological features and the number of metastatic lymph nodes was observed., Conclusion: A positive Fas expression correlates with more frequent occurrence of metastases to regional lymph nodes. Determination of this protein expression in cancer cells prior to surgery may be helpful for planning the surgical procedure, especially with respect to the extent of lymph node excision., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Aim: To evaluate the expression of Bcl-xL, Bak, and Bax proteins in correlation with particular clinico-histopathological parameters, including tumor invasion front, in patients with colorectal cancer., Methods: The expression of these proteins was evaluated with the use of the immunohistochemical method in 50 primary tumors., Results: According to observations, a low expression of Bax and Bak proteins is related to the localization of the tumor in the rectum (P < 0.05 and P < 0.05 respectively), which may explain an increased incidence of colorectal cancer in this area. A positive expression of Bax protein also correlates with the presence of cancer cell infiltration to lymph and blood vessels (P < 0.05), which may suggest the participation of this protein in the early stages of colorectal cancer progression. Moreover, a positive expression of Bcl-xL protein correlated with a positive expression of Bak protein. This may suggest a greater participation of Bcl-xL protein in the inhibition of the proapoptotic Bak protein, but not the Bax protein., Conclusion: Bax protein is probably very significant in the cancerogenesis mechanism in the large intestine.

B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) are members of the tumour necrosis factor (TNF) family. They are the main survival factors for immature, naive and activated B cells. We have analysed BAFF, APRIL and TRAIL serum concentrations in 52 patients with newly diagnosed IgG multiple myeloma and 20 healthy volunteers. The values were significantly higher in the studied patients and advanced diseases, decreasing after chemotherapy, compared to the control group. It was established that BAFF as APRIL (but not TRAIL) correlated with adverse prognostic factors such as IL-6 and lactate dehydrogenase. Furthermore, higher concentrations of APRIL and BAFF (but not TRAIL) predicted a shorter progression free survival, suggesting thereby an important prognostic marker and a possible therapeutic target in myeloma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background/aim: The aim of this study was to investigate the potential role of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as tumor markers for endometrial cancer., Patients and Methods: Serum samples were obtained from 40 women with endometrial cancer, 52 with myoma uteri and 52 healthy individuals. Class III, IV of ADH and total ADH activity was measured by a photometric method and class I, II ADH and ALDH activity, by a fluorometric method., Results: The total activity of ADH and ADH class I was significantly higher in the serum of patients with endometrial cancer than in healthy individuals and patients with myoma. The diagnostic sensitivity for ADH I was 69%, specificity 77%, positive predictive value and negative predictive value were 75% and 71% respectively. The area under curve for ADH I was 0.682 and for total ADH was 0.623., Conclusion: The results suggest a potential role of ADH I as a marker for endometrial cancer.

Background: The carbohydrate alterations in sialoglycoproteins and sialoglycolipids cause the high serum concentration of sialic acid in many types of cancers. The aim of this study was to evaluate the diagnostic accuracy of total sialic acid (TSA), lipid-bound sialic acid (LSA), and free sialic acid (FSA) in patients with primary pancreatic cancers., Methods: TSA and LSA concentrations in the sera of 42 patients were measured by the enzymatic and FSA by the thiobarbituric method., Results: The mean levels of TSA, LSA, and FSA in the sera of patients with pancreatic cancers were significantly higher than in controls. Taking into consideration the size and the location of the tumors, regional lymph node and distant metastases, there were no differences in TSA, FSA, and CA 19-9 levels. However, the location of tumors in the pancreas affects LSA levels. The sialic acids, contrary to CA 19-9, are not useful tools in the differential diagnosis of tumors and non-malignant diseases of the pancreas. LSA has the highest sensitivity, negative predictive value, accuracy, and the ability to discriminate cancer patients from healthy controls. The diagnostic power of LSA is similar to CA 19-9., Conclusions: We suggest that LSA can be useful in the diagnosis and evaluation of the tumor location in patients with primary pancreatic cancers.

The study objective was to determine the presence of MMP-7 in cancer tissue in correlation with its serum level in patients diagnosed with colorectal cancer (CRC). In 45 patients with CRC, MMP-7 expression was assessed immunohistochemically on FFPE slides in tumours (N = 37) and in the corresponding surgical margin sample. MMP-7 serum level was measured preoperatively. The expression of MMP-7 in cancer tissue was much stronger as compared to the normal intestinal mucosa. Also the level of MMP-7 in the serum of CRC patients was higher than in healthy subjects (N = 24) (p < 0.01). The tumour located in the colon showed higher expression of MMP-7 than CRCs located in the rectum (p < 0.05), whereas the higher MMP-7 serum level showed correlation with older age (p = 0.005), tumour size less than 5 cm (p < 0.05), higher Dukes' stage (p < 0.05) and distant metastases (p < 0.05). The increased serum level of MMP-7 in CRC patients may indicate the presence of distant metastases.

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.

Unlabelled: There are several antiproliferative and angiogenic factors, recently have been discovered (IL-27, IL-29, IL-31 and IL-33), but they have not been tested yet in lung cancer patients. The aim of this pilot study was to assess the clinical usefulness of determination of IL-27, IL-29, IL-31 and IL-33 in advanced stages of lung cancer., Patients and Methods: The study included 45 patients (38 males; mean age 62 years; 45 with advanced NSCLC). Serum and BALF cytokine concentrations were evaluated by ELISA method before chemotherapy. The comparative groups consisted of patients with sarcoidosis (BBS, n = 15), hypersensivity pneumonitis (HP, n = 8) and healthy subjects (n = 15)., Results: The serum IL-29 levels were higher in NSCLC patients than in the sarcoidosis group. However, serum IL-27, IL-31 and IL-33 did not differ markedly between: NSCLC, BBS, HP and the control group. Concentrations of IL-29 and IL-31 in BALF did not differ significantly between investigated groups. In all groups levels of IL-27 and IL-29 are significantly higher in serum than in BALF. Concentrations of IL-31 in BBS, HP and control groups tended to higher in BALF than in serum. These differences were significantly in NSCLC patients. Patients in stage IIIB of NSCLC had higher serum levels of IL-29 than these in stage IV. Lung cancer patients with partial remission (PR) after chemotherapy had significantly higher concentration of IL-27 in BALF than patients with SD. However, patients with SD had higher levels of IL-29 in BALF than patients with PD. A negative correlation was found between serum IL-31 levels before therapy and time to progression of NSCLC., Conclusion: Determination of IL-27, IL-29 and IL-31 in serum and BALF can be useful in clinical practice, but their practical significance needs further studies.

Introduction: Adhesion molecules take part in the interaction between host cells and cancer cells. In the current study the relationship between the soluble adhesion molecules sICAM-1 and sVCAM-1 and proangiogenic factor VEGF in colorectal cancer progression were measured., Materials and Methods: The study group consisted of 46 patients with colorectal carcinoma (classified due to TNM classification) and 40 controls. sICAM-1, sVCAM-1 and VEGF plasma concentration were measured by enzyme-linked immunosorbent assay (ELISA)., Results: All measured parameters levels were increased significantly in patients with colorectal cancer in comparison to controls (p<0.001). sICAM-1, sVCAM-1 and VEGF increased significantly due to colorectal cancer progression. There was a positive correlation between sICAM-1 and sVCAM-1 in all study groups., Conclusions: Our results demonstrated in CRC patients significantly increased levels of soluble adhesion molecules (VCAM-1 and sICAM-1) and angiogenic factor (VEGF) as compared to control group. The dynamics of these molecules showed the growing tendency along with tumor size and metastasis formation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The proteasome chymotrypsin-like (Cht-L) activity was determined in plasma of children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in correlation to baseline leukocytosis, immunophenotype, LDH at the time of diagnosis and after remission induction., Procedure: The activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n=25), acute lymphoblastic leukemia, ALL (n=95) and AML (n=17) patients., Results: As compared to healthy subjects, the plasma proteasome ChT-L activity was significantly increased (p=0.001) in ALL patients prior to treatment, especially in those with T-ALL immunophenotype and with high LDH activity. Similarly, in AML patients the plasma proteasome ChT-L activity was elevated (p=0.001). Following remission-inducing chemotherapy, the activity of the ChT-L proteasome was significantly reduced both in ALL and AML patients., Conclusion: Plasma proteasome ChT-L activity may serve as an additional marker in monitoring anticancer therapy.

Introduction: Changes in the structure of membrane glycoconjugates and activity of glycosidases and proteases are important in tumor formation., Objectives: The aim of the study was to compare the specific activity of lysosomal exoglycosidases: N-acetyl-β-D-hexosaminidase (HEX), its isoenzymes A (HEX A) and B (HEX B), β-D-galactosidase (GAL), α-fucosidase (FUC), and α-mannosidase (MAN) with the activity of cathepsin D (CD) in serum, urine, and carcinoma tissue of patients with colon adenocarcinoma., Patients and Methods: The specific activity of HEX, HEX A, HEX B, GAL, FUC, MAN, and CD was assayed in serum, urine, and carcinoma tissue of 12 patients with colon adenocarcinoma., Results: Lysosomal exoglycosidases and CD have similar specific activity in colon adenocarcinoma tissue and urine, which is higher than their activity in serum (with the exception of the highest specific activity of CD in urine). A positive correlation was observed between the specific activity of CD and that of HEX, HEX A, FUC, and MAN in the carcinoma tissue and urine as well as between CD and GAL in the urine of patients with colon adenocarcinoma. Negative correlations were observed between protein levels and the specific activity of HEX, HEX A, FUC, MAN, and CD in the carcinoma tissue and urine, and between protein levels and GAL in urine., Conclusions: Increased degradation and remodeling of glycoconjugates in the colon adenocarcinoma tissue is reflected by increased specific activity of exoglycosidases and CD. The results suggest a strong effect of exoglycosidase action on tissue degradation and a potential role of exoglycosidases in the initiation of proteolysis.

Background: This study was conducted in order to evaluate the significance of circulating free DNA (CFDNA), blood plasma p53 antibodies (p53-Ab) and mutations of KRAS gene in the prognosis of ovarian epithelial cancers., Patients and Methods: A total of 126 patients were included in this study. KRAS mutations and CFDNA were detected by means of the PCR-restriction fragment length polymorphism (PCR-RFLP) and enriched by the PCR-RFLP method. Enzyme-linked immunosorbent assay was used to analyze plasma p53-Ab., Results: KRAS mutations were detected in 27 (21.4%) of examined tumors. The frequency of KRAS mutations was especially high in mucinous cancers (P < 0.001). CFDNA and p53-Ab were frequently detected in patients with serous cancers in high grade (P < 0.001). The overall survival rate was significantly lower for patients with serous tumors and CFDNA and p53-Ab-positive than negative tumors (P = 0.022 and P < 0.001, respectively). In mucinous ovarian cancer, a worse overall survival was correlated with the KRAS mutations (P = 0.03)., Conclusions: The results of the present study suggested that a presence of KRAS mutations in mucinous ovarian cancer and CFDNA and p53-Ab in serous tumors was correlated with the highest risk of cancer progression.

The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer.

It has been suggested that interleukin-6 (IL-6) and C-reactive protein (CRP) play a potential role in the pathogenesis and growth of malignancies. CRP is produced by hepatocytes in response to inflammatory cytokines, especially IL-6. Production of IL-6 by gastric cancer cell lines has been reported. This cytokine may also act in a paracrine and autocrine fashion in tumor cells. Elevated concentrations of IL-6 and CRP were detected in the blood of patients with colorectal, lung, ovarian and gastric cancer. It has been shown that IL-6 and CRP levels correlated with clinicopathological features of gastric cancer, such as: tumor stage, depth of tumor invasion and the presence of lymph node metastasis. Some clinical investigations have suggested the potential significance of IL-6 as prognostic factor for the survival of gastric cancer patients.

Endometrial cancer is the most common gynecologic malignancy in more developed countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15-20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis and endometrioid histology and type II, associated with a poor prognosis and non-endometrioid histology. This review will focus primarily on the molecular biomarkers that have supported the dualistic model of endometrial carcinoma and help determine which patients would benefit from either adjuvant therapy or more aggressive primary treatment.