Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases.

The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs-i.e., Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)-as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.

Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities.

Angiogenesis, a complex, multistep process of forming new blood vessels, plays crucial role in normal development, embryogenesis, and wound healing. Malignant tumors characterized by increased proliferation also require new vasculature to provide an adequate supply of oxygen and nutrients for developing tumor. Gliomas are among the most frequent primary tumors of the central nervous system (CNS), characterized by increased new vessel formation. The processes of neoangiogenesis, necessary for glioma development, are mediated by numerous growth factors, cytokines, chemokines and other proteins. In contrast to other solid tumors, some biological conditions, such as the blood-brain barrier and the unique interplay between immune microenvironment and tumor, represent significant challenges in glioma therapy. Therefore, the objective of the study was to present the role of various proangiogenic factors in glioma angiogenesis as well as the differences between normal and tumoral angiogenesis. Another goal was to present novel therapeutic options in oncology approaches. We performed a thorough search via the PubMed database. In this paper we describe various proangiogenic factors in glioma vasculature development. The presented paper also reviews various antiangiogenic factors necessary in maintaining equilibrium between pro- and antiangiogenic processes. Furthermore, we present some novel possibilities of antiangiogenic therapy in this type of tumors.

The Role of Gut Microbiota and Gut-Brain Interplay in Selected Diseases of the Central Nervous System.

The gut microbiome has attracted increasing attention from researchers in recent years. The microbiota can have a specific and complex cross-talk with the host, particularly with the central nervous system (CNS), creating the so-called "gut-brain axis". Communication between the gut, intestinal microbiota, and the brain involves the secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components of bacteria, and signaling molecules. Moreover, an imbalance in the gut microbiota composition modulates the immune system and function of tissue barriers such as the blood-brain barrier (BBB). Therefore, the aim of this literature review is to describe how the gut-brain interplay may contribute to the development of various neurological disorders, combining the fields of gastroenterology and neuroscience. We present recent findings concerning the effect of the altered microbiota on neurodegeneration and neuroinflammation, including Alzheimer's and Parkinson's diseases, as well as multiple sclerosis. Moreover, the impact of the pathological shift in the microbiome on selected neuropsychological disorders, i.e., major depressive disorders (MDD) and autism spectrum disorder (ASD), is also discussed. Future research on the effect of balanced gut microbiota composition on the gut-brain axis would help to identify new potential opportunities for therapeutic interventions in the presented diseases.

The Role of Selected Chemokines and Their Receptors in the Development of Gliomas.

Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the worst prognosis. In their development, certain chemokine/receptor axes play important roles and promote proliferation, survival, metastasis, and neoangiogenesis. However, little is known about the significance of atypical receptors for chemokines (ACKRs) in these tumors. The objective of the study was to present the role of chemokines and their conventional and atypical receptors in CNS tumors. Therefore, we performed a thorough search for literature concerning our investigation via the PubMed database. We describe biological functions of chemokines/chemokine receptors from various groups and their significance in carcinogenesis, cancer-related inflammation, neo-angiogenesis, tumor growth, and metastasis. Furthermore, we discuss the role of chemokines in glioma development, with particular regard to their function in the transition from low-grade to high-grade tumors and angiogenic switch. We also depict various chemokine/receptor axes, such as CXCL8-CXCR1/2, CXCL12-CXCR4, CXCL16-CXCR6, CX3CL1-CX3CR1, CCL2-CCR2, and CCL5-CCR5 of special importance in gliomas, as well as atypical chemokine receptors ACKR1-4, CCRL2, and PITPMN3. Additionally, the diagnostic significance and usefulness of the measurement of some chemokines and their receptors in the blood and cerebrospinal fluid (CSF) of glioma patients is also presented.

The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD).

Although the causative role of the accumulation of amyloid ß 1-42 (Aß42) deposits in the pathogenesis of Alzheimer's disease (AD) has been under debate for many years, it is supposed that the toxicity soluble oligomers of Tau protein (TauOs) might be also the pathogenic factor acting on the initial stages of this disease. Therefore, we performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database. It was shown that soluble TauOs, especially granular forms, may be the most toxic form of this protein. Hyperphosphorylated TauOs can reduce the number of synapses by missorting into axonal compartments of neurons other than axon. Furthermore, soluble TauOs may be also responsible for seeding Tau pathology within AD brains, with probable link to AßOs toxicity. Additionally, the concentrations of TauOs in the cerebrospinal fluid (CSF) and plasma of AD patients were higher than in non-demented controls, and revealed a negative correlation with mini-mental state examination (MMSE) scores. It was postulated that adding the measurements of TauOs to the panel of CSF biomarkers could improve the diagnosis of AD.

Amyloid ß oligomers (AßOs) in Alzheimer's disease.

The causative role of amyloid ß 1-42 (Aß42) aggregation in the pathogenesis of Alzheimer's disease (AD) has been under debate for over 25 years. Primarily, scientific efforts have focused on the dyshomeostasis between production and clearance of Aß42. This imbalance may result from mutations either in genes for the substrate, i.e., amyloid precursor protein or in genes encoding presenilin, the enzyme of the reaction that generates Aß42. Currently, it is supposed that soluble oligomers of amyloid beta (AßOs) and not fibrillar Aß42 within neuritic plaques may be the toxic factors acting on a very early stage of AD, perhaps even initiating pathological cascade. For example, soluble AßOs isolated from AD patients' brains reduced number of synapses, inhibited long-term potentiation, and enhanced long-term synaptic depression in brain regions responsible for memory in animal models of AD. Concentrations of AßOs in the cerebrospinal fluid (CSF) of AD patients are often reported higher than in non-demented controls, and show a negative correlation with mini-mental state examination scores. Furthermore, increased Aß42/oligomer ratio in the CSF of AD/MCI patients indicated that the presence of soluble AßOs in CSF may be linked to lowering of natively measured monomeric Aß42 by epitopes masking, and hence, concentrations of AßOs in the CSF are postulated to as useful AD biomarkers.

Cellular Receptors of Amyloid ß Oligomers (AßOs) in Alzheimer's Disease.

It is estimated that Alzheimer's disease (AD) affects tens of millions of people, comprising not only suffering patients, but also their relatives and caregivers. AD is one of age-related neurodegenerative diseases (NDs) characterized by progressive synaptic damage and neuronal loss, which result in gradual cognitive impairment leading to dementia. The cause of AD remains still unresolved, despite being studied for more than a century. The hallmark pathological features of this disease are senile plaques within patients' brain composed of amyloid beta (Aß) and neurofibrillary tangles (NFTs) of Tau protein. However, the roles of Aß and Tau in AD pathology are being questioned and other causes of AD are postulated. One of the most interesting theories proposed is the causative role of amyloid β oligomers (AßOs) aggregation in the pathogenesis of AD. Moreover, binding of AßOs to cell membranes is probably mediated by certain proteins on the neuronal cell surface acting as AßO receptors. The aim of our paper is to describe alternative hypotheses of AD etiology, including genetic alterations and the role of misfolded proteins, especially Aß oligomers, in Alzheimer’s disease. Furthermore, in this review we present various putative cellular AßO receptors related to toxic activity of oligomers.

Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients.

The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients' survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.

Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections.

PURPOSE: Ticks transmit several pathogens and seem implicated in the production of specific IgE antibodies to alpha-1,3-galactose (α-gal sIgE). They cause delayed and immediate allergy to mammalian meat and medication including antivenoms, vaccines and monoclonal antibodies. METHODS: We assessed the prevalence of α-gal sIgE in forest workers and healthy controls in the Podlasie voivodeship, north-eastern Poland; the relationship between α-gal sIgE and allergy to α-gal-containing products; the correlation between α-gal sIgE and anti-Borrelia burgdorferi and anti-tick-borne encephalitis virus (TBEV) antibodies; the relationship between α-gal sIgE and markers of infection with lesser-known pathogens transmitted by ticks such as Anaplasma phagocytophilum. RESULTS: Production of α-gal sIgE was closely related to tick bites. The odds ratio for detectable α-gal sIgE was 9.31 times higher among people with a history of tick bites (OR 9.3; p < .05). There was no correlation with the history of TBE, Lyme disease or human granulocytic anaplasmosis. However, serum α-gal sIgE correlated with anti-TBEV IgM antibodies in CSF. There was a strong correlation between α-gal sIgE and total IgE and sIgE to pork and beef. CONCLUSIONS: Our data support the link between I.ricinus ticks and the production of α-gal sIgE and confirm that the pathogens carried by ticks we examined for do not seem implicated in this immune response.

[The role of matrix metalloproteinases in cardiovascular diseases]. / Metaloproteinazy macierzy zewnatrzkomórkowej w chorobach ukladu krazenia.

Matrix metalloproteinases (MMPs) belong to a large family of multidomain zinc endopeptidases. They are one of the most important proteolytic enzymes which digest components of the extracellular matrix and take part in many physiological processes, such as apoptosis or angiogenesis. It was shown that MMPs are also involved in the pathogenesis of many diseases such as malignant tumors and cardiovascular diseases. The discovery of the mechanisms of MMPs' action can have significant influence on therapeutic strategy, especially in cardiovascular diseases.

The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients.

PURPOSE: Tumor cells, including colorectal cancer (CRC), are able to produce and release matrix metalloproteinase 9 (MMP-9) which is involved in tumor invasion and metastasis. Natural tissue inhibitors of matrix metalloproteinases (TIMPs) regulate activity of MMPs and stimulate tumor growth and malignant transformation. The aim of the present study was to compare the clinical significance of serum MMP-9 with TIMP-1 in the diagnosis of CRC patients and in the differentiation between colorectal adenoma (CA) and cancer. METHODS: Serum MMP-9 and TIMP-1 were measured in 75 CRC patients, 35 CA, and 70 healthy subjects using enzyme-linked immunosorbent assay. Concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were determined by microparticle enzyme immunoassay. RESULTS: Serum levels of all proteins tested were significantly higher in CRC patients than in healthy subjects. Additionally, serum TIMP-1 was significantly higher in patients with CRC than in CA patients. Concentrations of TIMP-1 correlated with tumor stage, nodal involvement, presence of distant metastases, patients' survival, and tumor resectability. Diagnostic sensitivity of TIMP-1 was higher (61%) than those of other biomarkers (MMP-9, 55%; CEA, 39%; CA 19-9, 11%), and increased in combined use with MMP-9 (75%) or CEA (73%). The areas under receiver operating characteristic curves of TIMP-1 were larger than those of MMP-9. CONCLUSIONS: Our findings suggest better usefulness of serum TIMP-1 than MMP-9 in the diagnosis of CRC, especially in the assessment of Duke's classification of tumor stage, survival of cancer patients, resectability of tumor, and in the differentiation between CA and cancer.

Diagnostic usefulness of serum interleukin 6 (IL-6) and C-reactive protein (CRP) in the differentiation between pancreatic cancer and chronic pancreatitis.

Previous studies have shown elevated serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) in patients with pancreatic cancer (PC). The aim of this study was to assess the diagnostic usefulness of pretreatment serum levels of IL-6 and CRP to differentiate between PC and chronic pancreatitis (CP) patients. Serum levels of CRP, IL-6, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9) were determined in 78 patients with PC before surgery, in 45 patients with CP, and in 70 healthy controls. Serum levels of all the proteins tested were significantly higher in cancer patients when compared with CP and healthy subjects, and increased in more advanced tumor stages. Concentrations of IL-6 were significantly higher in nonresectable tumors and in patients who died during the 2-year observation period. Area under receiver operating characteristic curve for IL-6 was higher than for other substances tested in the differentiation between PC and CP. Cox's univariate analysis revealed serum IL-6 as a significant prognostic factor of patients' survival. Our findings suggest higher diagnostic usefulness of serum IL-6 than CRP, CEA, and CA 19-9 in the diagnosis and prognosis of patients with PC and in the differentiation with CP.

[The role of selected matrix metalloproteinases and their inhibitors in colorectal cancer development]. / Rola wybranych metaloproteinaz i ich inhibitorów w rozwoju raka jelita grubego.

Colorectal cancer is one of the most common malignant tumors of the gastrointestinal tract. The development of this tumor is a complex, long-term, and multi-step process, from small dysplastic lesions of normal colorectal mucosa, through adenomatous polyps, to carcinoma in situ. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in colorectal carcinogenesis. MMP-9 is able to degrade collagen IV from basement membranes and extracellular matrix, which is associated with tumor progression, including invasion, metastasis,growth, migration, and angiogenesis. It was demonstrated that increased expression of MMP-9plays a crucial role in the development of several human malignancies, including colorectal cancer.Increased expression of MMP-9 correlated with tumor stage, invasiveness, and poor survival of colorectal cancer patients.

Cerebrospinal Fluid and Blood CX3CL1 as a Potential Biomarker in Early Diagnosis and Prognosis of Dementia.

BACKGROUND: A growing body of evidence highlights the crucial role of neuroinflammation and chemokine involvement in cognitive impairment pathophysiology. Fractalkine (CX3CL1) appears to be a relevant causative factor in the development of dementia, particularly at the early stages of the disease. However, limited data are available on the levels of CX3CL1 in the cerebrospinal fluid (CSF) and blood. Additionally, to date, its utility as a biomarker for MCI or AD has not been studied. OBJECTIVE: The aim of the present study was to evaluate the clinical utility of CX3CL1 in the early diagnosis of cognitive impairment. We also compared the diagnostic usefulness of CX3CL1 with other biomarkers associated with neuroinflammation. METHODS: A total of 60 patients with cognitive impairment, including 42 patients with AD and 18 subjects with MCI, as well as 20 cognitively healthy controls were enrolled in the study. CSF and blood concentrations of CX3CL1, CCL-2, and YKL-40 were measured by ELISA. RESULTS: Significantly higher CSF and blood concentrations of CX3CL1 were observed in MCI and AD patients compared to older individuals without cognitive impairment. The increase in the levels of CX3CL1 and YKL-40 in non-demented subjects was associated with MCI. The area under the ROC curve for CX3CL1 in MCI subjects was larger in comparison to classical AD markers. CONCLUSION: Presented results indicate a crucial role of CX3CL1 in the pathology of cognitive impairment and the potential usefulness of this protein in the early diagnosis of MCI and AD.

Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients.

BACKGROUND: The invasion and metastases of gastric cancer (GC) depends on the activities of matrix metalloproteinases and tissue inhibitors of metalloproteinases. It was suggested that the concentration of plasma matrix metalloproteinase-9 (MMP-9) is better than the concentration of serum MMP-9 for prediction of evolution of GC. The aim of the present study was to compare the clinical usefulness of plasma and serum tissue inhibitor of metalloproteinases-1 (TIMP-1) in the diagnosis and prognosis of GC. METHODS: Plasma and serum concentrations of TIMP-1, MMP-9 and carcinoembryonic antigen (CEA) were assayed in 73 patients with GC and 61 healthy controls. The diagnostic criteria and prognostic value for the measurands were defined. RESULTS: Plasma and serum TIMP-1, MMP-9 and CEA were significantly higher in GC patients compared with healthy controls. The area under the ROC curve (AUC) (0.961), diagnostic sensitivity (89%) and accuracy (91%) of plasma TIMP-1 were higher than those for MMP-9 and CEA. An increased pre-treatment concentration of plasma TIMP-1 was a significant independent prognostic factor for the survival of patients with GC. CONCLUSIONS: These findings suggest that the plasma TIMP-1 is a better biomarker than the serum TIMP-1 and might be useful for the diagnosis of GC and prognosis of patient survival.

Expression and Concentration of Matrix Metalloproteinase 9 and Tissue Inhibitor of Matrix Metalloproteinases 1 in Laryngeal Squamous Cell Carcinoma.

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.

The diagnostic value of the measurement of matrix metalloproteinase 9 (MMP-9), squamous cell cancer antigen (SCC) and carcinoembryonic antigen (CEA) in the sera of esophageal cancer patients.

BACKGROUND: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases associated with tumor progression. It was proved that expression of MMP-9 in human esophageal cancer tissues correlated with stages of the disease. The aim of the present study was to determine potential clinical use of serum MMP-9 as a tumor marker of esophageal cancer. METHODS: The study included 89 patients with esophageal cancer and 30 healthy subjects (control group). We assayed serum levels of MMP-9 and classical tumor markers (SCC-Ag and CEA). We defined the prognostic value and diagnostic criteria for the measurands. RESULTS: Serum levels of MMP-9, CEA and SCC-Ag in esophageal cancer (EC) patients were statistically higher than in the control group. MMP-9 serum concentrations were associated with clinical stages of EC and tumor size. The diagnostic sensitivity of MMP-9 (70%) was higher than tumor markers and increased in combination with SCC-Ag (92%). The area under the ROC curve for MMP-9 (0.733) was lower than for SCC-Ag (0.811) and higher than for CEA (0.673). In Cox's univariate analysis serum MMP-9, SCC-Ag and CEA were not significant for prognosis of EC. CONCLUSION: The results suggest the usefulness of MMP-9 as a tumor marker in diagnosis, but not in prognosis of esophageal cancer.

[Cytokines as markers of osteolysis in the diagnostics of patients with bone metastases]. / Cytokiny jako markery osteolizy w diagnostyce pacjentów z przerzutami nowotworowymi do kosci.

In normal bone there are two essential processes of bone turnover, resorption and formation, which are disrupted by bone metastases. Two types of bone metastases are known, i.e. osteolytic lesions with dominant bone resorption and osteosclerotic tumors with enhanced osteoblastic bone formation. Numerous cytokines and growth factors regulate the activity of osteoclasts and/or osteoblasts in endo- or paracrine ways, playing crucial roles in the processes of bone turnover. Bone metastases are often the consequences of certain malignant tumors, such as breast, prostate, lung, and renal cancer. The diagnosis of bone metastasis is essential for a determination of the clinical stage of cancer and appropriate treatment. Tumor markers are useful in diagnosis, prognosis, staging, and, especially, monitoring treatment. Tumor markers are also useful in detecting bone metastases. There is growing evidence that various cytokines, especially M-CSF, TGFbeta, TNFalpha, and IL-6 and IL-7, may be new tumor markers useful in the diagnosis of neoplastic disease. The processes of bone turnover in normal bone and metastatic tumors as well as the significance of the most important cytokines in the development of osteolytic metastases and the possibility of their use in the diagnosis of the most frequent cancers presenting bone metastases are described in this article.

Soluble TREM-1 Serum Level can Early Predict Mortality of Patients with Sepsis, Severe Sepsis and Septic Shock.

Early prognostic prediction of sepsis is essential in adjusting therapeutic protocols to prevent deterioration and reduce mortality. We compared the predictive value of the serum concentration of the soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) for 28-day mortality and for the development of severe sepsis or septic shock on the third day with the levels of interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin (PCT). The study was conducted on 85 patients with sepsis. sTREM-1, CRP, PCT and IL-6 concentrations were measured upon study inclusion (day 0) and on days 1, 2, 3 and 5. APACHE II, SAPS II and SOFA scores were analyzed. The sTREM-1 levels (pg/ml) were higher in non-survivors than in survivors at admission (773 vs. 391, p < 0.001) and on days 1, 2, 3 and 5. In predicting the development of severe sepsis, the highest AUCs were found for PCT (0.744, 95% CI 0.638-0.85) and sTREM-1 (0.664, 95% CI 0.55-0.778); and in septic shock prediction, for PCT (0.766, 95% CI 0.665-0.867) and IL-6 (0.707, 95% CI 0.595-0.819). sTREM-1 positively correlated with APACHE II, SAPS II and SOFA scores. At inclusion, significant AUC for predicting 28-day mortality was 0.772 for the sTREM-1 (95% CI 0.672-0.871), 0.858 for APACHE II (95% CI 0.768-0.948), 0.847 for SAPS II (95% CI 0.733-0.96), 0.806 for SOFA score (95% CI 0.698-0.915). sTREM-1 can early predict the 28-day sepsis mortality, although its effectiveness is lower in comparison with clinical severity scores.

Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis.

BACKGROUND: Elevated serum concentrations of macrophage-colony stimulating factor (M-CSF) have been found in a variety of malignant diseases. The aim of our study was to assess correlations between serum levels of M-CSF and clinicopathological features and survival rates in patients with colorectal cancer (CRC). PATIENTS/METHODS: M-CSF and the established tumor markers (carcinoembryonic antigen - CEA and carbohydrate antigen - CA 19-9) were investigated in the sera of 116 colorectal cancer patients and correlated with the clinical parameters of the disease and with the survival of patients. We compared M-CSF serum levels in CRC with colorectal adenoma patients. M-CSF was determined using enzyme-linked immunosorbent assay (ELISA). Tumor markers were measured by microparticle enzyme immunoassays (MEIA). RESULTS: CRC patients had significantly higher M-CSF and tumor markers levels compared to healthy controls and colorectal adenoma patients, with a significant association between M-CSF levels, disease stage and lymph node metastasis. Serum levels of M-CSF and CEA decreased significantly after radical resection of the tumor. Moreover, the multivariate analysis showed that the serum level of M-CSF in CRC patients was an independent prognostic factor. CONCLUSION: These findings suggest the potential clinical use of circulating M-CSF measurements, particularly in estimating prognosis for patients with CRC.