OBJECTIVE: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. METHODS: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. RESULTS: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). CONCLUSION: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.

• Klíčová slova
• MMP-7, TIMP-1, biomarker, colorectal cancer, survival,
• MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 7 krev   MeSH
• metastázy nádorů MeSH
• nádorové biomarkery krev   MeSH
• tkáňový inhibitor metaloproteinasy 1 biosyntéza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 7 MeSH
• nádorové biomarkery MeSH
• TIMP1 protein, human MeSH Prohlížeč
• tkáňový inhibitor metaloproteinasy 1 MeSH

INTRODUCTION: PSA is a serine protease composed of 240 amino acids in a single polypeptide chain and is a routine parameter in prostate cancer diagnostics. The aim of our study was to test the long-term stability of tPSA and fPSA after 10 years' storage at -80°C. MATERIALS AND METHODS: We analyzed two aliquots from 55 serum samples. The first was assayed in routine testing at the time of establishing the diagnosis. The second was thawed for further testing after approximately 10 years' storage at -80°C. The mean of storage time was 10.41 years (min-max: 9.35-11.40 years). We compared the results of tPSA and fPSA. We calculated the fPSA/tPSA ratio and compared the results of clinical evaluation. Serum tPSA and fPSA levels were assayed using chemiluminescent kits Access Hybritech PSA and free PSA. All measurements were performed using the instrument UniCel® DxI 800. RESULTS: tPSA decreased 3.59% on average with a correlation r=0.9213, and fPSA increased at an average of 2.41% with a correlation r=0.9338. The fPSA/tPSA ratio increased 0.80% on average with a correlation r=0.9174. On clinical evaluation, five samples had fallen to a less malignant category and three samples had risen to a higher malignant category compared with the original results. CONCLUSION: The stability of tPSA and fPSA levels in serum is sufficient after 10 years' storage at -80°C. Calculation of the fPSA/tPSA ratio is not recommended due to the change in the category of malignancy of 15% of the samples.

• Klíčová slova
• fPSA/tPSA ratio, free PSA, prostate cancer, stability, storage, total PSA,
• Publikační typ
• časopisecké články MeSH

PURPOSE: To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers. METHODS: A literature search was performed in the PubMed and Web of Science databases using the keywords "renal cancer/renal cell carcinoma/kidney cancer" and "miR*/miRNA*/microRNA*". Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated. RESULTS: MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients. CONCLUSIONS: Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.

• MeSH
• karcinom z renálních buněk diagnóza   genetika   patologie   MeSH
• lidé MeSH
• mikro RNA biosyntéza   genetika   MeSH
• nádorové biomarkery biosyntéza   genetika   MeSH
• nádorové buněčné linie MeSH
• prognóza MeSH
• proliferace buněk genetika   MeSH
• PubMed MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• mikro RNA MeSH
• nádorové biomarkery MeSH

Interleukin-8 (IL-8, CXCL8) was originally discovered as a powerful attractor and activator of polymorphonuclear leukocytes. It was soon recognized that IL-8 also affects proliferation and migration of cancer cells, tumor angiogenesis and metastasis, and that it is expressed in many cancerous cell types. IL-8 protein expression is usually increased in serum of cancer patients, but markedly higher concentrations are found in cancer-associated non-vascular extracellular fluids, such as pleural effusion, ascites and cyst fluid. Elevated concentrations of IL-8 are indicative of malignant processes also in cerebrospinal fluid, urine, saliva, interstitial fluid and cervicovaginal secretions. Higher IL-8 levels are typically found in high-grade peritumoral fluids rather than low-grade tumors and benign conditions, with the exception of inflammatory processes. In line with recent molecular biology investigations, it appears that the local IL-8 production is related to its malignant origin and to tumor progression. Hence, IL-8 in peritumoral fluid is to be taken into consideration while assessing tumor character and monitoring the tumor progression/remission status. Besides, the data here collected justify the attempts to find an IL-8-targeted inhibitory therapy

• MeSH
• extracelulární tekutina metabolismus   MeSH
• interleukin-8 metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory metabolismus   patologie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• interleukin-8 MeSH
• nádorové biomarkery MeSH

Besides massive expression in inflammatory pleural effusions, inflammatory markers are also present in cancerinduced pleural effusions. Recent advances in cancer biology point to a role of inflammatory signaling in cancer and encourage reconsidering the diagnostic and prognostic value of inflammatory markers. Here an attempt was made to relate protein levels of inflammatory markers to underlying malignant processes in the pleural space. Pleural effusions from lung cancer patients (n=116) were subjected to a multifactorial analysis covering 13 inflammatory markers. The composition of tumor-associated effusions was compared with that of parainflammatory pleural effusions (n=30), transudates (n=18), and serum values, and evaluated in relation to cancer origin, histology, cytology, pleural involvement, treatment history, and survival time. Inflammatory markers were significantly expressed in pleural effusions of paraneoplastic origin when compared to transudates and most serum levels. Values in pleura-invading and metastatic tumor-associated effusions were typically higher than those of other tumors. Many markers correlated negatively with survival, most prominently IL-8 (r=-0.36, p=0.001) and VEGF (r=-0.35, p=0.001). It appears that most inflammatory markers are highly expressed in tumor-associated pleural effusions, reflecting to some extent tumor origin and localization. Despite the lower efficacy of inflammatory markers in the differentiation between exudative pleural effusions, some inflammatory markers may represent potential prognostic markers of malignant processes in the pleural space.

• MeSH
• analýza přežití MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní pleurální výpotek krev   chemie   diagnóza   MeSH
• mediátory zánětu analýza   krev   MeSH
• nádorové biomarkery analýza   krev   MeSH
• nádory plic krev   chemie   diagnóza   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mediátory zánětu MeSH
• nádorové biomarkery MeSH

Cathepsins S and H are present in immune cells and tissues and may play a role in the activation of an adoptive immune response. Our goal was to assess their protein levels in pleural fluids from 82 patients who underwent thoracentesis or thoracoscopy for therapeutic or diagnostic reasons and to relate them to an inflammatory, neoplastic or hemodynamic origin. Pleural effusions were also analyzed for a panel of 13 inflammatory or proliferative markers to test possible links to a nonspecific host reaction. Increased levels of cathepsin S were found in parainflammatory and cancer-related effusions compared to transudates. Cathepsin H levels were elevated only in parainflammatory effusions, whereas the levels in cancer-related effusions were comparable to transudates. Cathepsin S values significantly correlated with LDH, alpha-1-AT, VEGF, sICAM, sVCAM, MPO, uPA, MMP-9/TIMP-1, IL-8 and MCP-1, but not with CRP, IL-10 or cathepsin H. In contrast to cathepsin S, cathepsin H values did not correlate with markers of inflammation, indicating a specific role for cathepsin H in the pleural host response. In conclusion, the estimation of cathepsin S and cathepsin H may help to distinguish between effusions of different etiology.

• MeSH
• biologické markery krev   metabolismus   MeSH
• cysteinové endopeptidasy krev   metabolismus   MeSH
• kathepsin H MeSH
• kathepsiny krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• maligní pleurální výpotek enzymologie   MeSH
• nádorové biomarkery krev   metabolismus   MeSH
• nádory plic enzymologie   MeSH
• paraneoplastické syndromy enzymologie   MeSH
• pleurální výpotek enzymologie   MeSH
• pleuritida enzymologie   MeSH
• senioři MeSH
• zánět enzymologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cathepsin S MeSH Prohlížeč
• CTSH protein, human MeSH Prohlížeč
• cysteinové endopeptidasy MeSH
• kathepsin H MeSH
• kathepsiny MeSH
• nádorové biomarkery MeSH

Spectrometric-based surface-enhanced laser desorption/ionization ProteinChip (SELDI-TOF) facilitates rapid and easy analysis of protein mixtures and is often exploited to define potential diagnostic markers from sera. However, SELDI- TOF is a relatively insensitive technique and unable to detect circulating proteins at low levels even if they are differentially expressed in cancer patients. Therefore, we applied this technology to study tissues from renal cell carcinomas (RCC) in comparison to healthy controls. We found that different biomarkers are identified from tissues than those previously identified in serum, and that serum markers are often not produced by the tumors themselves at detectable levels, reflecting the nonspecific nature of many circulating biomarkers. We detected and characterized áB-crystallin as an overexpressed protein in RCC tissues and showed differential expression by immunohistochemistry. We conclude that SELDI-TOF is more useful for the identification of biomarkers that are synthesized by diseased tissues than for the identification of serum biomarkers and identifies a separate set of markers. We suggest that SELDI-TOF should be used to screen human cancer tissues to identify potential tissue-specific proteins and simpler and more sensitive techniques can then be applied to determine their validity as biomarkers in biological fluids.

• MeSH
• alfa-krystaliny - řetězec B analýza   krev   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk krev   chemie   diagnóza   MeSH
• ledviny chemie   MeSH
• lidé MeSH
• nádorové biomarkery analýza   krev   MeSH
• nádory ledvin krev   chemie   diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice metody   statistika a číselné údaje   MeSH
• studie případů a kontrol MeSH
• tkáňová distribuce MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa-krystaliny - řetězec B MeSH
• nádorové biomarkery MeSH

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• kolorektální nádory farmakoterapie   sekundární   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery moč   MeSH
• neopterin moč   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• neopterin MeSH

Immune dysfunction is prevalent in metastatic cancer. Few patients with colorectal cancer metastases are cured, and among the strategies aimed at improving the therapeutic results in patients with metastatic colorectal cancer, immunotherapy is being increasingly investigated. We evaluated retrospectively the prognostic significance of peripheral blood leukocytes in 59 patients with metastatic colorectal cancer. The relative numbers of CD3+, CD3+CD4+, CD3+CD8+, NK (CD3-CD16+CD56+), CD3+DR+, CD3+CD25+, CD3+CD69+, CD19+, CD19+CD23+, CD8+CD28+, CD8-CD28+, CD8+CD57+, CD14+DR+ and CD14+CD16+ leukocytes were analyzed by two-color flow cytometry. A three-step approach was adopted to identify predictors of prognosis using regression analysis. Based on the results of univariate survival analysis, the absolute number of white blood cells, NK/CD3+CD69+ and NK/white cell count ratios were significant indicators of prognosis. In the multivariate regression analysis a model was obtained using a single parameter, the NK/CD3+CD69+ ratio, predicting the survival with 10-15% power of regression. The present results indicate that the NK/CD3+CD69+ ratio in peripheral blood may be an independent variable in a regression model predicting the overall survival of patients with colorectal cancer metastases to be tested in prospective studies.

• MeSH
• antigeny CD3 analýza   MeSH
• CD antigeny analýza   MeSH
• diferenciační antigeny T-lymfocytů analýza   MeSH
• imunofenotypizace MeSH
• kolorektální nádory imunologie   mortalita   MeSH
• lektiny typu C MeSH
• leukocyty imunologie   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• průtoková cytometrie MeSH
• regresní analýza MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD3 MeSH
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• lektiny typu C MeSH