BACKGROUND: Matrix metalloproteinases are notable contributors to neuroinflammation and blood-brain barrier disruption in multiple sclerosis (MS). OBJECTIVE: The goal of this study was to determine the serum levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), and their tissue inhibitors (TIMP-1) and (TIMP-2), and to investigate their possible relations to type, disability, and severity of MS. MATERIALS AND METHODS: Eighty-seven patients with definite MS according to the McDonald criteria and 50 healthy controls were enrolled in the study. Their clinical status was evaluated with the Expanded Disability Status Scale. Serum levels were analyzed by enzyme-linked immunoassay. RESULTS: A significant elevation in MMP-9 serum levels and in the MMP-9/TIMP-1 ratio was found in the whole MS group (P<0.001), in the relapsing-remitting MS (RRMS) (P<0.001), and secondary-progressive MS (SPMS) (P<0.001) groups when compared with the controls. A significant elevation in MMP-2 serum levels and in the MMP-2/TIMP-2 ratio was observed in the primary progressive (P<0.001) and the SPMS (P<0.002) groups when compared with the RRMS group, and this increase was also associated with the disability (P<0.001) and severity (P<0.05) of the disease. CONCLUSION: We confirmed that metalloproteinases are useful biological markers in MS, providing information about the clinical type, disability, and severity of the disease.

• MeSH
• biologické markery krev   MeSH
• chronicko-progresivní roztroušená skleróza krev   patofyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 krev   MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• posuzování pracovní neschopnosti MeSH
• relabující-remitující roztroušená skleróza krev   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• tkáňový inhibitor metaloproteinasy 1 krev   MeSH
• tkáňový inhibitor metaloproteinasy 2 krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 9 MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

OBJECTIVES: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) play important roles in the function of the blood-brain barrier (BBB). To investigate the function of the BBB during tick-borne encephalitis (TBE), the levels of MMP-9 and its common tissue inhibitor, TIMP-1, were measured in serum from patients with acute phase of TBE. METHODS: Serum MMP-9 and TIMP-1 levels were measured in 147 patients with TBE and 153 controls by ELISA. RESULTS: Serum MMP-9 levels and MMP-9/TIMP-1 ratios of TBE patients were significantly higher than controls (p < 0.0001 and p < 0.005, respectively). There were no significant differences in serum TIMP-1 levels between TBE patients and controls. Serum MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratios were not associated with age of the patients. However, TBE-positive males with TBE had higher levels of MMP-9 than TBE-positive females (p < 0.05). CONCLUSIONS: Our results suggest that the increased serum level of MMP-9 and MMP-9/TIMP-1 ratio is associated with the pathogenesis of TBE. Serum MMP-9 can serve as an indicator of breakdown of the BBB and inflammatory brain damage during TBE.

• Klíčová slova
• Blood–brain barrier, Matrix metalloproteinase-9, Tick-borne encephalitis, Tissue inhibitor of metalloproteinase-1,
• MeSH
• biologické markery krev   MeSH
• dítě MeSH
• dospělí MeSH
• ELISA MeSH
• klíšťová encefalitida krev   enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neparametrická statistika MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tkáňový inhibitor metaloproteinasy 1 krev   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• matrixová metaloproteinasa 9 MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH

BACKGROUND: An essential step in the process of tumor invasion and metastasis involves the degradation of tissue barriers in the extracellular matrix (ECM), particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP-7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM degradation in connection with tumor invasion. The aim of our study was to assess the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal carcinoma tissue samples and to correlate them with the stage of the disease. PATIENTS AND METHODS: The study included samples of tumor tissue of 38 patients with colorectal carcinoma and samples of tissue of 11 patients with benign disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were quantified in tissue samples using the method of reverse transcription real-time PCR. RESULTS: The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples that in the control tissue (p<0.0005, p<0.0007 and p<0.0004). In addition the presence of mRNA MMP-2, MMP-7, TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly higher than in the control tissue (p<0.003, p<0.0001, p<0.0001 and p<0.05). CONCLUSION: This pilot study demonstrated that a significant difference in the level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between tumor colorectal and control colorectal tissues might be helpful for the prognosis of colorectal cancer.

• MeSH
• dospělí MeSH
• kolorektální nádory enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 biosyntéza   genetika   MeSH
• matrixová metaloproteinasa 7 biosyntéza   genetika   MeSH
• messenger RNA biosyntéza   genetika   MeSH
• polymerázová řetězová reakce MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• tkáňový inhibitor metaloproteinasy 1 biosyntéza   genetika   MeSH
• tkáňový inhibitor metaloproteinasy 2 biosyntéza   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 7 MeSH
• messenger RNA MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

BACKGROUND: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Recent trials in ICH, focusing on hematoma reduction, have not yielded significant clinical improvement. The modulation of matrix metalloproteinase (MMP)-9 may represent a potential therapeutic target for reducing perihematomal edema (PHE) and improving clinical outcome. METHODS: We searched Cochrane Library, Ovid/Medline, and PubMed databases using combinations of the following MeSH search terms: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". RESULTS: MMP-9 levels in animal models have largely shown detrimental correlations with mortality, clinical outcome, hematoma volume, and PHE. Animal models and clinical studies have established a timeline for MMP-9 expression and corresponding PHE that include an initial peak on days 1-3 and a secondary peak on day 7. Clinical studies evaluating MMP-9 levels in the acute phase (days 1-3) and subacute phase (day 7) of ICH suggest that MMP-9 may be detrimental in the acute phase through destruction of basal lamina, activation of vascular endothelial growth factor, and activation of apoptosis but assist in recovery in the subacute phase through angiogenesis. CONCLUSIONS: MMP-9 inhibition represents a potentially effective target for neuroprotection in ICH. However, as a ubiquitous protein, the inhibition of pathologic processes must be balanced against the preservation of neuroprotective angiogenesis. As the opposing roles of MMP-9 may have similar mechanisms, the most important factor may be the timing of MMP-9 inhibition. Further studies are necessary to delineate these mechanisms and their temporal relationship.

• Klíčová slova
• Matrix metalloproteinase, blood brain barrier, gelatinase B, intracerebral hemorrhage, neuroprotection, perihematomal edema,
• MeSH
• apoptóza účinky léků   MeSH
• časové faktory MeSH
• cerebrální krvácení komplikace   farmakoterapie   metabolismus   mortalita   patologie   MeSH
• edém mozku farmakoterapie   metabolismus   mortalita   MeSH
• hematom farmakoterapie   metabolismus   mortalita   MeSH
• inhibitory matrixových metaloproteinas terapeutické užití   MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• neuroprotektivní látky aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• inhibitory matrixových metaloproteinas MeSH
• matrixová metaloproteinasa 9 MeSH
• neuroprotektivní látky MeSH

PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers. METHODS: In this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics. FINDINGS: A total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t1/2 was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab. IMPLICATIONS: Andecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.

• Klíčová slova
• autoimmune diseases, cartilage matrix, matrix metalloproteinase-9, pharmacokinetics, rheumatoid arthritis, therapeutic antibody,
• MeSH
• antirevmatika * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory matrixových metaloproteinas * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• monoklonální protilátky * škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• andecaliximab MeSH Prohlížeč
• antirevmatika * MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory matrixových metaloproteinas * MeSH
• matrixová metaloproteinasa 9 MeSH
• monoklonální protilátky * MeSH

BACKGROUND: The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in tumor growth and in the process of invasion. The aim of our study was to test the levels of MMP-2, MMP-7, and the MMP inhibitors TIMP-1 and TIMP-2 mRNA in colorectal carcinoma tissue samples with the clinicopathological status of the disease. PATIENTS AND METHODS: Colorectal carcinoma tissue samples were obtained from 38 patients who underwent resection of colorectal carcinoma. The expression levels of mRNA of MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene were quantified in these tissue samples using the method of reverse transcription real-time PCR. RESULTS: It was found that the levels of mRNA expression of MMP-2, TIMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples than in the normal colorectal tissue (p < 0.0020, p < 0.0467, p < 0.0007 and p < 0.0003 respectively). The level of mRNA expression of MMP-2, MMP-7, TIMP-2 and TIMP-1 did not correlate with the stage of the disease, localization of the tumor, metastatic spread or with disease-free survival (DFI). We recorded a statistically significant inverse negative correlation (r = -0.85; p < 0.0001) between the levels of MMP-7 mRNA and TIMP-2 mRNA. Correlations between the values of mRNA MMP-7 vs. TIMP-1, MMP-2 vs. TIMP-2, MMP-2 vs. TIMP-1 and MMP-2 vs. MMP-7 were not statistically significant. CONCLUSION: We found that there were statistically significant differences in the levels of MMP-2, MMP-7, TIMP-1, TIMP-2 mRNA between normal colorectal tissue and tumor tissue, but we did not find any statistically significant correlation between mRNA levels of MMP-2, MMP-7, TIMP-1, TIMP-2 expression and localization of tumor, clinical stage or course of disease. We found an inverse negative statistically significant correlation between mRNA levels of MMP-7 and TIMP-2. On the basis of these results the clinical use of this approach to the determination of a prognosis is ambiguous.

• MeSH
• dospělí MeSH
• exprese genu MeSH
• kolorektální nádory metabolismus   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 biosyntéza   MeSH
• matrixová metaloproteinasa 7 biosyntéza   MeSH
• messenger RNA analýza   MeSH
• nádorové biomarkery analýza   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• tkáňový inhibitor metaloproteinasy 1 biosyntéza   MeSH
• tkáňový inhibitor metaloproteinasy 2 biosyntéza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• matrixová metaloproteinasa 2 MeSH
• matrixová metaloproteinasa 7 MeSH
• messenger RNA MeSH
• nádorové biomarkery MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

Matrix metalloproteinases (MMPs), also known as matrixins, belong to a group of zinc-dependent proteins, which are thought to play a central role in the breakdown of extracellular matrix. Collagen, elastin, gelatin and casein are major components cleaved by MMPs. The breakdown of these components is essential for many physiological processes such as embryonic development, morphogenesis, reproduction, and tissue resorption and remodelling. MMPs also participate in pathological processes such as arthritis, cancer, cardiovascular and neurological diseases. This review summarizes current knowledge regarding these proteins, their participation in physiological and pathophysiological roles, their involvement in activation and inhibition, and their interactions with other metal-binding proteins including metallothioneins.

• MeSH
• cystein metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• inhibitory matrixových metaloproteinas MeSH
• kardiovaskulární nemoci farmakoterapie   enzymologie   patofyziologie   MeSH
• lidé MeSH
• matrixové metaloproteinasy chemie   genetika   metabolismus   MeSH
• nádory farmakoterapie   enzymologie   patofyziologie   MeSH
• regulace genové exprese enzymů MeSH
• sloučeniny zinku chemie   metabolismus   farmakologie   MeSH
• substrátová specifita MeSH
• tkáňové inhibitory metaloproteinas metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cystein MeSH
• inhibitory matrixových metaloproteinas MeSH
• matrixové metaloproteinasy MeSH
• sloučeniny zinku MeSH
• tkáňové inhibitory metaloproteinas MeSH

Matrix metalloproteinases (MMPs) are a group of zinc and calcium endopeptidases which cleave extracellular matrix (ECM) proteins. They are also involved in the degradation of cell surface components and regulate multiple cellular processes, cell to cell interactions, cell proliferation, and cell signaling pathways. MMPs function in close interaction with the endogenous tissue inhibitors of matrix metalloproteinases (TIMPs), both of which regulate cell turnover, modulate various growth factors, and participate in the progression of tissue fibrosis and apoptosis. The multiple roles of MMPs and TIMPs are continuously elucidated in kidney development and repair, as well as in a number of kidney diseases. This chapter focuses on the current findings of the significance of MMPs and TIMPs in a wide range of kidney diseases, whether they result from kidney tissue changes, hemodynamic alterations, tubular epithelial cell apoptosis, inflammation, or fibrosis. In addition, the potential use of these endopeptidases as biomarkers of renal dysfunction and as targets for therapeutic interventions to attenuate kidney disease are also explored in this review.

• Klíčová slova
• Acute kidney injury, Chronic allograft nephropathy, Chronic kidney disease, Diabetic nephropathy, Glomerulonephritis, Glomerulosclerosis, Hemodialysis, Matrix metalloproteinases, Polycystic kidney disease, Tissue inhibitor of matrix metalloproteinases, Tubulointerstitial fibrosis,
• MeSH
• extracelulární matrix - proteiny MeSH
• lidé MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• nemoci ledvin * MeSH
• signální transdukce MeSH
• tkáňové inhibitory metaloproteinas * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• extracelulární matrix - proteiny MeSH
• matrixové metaloproteinasy MeSH
• tkáňové inhibitory metaloproteinas * MeSH

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.

• MeSH
• aneurysma břišní aorty metabolismus   MeSH
• arteriální okluzní nemoci metabolismus   MeSH
• imunohistochemie MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• myocyty hladké svaloviny metabolismus   MeSH
• nemoci aorty metabolismus   MeSH
• tkáňový inhibitor metaloproteinasy 1 metabolismus   MeSH
• tkáňový inhibitor metaloproteinasy 2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• matrixová metaloproteinasa 9 MeSH
• matrixové metaloproteinasy MeSH
• tkáňový inhibitor metaloproteinasy 1 MeSH
• tkáňový inhibitor metaloproteinasy 2 MeSH

The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.

• MeSH
• inhibitory matrixových metaloproteinas MeSH
• inhibitory proteas terapeutické užití   MeSH
• lidé MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• nádory štítné žlázy farmakoterapie   enzymologie   MeSH
• nádory farmakoterapie   enzymologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• inhibitory matrixových metaloproteinas MeSH
• inhibitory proteas MeSH
• matrixové metaloproteinasy MeSH