Rozprawy doktorskie: „Matrix Metalloproteinase 2 (MMP2)”

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Teh, Elaine. "Matrix metalloproteinase-2 (MMP2) and myocardial dysfunction associated with urgent cardiac surgery". Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/matrix-metalloproteinase2-mmp2-and-myocardial-dysfunction-associated-with-urgent-cardiac-surgery(de82119f-7ae0-4131-a743-03a8d168b62a).html.

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Background: Current management of patients presenting with acute coronary syndrome (ACS) includes aggressive and expeditious revascularisation, including surgical revascularisation. However, early surgery following ACS is associated with high mortality, as subsequent global ischaemia induced during surgery is imposed on infarcted myocardium. Emerging evidence suggests that matrix metalloproteinases (MMPs), especially MMP2, may have an important role in the acute myocardial dysfunction seen after global ischaemia-reperfusion injury, by targeting intracellular functional and structural proteins. Aims: To investigate whether MMP2 has a causative role in heart dysfunction when previously infarcted hearts were subjected to further global ischaemia-reperfusion, as occurs in cardiac surgery, with and without cardioplegic protection. Methods and Results: MI was surgically induced in male Wistar rats, (250-350 g body weight) by in vivo ligation of the left anterior descending artery. The animals were recovered for 7 days prior to excision of hearts and isolated Langendorff perfusion, followed by induction of further global ischaemia and reperfusion. The recovery of mechanical function (left ventricular developed pressure: LVDP) of the heart was assessed during reperfusion. MMP2 activity was also measured during the early reperfusion phase in the heart tissues. Infarcted hearts had less capacity to recover function after an additional period of global ischaemia, which was associated with higher MMP2 activity in the infarcted hearts compared to normal hearts. Inhibition of MMP2 improved recovery of function. When an MMP inhibitor was used as an adjunct to St Thomas’ Hospital cardioplegia, there was a trend towards improved recovery if the inhibitor was present before, during and after ischaemia. Conclusion: MMP2 has a role in causing cardiac dysfunction when infarcted hearts were subjected to further global ischaemia-reperfusion. Inhibition of MMP2 resulted in improved recovery of the function of the hearts during reperfusion. With cardioplegia, MMP2 inhibition before, during and after ischaemia was crucial to improve cardioprotection during early reperfusion.

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Kuittinen, O. (Outi). "Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in hematological malignancies". Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:951426942X.

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Abstract Gelatinases (MMP-2 and MMP-9) play a key role during invasion and metastazising of malignant cells and they have been shown to be associated to invasive phenotype and poor prognosis in several solid tumours. However little is known about their role in hematological malignancies. In the present work, gelatinase expression and its clinicopathological correlations were studied with immunohistochemical staining in 10 cases representing normal bone marrow aspirate smears, 123 cases representing diagnostic bone marrow samples of patients with different leukaemias (35 AML, 7 CLL, 6 CML, 75 ALL), 67 diagnostic paraffin-embedded lymph node biopsies from patients with Hodgkin's lymphoma and 57 biopsies from patients with non-Hodgkin's lymphomas. The lymphoma samples were also stained with factor VIII antibody to evaluate the extent of new vessel formation and the non-Hodgkin's lymphoma cases also with tissue inhibitor of metalloproteinases -1 (TIMP-1) antibody. CLL did not express either of the MMP enzymes, while CML in the chronic phase expressed strongly both of the enzymes. In ALL, gelatinase expression was weak and detectable in pediatric cases in only 12.7% and in the adults in 65% of the cases. In adult ALL, MMP-2 expression correlated strongly with an extramedullary and invasive pattern of disease presentation. In AML MMP-2 positivity had markedly favorable prognostic and predictive power. In lymphoma studies, no correlations could be detected between gelatinase expression and the clinical parameters of invasion. MMP-9 positivity was related to the presence of B symptoms, which difference was statistically significant in Hodgkin's lymphoma. In Hodgkin's lymphoma, strong MMP-9 expression also implicated decreased neovascularization. In both lymphoma types, strong MMP-9 expression correlated with unfavorable prognosis, which difference was statistically significant in non-Hodgkin's lymphomas and remained as a tendency in Hodgkin's lymphoma. MMP-2 had statistically significant association with a favorable prognosis in Hodgkin's lymphoma. Combination of the results of both stainings further increased prognostic power. All together these findings implicate that gelatinases could be used as prognostic tools in AML and lymphomas albeit this needs to be verified in larger materials.

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Coughlan, Andrew Richard. "Matrix metalloproteinase (MMP) 2 and 9 in canine arthritis". Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243201.

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Guo, Chung. "Divergent regulation of MMP-2 secretion and activation in adult rat cardiac fibroblasts". Thesis, De Montfort University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247642.

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Bergman, Robert Loring. "Matrix Metalloproteinases 2 and 9 in Normal Canine Cerebrospinal Fluid". Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/33750.

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Cerebrospinal fluid (CSF) analysis is a standard part of a diagnostic evaluation. Commonly evaluated components include the cell count, protein concentration, glucose, and cytology. CSF analysis can be diagnostic in some diseases such as fungal infections and CNS lymphoma. Often, CSF analysis is not specific, but more information can be obtained. Matrix Metalloproteinases (MMPs) are enzymes that have been found in human CSF. They are calcium and zinc dependent endoproteinases with overlapping substrates. They hydrolyze at least one component of tissue extracellular matrix (ECM), such as collagen or elastin. They are important in normal physiologic processes such as angiogenesis, reproduction and wound healing. One class of MMPs, the gelatinases, degrade gelatins and type IV collagen include MMP 2 and MMP 9. MMPs are important in many pathological processes that involve unregulated matrix destruction such as arthritis, neoplasia and CNS diseases. MMP2 is known to be constituitively produced in CSF while MMP 9 is present only in certain pathologic conditions such as multiple sclerosis, neoplasia and inflammatory diseases. We hypothesize that MMP2 is present in normal canine CSF while MMP 9 is absent. Cerebrospinal fluid samples were taken from 23 normal dogs that were being used for other research purposes. Each CSF sample was evaluated immediately for red blood cells (RBCs), white blood cells (WBCs), protein, and glucose, and then stored at -70Â°C. Cytological examination was also performed. CSF samples were considered normal if the protein was less than 25 mg/dl, WBCs were less than 6 Âµl, and RBCs were less than 25 Âµl. Each dog was euthanized and the brains processed for routine histopathology. MMP analysis was done using gelatin zymography and an enzyme linked immunosorbent assay (ELISA). Bands of enzyme activity were visible following staining due to enzyme degradation of the gelatin. A commercially available polyclonal sandwich ELISA was used to identify the pro form of MMP2. The mean WBC count for the CSF samples was 0.96 WBC/ml with a range of 0-3 WBC/ml. The mean protein was 12 mg/dl, with a range of 8-17 mg/dl. The mean RBC count was 3.65 RBC/ml with a range of 0-21 RBC/ml. All normal samples of CSF contained a band of clearing that corresponded to the human commercial standard of proMMP2. No other major bands of clearing were noted on normal samples. The commercial human standards also contained ProMMP2. Other bands were present, but were faint and variable. Using a polyclonal antibody based sandwich ELISA, with samples run in triplicate, the mean pro MMP 2 levels were determined to be 5.61 ng/ml with a range of 3.36 - 10.83 ng/ml. We conclude that normal CSF values are narrower than what has been previously reported for protein concentration and WBC count. Also, the pro form of MMP 2 is present in normal canine CSF based on results of gelatin zymography and ELISA.
Master of Science

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Renaud, Virginie. "Étude de la voie de présentation de l'antigène MMP-2 par les cellules tumorales". Nantes, 2009. http://www.theses.fr/2009NANT2099.

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Un nouvel antigène de tumeur, MMP-2, a été caractérisé dans notre laboratoire. Il est reconnu par un clone T CD8+ dans le contexte HLA-A*0201. De façon surprenante, les lignées de mélanome présentent cet antigène par la voie de présentation croisée (Godefroy et al. , 2005). Le sujet de cette thèse porte sur les mécanismes impliqués dans l’absence de présentation de la MMP-2 par la voie endogène. La MMP-2 est constitué de 8 ponts disulfures et nous avons voulu évaluer l’impact de ces ponts sur cette présentation. En remplaçant une cystéine par une alanine dans l’ADNc codant pour la MMP-2 puis en transfectant ces ADNc mutés dans des cellules tumorales, nous avons montré que l'élimination d’un pont disulfure dans la MMP-2 permet sa présentation par la voie endogène. Par cinétique de chasse, nous avons aussi démontré que la MMP-2 mutée est plus rapidement dégradée que la MMP-2 sauvage. La conformation de la MMP-2 semble jouer un rôle important dans son absence de présentation par la voie endogène classique. Ensuite, nous avons essayé de déterminer la voie cellulaire impliquée dans la présentation croisée de la MMP-2. En utilisant des drogues, nous avons mis en évidence que la présentation croisée de la MMP-2 nécessite la machinerie de rétrotranslocation, le protéasome et TAP, tous impliqués dans la voie de présentation endogène. Pour déterminer les compartiments impliqués dans cette présentation croisée, nous avons testé les « Organelles lights » (Invitrogen) dans le but de cibler des structures intracellulaires in vivo
From a patient still melanoma free after TIL injection, we characterized a new tumor antigen, MMP-2, recognized by a CD8 T cell clone in HLA-A*0201 context. Surprisingly melanoma cell lines present this tumor antigen by the cross presentation pathway (Godefroy & al. , 2005). In the first part, we wondered if disulfide bonds present in MMP-2 were not responsible for its absence of presentation by the endogenous pathway. By mutagenesis, we replaced a cystein by an alanine in the cDNA coding for MMP-2, in order to induce a disulfide bond deletion and then we transfected these cDNA mutants in COS-7 and human tumor cell lines. We showed that MMP-2 deletion of one disulfide bond induce its presentation by the endogenous pathway. By pulse chase experiments we also demonstrated that MMP-2 mutated form is more rapidly degraded than the wild form. MMP-2 folding and consequently conformation seems to play an important role in the absence of its presentation by the classical pathway. In the second part, we try to determine intracellular pathway implicated in MMP-2 cross-presentation in melanoma cells. Indeed, after secretion, MMP-2 is internalized by melanoma cells in an v3 dependent manner and by an unknown pathway. MMP-2 is finally processed by the proteasome and loaded on MHC class I molecule (Godefroy & al. , 2005). By using drugs, we determined that MMP-2 cross-presentation involves the retrotranslocation machinery, the proteasome and TAP, all implicated in the endogenous pathway. To determine compartments necessary to MMP-2 cross-presentation we tested Organelles lights (Invitrogen). These reagents provide a method for targeted specific subcellular structures within living cells

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Kuntze, Luciana Bärg. "Efeito inibitório do captopril sobre a Metaloproteinase-2 da Matriz Extracelular (MMP-2) in vitro". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-27072016-160209/.

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A MMP-2 é uma protease que está envolvida em muitos eventos fisiológicos e patológicos e que compartilha similaridades estruturais com a enzima conversora de angiotensina (ECA), de modo que os inibidores da ECA passaram a ser estudados com relação ao efeito inibitório também sobre a MMP-2. No entanto, este potencial inibitório não foi ainda testado na MMP-2 altamente purificada. Este estudo teve como objetivo investigar o potencial inibitório do captopril sobre a atividade da MMP- 2. Primeiramente, supôs-se que a dissolução do captopril poderia induzir a mudanças no pH de soluções tampão. Em segundo lugar, avaliou-se o efeito direto do captopril sobre a MMP-2 presente no plasma humano e a MMP-2 recombinante humana (rhMMP-2) produzida e purificada de E. coli. As análises de atividade in vitro incluíram zimogramas com gelatina e ensaios fluorimétricos com DQ gelatin. A solubilização do captopril reduziu significativamente o pH da solução tampão 50 mM (p<0,01) mas não alterou o pH da solução tampão 200 mM (p>0,05). Resultados de zimografia do plasma e da rhMMP-2 mostraram inibição da atividade gelatinolítica com significância estatística somente em concentrações iguais ou maiores que 4 e 1 mM de captopril, respectivamente (p<0,05). A presença de captopril nos ensaios de fluorimetria resultaram na inibição significante da atividade de rhMMP-2 somente em concentrações iguais ou maiores que 2 mM (p<0,01), enquanto a rhMMP-2 ativada com APMA apresentou inibição significativa diante de 0,5 mM de captopril (p<0,01). As concentrações de captopril efetivas em inibir a MMP-2 in vitro foram muito superiores àquelas referentes à concentração plasmática máxima encontrada no plasma humano após a administração de uma dose de 50 mg de captopril. Em conjunto nossos resultados sugerem que o captopril não parece promover inibição significativa da MMP-2 nas concentrações relatadas in vivo. Além disso, o pH das soluções tamponantes é um aspecto que requer mais atenção durante ensaios de inibição de protease in vitro.
MMP-2 is involved in many physiological and pathological processes. This protease shares structural similarities with the angiotensin-converting enzyme (ACE), and ACE inhibitors have been described to inhibit MMP-2. However, this inhibitory potential has not been tested using a highly purified MM-2 so far. This study aimed at investigating the inhibitory potential of captopril on MMP-2 activity. First it was tested whether the dissolution of captopril would induce changes in the pH of the solutions. Secondly, the direct inhibitory effect of captopril on plasma MMP-2 and on a recombinant human MMP-2 (rhMMP-2) produced and purified from E. coli was tested. The in vitro activity assays included gelatin zymography and a fluorimetric assay with DQ gelatin. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution (p<0.01) but did not decreased the pH of the 200 mM Tris Buffer solution (p>0.05). Zymography results of plasma and rhMMP-2 showed that inhibition of the activity only reached statistical significance >= 4 and 1 mM of captopril, respectively (p<0,05). The presence of captopril in the fluorimetric assay resulted in a significant inhibition of the rhMMP-2 activity only at concentrations >= 2 mM (p<0.01), whereas APMA-activated rhMMP-2 was inhibited by 0.5 mM of captopril (p<0.01). The captopril concentrations found to inhibit MMP-2 are several times of magnitude higher than the maximum plasma concentration after a dose of 50 mg of captopril. In conclusion, captopril does not seem to cause significant inhibition of MMP-2 in the concentrations found in vivo, and more attention has to be given to the pH of the solutions when testing protease inhibition in vitro.

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Vasala, K. (Kaija). "Matrix metalloproteinase MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in bladder carcinoma". Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514288746.

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Abstract Bladder cancer when superficial has a good prognosis but it has a high recurrence risk and about 10–15% of the superficial carcinomas will progress into muscle invasive or metastatic type. The most powerful factor for predicting the behavior of bladder carcinoma is the stage of the tumor. Invasion to the lamina propria increases the risk of recurrence and progress to muscle-invasive tumor. Also grade of the tumor and tumor multiplicity associates with high risk for recurrence. New markers are still needed to find those patients who need more and better treatments to avoid the recurrence and progress. The need for new non-invasive markers to diminish the need for frequent cystoscopy in follow-up is also obvious. Gelatinases MMP-2 and MMP-9 are known to associate to tumor invasion and progression. Also their tissue inhibitors TIMP-1 and TIMP-2 take part in these diversified processes and metastasis formation. In the present work the expression and clinical value of gelatinases MMP-2 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 were evaluated in bladder carcinoma. Primary tissue samples of 121 patients were analyzed for expression of MMP-2 and/or MMP-9 using immunohistochemistry. The serum samples of 87 patients who were treated in the Oncology Department of Oulu University Hospital were collected and studied with ELISA. The control group consisted of 44 healthy volunteers. Overexperssion of MMP-2 protein correlated significantly to disease-specific survival and showed an independent prognostic value as a biomarker. High MMP-9 expression instead correlated to favorable overall survival of bladder cancer patients. Circulating proMMP-2, TIMP-2 and MMP-2:TIMP-2 complex levels were lower in cancer patients than in healthy volunteers in control group. High levels of all these three markers correlated with better prognosis in bladder cancer patients.

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Kim, Yu Shin. "Correlation Between MMP-2 and -9 Levels and Local Stresses in Arteries Using a Heterogeneous Mechanical Model". Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16134.

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The mechanical environment influences vascular smooth muscle cell (VSMC) functions related to the vascular remodeling. However, the relationships are not appropriately addressed by most mechanical models of arteries assuming homogeneity. Accounting for the effects of heterogeneity is expected to be important to our understanding of VSMC functions. We hypothesized that local stresses computed using a heterogeneous mechanical model of arteries positively correlate to the levels of matrix metalloproteinase (MMP)-2 and -9 in situ. We developed a mathematical model of an arterial wall accounting for nonlinearity, residual strain, anisotropy, and structural heterogeneity. The distributions of elastin and collagen fibers, quantified using their optical properties, showed significant structural heterogeneity. Anisotropy was represented by the direction of collagen fibers, which was measured by the helical angle of VSMC nuclei. The recruiting points of collagen fibers were computed assuming a uniform strain of collagen fibers under physiological loading conditions; an assumption motivated by the morphology. This was supported by observed uniform length and orientation of VSMC nuclei under physiological loading. The distributions of circumferential stresses computed using both heterogeneous and corresponding homogeneous models were correlated to the distributions of expression and activation of MMP-2 and -9 in porcine common carotid arteries, which were incubated in an ex vivo perfusion organ culture system under either normotensive or hypertensive conditions for 48 hours. While strains computed using incompressibility were identical in both models, the heterogeneous model, unlike the homogeneous model, predicted higher circumferential stresses in the outer layer. The tissue levels of MMP-2 and -9 were positively correlated to circumferential stresses computed using the heterogeneous model, which implies that areas of high stress are expected to be sites of localized remodeling and agrees with results from cell culture studies. The results support the role of mechanical stress in vascular remodeling and suggest the importance of structural heterogeneity in studying mechanobiological responses.

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Farooqi, Owais Ali. "Effect of methamphetamine on gingival fibroblast production of matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in vitro". View the abstract Download the full-text PDF version, 2009. http://etd.utmem.edu/ABSTRACTS/2009-023-Farooqi-index.htm.

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Thesis (M.S.)--University of Tennessee Health Science Center, 2009.
Title from title page screen (viewed on August 5, 2009). Research advisor: David A. Tipton, D.D.S., Ph.D. Document formatted into pages (vi, 39 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 27-38).

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Bednarek, Nathalie. "Mmp-2, -9, timp-1, -2 : recherche de biomarqueurs de lésions cérébrales chez l'enfant prématuré et à terme". Paris 7, 2008. http://www.theses.fr/2008PA077103.

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Les atteintes cérébrales périnatales sont une cause majeure de décès ou de handicap. TJôtre hypothèse est que les MMP-2 et -9 et les TIMP-1, -2 pourraient être des marqueurs précoces de ces lésions cérébrales. Le profil cortical des MMP-2, -9, TIMP-1 et -2 a été étudié de la vie embryonnaire à l'âge adulte. Les profils plasmatiques de nouveaux-nés ont été étudiés en fonction de l'âge gestationnel, du sexe et des pathologies rencontrées en période néonatale. Le profil des MMP-2, -9, TIMP-1 et -2 ont été étudiés au niveau du cortex et du plasma dans des modèles animaux. MMP-2, leTIMP-1 et le TIMP-2 sont très exprimés respectivement pendant la période embryonnaire et en post-natal. MMP-9 est peu exprimée quel que soit le temps étudié. Le sexe n'influence pas l'expression des MMP-2 et -9 et des TIMP-1 et -2 chez l'animal et chez l'homme. Les MMP-9 et TIMP-1 sont élevés spécifiquement en cas d'EAI dans le plasma humain mais aussi chez la souris. Chez le nouveau-né présentant des lésions de substance blanche, il n'est pas observé de modifications des concentrations des MMP-9 et TIMP-1 alors que, chez l'animal, TIMP-1 s'élève exclusivement, de façon transitoire, dans le cortex et le plasma. Cette étude préliminaire apporte des arguments justifiant des explorations complémentaires concernant la MMP-9 et le TIMP-1 en tant que marqueurs de sévérité et pronostic de l'EAI
The perinal brain injuries are a major cause of death or handicap. We hypothezise that the MMP-2, -9, and the TIMP- 1 and 2 could be early markers of these cerebral lesions. The cortical profile of MMP-2, -9, TIMP-1 and -2 was studied during embryonic life to adulthood. The plasmatic neonatal profiles were studied according to the gestational age, gender and neonatal pathologies. They were also studied in animal models of perinatal brain injuries. MMP-2, TIMP-1 are largely expressed during embryonic life and TIMP-2 more likely in early post-natal period. MMP-9 is quasi undetectable whatever the moment. Gender does not influence the expression of MMP-2, -9 and their inhibitors in the new-born as well as in the mouse. In ischemic encephalopathy, MMP-9 and TIMP- 1 are specifically raised in new-born plasma but also in mice brain and plasma. In PWMD new-born, no gelatinase or inhibitor elevation was seen, but in mouse cortex and plasma, an exclusive and transitory raise of TIMP-1 is obvious. This preliminary study brings arguments to explore MMP-9 and TIMP-1 as severity and prognosis markers in hypoxic-ischemic encephalopathy

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Honkavuori-Toivola, M. (Maria). "The prognostic role of matrix metalloproteinase-2 and -9 and their tissue inhibitor-1 and -2 in endometrial carcinoma". Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526204505.

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Abstract Endometrial carcinoma is the most common gynegologic malignancy in developed countries. Due to early symptoms, including abnormal uterine bleeding, endometrial cancer is often diagnosed at an early stage and in that case usually has a good prognosis and high cure rates. However, the nature of the disease is heterogeneous. During the last decades, the improvement in survival rates among endometrial cancer patients has not been significant, suggesting that the traditional clinicopathological factors may be inadequate to identify patients with high-risk disease. Furthermore, aggressive adjuvant treatments can be costly and very toxic. Therefore, better prognostic markers associated with biological aggressiveness of endometrial carcinoma are needed to identify the patients with high-risk disease, and to be able to select the treatment more individually. Gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) have been found to play a role in tumor progression. In the present work, the expression and prognostic value of MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed in endometrial carcinoma. The patient material consisted of a total of 266 women diagnosed with primary endometrial carcinoma. The tissue expression of immunoreactive proteins was examined in paraffin-embedded tumor sections by immunohistochemical staining using specific antibodies, and the pretreatment serum levels of the proteins were quantitatively measured by ELISA. Tissue MMP-2 expression associated with a worsened prognosis, whereas tissue TIMP-2 overexpression was an indicator of a favorable outcome. Furthermore, we observed a combination of strong MMP-2 and weak TIMP-2 tissue expression to identify a group of women at high risk of adverse outcome in endometrial carcinoma. Patients with negative MMP-2 immunostaining had the best prognosis, regardless of TIMP-2 staining result. In serum measurements, high preoperative TIMP-1 concentration was a prognostic indicator of unfavorable outcome. These results indicate that tissue MMP-2 and TIMP-2 as well as circulating TIMP-1 may be prognostic markers in endometrial carcinoma. Of these, tissue MMP-2 seems to be the most potent prognostic marker. Studies with larger patient materials are needed to further explore the value of these enzymes in clinical practice in endometrial cancer
Tiivistelmä Kohdunrungon syöpä on yleisin gynekologinen maligniteetti kehittyneissä maissa. Varhaisten oireiden, kuten poikkeavan verisen vuodon, vuoksi kohdunrungon syöpä havaitaan usein varhaisessa vaiheessa, jolloin sen ennuste on hyvä. Taudin käyttäytyminen voi kuitenkin olla moninaista. Viime vuosikymmenten aikana kohdunrungon syöpään sairastuneiden ennuste ei ole merkittävästi parantunut. Vaikuttaisi siltä, että perinteiset ennustetekijät eivät ole riittävän tarkkoja ennustamaan syövän taudinkulkua. Lisäksi liitännäishoidot voivat olla kalliita, ja niihin voi liittyä vakavia haittavaikutuksia. Uusien biologisten ennustetekijöiden löytäminen olisi tärkeää, jotta aggressiivista syöpätyyppiä sairastavat potilaat pystyttäisiin tunnistamaan entistä paremmin, ja hoito kyettäisiin räätälöimään yksilöllisemmin taudinkuvaa vastaavasti. Gelatinaasien (MMP-2 ja MMP-9) sekä niiden kudosinhibiittoreiden (TIMP-1 ja TIMP-2) on havaittu osallistuvan syövän etenemiseen. Tässä tutkimuksessa tarkasteltiin MMP-2:n ja MMP-9:n sekä niiden kudosinhibiittoreiden TIMP-1:n ja TIMP-2:n ilmentymistä ja ennusteellista merkitystä kohdunrungon syövässä. Aineisto käsitti yhteensä 266 primaariseen kohdunrungon syöpään sairastunutta naista. Määritysmenetelminä käytettiin sekä immunohistokemiallista värjäystä parafiiniin valettujen kudosnäytteiden osalta että ELISA-määrityksiä ennen hoitoa otettujen seeruminäytteiden osalta. Syöpäkudoksen runsas MMP-2 -proteiinin ilmentyminen liittyi epäsuotuisaan ennusteeseen, kun taas kasvainkudoksen voimakas TIMP-2 -proteiinin ilmentyminen oli hyvän ennusteen merkki. Lisäksi kasvainkudoksen voimakkaan MMP-2- ja heikon TIMP-2 -proteiinien ilmentymisen yhdistelmän havaittiin liittyvän suurempaan syövästä johtuvaan kuolleisuuteen. MMP-2 -negatiivisten potilaiden eloonjäämisennuste oli paras, TIMP-2 -värjäystuloksesta riippumatta. Seerumin korkea TIMP-1 -pitoisuus oli merkittävä huonontuneen ennusteen merkki. Tutkimuksen tulokset viittaavat siihen, että kasvainkudoksessa esiintyvät MMP-2- ja TIMP-2 -proteiinit samoin kuin seerumin TIMP-1 -pitoisuus voivat ennustaa kohdunrungon syövän kliinistä käyttäytymistä. Kasvainkudoksessa esiintyvä MMP-2 -proteiini vaikuttaisi olevan merkittävin ennusteellinen tekijä, mutta tulosten varmistamiseksi tarvitaan lisää tutkimuksia suuremmilla potilasaineistoilla

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Amorim, Elaine Manoela Porto. "Efeito do diabete e da reposição com insulina sobre o processo de maturação da próstata ventral do rato Wistar = alterações morfológicas e na atividade de metaloproteinases de matriz MMP-2 e-9". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317948.

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Orientador: Sergio Luis Felisbino
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Diabetes mellitus é uma síndrome clínica heterogênea, causada pela falta de produção de insulina pelas células beta (?) pancreáticas ou pelo defeito nos receptores para insulina nas células-alvo, resultando em uma doença metabólica hiperglicêmica. Estudos têm demonstrado que as disfunções sexuais e reprodutivas incluindo impotência, redução da libido, prejuízo da espermatogênese, infertilidade e diminuição da qualidade espermática são frequentemente associadas com o diabete no homem e em animais de experimentação. Apesar dos efeitos do diabete sobre as funções testiculares e fertilidade de machos estarem bem esclarecidos, o impacto da doença sobre morfogênese e crescimento da próstata ainda não foi completamente descrito. Assim, o presente estudo teve por objetivo analisar os possíveis efeitos do diabete e da reposição com insulina durante o crescimento prostático na puberdade, com especial atenção para a atividade das metaloproteinases de matriz 2 e 9 (MMP-2 e MMP-9), enzimas envolvidas na remodelação dos componentes da matriz extracelular. Para tanto, foram realizadas análises morfológicas, morfométricas, imunoistoquímicas e bioquímicas de zimografia, nos lobos ventral, dorsolateral e anterior da próstata de ratos Wistar, nos quais o diabete foi induzido quimicamente aos 40 dias de idade por estreptozotocina. Nossos resultados mostraram que o diabete experimental prejudicou o crescimento glandular, caracterizado por um menor ganho de peso absoluto dos diferentes lobos da próstata e diminuição da relação parênquima/estroma, principalmente do lobo dorsolateral. O diabete causou diminuição nas concentrações plasmáticas de testosterona, mas não alterou a concentração de diidrotestosterona. As atividades das MMP-2 e MMP-9 foram menores no grupo diabético. O tratamento simultâneo e/ou tardio com insulina exógena além de reverter os parâmetros alterados nos animais diabéticos também foi efetivo em restaurar características histológicas e morfométricas dos lobos prostáticos em padrões semelhantes aos observados nos animais controles. Estes resultados permitem concluir que o diabete prejudica, mas não impede, o crescimento da próstata e causa importantes alterações estromais, evidenciadas pela diminuição da atividade das MMPs -2 e -9, reforçando o papel destas enzimas na próstata. Por outro lado, o tratamento com insulina reverteu os parâmetros alterados sugerindo que as alterações prostáticas causadas pelo diabete na próstata, nesta fase do desenvolvimento pós-natal, são aparentemente reversíveis.
Abstract: The Diabetes mellitus is a heterogeneous clinical syndrome caused by lack of insulin production by beta cells (?) or the pancreatic defect in insulin receptors on target cells, resulting in hyperglycemic metabolic disease. Studies have shown that the reproductive and sexual dysfunctions including impotence, decreased libido, impaired spermatogenesis and infertility, decreased sperm quality, are often associated with diabetes in humans and experimental animals. Although vast publications have checked the effects of diabetes on testicular function and fertility in males, the impact of disease on growth and morphogenesis of the prostate is still poor understood. Thus, this study aimed to examine the possible effects of diabetes and insulin replacement, during the maturation process prostate, with special attention to the matrix metalloproteinases 2 and 9 (MMP2 and MMP9), enzymes involved in the extracellular matrix components remodeling during development and growth of prostate. For both, analyze morphological, morphometric, immunocytochemical and biochemical zymography were done in the ventral, dorsolateral and anterior prostatic lobes of Wistar rats, which diabetes was chemically induced at 40 days old by streptozotocin. Our results showed that diabetes impaired th prostatic lobe growth, characterized by a low absolute weight gain and reduction in parenchyma/stroma ratio, mainly in the dorsolateral lobe. Diabetes caused a reduction in the testosterone plasma levels, but not in the dihydrotestosterone. The activities of MMP2 and MMP9 were reduced in the prostatic lobes from diabetic animals. Both simultaneous and late insulin treatment maintain and restored, respectively, the age-matched control morphological and morphometrical parameters. These results allow to conclude that diabetes interfere negatively in the prostate growth during puberty with important stromal changes, including reduction in MMP2 and MMP9 activities, reinforcing the role of these enzymes in the normal prostate morphogenesis. On the other hand, even a late insulin replacement can restore the deleterious effects of diabetes in the prostate during puberty.
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural

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14

Ranasinghe, Himani Sumudumalee. "Mechanisms underlying hypoxic ischemic injury to the developing brain: The significance of matrix metalloproteinase 2 and 9". Thesis, University of Auckland, 2009. http://hdl.handle.net/2292/4962.

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Perinatal hypoxic ischemic (HI) injury is a leading cause of long-term neurological complications in newborn babies. Matrix metalloproteinases (MMPs) are a family of endopeptidases that are capable of degrading the extracellular matrix (ECM) components. They are considered to be integral in many physiological processes. However, recently it has been demonstrated that the inappropriate activity of these proteases, particularly MMP-2 and 9, contribute to the pathogenesis of cerebral ischemia in the adult brain. Given that ECM disruption is frequently observed following injury to the developing brain, it is possible that MMPs play an important role in HI injury processes in the developing brain. Therefore, this thesis evaluated the hypothesis that MMP-2 and 9 participate in the pathophysiology of HI injury to the developing brain. Since ECM remodelling is a fundamental process during brain development it was important to first characterise the MMP-2 and 9 profiles in the normal developing forebrain. We demonstrated that MMP-2, which mainly was observed in cortical plate neurons, declined with age, thus indicating a potential role in the development and differentiation of the cortical plate. Conversely, MMP-9 was increased with age, particularly during active myelination, indicating that it may contribute in myelination. Secondly, we showed an upregulation of MMP-9 within the ischemic core during the early hours following HI injury, suggesting that MMP-9 may be involved in the development of delayed injury processes following hypoxic ischemia. On the contrary, MMP-2 was strongly upregulated during a later stage following injury surrounding the ischemic core possibly suggesting that it plays a role in wound repair processes. Thirdly, the profiles of tissue (tPA) and urokinase (uPA) plasminogen activators were characterised following HI injury since they are known to be major upstream activators of MMPs. uPA upregulation paralleled that of MMP-2 suggesting a function for uPA in wound repair processes following HI injury to the developing brain through activation of MMP-2. In contrast with uPA, tPA activity remained unaffected following injury at both ages. Finally, MMP-9 activity was inhibited using a very specific MMP-2/9 inhibitor, SB-3CT, to determine if the MMP-9 deficiency protects the developing brain from HI injury. The elevated MMP-9 activity following HI injury was attenuated by the SB-3CT treatment. Although SB-3CT failed to confer any significant neuroprotection, we recommend that further investigations are needed before discounting the role of MMP-9 during HI injury to the developing brain. In conclusion, we suggest that MMP-9 is induced following an insult to the developing brain potentially contributing to the delayed neuronal death whilst MMP-2 is involved in essential developmental, differentiation and wound repair processes.

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Westin, Maria Cristina do Amaral 1949. "Expressão das proteínas MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 e VEGF-A na NIC 3 e no carcinoma invasor do colo do útero = Expression of the proteins MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 and VEGF-A in the CIN 3 and cervical cancer". [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313599.

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Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos Santos
Texto em português e inglês
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O carcinoma escamoso do colo uterino é precedido pela neoplasia intraepitelial cervical grau 3 (NIC 3). A invasão tumoral envolve a degradação da matriz extracelular e membrana basal do epitélio por enzimas proteolíticas denominadas metaloproteinases (MMPs). Os inibidores teciduais das metaloproteinases (TIMPs) também interferem no processo de invasão. Angiogênese é condição indispensável para a progressão tumoral. Objetivo: Analisar a expressão de MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 e VEGF-A na NIC 3 e carcinoma do colo uterino. Sujeito e Métodos: Estudo do tipo comparativo observacional constituído de três grupos:- Grupo 1: 55 casos com diagnóstico de NIC 3, Grupo 2: 30 casos com NIC 3 e carcinoma associados e Grupo 3: 46 casos com carcinoma. A expressão protéica foi pesquisada separadamente nas células tumorais e estromais por reação imunoistoquímica. Para estabelecer a porcentagem de células imunopositivas utilizou-se software morfométrico. Análise Estatística: Aplicou-se o Teste T-pareado ou de Mann-Whitney ou Wilcoxon Signed Rank. Resultados: Em todos os grupos, a expressão tumoral de MMP-14 foi maior que a estromal. Inversamente, a expressão de TIMP-2 foi maior nas células estromais que nas tumorais, em cada grupo diagnóstico. A expressão de MMP-9 foi maior nas células estromais que nas tumorais, com exceção do componente invasor do Grupo 2. A expressão estromal de TIMP-1 foi maior que a tumoral no carcinoma e, ao contrário, sua expressão foi maior nas células tumorais da NIC 3. A expressão de VEGF-A foi maior apenas nas células tumorais da NIC 3. Comparando a expressão dos marcadores entre os grupos, foram encontradas as maiores diferenças entre grupos extremos, ou seja, entre NIC 3 e carcinoma. A expressão de MMP-2 nas células estromais foi maior no componente NIC 3 do Grupo 2 que no NIC 3 do Grupo 1. A expressão de VEGF-A nas células estromais do carcinoma foi maior que nas células estromais da NIC 3. Conclusões: Os resultados deste estudo sugerem que a expressão de TIMP-1 aumenta nas células do estroma e diminui nas células tumorais quando a NIC 3 progride para carcinoma invasor. MMP-9 e TIMP-2 tiveram expressão similar na NIC 3 e no carcinoma, o que limita inferências sobre seu papel na progressão neoplásica. O padrão imunoistoquímico da expressão das MMPs, TIMPs e VEGF-A na NIC 3 e no carcinoma invasivo, quando estas lesões estavam associadas, foi semelhante. A expressão do VEGF-A foi maior nas células tumorais do que nas estromais da NIC 3, porém quando esta lesão progride para carcinoma invasivo sua expressão aumenta nas células do estroma e não se altera nas tumorais. A expressão de MMP-14, MMP-2, TIMP-1 e VEGF-A aumentou com a gravidade da neoplasia
Abstract: Introduction: Squamous cell carcinoma of the cervix is preceded by cervical intraepithelial neoplasia grade 3 (CIN 3). Tumor invasion involves degradation of extracellular matrix and epithelium basement membrane by proteolytic enzymes called metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) are also involved in the invasion process. Angiogenesis is a prerequisite for tumor progression. Objective: To analyze the expression of MMP-2, MMP-9 and MMP-14, TIMP-1, TIMP-2 and VEGF-A in CIN 3 and invasive carcinoma. Subject and Methods: This comparative observational study was consists of three groups: Group 1: 55 cases diagnosed with CIN 3, Group 2: 30 cases with CIN 3 associated with invasive carcinoma and Group 3: 46 cases with invasive carcinoma. Protein expression was investigated separately in tumor and stromal cells by immunohistochemistry and evaluated by the percentage of cells positive for immunostaining using morphometric software. Statistical Analysis: Was performed applying paired t-test or Mann-Whitney or Wilcoxon Signed Rank. Results: In each diagnostic group, expression markers were significantly higher: MMP-14 in tumor cells, and TIMP-2 in stromal cells; also MMP-9 expression was significantly higher in stromal cells, except in invasive component of group 2, and TIMP-1 had significantly higher expression in stromal cells of invasive carcinoma and in tumor cells of CIN 3. VEGF-A expression was significantly higher only in tumor cells CIN 3. Comparing the expression of markers between groups, two by two, we find the greatest differences between the extreme groups, i.e. between invasive carcinoma and CIN 3. The expression of MMP-2 was significantly greater in the stromal component CIN 3 in group 2 than in CIN 3 only. The expression of VEGF-A was significantly higher in the group stromal cell carcinoma when compared to stromal cells CIN 3. Conclusions: The results of this study suggest that the expression of TIMP-1 increases in the stromal cells and decreases in tumor cells when CIN 3 progresses to invasive carcinoma. MMP-9 and TIMP-2 had similar expression in CIN 3 and invasive carcinoma, which limits inferences about its role in neoplastic progression. The immunohistochemical pattern of expression of MMPs, TIMPs and VEGF-A in CIN 3 and invasive carcinoma, as these lesions were associated, was similar. The expression of VEGF-A was higher in tumor cells than in stromal cells in CIN 3, but when the lesion progresses to invasive carcinoma its expression increases in the stromal cells and the tumor cells does not change. The expression of MMP-14, MMP-2, TIMP-1 and VEGF-A was increased with the severity of the neoplasia
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde

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16

Massif, Laurent. "Biofonctionnalisation du silicium poreux pour la détection de MMP-8 (Collagénase-2)". Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON12201.

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La métalloprotéinase matricielle (MMP)-8 ou collagénase-2 est capable de rompre les molécules natives, triples hélices, du collagène interstitiel, initiant ainsi le remodelage cellulaire lors du déplacement dentaire induit par une force orthodontique. C'est un bio-marqueur incontournable du remaniement tissulaire parodontal. L'augmentation de l'expression et de l'activation de MMP-8 dans le fluide gingival reflète l'activité du remodelage parodontal induit par les forces orthodontiques. En moyenne, la concentration de MMP-8 prélevée dans le fluide gingival des patients orthodontiques est 12 fois plus élevée (56 ± 50 µg/l contre 4,6 ± 4 µg/l) que chez les patients non orthodontiques. Le suivi des fluctuations de MMP-8 durant le déplacement orthodontique nécessite la mise au point d'un biocapteur. L'objectif de ce travail est d'utiliser une structure photonique à base de silicium poreux pour la conception d'un biocapteur optique de la MMP-8. Nous avons déterminé le choix du substrat de silicium poreux (PSi) le plus adapté à notre application avec une surface spécifique élevée et pores suffisamment ouverts pour l'infiltration des biomolécules qui sont des anticorps anti-MMP-8. Ensuite nous avons mis en place un procédé de fonctionnalisation chimique et biologique de la surface interne de ces échantillons
The matrix métalloprotéinase (MMP) 8 or collagenase 2 is able to cleave native molecules, triple helixes, of the interstitial collagen, so introducing the cellular reshaping during orthodontic tooth movement. It is a major biomarker of the periodontal tissular remodeling. The increase of the expression and the activation of MMP-8 in the gingival fluid reflects the activity of the periodontal remodeling. On average, the concentration of MMP-8 taken in the gingival fluid of the orthodontic patients is 12 times as raised(brought up) (56 ± 50 µg / l against 4,6 ± 4 µg / l) that at the not orthodontic patients. Followed it by fluctuations in MMP-8 during the orthodontic movement require the development of a biosensor. The objective of this work is to use a photonique structure with porous silicon for the conception of an optical biosensor of the MMP-8. We determined the choice of the substratum of porous silicon (PSi) the most adapted to our application with a high specific surface and pores opened enough for the infiltration of the biomolecules which are antibodies anti-MMP-8. Then we set up a process of chemical and biological fonctionnalisation of the internal surface of these samples

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Ruokolainen, H. (Henni). "The prognostic role of matrix metalloproteinase -2 and -9 (MMP-2, MMP-9) and their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in head and neck squamous cell carcinoma". Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514279174.

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Abstract Traditional clinicopathological factors are not accurate enough to predict the behavior of head and neck squamous cell carcinoma (HNSCC). The most powerful indicator of prognosis is the stage of the disease. New prognostic markers have, however, been searched for in order to better identify patient groups in need of different treatments or follow-up. Gelatinases (MMP-2, -9) are endopeptidases associated with tumor invasion and angiogenesis, and their tissue inhibitors (TIMP-1, -2) are also linked to cancer cell invasion and metastasis formation. In some cancer types they are even prognostic and relate with a more aggressive clinical course of the disease. In the present work the expression and the clinical significance of tumor tissue and circulating immunoreactive proteins for MMP-2, -9, TIMP-1 and -2 were assessed in HNSCC. The study group included 74 patients with HNSCC and 44 healthy controls. The expression of immunoreactive proteins was examined in paraffin-embedded tumor sections by immunohistochemical staining using specific antibodies, and the pretreatment serum levels of those proteins were quantitatively measured by ELISA assay. Immunohistochemical overexpression of MMP-9 in tumor was for the first time found to predict the prognosis for shortened survival in HNSCC, the cause-specific survival rates being 45% and 92% and relapse-free survival being 42% and 79% in MMP-9 positive or negative cases, respectively. Additionally, tissue TIMP-1, MMP-2 and TIMP-2 positivity were all also linked with poorer survival of patients with HNSCC. However, these differences remained less distinct than with MMP-9. The expression of gelatinases and their inhibitors in tumor tissue was also an indicator for later lymph node or hematogenic relapses in HNSCC patients. Circulating MMP-9 and TIMP-1 levels were significantly higher in HNSCC patients than in healthy controls. Further, the cause-specific and relapse-free survival rates were lower among HNSCC patients with high MMP-9 and TIMP-1 serum levels compared to patients with low levels of circulating MMP-9 and TIMP-1. A significant correlation was shown between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors. No correlation was found between tissue or circulating levels of gelatinases or their inhibitors and the traditional clinical or histopathological factors, except for the association between tissue and circulating TIMP-1 and the size of the primary tumor. Taken together, these results suggest that tissue expression of gelatinases and their inhibitors as well as pretreatment circulating MMP-9 and TIMP-1 levels could be prognostic in estimation of the clinical course of HNSCC. The results indicate further studies are needed with larger patient materials.

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Cruz, Luis Eduardo Rilling da Nova. "Avaliação da proporção de células mononucleares e de MMP-2 e 9 na periodontite crônica em fumantes e não-fumantes". Universidade Federal de Pelotas, 2010. http://repositorio.ufpel.edu.br/handle/ri/2243.

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The objective of the present study was the immunohistochemical evaluation of the proportion of mononuclear cells and the expression of MMP-2 and 9 on chronic periodontitis between smokers and non-smokers. From the 127 patients examined 31(16 non-smokers and 15 smokers) fulfill the inclusion criteria were included in the study. These patients underwent surgical procedures and 31 biopsies were collected and divided in two parts, one for histological preparation and the other for zymography. Each sample was histologically processed and exposed to monoclonal antibodies for B cells (anti-CD20), memory T cells (anti-CD45RO) and macrophages or monocytes (anti-CD68) detection. The samples showed a similar pattern, with connective tissue rich in inflammatory cells. The histometric analysis showed that the total amount of mononuclear inflammatory cells labeled did not differ significantly between smokers and non-smokers (p> 0.05). Evaluating each cell type separately, significant differences were not detected between groups (p> 0.05). When stratifying the samples into regions (coronal, middle and apical third) to evaluate the presence of individual cell types in each region significant differences between the groups were not detected (p> 0.05). The zymography of the samples suggested that the expression of MMP-2 and 9 showed no statistically significant differences between the two groups (p> 0.05). Thus, within the limits of this study, we can conclude that sites with chronic periodontitis in smokers and non-smokers did not differ in the amount of mononuclear inflammatory cells and in the expression of MMPs 2 and 9.
O estudo teve como objetivo a avaliação imunoistoquímica da proporção de células mononucleares e da expressão zimográfica da MMP-2 e 9 na periodontite crônica em fumantes e não-fumantes. Foram examinados 127 pacientes dos quais 31 preencheram os critérios de inclusão e foram inseridos no estudo, sendo 16 não-fumantes e 15 fumantes. Estes pacientes foram operados e 31 biópsias foram coletadas de área interproximal de dentes com bolsa periodontal >5mm e divididas longitudinalmente em duas partes, uma para análise histológica e outra para zimografia. As amostras foram processadas histologicamente e expostas aos anticorpos monoclonais para células B (anti-CD20), células T de memória (anti-CD45RO) e monócitos ou macrófagos (anti-CD68). De maneira geral, as amostras apresentaram padrão semelhante, com um tecido conjuntivo subjacente ao epitélio oral rico em células inflamatórias. A análise histométrica demonstrou que a quantidade total de células inflamatórias mononucleares marcadas não diferiu entre fumantes e não-fumantes (p>0,05). Ao avaliar cada tipo celular separadamente, também não foram detectadas diferenças estatisticamente significativas entre os grupos (p>0,05). Ao dividir as amostras em regiões (terço coronal, médio e apical) e avaliar a presença de cada tipo celular em cada uma das regiões também não foram detectadas diferenças estatísticas significantes entre os grupos (p>0,05). A avaliação das zimografias sugere que a expressão de MMP-2 e 9 não apresentaram diferenças estatisticamente significantes entre os dois grupos (p>0,05). Assim, dentro dos limites deste estudo, pode-se concluir que os sítios com periodontite crônica de fumantes e não-fumantes não diferem em relação à quantidade e localização de células inflamatórias mononucleares e na expressão de MMPs 2 e 9.

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Kilcullen, Niamh. "Heart-type fatty acid-binding protein (H-FABP) and matrix metalloproteinase-2 (MMP-2) in diagnosis and risk stratification in patients with acute coronary syndromes". Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434465.

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Rahko, E. (Eeva). "Evaluation of tumor suppressor gene p53, oncogene c-erbB-2 and matrix-metalloproteinase-9 as prognostic and predictive factors in breast carcinoma". Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514284571.

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Abstract Breast carcinoma is the most common malignancy in females in western countries. Classical prognostic factors such as the size of a primary tumor and the presence or absence of axillary lymph node metastases, malignancy grade and hormone receptor status reflect the subsequent risk of disease recurrence after primary therapy and the need for adjuvant therapies. However, most breast carcinomas are detected in the early stage of the disease and the value of these classical prognostic factors is limited. There is also a great need to find new factors predicting the clinical efficacy of the anticancer drugs available. In this thesis tumor suppressor gene p53, oncogene c-erbB-2 and matrix metalloproteinase-9 were evaluated for their prognostic relevance in breast carcinoma patients treated in Oulu University Hospital, and matrix metalloproteinase-9 was also analyzed in women with premalignant lesions in the breast tissue in order to examine its role in breast carcinogenesis. Histological analyses were carried out from formalin-fixed, paraffin-embedded primary tumor specimens and p53, c-erbB-2 and matrix metalloproteinase-9 (MMP-9) statuses were systematically analyzed by immunohistochemistry. P53 expression correlated with disease-free survival and overall survival in patients with early-stage breast carcinoma, regardless of adjuvant antiestrogen therapy. The co-expression of p53 and c-erbB-2 characterizes a tumor type with a clinically aggressive course of breast carcinoma. The clinical efficacy of anthracyline-based chemotherapy in metastatic carcinoma might be limited in patients with p53 expression in a primary tumor. When postmenopausal patients with lymph node metastases and receiving adjuvant antiestrogen therapy were examined, MMP-9 expression indicated a slightly greater risk of breast carcinoma recurrence in patients with estrogen receptor negative tumors. Hyperplastic breast tissue and invasive breast carcinoma lesions expressed some MMP-9 immunopositivity. However, the strongest positivity was seen in ductal carcinoma in situ samples, suggesting that MMP-9 participates in breast carcinogenesis in the preinvasive phase.

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Yeung, Oliver. "Differential regulation of matrix metalloproteinase-2 (MMP-2) by phorbol myrisate acetate, and by DL-Ã-difluoromethylornithine, in cell lines of varying tumorigenic and metastatic potential". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ46056.pdf.

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Müller, Olga [Verfasser], i Perihan [Akademischer Betreuer] Nalbant. "Die Rolle der Rho-GTPase RhoA in der Transkriptionskontrolle der Matrix Metalloproteinase 9 (MMP9) in U-2 OS Zellen / Olga Müller ; Betreuer: Perihan Nalbant". Duisburg, 2016. http://d-nb.info/1116941910/34.

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Souza, Markus Vinicius Campos. "Treinamento resistido e reposição hormonal aumentam a atividade das metaloproteinases-2 e a qualidade de osso de ratas ovariectomizadas". Universidade Federal de São Carlos, 2016. https://repositorio.ufscar.br/handle/ufscar/8146.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Purpose: The aim of the present study was to investigate the influence of resistance training (RT) and hormone replacement (HR) on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX) rats. Methods: Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group): shamoperated sedentary (SHAM Sed), ovariectomized sedentary (OVX Sed), sham-operated resistance training (SHAM RT), ovariectomized resistance training (OVX RT),(OVX Sed-HR), and OVX RT-HR. HR groups received implanted silastic capsules with a 5% solution of 17β-estradiol (50 mg 17β-estradiol/ml of sunflower oil). In a 12-week RT period (27 sessions; 4–9 climbs) the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. Results: Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load) demonstrated better bone tissue quality in the RT associated with HR. Conclusion: The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.
Objetivo: o objetivo do presente estudo foi investigar a influência do treinamento resistido (TR) e reposição hormonal (RH) na atividade das metalloproteinases 2 (MMP- 2), nas propriedades biomecânicas e biofísicas do osso de ratas ovariectomizadas (OVX). Métodos: fêmeas albinas foram agrupadas em seis grupos (11 animais por grupo): Sham Sedentário (SHAM Sed); Ovariectomizado Sedentário (OVX Sed); Sham Operado Treinamento Resistido (SHAM TR); Ovariectomizado Treinamento Resistido (OVX TR); Ovariectomizado Sedentário com Reposição Hormonal (OVX Sed-RH) e Ovariectomizado Treinamento Resistido com Reposição Hormonal (OVX TR-RH). Os animais dos grupos que receberam RH tiveram capsulas de silastic implantadas com uma solução de óleo de girassol com 180μg de 17β-estradiol/mL. Os animais foram submetidos ao TR por 12 semanas (3 vezes por semana, onde realizavam de 4-9 escaladas), o treinamento acontecia em uma escada vertical de 1,1m com os pesos fixados em sua cauda. As análises biomecânicas e biofísicas foram realizadas utilizando a máquina de teste universal e a atividade da MMP-2 por zimografia. Resultados: a densidade óssea e o conteúdo mineral ósseo foram maior nos grupos TR e RH. A atividade da MMP-2 também foi maior nos grupos que foram submetidos ao TR e RH. A análise biomecânica (rigidez, carga no ponto de fratura e carga máxima) utilizada para demonstrar a qualidade do osso foi maios no grupo TR com associação do RH. Conclusão: nossos resultados indicam que o TR e RH foram eficientes em aumentar a atividade da MMP-2, as propriedades biomecânicas e biofísicas dos ossos de ratas ovariectomizadas.

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Peres, Juliana Alves. "Avaliação histométrica do reparo de defeito ósseo em calvária de rato após implante de rhMMP-2 ligada à monoleína". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/58/58137/tde-18092012-154340/.

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As metaloproteinases da matriz (MMPs) são enzimas proteolíticas dependentes de zinco que degradam componentes da matriz extracelular, facilitando a remodelação tecidual e a migração celular. MMPs secretadas por osteoclastos exercem papel central na absorção óssea fisiológica e estão também associadas a processos de degradação patológica do osso. No entanto, o papel essencialmente degradador de osso das MMPs, particularmente da MMP-2, vem sendo questionado em anos recentes por estudos que evidenciam sua importância na diferenciação de células da linhagem osteoblástica e na formação de tecido ósseo em cultura. Neste sentido, é possível que a MMP-2 exerça um papel importante na formação de tecido ósseo em processo de reparação. O objetivo do presente trabalho foi investigar a pretensa ação osteo-estimulatória da rhMMP-2 ligada à monoleína (usada como carreador) implantada em defeito confeccionado na calvária de ratos. Foram confeccionados defeitos ósseos unilaterais de 4 mm de diâmetro na calvária de ratos adultos; nos animais controles o defeito ósseo foi mantido com o preenchimento natural de coágulo sanguíneo e nos animais implantados o defeito foi preenchido com monoleína ou com rhMMP-2 ligada à monoleína. Os animais foram eutanasiados após 2 e 4 semanas e a taxa de neoformação óssea foi estimada em cortes histológicos por um método histométrico de contagem diferencial de pontos. A taxa de neoformação óssea foi semelhante nos animais dos grupos controle e monoleína e significativamente maior nos animais do grupo MMP-2, em ambos os períodos analisados. Os resultados permitem concluir que a monoleína não interferiu com o processo reparacional e pareceu eficaz como carreador da rhMMP-2, e adicionam evidências á hipótese da importância da atividade da MMP-2 para a formação óssea, em um modelo experimental in vivo de reparo ósseo.
Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade extracellular matrix components, facilitating cell migration and tissue remodeling. MMPs secreted by osteclasts are important in the physiological bone resorption as in pathological bone degradation. However, the essentially bone absorbing hole of MMPs, particularly of the MMP-2, has been questioned in recent years by studies that show its importance in osteoblastic cells differentiation and in vitro bone formation. Therefore, the MMP-2 may have also an important hole in reparational bone formation. The purpose of the present study was to investigate the pretense osteostimulatory effect of the rhMMP-2 linked to monoolein (used as a carrier) implanted into rat calvarial defects. Bone defects of 4mm in diameter were created unilaterally in rats calvaria and filled with natural blood clot (control), monoolein or rhMMP-2 linked to monoolein. The animals were killed 2 and 4 weeks postoperatively and the rate of new bone formation was estimated in histological sections by a histometric differential point-counting method. The rate of reparational bone formation was similar in the animals from control and monoolein groups and was significantly greater in the MMP-2 group, in both periods. From the results it may be concluded that monoolein did not interfere with the reparacional process and seemed effective as a rhMMP-2 carrier. In addition, the results add evidence to the importance of MMP-2 activity for bone formation, in an in vivo bone healing experimental model.

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Meschiari, César Arruda. "Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-12032012-110848/.

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Metaloproteinases da matriz extracelular (MMPs) são uma família de endopeptidases zinco-dependentes conhecidas por degradar componentes do tecido conjuntivo em processos fisiológicos e patológicos. A regulação da atividade das MMPs pode ser feita pelos inibidores teciduais de metaloproteinases (TIMPs). A doença periodontal (DP) é a inflamação crônica em que atividade excessiva das MMPs e mieloperoxidase (MPO) são apontadas como responsáveis pela destruição dos tecidos suporte dos dentes. Os componentes da saliva são derivados da vascularização local sendo possível encontrar neste fluido o reflexo de muitas moléculas presentes no plasma. Desta forma, os objetivos deste trabalho foram: 1) Comparar os níveis de MMPs, TIMPs e MPO na saliva total estimulada (STE) e plasma de pacientes com DP antes (DA) e após (DT) o tratamento periodontal não cirúrgico, e em voluntários saudáveis no início do estudo (CA) e após 3 meses (CT); 2) Avaliar se existe correlação entre os resultados. Foram realizadas as dosagens de MMP-8, MMP-9, TIMP-1 e TIMP-2 pelo método de ELISA; a atividade gelatinolítica das formas da MMP-9 por zimografia; e a atividade da MPO por ensaio colorimétrico. Houve uma menor atividade gelatinolítica, assim como menores concentrações de MMP-8 e TIMP-2 na STE de DT quando comparadas a DA (p < 0,05). A atividade de MPO foi superior no grupo DA em relação a CA (p < 0,05). Foram encontradas correlações moderadas e estatisticamente significantes entre a MMP-9 quantificada por ELISA no plasma e todos os parâmetros resultantes da zimografia de STE, isto é, MMP-9 de massa molecular de 92 kDa (r = 0,37, p = 0,002), 130 kDa (r = 0,35, p =0,003 ), a soma da sua atividade gelatinolítica (130 + 92 kDa) (r = 0,43, p = 0,0002), gelatinase de 180 kDa (r = 0,35, p = 0,003), e soma da atividade gelatinolítica total (180+130+92 kDa ) (r = 0,37, p = 0,002). A MMP-8 plasmática apresentou correlação com a atividade gelatinolítica das bandas de 92 kDa (r = 0,30 e p = 0,01) e soma da atividade gelatinolítica (130 + 92 kDa) (r = 0,24 e p= 0,04) presentes na STE. Também foi possível observar uma correlação fraca entre a atividade gelatinolítica da MMP-9 de 92 kDa do plasma e a atividade gelatinolítica da banda de 180 kDa (r = 0,26 e p = 0,03), e uma correlação moderada entre o TIMP-2 do plasma e o TIMP-2 da STE (r = 0,32 e p =0,04). Os resultados mostram que a atividade gelatinolítica da STE pode estar refletindo as concentrações de marcadores inflamatórios sistêmicos tais como a MMP-8 e MMP-9, assim como a concentração de TIMP-2 na STE pode estar refletindo a concentração de TIMP-2 circulante. A avaliação conjunta destes resultados sugere que existe uma atenuação de alguns dos marcadores inflamatórios analisados na STE e no plasma após o tratamento da DP, e que os níveis salivares e plasmáticos de alguns destes marcadores se correlacionam. Como a coleta de saliva é menos invasiva, mais estudos sobre a correlação destes marcadores nestes dois fluidos pode ser muito interessante.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to cleave components of the connective tissue in physiological and pathological processes. The regulation of MMP activities is done by the tissue inhibitors of metalloproteinases (TIMPs). Periodontal disease (PD) is a chronic inflammation with excessive activity of MMPs, which degrade the tooth supporting tissues. The saliva components are derived from the local blood supply, and this fluid may therefore reflect the plasma. So, the objectives of this study were: 1) to compare the levels of MMPs, TIMPs and MPO in stimulated whole saliva (SWS) and plasma of PD patients before (PB) and 3 months after (PT) the non-surgical periodontal treatment, and in healthy volunteers at baseline (CB) and 3 months after baseline (CT), and 2) to evaluate the correlations between the results found. Measurements of MMP-8, MMP-9, TIMP-1 and TIMP-2 were performed by ELISA. Gelatinolitic activity of MMP-9 forms were determined by zymography, and the MPO activity was determined by colorimetric assay. There was lower gelatinolitic activity, and lower concentrations of MMP-8 and TIMP-2 in SWS on PT group compared with PB group (p <0.05). MPO activity was higher in PB compared to CB (p <0.05). Statistically significant moderate correlations were observed in all associations between MMP-9 performed by ELISA in plasma and gelatinolitic activity bands of STE: MMP-9 molecular form of 92 kDa (r = 0,37, p = 0,0017), MMP-9 molecular form of 130 kDa (r = 0,35, p = 0,003), the sum of its gelatinase activity (130 +92 kDa) (r = 0,43, p = 0,0002), gelatinase of 180 kDa (r = 0,35, p = 0,003), and the sum of total gelatinase activity (180+130+92 kDa) (r = 0,37, p = 0,002). Circulating MMP-8 levels correlate with salivary gelatinase activity bands of 92 kDa (r = 0,30, p = 0,01) and the sum of gelatinase activity (130 +92 kDa) (r = 0,24, p = 0,04). In addition, a weak correlation between gelatinase activity of plasmatic 92 kDa MMP-9 and gelatinase of 180 kDa in SWS (r= 0,26 p = 0,03) was found, and a moderate correlation between plasmatic TIMP-2 and TIMP-2 of SWS (r = 0,32, p = 0,004). The results show that the gelatinase activity of SWS may reflect the concentrations of systemic inflammatory markers such as MMP-8 and MMP-9, also the concentration of TIMP-2 in the SWS may reflect the circulating concentration of TIMP-2. The evaluation of these results suggests that there is an attenuation of some inflammatory markers analyzed in the SWS and in plasma after treatment of PD. Furthermore, there are correlations between salivary and plasma levels in some of these markers. Because saliva sampling is less invasive, more studies about the correlations between these markers in these two fluids are necessary.

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Fontanelli, Beatriz Aparecida Fioruci 1985. "Efeitos do consumo crônico de etanol sobre a atividade de MMP-2/MMP-9 e sobre o metabolismo do ácido retinóico nos lobos dorsais e laterais da próstata de ratos adultos = Effects of chronic ethanol consumption on the activity of MMP-2/MMP-9 and on retinoic acid metabolism in the dorsal and lateral prostate lobes of adult rats". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317953.

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Orientadores: Sérgio Luis Felisbino, Francisco Eduardo Martinez
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Pesquisadores têm mostrado que o consumo crônico de etanol altera a concentração do ácido retinóico, metabólito ativo da vitamina A, em muitos órgãos, incluindo a próstata. O ácido retinóico é essencial para o desenvolvimento normal da próstata e para a manutenção de sua homeostase. Alterações na concentração e no metabolismo do ácido retinóico estão relacionadas com o desenvolvimento de lesão na próstata. Adicionalmente, a atividade de metaloproteinases da matriz extracelular (MMPs), também está relacionada com o desenvolvimento de alterações na próstata. Assim, o presente trabalho teve por objetivo descrever os efeitos dos consumos, baixo e alto, de etanol sobre as proteínas envolvidas na síntese e no catabolismo do ácido retinóico (artigo I), bem como, sobre a atividade enzimática das MMPs (artigo II) nos lobos dorsais e laterais da próstata.Vinte ratos adultos (~ 90 dias de idade) de cada variedade, UChA e UChB, foram divididos nos grupos (n=10/grupo): UChA (consumo baixo de etanol, 0,2-2 g/kg/dia), UChAC (ratos que não consumiram etanol); UChB (consumo alto de etanol, > 2g/kg/dia), UChBC (ratos que não consumiram etanol).Após o período experimental (~ 150 dias de idade), os ratos foram eutanasiados por decapitação e os lobos dorsais e laterais das próstatas foram coletados e dissecados: (1) para avaliar os níveis e a localização das proteínas ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, CYP26B1, CYP2E1, através de western blot e imuno-histoquímica, bem como, a atividade catabólica das CYP26A1, CYP26B1, CYP2E1 por ensaio bioquímico e quantificação por HPLC-MS/MS; (2) e para avaliar a atividade da MMP-2 e da MMP-9, e os níveis dos inibidores teciduais de metaloproteinases (TIMP-1/ TIMP-2), através de zimografia e Elisa, respectivamente. No grupo UChA, a ALDH1A3 aumentou na próstata dorsal, enquanto as proteínas ALDH1A1 e ALDH1A2 diminuíram na próstata lateral. No grupo UChB, as proteínas ALDH1A1, ALDH1A2, e ALDH1A3 aumentaram na próstata dorsal, enquanto a ALDH1A3 diminuiu no lobo lateral. A concentração do ácido retinóico aumentou, indicando diminuição da atividade da CYP2E1, e diminuiu quando se avaliou a CYP26, indicando aumento de sua atividade na próstata dorsal do UChB. Além disso, o ácido retinóico diminuiu quando se avaliou a atividade de CYP total nos grupos experimentais, sendo somente aumentado na próstata lateral do UChA. O consumo baixo de etanol (grupo UChA) diminuiu a atividade das MMP-2 e MMP-9 e o nível das TIMP-2 e TIMP-1 na próstata lateral, enquanto que na próstata dorsal o etanol diminuiu a atividade de MMP-2 e o nível de TIMP-1. Por outro lado, no grupo UChB, o etanol diminuiu somente a atividade da MMP-9 na próstata lateral e não alterou os níveis de TIMP-1 e TIMP-2.Nossos resultados indicam que o etanol modula a síntese e o catabolismo do ácido retinóico na próstata do rato de modo dependente de sua concentração. Além disso, o consumo crônico e baixo de etanol diminui a atividade das metaloproteinases -2 e -9, sendo a próstata lateral o lobo afetado e, portanto, mais susceptível a estas alterações, do que o lobo prostático dorsal.
Abstract: Researchers have shown that chronic ethanol consumption alters the retinoic acid concentration, an active metabolite of vitamin A, in many organs including the prostate. The retinoic acid is essential for the normal development of prostate and for maintaining its glandular homeostasis. Changes in concentration and metabolism of retinoic acid are related to lesion development in the prostate. Additionally, the activity of matrix metalloproteinases (MMPs), also relates to development of alterations in prostate. Thus, this study aimed to describe the effects of low and high doses of ethanol consumption, on the proteins involved in the synthesis and catabolism of retinoic acid (Article I), as well as on the enzymatic activity of MMPs (Article II) the dorsal and lateral lobes of the prostate. Twenty adult rats (~ 90 days old) of each variety, UChA and UChB, were divided into groups (n = 10 / group): UChA (low ethanol consumption, 0.2-2 g /kg / day), UChAC (rats not consumed ethanol); UChB (high ethanol consumption, > 2 g/ kg/ day), UChBC (rats not consumed ethanol). After the experimental period (~ 150 days old), the rats were euthanized by decapitation and dorsal and lateral lobes of the prostates were collected and dissected: (1) for evaluate the levels and location of the proteins ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, CYP26B1, CYP2E1, by western blot and immunohistochemistry, as well as, catabolic activity of CYP26A1, CYP26B1, CYP2E1 by biochemical assay and quantification by HPLC¿MS/MS; (2) and to evaluate the activity of MMP-2 and MMP-9, and the levels of tissue inhibitors of metalloproteinases (TIMP-1 / TIMP-2) using zymography and ELISA, respectively. In the UChA group, ALDH1A3 increased in dorsal prostate, while the proteins ALDH1A2 and ALDH1A1 decreased in the lateral prostate. In the UChB group, the proteins ALDH1A1, ALDH1A2 and ALDH1A3 increased in the dorsal prostate, while ALDH1A3 decreased in the lateral lobe. The concentration of retinoic acid increased, indicating a decrease in the CYP2E1 activity, and decreased when evaluated CYP26, indicating increased of CYP26 activity in the UChB dorsal prostate. Furthermore, the retinoic acid decreased when assessing the CYP total activity in the experimental groups, but only increased in the lateral prostate of UChA. The low ethanol consumption (UChA group) reduced the activities of MMP-2 and MMP-9 and the levels of TIMP-2 and TIMP-1 in the lateral prostate, while dorsal prostate the ethanol decreased the MMP-2 activity and the level of TIMP-1. On the other hand, in the UChB group, ethanol only decreased the activity of MMP-9 in the lateral prostate and did not alter the levels of TIMP-1 and TIMP-2. Our results indicate that ethanol modulates the synthesis and catabolism of retinoic acid in the rat prostate in a concentration-dependent manner. In addition, the chronic and low consumption of ethanol decreases the activity of metalloproteinases -2 and -9 in the lateral lobe prostate, showing that this organ is more susceptible to these changes than dorsal lobe prostate
Doutorado
Anatomia
Doutora em Biologia Celular e Estrutural

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Tiano, Gilberto Carlos [UNESP]. "Estudo da expressão de MMP-2 e MMP-9 por fibroblastos gengivais de camundongos estimulados por NaF via NF-kB, p44/42, p38 e PI3K". Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/95474.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O declínio mundial da cárie dentária é atribuído ao uso abrangente do flúor. Embora esse elemento seja capaz de proteger os dentes, seu uso excessivo pode levar a uma ação citotóxica causando a inibição do crescimento celular, da síntese de proteínas e até mesmo a morte celular. O primeiro objetivo deste estudo foi investigar a concentração ideal do NaF (NaF) capaz de ativar os fibroblastos gengivais de camundongos sem induzir morte celular. Observou-se que, nesses fibroblastos, a concentração de 40 μg F/mL induziu morte celular de 62,6 %. Na concentração de 20 μg F/mL a morte celular foi de apenas 22,1%. Com base nesses resultados, optou-se por utilizar a concentração de 20 μg F/mL como dose máxima para investigar os mecanismos envolvidos na ativação dos fibroblastos gengivais. Dessa forma, avaliou-se a capacidade do NaF induzir a expressão de MMP-2 e MMP-9 pelos fibroblastos gengivais de camundongos na presença ou ausência de LPS, assim como a produção da quimiocina CCL-3/MIP-1α e óxido nítrico. Avaliou-se também a participação das vias de sinalização intracelular p44/42, p38, PI3K e NF-кB envolvidas durante essa ativação, por meio da utilização dos respectivos inibidores PD98059 (50 μM), SB202190 (10 μM), LY294002 (30 μM) e dexametasona (10 μM). Observou-se que o NaF foi capaz de estimular os fibroblastos gengivais a expressarem MMP-9, mas não MMP-2, na concentração de 20 μg F/mL com pico máximo 6 horas após, retornando aos níveis normais 24 horas após. A produção da quimiocina CCL3/MIP-1α pelos fibroblastos estimulados pelo NaF também foi observada com a concentração de 20 μg F/mL com pico máximo 6 horas após estímulo. Na presença de LPS, observou-se uma potenciação da expressão de MMP-9 e produção de CCL3/MIP-1α na concentração de 20 μg F/mL, 6 horas após.
The worldwide decline of the dental caries is attributed to the widespread use of fluoride. Although this element is capable of protecting the teeth, its excessive use, can lead to a cytotoxic action, causing an inhibition of the cell growth, of the protein synthesis and even the cellular death. Based on these results, we have chosen to use a concentration of 20 μ g F/mL as maximum concentration to investigate the mechanisms involved in the activation of the gingival fibroblasts. It was observed that, on those fibroblasts, the concentration of 40 μg F/mL has resulted in a death cellular index of 62.6%. In the concentration of 20 μg F/mL the cellular death was of 22.1% only. Based on these results, the concentration of 20 μg F/mL has been chosen as maximum concentration to investigate the mechanisms involved in the activation of the gingival fibroblasts. Later, the ability of NaF to induce the expression of MMP-2 and MMP-9 in gingival fibroblasts of mice in the presence or absence of LPS has been assessed, as well as the production of chemokine CCL-3/MIP-1a and nitric oxide. It also evaluated the participation of intracellular signaling pathways p44/42, p38, PI3K e NF-kB involved in this activation, through inhibitors PD98059 (50 μM), SB202190 (10 μM), LY294002 (30 μM) e dexamethasone (10 μM). It was observed that the NaF was capable to stimulate the gingival fibroblasts to express MMP-9, at the concentration of 20 μgF/mL with maximum peak 6 hours after, returning to normal levels 24 hours after. The expression of MMP-2 was not observed. The production of chemokine CCL3/MIP-1α was also observed with the concentration of 20 μgF/mL with maximum peak 6 hours after the stimulation. In the presence of LPS, it was observed an intensification in the expression of MMP-9 and also in the production of CCL3/MIP-1α at the concentration of 20 μgF/mL, 6 hours later.

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Miller, Crystal M. "Mmp2 regulates the matrix molecule Faulty attraction to promote motor axon targeting in Drosophila". Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1286816736.

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Edsparr, Karin. "Migration of natural killer cells : matrix interaction, locomotion and regulation of matrix metalloproteinases (MMPs) by IL-2 and chemokines /". Göteborg: Dept. of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, 2009. http://hdl.handle.net/2077/20450.

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Seabra, Fl?vio Roberto Guerra. "An?lise imuno-histoqu?mica das metaloproteinases da matriz ( MMP-1,MMP-2 e MMP-9) na doen?a periodontal". Universidade Federal do Rio Grande do Norte, 2006. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17147.

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The tissular destruction found in periodontal diseases is caused mainly by components of the host that have its production stimulated by the products of the microorganisms present on the plaque. Matrix Metalloproteinases (MMPs), a class of enzymes involved both in physiologic and pathologic extracellular matrix degradation are considered the main responsible for the characteristic tissular loss in periodontal disease, and the understanding of how this happens can have a series of beneficial implications for prevention, diagnosis and treatment of this illness. The aim of this work was to study the immunohistochemical expression of MMP-1, MMP-2, and MMP-9 in fragments of gingival biopsies with clinical diagnose of periodontal disease. MMP-1 has expressed significantly more than the others MMPs in gingivitis both in the epithelium (p=0,0008) and connective tissue (p=0,0049). In periodontitis, both MMP-1 and MMP-9 has expressed significantly more than MMP-2 in the epithelium (p<0,0001) and in the connective tissue (p=0,0002). MMP-1 and MMP-9 presented more expression in periodontitis than in gingivitis but MMP-1 only in the connective tissue (p=0,03) and MMP-9 in the epithelium (p=0,003) and in the connective tissue (p=0,04). In conclusion, these results indicate that the MMP-1 presents high expression in every stages of the periodontal diseases, and increases its expression in the connective tissue when the gingivitis evolves to periodontitis. Therefore, it may have an important role in connective tissue degradation and bone loss observed in disease, since early, in gingivitis, until late stages, in periodontitis, of the periodontal disease. MMP-9 has expressed more in periodontitis than in gingivitis, both in epithelium and in connective tissue. It means that this enzyme may have some importance in the progression of gingivitis to periodontitis by acting in bone resorption observed in this desease
A destrui??o tecidual observada na doen?a periodontal ? causada, principalmente, por componentes do hospedeiro que t?m sua produ??o estimulada pelos produtos liberados pelas bact?rias. As Metaloproteinases da Matriz ou MMPs, enzimas relacionadas ? degrada??o de matriz extracelular em processos tanto fisiol?gicos quanto patol?gicos s?o consideradas as principais respons?veis pela perda tecidual caracter?stica da doen?a periodontal, e o entendimento de como isso ocorre pode ter uma s?rie de implica??es ben?ficas em rela??o ? preven??o, ao diagn?stico e ao tratamento desta doen?a. Neste trabalho foi estudada a express?o imuno-histoqu?mica da MMP-1, da MMP-2 e da MMP-9 em gengivas clinicamente diagnosticadas com doen?a periodontal. A MMP-1 teve express?o significativamente maior que as outras duas nos casos de gengivite tanto no epit?lio (p=0,0008) quanto no tecido conjuntivo (p=0,0049). Na periodontite, a MMP-1 e MMP-9 tiveram express?es significativamente maiores que a MMP-2 tanto no epit?lio (p<0,0001) quanto no conjuntivo (p=0,0002). A MMP-1 e MMP-9 mostraram maior express?o na periodontite que na gengivite sendo a MMP-1 apenas no tecido conjuntivo (p=0,03) e a MMP-9 no epit?lio (p=0,003) e no conjuntivo (p=0,04). Concluiu-se portanto que a MMP-1 apresenta forte express?o em todos os est?gios da doen?a peridontal, aumentando no tecido conjuntivo no caso de progress?o para periodontite, podendo portanto ter um papel crucial na degrada??o de tecido conjuntivo e perda ?ssea observada na doen?a desde os est?gios iniciais de gengivite at? a progress?o para periodontite. A MMP-9, ? expressa mais na periodontite que na gengivite, tanto no epit?lio quanto no conjuntivo significando que esta enzima pode ter import?ncia na progress?o da gengivite para a periodontite atuando na reabsor??o ?ssea observada na doen?a periodontal

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Price, Simon J. "The molecular pathology of matrix metalloproteinase-2". Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393472.

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Justulin, Junior Luis Antonio. "Efeitos da doxazosina e da combinação doxasina mais finasterida sobre a interação parenquina-estroma na prostata de rato : proliferação, morte celular, atividade das MMPs-2 e 9 e expressão genica dos TIMPs 1 e 2". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317949.

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Orientador: Sergio Luis Felisbino
Tese (doutorado) - Universidade Estadual de Campinas, Insituto de Biologia
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Resumo: Finasterida (Fin), um inibidor da enzima 5a-redutase do tipo II e a Doxazosina (Dox), um inibidor do receptor a1-adrenérgico, tem sido amplamente utilizados no tratamento dos sintomas da Hiperplasia Prostática Benigna (HPB). Recentemente, dados clínicos demonstraram que a combinação destas drogas foi mais efetiva em prevenir o desenvolvimento de retenção urinária aguda. Além disso, tem sido demonstrado que tanto as drogas isoladas, como em associação também podem ser utilizadas na prevenção e tratamento do câncer de próstata, devido ao seu potencial de induzir apoptose em células epiteliais normais e tumorais. Apesar disso, pouco se conhece sobre os efeitos da Fin e da Dox administradas isoladas ou em associação sobre a morfofisiologia prostática, incluindo proliferação, morte celular, e indução de remodelação da matriz extracelular pelas metaloproteinases de matriz. Ratos wistar machos adultos (13 semanas) foram tratados com Dox (25mg/kg/dia) ou com a combinação de Fin+Dox (25mg/kg/dia). Após a eutanásia, os lobos prostáticos (ventral, dorsolateral e anterior) foram retirados, pesados e imersos em fixador para análises morfológicas ou congelados em nitrogênio líquido para posterior análises bioquímicas. Os resultados morfológicos e estereológicos demonstraram que o tratamento com a Dox isoladamente por 3 dias resultou em aumento do peso da próstata ventral, com acúmulo de secreção na luz glandular. Os pesos absoluto e relativo das próstatas dorsolateral e anterior não sofreram alteração neste período de tratamento. Entretanto, após 30 dias de tratamento, observou-se uma redução de aproximadamente 20% nos pesos absoluto e relativo de todos os lobos prostáticos e um aumento do volume glandular ocupado pelo colágeno no estroma nos três lobos prostáticos. O tratamento com doxazosina também reduziu o índice de proliferação celular e aumentou o índice apoptótico em todos os períodos analisados. A próstata ventral de ratos tratados com a combinação de Fin+Dox apresentou perda de peso após 30 dias de tratamento. Nos dois períodos de tratamento ocorreu diminuição do índice de proliferação celular, aumento de apoptose e do volume estromal de colágeno, mais evidentes quando comparados ao tratamento com as drogas isoladas. O tratamento combinado também provocou aumento da imunomarcação para o TGF-ß1 demonstrado por imunohistoquímica, principalmente no epitélio. A expressão dos RNAms para MMP-2, TIMPs-1 and - 2 dimunuiu após 30 dias de tratamento, enquanto o RNAm para a MMP-9 não foi detectado em nenhum grupo experimental. O tratamento com Fin+Dox por 30 dias promoveu uma diminuição na atividade gelatinolítica da MMP-2 e um aumento na atividade da MMP-9. Em conjunto, os resultados deste estudo demonstram que tanto o tratamento com doxazosina quanto o tratamento combinado de Fin+Dox induzem grandes alterações glandulares que levam a atrofia prostática, sendo ainda mais significativa com o tratamento combinado, possivelmente pela ação complementar destas duas drogas sobre o parênquima e o estroma glandulares. Nesta atrofia, a MMP-9 e o TGF-ß 1parecem desempenhar um papel importante. Desta forma, nossos resultados auxiliam o entendimento dos dados clínicos, demonstrando que a combinação dos dois fármacos pode ser mais eficaz no tratamento da HPB.
Abstract: Finasteride (Fin), an inhibitor of type II 5-a reductase, and Doxazosin (Dox), an a1- adrenergic blocker, have been widely used in treatment of Benign Prostate Hyperplasia (BPH) symptoms. Recently, clinical data have demonstrated that the combined therapy with Fin+Dox reduced the long-term risk of acute urinary retention and the need for invasive therapies than either drug alone. Moreover, both drugs, alone or in combination have been suggested to be effective in the treatment of prostate cancer by inducing apoptosis in normal and tumoral cells. However, little is known about the effects of these drugs administrated alone or their combination on prostate tissue morphohysiology, including prostate morphology, cell proliferation, apoptosis and matrix metalloproteinases activities. Male adult Wistar rats (13 weeks old) were treated with doxazosin (25mg/kg/day) or with finasteride (25mg/kg/day) or with the combination of both drugs. The ventral (VP), dorsolateral (DLP) and anterior prostate (AP) were excised and processed for histochemical, morphometric and biochemical analysis. The results of morphological and stereological analyses demonstrate that Dox treatment for 3 day resulted in an increased in ventral prostate absolute and relative weight with secretion accumulation. The weight of dorsolateral and anterior prostate did not change in this period of treatment. However, after 30 days, the prostate exhibited an absolute and relative weight reduction of about 20% and an increase in collagen volume fraction in the stromal space in the three prostatic lobes. Dox also reduced epithelial cell proliferation and increased apoptosis in the three prostatic lobes in all periods of tretament. Rat VP treated with Fin+Dox also presented a reduction in absolute and relative weight, decrease in epithelial cell proliferation, increase in apoptosis and collagen volume fraction in the stroma in all periods analyzed, more than Dox alone. Fin+Dox treatment also increased the TGF-ß 1 immunoreaction in the epithelium and in the stroma of VP. The mRNA for MMP-2, TIMPs-1 and - 2 expression after 30 days of treatment were decreased. The mRNA for MMP-9 was not detected in any groups analyzed. Fin+Dox treatment for 30 days promoted a decrease in gelatinolitic activity of MMP-2 and an increase in MMP-9. Take together, these results demonstrated that both Dox alone or in combination with Fin induced changes in glandular histoarchitecture, leading to a prostate atrophy, being the combined treatment more effective in inducing glandular atrophy, possibly to the complementary action of the Fin and Dox on prostate parenchyma and stroma, respectively. In this process, the MMP-9 and TGF-ß1 appear to participate effectively. Our results contribute to a better understanding of the clinical data, demonstrating that the combined treatment can be more effective in the BPH treatment.
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural

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Wenzel, Christian [Verfasser]. "Untersuchungen zu Isoenzymen der Matrix-Metalloproteinasen MMP-2 und MMP-9 bei adulten Patienten mit cystischer Fibrose / Christian Wenzel". Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065463413/34.

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Candido, Saverio. "Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinases (MMPs) as biomarkers of bladder cancer development and progression". Doctoral thesis, Università di Catania, 2016. http://hdl.handle.net/10761/3777.

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Neutrophil gelatinase-associated lipocalin (NGAL), also called lipocalin-2, is a secreted protein belonging to the lipocalin family proteins and actively participates into the proliferation, differentiation, and development of human tissues, including tumours. It positively modulates the activity of the matrix metalloproteinases-9 (MMP-9) that are involved in the enzymatic remodelling of the extracellular matrix. MMP-9 regulates the degradation of extracellular matrix in processes such as angiogenesis, tumour growth, and metastasis. By forming the NGAL/MMP-9 complex, NGAL protects MMP-9 from proteolytic degradation, a fundamental mechanism in controlling the activity of the proteins, and enhances its enzymatic activities. As a secreted protein, NGAL is detectable in many biologic fluids, including urine, where several neoplastic cells and other tumor microenvironmental factors can be directly released from the cancer. Our in silico analysis suggested an active role of NGAL in tumour development of several cancer types. Validation of these findings is here described in bladder cancer as a good tumor model in which investigate the role of this protein because urine is in direct contact with the primary tumor. On these bases, the release of NGAL in both urine and serum samples from 89 bladder cancer patients was measured. Further investigations, aimed to emphasize the role of NGAL in cancer, were performed by analysing MMP-9 and NGAL/MMP-9 complex levels in the same subset of bladder cancer patients. Control experiments were performed in 119 cancer-free controls, previously enrolled in a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. In conclusion, the present study deepens the knowledge of the molecular mechanisms sustaining NGAL expression in tumor cells and its effects on cancer metastatic behaviour. Furthermore, NGAL/MMP-9 pathway is associated with an aggressive phenotype of transitional cell carcinoma of the bladder (TCC). The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex make them candidate markers of exclusion test for TCC. These findings suggest that these proteins may be integrated in the surveillance of bladder cancer, thus improving patients complaints and diminishing their discomfort.

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Mattos, Maria Cecília Ribeiro de. "Análise do padrão de expressão de MMP-2, -9 e -8 em tecido humano pulpar normal e inflamado". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/25/25131/tde-25032010-162654/.

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As metaloproteinases da matriz (MMPs) foram relacionadas a diversas doenças inflamatórias como artrite e também ao câncer. O presente trabalho tem por objetivo estabelecer o papel da MMP-2, MMP-9 e MMP-8 no processo de inflamação pulpar. Foram adotadas as seguintes hipóteses nulas: (1) o padrão de expressão das MMP-2, MMP-9 e MMP-8 não sofre alteração nos diferentes estágios da polpa humana: normal, reversível, transição, irreversível ou necrose; (2) não há diferença de expressão das MMP-2, -9 e MMP-8, considerando-se um mesmo estágio de inflamação tecidual pulpar. Os métodos utilizados foram: (I) Obtenção dos espécimes, que foram divididos em grupos de acordo com critérios adotados de semiologia subjetiva e objetiva. Obtiveram-se os seguintes grupos: GI (Controle) dentes hígidos (n=7); GII (Pulpite Reversível n=4); GIII (Pulpite Transição n=4); GIV (Pulpite Irreversível/Necrose n=8). Logo após exodontia, os dentes obtidos foram cortados ligeiramente abaixo da junção amelodentinária e fixados em formol a 10% por 48h. Foram lavados em água corrente (24h) para então serem processados histologicamente. Foram obtidas secções de 4m, aderidas em lâminas silanizadas e submetidas à imunomarcação (Técnica da Peroxidase), utilizando os anticorpos anti MMP-2, MMP-9 e MMP-8 humanos. A presença de imunomarcação foi realizada através da análise semi-quantitativa por escores, sendo que a quantificação de marcação por corte seguiu o seguinte escore: 0= ausente; 1= leve; 2= moderada; 3= intensa. Realizou-se teste estatístico não paramétrico Kruskal-Wallis, p<0,05. As comparações intergrupos revelaram, para CO: (1)MMP-2 - GI=GII=GIII, GIII=GIV, GI>GIV (p<0,01) e GII>GIV (p<0,05); (2)MMP-9 GI=GII=GIV, GII=GIII e GIII>GI (p<0,01); (3)MMP-8 GI=GII=GIII=GIV. Na região central da polpa, obteve-se: (1)MMP-2 GI=GII=GIII, GIII=GIV, GI>GIV (p<0,001) e GII>GIV (p<0,01); (2)MMP-9 GI=GII=GIII, GIII=GIV, GIV>GI (p<0,001) e GIV>GII (p<0,01); (3)MMP-8 GI=GII, GIII=GIV, GIII>GI (p<0,05), GIV>GI (p<0,01), GIII>GII (p<0,05) e GIV>GII (p<0,05). Quanto às comparações intragrupos, na CO mostraram: (1)GI - MMP-2>MMP9 (p<0,001), MMP-2=MMP-8 e MMP-9=MMP-8; (2)GII MMP-2>MMP-9 (p<0,01); MMP-2=MMP-8 e MMP-9=MMP-8; (3)GIII e GIV MMP-2=MMP-9=MMP-8. Para a região mais central da polpa: (1)GI e GII MMP-2=MMP-9=MMP-8; (2)GIII MMP9>MMP-2 (p<0,05), MMP- 2=MMP-8 e MMP-9=MMP-8; (3)GIV MMP-9>MMP-2 (p<0,01), MMP-2=MMP-8 e MMP-9=MMP-8. Sendo assim, as duas hipóstese nulas foram rejeitadas. Conclui-se ainda que MMP-2, MMP-9 e MMP-8 atuam no processo de inflamação pulpar de maneira distinta na CO e polpa central; MMP-2 é mais expressa em polpa sadia; a maior expressão de MMP-9 relaciona-se à presença de inflamação pulpar; em polpas inflamadas, a expressão de MMP- 8 é maior quando comparadas a polpas normal, embora tal enzima seja também levemente expressada em tecido pulpar normal.
The matrix metalloproteinases (MMPs) have been related to various inflammatory diseases, such as arthritis, as well as to cancer. The aim of the present study was to establish the role of MMP-2, MMP-9 and MMP-8 in the process of dental pulp inflammation. The following null hypotheses were adopted: (1) the pattern of MMP-2, MMP-9 and MMP-8 expression does not undergo alteration in the following different stages of human pulp: normal, reversible, transition, irreversible or necrosis; (2) there is no difference in the expression of MMP-2, -9 and MMP-8, when considering the same stage of pulp tissue inflammation. The methods used were: (I) Obtainment of specimens, which were divided into groups according to the subjective and objective criteria of semiology adopted. The following groups were obtained: GI (Control) healthy teeth (n=7); GII (Reversible Pulpitis n=4); GIII (Transition Pulpitis n=4); GIV (Irreversible Pulpitis/Necrosis n=8). Soon after extraction the teeth obtained were cut slightly below the amelodentinal junction and fixed in 10% formol for 48h. They were washed under running water (24h) and were histologically processed afterwards. Sections of 4m were obtained, adhered to silanized slides, and submitted to immunomarking (Peroxidase Technique), using human anti MMP-2, MMP-9 and MMP- 8 antibodies. The presence of immunomarking was determined through semi-quantitative analysis by scores, and marking by cut was quantified using the following score: 0= absent; 1= slight; 2= moderate; 3= intense. The Kruskal-Wallis non-parametric statistical test was performed, p<0.05. Intergroup comparisons revealed the following: for CO: (1)MMP-2 - GI=GII=GIII, GIII=GIV, GI>GIV (p<0.01) and GII>GIV (p<0.05); (2)MMP-9 GI=GII=GIV, GII=GIII and GIII>GI (p<0,01); (3)MMP-8 GI=GII=GIII=GIV. In the central region of the pulp, the following results were obtained: (1)MMP-2 GI=GII=GIII, GIII=GIV, GI>GIV (p<0.001) and GII>GIV (p<0.01); (2)MMP-9 GI=GII=GIII, GIII=GIV, GIV>GI (p<0.001) and GIV>GII (p<0.01); (3)MMP-8 GI=GII, GIII=GIV, GIII>GI (p<0.05), GIV>GI (p<0.01), GIII>GII (p<0.05) and GIV>GII (p<0.05). With regard to intragroup comparisons, in CO the following were shown: (1)GI - MMP-2>MMP9 (p<0.001), MMP-2=MMP-8 and MMP-9=MMP-8; (2)GII MMP-2>MMP-9 (p<0.01); MMP-2=MMP-8 and MMP-9=MMP-8; (3)GIII and GIV MMP- 2=MMP-9=MMP-8. For the most central region of the pulp: (1)GI and GII MMP-2=MMP- 9=MMP-8; (2)GIII MMP9>MMP-2 (p<0.05), MMP-2=MMP-8 and MMP-9=MMP-8; (3)GIV MMP-9>MMP-2 (p<0.01), MMP-2=MMP-8 and MMP-9=MMP-8. Therefore, the two null hypotheses were rejected. Moreover, it was concluded that MMP-2, MMP-9 and MMP-8 act in the process of pulp inflammation in a distinct manner in CO and central pulp; more MMP-2 is expressed in healthy pulp; the highest expression of MMP-9 is related to the presence of pulp inflammation; in inflamed pulp, the expression of MMP-8 is higher when compared with that of normal pulp, although this enzyme is also slightly expressed in normal pulp tissue.

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Jamil, Aqeel. "The role of matrix metalloproteinase-2 in liver fibrosis". Thesis, University of Southampton, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445490.

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Hannas, Angélica Reis. "Determinação da expressão de MMP-2 e MMP-9 na saliva de pacientes portadores de lesões cervicais não cariosas e da influência das MMPs sobre lesões radiculares artificiais através de EDX". Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/25/25131/tde-30032009-155558/.

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As metaloproteinases da matriz (MMPs) foram identificadas na saliva, na placa dental, na dentina e no cemento. Este trabalho teve como objetivos: Estudo I (I) - avaliar a expressão de MMP-2 e MMP-9 presentes na saliva total e parotidiana e no fluido gengival crevicular (FGC) de pacientes portadores e não portadores de lesões cervicais não cariosas (LCNC); Estudo II (II) - investigar se a presença de MMP-8 e -9/TIMPs poderia influenciar a remineralização de lesões artificialmente criadas na superfície radicular, com ou sem desgaste por abrasão. Os métodos utilizados foram: (I) Coleta de amostras de saliva e do FGC de 32 pacientes, com (n=16) e sem LCNC (n=16). A atividade gelatinolítica das MMPs foi avaliada através de análise zimográfica e Western Blot. (II): Espécimes de dentina humana radicular foram obtidos. O grupo controle G1(10) não sofreu nenhum tratamento. Os demais segmentos radiculares foram desmineralizados G2(60). O Grupo A não foi submetido à escovação e o Grupo B foi submetido à abrasão por escovação em uma máquina de escovação simulada. G2(10) foi apenas desmineralizado, G3(10) desmineralizado e remineralizado, e os Grupos G4(10), G5(10), G6(10), G7(10) foram desmineralizados e remineralizados em presença de tampão neutro, TIMP, MMP-8 e -9, MMP-8,-9 e TIMP, respectivamente. Para a análise elemental, as concentrações de Ca+2, P, Mg+2 assim como a relação molar Ca/P e Mg/Ca foram determinadas através de uma sonda eletrônica para microanálise (EPMA). A análise qualitativa por retrodispersão (BSE) foi realizada para demonstrar a distribuição global da densidade mineral. Os resultados (I) mostraram que a principal gelatinase presente, tanto na saliva total quanto no FGC, é a proMMP-9. Na saliva secretada pela glândula parótida, não foram detectadas bandas indicando a presença de gelatinases. Os resultados do estudo (II) indicaram que os espécimes escovados apresentaram maior conteúdo de Ca+2 a 20µm e maior conteúdo de Mg+2 a 30 e 50µm. Em presença de TIMPs, ocorreu uma redução do conteúdo de Ca+2 a 20µm. Para os espécimes não escovados, em todas as profundidades, as amostras incubadas com MMPs apresentaram maiores valores de Ca+2. Portanto, pode-se concluir que (I) a comparação entre pacientes com e sem LCNC mostrou não haver diferença estatisticamente significante quanto à atividade gelatinolítica; (II) quando não inibidas pelos TIMPs, as MMPs degradaram o colágeno completamente desmineralizado na superfície radicular, permitindo melhor recalcificação na superfície subjacente. Esse fenômeno foi também facilitado pela abrasão por escovação.
Matrix metalloproteinases (MMPs) have been identified in saliva, plaque, gingival crevicular fluid (GCF), dentin and cementum. Study (I) aimed at evaluating the presence and quantity of gelatinases MMP-2 and MMP-9 in total and parotid saliva and in GCF (GCF) of subjects with and without NCCL. Study (II) aimed at investigating whether the presence of matrix metalloproteinase (MMP)-8 and - 9/TIMPs would influence the remineralization of artificial root lesions with and without mechanical wear. (I) Total stimulated saliva, parotid saliva, and GCF from patients with (n=16) and without NCCL (n=16) were collected and assessed for gelatin zymography and for western immunoblot analysis. (II) Human root segments from Group A (n=35) were not brushed and from Group B (n=35) were subjected to machine-controlled brushing, simulating mechanical wear. Specimens from Group 1 (control, n=10) were left untreated. Group 2 (n=10), was just demineralized; Group 3 (n=10) was demineralized and remineralized. The other samples G4 (n=10), G5 (n=10), G6 (n=10), G7 (n=10) were subjected to remineralization with HEPES buffer, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), activated MMP-8 and MMP-9 and activated MMP-8, MMP-9 and TIMP-2, respectively. Ca+2, P, Mg+2 concentrations as well as Ca/P and Mg/Ca molar ratios were determined through an Electron Probe Microanalyser (EPMA). (I) Densitometric analysis revealed that the main gelatinase was proMMP-9. No statistically significant difference was observed for MMP-2 and MMP-9 levels, separately. In parotid saliva, gelatinolytic activity was very low or absent. Western immunoblots revealed that, while little immunoreactivity was detected for MMP-2, there was positive immunoreaction for MMP-9, both in total saliva and in GCF. Gelatinases do not seem to originate from parotid gland. (II) The results indicated that the brushed specimens presented higher Ca+2 levels at 20 µm and higher Mg+2 content at 30 and 50 µm. Ca+2 content at 20 µm decreased in the presence of TIMPs. For the non-brushed specimens, in all depths, samples incubated with MMPs showed highest Ca+2 values. It can be concluded that (I) the main gelatinase present in the oral cavity is MMP-9. No significant differences were found in total gelatinolytic activity among NCCL+ and NCCL- patients. (II) When not inhibited by TIMPs, MMPs degraded the completely demineralized collagen in the root surface, allowing for better recalcification in the deeper areas. This phenomenon was also facilitated by the brushing procedure.

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Kuvaja, P. (Paula). "The prognostic role of matrix metalloproteinases MMP-2 and -9 and their tissue inhibitors TIMP-1 and -2 in primary breast carcinoma". Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514285998.

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Abstract Breast carcinoma is a heterogeneous disease with a prognosis that varies from excellent to very poor. Traditional tumour parameters and biological factors that are also predictive for treatment response are used in determining breast carcinoma prognosis and selecting appropriate treatment. Gelatinases MMP-2 and MMP-9 have been shown to associate with tumour progression. Their tissue inhibitors TIMP-1 and -2 are multifunctional molecules that have been suggested as prognostic markers in some previous reports. In the present work, the expression and prognostic value of gelatinases MMP-2 and MMP-9 and their tissue inhibitors TIMP-1 and -2 were assessed in primary breast carcinoma. The material consisted of a total of 416 patients. Tissue expression of TIMP-1 and -2 was analysed in a population of 203 patients using immunohistochemistry. Circulating gelatinases and their inhibitors were studied using ELISA in two different populations of 71 at preoperative state and 213 patients at pre- and postoperative state. High expression of TIMP-1 immunoreactive protein positively correlated with high histological grade of the tumour and associated with aggressive disease course in grade 2–3 subpopulation. High preoperative plasma TIMP-1 was prognostic for relapse in a modern patient series after a median follow-up time of 18 months. TIMP-1 as a continuous variable was prognostic in Cox regression univariate analysis, and was an independent prognostic variable superior to nodal status in multivariate analysis. High preoperative serum TIMP-1 was an independent prognostic variable for poor disease-specific survival, and TIMP-1 was found to maintain its prognostic value when assessed independently with different ELISA analyses, and was not very sensitive for preanalytical conditions. In addition, low circulating preoperative serum MMP-2 was observed to associate with high stage and positive nodal status in breast carcinoma. These results indicate that circulating TIMP-1 may be a potential new marker of worsened prognosis in breast carcinoma, although careful validation of assay platforms and identification of the sources of physiological variation are needed before it can be adopted into clinical decision-making.

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39

Risinger, George M. "Regulation of matrix metalloproteinase-2 in vascular smooth muscle cells". Oklahoma City : [s.n.], 2008.

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Furtado, Francisco NÃlson NÃbrega. "ImunoexpressÃo de metaloproteinases 2 e 14 e do inibidor TIMP-2 no cÃncer colorretal". Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8357.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O cÃncer colorretal(CCR) Ã altamente prevalente nos paÃses mais ricos e industrializados. As metaloproteinases de matriz (MMPs) sÃo importantes enzimas que facilitam a invasÃo e disseminaÃÃo do tumor em vÃrios tipos de cÃncer, inclusive o colorretal. Os inibidores teciduais de metaloproteinases (TIMPs) sÃo os principais inativadores fisiolÃgicos destas enzimas. Este estudo avaliou a expressÃo de metaloproteinase-2 (MMP-2), metaloproteinase-14 (MMP-14) e inibidor tecidual de metaloproteinases-2 (TIMP-2) no cÃncer colorretal. O imunomarcador CD68 foi utilizado para caracterizar a natureza das cÃlulas mononucleadas do estroma. Amostras teciduais de 50 casos de colectomias, devido ao cÃncer colorretal no perÃodo de 2004 a 2010, obtidas dos arquivos do Departamento de Patologia e Medicina Legal (DPML), Faculdade de Medicina da Universidade Federal do CearÃ (UFC), foram analisadas. Realizou-se tissue microarrays e a seguir imuno-histoquÃmica para avaliar a expressÃo de MMP-2, MMP-14 e TIMP-2 de acordo com os seguintes escores baseados em outros relatos: 0= sem imunomarcaÃÃo ou raras cÃlulas marcadas (<5%); 1 = discreta marcaÃÃo na maioria (> 50%) das cÃlulas tumorais ou cÃlulas mononucleares do estroma, ou moderada marcaÃÃo em uma minoria de cÃlulas (<50 %); 2 =marcaÃÃo moderada na maioria (> 50%) de cÃlulas tumorais ou cÃlulas mononucleares ou intensa marcaÃÃo em minoria de cÃlulas (<50%); 3 = marcaÃÃo intensa na maioria (> 50%) de cÃlulas tumorais ou cÃlulas mononucleares. Observou-se relaÃÃo entre a expressÃo aumentada de MMP-14 em mononucleares de tumor primÃrio e casos sem metÃstases linfonodais (MMP-14, escores 2 e 3/N0 : 23/24 = 95%; N1-N3: 14/20 = 70%, p = 0,0353). No entanto, nenhuma relaÃÃo significativa foi encontrada entre a expressÃo de MMP-14, MMP-2 e TIMP-2 nos tumores primÃrios em cÃlulas cancerosas ou mononucleares e outros parÃmetros clÃnico-patolÃgicos. A imunoexpressÃo de MMP-2 foi negativa nas cÃlulas neoplÃsicas, em tumores primÃrios (47/47=100%) e metastÃticos (12/12 = 100%). A imunorreatividade de MMP-14 em cÃlulas neoplÃsicas foi frequentemente positiva em tumores primÃrios (50/50 = 100%) e metastÃticos (7/8= 88%). Em mononucleares, a maioria dos quais macrÃfagos (corados pelo CD68), a expressÃo positiva de MMP-14 tambÃm predominou marcadamente, tanto em tumores primÃrios (46/47 = 98%) como em carcinomas metastÃticos (9/10 = 90%). A expressÃo de TIMP-2 em cÃlulas neoplÃsicas, discreta, ocorreu em 70% de tumores primÃrios (35/50 casos) e 100% dos metastÃticos (8/8). A imunocoloraÃÃo para TIMP-2 em macrÃfagos associados ao tumor (TAMs) foi ainda mais elevada do que nas cÃlulas neoplÃsicas. Em conclusÃo, a MMP-14 e TIMP-2 sÃo frequentemente expressas em carcinomas colo-retais em ambas localizaÃÃes anatÃmicas, principalmente nas metÃstases para linfonodos , sugerindo que estas proteases desempenham papel importante na invasÃo local e na progressÃo tumoral neste tipo de cÃncer. A predominÃncia destes marcadores nas cÃlulas mononucleares (sobretudo macrÃfagos) , claramente evidentes na positividade para a MMP-2, enfatiza a importÃncia do microambiente tumoral no desenvolvimento de neoplasias.
The colorectal cancer (RCC) is highly prevalent in richer and industrialized countries. The matrix metalloproteinases (MMPs) are regarded as important for facilitating tumor invasion and spread in various cancers, including colorectal. Tissue inhibitors of metalloproteinases (TIMPs) are the major physiological inhibitors of MMPs. The expression of metalloproteinase-2 (MMP-2), metalloproteinase 14 (MMP-14) and tissue inhibitor of metalloproteinases-2 ( TIMP-2) in colorectal cancer was assessed. CD68 immunostaininig was utilized to the characterization of mononuclear cells nature. Paraffin-embedded tissues from patients undergoing colectomy for colorectal cancer in the period 2004 to 2010, were selected from the files of the Department of Pathology and Forensic Medicine (DPML), Medical School , Federal University of CearÃ (UFC). Tissue microarrays were performed and slides were obtained for immunohistochemical detection of the expression of MMP-2, MMP-14 and TIMP-2 and the tissue samples analyzed. The following scores were applied: 0 = no immunostaining or rare labeled cells (<5%), 1 = slight marking the majority (> 50%) of tumor cells or stromal mononuclear cells, or moderate marking in a minority of cells (<50%) 2 = moderate labeling in the majority (> 50%) of tumor or mononuclear cells or intense marking in the minority of cells (<50%) and 3 = intense labeling in the majority (> 50%) of tumor cells or mononuclear cells. In this study, the relationship between increased expression of MMP-14 in mononuclear primary tumor cells and cases without lymph node metastases (MMP-14, 2 and 3/N0 scores: 23/26 = 88%; N1-N3: 14/21 = 67%, p = 0.0353) was stablished . However, no significant relationship was found between the immunohistochemical expression of MMP-14, MMP-2 and TIMP-2 in primary tumors in cancer cells and mononuclear cells and other clinico-pathological parameters. The expression of MMP-2 were negative in the neoplastic cells both in primary tumors (47/47 = 100%) and in metastatic ones (12/12 = 100%). The immunoreactivity of MMP-14 in neoplastic cells in primary tumors was positive (50/50 = 100%) and in all cases except one of metastatic carcinoma (7/8 = 88%). In mononuclear cells, most of them characterized as macrophages (CD68 stained), MMP-14 positive expression also predominated markedly, both in primary tumors (46/47 = 98%) and in metastatic carcinomas (9/10 = 90%). TIMP-2 expression in neoplastic cells of primary tumors occurred in 35/50 cases (70%) and lymph nodes showed positive immunostaining in all cases (8/8 = 100%). In both sites there were no cases with high expression. The TIMP-2 immunoreactivity in tumour associated macrophages (TAMs) was even higher than in the neoplastic cells. In conclusion, MMP-14 and TIMP-2 are frequently expressed in colorectal carcinomas in both anatomical sites , mainly in lymph node metastasis, suggesting that these proteases play an important role in local invasion and tumor progression of these cancers. The predominance of these biomarkers in mononuclear cells, clearly evident in the positivity for MMP-2, emphasizes the importance of tumor microenvironment in the development of neoplasms.

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Medeiros, Mildred Ferreira. "Hanseníase neural, aspectos diagnósticos da forma neural pura e mecanismos imunopatogênicos da lesão do nervo na doença. Participação de quimiocinas CCL2 e CXCL10 e metaloproteinases 2 e 9". Universidade do Estado do Rio de Janeiro, 2014. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=7356.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
O diagnóstico da hanseníase neural pura baseia-se em dados clínicos e laboratoriais do paciente, incluindo a histopatologia de espécimes de biópsia de nervo e detecção de DNA de Mycobacterium leprae (M. leprae) pelo PCR. Como o exame histopatológico e a técnica PCR podem não ser suficientes para confirmar o diagnóstico, a imunomarcação de lipoarabinomanana (LAM) e/ou Glicolipídio fenólico 1 (PGL1) - componentes de parede celular de M. leprae foi utilizada na primeira etapa deste estudo, na tentativa de detectar qualquer presença vestigial do M. leprae em amostras de nervo sem bacilos. Além disso, sabe-se que a lesão do nervo na hanseníase pode diretamente ser induzida pelo M. leprae nos estágios iniciais da infecção, no entanto, os mecanismos imunomediados adicionam severidade ao comprometimento da função neural em períodos sintomáticos da doença. Este estudo investigou também a expressão imuno-histoquímica de marcadores envolvidos nos mecanismos de patogenicidade do dano ao nervo na hanseníase. Os imunomarcadores selecionados foram: quimiocinas CXCL10, CCL2, CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, e metaloproteinases 2 e 9. O estudo foi desenvolvido em espécimes de biópsias congeladas de nervo coletados de pacientes com HNP (n=23 / 6 BAAR+ e 17 BAAR - PCR +) e pacientes diagnosticados com outras neuropatias (n=5) utilizados como controle. Todas as amostras foram criosseccionadas e submetidas à imunoperoxidase. Os resultados iniciais demonstraram que as 6 amostras de nervos BAAR+ são LAM+/PGL1+. Já entre as 17 amostras de nervos BAAR-, 8 são LAM+ e/ou PGL1+. Nas 17 amostras de nervos BAAR-PCR+, apenas 7 tiveram resultados LAM+ e/ou PGL1+. A detecção de imunorreatividade para LAM e PGL1 nas amostras de nervo do grupo HNP contribuiu para a maior eficiência diagnóstica na ausência recursos a diagnósticos moleculares. Os resultados da segunda parte deste estudo mostraram que foram encontradas imunoreatividade para CXCL10, CCL2, MMP2 e MMP9 nos nervos da hanseníase, mas não em amostras de nervos com outras neuropatias. Além disso, essa imunomarcação foi encontrada predominantemente em células de Schwann e em macrófagos da população celular inflamatória nos nervos HNP. Os outros marcadores de ativação imunológica foram encontrados em leucócitos (linfócitos T e macrófagos) do infiltrado inflamatório encontrados nos nervos. A expressão de todos os marcadores, exceto CXCL10, apresentou associação com a fibrose, no entanto, apenas a CCL2, independentemente dos outros imunomarcadores, estava associada a esse excessivo depósito de matriz extracelular. Nenhuma diferença na frequência da imunomarcação foi detectada entre os subgrupos BAAR+ e BAAR-, exceção feita apenas às células CD68+ e HLA-DR+, que apresentaram discreta diferença entre os grupos BAAR + e BAAR- com granuloma epitelioide. A expressão de MMP9 associada com fibrose é consistente com os resultados anteriores do grupo de pesquisa. Estes resultados indicam que as quimiocinas CCL2 e CXCL10 não são determinantes para o estabelecimento das lesões com ou sem bacilos nos em nervo em estágios avançados da doença, entretanto, a CCL2 está associada com o recrutamento de macrófagos e com o desenvolvimento da fibrose do nervo na lesão neural da hanseníase.
The diagnosis of pure neural leprosy (PNL) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of M. leprae DNA by polymerase chain reaction (PCR). Given that histopathological examination and PCR methods may not be sufficient to confirm diagnosis, immunolabeling of lipoarabinomanan (LAM) and/or phenolic glycolipid 1 (PGL1) M. leprae wall components were utilized in the first step of this investigation in an attempt to detect any vestigial presence of M. leprae in AFB- nerve samples. Furthermore, its well known that nerve damage in leprosy can be directly induced by Mycobacterium leprae in the early stages of infection; however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. Therefore, this study also investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. These markers selected were CXCL10, CCL2 chemokines and CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, metalloproteinases 2 and 9 in nerve biopsy specimens collected from leprosy (23) and nonleprosy patients (5) suffering peripheral neuropathy. Twenty-three PNL nerve samples (6 AFB+ and 17 AFB-PCR+) were cryosectioned and submitted to LAM and PGL1 immunohistochemical staining by immunoperoxidase; 5 nonleprosy nerve samples were used as controls. The 6 AFB-positive samples showed LAM/PGL1 immunoreactivity. Among the 17 AFB- samples, only 8 revealed LAM and/or PGL1 immunoreactivity. In 17 AFB-PCR+ patients, just 7 had LAM and/or PGL1-positive nerve results. In the PNL cases, the detection of immunolabeled LAM and PGL1 in the nerve samples would have contributed to enhanced diagnostic efficiency in the absence of molecular diagnostic facilities. The results of the second part of this study showed that CXCL10-, CCL2-, MMP2- and MMP9-immunoreactivities were found in the leprosy nerves but not in nonleprosy samples. Immunolabeling was predominantly found in recruited macrophages and Schwann cells composing the inflammatory cellular population in the leprosy-affected nerves. The immunohistochemical expression of all the markers, but CXCL10, was associated with fibrosis; however, only CCL2 was, independently from the other markers, associated with this excessive deposit of extracellular matrix. No difference in the frequency of the immunolabeling was detected between the AFB+ and AFB- leprosy subgroups of nerves, exception made to some statistical tendency to difference in regard to CD68+ and HLA-DR+ cells in the AFB- nerves exhibiting epithelioid granuloma. MMP9 expression associated with fibrosis is consistent with previous results of this research group. The findings conveys the idea that CCL2 and CXCL10 chemokines at least in advanced stages of leprosy nerve lesions are not determinant for the establishment of AFB+ or AFB- leprosy lesions, however, CCL2 is associated with macrophage recruitment and fibrosis.

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Parkin, Ben. "The role of matrix metalloproteinase-2 and its inhibitors in keratoconus". Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343282.

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Falkenberg, Sonja. "Expression der Matrix-Metalloproteinasen MMP-2, -7, -9 und -13 und ihrer Inhibitoren TIMP-1, -2 und -3 in Plattenepithelkarzinomen des oberen Aerodigestivtraktes". [S.l.] : [s.n.], 2004. http://archiv.ub.uni-marburg.de/diss/z2004/0679/.

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Haber, Thomas. "Einfluss der Zytomegalievirus-Infektion auf die Regulation des Matrix-Metalloproteinase-2-Gens". [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-60477.

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Clegg, Peter David. "Matrix metalloproteinase-2 and -9 and their inhibitors in equine joint disease". Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263792.

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Souza, Markus Vinicius Campos. "Efeito do treinamento resistido na avaliação da composição corporal e na atividade da MMP-2 nos músculos bíceps e gastrocnêmio de ratos obesos". Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/1349.

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The aim of the present study was to investigate the influence of resistance training on body composition and active matrix metalloproteinases 2 (MMP-2) on biceps and gastrocnemius muscles in rats with high fat diet. We evaluated 32 Wistar rats divided into four experimental groups (n=8/each) according to diet and exercise status: Control Group (C; standard diet), Obese Control Group [C-Ob; hiperlipidic diet (30% of fat)], Resistance Exercise (RE; standard diet) and Resistance Exercise Obese (RE-Ob; hiperlipidic diet). After weaning (day 21), animals were subjected to the experimental diet according to their groups during 24 weeks. A 12-week strength-training period was used, during which the animals climbed a 1.1-m vertical ladder with weights attached to their tails. The sessions were performed three times/week (Mondays, Wednesdays and Fridays, with 4 9 climbs/session and 8 12 dynamic movements/climb with two rest minutes. Resistance training induced a significant reduction in body mass, fat mass, fat percentage in group RE (p < 0,05). Resistance training increased the activity of MMP-2 on bicpes and gastrocnemius muscle (p < 0,05), favoring thus the tissue remodeling in both groups trained. Finally, the carrying load trained both groups was not statistically different, however, the relative strength (carrying load/body weight) was statistically higher in group RE (p < 0,05). Resistance training promoted significant changes in body composition, MMP-2 activity in the biceps and gastrocnemius and the relative strength. Thus resistance training may be a strategy to minimize the deleterious effects induced by consumption of a high fat diet and the co-morbidities associated with obesity in skeletal muscle.
O objetivo do presente estudo, foi investigar a influência do treinamento resistido na composição corporal e a atividade metaloproteinases de matrix 2 (MMP-2) nos músculos bíceps e gastrocnêmio em ratos alimentados com dieta hiperlipídica. Foram avaliados 32 ratos machos Wistar divididos em quarto grupos experimentais (n=8/cada) de acordo com o tipo de dieta e o treinamento: Controle (C; dieta padrão), Controle Obeso [C-Ob; dieta: hiperlipídica (30% de gordura)], Exercício Resistido (EX; dieta padrão) e Exercício Resistido Obeso (EX-Ob; dieta hiperlipídica). Após o desmame (dia 21), os animais foram submetidos à dieta experimental durante 24 semanas. Após 12 semanas de dieta os animais realizaram um período de 12 semanas de treinamento resistido, durante o qual os animais escalavam uma escada vertical de 1,1 metros com pesos atados a cauda. As sessões de treinamento foram realizadas três vezes por semana (segunda, quarta e sexta-feira) com 4 a 9 escaladas e 8 a 12 movimentos dinâmicos a cada subida com dois minutos de intervalo de recuperação. O treinamento resistido induziu redução significativa na massa corporal, massa gorda, percentual de gordura nos animais do grupo EX (p < 0,05). O grupo C apresentou massa corporal e massa gorda significativamente maiores e valores de massa magra significativamente menores quando comparado com os animais do grupo EX. O treinamento resistido aumentou a atividade da MMP-2 nos músculos bíceps e gastrocnêmio (p < 0.05), favorecendo dessa forma, o remodelamento tecidual em ambos os grupos treinados. Por fim, a carga de carregamento de ambos os grupos treinados não foi diferente estatisticamente, no entanto, a força relativa (carga de carregamento/massa corporal) foi estatisticamente maior no grupo EX (p<0.05). O treinamento resistido promoveu mudanças importantes na composição corporal, atividade da MMP-2 nos músculos bíceps e gastrocnêmio e na força relativa. Assim o treinamento resistido pode ser uma estratégia para minimizar os efeitos deletérios induzidos pelo consumo de uma dieta hiperlipídica e as co-morbidades associadas à obesidade no músculo esquelético

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Rollin, Jérôme. "Expression comparée de deux anti-protéases, TFPI-2 et RECK, et des métalloprotéases MMP-2 et MMP-9 dans le cancer broncho-pulmonaire non à petites cellules". Tours, 2006. http://www.theses.fr/2006TOUR3303.

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Le TFPI-2 et RECK sont des anti-protéases que régulent in vitro l’activation de plusieurs MMP impliquées dans la progression tumorale. Nous avons montré que l’expression de ces deux anti-protéases est diminuée dans, respectivement, 37% et 51% des tumeurs issues de cancer broncho-pulmonaire non à petites cellules. De plus, une hyperméthylation de la région promotrice du TFPI-2 est associée à une diminution d’expression du gène dans 50% des cas. Parallèlement, le pourcentage de formes actives de MMP-2 et de MMP-9 est plus élevé dans les tumeurs mais ne varie pas selon le niveau d’expression du TFPI-2 ou de RECK. Cette étude a également montré que la survie des patients portant le génotype MMP-2-735CC est significativement plus courte, bien que le niveau d’expression tumorale de la MMP-2 soit plus faible. En conclusion, ces résultats supportent que le TFPI-2 et RECK contribuent à inhiber la progression du cancer, mais les mécanismes impliqués in vivo restent à être identifiés
TFPI-2 and RECK are anti-proteases which regulate in vitro the activation of several MMP involve in cancer progression. We have demonstrated that gene expressions of these two inhibitors are decreased in 37% and 51% of non-small cell lung cancer tumours, respectively. In addition, hypermethylation of TFPI-2 gene promoter is associated with decreased expression of TFPI-2 gene in 50% of cases. On the other hand, the percentage of active forms of MMP-2 and MMP-9 was higher in tumours but did not significantly vary according to RECK or TFPI-2 gene expression. This study has also demonstrated that the survival time of patients with the MMP-2-735CC genotype was significantly shorter, despite tumour MMP-2 mRNA levels measured were significantly lower. In conclusion, these data support that TFPI-2 and RECK are likely contributing to inhibit tumour progression in NSCLC, but the exact mechanisms involved to regulate in vivo MMP remain to be identified

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Bakos, Stephen. "The Expression of Matrix Metalloproteinase-9 and -2 in Olfactory Injury and Recovery". VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/143.

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The olfactory system has the remarkable capacity for neurogenesis following injury. However, the molecular mechanisms important for reinnervation of the olfactory bulb (OB) remain unknown. The matrix metalloproteinases (MMPs) are important components in many central nervous system (CNS) injury paradigms, yet remain unexplored in olfactory injury and recovery. To address the role of MMPs, the temporal expressions of MMP-9 and MMP-2 were examined in 3 olfactory injury models: nerve transection (NTx), methyl bromide gas (MeBr) exposure, and nerve transection with Teflon barrier (NTx-TB). Each injury model represents a different degree of olfactory injury and neuronal recovery. In NTx, sensory axons are lesioned, leading to neuronal degeneration and subsequent reinnervation of the OB. MeBr exposure damages the cell bodies of sensory neurons in the peripheral olfactory epithelium (OE), leading to degeneration and reinnervation of the OB without direct trauma to the OB. In NTx-TB, sensory axons are lesioned and a barrier is inserted following injury that blocks regenerated neurons from reinnervation of the OB. Following NTx, MMP-9 increased immediately in the OB and was localized to neutrophils, an inflammatory leukocyte. The elevated levels of MMP-9 corresponded to neuronal degeneration. To confirm this relationship, MMP-9 expression was measured following MeBr injury. MMP-9 increased during neuronal degeneration in the OB and was localized to neutrophils in the area of sensory axon degradation. These experiments demonstrated that MMP-9 is important for both neuronal degeneration and the acute inflammatory response following olfactory injury. In NTx injury, MMP-2 expression peaked at day 7 and corresponded to the transition between degeneration and reinnervation of the OB. MMP-2 was localized to the granule cell and external plexiform layers in control and day 7 bulbs. Following NTx-TB, MMP-2 remained low and was not expressed by regenerated axons. The absence of a MMP-2 peak in the NTx-TB injury suggests that this peak depends on reinnervation of the OB. This study demonstrates a temporal correlation between MMP-9 and degeneration and MMP-2 and reinnervation following olfactory injury. These findings provide new insight into the molecular mechanisms underlying olfactory nerve injury. Modulation of MMPs could provide novel therapeutic interventions to improve neuronal recovery following injury.

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Freitas, Val?ria Souza. "Estudo da express?o imuno-histoqu?mica das MMPs -2, -7, -9 e -26 e TIMPs -1 e -2 em adenomas pleom?rficos e carcinomas aden?ides c?sticos de gl?ndulas salivares menores". Universidade Federal do Rio Grande do Norte, 2011. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17149.

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Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
The balance between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) has been related to various physiological and pathological processes, including salivary gland morphogenesis and tumor invasion and metastasis processes. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) respectively represent benign and malignant neoplasias of salivary glands. Although they share the same cell origin, they present distinct biological behavior. The aim of this study was to compare the immunohistochemical expression of MMPs -2, -7, -9 and -26, and of TIMPs -1 and -2, in cases of PA and ACC of minor salivary glands. Twenty cases of PA and twenty cases of ACC were assessed according to the presence, intensity and location of MMPs and TIMPs in the tumor parenchyma. Most of the PAs and ACCs presented a high expression of MMP -2, -7, -9 and -26 and of TIMP -1 and -2, predominantly located in tumor cells. There was no significant difference in the expression of MMPs -2 (p=0.359), -7 (p=0.081) and -26 (p=0.553), as well as of TIMPs -1 (p=0.657) and -2 (p=0.248), between the parenchyma of PAs and ACCs. However, MMP-9 showed a significant difference of expression between the two tumors, with the ACC showing more intense marking for this gelatinase (p=0.041). The strong expression of MMP-9 observed in the parenchyma suggests that this gelatinase may play an important role in the biological behavior of these tumors. On the other hand, although there was no significant difference between the marking of MMP -2, 7 and 26 in the studied tumors, the data, when analyzed as a whole, suggest that these proteases may take part in the process of tissue remodeling in both tumors, but do not present a direct relation with the pattern of aggressiveness of ACC. Nonetheless, matrilisins may indirectly influence the behavior of this tumor due to their capacity of activating MMP-9, strongly expressed in the parenchyma of ACC
O balan?o entre a express?o das metaloproteinases da matriz (MMPs) e seus inibidores teciduais (TIMPs) tem sido relacionado a v?rios processos fisiol?gicos e patol?gicos, incluindo a morfog?nese de gl?ndulas salivares e os processos de invas?o e met?stase tumoral. O adenoma pleom?rfico (AP) e o carcinoma aden?ide c?stico (CAC) representam, respectivamente, neoplasias benignas e malignas de gl?ndulas salivares que, embora compartilhem a mesma origem celular, apresentam comportamentos biol?gicos distintos. O prop?sito deste estudo foi comparar a express?o imuno-histoqu?mica das MMPs -2, -7, -9 e - 26 e dos TIMPs -1 e -2 em casos de AP e CAC de gl?ndulas salivares menores. Vinte casos de AP e vinte casos de CAC foram avaliados quanto ? presen?a, intensidade e localiza??o das MMPs e TIMPs no par?nquima tumoral. A maioria dos APs e CACs apresentaram alta express?o das MMPs e dos TIMPs, predominantemente localizada nas c?lulas tumorais. N?o houve diferen?a estatisticamente significativa na express?o das MMPs -2 (p=0,359), -7 (p=0,081) e -26 (p=0,553), bem como dos TIMPs -1 (p=0,657) e -2 (p=0,248), entre o par?nquima dos APs e CACs. A MMP-9 demonstrou uma diferen?a significativa de express?o entre os dois tumores, apresentando o CAC uma marca??o mais intensa para esta gelatinase (p=0,041). A forte express?o da MMP-9 observada no par?nquima dos CACs sugere que esta gelatinase possa desempenhar um papel importante no comportamento biol?gico destes tumores. Por outro lado, apesar de n?o ocorrer uma diferen?a significativa entre as m?dias das MMPs -2, 7 e 26 nos tumores estudados, os dados quando analisados em conjunto sugerem que estas proteases podem estar participando de processos de remodela??o tecidual em ambos os tumores, mas n?o apresentam uma rela??o direta com o padr?o de agressividade do CAC. Entretanto, as matrilisinas poderiam influenciar indiretamente o comportamento deste tumor devido a sua capacidade de ativar a MMP-9, fortemente expressa no par?nquima destes tumores

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Marangoni, Natalia Ribeiro. "Detecção das metaloproteinases-2 e -9 no plexo coróide e no liquor de cães naturalmente infectados por Leishmania chagasi /". Araçatuba : [s.n.], 2009. http://hdl.handle.net/11449/94704.

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Orientador: Gisele Fabrino Machado
Banca: Mary Marcondes
Banca: Antonio Carlos Alessi
Resumo: A leishmaniose visceral canina, causada pelo protozoário Leishmania (Leishmania) chagasi, é uma doença de grande ocorrência principalmente na América Latina. A caracterização das lesões sistêmicas associadas à infecção pelo parasita tem sido amplamente estudada, entretanto, poucos autores elucidam a patogenia na forma nervosa. Com o objetivo de compreender melhor os mecanismos envolvidos na inflamação do sistema nervoso central de cães naturalmente infectados por L. chagasi, amostras de liquor e plexo coróide foram colhidas e submetidas à zimografia para a detecção de metaloproteinases (MMPs). Amostras do plexo coróide e liquor de cães sadios foram avaliadas como controle. Os géis de zimograma foram analisados quanto à presença e atividade proteolítica das metaloproteinases -2 e -9. Formas inativas das proteases foram detectadas no plexo coróide, sendo que o Grupo de animais positivos não diferiu do negativo. No liquor foram encontradas formas ativas e inativas das MMPs-2 e -9 e a atividade proteolítica das mesmas diferiu entre os Grupos positivo e negativo. A MMP-2 teve maior detecção nos animais negativos e a MMP-9 nos positivos. O aumento da MMP- 9 no liquor dos cães doentes representa seu possível envolvimento na patogenia das lesões encefálicas ao ocasionarem o rompimento das barreiras hematoencefálica e/ou hematoliquórica, permitindo a passagem de células e proteínas envolvidas no processo inflamatório
Abstract: Canine visceral leishmaniasis, caused by the protozoan Leishmania (Leishmania) chagasi, is a disease with high occurrence in Latin America. The characteristics of the systemic lesions related to the infection have been widely studied, but few studies clarify the disease on a neurological aspect. With the aim of a better understanding of the inflammation mechanisms within the central nervous system of dogs naturally infected by L. chagasi, some samples of cerebrospinal fluid and choroid plexus were collected and submitted to zymography to detect metalloproteinases (MMPs). Samples of choroid plexus and cerebrospinal fluid from healthy dogs were evaluated as control. The zymogram gels were analysed taking into account the presence and the proteolytic activity of metalloproteinase -2 and -9. Inactive forms of the proteases were detected in the choroid plexus, and the group of positive animals did not differ from negative ones. In the cerebrospinal fluid, active and inactive forms of MMP-2 and -9 were found, and their proteolytic activity differed between negative and positive groups. MMP-2 had higher detection in the negative animals and MMP-9 in the positive ones. The increasing of MMP-9 in the cerebrospinal fluid of infected dogs represents its possible involvement in the brain injuries, by causing the disruption of blood-cerebrospinal fluid barrier and/or blood-brain-barrier, allowing the passage of cells and proteins involved in inflammation process
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