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1
Kumar, Deepak. "Mechanism of induction of matrix metalloproteinase-1 (MMP-1) during osteoarthritis /". Free to MU Campus, others may purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3144432.
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Sroka, Isis Calsoyas. "Regulation Of Membrane-Type 1 Matrix Metalloproteinase In Prostate Cancer". Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/194830.
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Membrane type-1 matrix metalloproteinase (MT1-MMP) is a metalloproteinase which becomes upregulated in prostate cancer and has been implicated in processes of prostate cancer metastasis. Here, we show that MT1-MMP is minimally expressed in nonmalignant primary prostate cells, moderately expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells. Using MT1-MMP promoter reporters and mobility shift assays, we show that Sp1 regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3-N cells using chromatin immunoprecipitation analysis and silencing RNA. Investigation of signaling pathways in these cells showed that DU-145 cells express constitutively phosphorylated extracellular stress-regulated kinase (ERK), whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c-Jun NH2 terminal kinase (JNK). We show that MT1-MMP and Sp1 levels are decreased in PC-3 and PC-3N cells when PI-3K and JNK are inhibited, and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited. Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or p85, and DU-145 cells with a dominant negative ERK, reduced MT1-MMP promoter activity. We also identified the insulin-like growth factor (IGF-1R) as an upstream regulatory component of MT1-MMP in PC-3N and LNCaP cells, which express high and low levels of the enzyme, respectively. Treatment of PC-3N cells with an IGF-1R specific inhibitor decreased MT1-MMP promoter activity, RNA and protein levels. Additionally, treatment of LNCaP cells with a synthetic androgen to increase IGF-1R levels and subsequent treatment with IGF-I increased MT1-MMP promoter activity, RNA and protein levels. Analysis of MT1-MMP and IGF-1R expression in human prostate cancer tissues demonstrated that MT1-MMP expression was high in the apical cytoplasmic regions of PIN and prostate cancer and less intense in the basalateral cytoplasmic membrane regions of benign glands. IGF-1R was expressed in normal glands and highly expressed in prostate cancer. In conclusion, we have identified several novel mechanisms regulating MT1-MMP expression in prostate cancer cell lines as well as differential localization of the enzyme in human prostate cancer tissues. These results provide insight into the complex mechanisms of prostate cancer metastasis and may be useful for developing future diagnostic procedures or therapies.
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Anand, Monika. "FUNCTION AND REGULATION OF MATRIX METALLOPROTEINASE-1 IN GLIOBLASTOMA MULTIFORME". VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2214.
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Glioblastoma Multiforme (GBM) is an aggressive and fatal cancer of the brain. It is characterized with augmented morbidity and elusion to therapies due in part to the incessant infiltration and spread of tumor cells in normal brain. We investigated the function of Matrix metalloproteinase-1, an important enzyme noted to be responsible for invasion in other cancers, in GBM and its regulation by epidermal growth factor receptor (EGFR) signaling. Previous studies from our laboratory demonstrated elevated levels of MMP-1 in GBM. Further studies indicated the involvement of MMP-1 in GBM invasion. The GBM cell lines T98G, U251MG and U87MG were used for this study. In T98G cell lines, inhibition of MMP-1 by siRNA significantly suppressed basal in vitro invasion without impacting cell viability. The over-expression of MMP-1 was accomplished in U251MG and U87MG using the mammalian expression vector, pIRES, encoding full length MMP-1 cDNA. The MMP-1 over-expressing U251MG and U87MG cells exhibited significantly enhanced invasion in vitro with no modification in the cell proliferation rates. A majority of GBM patients present defective EGFR signaling due to over-expression, amplification or mutation in the receptor. MMP-1 is known to be up-regulated by various stimulatory agents including growth factors. We examined the regulation of MMP-1 by EGFR activation and observed the induction of MMP-1 after EGF treatment. Inhibition of the receptor by pharmaceutic inhibitor treatment and genetic approaches led to reduction in MMP-1 levels. We also observed that this regulation is primarily mediated by the downstream MAPK pathway. Inhibition of MAPK and not PI3K pathway resulted in diminished MMP-1 protein levels even in the presence of EGF. These studies demonstrate the importance of the EGFR-MAPK signaling pathway in the induction of MMP-1 in glioma cell lines. In addition, MMP-1 plays a role in glioma cell invasion in vitro. These results along with the reports of MMP-1 over-expression in GBM warrant future studies examining the function of MMP-1 in vivo.
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Mullet, Emily. "Functional Consequences of Matrix Metalloproteinase-1 Over-Expression in Human Gliomas". VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1437.
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Nguyen, Khanh Vu Thuy. "The Effects of Scaling and Root Planing on the Systemic Levels of Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1)". VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd_retro/160.
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Balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is required for normal wound healing. Chronic inflammation, such as that seen in cardiovascular and periodontal diseases, may upset this balance. The aim of this study was to determine whether initial periodontal therapy would have an effect systemically on the levels of MMP-9 and TIMP-1. Twenty-one patients with generalized chronic periodontitis were enrolled in the study. Clinical examinations were conducted and parameters measured. Scaling and root planing was performed and blood analysis done to determine the plasma concentrations of MMP-9 and serum concentrations of TIMP-1. Initial periodontal therapy resulted in improvements in gingival inflammation and plaque levels. No effect on the plasma concentrations of MMP-9 and serum concentrations of TIMP-1 could be found following therapy.
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Arnold, Laurence. "Biophysical characterisation of collagen binding by the hemopexin domain of matrix metalloproteinase-1 (MMP-1)". Thesis, University of Portsmouth, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516871.
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Li, He. "A study of fibroblast-mediated contraction in ocular scarring : gene expression profiling and the role of small GTPases in Matrix Metalloproteinase 1 (MMP1) regulation". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10024949/.
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Understanding the molecular mechanisms involved in fibroblast-mediated tissue contraction is essential for developing future therapeutics for anti-scaring and fibrosis treatment not only for eyes, but also for a wide range of fibrotic diseases. The small Rho GTPase Rac1 is a master regulator of actin dynamics, which plays an essential role in protrusive activity, tissue repair and wound healing. A genome wide microarray study was performed with/without the transient treatment of human conjunctival fibroblasts with Rac1 inhibitor NSC23766 in a collagen gel contraction model to unveil the signalling events underlying contractile activity and the contribution of Rac1 activation. Through a comprehensive analysis that combined a pilot parallel study of scarring in an in vivo model in rabbit following glaucoma filtration surgery, and previously obtained microarray data of human ocular fibrotic diseases (including trachoma and thyroid-associated orbitopathy), it was identified that the contraction process consisted of two phases: an early phase that exhibited a classic serum/wound response profile with upregulation of genes related to inflammation, matrix remodelling, and transcription activation; and a late stage when the hyperactive signal receded and the gene profile progressed to promote fibrosis. The transient treatment with NSC23766 altered gene expression, and the early inhibition of Rac1 blocked the fibroblasts from entering the contractile phenotype as a whole. Interestingly, NSC23766 did not supress the mRNA expression of Matrix Metalloproteinase (MMP) 1, 3 and 10 during contraction, but reduced their enzymatic activity. The link between the activation of the Rho GTPase and MMP expression was subsequently investigated using MMP1 as an example. The results showed Rac1, Cdc42 and RhoA differently regulated MMP1 expression and secretion in fibroblasts during contraction, suggesting that the rate-limiting step for modulating MMP is the release in the extracellular medium rather than expression levels, drawing some interesting new prospects for therapies.
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Sritharan, Kajanatharshni. "The role of membrane type-1 matrix metalloproteinase (MT1-MMP) in carotid plaque instability". Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517390.
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Wang, Fang St George Clinical school UNSW. "Oxidative stress induced C-Jun N-terminal Kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression". Awarded by:University of New South Wales. St George Clinical school, 2006. http://handle.unsw.edu.au/1959.4/28815.
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To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons were evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 over-expression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.
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Harada, Tomika. "Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas". Kyoto University, 1999. http://hdl.handle.net/2433/181703.
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Zinzindohoue, Franck. "Influence de deux polymorphismes nucléotidiques fonctionnels des régions promotrices des gènes de MMP-1 (-1607ins/delG) et de MMP-3 (-1612ins/delA) au cours des cancers ORL et des cancers colorectaux". Paris 5, 2005. http://www.theses.fr/2005PA05S021.
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Nous avons étudié l'influence des polymorphismes nucléotidiques fonctionnels des régions promotrices de MMP-1 (-1607ins/delG) et de MMP-3 (-1612ins/delA). Nous avons montré dans une étude cas-témoin de cancers ORL, que les homozygotes MMP-1 -1607delG avaient un risque significativement plus élevé de cancer ORL. Dans une seconde étude, nous avons montré la valeur prédictive du polymorphisme de MMP-3 sur la réponse à la chimiothérapie néoadjuvante associant 5 FU - cisPt. Dans une troisième étude sur des malades atteints de cancers colorectaux, les homozygotes pour l'allèle MMP-1 1607insG stades 2 et 3 selon la classification TNM avaient une survie significativement plus courte. Au total, nos résultats confirment que des polymorphismes des régions promotrices des gènes MMP1 et MMP3 pourraient jouer un rôle dans le risque de survenue du cancer et dans son pronostic et qu'ils pourraient avoir une valeur prédictive de la réponse à la chimiothérapieWe studied the influence of functional nucleotide polymorphisms in MMP-1 (-1607ins/delG) and MMP-3 (-1612ins/delA) gene promoters in cancer. In a case-control study on head and neck squamous cell carcinoma, we demonstrate that MMP-1 -1607delG homozygous patients had a greater risk of cancer. In a second study, we demonstrated the predictive value of MMP-3 polymorphysm on response to 5FU-CisPt neoadjuvante chemotherapy. In a third study on a colorectal cancer patient series, MMP-1 1607insG stages 2 and 3 homozygous patients (TNM classification) had a shorter survival. In conclusion, our results confirm that nucleotide polymorphisms in MMP-1 and MMP-3 gene promoters could play a role in the occurrence of cancer, in its prognosis, and could be a factor of predictive value of response to neoadjuvante chemotherapy
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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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Kormi, I. (Immi). "Translational perspectives on matrix metalloproteinase 8 and other inflammatory biomarkers in cardiovascular diseases". Doctoral thesis, Oulun yliopisto, 2017. http://urn.fi/urn:isbn:9789526215297.
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Abstract Cardiovascular diseases (CVD), and especially atherosclerotic vascular diseases (ASVD), are the largest cause of morbidity and premature death worldwide. Coronary heart disease (CHD) and cerebrovascular disease (stroke) are common and severe manifestations of ASVD. Atherosclerosis is a chronic inflammatory disease and lipoprotein metabolism disorder. If the regulation of inflammatory process is disturbed, the systemic release of pro-inflammatory mediators, including matrix metalloproteinases (MMPs), may lead to a low-grade systemic inflammation, which is a risk factor for CVDs. MMPs are enzymes that are responsible for the degradation of the extracellular matrix (ECM) during growth and tissue renewal but also in many pathological conditions. These ECM degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture, leading to acute cardiovascular manifestations. The pivotal role of MMPs in atherosclerosis has raised interest in the development of drug therapies targeting these proteases. Doxycycline has inhibitory effects on some MMPs in addition to its antimicrobial properties. The main objective of this thesis project was to investigate the potential of these inflammatory mediators as biomarkers, risk factors, and therapeutic targets in CVD. The special focus was on MMP-8 and its main regulator, tissue inhibitor of matrix metalloproteinase (TIMP)-1. The results of this study show that a high serum MMP-8 concentration indicates an acute cardiac condition and predicts a future CVD event. In addition to MMP-8, MMP-7 is a potential biomarker for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture. Measurement of serum MMP-8 concentration is reliable, anti-invasive and inexpensive and can be done in hospital settings. We also show that regular-dose doxycycline decreases the systemic inflammatory burden in patients with earlier myocardial infarction and is a promising anti-inflammatory therapy in the prevention of CVDs with relatively minor side effects. In conclusion, MMP-8 and TIMP-1 can be considered inflammatory risk markers of CVD events and death, and they can be utilized both for diagnostic and screening purposes. The inhibition of MMP-8 by doxycycline may reduce the systemic inflammatory burden in patients with myocardial infarctionTiivistelmä Sydän- ja verisuonisairaudet, erityisesti ateroskleroottiset valtimosairaudet, ovat maailman yleisin sairastuvuuden ja ennenaikaisen kuoleman syy. Sepelvaltimotauti ja aivohaveri ovat ateroskleroottisen valtimosairauden yleisiä ja vakavia ilmenemismuotoja. Ateroskleroosi on krooninen tulehduksellinen sairaus ja lipoproteiiniaineenvaihdunnan häiriö. Jos tulehdustapahtuma häiriintyy, elimistöön vapautuvat tulehdusvälittäjäaineet, kuten matriksin metalloproteinaasit (MMP), voivat aiheuttaa elimistön matala-asteisen tulehduksen, joka on sydän- ja verisuonisairauksien riskitekijä. MMP:t ovat entsyymejä, jotka pilkkovat solunväliainetta kasvun ja kudosten uusiutumisen mutta myös monien tautitilojen yhteydessä. Nämä soluväliainetta hajottavat proteaasit ja niiden säätelijät ovat tärkeässä roolissa ateroskleroottisen plakin muodostumisessa ja repeämisessä, joka johtaa äkillisiin sydäntautitapahtumiin. Matriksin metalloproteinaasien keskeinen rooli ateroskleroosissa on herättänyt kiinnostusta niihin kohdistuvan lääkehoidon kehittämiseen. Doksisykliinillä on joidenkin MMP-entsyymien toimintaa estävä vaikutus antimikrobiaalisten ominaisuuksiensa lisäksi. Tämän väitöskirjatutkimuksen päätavoitteena oli tutkia näiden tulehdusvälittäjäaineiden mahdollisuuksia biomarkkereina, riskitekijöinä ja lääkehoidon kohteena sydän- ja verisuonisairauksissa. Erityinen kiinnostuksen kohde oli MMP-8 ja sen pääsäätelijä ja kudosestäjä, tissue inhibitor of matrix metalloproteinase (TIMP)-1. Tämän tutkimuksen tulokset osoittavat, että seerumin korkea MMP 8 pitoisuus viittaa akuuttiin sydäntautiin ja ennakoi tulevaa sydäntautitapahtumaa. MMP-8:n lisäksi MMP-7 on lupaava sydäntapahtuman biomarkkeri. Näiden matriksin metalloproteinaasien ja niiden kudossäätelijä TIMP-1:n välinen tasapaino voi liittyä ateroskleroottisen plakin haurauteen. Seerumin MMP-8:n mittaus on luotettavaa, kajoamatonta ja edullista, ja mahdollista toteuttaa myös sairaalaolosuhteissa. Näytämme myös, että doksisykliini vähentää elimistön tulehdustaakkaa sydäninfarktin sairastaneilla potilailla ja että se on sydäntautien ehkäisyssä lupaava anti-inflammatorinen lääke, jolla on suhteellisen vähän sivuvaikutuksia. Johtopäätöksenä on, että MMP-8:aa ja TIMP-1:tä voidaan pitää lupaavina sydän- ja verisuonitautien sekä kuoleman biomarkkereina sekä diagnostiikka- että seulontakäytössä. Lisäksi tutkimustulokset osoittavat, että MMP-8:n esto doksisykliinillä voi vähentää elimistön tulehdustaakkaa sydänkohtauksen sairastaneilla potilailla
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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'EAIThe 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 cancerTiivistelmä 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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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 SantosTexto 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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Mazzone, Marco. "Role of intracellular transport, sorting and release of membrane type 1 matrix metalloproteinase (MT1-MMP) in tumor cell invasion and metastic dissemination". Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422024.
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Solotskaya, Anna. "NEUTROPHIL PRODUCTS CONTROL THE EXPRESSION OF PROGESTERONE RECEPTORS AND MATRIX METALLOPROTEINASE-1 IN THE DECIDUAL AND MYOMETRIUM AND ARE POSSIBLE REGULATORS OF PREMATURE LABOR". VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2112.
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Neutrophils infiltrate myometrium and decidual tissue prior to parturition. Activated neutrophils release reactive oxygen species (ROS) and tumor necrosis factor α (TNFα), which might increase expression of pro-labor genes such as matrix metalloproteinase-1 (MMP-1), progesterone receptor (PR) A/B ratio, and cause demethylation of DNA. These changes might cause labor. Decidual tissue was obtained from consented, healthy women at term (37+ weeks of gestation) not in labor (no contractions, without cervical effacement), term labor and preterm labor (under 37 weeks of pregnancy). Decidual and myometrial cells in culture were treated with (1) ROS, (2) TNFα, or (3) 5-aza-2’-deoxycytidine. Total RNA was extracted, converted to cDNA and evaluated by qRT-PCR for MMP-1, PR-A+B and PR-B. TNFα increased MMP-1 by 17 fold in decidual cells and more than 12 fold in myometrial cells. PR-A/B was increased by 5.6 fold in decidua. ROS up-regulated MMP-1 by 6 fold and elevated the PR-A/B ratio by 4.5 fold in decidual tissue. DNA demethylation increased MMP-1 by about 4 and 11 fold in decidual and myometrium, respectively. The PR-A/B ratio was increased by 4 fold in decidua and the PR-B was decreased by 40% in the myometrium due to DNA demethylation. Decidual tissue in preterm labor showed a 7-fold increase in MMP-1 over term laboring and over a 15-fold increase over term not in labor tissue. In conclusion, MMP-1 expression and PR-A/B ratio was increased by neutrophil products possibly through a mechanism of DNA methylation in decidua and myometrium. Preterm decidua showed a dramatic increase in MMP-1 over normal labor tissue. TNFα and ROS increased expression of MMP-1 to possibly initiate parturition. These data might help explain mechanisms responsible for preterm labor unrelated to infection or premature rupture of membranes.
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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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Miki, Takao. "The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interacts with membrane type 1 matrix metalloproteinase (MT1-MMP) and CD13/aminopeptidase N (APN), and modulates their endocytic pathways". Kyoto University, 2007. http://hdl.handle.net/2433/135757.
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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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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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Previous issue date: 2006-09-19The 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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Juliasse, Luiz Eduardo Rodrigues. "Estudo da express?o imuno-histoqu?mica das prote?nas MMP-9, MMP-13 e TIMP-1 em ameloblastomas e tumores odontog?nicos ceratocistos". Universidade Federal do Rio Grande do Norte, 2014. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17136.
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Previous issue date: 2014-02-28Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs
Os ameloblastomas e tumores odontog?nicos ceratoc?sticos (TOC) representam les?es odontog?nicas que, apesar de sua natureza benigna, se destacam por um comportamento biol?gico distinto, caracterizado pelo crescimento localmente agressivo e epis?dios recidivantes. A reabsor??o dos ossos gn?ticos provocada pelo crescimento dessas les?es constitui um fator determinante ? expans?o das mesmas, sendo mediada tanto por c?lulas osteocl?sticas como pela a??o enzim?tica de diversas metaloproteinases de matriz (MMPs). A express?o de fatores estimuladores e inibidores da reabsor??o ?ssea vem sendo correlacionada com o desenvolvimento destas les?es, merecendo destaque algumas MMPs como as colagenases e as gelatinases e os inibidores teciduais de metaloproteinases (TIMPs), dentre outros. Baseados na premissa de que fatores estimuladores e inibidores de processos osteol?ticos podem ser determinantes para o ritmo de crescimento de les?es odontog?nicas intra?sseas, o objetivo de estudo foi avaliar a imunoexpress?o das prote?nas MMP-9, -13 e TIMP-1 no epit?lio e mes?nquima de esp?cimes de ameloblastomas e TOC. A an?lise estat?stica foi realizada atrav?s dos testes de Mann-Whitney e Wilcoxon com n?vel de signific?ncia estabelecido em 5%. Atrav?s de uma an?lise quantitativa das c?lulas imunomarcadas, foi observada a express?o imuno-histoqu?mica das MMP-9, -13 e TIMP-1 em 100% dos casos, tanto no epit?lio quanto no mes?nquima tumoral. Mais de 76% das c?lulas epiteliais (escore 3) dos TOC e ameloblastomas apresentaram imunomarca??o para MMP-9 (p=0,382) e MMP-13 (p=0,069), sendo estatisticamente significativa para o TIMP-1 (p=0,003) nos ameloblastomas. No mes?nquima, observou-se maior escore de imunomarca??o da MMP-13 (p=0,031) nos ameloblastomas em rela??o aos TOC, enquanto para a MMP-9 e TIMP-1 n?o se observou diferen?a estatisticamente significativa (p=0,403; p=1,000). O c?lculo da raz?o entre os escores de express?o das prote?nas revelou, de uma maneira geral, similaridade entre as les?es, sendo observado predom?nio significante de igualdade de express?o do TIMP-1 e da MMP-9 apenas no epit?lio dos ameloblastomas. A imunoexpress?o marcante das MMP-9, MMP-13 e TIMP-1 no epit?lio e mes?nquima das les?es estudadas indica que estas prote?nas participam na remodela??o da MEC necess?ria ? progress?o tumoral, no entanto, as diferen?as pontuais observadas na express?o de algumas destas prote?nas, n?o s?o suficientes para sugerir diferen?as no comportamento biol?gico dos ameloblastomas e dos TOCs
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Butt, Louise. "Structure-function relationships in matrix metalloproteinase-1". Thesis, University of Portsmouth, 2013. https://researchportal.port.ac.uk/portal/en/theses/structurefunction-relationships-in-matrix-metalloproteinase1(2b3318eb-8f07-48ab-8b00-b77a1e069d71).html.
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Collagenolysis, the catabolism of triple helical collagen, is essential for the physiological remodeling of connective tissues during growth and development. Aberrant collagen degradation is a feature of both inflammatory diseases and cancer cell invasion. Matrix metalloproteinase-1 (MMP-1) is a known collagenase and previous studies have implicated its hemopexin (HPX) domain in binding and possibly destabilising collagen in preparation for hydrolysis by the catalytic (CAT) domain. More recently, conformational freedom and domain separation of the CAT and HPX domains has been proposed to play a role in collagen degradation. This study aims to explore HPX mediated collagen recognition and the postulated flexible state of MMP-1, in order to enhance our understanding of the collagenolytic mechanism. Here, biophysical methods have been used to study the complex formed between the MMP-1 HPX domain and a synthetic triple helical peptide (THP) that encompasses the MMP-1 cleavage site of the collagen α1(I) chain. A programme of site-directed mutagenesis was used to produce an extensive library of recombinant proteins. Surface plasmon resonance (SPR) has been used to characterise a previously unknown collagen binding site (exosite) located in blade 1 of the HPX domain and small angle x-ray scattering has been used to probe the conformational freedom and transient domain separation in mutant forms of both zymogen and mature MMP-1 enzymes. Significant reductions in THP affinity were observed on mutation of either Phe301, Val319 and Asp338, residues forming part of a “ball and socket” joint in the CAT-HPX interface. Disruption of the CAT-HPX interface by mutagenesis, of any of these three residues, severely impacts collagen recognition. Conversely, the reduced collagen binding activity of a "stapled" mutant (in which the CAT and HPX domains are constrained with a disulphide bridge) indicates that the ability of the domains to transiently dislocate is also important. Thus, a balanced equilibrium between these compact and dislocated states is an essential feature of MMP-1 collagenolytic activity.
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Cox, Kathryn Elizabeth. "Matrix metalloproteinase-3 in uterus and endometriosis". free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012963.
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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 FelisbinoTese (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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Pullen, Nicholas. "THE INFLUENCES OF MATRIX METALLOPROTEINASE-1 EXPRESSION ON GLIOBLASTOMA PATHOLOGY". VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2037.
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Glioblastoma multiforme (GBM) is an aggressive central nervous system (CNS) cancer characterized by enhanced tumor cell motility, pernicious invasion into the normal brain, extensive tumor-induced angiogenesis, and adaptive resistance to current therapeutic paradigms. One of the difficulties associated with GBM is the ability of the tumor cells to infiltrate normal CNS tissue. Neurosurgeons can remove the primary tumor mass, but peripheral cells that are inaccessible will ultimately result in a secondary lesion that can lead to death. The matrix metalloproteinases (MMP) are well known for their abilities to facilitate processes of cellular motility and invasion through their clearance of extracellular matrix (ECM). A specific member of this family, MMP-1, is not observed in normal brain, yet its expression is a common characteristic of GBM. The various causes of MMP-1 expression, and its consequences in GBM cells are unknown. As such, functional studies were conducted related to the induction of MMP-1 expression via another molecule intrinsic to GBM, nitric oxide (NO). The exposure of GBM cell lines to nanomolar concentrations of NO produced significant inductions of MMP-1 expression and GBM cell motility. The specific removal of MMP-1 with siRNA elicited an abrogation of NO-stimulated motility, suggesting a pathological contribution by this enzyme. Furthermore, recent accumulating evidence suggests that MMP-1 contributes to tumor cell survival and related angiogenesis in other cancer settings. To investigate these capabilities in GBM, cell lines were stably engineered to have either MMP-1 over-expression or knock-down. Both tumor formation and size were significantly reduced with MMP-1 knock-down and significantly increased with over-expression. In a model of GBM cell-induced angiogenesis, the presence of MMP-1 contributed to an angiogenic phenotype. Further angiogenesis studies revealed a significant recruitment of host endothelium to the tumor interstitium in vivo. Proteomic studies suggest that one mechanism by which MMP-1 could influence angiogenesis is through the easement of the anti-angiogenic tissue inhibitor of metalloproteinases-4 (TIMP-4), since the removal of MMP-1 elicits a significant increase in TIMP-4 detection. Altogether, these functional data present MMP-1 as a promising target for future therapeutic investigation, because it is unique to the GBM environment and contributes to key overlapping GBM pathologies.
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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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Lehti, Kaisa I. "Membrane-type-1 matrix metalloproteinase in pericellular proteolysis and cell migration". Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/laa/haart/vk/lehti/.
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Javaid, Mohammad. "Platelet factor 4 upregulates matrix metalloproteinase-1 production in gingival fibroblasts". Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/60244.
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Background and Objective: Periodontitis is a highly prevalent chronic inflammatory disease that causes tooth loss, morbidity and confers an increased risk for systemic disease. Tissue destruction during periodontitis is due in large part to collagen-degrading matrix metalloproteinases (MMPs) released by resident cells of the periodontium in response to pro-inflammatory cytokines. Platelets are immune-competent blood cells with a newly recognized role in chronic inflammation, however their role in the pathogenesis of periodontitis is undefined. Consequently, the objective of this study was to assess the effect of platelet factor 4 (PF4), a major platelet-derived cytokine, on MMP-1 (collagenase) expression in human gingival fibroblasts (HGFs).
Methods: HGFs were cultured in the presence or absence of recombinant PF4. Pro-MMP-1 secretion was quantified by enzyme-linked immunosorbent assay (ELISA) analysis of the cell culture supernatants. MMP-1 transcription was quantified by real-time polymerase chain reaction (qPCR). Regulation of MMP-1 production by the p44/42 MAP kinase (MAPK) signaling pathway was examined in the presence or absence of PF4.
Results: Exposure to PF4 caused a ~2-3-fold increase in MMP-1 transcription and secretion from cultured human gingival fibroblasts (HGFs). PF4 treatment also enhanced phosphorylation of p44/42 MAP kinase (MAPK), which has been previously shown to induce MMP-1 expression in fibroblasts. Blockade of p44/42 MAPK signaling with the cell-permeant inhibitors PD98059 and PD184352 abrogated PF4-induced pro-MMP-1 transcription upregulation and release from cultured HGFs.
Conclusion: We conclude that platelet factor 4 upregulates MMP-1 expression in human gingival fibroblasts in a p44/42 MAPK-dependent manner. These findings point to a previously unidentified role for platelets in the pathogenesis of periodontal diseases.Dentistry, Faculty of
Graduate
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Labbene, Azza [Verfasser], e Nikolas [Akademischer Betreuer] Mirow. "Rolle der Matrix-Metalloproteinasen bei der Mitralklappeninsuffizienz: Assoziation zwischen der Expression von MMP-1, MMP-9, TIMP-1 und TIMP-2, dem Mitralinsuffizienzgrad und der Ätiologie / Azza Labbene ; Betreuer: Nikolas Mirow". Marburg : Philipps-Universität Marburg, 2019. http://d-nb.info/1199537500/34.
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Naveed, Shams-un-nisa. "Matrix metalloproteinase-1 mediated extra-cellular matrix remodelling contributes to airway smooth muscle growth and asthma severity". Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/50577/.
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Introduction Airway remodelling describes the histopathological changes in tissue architecture observed in obstructive lung diseases such as asthma and may have a negative impact on lung function. These changes do not appear to be treated by current asthma treatments. Changes observed during airway remodelling include increased thickness of airway smooth muscle (ASM) layer and enhanced extracellular matrix (ECM) deposition. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which facilitate tissue remodelling via ECM protein degradation. Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of patients with asthma (but not in healthy people). MMPs expression is highly regulated in lungs and is increased in disease states. My project aimed to assess MMP-1, -2 and -9 expression and activity in asthma airways. Furthermore, the underlying mechanism of MMP-1 activation and subsequently its role in airway remodelling and worsening asthma severity was investigated in the context of asthma exacerbation, which is thought to be an exaggerated lower airway inflammatory response to an environmental exposure such as respiratory virus infection. Methods Patients with stable asthma and healthy controls underwent spirometry, methacholine airway (PC20 ) challenge, exhaled nitric oxide (FeNO) test, bronchoscopy/bronchial washings and primary airway smooth muscle (ASM) cell cultures. A second asthma group (mild to moderate severity) and controls had symptom scores, spirometry and bronchoalveolar lavage (BAL) before and after rhinovirus inoculation. ECM was prepared from decellularised primary ASM cultures. MMP-1 protein levels and activity were assessed in bronchial fluid samples by enzyme-linked immunosorbent assay (ELISA), western blotting and fluorescent activity assay. ASM cell growth was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) reduction assay and cell counts. Bronchial fluid gelatinase (MMP-2 and -9) expression and activity was assessed by gelatin zymography. Results MMP-1 and MMP-9 expression was enhanced in both stable asthma and during asthma exacerbations, whilst MMP-2 expression was only increased during asthma exacerbations. MMP-1 can be activated by tryptase, which is an inflammatory product of mast cell degranulation. Activated (degranulated) mast cells enhanced proliferation of both control and asthma ASM cells via the production of a pro-proliferative ECM in vitro and the proliferative effect was dependent on MMP-1. In patients with asthma, mast cells numbers within ASM bundles were associated with ASM growth. MMP-1 protein levels were related to bronchial reactivity and MMP-1 activity increased during asthma exacerbations, where its levels were related to exacerbation severity. Conclusion This study suggests that MMP-1 plays an important role in asthma pathophysiology and that ASM/mast cell interactions contribute to asthma severity by transiently increasing MMP-1 activation, ASM growth and airway responsiveness. Moreover, there is increased expression of MMP-2 and -9 during asthma exacerbations compared with stable asthma. As both MMP-2 and -9 act as mediators of inflammation (Okada, S. et al., 1997) (Elkington, P.T.G., 2006) and tissue remodelling (Oshita, Y. et al., 2003), an increase in gelatinolytic activity linked to MMP-2 and MMP-9 is also likely to play a significant role in the pathophysiology of asthma exacerbations.
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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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Hussain, Shaista. "Signalling pathways implicated in the growth factor and cytokine mediated up regulation of gelantinase B, collagenase 1 and stromelysin-1 in rabbit aortic smooth muscle cells in vitro". Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340275.
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Hartland, Stephen. "Mechanistic analyses of transforming growth factor-Î’-mediated repression of matrix metalloproteinase-1". Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430407.
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Durkan, Garrett Christopher. "Matrix metalloproteinase-1 and -9 and tissue inhibitor of metalloproteinase-1 in bladder cancer : pathophysiological significance and relationship to epidermal growth factor receptor expression". Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369832.
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Fischoeder, Arne [Verfasser]. "Regulation von Matrix Metalloproteinase-9 durch Insulin in humanen THP-1 Monozyten / Arne Fischoeder". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023784432/34.
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Shimizu, Makoto. "Hyaluronan Inhibits Matrix Metalloproteinase-1 Production by Rheumatoid Synovial Fibroblasts Stimulated by Proinflammatory Cytokines". Kyoto University, 2004. http://hdl.handle.net/2433/147561.
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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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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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Hovell, Christopher John. "Membrane-type 1 matrix metalloproteinase expression by hepatic stellate cells : its role in liver fibrosis". Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322017.
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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 SuperiorO 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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Koch, Sabine. "Die Expression und Aktivität von Matrix-Metalloproteinase-1 wird durch Stickstoffmonoxid, reduzierte Thiole und Zytokine reguliert". [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=983272174.
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McCready, Jessica. "The Influence of a Single Nucleotide Polymorphism In The Matrix Metalloproteinase-1 Promoter on Glioma Biology". VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd/1123.
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Glioblastomas are an incurable type of brain tumor with a mean survival time of 9-12 months following diagnosis. One of the reasons for this poor prognosis is the ability of tumor cells to invade the surrounding normal brain tissue. Enzymes responsible for this invasive nature include the matrix metalloproteinase family. MMP-1 is a member of this family which has been well studied in many types of invasive tumors, with gliomas being an exception. We studied a single nucleotide polymorphism (SNP) in the MMP-1 promoter that may influence glioma biology. This SNP consists of the presence (2G) or absence (1G) of a guanine nucleotide at position -1607. The additional guanine nucleotide creates a binding site for ETS transcription factors and combined with the AP-1 binding site at position -1602 creates a Ras Responsive Element. We determined that the distribution of the MMP-1 genotype differed significantly between the healthy population and the glioblastoma patient population, with the 2G/2G genotype more prevalent in the glioblastoma patients. In addition, MMP-1 mRNA and protein examined in a select group of patient tissue had significantly higher levels when compared to normal brain controls, however, there was no correlation with genotype. Promoter reporter assays indicated that the 2G promoter was approximately three times more active than the 1G promoter in three different glioma cell lines.We investigated potential signaling mechanisms responsible for increases in MMP-1 transcription due to the presence of the RAS responsive element. Treatment of glioma cell lines with hepatocyte growth factor/scatter factor (HGF/SF) led to significant increases in MMP-1 transcription, via the MAP kinase ERK pathway. AP-1 transcription factor proteins, cJun and cFos were increased in response to HGF treatment but not Ets-1 and ETV-1. HGF/SF treatment of glioma cell lines differing in their MMP-1 genotype affected binding of ETS and AP-1 proteins to the endogenous MMP-1 distal promoter. Using chromatin immunoprecipitation assays, we identified these differentially DNA-bound AP-1 and ETS proteins. The data presented indicate that the MMP-1 SNP (-1607) is important in glioma biology and may contribute to tumor function and future investigations into its role in glioma biology is warranted.
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Pacheco, Fernández Natalia María [Verfasser], e Reinhard [Akademischer Betreuer] Fässler. "Nucleobindin-1 modulates extracellular matrix remodeling by promoting intra-Golgi trafficking of matrix metalloproteinase 2 / Natalia María Pacheco Fernández ; Betreuer: Reinhard Fässler". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1215499892/34.
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Prothero, Joanna. "Matrix metalloproteinase-3 (stromelysin-1) gene promoter polymorphism in relation to predisposition to inflammatory bowel disease (IBD)". Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436934.
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Rauvala, M. (Marita). "Matrix metalloproteinases -2 and -9 and tissue inhibitors of metalloproteinases -1 and -2 in gynaecological cancers". Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:951428187X.
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Abstract
The invasion of a tumour through tissue limiting basement membranes is the critical step in malignant growth. Gelatinases (MMP-2 and MMP-9) are endopeptidases capable of degrading extracellular and pericellular matrix proteins such as collagen IV, the major component of basement membranes. An over-expression of these gelatinases is generally found in malignant tumours and is linked to impaired prognosis in many cancer types. Tissue inhibitors of metalloproteinases (TIMPs), endogenous regulators of the MMP activity, have recently been introduced as multifunctional proteins, which have paradoxical roles in tumour growth. Little data exists on the clinical significance of the gelatinases and TIMPs in gynaecological cancers.
In this study the clinical significance of the gelatinases was studied in endometrial and uterine cervical cancers by using immunohistochemical staining with specific antibodies. In epithelial ovarian cancer (EOC) these enzymes and their TIMPs were studied in the preoperative serum samples using ELISA assay. Additionally, sequential serum measurements were performed during chemotherapy to evaluate them as treatment response indicators.
In endometrial cancer, MMP-9 positivity correlated to a poor histological differentiation and an advanced clinical stage. High MMP-2 expression correlated to a poor differentiation, and unfavourable survival in stage I cancers, with mortality rates of 5% and 19% in patients with MMP-2 negative versus intensively MMP-2 positive tumours, respectively. In cervical cancers high MMP-2 expression correlated to an increased mortality risk. High MMP-9 expression was connected to a good differentiation of a tumour.
In EOC, a high circulating TIMP-1 value correlated to all the examined aggressive features of EOC, including poor survival. The serum measurements of TIMP-1 were uninformative about response evaluation during chemotherapy but paradoxically, an increase in gelatinases and TIMP-2 seemed to reflect a good response to treatment.
In conclusion, the data from this study show that high MMP-2 expression in tumour tissue could be prognostic in endometrial and cervical cancer, and preoperative circulating TIMP-1 could serve as an additional prognostic marker in EOC. Studies with larger patient cohorts would be necessary to further explore the value of these enzymes in clinical practice in gynaecological cancers.
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Pradhan-Palikhe, P. (Pratikshya). "Matrix metalloproteinase-8 as a diagnostic tool for the inflammatory and malignant diseases". Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514295096.
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Abstract Matrix metalloproteinases (MMPs) are the zinc-dependent endopeptidases which belong to a large family of proteases. MMPs are responsible for degradation and remodeling of extracellular matrix proteins during growth, organogenesis and tissue turnover. Besides their role in physiological processes, MMPs also influence various pathological processes, i.e., inflammatory diseases and cancers, in which MMPs may ultimately lead to unwanted tissue destruction. One of the most widely studied MMPs is MMP-8. MMP-8 was previously thought to be expressed only by neutrophils. Presently, it is evident that MMP-8 can be expressed in a wide range of cells such as macrophages, plasma cells, T-cells, endothelial cells, smooth muscle cells, oral epithelial cells, fibroblasts etc. MMP-8 has been previously studied in inflammation and malignancies. High serum MMP-8 concentration is associated with the presence of atherosclerosis and poor cardiovascular disease prognosis, while higher plasma MMP-8 levels protect against lymph node metastasis. Certain MMP-8 gene variations can alter promoter activity and subsequent gene expression. MMP-8 gene variation influences obstetrical outcomes, and lung and breast cancer prognosis. For our study, we hypothesized that systemic levels of MMP-8 correlate with its genetic variations and appear as novel risk markers for disease. We aimed to address the potential role of MMPs and their regulators with a special focus on MMP-8 in distinct sets of inflammatory and malignant diseases, i.e. arterial diseases, and head and neck squamous cell cancer (HNSCC). We demonstrated that the combination of high serum MMP-8 and low myeloperoxidase (MPO) levels is an important risk marker for arterial disease. Further, we demonstrated that MMP-8 gene variation is protective against arterial diseases. Interestingly, we were able to demonstrate an association between MMP-8 gene variation and serum MMP-8 concentration in a healthy population. On the other hand, we showed that plasma tissue inhibitor of matrix metalloproteinases (TIMP-1) concentration is associated with survival in HNSCC patients and TIMP-1 genotype is associated with plasma TIMP-1 levels in women only. Collectively, our study showed that serum MMP-8 levels can be used as an important risk marker in arterial disease and TIMP-1 levels in HNSCC patients. Based on our results, the hypothesis raised has been widely confirmed. Additionally, our study has warranted the need for further investigation involving a larger number of patients. If our results are replicable, serum MMP-8 and plasma TIMP-1 could be used to develop diagnostic tools as well as treatment regimes in clinicsTiivistelmä Matriksin metalloproteinaasit (MMP:t) ovat sinkkiriippuvaisia endopeptidaaseja, jotka kuuluvat laajaan proteiineja pilkkovaan proteolyyttiseen entsyymi perheeseen. MMP:ien tehtävä on pilkkoa ja uudelleen muokata soluväliaineen proteiineja kasvun, elinten kehityksen ja kudosten uusiutumisen aikana, mutta MMP:t toimivat aktiivisesti myös patologisissa prosesseissa, kuten tulehdustiloissa ja syövissä. Syövissä MMP:en vaikutus voi johtaa ei-toivottuun kudostuhoon. Yksi laajimmin tutkituista MMP-ryhmän entsyymeistä on MMP-8, jonka alunpitäen ajateltiin ilmenevän vain neutrofiileissä. Nykytietämyksen mukaan MMP-8:aa ilmentyy myös mm. makrofaageissa, plasmasoluissa, T-soluissa, endoteelisoluissa, sileälihassoluissa, suun limakalvon epiteelisoluissa ja fibroplasteissa. MMP-8:aa on aikaisemmin tutkittu erityisesti tulehdustiloissa ja pahanlaatuisissa kasvaimissa. Korkean MMP-8 seerumipitoisuuden on havaittu liittyvän valtimokovettumatautiin ja huonoon ennusteeseen sydän- ja verisuonisairauksissa, kun taas kohonnut MMP-8:n pitoisuus plasmassa suojaa imusolmuke-etäpesäkkeiltä. Tiedetään, että tietyt muutokset MMP-8:n geenissä voivat muuttaa sen promoottoriaktiviteettia ja täten säädellä geenin ilmentymistä. MMP-8:n geenimuutokset vaikuttanevat raskaudenkulkuun sekä keuhko- ja rintasyövän ennusteeseen. Tutkimushypoteesimme mukaan MMP-8:n seerumipitoisuudet riippuvat vaihtelusta MMP-8:aa koodaavassa geenissä ja niitä voidaan pitää uusina riskinarvioinnin merkkiaineina tautitiloissa. Tavoitteenamme oli osoittaa yleisesti MMP:ien ja erityisesti MMP-8:n sekä näiden proteinaasien säätelytekijöiden merkitys tietyissä tulehdustiloissa ja maligniteeteissa, kuten sepelvaltimotaudissa ja pään ja kaulan alueen syövissä. Havaitsimme, että korkea MMP-8 seerumipitoisuus ja alhainen myeloperoksidaasitaso yhdistyvät vahvasti valtimotautiriskiin. Lisäksi osoitimme, että tietty MMP-8:n geenimuunnos on suojaava tekijä valtimotaudille ja että MMP-8:n seerumikonsentraatio on siitä riippuvainen terveillä tutkituilla. Tämän lisäksi todensimme, että MMP:n kudosestäjän (tissue inhibitor of matrix metalloproteinases, TIMP-1) plasmapitoisuus liittyy pään ja kaulan alueen levyepiteelisyöpää sairastavien potilaiden eloonjääntiin ja että TIMP-1:n genotyyppi liittyy sen plasmapitoisuuteen ainoastaan naisilla. Tulostemme mukaan seerumin MMP-8-pitoisuutta voidaan pitää hyvänä riskinarviointivälineenä verisuonitaudeissa sekä TIMP-1-pitoisuutta vastaavasti pään ja kaulan alueen levyepiteelisyövissä. Saadut tulokset tukevat olettamustamme, jonka mukaan MMP-8 on tärkeä tautimarkkeri. Tämä on lisännyt kiinnostusta selvittää MMP:ien merkitystä laajemmin muissa tulehdustiloissa ja syövissä. Jos tulokset saadaan toistetuksi laajemmassa tutkimusaineistossa, seerumin MMP-8:sta voidaan kehittää kliinisten ja analyyttisten laboratorioiden käyttöön sopiva diagnostinen menetelmä
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Walia, Baljit S. "Matrix metalloproteinase activation in heart failure due to volume-overloa and the effect of AT¦1 receptor blockade". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ45160.pdf.
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Yoshida, Masahiro. "Prostaglandin F2α, cytokines, and cyclic mechanical stretch augment matrix metalloproteinase-1 secretion from cultured human uterine cervical fibroblast cells". Kyoto University, 2004. http://hdl.handle.net/2433/147549.
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