Dissertations / Theses on the topic 'Tissuee inhibitors of metalloproteinase'
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Kranzhöfer, Alexander Friedrich. "Regulation of metalloproteinase expression in vascular pathology." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251550.
Full textKyllönen, H. (Heli). "Gelatinases, their tissue inhibitors and p53 in lymphomas." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514291319.
Full textParkin, Ben. "The role of matrix metalloproteinase-2 and its inhibitors in keratoconus." Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343282.
Full textWilliams, Darren Malfryn. "Investigation of the effects of hypoxia on matrix metalloproteinase and tissue inhibitors of matrix metalloproteinases expression in pancreatic cancer." Thesis, University of Birmingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393836.
Full textTwitty, Anne. "The expression of tissue inhibitor of metalloproteinase during the early stages of bone graft healing." Thesis, Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B21804023.
Full textRauvala, 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.
Full textMcCrudden, Raymond. "Regulation of the synthesis of tissue inhibitors of metalloproteinase-1 and -2 by hepatic and pancreatic stellate cells." Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/372931/.
Full textTitz, Tiago de Oliveira. "Avaliação fenotípica e funcional dos eosinófilos da dermatite atópica do adulto." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5133/tde-20052015-121525/.
Full textIntroduction: Atopic dermatitis (AD) is an inflammatory, chronic and recurrent skin disease characterized by intense pruritus and xerosis. AD has a complex etiopathogenesis, which involves the influence of genetics, environment, and immunological disorders, among others. Eosinophils are multifunctional polymorphonuclear leukocytes that contribute to the pathogenesis of several inflammatory processes, such as AD. In addition to the production and secretion of diverse proteins of the cytoplasmic granules, eosinophils have also the potential to secrete metalloproteinases (MMPs), proteolytic enzymes with a primary role for degrading several extracellular matrix components, present in distinct physiological and pathological processes. Objective: To evaluate:1) the phenotypic profile of eosinophils in adults with atopic dermatitis through the expression of CCR3, CD23, CD38, CD69 and CD62L molecules; 2) the functional profile through secretion of MMPs, tissue inhibitors of metalloproteinases 1 and 2 ( TIMP-1 and TIMP-2) and RANTES by purified eosinophils. Methods: This work enrolled 41 patients with AD, diagnosed according to Hanifin & Rajka\'s criteria) and 45 healthy controls. Severity of the disease was established utilizing EASI (Eczema Area and Severity Index). Eosinophils (Lineage cocktail 1- CCR3+) from peripheral blood were analyzed for CCR3, CD38, CD69, CD23 and CD62L by flow cytometry (LSRFortessa, BD Biosciences), and analysis was performed using the FlowJo 7.5.6 software. Purified eosinophils were stimulated with Staphylococcus aureus enterotoxin B (SEB) FSL-1 (Toll-like receptor 2/6 agonist), and supernatants were collected for MMPs, TIMPs and RANTES secretion, evaluated by ELISA and cytometric bead array (CBA). Results: Patients with AD have a higher frequency of eosinophils (LIN1- CCR3+), related to disease severity. Moreover, the frequency of CD62L (L-selectin) and CD23 (low-affinity receptor for IgE) in (LIN1- CCR3+) eosinophils was reduced in individuals with AD. CD69 and CD38 (early and late activation receptors) did not show significant difference in the studied groups. Serum levels of MMPs and of TIMP-1 and TIMP-2 were similar in healthy controls and AD patients. When analyzing secretion of MMPs and TIMPs by purified eosinophils from AD individuals, we detected a decrease in baseline levels of TIMP-1, TIMP-2, and reduced RANTES-mediated chemotaxis. Conclusions: Eosinophils in AD exhibit an activation profile of acute phase, with enhanced CCR3 expression, high potential for migration due to reduced expression of CD62, defective activation mechanisms via CD23, altered tissue remodeling process mediated by TIMP-1 and TIMP-2 and reduced RANTES-mediated chemotaxis
Phillips, Blaine Wesley. "Transcriptional regulation of the tissue inhibitors of metalloproteinases." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0027/NQ49530.pdf.
Full textGroft, Lori Lynne. "Tissue inhibitors of metalloproteinases in human malignant gliomas." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0018/MQ48004.pdf.
Full textDodds, Philippa. "Glycosaminoglycan interactions with the tissue inhibitors of metalloproteinases." Thesis, University of East Anglia, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410232.
Full textRuokolainen, 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.
Full textViani, Mary Anne. "Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the hematopoietic microenvironment." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ54084.pdf.
Full textLangton, Kevin Pearce. "Molecular characterisation of tissue inhibitor of metalloproteinases-3." Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340186.
Full textHowell, Robert Duncan. "An investigation into the role of matrix metalloproteinases in liver metastases from colorectal cancer." Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274565.
Full textMcIntush, Eric W. "Tissue inhibitor of metalloproteinases (TIMP-1) in luteal function /." free to MU campus, to others for purchase, 1996. http://wwwlib.umi.com/cr/mo/fullcit?p9737849.
Full textSteén, Björn. "Matrix metalloproteinases and their inhibitors in ocular neovascularization /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-712-6/.
Full textPickering, Judith Ann. "Function of tissue inhibitor of metalloproteinase-1 in liver fibrosis." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244995.
Full textMcElligott, Anthony Morgan. "The role of matrix metalloproteinases and their inhibitors, the tissue inhibitors of metalloproteinases, in renal cell carcinoma cell invasion and metastasis." Thesis, University of Ulster, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326125.
Full textRapti, Magdalini. "Molecular basis of the inhibition of matrix metalloproteinases (MMPs) by the tissue inhibitors of metalloproteinases (TIMPs)." Thesis, University of Kent, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404554.
Full textLind, Anna Karin. "Human ovulation : studies on collagens, gelatinases and tissue inhibitors of metalloproteinases /." Göteborg : Department of Obstetrics and Gynecolgy, Institute of Clinical Sciences, Sahlgrenska University Hospital, The Sahlgrenska Academy at Göteborg University, 2006. http://hdl.handle.net/2077/773.
Full textHalbgewachs, Birgit. "Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) als prometastatischer Faktor." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-117789.
Full textFrench, Matthew. "The role of metalloproteinases and their tissue inhibitors in adipose tissue remodelling and metabolic risk." Thesis, University of East Anglia, 2017. https://ueaeprints.uea.ac.uk/67760/.
Full textFata, Jimmie Eugene. "Tissue inhibitors of metalloproteinases (TIMPS) in mammary gland morphogenesis, differentiation, and apoptosis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ59007.pdf.
Full textMichael, Angharad Wyn. "The regulation of tissue inhibitors of Matrix metalloproteinases (TIMPs) in the gastric epothelium." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501606.
Full textBotelho, Fernando M. "Oncostatin M regulation of the tissue inhibitor of matrix metalloproteinases-1 promoter." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0031/NQ66255.pdf.
Full textWilliamson, Richard A. "Studies on the structure and function of tissue inhibitor of metalloproteinases (TIMP)." Thesis, University of Kent, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257205.
Full textStilley, Julie Ann Weaver Sharpe-Timms Kathy L. "Tissue inhibitor of metalloproteinase-1 contributes to reduced fecundity in a rat model of endometriosis." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6072.
Full textHembry, Rosalind Marian. "The immunolocalization of the metalloproteinases and their inhibitor, TIMP, in cells and tissues." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303185.
Full textPaiva, Katiucia Batista da Silva. "Desenvolvimento osseo e dentario : aspectos biologicos, bioquimicos e moleculares da remodelação da matriz extracelular regulada pelas metaloproteinases de matriz e seus inibidores." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314765.
Full textTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O objetivo deste trabalho foi delinear o perfil de expressão temporal e espacial das MMP-2 e -9, TIMP-1 e -2 e RECK durante os eventos de formação de tecidos mineralizados (osso, esmalte e dentina) em camundongos em fase embrionária, recém nascidos e indivíduos adultos através de imunohistoquímica e hibridização in situ. Durante a amelogênese em incisivos de rato adulto, na fase de secreção, as MMPs e RECK foram imunocoradas na região infracelular dos ameloblastos de secreção e RECK foi ainda detectado difuso no citoplasma destas células. MMP-9 foi localizada nas células do retículo estrelado e RECK nas células do epitélio externo. Na fase de transição, detectados uma fraca imunomarcação ao nível da membrana dos ameloblastos de transição para as MMPs e RECK esteve difuso no citoplasma destas células. Na camada papilar, as MMPs e RECK foram imunomarcadas nos macrófagos ou células dendríticas. Do início ao final da fase de maturação, a expressão de RECK foi aumentando nos ameloblastos de maturação e nas células da camada papilar, enquanto que a expressão das MMPs foi diminuindo nestas células. AS TIMPs foram detectadas somente nos ameloblastos na fase de maturação. Nós observamos RECK e a MMP-9 no citoplasma do odontoblastos, provavelmente, no complexo de Golgi ou na rede do retículo endoplasmático rugoso. Durante a ossificação intramembranosa da mandíbula e maxila, os osteoblastos foram imunocorados pelas MMPs, TIMPs e RECK. Na degradação da cartilagem de Meckel, MMPs, TIMPs e RECK foram imunomarcadas nas células do pericôndrio, bem como o mRNA de RECK. Durante a odontogênese, RECK foi imunocorado nas células do epitélio oral migrando ao ecto-mesênquima, na fase de broto, no epitélio interno do órgão do esmalte, na fase de capuz e em odontoblastos e ameloblastos na fase final de campânula. Transcritos de RECK foram localizados em todo o germe dentário na fase de capuz, mais concentrado no nó-do-esmalte secundário, na fase de campânula inicial e nos odontoblastos e ameloblastos, na fase final de campânula. O osso alveolar foi marcado em todos os períodos. Durante a ossificação endocondral, os condrócitos foram imunopositivos para as MMPs, TIMPs e RECK, na fase de diferenciação dos condrócitos (E13). Na fase de molde cartilaginoso (E14) os condrócitos hipertróficos foram imunocorados para as MMPs e RECK. RECK e TIMPs foram também encontradas no pericôndrio. Na fase de invasão vascular e celular (E15), MMPs, TIMPs e RECK foram expressos por células que migram do colar ósseo para o centro da diáfise, bem como por osteoclastos/condroclastos próximos ao septo transverso. Os condrócitos hipertróficos continuam imunocorados. De E16 a PN1, as MMPs, TIMPs e RECK foram expressas por osteoblastos e condrócitos hipertróficos na placa de crescimento e pelas células do periósteo e pericôndrio. Os resultados obtidos apontam para a expressão diferenciada de MMPs, TIMPs e RECK nos diversos eventos estudados, sugerindo que a atividade biológica destas proteínas regula a degradação da matriz extracelular tanto durante o desenvolvimento dos tecidos como sua manutenção. Além disso, pela primeira vez, demonstra-se a expressão de RECK pelas células formadoras de tecido ósseo e dentário.
Abstract: Our objective was to analyse the spatial-temporal distribution of MMP-2, MMP-9, TIMP-1, TIMP-2 and RECK during development of mineralized tissue (bone, enamel, and dentine) in embryos, newborn, and adult mice by immunohistochemistry and in situ hybridization. During rat amelogenesis, at the secretion phase, MMPs and RECK were immunostained in the ameloblast infracelular region and RECK was also detected in the cytoplasm of these cells. MMP-9 was localized in the stellated cells and RECK in the outer enamel epithelium cells. At the transition phase, a weak immunostaining was observed at the ameloblast membranes for MMPs and RECK. RECK was also detected in the cytoplasm of these cells. At the papillary layer, MMPs and RECK have been observed in macrophages and/or dendritic cells. At early and late maturation phases, MMPs and Reck profiles were similar to the transition phase, but the immunostaining was less pronounced. TIMPs were identified exclusively in maturation ameloblasts throughout the maturation phase. We also observed that the cytoplasm of odontoblasts, probably at the Golgi apparatus and/or the RER network were immunostained for Reck and MMP-9. During mandible and maxillae intramembranous ossification, osteoblasts were immunostained for MMPs (early stage), TIMPs (late stage) and RECK. In Meckel cartilage degradation, MMPs, RECK and TIMPs mRNA and protein were found in perichondrial cells. During odontogenesis migrating epithelial cells in bud stage, enamel inner epithelial cells in cap stage, and ameloblasts and odontoblasts in bell stage were immunostained for RECK. Also, RECK mRNA was found difuse in all tooth germ in cap stage, mainly localized in primary enamel knout in early bell stage, and in ameloblasts and odontoblasts in late bell stage. The alveolar bone was immunolabelled in all periods. During endochondral ossification, chondrocytes were immunopositive for MMPs, RECK, and TIMPs during chondrocyte differentiation (E13). At the cartilaginous template (E14), the hypertrophic chondrocytes (HC) were immunostained for MMPs and RECK. RECK and TIMPs immunopositive cells were found in the perichondrium. At the vascular and cellular invasion (E15), MMPs, RECK and TIMPs were expressed by migrating cells from bone collar as well as by osteoclasts/chondroclasts close to the transverse septum. HC remained immunostained. From E16 to PN1, MMPs, TIMPs, and RECK were expressed by osteoblasts and HC in the growth plate and by cells in the perichondrium and periosteum. The results show the differential expression of MMPs, TIMPs, and RECK during the processess studied, sugesting that the biological activity these proteins regulates the MEC degradation and its maintenance in tissue development. Our results show for the first time that RECK is expressed by bone-forming and tooth-forming cells during mouse endochondral and intramembranous and in embryonic and adult odontogenesis, even if these cells are from different embryonic origins.
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular
Fujimoto, Motoaki. "Tissue inhibitor of metalloproteinases protect blood?brain barrier disruption in focal cerebral ischemia." Kyoto University, 2009. http://hdl.handle.net/2433/124303.
Full textFarooqi, 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.
Full textTitle 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).
Li, Wenqing. "Regulation of tissue inhibitor of metalloproteinases-3 gene by growth factors and antioxidants in connective tissue cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ65318.pdf.
Full textO'Connell, James P. "Matrix metalloproteinase activation and inhibition." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338338.
Full textParikka, M. (Mataleena). "Collagen XVII and TIMP-1 in epithelial cell migration." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:951427198X.
Full textIredale, John Peter. "Tissue inhibitor of metalloproteinase-1 expression by human hepatic lipocytes and its role in liver disease." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295679.
Full textDurkan, 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.
Full textHan, Fei, Naoki Ishiguro, Takayasu Ito, Tadahiro Sakai, and Hisashi Iwata. "Effects of sodium hyaluronate on experimental osteoarthritis in rabbit knee joints." Nagoya University School of Medicine, 1999. http://hdl.handle.net/2237/5343.
Full textFranks, Helen. "The design and synthesis of novel matrix metalloproteinase inhibitors." Thesis, University of Southampton, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420271.
Full textHOSHINO, TAKESHI, TARO HAYAKAWA, KYOKO YAMASHITA, KOJI NISHIO, and HANG LI. "CELL CYCLE-DEPENDENT LOCALIZATION OF TISSUE INHIBITOR OF METALLOPROTEINASES-1 IMMUNOREACTIVITY IN CULTURED HUMAN GINGIVAL FIBROBLASTS." Nagoya University School of Medicine, 1995. http://hdl.handle.net/2237/16089.
Full textAhtikoski, A. (Anne). "Synthesis and degradation of muscle collagen during immobilization, glucocorticoid treatment and in neuromuscular diseases." Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514272374.
Full textMurphy, Francis Robert. "An investigation of the effect of tissue inhibitors of metalloproteinases-1 and -2 on hepatic stellate cell survival." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398826.
Full textLamlum, Hanan. "Variation in human tissue inhibitor of metalloproteinase 1 gene and its effect on the control of connective tissue remodelling in cardiovascular disease." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365809.
Full textNguyen, 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.
Full textGonçalves, Flávia Magazoni 1983. "Efeitos de polimorfismos genéticos sobre as concentrações circulantes de metaloproteinases da matriz extracelular em mulheres com migrânea = Effects of genetic polymorphisms on the circulating concentrations of extracellular matrix metalloproteinases in women with migraine." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310018.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A migrânea é uma cefaleia primária comum e altamente incapacitante que atinge cerca de 10% da população mundial, especialmente as mulheres. Apesar dos esforços, a fisiopatologia da migrânea não está completamente elucidada. No entanto, acredita-se que as metaloproteinases da matriz (MMPs) estejam envolvidas no rompimento da barreira-hematoencefálica durante uma crise de migrânea. O objetivo do presente trabalho é avaliar se polimorfismos funcionais nos genes da MMP-2 (C-1306T e C-735T) e da MMP-9 (C-1562T, -90(CA)n e R(279)Q) e haplótipos estão associados com a migrânea e se eles podem modificar os níveis circulantes de MMPs na migrânea. Para avaliar o efeito de polimorfismos da MMP-9, foram estudadas 102 mulheres sem migrânea (grupo controle) e 187 mulheres com migrânea (141 com migrânea sem aura; MSA e 46 com migrânea com aura; MA). As genotipagens para os polimorfismos C-1562T, -90(CA)n e R(279)Q da MMP-9 foram realizadas por PCR-RFLP, PCR convencional seguida de eletroforese em gel de poliacrilamida e PCR em Tempo Real, utilizando-se o sistema Taqman® para discriminação de alelo, respectivamente. As concentrações plasmáticas de MMP-9 e TIMP-1 foram determinadas por ELISA. Os genótipos para os polimorfismos da MMP-2 foram determinados por PCR em Tempo Real, utilizando-se o sistema Taqman® para discriminação de alelo em 148 mulheres sem migrânea e em 204 mulheres com migrânea (153 MSA e 51 MA). As concentrações plasmáticas da MMP-2 e do TIMP-2 foram avaliadas, respectivamente, por zimografia e por ELISA. Os haplótipos foram inferidos utilizando o programa PHASE. Este estudo é o primeiro a mostrar que polimorfismos funcionais e haplótipos nos genes da MMP-2 e da MMP-9 podem afetar os níveis circulantes das MMPs em pacientes com migrânea. Enquanto o haplótipo H6 (CLQ) da MMP-9 foi associado aos maiores níveis plasmáticos de MMP-9 nas pacientes com migrânea (359,8±69,53ng/ml versus 195,8±9,70ng/ml para o CLR; 201,5±18,67ng/ml para o CHR e 200,2±17,02ng/ml para o CHQ), as maiores concentrações de MMP-2 foram encontradas nas pacientes com migrânea com aura com o genótipo CC para o polimorfismo C-735T (1,29±0,07U.A. versus 0,96±0,06U.A. para os genótipos CT ou TT) e com o haplótipo H1 (CC) (1,24±0,05U.A. versus 0,94±0,05U.A. para o haplótipo CT) no gene da MMP-2. Apesar de não investigarmos os mecanismos moleculares que explicam esses resultados, podemos sugerir que o aumento dos níveis das MMPs associados a genótipos e haplótipos específicos podem predispor essas pacientes a um aumento da permeabilidade vascular da barreira hematoencefálica, promovendo assim o desenvolvimento de um ambiente neuroinflamatório no sistema nervoso central, contribuindo para uma crise de migrânea
Abstract: Migraine is a common primary headache and highly disabling, affecting approximately 10% of the population worldwide, especially women. Despite the efforts, the pathophysiology of migraine is not completely understood. However, it is believed that the matrix metalloproteinases (MMPs) are involved in the disruption of blood-brain barrier (BBB) during migraine attacks. The aim of this study was to evaluate whether functional polymorphisms in MMP-2 (C-1306T and C-735T) and MMP-9 (C-1562T, -90(CA)n and R(279)Q) genes and haplotypes are associated with migraine and whether they modify circulating MMPs levels in migraine. To evaluate the effect of MMP-9 polymorphisms, we studied 102 healthy women (controls) and 187 women with migraine (141 migraine without aura; MWA, and 46 migraine with aura; MA). Genotypes for C-1562T, -90(CA)n e R(279)Q MMP-9 polymorphisms were determined by PCR-RFLP, by conventional PCR followed by electrophoresis in polyacrylamide gels and by real time-PCR using Taqman® allele discrimination assays, respectively. The plasma MMP-9 and TIMP-1 concentrations were measured by ELISA. Genotypes for MMP-2 polymorphisms were determined by real time-PCR using Taqman® allele discrimination assays in 148 healthy women without history of migraine and in 204 women with migraine (153 MWA and 51 MA). The plasma concentrations of MMP-2 and TIMP-2 were evaluated by gelatin zymography and ELISA, respectively. Haplotypes were inferred using the PHASE program. This is the first study to show that functional MMP-2 and MMP-9 polymorphisms and haplotypes can affect the circulating MMPs levels in patients with migraine. While the MMP-9 H6 (CLQ) haplotyple is associated with high MMP-9 concentrations in patients with migraine (359,8±69,53ng/ml versus 195,8±9,70ng/ml for CLR; 201,5±18,67ng/ml for CHR and 200,2±17,02ng/ml for CHQ) , the highest concentrations of MMP-2 were found in patients with migraine with aura carrying the CC genotype for C-735T polymorphism (1,29±0,07A.U. versus 0,96±0,06A.U. for CT or TT genotypes) and the H1 (CC) haplotype (1,24±0,05A.U. versus 0,94±0,05A.U. for CT haplotype) in the MMP-2 gene. Although we have not investigated the molecular mechanisms explaining these results, we can suggest that an increase of the MMPs levels associated with these genotypes and haplotypes may predispose these patients to increased vascular BBB permeability, thus promoting the development of an inflammatory environment in their central nervous systems, which contributes to migraine attacks
Doutorado
Farmacologia
Doutora em Farmacologia
Smart, David Edward. "The transcriptional regulation of the tissue inhibitor of metalloproteinases-1 (TIMP-1) gene in hepatic stellate cells." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393919.
Full textFowell, Andrew. "The investigation of strategies to inhibit liver fibrosis by targeting tissue inhibitor of metalloproteinases with RNA interference." Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/362765/.
Full textFurtado, Francisco NÃlson NÃbrega. "ImunoexpressÃo de metaloproteinases 2 e 14 e do inibidor TIMP-2 no cÃncer colorretal." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8357.
Full textO cÃncer colorretal(CCR) à altamente prevalente nos paÃses mais ricos e industrializados. As metaloproteinases de matriz (MMPs) sÃo importantes enzimas que facilitam a invasÃo e disseminaÃÃo do tumor em vÃrios tipos de cÃncer, inclusive o colorretal. Os inibidores teciduais de metaloproteinases (TIMPs) sÃo os principais inativadores fisiolÃgicos destas enzimas. Este estudo avaliou a expressÃo de metaloproteinase-2 (MMP-2), metaloproteinase-14 (MMP-14) e inibidor tecidual de metaloproteinases-2 (TIMP-2) no cÃncer colorretal. O imunomarcador CD68 foi utilizado para caracterizar a natureza das cÃlulas mononucleadas do estroma. Amostras teciduais de 50 casos de colectomias, devido ao cÃncer colorretal no perÃodo de 2004 a 2010, obtidas dos arquivos do Departamento de Patologia e Medicina Legal (DPML), Faculdade de Medicina da Universidade Federal do Cearà (UFC), foram analisadas. Realizou-se tissue microarrays e a seguir imuno-histoquÃmica para avaliar a expressÃo de MMP-2, MMP-14 e TIMP-2 de acordo com os seguintes escores baseados em outros relatos: 0= sem imunomarcaÃÃo ou raras cÃlulas marcadas (<5%); 1 = discreta marcaÃÃo na maioria (> 50%) das cÃlulas tumorais ou cÃlulas mononucleares do estroma, ou moderada marcaÃÃo em uma minoria de cÃlulas (<50 %); 2 =marcaÃÃo moderada na maioria (> 50%) de cÃlulas tumorais ou cÃlulas mononucleares ou intensa marcaÃÃo em minoria de cÃlulas (<50%); 3 = marcaÃÃo intensa na maioria (> 50%) de cÃlulas tumorais ou cÃlulas mononucleares. Observou-se relaÃÃo entre a expressÃo aumentada de MMP-14 em mononucleares de tumor primÃrio e casos sem metÃstases linfonodais (MMP-14, escores 2 e 3/N0 : 23/24 = 95%; N1-N3: 14/20 = 70%, p = 0,0353). No entanto, nenhuma relaÃÃo significativa foi encontrada entre a expressÃo de MMP-14, MMP-2 e TIMP-2 nos tumores primÃrios em cÃlulas cancerosas ou mononucleares e outros parÃmetros clÃnico-patolÃgicos. A imunoexpressÃo de MMP-2 foi negativa nas cÃlulas neoplÃsicas, em tumores primÃrios (47/47=100%) e metastÃticos (12/12 = 100%). A imunorreatividade de MMP-14 em cÃlulas neoplÃsicas foi frequentemente positiva em tumores primÃrios (50/50 = 100%) e metastÃticos (7/8= 88%). Em mononucleares, a maioria dos quais macrÃfagos (corados pelo CD68), a expressÃo positiva de MMP-14 tambÃm predominou marcadamente, tanto em tumores primÃrios (46/47 = 98%) como em carcinomas metastÃticos (9/10 = 90%). A expressÃo de TIMP-2 em cÃlulas neoplÃsicas, discreta, ocorreu em 70% de tumores primÃrios (35/50 casos) e 100% dos metastÃticos (8/8). A imunocoloraÃÃo para TIMP-2 em macrÃfagos associados ao tumor (TAMs) foi ainda mais elevada do que nas cÃlulas neoplÃsicas. Em conclusÃo, a MMP-14 e TIMP-2 sÃo frequentemente expressas em carcinomas colo-retais em ambas localizaÃÃes anatÃmicas, principalmente nas metÃstases para linfonodos , sugerindo que estas proteases desempenham papel importante na invasÃo local e na progressÃo tumoral neste tipo de cÃncer. A predominÃncia destes marcadores nas cÃlulas mononucleares (sobretudo macrÃfagos) , claramente evidentes na positividade para a MMP-2, enfatiza a importÃncia do microambiente tumoral no desenvolvimento de neoplasias.
The colorectal cancer (RCC) is highly prevalent in richer and industrialized countries. The matrix metalloproteinases (MMPs) are regarded as important for facilitating tumor invasion and spread in various cancers, including colorectal. Tissue inhibitors of metalloproteinases (TIMPs) are the major physiological inhibitors of MMPs. The expression of metalloproteinase-2 (MMP-2), metalloproteinase 14 (MMP-14) and tissue inhibitor of metalloproteinases-2 ( TIMP-2) in colorectal cancer was assessed. CD68 immunostaininig was utilized to the characterization of mononuclear cells nature. Paraffin-embedded tissues from patients undergoing colectomy for colorectal cancer in the period 2004 to 2010, were selected from the files of the Department of Pathology and Forensic Medicine (DPML), Medical School , Federal University of Cearà (UFC). Tissue microarrays were performed and slides were obtained for immunohistochemical detection of the expression of MMP-2, MMP-14 and TIMP-2 and the tissue samples analyzed. The following scores were applied: 0 = no immunostaining or rare labeled cells (<5%), 1 = slight marking the majority (> 50%) of tumor cells or stromal mononuclear cells, or moderate marking in a minority of cells (<50%) 2 = moderate labeling in the majority (> 50%) of tumor or mononuclear cells or intense marking in the minority of cells (<50%) and 3 = intense labeling in the majority (> 50%) of tumor cells or mononuclear cells. In this study, the relationship between increased expression of MMP-14 in mononuclear primary tumor cells and cases without lymph node metastases (MMP-14, 2 and 3/N0 scores: 23/26 = 88%; N1-N3: 14/21 = 67%, p = 0.0353) was stablished . However, no significant relationship was found between the immunohistochemical expression of MMP-14, MMP-2 and TIMP-2 in primary tumors in cancer cells and mononuclear cells and other clinico-pathological parameters. The expression of MMP-2 were negative in the neoplastic cells both in primary tumors (47/47 = 100%) and in metastatic ones (12/12 = 100%). The immunoreactivity of MMP-14 in neoplastic cells in primary tumors was positive (50/50 = 100%) and in all cases except one of metastatic carcinoma (7/8 = 88%). In mononuclear cells, most of them characterized as macrophages (CD68 stained), MMP-14 positive expression also predominated markedly, both in primary tumors (46/47 = 98%) and in metastatic carcinomas (9/10 = 90%). TIMP-2 expression in neoplastic cells of primary tumors occurred in 35/50 cases (70%) and lymph nodes showed positive immunostaining in all cases (8/8 = 100%). In both sites there were no cases with high expression. The TIMP-2 immunoreactivity in tumour associated macrophages (TAMs) was even higher than in the neoplastic cells. In conclusion, MMP-14 and TIMP-2 are frequently expressed in colorectal carcinomas in both anatomical sites , mainly in lymph node metastasis, suggesting that these proteases play an important role in local invasion and tumor progression of these cancers. The predominance of these biomarkers in mononuclear cells, clearly evident in the positivity for MMP-2, emphasizes the importance of tumor microenvironment in the development of neoplasms.
Pasternak, Björn. "Towards surgical use of matrix metalloproteinase biology." Doctoral thesis, Linköpings universitet, Ortopedi och idrottsmedicin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11489.
Full textHonkavuori-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.
Full textTiivistelmä 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