6. Arthritis research: inflammationJosé António Pereira da Silva (HUC, FMUC), Fern<strong>and</strong>o Judas (HUC), Alex<strong>and</strong>rina Mendes (FFUC, <strong>CNC</strong>) CarlosCavaleiro (CEF/FFUC), Ali Mobasheri (U. Nottingham,U.K.), Margarida Carneiro (<strong>CNC</strong>), Celeste Lopes (FFUC, <strong>CNC</strong>)In collaboration with the Orthopedic <strong>and</strong> Bone Bank Departments <strong>of</strong> HUC, we are developing threeprojects, using normal <strong>and</strong> osteoarthritic (OA) human articular cartilage <strong>and</strong> chondrocytes, that aim at 1)improving the survival rate <strong>of</strong> implanted osteochondral allografts, thus direct <strong>and</strong> positively affecting theclinical outcome; 2) identifying cellular <strong>and</strong> molecular mechanisms relevant in OA pathogenesis that canbe translated into new therapeutic strategies; <strong>and</strong> 3) identifying compounds with potential antiosteoarthriticactivity. The first project identified arbutin as a new cryoprotective agent more effective thantraditional agents. In the second project, developed in collaboration with the School <strong>of</strong> Veterinary Science<strong>and</strong> Medicine, University <strong>of</strong> Nottingham, we found that OA chondrocytes under hyperglycemia areunable to adjust glucose transport rate <strong>and</strong> undergo oxidative stress. We are currently investigating themechanisms that regulate glucose transport in normal chondrocytes under hyperglycemia <strong>and</strong> whetherthe defective mechanism in OA chondrocytes is a pre‐existing condition related or not to chondrocyteaging. The third project, developed in collaboration with CEF/FFUC, identified ‐pinene as a NF‐B <strong>and</strong>NO production inhibitor. Current work is underway to identify active compounds present in otherfractions <strong>of</strong> the same essential oil.CD8+ T cells represent 40% <strong>of</strong> the total T cells infiltrating the rheumatoid synovial membrane, <strong>and</strong> around50% <strong>of</strong> the T cells found in the synovial fluid <strong>of</strong> rheumatoid arthritis (RA) patients. However, their role inRA is still ill defined. Our recent data in a mouse model <strong>of</strong> chronic polyarthritis, show that CD8+ T cellsmight have a dual role in the disease, with both cytotoxic <strong>and</strong> regulatory functions. Our present projectaims at underst<strong>and</strong>ing how CD8+ T cells participate in the recruitment <strong>and</strong>/or regulation <strong>of</strong> other immunecells <strong>and</strong> in the maintenance <strong>of</strong> the chronic inflammation in RA.Publications90Rosa SC, Judas F, Lopes MC, Mendes AF (<strong>2008</strong>) Nitric oxide synthase is<strong>of</strong>orms <strong>and</strong> NF‐B activity in normal<strong>and</strong> osteoarthritic human chondrocytes: Regulation by inducible nitric oxide. Nitric Oxide 19: 276‐283.Mobasheri A, Bondy CA, Moley K, Mendes AF, Rosa SC, Richardson S, Hoyl<strong>and</strong> JA, Barrett‐Jolley R,Shakibaei M (<strong>2008</strong>) Articular Chondrocytes: Expression, Distribution <strong>and</strong> Functional Regulation <strong>of</strong>GLUT Is<strong>of</strong>orms by Hypoxia, Hypoxia Mimetics, Growth Factors <strong>and</strong> Pro‐Inflammatory Cytokines. Adv.Anat. Embryol. Cell Biol. 200:1‐84.Lopes MC, Rosa SC, Gonçalves J, Judas F, Mendes AF. (<strong>2008</strong>) Cryoprotection <strong>of</strong> human articularchondrocytes by the glycosylated hidroquinone, arbutin. Rev. Farmacol. Chile 1: 199.Rosa SC, Gonçalves J, Judas F, Lopes MC, Mendes AF (<strong>2008</strong>) Evaluation <strong>of</strong> the cryoprotective efficacy <strong>of</strong>combinations <strong>of</strong> dimethylsulfoxide, glycerol <strong>and</strong> arbutin in human tibial plateaus. Osteoarthritis Cartilage16: 489.Rosa SC, Judas F, Mobasheri A, Lopes MC, Mendes AF (<strong>2008</strong>) Dysregulation <strong>of</strong> glucose transport <strong>and</strong>GLUT‐1 protein in osteoarthritic chondrocytes in response to high extracellular glucose. OsteoarthritisCartilage 16:202.Gonçalves J, Rosa SC, Judas F, Salgueiro L, Cavaleiro C, Lopes MC, Mendes AF (<strong>2008</strong>) Dual inhibition <strong>of</strong>IL‐1‐induced NF‐B activation <strong>and</strong> iNOS enzyme activity, in human chondrocytes, by natural <strong>and</strong>commercial ‐pinene. Osteoarthritis Cartilage 16: 546.
7. Research in brain cancer: genetic heterogeneity <strong>of</strong> gliomasAlberto Orfão (CSIC, Univ. Salamanca), Fern<strong>and</strong>o Gomes (HUC), Olinda Rebelo (HUC), Celeste Lopes (FFUC,<strong>CNC</strong>)The project entitled “Whole human genome analysis <strong>of</strong> genetic imbalance <strong>and</strong> numerical abnormalities bysingle‐nucleotide polymorphism (SNP)‐arrays in gliomas: correlation with clinical <strong>and</strong> biological features<strong>of</strong> the disease” is being developed in collaboration with the Neuropathology Laboratory <strong>and</strong>Neurosurgery Service <strong>of</strong> the University Hospital <strong>of</strong> Coimbra <strong>and</strong> with the <strong>Center</strong> <strong>for</strong> Cancer Research <strong>of</strong>Salamanca. In this project, allelic imbalances in chromosome regions <strong>of</strong> human gliomas are evaluatedusing interphase fluorescence in situ‐ hybridization (iFISH). The gene expression pr<strong>of</strong>iling is per<strong>for</strong>med bycDNA micro‐arrays, <strong>and</strong> a full screening <strong>of</strong> the tumoral cell genome is being done by single‐nucleotidepolymorphism (SNP)‐array analysis. The tissue samples are obtained from patients diagnosed withgliomas undergoing surgery at the University Hospital <strong>of</strong> Coimbra. Our data, <strong>of</strong> iFISH evaluation,revealed a complex cytogenetic heterogeneity in these type <strong>of</strong> tumours <strong>and</strong> distinct gene expressionpr<strong>of</strong>iles were found between tumours <strong>of</strong> different histological grades. Now, genome‐wide allelotyping, <strong>for</strong>detection <strong>of</strong> new genetic lesions, are being per<strong>for</strong>med in gliomas <strong>and</strong> this analysis will facilitate theidentification <strong>of</strong> new genetic/chromosomal changes, relevant <strong>for</strong> the underst<strong>and</strong>ing <strong>of</strong> the pathogenesis <strong>of</strong>the disease.PublicationsTabernero MD, Maillo A, Gil‐Bellosta CJ, Castrillo A, Sousa P, Merino M, Orfao A (<strong>2008</strong>) Gene ExpressionPr<strong>of</strong>iles <strong>of</strong> Meningiomas are Associated with Tumor Cytogenetics <strong>and</strong> Patient Outcome. Brain Pathol.112:4609‐16.Carmo A, Patricio M, Amaro P, Cruz MT, Lopes MC (<strong>2008</strong>) CXCR4 expression mediates the survival <strong>and</strong>proliferation <strong>of</strong> glioma cells. Europ. J. Cancer 6: 20.91
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General ObjectivesThe CNC major mis
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per year) will be proposed by the g
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