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read it Gliomas are the most common primary brain tumors, accounting for more than80% of all neoplasms arising in the Central Nervous System (CNS) and are currentlyclassified by the World Health Organization (WHO) into astrocytomas,oligodendrogliomas, mixed gliomas and ependymomas. The diagnosis andclassification are based on their histopathological appearance, which sometimes may bedifficult. Despite advances in neurosurgery, chemotherapy and radiotherapy, theprognosis of most glioma patients remains dismal.In recent years, extensive molecular studies have identified diagnostic, prognosticand predictive markers in gliomas that reinforce the WHO histological classification.The 1p19q coleletion in oligodendroglial tumors, the presence of somatic mutations inthe genes enconding isocitrate dehydrogensase 1 and 2 (IDH1 and IDH2) inastrocytomas, oligodendrogliomas e oligoastrocytomas and the hypermethylation of thepromoter of O6-methylguanine DNA methyltransferase (MGMT) gene in glioblastomasare currently the three most pertinent markers in diffuse gliomas.Previous studies suggest that codeletion of chromosome arms 1p and 19q hasproven to be a powerful diagnostic and prognostic marker. Combined loss of 1p and 19qhas been associated with morphology of oligodendrogliomas and with enhancedsurvival in these tumors. However, in other glial tumors, an oligodendroglial componentcan mean a better prognostic. Therefore, one of the aims of this Project is the 1p/19qevaluation concerning the patients’ diagnostic and prognostic.Recent published studies considered that mutations in IDH1 and IDH2, are animportant diagnostic and prognostic marker but that is still unclear. Also, patients withtumors harboring mutation of IDH1 or IDH2 genes seem to have a better outcome thanpatients with non mutated tumors. Thus, another goal of this study focus on theidentification and characterization of mutations, difference in survival at a populationlevel and to assess whether they allow reliable discrimination between primary (denovo) glioblastomas and secondary glioblastomas (that progressed from low-grade oranaplastic gliomas). DNA repair protein, MGMT, is one implicated factor in glioma chemoresistance.The prognostic and predictive value of MGMT promoter hypermethylation howeverremains controversial. An additional aim of this study regards the evaluation of theprognostic significance of MGMT in patients with glioblastomas. viiIn total, we analysed 141 patient samples for a series of patients followed in theUniversity Hospital of Coimbra with astrocitomas (n = 111), oligodendrogliomas (n =18), mixed gliomas (n = 8) and ependymomas (n = 4). In our study, the 1p/19q statuswas assessed by interphase Fluorescence In Situ Hybridization (iFISH) (n = 130),somatic mutations analysis of IDH1 and IDH2 genes was directed sequenced (n = 128)and MGMT hypermethylation analysis was performed by using Methylation-SpecificMultiplex Ligation-dependent Probe Amplification (MS-MLPA) on the glioma samples(n = 38).Our data suggested that deletions of chromosome arms 1p and 19q are associatedwith oligodendrogliomas morphology (pHowever, this alteration is not associated with chemosensitivity and enhanced survival.IDH1 mutations were detected in 17 of 128 gliomas, in which 3 differentmutations were identified. This study indicated that IDH1 mutations are frequent insecondary glioblastomas but rare in primary glioblastomas (100% vs 1,1%, pTherefore, IDH1 mutations also seem to be a more favorable prognostic factor. None ofthe 128 gliomas analyzed contained an IDH2 mutation.The MGMT gene promoter was methylated in 67% and unmethylated in 33% ofglioblastoma patients. This marker can be a predictor factor of response tochemotherapy because the patients who had the promoter hypermethylation andunderwent chemotherapy had increased their
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Install Instructions:1. Disconnect from Internet2. Run Installer, select "Try" instead of "Install"3. While still disconnected from the internet run Flash CS6 once4. Close the application5. Go to "/Applications/Adobe Flash CS6/" folder, command-click on the applicationand select "Show Package Contents"6. Go to "/Contents/Frameworks/" and rename "amtlib.framework" to "amtlib.framework_old"7. Copy and paste the "amtlib.framework" included with this into the "/Contents/Frameworks" folder.8. Go to "/Applications/Adobe Media Encoder CS6/" folder, command-click on the applicationand select "Show Package Contents"9. Go to "/Contents/Frameworks/" and rename "amtlib.framework" to "amtlib.framework_old"10. Copy and paste the "amtlib.framework" included with this into the "/Contents/Frameworks" folder.11. Open up Terminal12. Type: "sudo nano /private/etc/hosts"13. Add the following to the text file, afterwards pressing control-o and thencontrol-x to save and exit:# Block Adobe Activation127.0.0.1 activate.adobe.com127.0.0.1 practivate.adobe.com127.0.0.1 ereg.adobe.com127.0.0.1 activate.wip3.adobe.com127.0.0.1 wip3.adobe.com127.0.0.1 3dns-3.adobe.com127.0.0.1 3dns-2.adobe.com127.0.0.1 adobe-dns.adobe.com127.0.0.1 adobe-dns-2.adobe.com127.0.0.1 adobe-dns-3.adobe.com127.0.0.1 ereg.wip3.adobe.com127.0.0.1 activate-sea.adobe.com127.0.0.1 wwis-dubc1-vip60.adobe.com127.0.0.1 activate-sjc0.adobe.com127.0.0.1 hl2rcv.adobe.com# 74.208.10.249 gs.apple.com# 127.0.0.1 gs.apple.com#74.208.10.249 gs.apple.com127.0.0.1 192.150.14.69127.0.0.1 192.150.18.101127.0.0.1 192.150.18.108127.0.0.1 192.150.22.40127.0.0.1 192.150.8.100127.0.0.1 192.150.8.118127.0.0.1 209-34-83-73.ood.opsource.net127.0.0.1 3dns-1.adobe.com127.0.0.1 3dns-2.adobe.com127.0.0.1 3dns-2.adobe.com127.0.0.1 3dns-3.adobe.com127.0.0.1 3dns-3.adobe.com127.0.0.1 3dns-4.adobe.com127.0.0.1 3dns.adobe.com127.0.0.1 activate-sea.adobe.com127.0.0.1 activate-sea.adobe.com127.0.0.1 activate-sjc0.adobe.com127.0.0.1 activate-sjc0.adobe.com127.0.0.1 activate.adobe.com127.0.0.1 activate.adobe.com127.0.0.1 activate.wip.adobe.com127.0.0.1 activate.wip1.adobe.com127.0.0.1 activate.wip2.adobe.com127.0.0.1 activate.wip3.adobe.com127.0.0.1 activate.wip3.adobe.com127.0.0.1 activate.wip4.adobe.com127.0.0.1 adobe-dns-1.adobe.com127.0.0.1 adobe-dns-2.adobe.com127.0.0.1 adobe-dns-2.adobe.com127.0.0.1 adobe-dns-3.adobe.com127.0.0.1 adobe-dns-3.adobe.com127.0.0.1 adobe-dns-4.adobe.com127.0.0.1 adobe-dns.adobe.com127.0.0.1 adobe-dns.adobe.com127.0.0.1 adobe.activate.com127.0.0.1 adobeereg.com127.0.0.1 crl.verisign.net127.0.0.1 CRL.VERISIGN.NET.*127.0.0.1 ereg.adobe.com127.0.0.1 ereg.adobe.com127.0.0.1 ereg.wip.adobe.com127.0.0.1 ereg.wip1.adobe.com127.0.0.1 ereg.wip2.adobe.com127.0.0.1 ereg.wip3.adobe.com127.0.0.1 ereg.wip3.adobe.com127.0.0.1 ereg.wip4.adobe.com127.0.0.1 hl2rcv.adobe.com127.0.0.1 ood.opsource.net127.0.0.1 practivate.adobe127.0.0.1 practivate.adobe.*127.0.0.1 practivate.adobe.com127.0.0.1 practivate.adobe.com127.0.0.1 practivate.adobe.ipp127.0.0.1 practivate.adobe.newoa127.0.0.1 practivate.adobe.ntp127.0.0.1 tss-geotrust-crl.thawte.com127.0.0.1 wip.adobe.com127.0.0.1 wip1.adobe.com127.0.0.1 wip2.adobe.com127.0.0.1 wip3.adobe.com127.0.0.1 wip3.adobe.com127.0.0.1 wip4.adobe.com127.0.0.1 wwis-dubc1-vip60.adobe.com127.0.0.1 wwis-dubc1-vip60.adobe.com127.0.0.1 wwis-dubc1-vip60.adobe.com
