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dc.contributor.advisorMärtson, Aare, juhendaja
dc.contributor.advisorMaasalu, Katre, juhendaja
dc.contributor.advisorKoks, Sulev, juhendaja
dc.contributor.authorHo, Xuan Dung
dc.contributor.otherTartu Ülikool. Meditsiiniteaduste valdkondet
dc.date.accessioned2018-10-26T12:40:33Z
dc.date.available2018-10-26T12:40:33Z
dc.date.issued2018-10-26
dc.identifier.isbn978-9949-77-865-2
dc.identifier.isbn978-9949-77-866-9 (pdf)
dc.identifier.issn1024-395X
dc.identifier.urihttp://hdl.handle.net/10062/62523
dc.descriptionVäitekirja elektrooniline versioon ei sisalda publikatsiooneet
dc.description.abstractOsteosarkoom (OS) on kõige sagedamini esinev esmase luu pahaloomulise kasvaja vorm. Igal aastal diagnoositakse ligikaudu 3 esmast OS juhtumit miljoni elaniku kohta. Haigus esineb sagedamini noorematel ja meessoost isikutel. Esmased haigussümptomid on mittespetsiifilised, mistõttu võib haigus esmasel pöördumisel tähelepanuta jääda. Sagedamini esineb OS suurtes toruluudes nagu reieluu, sääreluu ja õlavarreluu ning levib sagedamini kopsukoesse. Ehkki keemiaravi kombineerituna operatiivse sekkumisega aitab oluliselt elulemust parandada ei pruugi need aidata tervistuda. Seetõttu on OS-i prognoos halb ning pole muutunud 1980 aastatest. OS-i põhjus ja tekkemehhanism ei ole teada ning seetõttu pole leitud ks uusi raviviise. Viimasel ajal on hoogustunud ODi genoomika uuringud parandamaks selle haiguse tekkemehhanismidest arusaamist. Selle tulemusena on kirjeldatud mitmeid muutusi genoomi struktuuris. Geenide ekspressiooni diferentsiaalanalüüsid on kirjeldanud mitmesuguseid leide, kuid uuringudisainide erinevused ei ole senini võimaldanud saavutada terviklikke tulemusi. Oma töös rakendasime paarisdisaini, kus võrldesime samade isikute kasvajalise ja terve luukoe transkriptoomi. Proovide arvu suurendamiseks kasutasime ka parafiinsisestatud arhiivimaterjali, mis võimaldas hinnata keemiaraviist tingtud transkriptoomi muutusi. Normaalse ja kasvajalise koe vahel leidsime ekspressiooni erinevusi 5000 geeni puhul. Suur osa geene oli seotud luukoe reorganiseerimisega, dediferentseerumise ja invasioonida. Lisaks uurisime ka transposoonide ja korduselementide ekspressiooni muutusi. Tuvastasime SAR ja HSATII elementide ja (CATTC)n lihtjärjestuse üleekspressiooni osteosarkoomi koes. Tegemist on osteosarkoomile spetsifiliste makeritega, mis võivad aidata mõista osetosarkoomi patogeneesi.et
dc.description.abstractOsteosarcoma (OS) is the most frequent type of primary bone cancer. About 3 cases per million population are diagnosed each year. It especially affects the young around puberty with slightly higher prevalence in male than in the female. The complaints of affected patients are very unspecific. Hence, the disease is easily neglected by the primary care doctors. Femur, tibia, and humerus are the most common sites of OS. It is a highly metastasized disease and lung is the most preferable metastatic site. The introduction of chemotherapy in the late 70s and early 80s has clearly improved the survival rate of OS and makes it possible for conservative operation. However, the prognosis of OS is still poor and unchanged since the 1980s. The cause and mechanism of OS are still poorly understood. The number of studies on OS is growing dramatically with aims to understand its mechanism and to seek new therapeutic targets. Recently, genomic alterations in OS were studied with modern techniques. The differential expression of genes in OS has been reported with diverse findings, which may be due to the diversity of OS or design-associated limitations such as a small number of study subjects, variations in control groups, different laboratory protocols, and analysis techniques. We tried to overcome the present common limitations by analyzing paired samples of tumoral vs non-tumoral fresh bone specimens from the same patient and the paraffin blocks with RNA sequencing technique. Over 5000 genes were found to be differentially expressed between the normal and OS tissues. The most significantly differentially expressed genes were recognized to be further studied. The degradation of collagen seems to be an important mechanism of OS and should be further evaluated to serve as a biomarker for OS. The repetitive elements SAR, HSATII, and simple repeat (CATTC)n which were overexpressed in carcinoma in previous studies were also upregulated in OS and should be evaluated for biomarkers of this disease.en
dc.language.isoenget
dc.relation.ispartofseriesDissertationes medicinae Universitatis Tartuensis;276
dc.rightsopenAccesset
dc.rightsAutorile viitamine + Mitteäriline eesmärk + Tuletatud teoste keeld 3.0 Eesti*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/ee/*
dc.subjectsarcomaen
dc.subjecttransforming growth factoren
dc.subjectgene expressionen
dc.subjectnucleotide sequenceen
dc.subject.otherdissertatsioonidet
dc.subject.otherETDet
dc.subject.otherdissertationset
dc.subject.otherväitekirjadet
dc.subject.othersarkoomet
dc.subject.otherkasvufaktor TGFet
dc.subject.othergeeniekspressioonet
dc.subject.othernukleotiidjärjestuset
dc.titleCharacterization of the genomic profile of osteosarcomaen
dc.title.alternativeOsteosarkoomi geneetilise profiili iseloomustuset
dc.title.alternativeTổng quan ung thư tạo xươnget
dc.typeThesiset


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