Ekspresija proteina sFRP3 i DVL3, ključnih molekula signalnog puta Wnt u glioblastomu

master's thesis

• Title (english): Expression of proteins sFRP3 and DVL3, key molecules of Wnt signaling pathway in glioblastoma
• Author: Tea Gabud
• Mentor: Nives Pećina-Šlaus (mentor)
• Mentor: Gordana Lacković-Venturin (mentor)
• Committee member: Gordana Lacković-Venturin (predsjednik povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Oboljeli od glioblastoma uz trenutno dostupne terapije imaju medijan preživljenja kraći od godinu dana. Cilj diplomskog rada je identificirati status ključnih proteina signalnog puta Wnt (sFRP3 I DVL3) u stanicama ljudskog glioblastoma, provjeriti postoji li poveznica statusa s kliničkim karakteristikama bolesnika i ukazati na eventualne nove mete za razvoj ciljnih terapija. Na preparatima ljudskog glioblastoma proteini su detektirani metodom imunohistokemije. Tkiva su analizirana pod svjetlosnim mikroskopom (Olympus BH-2). Razina ekspresije proteina određena je semikvantitativnom metodom u 3 stupnja jačine signala uz oznaku tkivne i subcelularne lokalizacije. Oba proteina su eksprimirana u stanicama glioblastoma. Nema korelacije između njihove ekspresije, kao ni korelacije jačine signala s kliničkim parametrima. Dominacija jakog signala u stanicama dovedena je u vezu sa simultanom lokalizacijom proteina DVL3 u citoplazmi i nukleusu, te proteina sFRP3 simultano u citoplazmi i ekstracelularno uz izostanak signala u nukleusu. Prognoze oboljelih od glioblastoma su loše čak i uz kombiniranje dostupnih terapija, jer je glioblastom jedan od agresivnijih i malignijih tipova tumora, često neoperabilan zbog lokalizacije. Glioblastom je vrlo heterogenog porijekla i histopatološke slike, specifičan za oboljelog, bitno je razviti metode kojima će se detektirati individualna slika stanja. Tek će detaljnije poznavanje mreže signalnih puteva moći ukazati na optimalne pristupe terapijskim rješenjima.

Abstract (english)

Glioblastoma patients have a median survival of less than a year. Thesis aim is to identify key proteins' (sFRP3 and DVL3) status in Wnt signaling pathway in human glioblastoma samples, search for their connection with clinical data and point out possible new target therapy objects. Proteins are detected by immunohistochemistry. Tissues are analyzed under a light microscope (Olympus BH-2). The expression levels are determined by the semiquantitative method in the 3-stage signal strength with tissue and subcellular localization labels. Both proteins are expressed in glioblastoma. There is no correlation between their expression, as well as signal strength correlation with clinical parameters. Strong signal dominance was brought into connection with simultaneous localization of DVL3 in the cytoplasm and nucleus, and sFRP3 simultaneously in the cytoplasm and extracellularly along with the absence of signal in the nucleus. Prognosis for glioblastoma patients are bad even with the combination of all available therapies. It is one of the most aggressive and malignant tumor types, often inoperable due to localization. Glioblastoma is highly heterogeneous in origin and histopathological images so developing methods for detecting individual condition traits are essential. Only a more detailed knowledge of signaling pathways network could give the optimal therapeutic solutions.

• Keywords: imunohistokemija; karcinom; maligni gliom; β-katenin; signalizacija; DAB
• Keywords (english): immunohistochemistry; cancer; malignant glioma; β-catenin; signaling; DAB
• Language: croatian
• URN:NBN: urn:nbn:hr:217:907670
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-21 10:03:59