Ekspresija čimbenika stanične smrti u neuroblastomu

doctoral thesis

• Title (english): Cell-death factors expression in neuroblastoma
• Author: Marko Bogović
• Mentor: Tomislav Luetić (mentor); MBZ: 175021
• Mentor: Ines Mrakovčić-Šutić (sumentor); MBZ: 146280
• Committee member: Andreja Ambriović Ristov (član povjerenstva); MBZ: 173311
• Committee member: Sonja Levanat (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Cilj istraživanja bio je utvrditi povezanost između ekspresije čimbenika stanične smrti – Fas, FasL, perforina i HSP70 i bioloških karakteristika neuroblastoma. Uključena su sva djeca s dijagnozom neuroblastoma operirana na KBC Zagreb u razdoblju od 1994. do 2013. godine, a kriterije je zadovoljilo 42 ispitanika. Na parafinskim blokovima izuzetim prije početka kemoterapije imunohistokemijskim bojanjem određen je izražaj Fas i FasL molekule na stanicama neuroblastoma, broj citotoksičnih T limfocita u okolini stanica neuroblastoma, izražaj perforina na citotoksičnim T limfocitima te izražaj HSP70 na stanicama neuroblastoma. Utvrđeno je da je Fas smanjeno izražen na metastatskim stadijima tumora pa se može pretpostaviti da tumor smanjenjem ekspresije Fas-a na svojoj površini može izbjeći lokalni odgovor imunološkog sustava i tako metastazirati. Također je utvrđena povezanost ekspresije HSP70 i stadija neuroblastoma. Viši stadiji imaju smanjenu ekspresiju što je u suprotnosti s većinom tumora koji su do sada istraživani, no s druge strane se slaže s istraživanjima na nefroblastomu, drugom najčešćem solidnom tumoru dječje dobi. Najvjerojatnije objašnjenje, prema dosadašnjim istraživanjima, je da kod tumora dječje dobi sudjelovanje HSP70 u inhibiciji apoptoze nije toliko značajno kao sudjelovanje u diferencijaciji tumora te da njegova pojačana ekspresija u neuroblastoma dovodi do sazrijevanja tumora.

Abstract (english)

The aim of this study was to investigate the correlation between the expression of cell death factors - Fas, FasL, perforin and HSP70 and biological characteristics of neuroblastoma. All children diagnosed with neuroblastoma operated at KBC Zagreb in the period since 1994. to 2013. were included and 42 of them met our criteria. On paraffin blocks excluded before the start of chemotherapy through immunohistochemical staining the expression of Fas and FasL molecules on neuroblastoma cells, the number and expression of perforin on cytotoxic T lymphocytes in the vicinity of neuroblastoma cells and expression of HSP70 in neuroblastoma cells was analyzed. Reduced Fas expression was found in metastatic tumor stages so it can be assumed that by lowering expression of Fas on its surface, tumor can avoid the local immune response and thus metastasize. The connection of HSP70 expression and stage neuroblastoma is also found. Higher stages have decreased expression of which is in contrast with the majority of tumors that have been studied, but on the other hand agrees with research on nephroblastoma, the second most common solid tumor in children. The most likely explanation for that, according to available data and considering pediatric tumors, is that the role of HSP70 in inhibition of apoptosis is not as important as participation in the differentiation of the tumor and its overexpression in neuroblastoma leads to the maturation of the tumor.

• Keywords: neuroblastom; Fas; FasL; perforin; HSP70; citotoksični T limfociti
• Keywords (english): neuroblastoma; Fas; FasL; perforin; HSP70; cytotoxic T cells
• Language: croatian
• URN:NBN: urn:nbn:hr:217:181100
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-23 12:52:07