Ispitivanje fenotipa stanica humanog melanoma nakon tretmana vemurafenibom

master's thesis

• Title (english): Characterization of human melanoma cell phenotype after vemurafenib treatment
• Author: Ivana Bobić
• Mentor: Maja Herak Bosnar (mentor)
• Committee member: Morana Dulić (predsjednik povjerenstva)
• Committee member: Sanda Rončević (član povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2019-02-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Maligni melanom je najagresivniji i najzloćudniji oblik raka kože. U većini melanoma utvrđeno je prisustvo mutacije gena BRAF pa liječenje uključuje i terapiju kemoterapeuticima, vrlo često vemurafenibom, inhibitorom enzima BRAF. Međutim, stanice melanoma obično razvijaju otpornost i dugotrajnim tretmanom vemurafenibom in vitro stanice s tipično epitelnom morfologijom poprimaju izduženi, vretenasti oblik. Takva promjena fenotipa upućuje na indukciju procesa epitelno-mezenhimalne tranzicije kojim stanice poprimaju još zloćudnija svojstva. Cilj ovog rada bio je okarakterizirati stanične linije humanog melanoma A375M i WM793B nakon višemjesečnog tretmana vemurafenibom utvrđivanjem vijabilnosti stanica, ekspresije i lokalizacije ključnih biljega epitelno-mezenhimalne tranzicije te ekspresije supresorā metastaziranja, NME1 i NME2. U tu svrhu korišteni su test MTT te metode Western blot i fluorescentna imunocitokemija.

Abstract (english)

Human melanoma is the most aggressive and most malignant of all skin cancers. Most cases of melanoma harbour BRAF gene mutation; therefore, treatment includes chemotherapeutics, commonly vemurafenib, a BRAF enzyme inhibitor. However, melanoma cells usually develop resistance and, after long-term vemurafenib treatment, cultured cells with an epithelial-like morphology acquire a more elongated, spindle-like shape. This change indicates the induction of a process called epithelial-mesenchymal transition which prompts even more malignant behaviour. The aim of this study was to characterize human melanoma cell lines A375M and WM793B after several months of vemurafenib treatment, by determining cell viability, expression and localization of key epithelial-mesenchymal transition markers and expression of metastasis suppressors, NME1 and NME2. For that purpose, MTT assay, Western blot and fluorescent immunocytochemistry methods were used.

• Keywords: BRAF; epitelno-mezenhimalna tranzicija; melanom; otpornost; vemurafenib
• Keywords (english): BRAF; epithelial-mesenchymal transition; melanoma; resistance; vemurafenib
• Language: croatian
• URN:NBN: urn:nbn:hr:217:639282
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-02-15
• Created on: 2019-02-18 13:21:25