Uloga receptora TLR3 u razvoju i liječenju tumora glave i vrata čovjeka

doctoral thesis

• Title (english): The role of TLR3 receptor in the development and treatment of human head and neck cancer
• Author: Martina Mikulandra
• Mentor: Tanja Matijević Glavan (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2019-11-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Receptor Toll-like 3 (TLR3) je transmembranski protein čija je ekspresija prvotno otkrivena na stanicama imunološkog sustava. TLR3 je eksprimiran i u stanicama brojnih zdravih i tumorskih tkiva, između ostalog tumora glave i vrata gdje ima dvojaku ulogu. Aktivacija TLR3 može pokrenuti preživljenje i progresiju tumora, ali i apoptozu stanica tumora. U ovom smo radu željeli istražiti je li, i na koji način, moguće potaknuti smrt stanica tumora kombinirajući agonist TLR3, poly(I:C), sa standardnim liječenjem cisplatinom uz zračenje. Naši rezultati pokazali su da poly(I:C) u kombinaciji s cisplatinom inhibira rast stanica tumora, potiče apoptozu aktivacijom kaspaza -3 i -7 i smanjivanjem ekspresije gena inhibitora apoptoze, potiče stvaranje reaktivnih oblika kisika i inducira zaustavljanje staničnog ciklusa u fazi G2/M. Navedeni rezultati ukazuju na to da poly(I:C) sinergistički s cisplatinom smanjuje preživljenje stanica tumora te povećava osjetljivost stanica tumora na zračenje, što ga čini vrijednom terapijskom opcijom u liječenju tumora glave i vrata.

Abstract (english)

Toll-like receptor 3 (TLR3) is a transmembrane protein initially found to be expressed in cells of the immune system, but later also found in the cells of numerous normal and tumor tissues, including the head and neck tumors. TLR3 activation can initiate tumor cell survival and progression, but also tumor cell apoptosis. We have investigated whether it is possible to induce tumor cell death by combining TLR3 agonist poly(I:C) with standard treatment with cisplatin and irradiation. Our results showed that poly (I:C) in combination with cisplatin decreases tumor cell growth, promotes apoptosis via caspase -3 and -7 activation and via suppression of genes that inhibit apoptosis, induces ROS formation and cell cycle arrest in G2/M phase. These results suggest that poly(I:C) with cisplatin synergistically reduces the survival and increases the radiosensitivity of tumor cells, thus showing it is a valuable therapeutic option in the treatment of head and neck tumors.

• Keywords: TLR3; tumori glave i vrata; liječenje; cisplatina; radiosenzitizacija
• Keywords (english): TLR; head and neck cancer; treatment; cisplatin; radio-sensitisation
• Language: croatian
• URN:NBN: urn:nbn:hr:217:208233
• 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; Embargo expiration date: 2021-11-14
• Created on: 2019-12-12 10:46:56