PARP-inhibitori u liječenju karcinoma endometrija

master's thesis

• Title (english): PARP-inhibitors in the treatment of endometrial carcinoma
• Author: Lea Bošnjak
• Mentor: Pavao Planinić (mentor)
• Committee member: Goran Vujić (predsjednik povjerenstva)
• Committee member: Željko Duić (član povjerenstva)
• Committee member: Pavao Planinić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Gynecology and Obstetrics); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Gynecology and Obstetrics
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Naše su stanice konstantno izložene brojnim vrstama genotoksičnih stresova koji s vremenom mogu dovesti do oštećenja DNA i stanične smrti. Posjedujemo niz mehanizama za otkrivanje oštećenja koji mogu otkriti oštećenje DNA i naglo reagirati kako bi se popravila i očuvala genomska stabilnost. PARP-ovi, koji su obilno izraženi nuklearni enzimi, igraju važnu ulogu u ovoj funkciji. Poli (ADP-riboza) polimeraza ili PARP predstavlja obitelj od 18 strukturno i funkcionalno različitih proteina koji imaju značajnu ulogu u vitalnosti stanica. Oni otkrivaju oštećenje DNA i započinju put popravljanja dodavanjem ADP riboznih lanaca na proteine poznato pod nazivom PARilacija. S druge strane, PARP inhibitori skupina su farmakoloških inhibitora koji se koriste u liječenju tumora. Budući da je karcinom endometrija vrlo česta vrsta raka, provedena su mnoga istraživanja kombinirajući funkciju PARP inhibitora s ostalim kemoterapeuticima i ionizacijskim zračenjem. Stanice tumora češće se repliciraju, pa se pogreške u transkripciji i translaciji događaju češće i lakše. Te mitotičke nedostatke obično popravljaju enzimi za popravak DNA, poput BRCA 1 i 2, koji i sami mogu biti oštećeni kod nekih osoba s karcinomom endometrija. Ukoliko kombiniramo PARP inhibitore i ionizacijsku terapiju kod pacijenata s oštećenim BRCA 1 i 2 genima, u osnovi inhibiramo popravak ovih tumorskih stanica što dovodi do njihove smrti, čineći tumor sve manjim i manjim.

Abstract (english)

Our cells are constantly exposed to numerous types of genotoxic stresses that can eventually lead to DNA damage and cell death. We have a variety of damage detection mechanisms that can detect DNA impairment and react abruptly to repair and preserve genomic stability. PARPs, which are abundantly expressed nuclear enzymes, play an important role in this function. Poly (ADP-ribose) polymerase or PARP represents a family of 18 structurally and functionally distinct proteins that play a significant role in cell vitality. They sensor DNA damage and initiate the base excision repair pathway by adding ADP ribose chains to proteins also known as parylation. PARP inhibitors, on the other hand, are a group of pharmacological inhibitors used in the treatment of cancer. Since endometrial carcinoma is a very common type of cancer, we have conducted many studies combining the function of PARP inhibitors with ionization treatments. Tumor cells replicate more frequently, so transcription and translation errors can occur much more easily. These mitotic defects are normally repaired by DNA repair enzymes, such as BRCA 1 and 2, which themselves may be defective in some individuals with endometrial carcinoma. If we combine PARP inhibitors and ionization therapy in these defective BRCA 1 or 2 patients, we are basically inhibiting the repair of these tumor cells leading to their death, making the tumor smaller and smaller.

• Keywords: PARP-inhibitori; liječenje; karcinom endometrija; oštećenje DNA; popravak DNA; parilacija
• Keywords (english): PARP-inhibitors; treatment; endometrial carcinoma; DNA damage; DNA repair; parylation
• Language: croatian
• URN:NBN: urn:nbn:hr:105:672959
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Public note: Pohranitelj objekta unio ključne riječi.
• Created on: 2022-01-28 10:59:58