Patofiziološko značenje metaboličkih promjena u solidnim tumorima

master's thesis

• Title (english): Pathophysiological significance of metabolic changes in solid tumors
• Author: Helena Penić-Grgaš
• Mentor: Maja Sirotković Skerlev (mentor)
• Committee member: Filip Sedlić (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Maja Sirotković Skerlev (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathophysiology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathophysiology

Abstract

Metaboličke promjene u tumorima prepoznate su kao jedna od ključnih značajki tumora. Rezultat su genskih promjena protoonkogena i tumor supresora. Produkti i supstrati metaboličkih reakcija, malene su molekule, metaboliti i predmet su interesa jedne od mlađih među „omikama“ – metabolomike. Metabolomika je našla svoju primjenu u različitim znanostima i granama medicine, a jedno od posebnog područja interesa su maligne bolesti. Predstavlja koristan „alat“ u razvoju spoznaja o tumorskoj biologiji, razvoju novih tumorskih biljega i terapija. Bavi se identifikacijom i kvantifikacijom metabolita u tjelesnim uzorcima te njihovim ulogama i međusobnim odnosima u metaboličkim putevima. Osnovne platforme u metabolomici su masena spektrofotometrija i nuklearna magnetska rezonancija. Integracijom spoznaja iz metabolomike i drugih „omika“ dobivamo uvid u interakciju genoma i okoliša, a rezultat tih odnosa najbolje se očituje u metabolomu. Složene interakcije rezultiraju promjenama u metabolizmu osnovnih skupina hranjivih tvari – ugljikohidrata, aminokiselina i lipida. Prikazana je patofiziologija metaboličkih promjena po skupinama osnovnih hranjivih tvari, uz istaknute posebnosti u metabolizmu četiriju podtipova tumora dojke te tumora prostate. Osobine tumorskog metabolizma koreliraju s genskim abnormalnostima tumora i određene metaboličke promjene odlika su agresivnijih tipova tumora. Opisane su najvažnije genske promjene koje imaju za posljedicu promijenjenu ekspresiju i aktivnost metaboličkih enzima te način kako njihova aktivnost doprinosi tumorskom rastu. Metabolizam tumora nije stacionaran u vremenu i prostoru, mijenja se tijekom četiri osnovna stadija u razvoju tumora u skladu s promijenjenim potrebama za energijom i gradivnim jednicama. Razlike u metabolizmu tumorskih i normalnih stanica koriste se za razvoj novih protu-tumorskih lijekova i vrijedna su nadopuna klasičnim oblicima liječenja.

Abstract (english)

Metabolic changes are recognized as one of cancer's hallmarks. They are a result of changes in proto-oncogenes and tumor suppressors. Metabolites are products and substrates of metabolic reactions, and also, a field of interest among one of the youngest of „omics“ – metabolomics. Metabolomics found its use in various sciences and fields of medicine, and one of the main fields of interest are malignant diseases. It is a useful tool in gathering knowledge about tumor biology, development of new tumor biomarkers and therapies. Metabolomics identifies and quantifies metabolites in biospecimens, and determines their functions and interconnectivity in metabolic pathways. The main platforms in metabolomics are mass spectrophotometry and nuclear magnetic resonance. Due to integration of knowledge from metabolomics and other omics, we are getting an insight in the interaction of genome and environment, best reflecting in metabolome. Complex interactions result in changes in main nutrient metabolism – carbohydrates, aminoacids and lipids. Pathophysiology of metabolic changes is shown separately in every nutrient group, with an emphasis on special metabolic features of four breast cancer subtypes and prostatic cancer. Metabolic features of tumors correlate with genetic abnormalities and some of them are hallmarks of aggressive tumors. The most important genetic changes and their contribution to tumor growth are described. They lead to altered expression and activity of metabolic enzymes. Tumor metabolism is not stationary in time and space, it is changing through four main stages in tumor development in accordance with altered energy demands and building units. Differences in the tumor and normal cells metabolism are used in the development of new anti-tumor drugs, which are a valuable addition to classic modes of treatment.

• Keywords: metabolomika; rak dojke; rak prostate; regulacija
• Keywords (english): metabolomics; breast cancer; prostatic cancer; regulation
• Language: croatian
• URN:NBN: urn:nbn:hr:105:587982
• 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
• Created on: 2019-12-12 10:48:00