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Določanje nekaterih označevalcev oksidativnega stresa pri pacientih z napredovalim rakom trebušne slinavke
ID Štojs, Denis (Author), ID Osredkar, Joško (Mentor) More about this mentor... This link opens in a new window, ID Janša, Rado (Comentor)

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Abstract
Rak trebušne slinavke je kljub napredku v znanosti in medicini ena od rakavih bolezni z najslabšo napovedjo, saj je ob postavitvi diagnoze le petina bolnikov primernih za kirurško zdravljenje, medtem ko je pri večini bolezen že v napredovalih fazah oz. je razsejana. Bolezen zaradi poznega pojava simptomov in njihove nespecifičnosti predstavlja zahteven diagnostični izziv, zaradi česar se vse več raziskav usmerja v nove načine zdravljenja in spremljanja bolnikov, ki prejemajo terapijo. Trenutno so v ta namen v rutinski uporabi predvsem različne slikovne preiskave in določanje tumorskih označevalcev, medtem ko na podlagi dognanj različnih študij, ki so dokazale da so visoke vrednosti reaktivnih kisikovih spojin, spremembe v redoks zaporedjih in slabo uravnavanje redoks signaliziranja pogosti kazalniki napredovanja raka in odpornosti na terapijo, vse več pozornosti posvečajo označevalcem oksidativnega stresa. Preučevanje njihovih koncentracij v urinu predstavlja učinkovit in neinvaziven način ugotavljanja, kako se redoks ravnovesje spreminja na daljši rok, saj se z urinom izločajo oksidirani produkti, nastali ob popravljanju poškodovane DNK. V magistrski nalogi smo se na podlagi izsledkov predhodnih raziskav odločili preveriti, kakšne so možnosti uporabe določenih označevalcev oksidativnega stresa v urinu pri pacientih z napredovalim rakom trebušne slinavke. Zanje smo se odločili zato, ker naj bi predstavljali trenutno najbolj priporočljive oziroma obetavne označevalce za oceno oksidativnega statusa na daljši rok. Izbrali smo naslednje analite: 8-hidroksideoksigvanozin, 8-izoprostan, ditirozin in heksanoil lizin, ki predstavljajo produkte oksidativnih poškodb nukleinskih kislin, proteinov ter lipidov. Meritev koncentracij izbranih analitov smo opravili s pomočjo komercialno dostopnih testnih kompletov ELISA. Rezultate smo primerjali glede na trenutno najbolj široko uporabnima tumorskima označevalcema CA 19-9 in CEA ter stopnjo napredovanja bolezni in učinkovitost terapije, pri preiskovancih. Z analizo naših rezultatov smo pri preiskovancih z rakom trebušne slinavke, glede na dostopne referenčne vrednosti, zaznali nekatere trajne oz. značilno spremenjene koncentracije analitov. Tako smo ugotovili, da se napredovanje bolezni pogosto kaže kot naraščanje koncentracij 8-hidroksideoksigvanozina, 8-izoprostana, ditirozina in heksanoil lizina, medtem ko učinkovita terapija koncentracije znižuje. Z upoštevanjem podatkov o stadiju bolezni smo prav tako dokazali, da nižje vrednosti 8-hidroksideoksigvanozina ob prvem odvzemu vzorca urina pogosto napovedujejo boljše preživetje. Po drugi strani pa smo ob primerjavi s tumorskima označevalcema CA 19-9 in CEA ugotovili, da vrednosti preučevanih analitov ne korelirajo vedno z njunimi nivoji, pri čemer je visoko stopnjo korelacij izkazoval le ditirozin. Na podlagi izsledkov naše raziskave menimo, da bi bilo označevalce oksidativnega stresa v urinu smiselno vpeljati v algoritem spremljanja bolnikov z napredovalim rakom trebušne slinavke.

Language:Slovenian
Keywords:rak trebušne slinavke, oksidativni stres, biološki označevalci, redoks ravnovesje
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2023
PID:20.500.12556/RUL-146144 This link opens in a new window
Publication date in RUL:21.05.2023
Views:535
Downloads:58
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Secondary language

Language:English
Title:Determination of some oxidative stress markers in advanced pancreatic cancer patients
Abstract:
Pancreatic cancer is, despite advances in science and medicine, one of the cancer diseases with the worst prognosis. Only one fifth of all patients are suitable for surgical treatment upon diagnosis, while the majority are already in advanced stages of the disease with metastases present. Due to the late onset of symptoms and their non-specificity, the disease represents an arduous diagnostic challenge, which is why more and more research is being directed towards new ways of treating and monitoring patients who are receiving therapy. Currently, various imaging tests and measurement of tumor markers are in routine use for this purpose. However, based on the findings of various studies, which proved that high levels of reactive oxygen compounds, changes in redox sequences and poor regulation of redox signalling are common indicators of cancer progression and resistance to therapy, more and more attention is being paid to markers of oxidative stress. Examining their concentrations in urine is an efficient and non-invasive way of determining how the redox balance has changed in the long term, as oxidized products that were formed during the repair of damaged DNA are excreted in the urine. Based on previous research, this assignment aims to check the possibilities of using certain markers of oxidative stress in urine of patients with advanced pancreatic cancer. We decided for those because they are currently the most recommended or promising markers for long-term assessment of oxidative status. We selected the analytes 8-hydroxydeoxyguanosine, 8-isoprostane, dityrosine and hexanoyl lysine, which represent the products of oxidative damage to nucleic acids, proteins and lipids. The concentrations of selected analytes were measured using commercially available ELISA test kits. The results were compared to currently most widely used tumour markers CA 19-9 and CEA, as well as regarding the degree of disease progression and the effectiveness of the therapy received by the subjects. By analysing the data obtained during the research, we detected some permanent and characteristically changed concentrations of analytes in subjects with pancreatic cancer compared to available reference values. We found that the progression of the disease is often manifested as an increase in concentration of 8-hydroxydeoxyguanosine, 8-isoprostane, dityrosine and hexanoyl lysine, while effective therapy lowers concentrations. Based on data on various disease stages, we also proved that lower values of 8-hydroxydeoxyguanosine at the first sampling often predict a better survival. On the other hand, when compared to the tumour markers CA 19-9 and CEA, we found that the values of 8-hydroxydeoxyguanosine, 8-isoprostane, dityrosine and hexanoyl lysine do not always correlate with them, and only dityrosine showed a high proportion of correlations. Based on the results of the our research, it would be reasonable to introduce markers of oxidative stress in the urine into the monitoring algorithm of patients with advanced pancreatic cancer.

Keywords:pancreatic cancer, oxidative stress, biological markers, redox balance

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