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Prepoznavanje ogroženosti za nastanek raka dojk na mamografskih slikah
Žan Klaneček, Andrej Studen, Katja Jarm, Mateja Krajc, Miloš Vrhovec, Robert Jeraj, 2024, published professional conference contribution

Abstract: Za prehod s populacijskega na personalizirano presejanje za raka dojk je v prvi vrsti potrebno natančno prepoznavanje ogroženosti za razvoj raka dojk. Standardni modeli, ki temeljijo na klasičnih značilkah, niso najbolj zanesljivi. Z razvojem umetne inteligence, predvsem na področju globokega učenja, se je izkazalo, da modeli, ki so naučeni na mamografskih slikah, dosegajo signifikantno boljše rezultate pri napovedovanju ogroženosti. Trenutno je najboljši model za napovedovanje ogroženosti MIRAI, ki je bil uspešno validiran na različnih populacijah. A vendar so rezultati še daleč od popolnih in možnosti za izboljšave je ogromno, predvsem na področju razširitve uporabnosti modela za različne proizvajalce mamografskih aparatov, vključevanja longitudinalnih sprememb in uporabe segmentiranih slik dojke.
Keywords: obvladovanje raka, presejalni programi, rak dojk, mamografija
Published in DiRROS: 06.06.2024; Views: 86; Downloads: 43
.pdf Full text (85,28 KB)

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Napovedovanje neželenih učinkov pri imunoterapiji metastatskega melanoma na podlagi slik FDG-PET
Katja Strašek, Martina Reberšek, 2024, published professional conference contribution

Abstract: Imunoterapija je preoblikovala zdravljenje metastatskih rakov, saj je izboljšala preživetje in kakovost življenja bolnikov. Kljub temu povzroča imunsko pogojene neželene učinke, ki zahtevajo prekinitev zdravljenja. Njihovo zgodnje odkrivanje je zato ključnega pomena, njihova diagnoza pa temelji predvsem na kliničnih simptomih in laboratorijskih izvidih. Razmah razvoja umetne inteligence v preteklih letih je omogočil bolj kvantitativno analizo 18F-FDG PET/CT slik. Prvi korak, kjer umetna inteligenca pripomore k hitrejši diagnozi imunsko pogojenih neželenih učinkov, so nevronske mreže, razvite za segmentacijo organov na CT-slikah. Uporaba takšnih avtomatskih orodij za segmentacijo organov je hitrejša in bolj natančna v primerjavi z ročno segmentacijo. Omogoča tudi razvoj kvantitativnih slikovnih bioloških označevalcev, izvlečenih iz PET-slik s pomočjo pridobljenih segmentacij, kar je pripomoglo tudi k razmahu razvoja napovednih modelov. V retrospektivni raziskavi, ki je vključevala 58 bolnikov z metastatskim melanomom, so se percentili porazdelitve FDG v ščitnici, črevesju in pljučih izkazali kot orodje za ločevanje med bolniki, ki bodo razvili imunsko pogojene neželene učinke, in tistimi, ki jih ne bodo. Validacija teh kvantitativnih slikovnih bioloških označevalcev (angl. Quantitative Imaging Biomarkers, QIB) za napovedovanje imunsko pogojenih neželenih učinkov trenutno poteka v prospektivni neinterventni klinični raziskavi na Onkološkem inštitutu Ljubljana. Prvi izsledki kažejo, da so razviti označevalci v pomoč klinikom pri zgodnji diagnozi imunsko pogojenih neželenih učinkov, kar omogoči hitrejše ukrepanje pred razvojem kliničnih simptomov, a včasih tudi lažno napovedo možen razvoj neželenih učinkov. Naslednji koraki so razvoj modela za napoved časa razvoja imunsko pogojenih neželenih učinkov, a je za razvoj takšnih modelov potrebno večje število podatkov, za kar so potrebne multicentrične klinične raziskave. 18 Ključne besede: imunoterapija, neželeni učinki, kvantifikacija, FDG-PET/CT, napovedovanje neželenih učinkov, kvantitativni slikovni biološki označevalci
Keywords: metastatski melanom, imunoterapija, neželeni učinki
Published in DiRROS: 06.06.2024; Views: 90; Downloads: 45
.pdf Full text (216,10 KB)

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Nature-inspired substituted 3-(imidazol-2-yl) morpholines targeting human topoisomerase IIα : dynophore-derived discovery
Barbara Herlah, Matej Janežič, Iza Ogris, Simona Golič Grdadolnik, Katja Kološa, Sonja Žabkar, Bojana Žegura, Andrej Perdih, 2024, original scientific article

Abstract: The molecular nanomachine, human DNA topoisomerase IIα, plays a crucial role in replication, transcription, and recombination by catalyzing topological changes in the DNA, rendering it an optimal target for cancer chemotherapy. Current clinical topoisomerase II poisons often cause secondary tumors as side effects due to the accumulation of double-strand breaks in the DNA, spurring the development of catalytic inhibitors. Here, we used a dynamic pharmacophore approach to develop catalytic inhibitors targeting the ATP binding site of human DNA topoisomerase IIα. Our screening of a library of nature-inspired compounds led to the discovery of a class of 3-(imidazol-2-yl) morpholines as potent catalytic inhibitors that bind to the ATPase domain. Further experimental and computational studies identified hit compound 17, which exhibited selectivity against the human DNA topoisomerase IIα versus human protein kinases, cytotoxicity against several human cancer cells, and did not induce DNA double-strand breaks, making it distinct from clinical topoisomerase II poisons. This study integrates an innovative natural product-inspired chemistry and successful implementation of a molecular design strategy that incorporates a dynamic component of ligand-target molecular recognition, with comprehensive experimental characterization leading to hit compounds with potential impact on the development of more efficient chemotherapies.
Keywords: topoisomerase II, catalytic inhibitors, chemotherapy, DNA damage, cancer
Published in DiRROS: 03.06.2024; Views: 191; Downloads: 71
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Cancer burden in Slovenia with the time trends analysis
Vesna Zadnik, Maja Primic-Žakelj, Katarina Lokar, Katja Jarm, Urška Ivanuš, Tina Žagar, 2017, original scientific article

Abstract: Background The aim of our study was to describe cancer burden and time trends of all cancers combined, the most frequent as well as the rare cancers in Slovenia. Patients and methods The principal data source was the population-based Cancer Registry of Republic of Slovenia. The cancer burden is presented by incidence and prevalence for the period 1950%2013 and by mortality for years 1985%2013. The time trends were characterized in terms of an average annual percent change estimated by the log-linear joinpoint regression. The Dyba-Hakulinen method was used for estimation of incidence in 2016 and the projections of cancer incidence for the year 2025 were calculated applying the Globocan projection software. Results In recent years, near 14,000 Slovenes were diagnosed with cancer per year and just over 6,000 died; more than 94,000 people who were ever diagnosed with cancer are currently living among us. The total burden of cancer is dominated by five most common cancer sites: skin (non-melanoma), colon and rectum, lung, breast and prostate, together representing almost 60% of all new cancer cases. On average the incidence of common cancers in Slovenia is increasing for 3.0% per year in last decade, but the incidence of rare cancers is stable. Conclusions Because cancer occurs more among the elderly, and additionally more numerous post-war generation is entering this age group, it is expected that the burden of this disease will be growing further, even if the level of risk factors remains the same as today.
Keywords: cancer burden, cancer registry, incidence, prevalence
Published in DiRROS: 24.05.2024; Views: 131; Downloads: 119
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Genotoxicity and heating performance of VxFe3-xO4 nanoparticles in health applications
Beatriz Sanz-Sagué, Amaia Sáenz-Hernández, Bojana Žegura, Alja Štern, Katja Kološa, Iza Rozman, 2024, original scientific article

Abstract: The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects—types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.
Keywords: magnetic nanoparticles, vanadium ferrite, cytotoxicity, genotoxicity, specific power absorption, cell viability
Published in DiRROS: 23.05.2024; Views: 114; Downloads: 118
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