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New insights in ATP synthesis as therapeutic target in cancer and angiogenic ocular diseases
Cornelis J. F. van Noorden, Bahar Yetkin-Arik, Paola Serrano Martinez, Noëlle Bakker, Mathilda E. van Breest Smallenburg, Reinier O. Schlingemann, Ingeborg Klaassen, Bernarda Majc, Anamarija Habič, Urban Bogataj, Katrin S. Galun, Miloš Vittori, Mateja Erdani-Kreft, Metka Novak, Barbara Breznik, Vashendriya V. V. Hira, 2024, review article

Abstract: Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production.
Keywords: aerobic glycolysis, anaerobic glycolysis, angiogenesis, ATP synthesis, cancer cells, cancer stem cells, endothelial cells, energy metabolism, eye diseases, oxidative phosphorylation, pericytes, retina, Warburg effect
Published in DiRROS: 18.06.2024; Views: 90; Downloads: 62
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3.
Evaluating mineral matter dynamics within the peatland as reflected in water composition
Valentina Pezdir, Luka Serianz, Mateja Gosar, 2024, original scientific article

Abstract: Peatland hydrology plays an important role in preserving or changing the record in any consideration of past atmospheric deposition records in peat bogs. The Šijec bog, located on the Pokljuka plateau in Slovenia, is one of the largest ombrotrophic peatlands. We sampled the surface pools, pore water, drainage from the peatland, and karst streams not connected to the peatland. Additionally, we sampled the precipitation, as ombrotrophic peatlands receive mineral matter solely from the atmosphere. The results of the evaluation of the chemical and isotopic composition indicated different origins of dissolved mineral matter in different water types. The components originating from the bedrock and surrounding soils (Ca, Mg, Al, Si, Sr) predominated in the streams. The chemical composition of the peatland drainage water revealed the significant removal of major components from the peatland, particularly elements like Al, Fe, and REE, and metals that are readily dissolved in an acidic environment or mobile in their reduced state. Despite their solubility, concentrations of metals (As, Cr, Cu, Fe, Ni, Pb, Ti) and REE in surface pools remained higher than in the drainage due to incomplete elimination from the peatland. The composition of pore water reflects variations among the W and E parts of the peatland, indicating a heterogenous hydrological structure with different dynamics, such as an additional source of water at approximately 90 cm depth in the NW part. The chemical composition and isotope signature (18O and 2H) of pore water additionally indicated a heterogeneous recharge with residence times of less than a year. The overall analysis indicated a predominantly ombrotrophic type and a small part in the NW area of the peatland as a minerotrophic type of peat.
Keywords: peatland, hydrogeochemistry, isotopes
Published in DiRROS: 18.06.2024; Views: 99; Downloads: 41
.pdf Full text (7,67 MB)

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Interval cancers after negative immunochemical test compared to screen and non-respondersʼ detected cancers in Slovenian colorectal cancer screening programme
Dominika Novak-Mlakar, Tatjana Kofol-Bric, Ana Lucija Škrjanec, Mateja Krajc, 2018, original scientific article

Abstract: We assessed the incidence and characteristics of interval cancers after faecal immunochemical occult blood test and calculated the test sensitivity in Slovenian colorectal cancer screening programme. Patients and methods. The analysis included the population aged between 50 to 69 years, which was invited for screening between April 2011 and December 2012. The persons were followed-up until the next foreseen invitation, in average for 2 years. The data on interval cancers and cancers in non-responders were obtained from cancer registry. Gender, age, years of schooling, the cancer site and stage were compared among three observed groups. We used the proportional incidence method to calculate the screening test sensitivity. Results. Among 502,488 persons invited for screening, 493 cancers were detected after positive screening test, 79 interval cancers after negative faecal immunochemical test and 395 in non-responders. The proportion of interval cancers was 13.8%. Among the three observed groups cancers were more frequent in men (p = 0.009) and in persons aged 60+ years (p < 0.001). Comparing screen detected and cancers in non-responders with interval cancers more interval cancers were detected in persons with 10 years of schooling or more (p = 0.029 and p = 0.001), in stage III (p = 0.027) and IV (p < 0.001), and in right hemicolon (p < 0.001). Interval cancers were more frequently in stage I than non-responders cancers (p = 0.004). Test sensitivity of faecal immunochemical test was 88.45%. Conclusions. Interval cancers in Slovenian screening programme were detected in expected proportions as in similar programmes. Test sensitivity was among the highest when compared to similar programmes and was accomplished using test kit for two stool samples.
Keywords: cancer screening, colorectal cancer, faecal immunochemical test, test sensitivity
Published in DiRROS: 10.06.2024; Views: 80; Downloads: 25
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7.
Spremljanje bolnikov in njihovih zdravih svojcev po diagnozi dedne predispozicije za raka
Mateja Krajc, 2024, published professional conference contribution

Abstract: Vsaj pet odstotkov vseh novih diagnoz raka povezujemo z dedno predispozicijo. Posamezniki, ki podedujejo patogeno ali verjetno patogeno različico, so bolj ogroženi, da bodo zboleli za rakom, ki ga povezujemo z določenim dednim sindromom oziroma z okvaro določenega gena. Običajno te posameznike, ne glede na to, ali so že zboleli za rakom ali ne, vabimo na presejalne preglede za rake, za katere so ogroženi. Večinoma je program spremljanja organiziran skladno s trenutno uveljavljenimi mednarodnimi smernicami in konsenzom strokovnjakov na področjih, kjer nimamo dovolj z dokazi podrtih ukrepov zaradi redkosti sindroma. Prav zato velikokrat spremljanje sloni na klinični presoji zdravnika, ki te posameznike obravnava, upoštevajoč splošno zmogljivost, zdravstveno stanje, morebitne pridružene bolezni in pričakovano življenjsko dobo. Zato mnoge države uporabljajo spremljanja v okviru raziskovalnih projektov, kjer se optimalni intervali spremljanja in določitev primernih presejalnih testov za zgodnje odkrivanje raka pri redkih dednih sindromih za raka šele razvijajo. Tako kot je že dokazano pri presejalnih programih za raka, kamor vključujemo splošno populacijo, je tudi pri presejanju bolj ogroženih lahko prisotna psihološka stiska. Med spremljanjem namreč veliko razmišljajo o tem, ali jim bo odkrit rak, zaradi katerega so zboleli in/ali umrli njihovi svojci. V tej populaciji je zato še posebej pomembno, da posameznikom nudimo ustrezno svetovanje pred vključitvijo v program spremljanja, predamo natančen protokol pregledov in predstavimo prednosti in omejitve presejanja in spremljanja ter nudimo ustrezno psihološko pomoč.
Keywords: bolniki, genetske preiskave, spremljanje bolnikov, denost
Published in DiRROS: 06.06.2024; Views: 114; Downloads: 93
.pdf Full text (74,07 KB)

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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: 140; Downloads: 93
.pdf Full text (85,28 KB)

9.
Genetic counselling, BRCA1/2 status and clinico-pathologic characteristics of patients with ovarian cancer before 50 years of age
Mirjam Cvelbar, Marko Hočevar, Srdjan Novaković, Vida Stegel, Andraž Perhavec, Mateja Krajc, 2017, original scientific article

Abstract: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods. All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results. Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions. The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered.
Keywords: ovarian cancer, BRCA 1/2, genetic counseling
Published in DiRROS: 24.05.2024; Views: 178; Downloads: 135
.pdf Full text (513,68 KB)

10.
Towards the development of a landslide activity map in Slovenia
Mateja Jemec Auflič, Krištof Oštir, Tanja Grabrijan, Matjaž Ivačič, Tina Peternel, Ela Šegina, 2024, original scientific article

Abstract: To create the landslide activity map, we implemented and tested the procedure to fully utilise the 6-day repeatability of the Sentinel-1 constellation in three pilot areas in Slovenia for the observation period from 2017 to 2021. The interferometric processing of the Sentinel-1 images was carried out with ENVI SARScape, while the interpretation of the persistent scatterers InSAR data was done in three steps. In the first step, a preliminary interpretation of the landslide areas was performed by integrating the PS InSAR data into a GIS environment with information that could be relevant to explain the movement patterns of the PS InSAR points. In the second step, a field validation was performed to check the PS InSAR in the field and record the potential damage to the objects indicating the slope mass movements. In the third step, the deformations were identified, and areas of significant movement were determined, consisting of clusters of at least 3 persistent scatterers (PS) with a maximum spacing of 10 m. The landslide activity map was created based on the landslide areas categorised into four classes based on the geotechnical analyses, yearly velocity data obtained by PS InSAR, and validation of annual velocity data obtained by in-situ and GNSS monitoring and field observation. A total of 21 polygons with different landslide activities were identified in three study areas. The overall methodology will help stakeholders in the early mapping and monitoring of landslides to increase the urban resilience.
Keywords: landslides, EO data, sentinel, time series, methodology, Slovenia
Published in DiRROS: 30.04.2024; Views: 221; Downloads: 164
.pdf Full text (73,45 MB)

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