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1.
Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapy
Martina Vrankar, Mojca Unk, 2018, pregledni znanstveni članek

Povzetek: Uncommon responses during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria solid tumors (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease. Methods. A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer. Results. In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy. Conclusions. As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.
Ključne besede: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer
Objavljeno v DiRROS: 11.06.2024; Ogledov: 32; Prenosov: 7
.pdf Celotno besedilo (426,11 KB)

2.
Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced melanoma
Maja Ebert Moltara, Srdjan Novaković, Marko Boc, Marina Bučić, Martina Reberšek, Vesna Zadnik, Janja Ocvirk, 2018, izvirni znanstveni članek

Povzetek: BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues that influence on treatment decisions in metastatic melanoma patients. Mutation frequency and their correlation with histological characteristics in Slovenian population have not been investigated yet. Patients and methods. In our retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in 230 pathological samples of patients who were intended to be treated with systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana between 2013 and 2016. We collected also histological characteristics of primary tumours and clinical data of patients and correlated them with mutational status of tumour samples. Results. The study population consisted of 230 patients with a mean age 59 years (range 25%85). 141 (61.3%) were males and 89 (38.7%) females. BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3 (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%) patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations were too low for any statistical correlation, but there was one out of 3 melanoma located in mucus membranes. Conclusions. The analysis detected high rate of BRAF mutations, low NRAS mutations and low c-KIT mutations compared to previously published studies in Europe and North America. One of the main reasons for this observation is specific characteristics of study population.
Ključne besede: BRAF, NRAS, c-KIT, melanoma
Objavljeno v DiRROS: 10.06.2024; Ogledov: 52; Prenosov: 37
.pdf Celotno besedilo (291,53 KB)
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3.
Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapy
Martina Vrankar, Karmen Stanič, 2018, izvirni znanstveni članek

Povzetek: Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.
Ključne besede: NSCLC, non-small cell lung cancer, locally advanced, immunotherapy, chemoradiotherapy
Objavljeno v DiRROS: 10.06.2024; Ogledov: 46; Prenosov: 35
.pdf Celotno besedilo (500,20 KB)
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4.
Napovedovanje neželenih učinkov pri imunoterapiji metastatskega melanoma na podlagi slik FDG-PET
Katja Strašek, Martina Reberšek, 2024, objavljeni strokovni prispevek na konferenci

Povzetek: 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
Ključne besede: metastatski melanom, imunoterapija, neželeni učinki
Objavljeno v DiRROS: 06.06.2024; Ogledov: 89; Prenosov: 44
.pdf Celotno besedilo (216,10 KB)

5.
New records of rarely reported species in the Mediterranean Sea (March 2024)
Markos Digenis, Okan Akyol, Laure Benoit, Marina Biel-Cabanelas, Öznur Yazılan Çamlik, Konstantinos Charalampous, Archontia Chatzispyrou, Borut Mavrič, Martina Orlando-Bonaca, Leon Lojze Zamuda, 2024, izvirni znanstveni članek

Povzetek: This Collective Article presents information about 30 species with records in eight countries (Greece, Israel, Italy, Montenegro, Slovenia, Spain, Syria and Türkiye) and six ecoregions extending from the Alboran to the Levantine Seas. The recorded species belong to eight Phyla (4 Chlorophyta, 1 Rhodophyta, 1 Porifera, 3 Cnidaria, 2 Platyhelminthes, 2 Arthropoda, 2 Mollusca and 15 Chordata) as follows: Chlorophyta: Didymosporangium repens, Ochlochaete hystrix and Phaeophila hirsuta are reported for the first time from the Aegean coasts of Türkiye and Penicillus capitatus is firstly recorded in Slovenian coastal waters; Rhodophyta: Ptilophora dentata is recorded for the first time in Turkish coasts, from the entrance of a marine cave; Porifera: Tethya meloni is reported from Montenegrin waters; Cnidaria: Savalia savaglia and Dendrophyllia ramea are firstly observed north of the Almeria-Oran front in the southeastern Iberian Peninsula, while Spinimuricea cf. atlantica is firstly recorded in the Gulf of Lion constituting the easternmost record of the species in the Mediterranean Sea; Platyhelminthes: the polyclad flatworms Thysanozoon brocchii and Planocera graffi are reported for the first time from Greek waters, observed inside marine caves; Mollusca: Ascobulla fragilis is firstly reported from the Eastern Levantine Sea while the blanket octopus Tremoctopus violaceus is recorded in Izmir Bay constituting its fifth sighting in the Aegean Sea after a quarter of a century; Arthropoda: the copepod Ditrychocorycaeus africanus is firstly recorded in the Ionian Sea while the tufted ghost crab Ocypode cursor is detected further north in the Tyrrhenian Sea; Chordata: the bothid flounder Arnoglossus grohmanni is firstly reported in Spain while specimens of the rare bythitid Bellottia apoda are presented for the Adriatic Sea; the chondrichthyans Chimaera monstrosa, Dalatias licha, Heptranchias perlo, Leucoraja circularis, Mustelus mustelus, Oxynotus centrina, Squatina aculeata and Torpedo marmorata are presented as collected within 13 continuous years in the bathyal zone of the Antalya Bay; the speleophilic fish Grammonus ater is firstly recorded in the Alboran Sea, observed in a marine cave; the critically endangered sandy ray Leucoraja circularis is reported from the eastern Ionian Sea; the crested oarfish Lophotus lacepede is reported for the first time from Sardinia, based on evidence dating back 20 years; the white trevally Pseudocaranx dentex is firstly recorded in Tremiti Islands (Adriatic Sea, Italy) while the phaeton dragonet Synchiropus phaeton and the gobid Zebrus pallaoroi are firstly reported from Syrian and Italian waters, respectively.
Ključne besede: Mediterranean Sea, rare species, flora, fauna
Objavljeno v DiRROS: 03.06.2024; Ogledov: 111; Prenosov: 81
.pdf Celotno besedilo (7,52 MB)
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6.
Rare Middle Triassic coleoids from the Alpine-Carpathian system: new records from Slovakia and their signifcance
Martin Košťák, Ján Schlögl, Dirk Fuchs, Milan Havrila, Tea Kolar-Jurkovšek, Attila Vörös, Martina Havelcová, Juraj Šurka, Jakub Havrila, Katarína Holcová, 2024, izvirni znanstveni članek

Povzetek: Two stratigraphically well constrained (by ammonites and conodonts) coleoid remains have been recorded from the Triassic (Anisian) dark-grey organodetritic limestones (Ráztoka Limestone) of Western Carpathians (Hronic Nappe). The limestones deposited at the periphery of a former carbonate platform. It yields a highly diverse cephalopod fauna including nautiloids (2 taxa), ammonoids (7 taxa) and indetermined aulacoceratids. Two unusual coleoid specimens are referred to genus Mojsisovicsteuthis (M. boeckhi) and probably to a new taxon (described as Breviconoteuthis aff. breviconus herein) possessing similar morphological features of genus Breviconoteuthis (Phragmoteuthida) and/or Zugmontites. Based on index ammonites and conodonts, both records are of the uppermost Trinodosus through the lowermost Reitzi zones (Anisian—lower Illyrian). While the genus Mojsisovicsteuthis has been widely dispersed (however its records are rare), the occurrence of Breviconoteuthis and Zugmontites is strictly limited to the Alpine-Carpathian region. Comparing with the holotype and additional specimens stored in the Hungarian Natural History Museum, the overal shell of Mojsisovicsteuthis and its size has been reconstructed. Its relationship to aulacoceratids and phragmoteuthids is briefly discussed. Geochemical record (n-alkanes from the bulk rock) provided a relevant signal of the existence of algal meadows.
Ključne besede: Cephalopods, Conodonts, Anisian, Palaeoenvironment
Objavljeno v DiRROS: 21.05.2024; Ogledov: 119; Prenosov: 161
.pdf Celotno besedilo (6,08 MB)
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7.
Too hot to handle : effects of water temperature on the early life stages of Gongolaria barbata (Fucales)
Ana Lokovšek, Valentina Pitacco, Annalisa Falace, Domen Trkov, Martina Orlando-Bonaca, 2024, izvirni znanstveni članek

Povzetek: Gongolaria barbata plays a crucial role as a habitat-forming Fucales species in the Mediterranean Sea, thriving in shallow, sheltered coastal regions, where it exhibits optimal growth in a temperature range of 10 to 25 °C. In the northern Adriatic Sea, a semi-enclosed part of the Mediterranean, there has been a remarkable increase in seawater temperatures in recent decades, often exceeding 28 °C in summer. These high temperatures pose a significant threat to the vulnerable early life stages of G. barbata. This study delves into the effects of four temperatures (15, 18, 24, and 28 °C) on the growth of G. barbata over its first 16 days, closely monitoring mortality, deformities, and overall survival. Our experiments reveal that higher temperatures can result in deformities and increased mortality of germlings. Notably, a temperature of 28 °C resulted in the death of all germlings within the first week, whereas those exposed to 24 °C survived until the second week, albeit with significant deformities prior to death. In contrast, germlings cultivated at 15 and 18 °C exhibited normal development with minimal deformities. These results highlight the susceptibility of the early life stages of G. barbata to temperature-induced stress and provide valuable insights into the potential consequences of rising seawater temperatures in the Mediterranean.
Ključne besede: sea ​​temperature, early stages of growth, deformations, macroalgae, climate change, Mediterranean Sea
Objavljeno v DiRROS: 17.05.2024; Ogledov: 161; Prenosov: 258
.pdf Celotno besedilo (2,43 MB)
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8.
Annual recurrence of prokaryotic climax communities in shallow waters of the North Mediterranean
Mauro Celussi, Vincenzo Manna, Elisa Banchi, Viviana Fonti, Matteo Bazzaro, Vesna Flander-Putrle, Katja Klun, Martina Kralj, Neža Orel, Tinkara Tinta, 2024, izvirni znanstveni članek

Povzetek: In temperate coastal environments, wide fluctuations of biotic and abiotic factors drive microbiome dynamics. To link recurrent ecological patterns with planktonic microbial communities, we analysed a monthly-sampled 3-year time series of 16S rRNA amplicon sequencing data, alongside environmental variables, collected at two stations in the northern Adriatic Sea. Time series multivariate analyses allowed us to identify three stable, mature communities (climaxes), whose recurrence was mainly driven by changes in photoperiod and temperature. Mixotrophs (e.g., Ca. Nitrosopumilus, SUP05 clade, and Marine Group II) thrived under oligotrophic, low-light conditions, whereas copiotrophs (e.g., NS4 and NS5 clades) bloomed at higher temperatures and substrate availability. The early spring climax was characterised by a more diverse set of amplicon sequence variants, including copiotrophs associated with phytoplankton-derived organic matter degradation, and photo-auto/heterotrophic organisms (e.g., Synechococcus sp., Roseobacter clade), whose rhythmicity was linked to photoperiod lengthening. Through the identification of recurrent climax assemblages, we begin to delineate a typology of ecosystem based on microbiome composition and functionality, allowing for the intercomparison of microbial assemblages among different biomes, a still underachieved goal in the omics era.
Ključne besede: marine microbial ecology, coastal seas, microbial community analyses, marine biology, marine ecology
Objavljeno v DiRROS: 17.05.2024; Ogledov: 144; Prenosov: 181
.pdf Celotno besedilo (10,22 MB)
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9.
Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer : single center experience
Janja Ocvirk, Maja Ebert Moltara, Tanja Mesti, Marko Boc, Martina Reberšek, Neva Volk, Jernej Benedik, Zvezdana Hlebanja, 2016, izvirni znanstveni članek

Povzetek: Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients% register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (% 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7%16.2) and 11.3 (95% CI, 10.2%12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4%28.9) and 27.4 (95% CI, 22.7%31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions. In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and welltolerated regimen in elderly patients with metastatic colorectal cancer.
Ključne besede: metastatic colorectal cancer, bevacizumab, chemotherapy, elderly
Objavljeno v DiRROS: 30.04.2024; Ogledov: 186; Prenosov: 56
.pdf Celotno besedilo (620,74 KB)

10.
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