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1582. Results of postoperative radiochemotherapy of the patients with resectable gastroesophageal junction adenocarcinoma in SloveniaAna Jeromen, Irena Oblak, Franc Anderluh, Vaneja Velenik, Marija Skoblar Vidmar, Ivica Ratoša, 2012, izvirni znanstveni članek Ključne besede: gastroesophageal junction adenocarcinoma, postoperative radiochemotherapy, toxicity Objavljeno v DiRROS: 21.03.2024; Ogledov: 381; Prenosov: 105
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1583. Effects of electrochemotherapy on immunologically important modifications in tumor cellsUrša Kešar, Boštjan Markelc, Tanja Jesenko, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2023, izvirni znanstveni članek Povzetek: Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. Electrochemotherapy with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this is ubiquitous over different cancer types and for other clinically relevant chemotherapeutics used with electrochemotherapy is unknown. Here, we evaluated in vitro in the B16-F10, 4T1 and CT26 murine tumor cell lines, the electrochemotherapy triggered changes in the ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin (CRT), ATP, High Mobility Group Box 1 (HMGB1), and four immunologically important cellular markers: MHCI, MHC II, PD-L1 and CD40. The changes in these markers were investigated in time up to 48 h after ECT. We showed that electrochemotherapy with all three tested chemotherapeutics induced ICD-associated DAMPs, but the induced DAMP signature was cell line and chemotherapeutic concentration specific. Similarly, electrochemotherapy with CDDP, OXA or BLM modified the expression of MHC I, MHC II, PD-L1 and CD40. The potential of electrochemotherapy to change their expression was also cell line and chemotherapeutic concentration specific. Our results thus put the electrochemotherapy with clinically relevant chemotherapeutics CDDP, OXA and BLM on the map of ICD inducing therapies. Ključne besede: electrochemotherapy, cisplatin, immune response Objavljeno v DiRROS: 21.03.2024; Ogledov: 391; Prenosov: 230
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1584. Short term effect of plant hybridosomes on growth of phaeodactylum tricornutum cultureAnna Romolo, Matej Hočevar, Aleš Iglič, Tjaša Griessler Bulc, Veronika Kralj-Iglič, 2023, objavljeni znanstveni prispevek na konferenci Ključne besede: Phaeodactylum tricornutum, hybridosomes, liposomes, nanoalgosomes, extracellular vesicles, small cellular particles, microalgae Objavljeno v DiRROS: 21.03.2024; Ogledov: 337; Prenosov: 178
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1585. Gene immunotherapy of colon carcinoma with IL-2 and IL-12 using gene electrotransferTilen Komel, Maša Omerzel, Urška Kamenšek, Katarina Žnidar, Urša Lampreht Tratar, Simona Kranjc Brezar, Klemen Dolinar, Sergej Pirkmajer, Gregor Serša, Maja Čemažar, 2023, izvirni znanstveni članek Povzetek: Gene immunotherapy has become an important approach in the treatment of cancer. One example is the introduction of genes encoding immunostimulatory cytokines, such as interleukin 2 and interleukin 12, which stimulate immune cells in tumours. The aim of our study was to determine the effects of gene electrotransfer of plasmids encoding interleukin 2 and interleukin 12 individually and in combination in the CT26 murine colon carcinoma cell line in mice. In the in vitro experiment, the pulse protocol that resulted in the highest expression of IL-2 and IL-12 mRNA and proteins was used for the in vivo part. In vivo, tumour growth delay and also complete response were observed in the group treated with the plasmid combination. Compared to the control group, the highest levels of various immunostimulatory cytokines and increased immune infiltration were observed in the combination group. Long-term anti-tumour immunity was observed in the combination group after tumour re-challenge. In conclusion, our combination therapy efficiently eradicated CT26 colon carcinoma in mice and also generated strong anti-tumour immune memory. Ključne besede: colon carcinoma, gene electrotransfer, gene immunotherapy Objavljeno v DiRROS: 21.03.2024; Ogledov: 362; Prenosov: 155
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1586. Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidenceTjaša Oblak, Petra Škerl, Benjamin J. Narang, Rok Blagus, Mateja Krajc, Srdjan Novaković, Janez Žgajnar, 2023, izvirni znanstveni članek Povzetek: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC. Ključne besede: early breast cancer, polygenic risk score, risk prediction Objavljeno v DiRROS: 21.03.2024; Ogledov: 353; Prenosov: 109
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1587. Numerical modelling of macrosegregation in three-dimensional continuous casting of steel billetsKatarina Mramor, Robert Vertnik, Božidar Šarler, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Macrosegregation presents a considerable defect in the continuous casting of billets and can critically affect the final properties of the product. The numerical modelling can help to predict and better understand the segregation and flow patterns inside the mould. The process is modelled with a physical model described by a set of conservation equations describing the t heat transfer, turbulence, fluid flow, solidification and segregation. A two-equation low-Re k-epsilon model and Abe-Kondoh-Nagano closures are used to close governing equations in this incompressible fluid flow example. The Boussinesq approximation is applied to account for the thermo-solutal buoyancy effects, and the Darcy approximation is applied for the description of the flow through the porous mushy zone. On a microscale, a lever rule solidification model is used to couple liquid fraction, temperature and concentration. The three-dimensional model is solved with the method based on local collocation with multiquadric radial basis functions on seven-nodded subdomains. The aim of this contribution is to explore the three-dimensional macrosegregation patterns of 0.51 wt% carbon steel in the solidified shell of the steel in the mould. Ključne besede: modeling, continuous casting of steel, CFD, turbulence modeling, LES, meshless methods, RANS Objavljeno v DiRROS: 21.03.2024; Ogledov: 335; Prenosov: 200
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1588. The prognostic and predictive value of human gastrointestinal microbiome and exosomal mRNA expression of PD-L1 and IFNγ for immune checkpoint inhibitors response in metastatic melanoma patients : protocol trialAna Erman, Marija Ignjatović, Katja Leskovšek, Simona Miceska, Urša Lampreht Tratar, Maša Omerzel, Veronika Kloboves-Prevodnik, Maja Čemažar, Lidija Kandolf Sekulović, Gorazd Avguštin, Janja Ocvirk, Tanja Mesti, 2023, izvirni znanstveni članek Povzetek: Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients. Ključne besede: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma Objavljeno v DiRROS: 21.03.2024; Ogledov: 344; Prenosov: 191
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1589. Meshless simulation of a macrosegregation benchmark considering the solid motionViktor Govže, Igor Vušanović, Božidar Šarler, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: We have extended the existing two-dimensional rigid solid phase benchmark for binary substance with the solid phase motion in the present paper. Incompressible laminar Newtonian flow is assumed, and a standard mixture formulation is used for the mass, momentum, energy, and solute transport. A coherency solid motion model accounts for the free-floating grains, assuming that the solid velocity is proportional to the mixture velocity and the liquid fraction. The lever rule is used to describe the mass fractions of the phases. A two-dimensional benchmark is solved using the semi-implicit meshless diffuse approximate method with an adaptive subdomain upwinding strategy. The results of the meshless method are compared to the finite volume method results with a reasonable agreement. The new benchmark results show that the solid motion has an essential effect on the macrosegregation pattern. Ključne besede: solidification, meshless methods, grain motion, benchmarks Objavljeno v DiRROS: 21.03.2024; Ogledov: 398; Prenosov: 158
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1590. Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicityAleš Sedlar, Tanja Jesenko, Boštjan Markelc, Lara Prosen, Simona Kranjc Brezar, Maša Omerzel, Tanja Blagus, Maja Čemažar, Gregor Serša, 2012, izvirni znanstveni članek Objavljeno v DiRROS: 21.03.2024; Ogledov: 355; Prenosov: 128
Celotno besedilo (684,68 KB) |