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Adjuvant TNF-a therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness
Maja Čemažar, Vesna Todorović, Janez Ščančar, Urša Lampreht Tratar, Monika Savarin, Urška Kamenšek, Simona Kranjc Brezar, Andrej Cör, Gregor Serša, 2015, izvirni znanstveni članek

Povzetek: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Ključne besede: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Objavljeno v DiRROS: 17.04.2024; Ogledov: 44; Prenosov: 5
.pdf Celotno besedilo (978,26 KB)

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Dnevi internistične onkologije 2024 : inovativna zdravila v onkologiji
2024, zbornik strokovnih ali nerecenziranih znanstvenih prispevkov na konferenci

Objavljeno v DiRROS: 04.04.2024; Ogledov: 84; Prenosov: 30
.pdf Celotno besedilo (9,80 MB)

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Radiotherapy for inverted papilloma : a case report and review of the literature
Primož Strojan, Simona Jereb, Imre Boršoš, Jasna But-Hadžić, Nina Zidar, 2013, izvirni znanstveni članek

Objavljeno v DiRROS: 22.03.2024; Ogledov: 80; Prenosov: 33
.pdf Celotno besedilo (961,47 KB)

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The development of nuclear medicine in Slovenia and Ljubljana; half a century of nuclear medicine in Slovenia
Zvonka Zupanič Slavec, Simona Gaberšček, Ksenija Slavec, 2012, pregledni znanstveni članek

Povzetek: Background. Nuclear medicine began to be developed in the USA after 1938 when radionuclides were introduced into medicine and in Europe after radionuclides began to be produced at the Harwell reactor (England, 1947). Slovenia began its first investigations in the 1950s. This article describes the development of nucleor medicine in Slovenia and Ljubljana. The first nuclear medicine interventions were performed in Slovenia at the Internal Clinic in Ljubljana in the period 1954-1959. ln 1954, Dr Jože Satler started using radioactive iodine for thyroid investigations. In the same year, Dr Bojan Varl, who is considered the pioneer of nuclear medicine in Slovenia, began systematically introducing nuclear medicine. The first radioisotope laboratories were established in January 1960 at the Institute of Oncology and at the Internal Clinic. Under the direction of Dr. Varl, the laboratory at the Internal Clinicdeveloped gradually and in 1973 became the Clinic for Nuclear Medicine with departments for in viva and in vi/ro diagnostics and for the treatment ofinpatients and outpatients at the thyroid department. The Clinic for NuclearMedicine beca me a teaching unit of the Medical Faculty and developed its own post-graduate programme- the first student enrolled in 1972. In the 1960s, radioisotope laboratories opened in the general hospitals of Slovenj Gradec and Celje, and in the I 970s also in Maribor. Izola and Šempeter pri Novi Gorici. Conclusions. Nowadays, nuclear medicine units are modernly equipped and the staff is trained in morphological, functional and laboratory diagnostics in c1inical medicine. They also work on the treatment of cancer, increased thyroid function and other diseases.
Objavljeno v DiRROS: 22.03.2024; Ogledov: 69; Prenosov: 39
.pdf Celotno besedilo (552,70 KB)
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Gene immunotherapy of colon carcinoma with IL-2 and IL-12 using gene electrotransfer
Tilen 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: 95; Prenosov: 47
.pdf Celotno besedilo (6,92 MB)
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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 trial
Ana 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: 71; Prenosov: 36
.pdf Celotno besedilo (642,09 KB)
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Triple negative breast cancer : prognostic factors and survival
Tanja Ovčariček, Snježana Frković-Grazio, Erika Matos, Barbara Možina, Simona Borštnar, 2011, izvirni znanstveni članek

Povzetek: Background. Triple negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesteron(PgR) receptors as well as human epidermal growth factor receptor 2 (HER2). Our retrospective analysis addressed prognostic factors for short- and long-term outcomes of patients (pts) with TNBC pts treated in routine clinical practice. Patient and methods.Our retrospective study included 269 TNBC treated at Institute of Oncology Ljubljana between March 2000 and December 2006. The collected data included patientsć, tumoursć and treatmentsć characteristics. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis. Results. The median age ofour patients was 55.3 yrs (23-88.5) and the median follow-up was 5.9 yrs (0.3-9.6). Six (2%) pts experienced local only, 79 (92%) pts distal recurrenceand 66 (24%) died. The predominant localisation of the first relapsewas in visceral organs (70.4%). The 5-year disease-free survival (DFS) for the entire group was 68.2% and the 5-year overall survival (OS) was 74.5%.We found a pattern of high recurrence rate in the first 3 years following the diagnosis and a clear decline in recurrence rate over the next 3years. In the univariate analysis age, nodal status, size and lymphovascular invasion (LVI) were found to have a significant impact on DFS as well as on OS. In the multivariate analysis only age (HR=1.79; 95%CI=1.14-2.82; p=0.012) and nodal status (HR=2.71; 95%CI=1.64-4.46; p<0.001) retained their independent prognostic value for DFS and for OS only the nodal status (HR=2.96; 95%CI=1.51-5.82; p=0.002). (Abstract truncated at 2000 characters)
Objavljeno v DiRROS: 19.03.2024; Ogledov: 92; Prenosov: 30
.pdf Celotno besedilo (536,99 KB)

10.
Influence of geology, hydrogeology, and climate on ground source heat pump distribution in Slovenia and selected European countries
Simona Adrinek, Mitja Janža, Rao Martand Singh, 2024, izvirni znanstveni članek

Povzetek: Shallow geothermal energy (SGE) is a renewable energy that could contribute to the decarbonatization of the heating and cooling sector. SGE is predominantly harnessed through ground source heat pump (GSHP) systems. The choice of which type of GSHP system depends on various factors. Understanding these factors is crucial for optimizing the efficiency of GSHP systems and fostering their implementation. In this paper, we have analysed the spatial distribution of GSHPs in Slovenia. We identified 1073 groundwater and 1122 ground-coupled heat pump systems with a total heat pump capacity of almost 30 MW. We quantitatively assessed the influence of geological, hydrogeological, and climate conditions on their spatial distribution. Using the χ2 test and information value method, we identified hydrogeological conditions as the most influential factor for the GSHP systems’ spatial distribution. We also performed the spatial analysis of geological and hydrogeological data in 22 European countries, including Slovenia. We collected the reported numbers of installed GSHP units in 2020 and were able to distinguish the shares of groundwater and ground-coupled heat pump systems for 12 of these countries. The analysis showed that ground-coupled heat pumps predominate in most countries, even if the natural conditions are favourable for groundwater heat pumps.
Ključne besede: shallow geothermal energy, renewable heating and cooling, ground-source heat pump, spatial distribution, natural condition
Objavljeno v DiRROS: 19.03.2024; Ogledov: 75; Prenosov: 39
.pdf Celotno besedilo (15,39 MB)

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