1. Effect of tirzepatide-induced weight loss on adipose tissue in obesity : rationale and design of the randomized placebo-controlled Tirzepatide Brown and Beige Adipose Tissue Activation (TABFAT) trialRok Herman, Mojca Jensterle Sever, Simon Horvat, Luka Ležaič, Žiga Snoj, Igor Pušnik, Katja Goričar, Andrej Cör, Luka Pušnik, Vid Mlačnik, Lara Hanželič, Andrej Janež, 2025, izvirni znanstveni članek Povzetek: Background Obesity is a complex disease marked by excessive, dysfunctional adipose tissue accumulation. Recent research underscores the pivotal role of brown adipose tissue (BAT) in metabolic health and its potential as a thera- peutic target for obesity management. Emerging preclinical and clinical evidence suggests that second-generation anti-obesity drugs, especially dual agonists such as tirzepatide, may enhance BAT activity. Additionally, beige adipose tissue, derived from white adipose tissue (WAT), may contribute significantly to whole-body thermogenesis, yet its role remains underexplored. Methods This investigator-initiated, randomized, placebo-controlled clinical trial aims to evaluate the effects of tirzepatide on BAT activity and WAT browning in premenopausal women with obesity. Thirty-four participants will be randomized 1:1 to receive either tirzepatide or a placebo for 24 weeks. Primary outcomes include changes in BAT volume and activity, assessed using 18F-FDG-PET/CT, MRI, and infrared thermography, as well as the induction of WAT browning, evaluated through changes in mRNA expression patterns and histomorphometric alterations in subcuta- neous adipose tissue samples. Secondary outcomes will involve the assessment of whole-body composition, resting energy expenditure, and various metabolic health markers, correlated with thermogenic adipose tissue changes. Comparative analysis of BAT assessment methods will refine protocols for research and clinical use. Discussion This study is the first to systematically explore the potential of pharmacological obesity management to enhance BAT activity and induce WAT browning. Results may establish thermogenic adipose tissue augmentation as a novel mechanism of action for second-generation anti-obesity medications.
Ključne besede: brown adipose tissue, beige adipose tissue, pancreas resection, tirzepatide, obesity
Objavljeno v DiRROS: 26.11.2025; Ogledov: 144; Prenosov: 90
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2. DED-LB manufactured Ti–6Al–4V–4Cu alloy : materials development, characterization, and in vivo biocompatibilityAndrej Jeromen, Anish Nair, Peter Rodič, Denis Sačer, Barbara Kapun, Maša Čater, Ana Brunčić, Katarina Kozlica, Radmila Milačič Ščančar, Andrej Cör, Edvard Govekar, Ingrid Milošev, Simon Horvat, 2025, izvirni znanstveni članek Ključne besede: Ti–6Al–4V–4Cu alloy, additive manufacturing, laser-based directed energy deposition (DED-LB), microstructure and phase analyses, corrosion, in vivo biocompatibility
Objavljeno v DiRROS: 10.11.2025; Ogledov: 216; Prenosov: 91
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4. Molecular heterogeneity in breast carcinoma cells with increased invasive capacitiesGiulia Negro, Bertram Aschenbrenner, Simona Kranjc Brezar, Maja Čemažar, Andrej Cör, Gorana Gašljević, Maxim Sorokin, Anton A. Buzdin, Maurizio Callari, Irma Kvitsaridze, 2020, izvirni znanstveni članek Povzetek: Metastatic progression of breast cancer is still a challenge in clinical oncology. Therefore, an elucidation how carcinoma cells belonging to different breast cancer subtypes realize their metastatic capacities is needed. The aim of this study was to elucidate a similarity of activated molecular pathways underlying an enhancement of invasiveness of carcinoma cells belonging to different breast carcinoma subtypes. Materials and methods. In order to reach this aim, parental and invasive (INV) MDA-MB-231 (triple-negative), T47D (hormone receptor-positive), and Au565 (Her2-positive) breast carcinoma cells were used and their molecular phenotypes were compared using a proteomic approach. Results. Independently from breast cancer subtypes, INV cells have demonstrated fibroblast-like morphology accompanied by enhancement of invasive and migratory capacities, increased expression of cancer stem cell markers, and delayed tumor growth in in vivo animal models. However, the global proteomic analysis has highlighted that INV cells were different in protein expressions from the parental cells, and Her2-positive Au565-INV cells showed the most pronounced molecular differences compared to the triple-negative MDA-MB-231-INV and hormone receptor-positive T47D-INV cells. Although Au565-INV breast carcinoma cells possessed the highest number of deregulated proteins, they had the lowest overlapping in proteins commonly expressed in MDA-MB-231-INV and T47D-INV cells. Conclusions. We can conclude that hormone receptor-positive cells with increased invasiveness acquire the molecular characteristics of triple-negative breast cancer cells, whereas Her2-positive INV cells specifically changed their own molecular phenotype with very limited partaking in the involved pathways found in the MDA-MB-231-INV and T47D-INV cells. Since hormone receptor-positive invasive cells share their molecular properties with triple-negative breast cancer cells, we assume that these types of metastatic disease can be treated rather equally with an option to add anti-hormonal agents. In contrast, Her2-positive metastasis should be carefully evaluated for more effective therapeutic approaches which are distinct from the triple-negative and hormone-positive metastatic breast cancers.
Ključne besede: breast cancer, cancer stem cells, invasiveness, migration, metastasis
Objavljeno v DiRROS: 11.07.2024; Ogledov: 1266; Prenosov: 430
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5. Adjuvant TNF-a therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectivenessMaja 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: 1493; Prenosov: 403
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6. Electrogene therapy with interleukin-12 in canine mast cell tumorsDarja Pavlin, Maja Čemažar, Andrej Cör, Gregor Serša, Azra Pogačnik, Nataša Tozon, 2011, izvirni znanstveni članek Ključne besede: psi, tumor, zdravljenje, elektrogenska terapija, plazmidi
Objavljeno v DiRROS: 19.03.2024; Ogledov: 1089; Prenosov: 381
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9. Detection of apoptotic cells in tumour paraffin sectionsJože Pižem, Andrej Cör, 2003, strokovni članek Povzetek: Apoptosis is a distinct form of cell death characterised by specific morphological features and regulated by complex molecular mechanisms. Its deregulation is fundamental for tumour growth and progression and, moreover, anticancer therapies suppress tumour growth mainly by induction of apoptosis. Since the extent of apoptosis in a tumour may have prognostic as well as therapeutic implications, much effort has been invested in developing specificmethods that can be routinely used to detect apoptotic cells in archival formalin fixed paraffin-embedded tissue. Complex molecular pathways are involved in the regulation of apoptosis. Pro-apoptotic signals trigger activation of caspases that specifically cleave target proteins. Cleavage of proteins (caspase substrates) is responsible for morphological changes of apoptotic cells and DNA fragmentation. In the last decade, detection of apoptotic cells in formalin fixed tumour tissue sections has been based mainlyon morphology and characteristic DNA fragmentation. Recently, specific antibodies to activated caspases and cleaved target proteins (including cytokeratin 18, actin and PARP) have been produced that enable accurate detection of apoptosis in paraffin sections.
Objavljeno v DiRROS: 06.02.2024; Ogledov: 1435; Prenosov: 298
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10. Survivin - an inhibitor of apoptosis and a new therapeutic target in cancerJože Pižem, Andrej Cör, 2003, strokovni članek Povzetek: Survivin is a unique member of the inhibitor of apoptosis (IAP) protein family. It inhibits apoptosis by interfering with post-mitochondrial events during apoptosis, thus blocking activation of caspases. The expression of survivin is among the most tumour specific of all human genes. It is overexpressed in most human cancers but is not detected in most normal tissues. Some molecular mechanisms of survivin upregulation in cancer have been elucidated, including loss of the wild-type p53. Tumours that overexpresssurvivin generally bear a worse prognosis and are associated with resistance to therapy. Its differential expression in caneer versus normal tissues makes survivin detection a useful tool in cancer diagnostics and a promising therapeutic target. Survivin targeting has resulted in increased spontaneous and induced apoptosis and inhibition of tumourgrowth. Some anticaneer drugs currently introduced into clinical practice might well act byinactivaring survivin.
Objavljeno v DiRROS: 06.02.2024; Ogledov: 1101; Prenosov: 295
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