1621. In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]Simona Kranjc Brezar, Maja Čemažar, Gregor Serša, Janez Ščančar, Sabina Grabner, 2017, original scientific article Abstract: Background. Cisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compound trans- [PtCl2(3-Hmpy)2] (3-Hmpy = 3-hydroxymethylpyridine) (compound 2) showed a considerable cytotoxic and antitumour effectiveness. To improve compound 2 cytotoxicity in vitro and antitumour effectiveness in vivo, electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy). Materials and methods. In vitro, survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound 2 or cisplatin electrochemotherapy. In vivo, the antitumour effectiveness of electrochemotherapy with compound 2 or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry. Results. In vitro, cell survival after treatment with compound 2 electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound 2 cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. In vivo, the growth delay of subcutaneous tumours after treatment with compound 2 electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound 2 electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound 2 induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound 2 or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed. Conclusions. The obtained results in vitro and in vivo suggest compound 2 as a potential antitumour agent in electrochemotherapy.
Keywords: platinum analogue, cisplatin, elektroporation, electrochemotherapy, 3-Hmpy
Published in DiRROS: 31.05.2024; Views: 473; Downloads: 195
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1622. Unearthing the soil-borne microbiome of land plantsRaúl Ochoa-Hueso, David J. Eldridge, Miguel Berdugo, Pankaj Trivedi, Blessing Sokoya, Concha Cano-Díaz, Sebastian Abades, Fernando D. Alfaro, Adebola R. Bamigboye, Felipe Bastida, Tine Grebenc, Tina Unuk Nahberger, 2024, original scientific article Abstract: Plant–soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate organisms consistently associated with land plants (i.e., their consistent soil-borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.
Keywords: belowground networks, environmental thresholds, moss microbiome, plant microbiome, plant–soil interactions
Published in DiRROS: 31.05.2024; Views: 447; Downloads: 227
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1623. On some aspects of spectral theory for infinite bounded non-negative matrices in max algebraVladimir Müller, Aljoša Peperko, 2024, original scientific article Abstract: Several spectral radii formulas for infinite bounded non-negative matrices in max algebra are obtained. We also prove some Perron–Frobenius type results for such matrices. In particular, we obtain results on block triangular forms, which are similar to results on Frobenius normal form of $n \times n$ matrices. Some continuity results are also established.
Keywords: non-negative matrices, infinite bounded matrices, max algebra, Bonsall’s cone spectral radius, eigenvalues, continuity
Published in DiRROS: 30.05.2024; Views: 446; Downloads: 314
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1626. International Conference Decade of Decadence: 1914–1924 : spaces, societies and belongings in the Adriatic borderland in historical comparison2024, other monographs and other completed works Abstract: Historians have long come to realize the importance of the World War I as the seminal event leading to a short 20th century. If traditional research has often conceptualized the war and post-war years as two distinct historical periods, new studies have emphasized entangle-ments and intertwinements between war- and post-war processes. This turn was influenced by a gradual geographical balance and the inclusion of Eastern and Central Europe in the re-search focus. Wars, collapse of Empires and long-existing State structures, and similar events brought about processes of redefinition of territories and its peoples. The focus on volatile, overlapping and, at times, competing centers of power (States, national, regional and local structures), will allow us to reconsider criteria and concepts of citizenship and belonging that have shaped European politics of governance. Our conference focuses on the Northern Adri-atic transnational borderland from the beginning of World War I in July 1914 to the Treaty of Rome in January 1924, when the Adriatic question was temporarily settled. This decade is of fundamental importance at the global level, while the Northern Adriatic represents a unique laboratory to study the transformations of Europe in the Twentieth Century. The focus is on the question of citizenship beyond nation-state frameworks and monothematic disciplines, in which the question of citizenship is linked to the migratory movement of people. Taking the Northern Adriatic as a case study, this conference aims at rethinking the questions of citizen-ships, national affiliations, territorial belongings and state sovereignty. This will enable us to contribute to a growing dialogue in international academia and to contemporary societal de-bates at a time, when citizenship and the rights linked to it are the subject of intense discus-sions. We aim at reconsidering rigid understandings of center and periphery and restoring a more composite history of twentieth century Europe.
Published in DiRROS: 29.05.2024; Views: 369; Downloads: 310
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1627. Mechanism of action, potency and efficacy : considerations for cell therapiesCarl G. Simon Jr., Erich H. Bozenhardt, Christina M. Celluzzi, David Dobnik, Melanie L. Grant, Uma Lakshmipathy, Thiana Nebel, 2024, original scientific article Abstract: One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be “potent but not efficacious” or “not potent but efficacious” are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product’s MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs.
Keywords: cell therapy product, efficacy endpoint test, mechanism of action, potency test, metrology
Published in DiRROS: 27.05.2024; Views: 383; Downloads: 339
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1628. Mutual-visibility problems on graphs of diameter twoSerafino Cicerone, Gabriele Di Stefano, Sandi Klavžar, Ismael G. Yero, 2024, original scientific article Abstract: The mutual-visibility problem in a graph $G$ asks for the cardinality of a largest set of vertices $S\subseteq V(G)$ so that for any two vertices $x,y \in S$ there is a shortest $x,y$-path $P$ so that all internal vertices of $P$ are not in $S$. This is also said as $x,y$ are visible with respect to $S$, or $S$-visible for short. Variations of this problem are known, based on the extension of the visibility property of vertices that are in and/or outside $S$. Such variations are called total, outer and dual mutual-visibility problems. This work is focused on studying the corresponding four visibility parameters in graphs of diameter two, throughout showing bounds and/or closed formulae for these parameters. The mutual-visibility problem in the Cartesian product of two complete graphs is equivalent to (an instance of) the celebrated Zarankiewicz's problem. Here we study the dual and outer mutual-visibility problem for the Cartesian product of two complete graphs and all the mutual-visibility problems for the direct product of such graphs as well. We also study all the mutual-visibility problems for the line graphs of complete and complete bipartite graphs. As a consequence of this study, we present several relationships between the mentioned problems and some instances of the classical Turán problem. Moreover, we study the visibility problems for cographs and several non-trivial diameter-two graphs of minimum size.
Keywords: mutual-visibility set, mutual-visibility number, diameter-two graphs, line graphs, cographs
Published in DiRROS: 27.05.2024; Views: 451; Downloads: 309
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1629. Health-related quality of life assessed by the EORTC QLQ-C30 questionnaire in the general Slovenian populationVaneja Velenik, Ajra Šečerov Ermenc, Jasna But-Hadžić, Vesna Zadnik, 2017, original scientific article Abstract: The aim of our study was to obtain reference data of the EORTC QLQ-C30 quality of life dimensions for the general Slovenian population. We intend to provide the researchers and clinicians in our country with the expected mean health-related quality of life (HRQL) scores for distinctive socio-demographic population groups. Methods. The EORTC QLQ-C30 questionnaire supplemented by a socio-demographic inquiry was mailed or distributed to 1,685 randomly selected individuals in the Slovenian population aged 18 % 90. Answers from 1,231 subjects representing socio-demographic diversity of the Slovenian population were collected and transformed into EORTC dimensions and symptoms. The impact of socio-demographic features on HRQL scores was assessed by multiple linear regression models. Results. Gender, age and self-rated social class are the important confounders in the quality of life scores in our population. Men reported better quality of life on the majority of the specific scales and, at the same time, reported fewer symptoms. There was no gender-specific difference in cognitive functioning. The mean scores were consistently lower with age in both sexes. Conclusions. This is the first study to report the normative EORTC QLQ-C30 scores for one of the south-eastern European populations. The reported expected mean scores allow Slovenian oncologists to estimate what the quality of life in cancer patients would be, had they not been ill. As they are derived by common methodology, our results can easily be included in any further international comparisons or in the calculation of European summarized HRQL scores.
Published in DiRROS: 24.05.2024; Views: 383; Downloads: 202
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1630. Treatment-related cardiovascular toxicity in long-term survivors of testicular cancerJasenka Gugić Kevo, Lorna Zadravec-Zaletel, Irena Oblak, 2017, review article Abstract: Testicular cancer is the most common malignancy in young men. Considering increasing incidence, exceptionally high cure rate, as well as long life expectancy, assessment of long term toxicity in testicular cancer survivors is of great importance. In the last decades a major effort has been made in order to reduce toxicity of treatment, while maintaining its high effectiveness. Conclusions Actual knowledge on treatment toxicity is based on outdated treatment modalities. Hopefully, modern treatment modalities could reduce toxicity, but, there is no firm confirmation for that at the moment, as data dealing with late sequelae of modern treatment of testicular cancer are not available yet due to the short period of observation. The life-threatening cardiovascular toxicity in testicular cancer survivors is major complication of platinum-based chemotherapy, mediastinal radiotherapy and even subdiaphragmatic radiotherapy.
Keywords: testicular cancer, cardiovascular toxicity, long-term survivors
Published in DiRROS: 24.05.2024; Views: 509; Downloads: 225
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