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1.
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, original scientific article

Abstract: 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.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in RUP: 09.08.2016; Views: 5589; Downloads: 135
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2.
Endoglin (CD105) silencing mediated by shRNA under the control of Endothelin-1 promoter for targeted gene therapy of Melanoma
Nataša Tešić, Urška Kamenšek, Gregor Serša, Simona Kranjc Brezar, Monika Savarin, Urša Lampreht Tratar, Véronique Préat, Gaëlle Vandermeulen, Miha Butinar, Boris Turk, Maja Čemažar, 2015, original scientific article

Abstract: Endoglin (CD105), a transforming growth factor (TGF)-% coreceptor, and endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor endothelial and melanoma cells. Their targeting is therefore a promising therapeutic approach for melanoma tumors. The aim of our study was to construct a eukaryotic expression plasmid encoding the shRNA molecules against CD105 under the control of endothelin-1 promoter and to evaluate its therapeutic potential both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA against CD105 under the control of the constitutive U6 promoter was used as a control. We demonstrated the antiproliferative and antiangiogenic effects of both plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence that targeting melanoma with shRNA molecules against CD105 under the control of endothelin-1 promoter is a feasible and effective treatment, especially for the reduction of metastatic spread.
Keywords: melanoma, electroporation, endoglin (CD105), endothelin-1, gene therapy
Published in RUP: 14.10.2015; Views: 3645; Downloads: 131
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3.
Developmental levels of the child's storytelling
Ljubica Marjanovič Umek, Simona Kranjc, Urška Fekonja, 2002, published scientific conference contribution

Abstract: The purpose of the present study was to explore the development of the child's storytelling, an important ability of the child's pragmatic use of language, within the broader context of the child's language development. Taking into account several already established criteria (e.g. Fein, 1995; Stein, 1997), we defined key elements for evaluating developmental levels of the child's storytelling, specifically in terms of story coherence and cohesion. The coherence of a story refers to its structure and the connection between different parts of the story. The cohesion refers to the construction of the story. The criteria for evaluating the coherence of the child's story were divided into five different developmental levels: 1. a story without a structure; 2. a story with a structure and simple descriptions of the illustrations; 3. a story with a structure and simple temporal ection sequences; 4. a story with a structure and descriptions of the characters' thoughts, emotions or the relations among them; 5. a story with a structure and causal goal-based sequence of events. The criteria for evaluating the coherence of the story were referring to the thematic arrangement (linear arrangement with and without thematic leaps) of the story and the means for preserving the reference (literal repetition and repetition with pronouns). Assuming that children of different ages do not possess the same concept of story, we used the criteria developed in the first part to analyze and compare 45 stories told by four-, six-, and eight-year-old boys and girls. The children were first read a story from a picture book and then asked to retell it freely while looking at pictures in the book. The results show differences among age groups both in story content and structure and as such support the significance of storytelling as an educational method for language development with consideration of the child's developmental abilities.
Keywords: pripovedovanje zgodb, razvojne stopnje, razvojna psihologija, razvoj jezika, starostne razlike
Published in RUP: 15.10.2013; Views: 3921; Downloads: 43
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