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Princess or Heroine? – A Qualitative Analysis on How the Portrayal of Female Characters Has Evolved Between Disney’s Originals Films and its Modern RemakesMeckesheimer, Tonja January 2021 (has links)
No description available.
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ESCAPIST CATHARSIS: REPRESENTATION, OBJECTIFICATION, AND PARODY ON THE PANTOMIME STAGEKallemeyn, Rebecca 25 June 2008 (has links)
No description available.
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Poly(Propylene imine)-based polyplexes for non-viral, targeted delivery of nucleic acids into PSCA-positive tumor cellsJugel, Willi 17 January 2024 (has links)
Delivery of siRNAs for the treatment of tumors critically depends on the development of efficient nucleic acid carrier systems. The complexation of dendritic polymers (dendrimers) results in nanoparticles, called dendriplexes, that protect siRNA from degradation and mediate non-specific cellular uptake of siRNA. However, large siRNA doses are required for in vivo use due to accumulation of the nanoparticles in sinks such as the lung, liver, and spleen. This suggests the exploration of targeted nanoparticles for enhancing tumor cell specificity and achieving higher siRNA levels in tumors. In this work, we report on the targeted delivery of a therapeutic siRNA specific for BIRC5/Survivin in vitro and in vivo to tumor cells expressing the surface marker prostate stem cell antigen (PSCA). For this, polyplexes consisting of single-chain antibody fragments specific for PSCA conjugated to siRNA/maltose-modified poly(propylene imine) dendriplexes were used. These polyplexes were endocytosed by PSCA-positive 293TPSCA/ffLuc and PC3PSCA cells and caused knockdown of reporter gene firefly luciferase and Survivin expression, respectively. In a therapeutic study in PC3PSCA xenograft-bearing mice, significant anti-tumor effects were observed upon systemic administration of the targeted polyplexes. This indicates superior anti-tumor efficacy when employing targeted delivery of Survivin-specific siRNA, based on the additive effects of siRNA-mediated Survivin knockdown in combination with scFv-mediated PSCA inhibition. Among non-viral vectors, cationic polymers, such as poly(propylene imine) (PPI), play also a prominent role in plasmid DNA delivery. However, limitations of polycationic polymer-based DNA delivery systems are (i) insufficient target specificity, (ii) unsatisfactory transgene expression, and (iii) undesired transfer of therapeutic DNA into non-target cells. We developed single-chain antibody fragment (scFv)-directed hybrid polyplexes for targeted gene therapy of prostate stem cell antigen (PSCA)-positive tumors. Besides mono-biotinylated PSCA-specific single-chain antibodies (scFv(AM1-P-BAP)) conjugated to neutravidin, the hybrid polyplexes comprise β cyclodextrin-modified PPI as well as biotin/maltose-modified PPI as carriers for minicircle DNAs encoding for Sleeping Beauty transposase and a transposon encoding the gene of interest. The PSCA-specific hybrid polyplexes efficiently delivered a GFP gene in PSCA-positive tumor cells, whereas control hybrid polyplexes showed low gene transfer efficiency. In an experimental gene therapy approach, targeted transposition of a codon-optimized p53 into p53 deficient HCT116p53-/-/PSCA cells demonstrated decreased clonogenic survival when compared to mock controls. Noteworthily, p53 transposition in PTEN-deficient H4PSCA glioma cells caused nearly complete loss of clonogenic survival. These results demonstrate the feasibility of combining tumor-targeting hybrid polyplexes and Sleeping Beauty gene transposition, which, due to the modular design, can be extended to other target genes and tumor entities.
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Reversing Cancer Cell Fate: Driving Therapeutic Differentiation of Hepatoblastoma to Functional Hepatocyte-Like CellsSmith, Jordan L. 20 March 2020 (has links)
Background & Aims: Despite advances in surgical care and chemotherapeutic regimens, the five-year survival rate for Stage IV Hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. YAP1 and β-Catenin co-activation occurs in 80% of children’s HB; however, a lack of conditional genetic models precludes exploration of tumor maintenance and therapeutic targets. Thus, the clinical need for a targeted therapy remains unmet. Given the predominance of YAP1 and β-catenin activation in children’s tumors, I sought to evaluate YAP1 as a therapeutic target in HB.
Approach & Results: Herein, I engineered the first conditional murine model of HB using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A, constitutive β-CateninDelN90, and a luciferase reporter to murine liver. Tumor regression was evaluated using in vivo bioluminescent imaging, and tumor landscape characterized using RNA sequencing, ATAC sequencing and DNA foot-printing. Here I show that YAP1 withdrawal in mice mediates >90% tumor regression with survival for 230+ days. Mechanistically, YAP1 withdrawal promotes apoptosis in a subset of tumor cells and in remaining cells induces a cell fate switch driving therapeutic differentiation of HB tumors into Ki-67 negative “hbHep cells.” hbHep cells have hepatocyte-like morphology and partially restored mature hepatocyte gene expression. YAP1 withdrawal drives formation of hbHeps by modulating liver differentiation transcription factor (TF) occupancy. Indeed, tumor-derived hbHeps, consistent with their reprogrammed transcriptional landscape, regain partial hepatocyte function and can rescue liver damage in mice.
Conclusions: YAP1 withdrawal, without modulation of oncogenic β-Catenin, significantly regresses hepatoblastoma, providing the first in vivo data to support YAP1 as a therapeutic target for HB. Modulating YAP1 expression alone is sufficient to drive long-term regression in hepatoblastoma because it promotes cell death in a subset of tumor cells and modulates transcription factor occupancy to reverse the fate of residual tumor cells to mimic functional hepatocytes.
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From Snow White to Frozen : An evaluation of popular gender representation indicators applied to Disney’s princess films / Från Snövit till Frost : En utvärdering av populära könsrepresentations-indikatorer tillämpade på Disneys prinsessfilmerNyh, Johan January 2015 (has links)
Simple content analysis methods, such as the Bechdel test and measuring percentage of female talk time or characters, have seen a surge of attention from mainstream media and in social media the last couple of years. Underlying assumptions are generally shared with the gender role socialization model and consequently, an importance is stated, due to a high degree to which impressions from media shape in particular young children’s identification processes. For young girls, the Disney Princesses franchise (with Frozen included) stands out as the number one player commercially as well as in customer awareness. The vertical lineup of Disney princesses spans from the passive and domestic working Snow White in 1937 to independent and super-power wielding princess Elsa in 2013, which makes the line of films an optimal test subject in evaluating above-mentioned simple content analysis methods. As a control, a meta-study has been conducted on previous academic studies on the same range of films. The sampled research, within fields spanning from qualitative content analysis and semiotics to coded content analysis, all come to the same conclusions regarding the general changes over time in representations of female characters. The objective of this thesis is to answer whether or not there is a correlation between these changes and those indicated by the simple content analysis methods, i.e. whether or not the simple popular methods are in general coherence with the more intricate academic methods. / <p>Betyg VG (skala IG-VG)</p>
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