Harnessing the cellular and molecular complexity of high-risk neuroblastoma to investigate novel potential treatment approaches

Neuroblastoma (NB) is the most common type of tumor in infants and the third most common cancer in children. Current clinical practices employ a variety of strategies for NB treatment, ranging from standard chemotherapy to immunotherapy. Due to a lack of knowledge about the molecular mechanisms underlying the disease's onset, aggressive phenotype, and therapeutic resistance, these approaches are ineffective in the majority of instances. MYCN amplification is one of the most well-known genetic alterations associated with high risk in NB. The following work is divided into three sections and aims to provide new insights into the biology of NB and hypothetical new treatment strategies. First, we identified RUNX1T1 as a key gene involved in MYCN-driven NB onset in a transgenic mouse model. Our results suggested that that RUNX1T1 may recruit the Co-REST complex on target genes that regulate the differentiation of NB cells and that the interaction with RCOR3 is essential. Second, we provided insights into the role of MYCN in dysregulating the CDK/RB/E2F pathway controlling the G1/S transition of the cell cycle. We found that RB is dispensable in regulating MYCN amplified NB's cell cycle, providing the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression. Third, we generated an M13 bacteriophage platform to target GD2-expressing cells in NB. Here, we generated a recombinant M13 phage capable of binding GD2-expressing cells selectively (M13GD2). Our results showed that M13GD2 chemically conjugated with the photosensitizer ECB04 preserves the retargeting capability, inducing cell death even at picomolar concentrations upon light irradiation. These results provided proof of concept for M13 phage employment in targeted photodynamic therapy for NB, an exciting strategy to overcome resistance to classical immunotherapy.

Fresh Produce Safety and Good Agricultural Practices: Stakeholders' Perception and Consumers' Choice in Thailand

Concerns of Thai consumers on food safety have been recently increasing, especially in urban areas and for fresh produce because food safety scandals, such as chemical residues on fresh produce (e.g., cabbage) still frequently occur. The Thai government tried to meet consumer needs by imposing in the domestic market a stronger regulation aimed at increasing the baseline level of food safety assurance and by introducing a voluntary standard (based on Good Agricultural Practices or GAPs and known as Q-GAP) and the related food safety label (i.e., Q mark). However, since standards and regulations are weakly implemented in the domestic market compared to exported products, there is still a lack of Thai consumers’ confidence in the safety of local food products. In this work the current situation of GAPs adoption in Thai fresh produce production is analysed. Furthermore, it is studied whether Thai consumers place value on food safety labels available on the market, to know whether consumer demand could drive the market of certified safer products. This study contains three essays: 1) a review of the literature, 2) a qualitative study on stakeholders' perception toward GAPs adoption and 3) a quantitative study, aimed at analysing consumers' preferences and willingness-to-pay for food safety labels on fresh produce using a discrete choice experiment. This dissertation contributes to the economics of quality assurance and labelling, specifically addressing GAPs and food safety label in the fresh produce supply chain. Results show that Q-GAP could be effectively used to improve food safety in Thai domestic market, but its credibility should be improved. Stakeholder’s awareness toward food safety issues and the delivery of reliable and sound information are crucial. Thai consumers are willing to pay a premium price for food safety labelled produce over unlabelled ones. Implications for both government and business decision-makers are discussed.

Towards the Enabling City: Intermediate Places between Practices and Planning for Social Innovation in Bologna

The research investigates the interaction between social innovation practices and urban planning, assuming as a case study and field of application the city of Bologna, observed from the point of view of the production of urban policies and with respect to the places where it is practiced. Social innovation are localised actions tackling current urban complexities with micro-scale practices of service and urban production, by which new urban actors find answers to social needs, which are less afforded by the market and the public sectors. Planning and social innovation practices are two dimensions working in the city in different but complementary ways, subject to a mismatch. Through the lenses of interaction, the research explores the context of Bologna, a paradigmatic study and application field, a laboratory of innovative policies where a tradition of collective civic initiatives intertwines with a more responsible institutional planning framework. After drawing from area-based policies of Berlin and Barcelona, the thesis reads the role of specific intermediate places, mediators in bridging the level of institutions and the practices. Through an inventory and a cross-cutting taxonomy of intermediate places, the research draws the knowledge to inform a new urban model for the city of Bologna, aimed at overtake the mismatches by enabling the practices to act, allowing urban planning to frame them in a cross-fertilisation dimension. The proposed urban diagrammatic model, foresees intermediate places as local socio-urban observatories for research and development, interacting with both institutions and communities. The goal is to critically explore the limits and widen the meaning of the capacity of action of social innovation practices engaging in mutual-learning with the city. The model suggests a new possibility for reflection on urban planning as a more flexible approach, which translates the numerous experiences of the city into alternatives and multiple visions.