Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy (Chem) treatment suggesting the need for advanced methods to assist with the early diagnosis and treatment. However, the newest methods combine cytoreductive surgery with hyperthermic intraperitoneal Chem (HIPEC), which uses mild hyperthermia (Hyp) by circulation of a hot fluid to boost the diffusion and cytotoxic effect of drugs. A recent development in patients with unresectable PM is pressurized intraperitoneal aerosol Chem (PIPAC) that combines a diagnostic laparoscopy with locoregional administration of Chem as an aerosol. Non-selective biodistribution, low bioavailability, high drug concentrations, limited drug circulation time, and various side-effects limit the utilisation of HIPEC and PIPAC. Innovative drug delivery system with the controlled drug release at tumour site can enhance the therapeutic efficacy. Utilisation of nanoparticles (NPs) as carriers to deliver drugs with the possibility of tagging them with targeting agents will overcome the off-site toxicity. Cyto/hemocompatible magnetic hybrid NPs (Silver sulphide-Iron oxide) with luminescence in the near-infrared region for combinational therapy of peritoneal metastasis (SANTE) project aims to develop multimodal therapy approach for diagnosis and treatment of PM. It intends to enhance the efficacy of PM treatment using a combination of image guided remotely activated nanoHyp coupled with targeted Chem. Tumour targeted Ag2S will allow preoperative detection of microscopic or residual tumours to improve resection before Chem/Hyp. Iron oxide, targeting agent(cetuximab), and the chemotherapeutic drug(cisplatin) are all clinically used for the treatment of various type of cancers. The result of this fellowship will enable scientists in the PM field to translate the novel diagnostic and therapeutic methods into clinical practice and market.a
Ischemic stroke is the second cause of death worldwide. Recombinant tissue plasminogen activator (rtPA) is the only approved therapeutic agent. However, stroke patients often suffer from hemorrhages caused by oxidative stress, leading to high immobility rates. The project conducted at Université Paris Cité is at the cross-section of material science and nanomedicine. It aims to develop a nanomedicine for clot targeting, dissolution, and antioxidant therapy to treat ischemic stroke against oxidative stress. Combining the robust antioxidant activity of the cerium oxide nanoparticles (CeNPs) with the clinical-proven rtPA as a delivery vector, the novel nanomedicine will find its potential application for the care of stroke patients and beyond. CeNPs will be optimized to achieve the maximum antioxidant activity. It will be assembled with polymers and rtPA to preserve circulation time and delivery efficiency. The nanoassembly will be evaluated against oxidative stress and clot dissolution efficiency. The project combines the Researcher's experiences in developing advanced nanomaterials and the hosts' expertise in translating nanomaterials from synthesis to preclinical studies. The project targets treating non-communicable diseases, relevant to the Health pillar of the Horizon Europe programme and the emphasis on developing Advanced Materials by European Commission. It shows a great impact in helping people suffering from the high risks of already approved medication. The project will enable the Researcher to acquire professional maturity related to nanomedicine development. The dissemination of results producing multiple publications in peer-reviewed journals, talks at scientific meetings, and outreach to the general public about the development of the novel antioxidant-related stroke treatment is very probable with the completion of this project. It also creates a potential platform for the scaling process of nanomedicine through collaboration with industrial partners.
The following project, SMiPAX4, conducted in the academic group of Jean-Philippe Herbeuval (Univeristy of Paris, France), is at the cross section of immunology and pharmacology. Moreover, due to its direct application potential and the subsequent industrial placement at Ermium Therapeutics it is also cross sectional between academia and industry. The main objective of the project is to understand the mode of action of small molecules, functionally causing a reduction of immune response, binding into the minor binding pocket of the G protein coupled receptor CXCR4. The signalling cascade as well as the implication of different expression levels of the target CXCR4 will be explored through different biochemical techniques and finalised by the establishing of a medium to high-throughput screening assay. Protein-protein interactions will be identified using Bioluminescence energy transfer (BRET) techniques, increase or decrease of second messenger molecules will be identified using biosensors, and phosphorylation states, up- or downregulation of (signalling) proteins will be measured using flow cytometry or western blotting. Inflammation of cells when controlling the impact of silencing certain signalling molecules will be controlled by measuring the levels of inflammation markers. Due to the projects implication in (auto)immune and other inflammation diseases it is relevant for cluster 1, Health, of the Horizon Europe programme. The project shows great potential in the area of impact due to its unique target potentially helping people that do not respond well to already approved medication. Both, the dissemination of results producing multiple publications in peer reviewed journals, talks and posters at scientific meetings as well as the potential of creating market within the EU are very probable with completion of this project.
Comparative effectiveness research (CER) has recently emerged as a key component of health care decision-making, specifically designed to provide evidence of the effectiveness of different health care treatments. The latter are becoming increasingly complex, and there is now intense interest in deploying advanced statistical tools to study and guide the development of such complex systems. Complex interventions might also involve interactions through time, where actions in the past affect the future decision making context. In this case, the temporal dimension should be taken into account into the statistical model, yielding in turn more precise guidelines for health care decision-making. However, current CER methodologies are not well-suited to understand such complex systems or characterise their future behaviour. Statistical methods based on dynamic modelling are therefore needed to advance progress of the state-of-the art of CER research. In particular, this fellowship will tackle the problem by developing novel statistical methodologies for the study of the temporal dynamics of complex health care interventions, both for primary research and evidence synthesis. For primary research, the fellowship will explore the emerging case of pervasive and technology-based interventions, which are by nature dynamic. For evidence synthesis - which is the procedure of summarising evidence from different primary studies of a specific health condition - the innovative tool of network meta-analysis will be deployed and an extension for dynamically monitoring and updating the results of existing network meta-analyses will be developed.
This proposal develops in the framework of applications of set theory to C*-algebras and it is organized into three main themes: (1) the set-theoretic study of the Calkin algebra, (2) Naimark's problem, (3) the Stone-Weierstrass problem for noncommutative C*-algebras. The first part of the project consists of a systematic analysis of the class of the C*-algebras which embed into the Calkin algebra and of how set-theoretic principles influence such class. This study will be achieved by means of forcing techniques and through the adaptation of methods coming from the framework of boolean algebras. The main objectives are to reach a deeper understanding of the structure of the Calkin algebra, and to provide a benchmark for future applications of forcing methods in a more abstract C*-algebraic context. The second part of the proposal is in continuity with the line of research opened by Akemann and Weaver in the study of Naimark's problem, and it involves a series of applications of set-theoretic combinatorial statements in the construction of nonseparable C*-algebras with peculiar properties, specifically for what concerns their representation theory. With these investigations we aim to extend, by means of set theory, the current knowledge on the discrepancies between the nonseparable and the separable framework in operator algebras. The last part of the project regards the Stone-Weierstrass problem for noncommutative C*-algebras, an old open question which asks whether the classical Stone-Weierstrass theorem can be generalized to all C*-algebras. We plan to study this topic using set-theoretic methods, with the objective to find new consistency results, and extend to the nonseparable setting the known theorems holding for separable C*-algebras.