ITQB: ACM-MA Dissertations
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- A 3D hepatic model to address immune‐mediated drug hepatotoxicityPublication . Oliveira, Jhenifer"The liver is a complex organ involved in many important physiological functions. Several hepatic diseases, such as alcohol-related liver disease and drug-induced hepatotoxicity, are associated with liver inflammation. Thus, it is of extreme relevance to understand the mechanisms involved in liver inflammation to develop the best strategies to fight these diseases. The hepatic macrophages, resident Kupffer cells and monocyte-derived macrophages, are known to play a critical role in the liver inflammatory response. Although the diversity of experimental models available to address hepatic diseases has been growing, there is still a need for models that can depict the contribution of macrophages to the inflammatory response upon injury.(...)"
- Pre-Clinical Evaluation of Targeted Therapies Using 3D Cell Models of Breast CancerPublication . Trindade, Gonçalo"Breast cancer (BC) is the most frequent malignancy and the deadliest cancer death in women. It is a heterogeneous disease characterized by high variability in tumor morphology, molecular characteristics, and clinical response. Development of targeted therapies has revolutionized cancer treatment; however, these therapies are associated with increased resistance. Development of novel therapies often fails due to lack of representation of the tumor microenvironment (TME), revealing the need for recapitulative models.(...)"
- Exploring induced pluripotent stem cell derived 3D neural cultures to model Mucopolysaccharidosis type VIIPublication . Painho, Beatriz; Brito, Catarina; Terasso, Ana Paula"Mucopolysaccharidosis type VII (MPSVII) is an ultra-rare lysosomal storage disease, occurring due to mutations in the gene encoding β-glucuronidase, one of the enzymes responsible for the step-wise degradation of glycosaminoglycans. Enzyme deficiency leads to intralysosomal accumulation of partially degraded glycosaminoglycans in many tissues, including the brain. Currently, the link between endosomal-lysosomal system dysfunction and neurological symptoms remains unclear.(...)"
- Towards the development of a 3D cell model to study interactions between glioma cells and microgliaPublication . de Castro Sobral, Francisco"Gliomas are central nervous system tumors with glial origin. A subset of aggressive, highgrade gliomas, which includes glioblastoma (GBM) and several pediatric gliomas, is characterized by immunosuppressive tumor microenvironments (TMEs). These immunosuppressive TMEs were recently associated with increased tumorigenicity and reduced effectiveness of immunotherapies. The molecular crosstalk between cancer and non-cancer cells (e.g., microglia, astrocytes) establishes and sustains the immunosuppressive TME. However, the molecular mechanisms underlying immunosuppression in different glioma subtypes are not well described, mainly due to the lack of adequate experimental models to address them. Most glioma cell models fail to include the different cell types of the TME. (...)"
- Exploring Tumor Macrophage Interaction in Anaplastic Thyroid CancerPublication . Eduardo, Rodrigo"Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, with very high mortality rate. Tumor-associated macrophages (TAMs) can represent up to 70% of ATC’s tumor mass, making them an interesting target for novel therapies. In this thesis, the aim was to further understand the crosstalk between ATC and TAMs. To achieve that, cell surface proteomics of two ATC cell lines (C3948 and T235), in mono- or co-culture with THP-1-derived macrophage-like cells, was performed. The protein Spry-4, an inhibitor of the MAPK-ERK pathway, was found to be downregulated in C3948 cells upon co-culture. Spry-4 protein levels were further evaluated by Western blot; only T235 in co-culture showed a trend for downregulation, although without statistical significance.(...)"
- Patient-derived explant cultures for cancer modellingPublication . Teixeira, Marta Carolina Jesus"Cancer remains one of the deadliest diseases in the world. The process of drug discovery to find new drugs for oncology treatment takes more than a decade of research and it is associated with high attrition rates during clinical trials. One of the most common reasons claimed for the poor efficiency of new developed drugs is the lack of physiological relevance of the in vitro models used to select the novel compounds and to evaluate their potency. The role of tumor microenvironment on tumor progression and drug sensitivity is being increasingly studied and it is expected to provide significant clues for the development of novel therapies. Therefore, the incorporation of microenvironment features on cancer cell models during pre- clinical stages of research has the potential to improve significantly their predictive value. (...)"