Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 31 for “"Settore MEDS-02/A - Patologia generale"”.
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LINKING TRANSCRIPTIONAL AND MORPHOLOGICAL HETEROGENEITY TO THERAPEUTIC VULNERABILITIES IN GLIOBLASTOMA
This thesis is the result of my doctoral studies conducted within the Iorio Laboratory at Human Technopole and whose overarching goal has been to design and use data-driven approaches for the integration of molecular and functional-genetics data from preclinical models with the aim of prioritizing …
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Targeting LGALS3 to treat steatotic liver disease and hepatocarcinogenesis
Non-alcoholic fatty liver disease (NAFLD), recently renamed as Metabolic dysfunction-associated steatotic liver disease (MASLD), is the leading cause of chronic liver disease (CLD) and liver-related morbidity and mortality worldwide. NAFLD, characterized by hepatic fat accumulation and coexisting …
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A NOVEL, RAS-INDEPENDENT ROLE FOR NF1 IN MICROTUBULE DYNAMICS AND DAMAGE REPAIR DICTATES SENSITIVITY TO T-DM1 IN HER2 POSITIVE BREAST CANCER.
Neurofibromatosis 1 (NF1) is among the first tumor suppressor genes to be cloned. Loss-of-function (LoF) mutations in NF1 are at the basis of the onco-developmental syndrome Neurofibromatosis type 1 and are frequently found at the somatic level across multiple tumors. In breast cancer, NF1 LoF has …
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TARGETING TYPE-I PRMTS RESTORES PLATINUM SENSITIVITY IN OVARIAN CARCINOMA THROUGH MITOCHONDRIAL METABOLISM
… arginine methyltransferases (PRMTs) with MS023 re-sensitizes A2780R cells to carboplatin, reducing IC50 by up to 56%, and abrogates the enhanced mitochondrial activity. MS023 treatment induces depolarization of the mitochondrial membrane, diminishes mitochondrial volume and network …
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THE ROLE OF EXTRACELLULAR VESICLES IN HEART DISEASES
… HFrEF, and HFpEF. HCM diagnosis followed the 2023 ESC criteria, including cardiac imaging, clinical assessment, and genetic screening using next-generation sequencing of 54 sarcomere-related genes. Echocardiographic imaging was performed to assess structural and functional parameters in all …
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DISSECTING THE ROLE OF GOLGI TRAFFIC IN BRAIN DEVELOPMENT ACROSS HEALTH AND DISEASE: A LESSON FROM COG5-CDG STUDIES
Neurons forming the neocortex are generated during embryonic development from two main classes of neural progenitor cells: apical and basal progenitors (APs and BPs, respectively). The cell fate switch from AP to BP is accompanied by changes in polarization and intracellular architecture. …
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ROLE OF A SPECIFIC NANOG SUPER-ENHANCER ERNA IN EPIGENETIC REMODELING AND ENHANCER-PROMOTER INTERACTION
During last years, the role of enhancer RNAs has been in part explored; however, it’s still not clear the exact role these transcripts carry out concerning gene regulation. In this work, the role of eRNAs transcribed from the region 5kb upper the TSS of Nanog gene in mESCs has been investigated. In …
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EXPLORING THE MUTATIONAL LANDSCAPE OF MITOCHONDRIAL GENOME IN HEMATOLOGIC MALIGNANCIES
Mitochondria are key regulators of energy metabolism, apoptosis, and redox signaling, and their genome (mtDNA) is particularly vulnerable to genomic alterations due to its proximity to the respiratory chain, lack of protective histones, and limited repair capacity. Although mtDNA mutations have …
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ENDOCYTIC CONTROL OF CELL-AUTONOMOUS AND NON-CELL-AUTONOMOUS FUNCTIONS OF P53
NUMB is a multifunctional adaptor protein historically recognized for its role in determining cell fate decisions through inhibition of NOTCH signaling, a process achieved via endocytic trafficking. Subsequently, NUMB has emerged as a significant tumor suppressor, particularly in the context of …
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A SEARCH FOR EPIGENETIC VULNERABILITIES OF AML CELLS PERFORMED BY A CDK INHIBITOR¿BASED CRISPR SCREENING
Acute myeloid leukemia is an aggressive hematologic malignancy characterized by uncontrolled proliferation and impaired differentiation of hematopoietic progenitors. Epigenetic dysregulation plays a central role in AML pathogenesis, and targeting chromatin-modifying enzymes has emerged as a …
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ASSESSING PREDICTIVE MODELING APPROACHES FOR OPTIMIZING THERAPY IN ADVANCED LARYNGEAL AND HYPOPHARYNGEAL CANCERS
Background: Laryngeal (LC) and hypopharyngeal (HPC) cancers are often diagnosed at an advanced stage (III or IV) due to the absence of early symptoms and biomarkers. First-line therapies include both surgical and non-surgical approaches. Since surgical removal, comprising total and partial …
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ELUCIDATING THE IMPACT OF ASCITES ON HIGH GRADE SEROUS OVARIAN CANCER THROUGH MULTIPLE IN VITRO PATIENT-SPECIFIC MODELS
High-grade serous ovarian cancer (HGSOC) is a highly heterogeneous and aggressive malignancy characterized by marked inter-/intra-tumor variability and a dynamic tumor microenvironment (TME). The TME, and particularly ascitic fluid (AF), plays a critical role in OC progression by influencing tumor …
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INSIGHTS INTO THE SELECTION AND FUNCTION OF COPY-NUMBER ALTERATIONS DURING CANCER EVOLUTION
Cancer evolution is a complex process mostly driven by genomic instability, including large- and small-scale alterations, such as copy-number alterations (CNAs) or single-nucleotide mutations, respectively. Those alterations play a critical role in tumor development, genetic diversity, and …
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DISSECTING THE ROLE OF THE TETRASPANIN MS4A4A IN MODULATING MACROPHAGE PLASTICITY AND FUNCTION
MS4A4A belongs to the membrane-spanning 4A (MS4A) family, whose proteins show preferential expression in distinct cell types and structural similarities to tetraspanins, including the ability to interact with and modulate the activity of various immunoreceptors, such as pattern recognition …
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DISSECTION OF HOST-VIRUS INTERACTIONS IN THE HUMAN CENTRAL NERVOUS SYSTEM
Viral encephalitis is an inflammatory brain that can lead to severe neurological deficits, despite antiviral treatment. Neurotropic viruses cause viral encephalitis due to their ability to invade the central nervous system (CNS), and the most common cause is HSV-1. Inborn errors of immunity (IEIs) …
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LARGE-SCALE METAGENOMIC ANALYSIS TO IDENTIFY HUMAN GUT MICROBIOME BIOMARKERS OF CARDIOMETABOLIC HEALTH
The human gut microbiome, a complex community of microorganisms inhabiting the human gastrointestinal tract, is recognized as a critical modulator of host physiology. Imbalances in its composition have been linked with a range of human diseases, including cardiometabolic disorders. Diet is both a …
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EVALUATION OF THE RISK OF SECONDARY LEUKEMIAS IN CANCER SURVIVORS
Therapy-related myeloid neoplasms (t-MNs) are severe late complications of chemotherapy and/or radiotherapy in cancer survivors, characterized by dismal prognosis and resistance to treatment. Chemotherapy may also play a role in increasing clonal hematopoiesis (CH), a clinical entity associated …
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EXPLORING THE PRE-LEUKEMIC PHASE OF ACUTE PROMYELOCYTIC LEUKEMIA: INSIGHTS FROM STUDIES OF SINGLE CELL ¿OMICS¿
Acute Promyelocytic Leukemia (APL) is a distinct subtype of Acute Myeloid Leukemia (AML) driven by the oncogenic fusion protein PML-RAR, which acts as an aberrant transcription factor and blocks myeloid maturation at the promyelocyte stage. In vivo, the expression of PML-RAR is necessary but not …
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MULTI-ORGAN FAILURE DRIVEN BY TELOMERE UNCAPPING
The telomere-bound shelterin complex safeguards chromosome ends from being recognized as DNA double-strand breaks, a function mostly dependent on TRF2. Loss of TRF2 results in telomere uncapping, activation of the DNA damage response, and chromosomal end-to-end fusions, with dramatic consequences …
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