The role of complement in pancreatic cancer: from complement activation triggering and effector mechanism/s to combination with therapy

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Although the complement system has long been considered a component of immune surveillance, accumulating evidence indicates its pro-tumoral role in several cancer types. In this thesis, we explored the contribution of complement activation to PDAC progression using preclinical pancreatic tumor models and animals deficient for C3-upstream (C1q-/-, C4-/-, MBL1/2-/-, fB-...

Studio focalizzato sulla MAPK pathway e sull'intorno molecolare di KRASG12D nel cancro al colon attraverso l'utilizzo di organoidi derivanti da pazienti per il trattamento personalizzato

Il cancro al colon (CRC) comprende una famiglia complessa di tumori diversi per morfologia, infiltrazione del sistema immunitario, risposta ai farmaci e mutazioni genetiche, tra cui APC/KRAS/TP53/SMAD4. Le mutazioni nell'oncogene KRAS, soprattutto ai codoni 12 e 13, sono associate all'inizio e alla progressione del CRC, ma mancano in clinica di trattamenti bersaglio-specifici. Gli organoidi derivanti da pazienti (PDOs) sono stati dimostrati una nuova tecnologia di modello in vitro 3D utilizza...

Response prediction and mutation profiling by circulating tumor DNA (ctDNA) of Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) patients receiving Glofitamab

Diffuse Large B-cell Lymphoma (DLBCL) represents the most common subtype of aggressive Non-Hodking Lymphoma (NHL). Bispecific antibodies (BsAbs) such as Glofitamab, have expanded therapeutic options for relapsed/refractory (R/R) DLBCL, including patients failing CAR-T. Despite high response rates, resistance and relapse remain major challenges, and current prognostic tools fail to accurately stratify patients and capture disease heterogeneity. In this context, circulating tumor DNA (ctDNA) an...

Functional regulation of lymphoid cells by IL-1R8 targeting in cancer

Interleukin-1 receptor 8 (IL-1R8) is an atypical Interleukin-1 receptor (ILR) family member that mitigates inflammatory responses by dampening ILR and Toll-like receptor (TLR) signaling. Studies conducted on IL-1R8-deficient NK cells established its key role as immune checkpoint and negative regulator of IL-18-dependent activation. In particular, IL-1R8-deficiency unleashes NK cell-mediated immune surveillance against hematogenous metastasis, liver cancer and viral dissemination. However, the...

RADIOMIC FEATURES OF TUMOR AND OF LIVER-TUMOR INTERFACE IN PATIENTS WITH COLORECTAL LIVER METASTASES. IDENTIFICATION OF NEW PROGNOSTIC BIOMARKERS.

BACKGROUND: Surgery with perioperative chemotherapy offers a potentially curative treatment for colorectal liver metastases (CRLM), but a subset of resectable patients does not achieve long-term benefit. Patient selection relies on survival prediction, but available prognostic factors have limited reliability. PURPOSE: To investigate the potential of preoperative CT-based radiomics for survival prediction in CRLM patients, focusing on the impact of CT-surgery interval and comparison with clin...

Relapsed Diffuse Large B-cell Lymphoma is Shaped by Molecular Subtypes and Genomic Alterations

Investigating the physiological and molecular effects of inflammation episode on neurodevelopment and ASD risk

Neurodevelopmental disorders (NDDs) are a group of conditions including autism spectrum disorders (ASD). These disorders affect brain development and are characterized by social and cognitive deficits with onset in early life and long-lasting consequences. Several studies already demonstrated the genetic contribution to NDD risk, while more recently a strong impact of environmental factors, such as fever or other inflammatory insults, has emerged underlining a multifactorial origin. More spec...

Valosin Containing Protein (VCP): Biomarker Of Radioresistance In Glioblastoma (Valor Study)

Background Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, char-acterized by poor prognosis and a high degree of therapeutic resistance. Despite ad-vances in surgery, radiotherapy, and temozolomide-based chemotherapy, median overall survival rarely exceeds 18 months. Radioresistance represents a major obstacle to effec-tive local control, often resulting from both intrinsic and adaptive cellular mechanisms. Among molecular mediators involved in DNA damage respons...

The role of neuronal sumoylation in the pathogenesis of the Angelman Syndrome

The Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of the maternally expressed UBE3A gene, which encodes an E3 ubiquitin ligase. Although considerable efforts have been put to dissect UBE3A function in the brain, the pathogenic mechanisms remain largely unknown and effective treatments are not available yet. Being an E3 ubiquitin ligase, defective ubiquitination, which may occur in either nuclear or cytosolic compartments, is thought to be a primary mechanism ...