Maria Beatrice Arasi

Scopus Publications

Biallelic BAIAP3 Variants Are Associated with Isolated Retinitis Pigmentosa
Viviana Cordeddu, Elisabetta Flex, Luca Mignini, Alessandro Bruselles, Serena Cecchetti, et al.
International Journal of Molecular Sciences, 2025
A class of retinal dystrophies known as retinitis pigmentosa (RP) is caused by the loss of photoreceptor cells. RP can be genetically transmitted as an autosomal dominant, autosomal recessive, or X-linked trait. About one-third of genes implicated in retinal degeneration encode for proteins whose functional dysregulation affects the “connecting cilium” in photoreceptors, altering its structure and function. Here we report on a 33-year-old woman who was referred for clinical genetic testing following a previous diagnosis of degenerative retinopathy, which was not informative. She was enrolled in a research program dedicated to undiagnosed retinal disorders, where a whole genome sequencing approach was employed to understand the underlying genetic basis. The genomic analysis documented the occurrence of compound heterozygosity for two functionally relevant missense variants in BAIAP3, which encodes a protein with a well-documented role in SNARE-mediated trafficking and ciliogenesis. Confocal microscopy analysis showed elongated cilia in patient-derived and BAIAP3-depleted fibroblasts compared to control cells. Real-time PCR analyses showed a consistent significant reduction of GLI1 mRNA levels in patient-derived and BAIAP3-depleted cells, both in basal conditions and after treatment with Smoothened agonist, SAG, indicating Sonic hedgehog signaling dysregulation. Collectively, these data suggest that biallelic loss-of-function variants of BAIAP3 may cause photoreceptor degeneration and underlie isolated RP.
A New Antibody–Cytokine Construct Targeting Natural Killer Cells: An Immunotherapeutic Approach to Chronic Lymphocytic Leukemia
Michela Flego, Mauro Andreotti, Francesca Romana Mauro, Maria Beatrice Arasi, Silvia Zamboni, et al.
Biomolecules, 2025
In chronic lymphocytic leukemia (CLL), natural killer (NK) cells show a dysfunctional phenotype that correlates with disease progression. Our aim was to restore NK cell functionality in CLL through a specifically targeted IL15-stimulating activity; IL15 targeting could, in fact, potentiate the activity of NK cells and reduce off-target effects. We designed and developed a cis-acting immunocytokine composed of an anti-CD56 single-chain Fragment variable (scFv) and IL15, labeled scFvB1IL15. scFvB1IL15 was tested in vitro on peripheral blood mononuclear cells (PBMCs) obtained from both different healthy donors (HDs) and CLL patients in order to evaluate its ability to target NK cells and enhance their activation and NK-mediated directed cytotoxicity. scFvB1IL15 specifically induced strong degranulation and cytokine and chemokine production in NK cells in both HD- and CLL patient-derived PBMC samples. Furthermore, compared to IL15 alone, it was able to induce higher levels of NKG2D- and NKp30-activating receptors and restore NK-mediated direct killing in the CLL patient-derived samples. The preliminary data presented in this work suggest that IL15’s targeting of NK cells via scFvB1 potentiates the effects of IL15 and that scFvB1IL15 can be a useful agent for overcoming NK functional gaps and contribute to NK-cell-based immunotherapies.
MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance
Maria Beatrice Arasi, Gabriele De Luca, Laura Chronopoulou, Francesca Pedini, Eleonora Petrucci, et al.
Molecular Therapy, 2024
BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers
Giorgia Castellani, Mariachiara Buccarelli, Maria Beatrice Arasi, Stefania Rossi, Maria Elena Pisanu, et al.
Cancers, 2023
Melanoma is an aggressive form of skin cancer resulting from the malignant transformation of melanocytes. Recent therapeutic approaches, including targeted therapy and immunotherapy, have improved the prognosis and outcome of melanoma patients. BRAF is one of the most frequently mutated oncogenes recognised in melanoma. The most frequent oncogenic BRAF mutations consist of a single point mutation at codon 600 (mostly V600E) that leads to constitutive activation of the BRAF/MEK/ERK (MAPK) signalling pathway. Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results. However, several resistance mechanisms invariably develop leading to therapeutic failure. The aim of this manuscript is to review the role of BRAF mutational status in the pathogenesis of melanoma and its impact on differentiation and inflammation. Moreover, this review focuses on the mechanisms responsible for resistance to targeted therapies in BRAF-mutated melanoma and provides an overview of circulating biomarkers including circulating tumour cells, circulating tumour DNA, and non-coding RNAs.
Advances in natural or synthetic nanoparticles for metastatic melanoma therapy and diagnosis
Maria Beatrice Arasi, Francesca Pedini, Sonia Valentini, Nadia Felli, Federica Felicetti
Cancers, 2020
Advanced melanoma is still a major challenge in oncology. In the early stages, melanoma can be treated successfully with surgery and the survival rate is high, nevertheless the survival rate drops drastically after metastasis dissemination. The identification of parameters predictive of the prognosis to support clinical decisions and of new efficacious therapies are important to ensure patients the best possible prognosis. Recent progress in nanotechnology allowed the development of nanoparticles able to protect drugs from degradation and to deliver the drug to the tumor. Modification of the nanoparticle surface by specific molecules improves retention and accumulation in the target tissue. In this review, we describe the potential role of nanoparticles in advanced melanoma treatment and discuss the current efforts of designing polymeric nanoparticles for controlled drug release at the site upon injection. In addition, we highlight the advances as well as the challenges of exosome-based nanocarriers as drug vehicles. We place special focus on the advantages of these natural nanocarriers in delivering various cargoes in advanced melanoma treatment. We also describe the current advances in knowledge of melanoma-related exosomes, including their biogenesis, molecular contents and biological functions, focusing our attention on their utilization for early diagnosis and prognosis in melanoma disease.
Joint action of miR-126 and MAPK/PI3K inhibitors against metastatic melanoma
Francesca Pedini, Gabriele De Luca, Federica Felicetti, Rossella Puglisi, Alessandra Boe, et al.
Molecular Oncology, 2019
Emerging data support the rationale of combined therapies in advanced melanoma. Specifically, the combined use of drugs with different mechanisms of action can reduce the probability of selecting resistant clones. To identify agents active against melanoma cells, we screened a library of 349 anti‐cancer compounds, currently in clinical use or trials, and selected PIK‐75, an inhibitor of the phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) pathway, as the ‘top active’ drug. PIK‐75 was then used alone or in combination with vemurafenib, the first BRAF inhibitor approved for patients with melanoma harboring BRAF mutations. We identified a combined dose of PIK‐75 and vemurafenib that inhibited both the PI3K/AKT and mitogen‐activated protein kinase pathways, thereby overcoming any compensatory activation. In view of the important tumor suppressor function induced by restoring expression of microRNA (miR)‐126 in metastatic melanoma cells, we examined whether miR‐126 has a synergistic role when included in a triple combination alongside PIK‐75 and vemurafenib. We found that enforced expression of miR‐126 (which alone can reduce tumorigenicity) significantly increased PIK‐75 activity when used as either a single agent or in combination with vemurafenib. Interestingly, PIK‐75 proved to be effective against early passage cell lines derived from patients’ biopsies and on melanoma cell lines resistant to either vemurafenib or dabrafenib, thus suggesting that it potentially has the capability to overcome drug resistance. Finally, the synergistic role played by miR‐126 in combination with vemurafenib and/or PIK‐75 was demonstrated in vivo in mouse xenograft models, in which tumor growth inhibition was associated with increased apoptosis. These results not only show the efficacy of PIK‐75 and vemurafenib co‐treatment but also indicate that restoration of miR‐126 expression in advanced melanoma can enhance their antitumor activity, which may possibly allow dose reduction to decrease adverse events without reducing the therapeutic benefits.