@article{%a1.%Y_211,

title = {FACILITY: feeding the family-the intergenerational approach to fight obesity, a cross-sectional study protocol},

author = {Vincenti A and Calcaterra V and Santero S and Viroli G and Di Napoli I and Biino G and Daconto L and Cusumano M and Zuccotti G and Cena H},

url = {https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2025.1450324/full},

doi = {10.3389/fped.2025.1450324},

year  = {2025},

date = {2025-06-10},

journal = {Frontiers in pediatrics},

volume = {13},

pages = {1450324},

abstract = {Introduction: Paediatric obesity has been described by the World Health Organization as one of the most serious health challenges of the 21st century. Over the past four decades, the number of children and adolescents with obesity has increased between 10 and 12-fold worldwide. Methods: Childhood obesity is a complex and multifactorial outcome which can be attributed to factors such as socioeconomic status, ethnicity, lifestyle and eating habits. Beside personal-children-related factors, maternal (education, food knowledge, income) and environmental ones (food environment's features and accessibility) have been proven but their influences are still worth discussion. The cross-sectional study of the "FACILITY: feeding the family-the intergenerational approach to fight obesity" project aims at estimating children prevalence of overweight and obesity and assessing the impacts of lifestyle and of socio-economic-cultural and environmental factors on overweight and obesity. Results: Due to the current importance of developing multidisciplinary mother-child centred prevention programs, FACILITY cross-sectional study will investigate maternal and child socio-cultural, economic, environmental, health and lifestyle-related risk factors for the development of obesity. Discussion: The knowledge gained will provide the basis to develop a "primordial prevention program" to early tackle childhood obesity. Clinical trial registration: ClinicalTrials.gov, identifier (NCT06179381).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_210,

title = {DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue},

author = {Modafferi S and Farina S and Esposito F and Brandi O and Di Salvio M and Della Valle I and D'Uva S and Scarian E and Cicio G and Riccardi A and Pisati F and Garbelli A and Santini T and Pansarasa O and Morlando M and D'Ambrosi N and Cozzolino M and Cestra G and d'Adda di Fagagna F and Gioia U and Francia S},

url = {https://www.nature.com/articles/s41418-025-01530-7},

doi = {10.1038/s41418-025-01530-7},

year  = {2025},

date = {2025-06-10},

journal = {Cell death and differentiation},

abstract = {Formation of cytoplasmic inclusions (CIs) of TDP-43 and FUS, along with DNA damage accumulation, is a hallmark of affected motor neurons in Amyotrophic Lateral Sclerosis (ALS). However, the impact of CIs on DNA damage response (DDR) and repair in this pathology remains unprobed. Here, we show that CIs of TDP-43 and FUSP525L, co-localizing with stress granules, lead to a dysfunctional DDR activation associated with physical DNA breakage. Inhibition of the activity of the DDR kinase ATM, but not of ATR, abolishes DDR signaling, indicating that DNA double-strand breaks (DSBs) are the primary source of DDR activation. In addition, cells with TDP-43 and FUSP525L CIs exhibit reduced DNA damage-induced RNA synthesis at DSBs. We previously showed that the two endoribonucleases DROSHA and DICER, also known to interact with TDP-43 and FUS during small RNA processing, contribute to DDR signaling at DSBs. Treatment with enoxacin, which stimulates DDR and repair by boosting the enzymatic activity of DICER, restores a proficient DDR and reduces DNA damage accumulation in cultured cells with CIs and in vivo in a murine model of ALS. In Drosophila melanogaster, Dicer-2 overexpression rescues TDP-43-mediated retinal degeneration. In summary, our results indicate that the harmful effects caused by TDP-43 and FUS CIs include genotoxic stress and that the pharmacological stimulation of the DNA damage signaling and repair counteracts it.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_209,

title = {Combining prelamin A accumulation and oxidative stress: A strategy to target glioblastoma},

author = {Marvi MV and Evangelisti C and Cerchier CB and Fazio A and Neri I and Koufi FD and Blalock W and Cenni V and Zoli M and Asioli S and Morandi L and Franceschi E and Manzoli L and Capanni C and Ratti S},

url = {https://www.sciencedirect.com/science/article/pii/S0171933525000160?via%3Dihub},

doi = {10.1016/j.ejcb.2025.151491},

year  = {2025},

date = {2025-06-10},

journal = {European journal of cell biology},

volume = {104},

issue = {2},

pages = {151491},

abstract = {Glioblastoma is the most aggressive and prevalent tumor of the Central Nervous System (CNS) with limited treatment options and poor patient outcomes. Standard therapies, including surgery, radiation, and chemotherapy, provide only modest survival benefits, highlighting the need for innovative therapeutic approaches. This study investigates a novel strategy targeting prelamin A processing in glioblastoma cells. By inhibiting the farnesyltransferase enzyme using SCH66336 (Lonafarnib), we promote the accumulation of lamin A precursor (prelamin A) in glioblastoma cells, thereby increasing their susceptibility to oxidative stress induced by Menadione administration, while sparing normal human astrocytes. Notably, the combined SCH66336-Menadione treatment reduced cell proliferation, modified the expression of stemness markers, and decreased viability in patient-derived glioblastoma stem cells, which represent the population responsible for tumor aggressiveness and recurrence. These findings indicate that inhibiting prelamin A processing could be a potential strategy to reduce glioblastoma aggressiveness and enhance therapeutic outcomes, particularly for treatment-resistant glioblastoma stem cell populations. This approach shows potential for integrating prelamin A processing disruption as a complementary strategy in glioblastoma therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_208,

title = {A Novel Cognitive Frailty Index for Geriatric Mice},

author = {Marcozzi S and Bigossi G and Giuliani ME and Lai G and Bartozzi B and Balietti M and Casoli T and Orlando F and Amoroso A and Giacconi R and Cardelli M and Piacenza F and Lattanzio F and Olivieri F and de Keizer PLJ and {d'Adda di Fagagna F} and Malavolta M},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.70056},

doi = {10.1111/acel.70056},

year  = {2025},

date = {2025-06-10},

journal = {Aging Cell},

abstract = {Loss of cognitive function is a significant challenge in aging, and developing models to understand and target cognitive decline is crucial for the development of Geroscience-based interventions. Aged mice offer a valuable model as they share features of cognitive decline with humans. Despite numerous studies, knowledge of longitudinal age-related cognitive changes and cognitive frailty in naturally aging mice is limited, particularly in cohorts exceeding 30 months of age, where cognitive decline is more pronounced. Moreover, the impaired physical function of aged mice is known to affect latency-based strategies to measure cognitive performances. Here, we show a comprehensive longitudinal assessment using the Barnes Maze test in a large cohort of 424 aged (≥ 21 months) C57BL/6J mice. We introduced a new metric, the Cognitive Frailty Index (CoFI), which summarizes different age-associated Barnes Maze parameters into a unique function. CoFI strongly associates with advancing age and mortality, offering a reliable ability to discriminate long- and short-lived mice. We also established a CoFI cut-off and a physically adjusted CoFI, both of which can distinguish between physical and cognitive frailty. This is further supported by the enhanced predictive power when physical and cognitive frailty are combined to assess short-term mortality. Moreover, the computation method for CoFI is adaptable to various cognitive assessment tests, leveraging procedures akin to those used for calculating other frailty indices. In conclusion, through robust longitudinal tracking, CoFI has the potential to become an important ally in assessing the effectiveness of Geroscience-based interventions to counteract age-related cognitive impairment.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y_207,

title = {Amy and Friends: improving the lives of individuals affected by DNA repair disorders},

author = {Hughes J and Orioli D and Arseni L},

url = {https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.70049},

doi = {10.1002/1873-3468.70049},

year  = {2025},

date = {2025-06-10},

journal = {FEBS letters},

volume = {599},

issue = {10},

pages = {1339-1345},

abstract = {DNA repair disorders are rare genetic conditions characterized by defects in the mechanisms responsible for repairing damaged DNA. DNA damage occurs frequently due to environmental factors, and in healthy cells, repair systems fix this damage to maintain genomic integrity. In individuals with DNA repair disorders, these mechanisms are impaired, leading to accumulated damage, cellular dysfunction, premature aging, and cell death. Symptoms vary depending on the specific repair pathway defect, with examples including Cockayne syndrome (CS), trichothiodystrophy (TTD), and xeroderma pigmentosum. Amy and Friends was founded by Jayne Hughes in the UK in 2007 to support children/young adults and families suffering from CS, TTD, and linked DNA repair disorders. In this second of a new series on patient advocacy, FEBS Letters interviews Founder and CEO Jayne Hughes and molecular geneticist and specialist team member Prof. Donata Orioli on the aims, achievements, and activities of Amy and Friends.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_206,

title = {Surface Charge Overrides Protein Corona Formation in Determining the Cytotoxicity, Cellular Uptake, and Biodistribution of Silver Nanoparticles},

author = {Barbalinardo M and Chiarini F and Teti G and Paganelli F and Mercadelli E and Bartoletti A and Migliori A and Piazzi M and Bertacchini J and Sena P and Sanson A and Falconi M and Palumbo C and Cavallini M and Gentili D},

url = {https://pubs.acs.org/doi/10.1021/acsabm.5c00392},

doi = {10.1021/acsabm.5c00392},

year  = {2025},

date = {2025-06-10},

journal = {ACS applied bio materials},

abstract = {Silver nanoparticles (AgNPs) hold great promise in biomedical applications due to their unique properties and potential for specific tissue targeting. However, the clinical translation of nanoparticle-based therapeutics remains challenging, primarily due to an incomplete understanding of how nanoparticle properties influence interactions at the nano-bio interface, as well as the role of surface-adsorbed proteins (i.e., protein corona) in modulating nanoparticle-cell interactions. This study demonstrates that the surface charge has a greater influence than protein corona formation in determining the cytotoxicity, cellular uptake, and biodistribution of AgNPs. Using negatively and positively charged AgNPs, we show that while protein corona formation is essential for ensuring nanoparticle availability for cellular interactions, the adsorption of biomolecules is nonspecific and independent of surface charge. Conversely, the surface charge significantly influences the interactions of AgNPs with cells. Positively charged nanoparticles exhibit enhanced cellular uptake, preferential accumulation in lysosomes, and pronounced mitochondrial damage compared to their negatively charged counterparts, resulting in greater cytotoxic effects. This effect is particularly evident in human breast cancer cells, where negatively charged nanoparticles show minimal uptake and cytotoxicity. These findings demonstrate that surface charge is the primary factor governing nanoparticle-cell interactions rather than protein corona formation. Nonetheless, the protein corona plays a critical role in stabilizing nanoparticles in physiological environments.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y__198,

title = {The complex interplay between aging and cancer},

author = {Trastus LA and {d'Adda di Fagagna F}},

url = {https://www.nature.com/articles/s43587-025-00827-z},

doi = {10.1038/s43587-025-00827-z},

year  = {2025},

date = {2025-04-09},

journal = {Nature aging},

volume = {5},

issue = {3},

pages = {350-365},

abstract = {Cancer is an age-related disease, but the interplay between cancer and aging is complex and their shared molecular drivers are deeply intertwined. This Review provides an overview of how different biological pathways affect cancer and aging, leveraging evidence mainly derived from animal studies. We discuss how genome maintenance and accumulation of DNA mutations affect tumorigenesis and tissue homeostasis during aging. We describe how age-related telomere dysfunction and cellular senescence intricately modulate tumor development through mechanisms involving genomic instability and inflammation. We examine how an aged immune system and chronic inflammation shape tumor immunosurveillance, fueling DNA damage and cellular senescence. Finally, as animal models are important to untangling the relative contributions of these aging-modulated pathways to cancer progression and to test interventions, we discuss some of the limitations of physiological and accelerated aging models, aiming to improve experimental designs and enhance translation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__197,

title = {V-ATPase in glioma stem cells: a novel metabolic vulnerability},

author = {Storaci AM and Bertolini I and Martelli C and De Turris G and Mansour N and Crosti M and De Filippo MR and Ottobrini L and Valenti L and Polledri E and Fustinoni S and Caroli M and Fanizzi C and Bosari S and Ferrero S and Zadra G and Vaira V},

url = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03280-3},

doi = {10.1186/s13046-025-03280-3},

year  = {2025},

date = {2025-04-09},

urldate = {2025-04-09},

journal = {Journal of experimental & clinical cancer research},

volume = {44},

issue = {1},

pages = {17},

abstract = {Background: Glioblastoma (GBM) is a lethal brain tumor characterized by the glioma stem cell (GSC) niche. The V-ATPase proton pump has been described as a crucial factor in sustaining GSC viability and tumorigenicity. Here we studied how patients-derived GSCs rely on V-ATPase activity to sustain mitochondrial bioenergetics and cell growth.,Methods: V-ATPase activity in GSC cultures was modulated using Bafilomycin A1 (BafA1) and cell viability and metabolic traits were analyzed using live assays. The GBM patients-derived orthotopic xenografts were used as in vivo models of disease. Cell extracts, proximity-ligation assay and advanced microscopy was used to analyze subcellular presence of proteins. A metabolomic screening was performed using Biocrates p180 kit, whereas transcriptomic analysis was performed using Nanostring panels. Results: Perturbation of V-ATPase activity reduces GSC growth in vitro and in vivo. In GSC there is a pool of V-ATPase that localize in mitochondria. At the functional level, V-ATPase inhibition in GSC induces ROS production, mitochondrial damage, while hindering mitochondrial oxidative phosphorylation and reducing protein synthesis. This metabolic rewiring is accompanied by a higher glycolytic rate and intracellular lactate accumulation, which is not exploited by GSCs for biosynthetic or survival purposes. Conclusions: V-ATPase activity in GSC is critical for mitochondrial metabolism and cell growth. Targeting V-ATPase activity may be a novel potential vulnerability for glioblastoma treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__196,

title = {Synthesis and biological investigation of peptidomimetic SARS-CoV-2 main protease inhibitors bearing quinoline-based heterocycles at P3},

author = {Rossi S and Deidda G and Fiaschi L and Ibba R and Pieroni M and Dichiara M and Carullo G and Butini S and Ramunno A and Brogi S and Lolicato M and Arrigoni C and Cabella N and Bavagnoli L and Maga G and Varasi I and Biba C and Vicenti I and Gemma S and Crespan E and Zazzi M and Campiani G},

url = {https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400812},

doi = {10.1002/ardp.202400812},

year  = {2025},

date = {2025-04-09},

journal = {Archiv der Pharmazie},

volume = {358},

issue = {1},

pages = {e240081},

abstract = {In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (Mpro) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic Mpro covalent inhibitors characterized by quinoline-based P3 moieties. Structure-activity relationships (SARs) were also investigated at P1 and P2, as well as for different warheads. The binding modes of the designed inhibitors were assessed using X-ray crystallographic and molecular docking studies. The identified Mpro inhibitors were tested for their antiviral activities in cell-based assays, and the results were encouraging. The SAR studies presented here can contribute to the future design of improved inhibitors by addressing some of the current or prospective issues regarding Mpro inhibitors currently used in therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__195,

title = {Angiogenic Events Positively Modulated by Complex Magnetic Fields in an In Vitro Endothelial Cell Model},

author = {Ricci A and Cataldi A and Gallorini M and di Giacomo V and Rapino M and Di Pietro N and Mantarro M and Piattelli A and Zara S},

url = {https://www.mdpi.com/2073-4409/14/5/332},

doi = {10.3390/cells14050332},

year  = {2025},

date = {2025-04-08},

journal = {Cells},

volume = {14},

issue = {5},

pages = {332},

abstract = {The vascular system is primarily responsible for orchestrating the underlying healing processes to achieve tissue regeneration, thus the promotion of angiogenic events could be a useful strategy to repair injured tissues. Among several approaches to stimulate tissue regeneration, non-invasive devices are currently widely diffused. Complex Magnetic Fields (CMFs) are innovative pulsed multifrequency electromagnetic fields used for their promising results in clinical applications, such as diabetic foot treatment or edema resorption. Nevertheless, few papers are available demonstrating the biological mechanisms involved. In this paper, in order to understand CMFs' capability to promote angiogenic events, Regenerative Tissue Program (RTP) was applied to an in vitro Endothelial Cells (ECs) model. ECs were stimulated with (I) 2 RTP consecutive cycles, (II) with an interval of 8 h (T0 + T8), or (III) 24 h (T0 + T24) from one cycle to another. Results demonstrate that (I) extracellular matrix degradation is promoted through matrix metalloproteinases 2 and 9 modulation, leading to an increased cell migratory capability; (II) CMFs support EC growth, activating Integrin β1-Erk-Cdk2 pathway and sustaining G1/S transition; (III) vessel morphogenesis is promoted when CMFs are applied. In conclusion, the promising clinical results are supported by in vitro analyses which evidence that main angiogenic events are stimulated by CMFs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__194,

title = {On the tracks of an uninvited guest, the Asian tiger mosquito, Aedes albopictus in Cyprus},

author = {Piccinno R and Fiorenza G and Vasquez MI and Bouyer J and Notarides G and Gomulski LM and Meletiou S and Akiner M and Michaelakis A and Forneris F and Maga G and Gasperi G and Malacrida AR},

url = {https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06651-5},

doi = {10.1186/s13071-024-06651-5},

year  = {2025},

date = {2025-04-08},

urldate = {2025-04-08},

journal = {Parasites & vectors},

volume = {18},

issue = {1},

pages = {39},

abstract = {Background: Aedes albopictus, the Asian tiger mosquito, which is listed among the world's 100 most dangerous invasive species, is the main vector of chikungunya, dengue and Zika viruses. This mosquito species has rapidly dispersed and invaded much of the globe assisted by its life history traits and high propagule pressure driven by human activities. Aedes albopictus is currently widespread across mainland Europe and the Mediterranean region, including the islands. Cyprus remained free of Ae. albopictus until October 2022, when specimens were recorded for the first time in Limassol district, including the port area. Understanding the processes associated with the introduction, expansion and establishment of this vector in Cyprus is of primary importance to mitigate its dispersal on the island, and to implement control methods to prevent disease outbreaks. A genetic analysis of these invasive specimens collected in Limassol district and in areas from the Central Mediterranean was performed to obtain a genetic portrait of the demographic history of the invasive mosquitoes on Cyprus. Methods: We applied highly polymorphic simple sequence repeat (SSR) markers to the Ae. albopictus mosquitoes collected in Cyprus and to specimens from Italy, France, Switzerland, the Balkans, Greece and Turkey to construct an SSR individual genotype dataset that would enable the invasion pattern of Ae. albopictus in Cyprus to be traced. Bayesian clustering analyses using STRUCTURE and BayesAss version 3 were employed to derive information on the degree of ancestry among Cypriot and Mediterranean mosquitoes and on recent mosquito movements both within Cyprus and between Cyprus and the Central Mediterranean areas. Results: The Cypriot mosquitoes appear to be highly polymorphic with no signs of genetic drift due to recent founder effects. An ongoing mosquito dispersal within the Limassol district was detected, suggesting the presence of established, hidden adventive populations. These mosquitoes share a high degree of ancestry with those in the Balkans and parts of northern Italy that border the Adriatic Sea. Conclusions: Considering the trade connections of Limassol port, Cyprus with the Balkans and the Adriatic Italian region, we hypothesise that these areas may be involved in the incursion of Ae. albopictus into Cyprus. As the Balkan and Italian mosquitoes display high competence for CHIKV, questions arise about possible arbovirus outbreaks in Cyprus and highlight the need to implement surveillance and control measures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__193,

title = {At the nucleus of cancer: how the nuclear envelope controls tumor progression},

author = {Paganelli F and Poli A and Truocchio S and Martelli AM and Palumbo C and Lattanzi G and Chiarini F},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11758262/},

doi = {10.1002/mco2.70073},

year  = {2025},

date = {2025-04-08},

journal = {MedComm},

volume = {6},

issue = {2},

pages = {e70073},

abstract = {Historically considered downstream effects of tumorigenesis-arising from changes in DNA content or chromatin organization-nuclear alterations have long been seen as mere prognostic markers within a genome-centric model of cancer. However, recent findings have placed the nuclear envelope (NE) at the forefront of tumor progression, highlighting its active role in mediating cellular responses to mechanical forces. Despite significant progress, the precise interplay between NE components and cancer progression remains under debate. In this review, we provide a comprehensive and up-to-date overview of how changes in NE composition affect nuclear mechanics and facilitate malignant transformation, grounded in the latest molecular and functional studies. We also review recent research that uses advanced technologies, including artificial intelligence, to predict malignancy risk and treatment outcomes by analyzing nuclear morphology. Finally, we discuss how progress in understanding nuclear mechanics has paved the way for mechanotherapy-a promising cancer treatment approach that exploits the mechanical differences between cancerous and healthy cells. Shifting the perspective on NE alterations from mere diagnostic markers to potential therapeutic targets, this review calls for further investigation into the evolving role of the NE in cancer, highlighting the potential for innovative strategies to transform conventional cancer therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__192,

title = {Non-canonical NF-κB signaling in dendritic cells is required for ATP-driven indoleamine 2,3-dioxygenase 1 induction through P2Y11 receptor},

author = {Ocadlikova D and Fiordi B and Trabanelli S and Salvestrini V and Ciciarello M and Forte D and Campazzi E and Vitali L and Cipollitta SC and Pegoraro A and Jandus C and Di Virgilio F and Adinolfi E and Cavo M and Curti A},

url = {https://academic.oup.com/jleukbio/advance-article/doi/10.1093/jleuko/qiaf010/7997481?login=true},

doi = {10.1093/jleuko/qiaf010},

year  = {2025},

date = {2025-04-08},

journal = {Journal of leukocyte biology},

abstract = {Extracellular ATP released from dying cells, including tumor cells, is a key mediator of inflammation and tolerance by binding to purinergic receptors on dendritic cells, resulting in inflammasome activation (via P2X7R), dendritic cell maturation (via P2Y11R), and Indoleamine-2,3-dioxygenase 1 upregulation. However, the regulation of ATP-driven Indoleamine-2,3-dioxygenase 1 expression in human dendritic cells has been poorly investigated. In this work we aimed to investigate the ATP-driven molecular regulation of Indoleamine-2,3-dioxygenase 1 expression via purinergic receptors and to provide an in-depth characterization of ATP-driven T regulatory cells induced by Indoleamine-2,3-dioxygenase 1-expressing dendritic cells. We identified P2Y11R as being responsible for ATP-driven Indoleamine-2,3-dioxygenase 1 upregulation, and non-canonical NF-kB as a molecular pathway associated with ATP-dependent Indoleamine-2,3-dioxygenase 1 induction through P2Y11R. Then we investigated - but did not confirm - an involvement of inflammasome machinery through P2X7R in Indoleamine-2,3-dioxygenase 1 upregulation. Finally, we evaluated the role of ATP catabolism via ATP ectonucleotidases, i.e. CD39 and CD73 and its main product adenosine, in regulating the generation of Indoleamine-2,3-dioxygenase 1-driven T regulatory cells. We found that ATP-driven Indoleamine-2,3-dioxygenase 1 upregulation is associated with CD73 upregulation and adenosine production. Additionally, ATP-treated Indoleamine-2,3-dioxygenase 1-positive mature dendritic cells induce PD-1-expressing bone fide suppressive T regulatory cells via adenosine A2AR. Collectively, a more in-depth understanding of ATP-driven immune-regulatory mechanisms through Indoleamine-2,3-dioxygenase 1 regulation in human dendritic cells leading to the induction of T regulatory cells can have clinical implications for the development of Indoleamine-2,3-dioxygenase 1 inhibitors in cancer patients, especially in combination with immunotherapy such as an anti-CD73 or adenosine receptor agonist and immunogenic chemotherapy.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{%a1.%Y__191,

title = {Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma},

author = {Montico B and Giurato G and Guerrieri R and Colizzi F and Salvati A and Nassa G and Lamberti J and Memoli D and Sabatelli P and Comelli M and Bellazzo A and Fejza A and Camicia L and Baboci L and Dal Bo M and Covre A and Nyman TA and Weisz A and Steffan A and Maio M and Sigalotti L and Mongiat M and Andreuzzi E and Fratta E},

url = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-025-03289-8},

doi = {10.1186/s13046-025-03289-8},

year  = {2025},

date = {2025-04-08},

journal = {Journal of experimental & clinical cancer research},

volume = {44},

number = {53},

issue = {1},

abstract = {Background: About 50% of cutaneous melanoma (CM) harbors the activating BRAFV600 mutation which exerts most of the oncogenic effects through the MAPK signaling pathway. In the last years, a number of MAPK modulators have been identified, including Spry1. In this context, we have recently demonstrated that knockout of Spry1 (Spry1KO) in BRAFV600-mutant CM led to cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and reduced tumor growth in vivo. Despite these findings, however, the precise molecular mechanism linking Spry1 to BRAFV600-mutant CM remains to be elucidated. Materials and methods: Immunoprecipitation coupled to mass spectrometry was employed to gain insight into Spry1 interactome. Spry1 gene was knocked-out using the CRISPR strategy in the BRAF-mutant cell lines. Transmission electron microscopy was used to assess the relationship between Spry1 expression and mitochondrial morphology. By using in vitro and in vivo models, the effects of Spry1KO were investigated through RNA-sequencing, quantitative real-time PCR, Western blot, and immunofluorescence analyses. The Seahorse XF24 assay allowed real-time measurement of cellular metabolism in our model. Angiogenic potential was assessed through in vitro tube formation assays and in vivo CD31 staining. Results: Spry1 was mainly located in mitochondria in BRAFV600-mutant CM cells where it interacted with key molecules involved in mitochondrial homeostasis. Spry1 loss resulted in mitochondrial shape alterations and dysfunction, which associated with increased reactive oxygen species production. In agreement, we found that nuclear hypoxia-inducible factor-1 alpha (HIF1α) protein levels were reduced in Spry1KO clones both in vitro and in vivo along with the expression of its glycolysis related genes. Accordingly, Ingenuity Pathway Analysis identified "HIF1α Signaling" as the most significant molecular and cellular function affected by Spry1 silencing, whereas the glycolytic function was significantly impaired in Spry1 depleted BRAFV600-mutant CM cells. In addition, our results indicated that the expression of the vascular endothelial growth factor A was down-regulated following Spry1KO, possibly as a result of mitochondrial dysfunction. Consistently, we observed a substantial impairment of angiogenesis, as assessed by the tube formation assay in vitro and the immunofluorescence staining of CD31 in vivo. Conclusions: Altogether, these findings identify Spry1 as a potential regulator of mitochondrial homeostasis, and uncover a previously unrecognized role for Spry1 in regulating nuclear HIF1α expression and angiogenesis in BRAFV600-mutant CM. Significance: Spry1KO profoundly impacts on mitochondria homeostasis, while concomitantly impairing HIF1α-dependent glycolysis and reducing angiogenesis in BRAF-mutant CM cells, thus providing a potential therapeutic target to improve BRAFV600-mutant CM treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_182,

title = {Traffic light at DSB-transit regulation between gene transcription and DNA repair},

author = {Modafferi S and Esposito F and Tavella S and Gioia U and Francia S},

url = {https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.15024},

doi = {10.1002/1873-3468.15024},

year  = {2025},

date = {2025-01-16},

urldate = {2024-10-21},

journal = {FEBS letters},

volume = {599},

issue = {2},

pages = {177-189},

abstract = {Transcription of actively expressed genes is dampened for kilobases around DNA lesions via chromatin modifications. This is believed to favour repair and prevent genome instability. Nonetheless, mounting evidence suggests that transcription may be induced by DNA breakage, resulting in the local de novo synthesis of non-coding RNAs (ncRNAs). Such transcripts have been proposed to play important functions in both DNA damage signalling and repair. Here, we review the recently identified mechanistic details of transcriptional silencing at damaged chromatin, highlighting how post-translational histone modifications can also be modulated by the local synthesis of DNA damage-induced ncRNAs. Finally, we envision that these entangled transcriptional events at DNA breakages can be targeted to modulate DNA repair, with potential implications for locus-specific therapeutic strategies},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__184,

title = {CRISPR/Cas9 screens identify LIG1 as a sensitizer of PARP inhibitors in castration-resistant prostate cancer},

author = {Fracassi G and Lorenzin F and Orlando F and Gioia U and D'Amato G and Casaramona AS and Cantore T and Prandi D and Santer FR and Klocker H and {d'Adda di Fagagna F} and Mateo J and Demichelis F},

url = {https://www.jci.org/articles/view/179393},

doi = {10.1172/JCI179393},

year  = {2024},

date = {2024-12-12},

journal = {Journal of clinical investigation},

volume = {135},

issue = {4},

pages = {e179393},

abstract = {PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment. We identified LIG1, EME1, and FAAP24 losses as PARPi sensitizers and assessed their frequencies from 3 to 6% among CRPC patients. We showed that concomitant inactivation of LIG1 and PARP induced replication stress and DNA double-strand breaks, ultimately leading to apoptosis. This synthetic lethality (SL) is conserved across multiple tumor types (e.g., lung, breast, and colorectal), and its applicability might be extended to LIG1-functional tumors through a pharmacological combinatorial approach. Importantly, the sensitivity of LIG1-deficient cells to PARPi was confirmed in vivo. Altogether, our results argue for the relevance of determining the status of LIG1, and potentially other non-HRR DRG for CRPC patient stratification and provide evidence to expand their therapeutic options.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__180,

title = {A multiparametric screen uncovers FDA-approved small molecules that potentiate the nuclear mechano-dysfunctions in ATR-defective cells},

author = {Cera MR and Bastianello G and Purushothaman D and Andronache A and Ascione F and Robusto M, Faga' G and Pasi M and Meroni G and Li Q and Choudhary R and Varasi M and Foiani M and Mercurio C},

url = {https://www.nature.com/articles/s41598-024-80837-w},

doi = {10.1038/s41598-024-80837-w},

year  = {2024},

date = {2024-12-12},

urldate = {2024-12-12},

journal = {Scientific reports},

volume = {14},

issue = {1},

pages = {30786},

abstract = {Targeting nuclear mechanics is emerging as a promising therapeutic strategy for sensitizing cancer cells to immunotherapy. Inhibition of the mechano-sensory kinase ATR leads to mechanical vulnerability of cancer cells, causing nuclear envelope softness and collapse and activation of the cGAS-STING-mediated innate immune response. Finding novel compounds that interfere with the non-canonical role of ATR in controlling nuclear mechanics presents an intriguing therapeutic opportunity. We carried out a multiparametric high-content screen to identify small molecules that affect nuclear envelope shape and to uncover novel players that could either ameliorate or further compromise the nuclear mechanical abnormalities of ATR-defective cells. The screen was performed in HeLa cells genetically depleted for ATR. Candidate hits were also tested in combination with the chemical inhibition of ATR by AZD6738, and their efficacy was further validated in the triple-negative breast cancer cell lines BT549 and HCC1937. We show that those compounds enhancing the abnormal nuclear shape of ATR-defective cells also synergize with AZD6738 to boost the expression of interferon-stimulated genes, highlighting the power of multiparametric screens to identify novel combined therapeutic interventions targeting nuclear mechanics for cancer immunotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__190,

title = {A Novel G-Quadruplex Structure within Apolipoprotein E Promoter: A New Promising Target in Cancer and Dementia Fight?},

author = {Pirota V and Stritto AD and Magnaghi LR and Biesuz R and Doria F and Mella M and Freccero M and Crespan E},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11561760/},

doi = {10.1021/acsomega.4c06430},

year  = {2024},

date = {2024-12-11},

journal = {ACS omega},

volume = {9},

issue = {45},

pages = {45203-45213},

abstract = {Human apolipoprotein E (APOE) is a crucial lipid transport glycoprotein involved in various biological processes, including lipid metabolism, immune response, and neurodegeneration. Elevated APOE levels are linked to poor prognosis in several cancers and increased risk of Alzheimer's disease (AD). Therefore, modulating APOE expression presents a promising therapeutic strategy for both cancer and AD. Considering the pivotal role of G-quadruplex (G4) structures in medicinal chemistry as modulators of gene expression, here, we present a newly discovered G-quadruplex (G4) structure within the ApoE gene promoter. Bioinformatic analysis identified 21 potential G4-forming sequences in the ApoE promoter, with the more proximal to the transcription start site, pApoE, showing the highest G-score. Biophysical studies confirmed the folding of pApoE into a stable parallel G4 under physiological conditions, supported by circular dichroism, NMR spectroscopy, UV-melting, and a quantitative PCR stop assay. Moreover, the ability to modulate pApoE-G4 folding was demonstrated by using G4-stabilizing ligands (HPHAM, Braco19, and PDS), which increased the thermal stability of pApoE-G4. In contrast, peptide nucleic acid conjugates were synthesized to disrupt G4 formation, effectively hybridizing with pApoE sequences, and confirming the potential to unfold G4 structures. Overall, our findings provide a mainstay for future therapeutic approaches targeting ApoE-G4s to regulate APOE expression, offering potential advancements in cancer and AD treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__187,

title = {Aging research from bench to bedside and beyond: What we learned from Sammy Basso},

author = {Lattanzi G and Lanzuolo C and Cugudda E and Maggi L and Politano L and Santiago-Fernández O and Ricci G and Squarzoni S and Lopez-Otin C},

url = {https://onlinelibrary.wiley.com/doi/10.1111/acel.14414},

doi = {10.1111/acel.14414},

year  = {2024},

date = {2024-12-11},

journal = {Aging Cell},

volume = {23},

issue = {12},

pages = {e14414},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__183,

title = {Separation of function mutants underline multiple roles of the Srs2 helicase/translocase in break-induced replication in Saccharomyces cerevisiae},

author = {Di Terlizzi M and Liberi G and Pellicioli A},

url = {https://pmc.ncbi.nlm.nih.gov/articles/PMC11582884/},

doi = {10.17912/micropub.biology.001369},

year  = {2024},

date = {2024-12-11},

journal = {microPublication biology},

abstract = {All cells are commonly exposed to DNA double-strand breaks (DSBs), which must be properly repaired to avoid genomic instability. Break-Induced Replication (BIR) is a Homologous Recombination subpathway, which repairs DSBs resulting in mutagenesis, chromosome translocations and loss of heterozygosity. In budding yeast, the Srs2 DNA helicase/translocase plays both anti- and pro-recombination roles. Interestingly, Srs2 activities are required to support BIR completion. Here, we employ a interchromosomal BIR assay in S. cerevisiae to characterize Cdk1-dependent phosphorylation, ATPase and helicase activities of Srs2. Our results further expand our understanding of the multifaced role played by Srs2 in DSB recombination repair},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__182,

title = {Corrigendum to "Applying molecular hybridization to design a new class of pyrazolo[3,4-d] pyrimidines as Src inhibitors active in hepatocellular carcinoma" [Eur. J. Med. Chem. 280 (2024) 116929]},

author = {{Di Maria S} and Passannanti R and Poggialini F and Vagaggini C and Serafinelli A and Bianchi E and Governa P and Botta L and Maga G and Crespan E and Manetti F and Dreassi E and Musumeci F and Carbone A and Schenone S.},

url = {https://www.sciencedirect.com/science/article/pii/S0223523425000509?via%3Dihub},

doi = {10.1016/j.ejmech.2025.117285},

year  = {2024},

date = {2024-12-11},

journal = {European journal of medicinal chemistry},

volume = {286},

pages = {117285},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__181,

title = {Human head and neck cancer cell lines response to cold atmospheric plasma activated media is affected by the chemistry of culture media},

author = {di Giacomo V and Balaha M and Pece A and Cela I and Fulgenzi G and Orsini G and Spadoni T and Acharya TR and Kaushik NK and Choi EH and Rapino M and Mazzone M and Mincione G and Sala G and Sardella E and Perrotti V},

url = {https://www.sciencedirect.com/science/article/pii/S2405844024174890?via%3Dihub},

doi = {10.1016/j.heliyon.2024.e41458},

year  = {2024},

date = {2024-12-11},

journal = {Heliyon},

volume = {11},

issue = {1},

pages = {e41458},

abstract = {Survival rate of head and neck squamous cell carcinomas (HNSCC) patients are still to date very poor, and the application of innovative clinical approaches are urgently needed. Cold atmospheric plasmas (CAPs) are partially ionized gases that have shown anti-tumor effectiveness over a wide range of cancer types with potential application into clinics. However, the comprehension of the mechanisms underlying indirect CAP effects plays a key role for the prediction of treatment outcomes. In our work, we assessed the potential application of indirect CAP, by using plasma activated media (PAM) and plasma-treated liquids (PTL), as therapeutic strategies for HNSCC treatment. The impact of PAM obtained from exposure to CAP for different times was evaluated in three head and neck cancer (HNC) cell lines (HSC3, FaDu, CAL-27). Cytotoxic effects as inhibition of proliferation, apoptosis rate and cell cycle modifications were tested for the different PAM, showing a time- and cell culture media-dependence tightly related to the chemical composition of PAM considered. In addition, cytotoxic effects were also observed on HNC, two bladder cancer models and one breast cancer cell line when considering PTL, paving the way for their application into a clinical setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {Impact of heat and cold shock on epigenetics and chromatin structure},

author = {Casali C and Galgano L and Zannino L and Siciliani S and Cavallo M and Mazzini G and Biggiogera M},

url = {https://www.sciencedirect.com/science/article/pii/S0171933523000882?via%3Dihub},

doi = {10.1016/j.ejcb.2023.151373},

year  = {2024},

date = {2024-12-11},

urldate = {2024-12-11},

journal = {European journal of cell biology},

volume = {103},

issue = {1},

pages = {151373},

abstract = {Cells are continuously exposed to various sources of insults, among which temperature variations are extremely common. Epigenetic mechanisms, critical players in gene expression regulation, undergo alterations due to these stressors, potentially leading to health issues. Despite the significance of DNA methylation and histone modifications in gene expression regulation, their changes following heat and cold shock in human cells remain poorly understood. In this study, we investigated the epigenetic profiles of human cells subjected to hyperthermia and hypothermia, revealing significant variations. Heat shock primarily led to DNA methylation increments and epigenetic modifications associated with gene expression silencing. In contrast, cold shock presented a complex scenario, with both methylation and demethylation levels increasing, indicating different epigenetic responses to the opposite thermal stresses. These temperature-induced alterations in the epigenome, particularly their impact on chromatin structural organization, represent an understudied area that could offer important insights into genome function and potential prospects for therapeutic targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_179,

title = {Restored Collagen VI Microfilaments Network in the Extracellular Matrix of CRISPR-Edited Ullrich Congenital Muscular Dystrophy Fibroblasts},

author = {Benati D and Cattin E and Corradi F and Ferrari T and Pedrazzoli E and Patrizi C and Marchionni M and Bertorelli R and De Sanctis V and Merlini L and Ferlini A and Sabatelli P and Gualandi F and Recchia A},

url = {https://www.mdpi.com/2218-273X/14/11/1412},

doi = {10.3390/biom14111412},

year  = {2024},

date = {2024-12-11},

urldate = {2024-12-11},

journal = {Biomolecules},

volume = {14},

number = {1412},

issue = {11},

abstract = {Collagen VI is an essential component of the extracellular matrix (ECM) composed by α1, α2 and α3 chains and encoded by COL6A1, COL6A2 and COL6A3 genes. Dominant negative pathogenic variants in COL6A genes result in defects in collagen VI protein and are implicated in the pathogenesis of muscular diseases, including Ullrich congenital muscular dystrophy (UCMD). Here, we designed a CRISPR genome editing strategy to tackle a dominant heterozygous deletion c.824_838del in exon 9 of the COL6A1 gene, causing a lack of secreted collagen VI in a patient's dermal fibroblasts. The evaluation of efficiency and specificity of gene editing in treating patient's fibroblasts revealed the 32% efficiency of editing the mutated allele but negligible editing of the wild-type allele. CRISPR-treated UCMD skin fibroblasts rescued the secretion of collagen VI in the ECM, which restored the ultrastructure of the collagen VI microfibril network. By using normal melanocytes as surrogates of muscle cells, we found that collagen VI secreted by the corrected patient's skin fibroblasts recovered the anchorage to the cell surface, pointing to a functional improvement of the protein properties. These results support the application of the CRISPR editing approach to knock out COL6A1 mutated alleles and rescue the UCMD phenotype in patient-derived fibroblasts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__186,

title = {Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma},

author = {Grisendi G and Dall'Ora M and Casari G and Spattini G and Farshchian M and Melandri A and Masicale V and Lepore F and Banchelli F and Costantini RC and D'Esposito A and Chiavelli C and Spano C and Spallanzani A and Petrachi T and Veronesi E and Ferracin M and Roncarati R and Vinet J and Magistri P and Catellani B and Candini O and Marra C and Eccher A and Bonetti LR and Horwtiz EM and Di Benedetto F and Dominici M},

url = {https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00406-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379124004063%3Fshowall%3Dtrue},

doi = {10.1016/j.xcrm.2024.101685},

year  = {2024},

date = {2024-12-10},

journal = {Cell reports medicine},

volume = {5},

issue = {8},

pages = {101685},

abstract = {Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__188,

title = {A New Vista of Aldehyde Dehydrogenase 1A3 (ALDH1A3): New Specific Inhibitors and Activity-Based Probes Targeting ALDH1A3 Dependent Pathways in Glioblastoma, Mesothelioma and Other Cancers },

author = {Magrassi L and Pinton G and Luzzi S and Comincini S and Scravaglieri A and Gigliotti V and Bernardoni BL and D'Agostino I and Juretich F and La Motta C and Garavaglia S.},

url = {https://www.mdpi.com/2072-6694/16/13/2397},

doi = {10.3390/cancers16132397},

year  = {2024},

date = {2024-12-04},

journal = {Cancers (Basel)},

volume = {16},

issue = {13},

pages = {2397},

abstract = {Aldehyde dehydrogenases of the subfamily 1A (ALDH1A) are enzymes necessary for the oxidation of all-trans or 9-cis retinal to retinoic acid (RA). Retinoic acid and its derivatives are important for normal development and maintenance of epithelia, reproduction, memory, and immune function in adults. Moreover, in recent years, it has been demonstrated that ALDH1A members are also expressed and functional in several human cancers where their role is not limited to the synthesis of RA. Here, we review the current knowledge about ALDH1A3, one of the 1A isoforms, in cancers with an emphasis on two of the deadliest tumors that affect humans: glioblastoma multiforme and mesothelioma. In both tumors, ALDH1A3 is considered a negative prognostic factor, and its level correlates with excessive proliferation, chemoresistance, and invasiveness. We also review the recent attempts to develop both ALDH1A3-selective inhibitors for cancer therapy and ALDH1A3-specific fluorescent substrates for fluorescence-guided tumor resection. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__178,

title = {Myoblast-Derived Galectin 3 Impairs the Early Phases of Osteogenesis Affecting Notch and Akt Activity},

author = {Amore E and Cenni V and Piazzi M and Signore M and Orlandi G and Neri S and Biressi S and Barone R and Di Felice V and Follo MY and Bertacchini J and Palumbo C},

url = {https://www.mdpi.com/2218-273X/14/10/1243},

doi = {10.3390/biom14101243},

year  = {2024},

date = {2024-12-02},

urldate = {2024-12-02},

journal = {Biomolecules},

volume = {14},

issue = {10},

pages = {1243},

abstract = {Galectin-3 (Gal-3) is a pleiotropic lectin produced by most cell types, which regulates multiple cellular processes in various tissues. In bone, depending on its cellular localization, Gal-3 has a dual and opposite role. If, on the one hand, intracellular Gal-3 promotes bone formation, on the other, its circulating form affects bone remodeling, antagonizing osteoblast differentiation and increasing osteoclast activity. From an analysis of the secretome of cultured differentiating myoblasts, we interestingly found the presence of Gal-3. After that, we confirmed that Gal-3 was expressed and released in the extracellular environment from myoblast cells during their differentiation into myotubes, as well as after mechanical strain. An in vivo analysis revealed that Gal-3 was triggered by trained exercise and was specifically produced by fast muscle fibers. Speculating a role for this peptide in the muscle-to-bone cross talk, a direct co-culture in vitro system, simultaneously combining media that were obtained from differentiated myoblasts and osteoblast cells, confirmed that Gal-3 is a mediator of osteoblast differentiation. Molecular and proteomic analyses revealed that the secreted Gal-3 modulated the biochemical processes occurring in the early phases of bone formation, in particular impairing the activity of the STAT3 and PDK1/Akt signaling pathways and, at the same time, triggering that one of Notch. Circulating Gal-3 also affected the expression of the most common factors involved in osteogenetic processes, including BMP-2, -6, and -7. Intriguingly, Gal-3 was able to interfere with the ability of differentiating osteoblasts to interact with the components of the extracellular bone matrix, a crucial condition required for a proper osteoblast differentiation. All in all, our evidence lays the foundation for further studies to present this lectin as a novel myokine involved in muscle-to-bone crosstalk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_183,

title = {Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants},

author = {Young WJ and van der Most PJ and Bartz TM and Bos MM and Biino G and Duong T and Foco L and Lominchar JT and Muller-Nurasyid M and Nardone GG and Pecori A and Ramirez J and Repetto L and Schramm K and Shen X and van Duijvenboden S and van Heemst D and Weiss S and Yao J and Benjamins JW and Alonso A and Spedicati B and Biggs ML and Brody JA and Dörr M and Fuchsberger C and Gögele M and Guo X and Ikram MA and Jukema JW and Kaab S and Kanters JK; Lifelines Cohort Study; Lin HJ and Linneberg A and Nauck M and Nolte IM and Pianigiani G and Santin A and Soliman EZ and Tesolin P and Vaccargiu S and Waldenberger M and van der Harst P and Verweij N and Arking DE and Concas MP and De Grandi A and Girotto G and Grarup N and Kavousi M and Mook-Kanamori DO and Navarro P and Orini M and Padmanabhan S and Pattaro C and Peters A and Pirastu M and Pramstaller PP and Heckbert SR and Sinner M and Snieder H and Volker U and Wilson JF and Gauderman WJ and Lambiase PD and Sotoodehnia N and Tinker A and Warren HR and Noordam R and Munroe PB.},

url = {https://www.ahajournals.org/doi/10.1161/JAHA.123.034760?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed},

doi = {10.1161/JAHA.123.034760},

year  = {2024},

date = {2024-10-21},

journal = {Journal of the American Heart Association},

volume = {13},

issue = {17},

pages = {e034760},

abstract = {Background: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. Methods and results: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5×10-8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). Conclusions: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_181,

title = {Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families},

author = {Martina MG and Carlen V and Van der Reysen S and Bianchi E and Cabella N and Crespan E and Radi M and Cagno V},

url = {https://www.sciencedirect.com/science/article/pii/S0166354224002122?via%3Dihub},

doi = {10.1016/j.antiviral.2024.106003},

year  = {2024},

date = {2024-10-21},

urldate = {2024-10-21},

journal = {Antiviral research},

volume = {231},

pages = {106003},

abstract = {Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the Picornaviridae family. Herein we describe the optimization of bithiazole PI4KB inhibitors as broad-spectrum antivirals (BSAs) active against different members of the Picornaviridae, Coronaviridae, Flaviviridae and Poxviridae families. Since some of these viruses are transmitted via respiratory route, the efficacy of one of the most promising compounds was evaluated in an airway model. The molecule showed complete viral inhibition and absence of toxicity. These results pave the road for the development of new BSAs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_180,

title = {A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4'-dihydroxy- trans- stilbene},

author = {Livraghi V and Mazza L and Chiappori F and Cardano M and Cazzalini O and Puglisi R and Capoferri R and Pozzi A and Stivala LA and Zannini L and Savio M},

url = {https://www.sciencedirect.com/science/article/pii/S2225411024000208?via%3Dihub},

doi = {10.1016/j.jtcme.2024.03.001},

year  = {2024},

date = {2024-10-21},

journal = {Journal of traditional and complementary medicine},

volume = {14},

number = {543},

issue = {5},

abstract = {Background and aim: Resveratrol (RSV), is a stilbene-based compound exerting wide biological properties. Its analogue 4,4'-dihydroxy-trans-stilbene (DHS) has shown improved bioavailability and antiproliferative activity in vitro and in vivo. One of the hypotheses on how resveratrol works is based on SIRT1 activation. Since their strict structural similarities, we have explored a potential interaction between DHS and SIRT1, in comparison with the parental molecule. Experimental procedure: Timing of incubation and concentrations of DHS have been determined using MTT assay in normal human lung fibroblasts. Untreated, DHS- or RSV-treated cells were harvested and analysed by Western Blotting or RT-PCR, in order to evaluate SIRT1 levels/activity and expression, and by Cellular Thermal shift assay (CETSA) to check potential DHS or RSV-SIRT1 interaction. Transfection experiments have been performed with two SIRT1 mutants, based on the potential binding pockets identified by Molecular Docking analysis. Results and conclusion: We unexpectedly found that DHS, but not RSV, exerted a time-dependent inhibitory effect on both SIRT1 protein levels and activity, the latter measured as p53 acetylation. At the mRNA level no significant changes were observed, whereas a proteasome-dependent mechanism was highlighted for the reduction of SIRT1 levels by DHS in experiments performed with the proteasome inhibitor MG132. Bioinformatics analysis suggested a higher affinity of RSV in binding all SIRT1 complexes compared to DHS, except comparable results for complex SIRT1-p53. Nevertheless, both CETSA and SIRT1 mutants transfected in cells did not confirm this interaction. In conclusion, DHS reduces SIRT1 protein level, thereby inhibiting its activity through a proteasome-mediated mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_179,

title = {Applying molecular hybridization to design a new class of pyrazolo[3,4-d]pyrimidines as Src inhibitors active in hepatocellular carcinoma},

author = {{Di Maria S} and Passannanti R and Poggialini F and Vagaggini C and Serafinelli A and Bianchi E and Governa P and Botta L and Maga G and Crespan E and Manetti F and Dreassi E and Musumeci F and Carbone A and Schenone S},

url = {https://www.sciencedirect.com/science/article/pii/S0223523424008109?via%3Dihub},

doi = {10.1016/j.ejmech.2024.116929},

year  = {2024},

date = {2024-10-21},

journal = {European journal of medicinal chemistry},

volume = {280},

pages = {116929},

abstract = {Hepatocellular carcinoma (HCC) is the most common type of liver solid tumor and the second leading cause of cancer-related deaths worldwide. Although new treatment options have been recently approved, the development of tumor resistance and the poor prognosis for advanced HCC make the current standard of care unsatisfying. In this scenario, the non-receptor tyrosine kinase (TK) c-Src emerged as a promising target for developing new anti-HCC agents. Our group reported a large library of pyrazolo[3,4-d]pyrimidines active as potent c-Src inhibitors. Starting from these data, we applied a molecular hybridization approach to combine the in-house pyrazolo[3,4-d]pyrimidine SI192 with the approved TK inhibitor (TKI) dasatinib, with the aim of identifying a new generation of Src inhibitors. Enzymatic results prompted us to design second-generation compounds with a better binding profile based on a hit optimization protocol comprised of molecular modeling and on-paper rational design. This investigation led to the identification of a few nanomolar Src inhibitors active toward two HCC cell lines (HepG2 and HUH-7) selected according to their high and low c-Src expression, respectively. In particular, 7e showed an IC50 value of 0.7 nM toward Src and a relevant antiproliferative efficacy on HepG2 cells after 72h (IC50 = 2.47 μM). Furthermore, 7e exhibited a cytotoxic profile better than dasatinib. The ADME profile suggested that 7e deserves further investigation as a promising TKI in cancer therapies. Finally, 7e's ability to inhibit HepG2 cell proliferation, elicit an irreversible cytotoxic effect, arrest cellular migration, and induce apoptotic-mediated cell death was assessed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__172,

title = {Phospholipase Cdelta-4 (PLCdelta4) Acts as a Nuclear Player to Influence Cyclin B Expression in the Embryonal Rhabdomyosarcoma Cell Lines RD and A204},

author = {Salucci S and Bavelloni A and Versari I and Burattini S and Bavelloni F and Gobbi P and Fanzani A and Codenotti S and Blalock W and Scotlandi K and Faenza I},

url = {https://www.mdpi.com/2218-273X/14/9/1180},

doi = {10.3390/biom14091180},

year  = {2024},

date = {2024-10-21},

journal = {Biomolecules},

volume = {14},

issue = {9},

pages = {1180},

abstract = {Rhabdomyosarcoma (RMS), the most common form of sarcoma typical of pediatric age, arises from the malignant transformation of the mesenchymal precursors that fail to differentiate into skeletal muscle cells. Here, we investigated whether the protein phospholipase C delta4 (PLCdelta4), a member of the PLC family involved in proliferation and senescence mechanisms of mesenchymal stromal stem cells, may play a role in RMS. Our molecular and morpho-functional data reveal that PLCδ4 is highly expressed in the fusion-negative, p53-positive, SMARCB1 heterozygous mutated embryonal RMS (ERMS) cell line A204, while it is poorly expressed in the ERMS cell lines RD (fusion-negative, MYC amplification, N-RAS (Q61H), homozygous mutated p53) and Hs729 (homozygous mutated p53) and the alveolar rhabdosarcoma (ARMS) cell line SJCRH30 (RH30; fusion positive, heterozygous mutated RARA, polyheterozygous mutated p53). To characterize the role of PLCdelta4, the RD cell line was stably transfected with wild-type PLCδ4 (RD/PLCδ4). Overexpressed PLCδ4 mainly localized to the nucleus in RD cells and contributed to the phosphorylation of PRAS40 (T246), Chk2(T68), WNK1(T60), and Akt 1/273 (S473), as revealed by proteome profiler array analysis. Overexpression of PLCdelta4 in RD cells enhanced cyclin B1 expression and resulted in G2/M-phase cell cycle arrest. In contrast, siRNA-mediated knockdown of PLCdelta4 in A204 cells resulted in reduced cyclin B1 expression. Our study identifies a novel role for nuclear PLCdelta4 as a regulator of cyclin B1 via Akt-dependent phosphorylation. The modulation of PLCdelta4 expression and its downstream targets could represent a crucial signaling pathway to block embryonal RMS cell proliferation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__171,

title = {MicroRNA dysregulation in ataxia telangiectasia},

author = {Cirillo E and Tarallo A and Toriello E and Carissimo A and Giardino G and De Rosa A and Damiano C and Soresina A and Badolato R and Dellepiane RM and Baselli LA and Carrabba M and Fabio G and Bertolini P and Montin D and Conti F and Romano R and Pozzi E and Ferrero G and Roncarati R and Ferracin M and Brusco A and Parenti G and Pignata C},

url = {https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1444130/full},

doi = {10.3389/fimmu.2024.1444130},

year  = {2024},

date = {2024-10-21},

journal = {Frontiers in immunology},

volume = {15},

pages = {1444130},

abstract = {Introduction: Ataxia telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, a predisposition to malignancies, and high clinical variability. Profiling of microRNAs (miRNAs) may offer insights into the underlying mechanisms of complex rare human diseases, as miRNAs play a role in various biological functions including proliferation, differentiation, and DNA repair. In this study, we investigate the differential expression of miRNAs in samples from AT patients to identify miRNA patterns and analyze how these patterns are related to the disease. Methods: We enrolled 20 AT patients (mean age 17.7 ± 9.6 years old) and collected clinical and genetic data. We performed short non-coding RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and fibroblasts to compare the miRNA expression profile between AT patients and controls. Results: We observed 42 differentially expressed (DE)-miRNAs in blood samples and 26 in fibroblast samples. Among these, three DE-miRNAs, miR-342-3p, miR-30a-5p, and miR-195-5p, were further validated in additional AT samples, confirming their dysregulation. Discussion: We identified an AT-related miRNA signature in blood cells and fibroblast samples collected from a group of AT patients. We also predicted several dysregulated pathways, primarily related to cancer, immune system control, or inflammatory processes. The findings suggest that miRNAs may provide insights into the pathophysiology and tumorigenesis of AT and have the potential to serve as useful biomarkers in cancer research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_162,

title = {CAPE derivatives: Multifaceted agents for chronic wound healing},

author = {Balaha M and Cataldi A and Ammazzalorso A and Cacciatore I and De Filippis B and Di Stefano A and Maccallini C and Rapino M and {Korona-Glowniak I} and Przekora A and {di Giacomo V}},

url = {https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400165},

doi = {10.1002/ardp.202400165},

year  = {2024},

date = {2024-10-02},

urldate = {2024-08-06},

journal = {Archiv der Pharmazie},

abstract = {Chronic wounds significantly impact the patients' quality of life, creating an urgent interdisciplinary clinical challenge. The development of novel agents capable of accelerating the healing process is essential. Caffeic acid phenethyl ester (CAPE) has demonstrated positive effects on skin regeneration. However, its susceptibility to degradation limits its pharmaceutical application. Chemical modification of the structure improves the pharmacokinetics of this bioactive phenol. Hence, two novel series of CAPE hybrids were designed, synthesized, and investigated as potential skin regenerative agents. To enhance the stability and therapeutic efficacy, a caffeic acid frame was combined with quinolines or isoquinolines by an ester (1a-f) or an amide linkage (2a-f). The effects on cell viability of human gingival fibroblasts (HGFs) and HaCaT cells were evaluated at different concentrations; they are not cytotoxic, and some proved to stimulate cell proliferation. The most promising compounds underwent a wound-healing assay in HGFs and HaCaT at the lowest concentrations. Antimicrobial antioxidant properties were also explored. The chemical and thermal stabilities of the best compounds were assessed. In silico predictions were employed to anticipate skin penetration capabilities. Our findings highlight the therapeutic potential of caffeic acid phenethyl ester (CAPE) derivatives 1a and 1d as skin regenerative agents, being able to stimulate cell proliferation, control bacterial growth, regulate ROS levels, and being thermally and chemically stable. An interesting structure-activity relationship was discussed to suggest a promising multitargeted approach for enhanced wound healing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_176,

title = {Sch9S6K controls DNA repair and DNA damage response efficiency in aging cells },

author = {Lucca C AND Ferrari E AND Shubassi G AND Ajazi A AND Choudhary R AND Bruhn C AND Matafora V AND Bachi A AND Foiani M},

url = {https://www.sciencedirect.com/science/article/pii/S2211124724006090?via%3Dihub},

doi = {10.1016/j.celrep.2024.114281},

year  = {2024},

date = {2024-09-05},

journal = {Cell Reports},

volume = {43},

issue = {6},

pages = {114281},

abstract = {Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1ATR DNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1ATR. We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1AMPK rescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9S6K axis restores NER and enhances DDR by tuning PP2A activity, specifically in aging cells. Age-related repair deficiency depends on Snf1AMPK-mediated phosphorylation of Sch9S6K on Ser160 and Ser163. PP2A activity in old cells is detrimental for DDR and influences NER by modulating Snf1AMPK and Sch9S6K. Hence, the DDR and repair pathways in aging cells are influenced by the metabolic tuning of opposing AMPK and TORC1 networks and by PP2A activity. Specific Sch9S6K phospho-isoforms control DDR and NER efficiency, specifically during aging. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y,

title = {Mechanical stress during confined migration causes aberrant mitoses and c-MYC amplification },

author = {Bastianello G AND Kidiyoor GR AND Lowndes C AND Li Q AND Bonnal R AND Godwin J AND Iannelli F AND Drufuca L AND Bason R AND Orsenigo F AND Parazzoli D AND Pavani M AND Cancila V AND Piccolo S AND Scita G AND Ciliberto A AND Tripodo C AND Pagani M AND Foiani M},

url = {https://www.pnas.org/doi/abs/10.1073/pnas.2404551121?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed},

doi = {10.1073/pnas.2404551121},

year  = {2024},

date = {2024-09-05},

urldate = {2024-09-05},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {121},

issue = {29},

pages = {e2404551121},

abstract = {Confined cell migration hampers genome integrity and activates the ATR and ATM mechano-transduction pathways. We investigated whether the mechanical stress generated by metastatic interstitial migration contributes to the enhanced chromosomal instability observed in metastatic tumor cells. We employed live cell imaging, micro-fluidic approaches, and scRNA-seq to follow the fate of tumor cells experiencing confined migration. We found that, despite functional ATR, ATM, and spindle assembly checkpoint (SAC) pathways, tumor cells dividing across constriction frequently exhibited altered spindle pole organization, chromosome mis-segregations, micronuclei formation, chromosome fragility, high gene copy number variation, and transcriptional de-regulation and up-regulation of c-MYC oncogenic transcriptional signature via c-MYC locus amplifications. In vivo tumor settings showed that malignant cells populating metastatic foci or infiltrating the interstitial stroma gave rise to cells expressing high levels of c-MYC. Altogether, our data suggest that mechanical stress during metastatic migration contributes to override the checkpoint controls and boosts genotoxic and oncogenic events. Our findings may explain why cancer aneuploidy often does not correlate with mutations in SAC genes and why c-MYC amplification is strongly linked to metastatic tumors. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y__169,

title = {Synergistic action of human RNaseH2 and the RNA helicase-nuclease DDX3X in processing R-loops},

author = {Secchi M and Garbelli A and Riva V and Deidda G and Santonicola C and Formica TM and Sabbioneda S and Crespan E and Maga G},

url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkae731/7742382?login=true},

doi = {10.1093/nar/gkae731},

year  = {2024},

date = {2024-09-02},

urldate = {2024-09-02},

journal = {Nucleic acids research},

volume = {52},

issue = {19},

pages = {11641-11658},

abstract = {R-loops are three-stranded RNA-DNA hybrid structures that play important regulatory roles, but excessive or deregulated R-loops formation can trigger DNA damage and genome instability. Digestion of R-loops is mainly relying on the action of two specialized ribonucleases: RNaseH1 and RNaseH2. RNaseH2 is the main enzyme carrying out the removal of misincorporated rNMPs during DNA replication or repair, through the Ribonucleotide Excision Repair (RER) pathway. We have recently shown that the human RNA helicase DDX3X possessed RNaseH2-like activity, being able to substitute RNaseH2 in reconstituted RER reactions. Here, using synthetic R-loop mimicking substrates, we could show that human DDX3X alone was able to both displace and degrade the ssRNA strand hybridized to DNA. Moreover, DDX3X was found to physically interact with human RNaseH2. Such interaction suppressed the nuclease and helicase activities of DDX3X, but stimulated severalfold the catalytic activity of the trimeric RNaseH2, but not of RNaseH1. Finally, silencing of DDX3X in human cells caused accumulation of RNA-DNA hybrids and phosphorylated RPA foci. These results support a role of DDX3X as a scaffolding protein and auxiliary factor for RNaseH2 during R-loop degradation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_,

title = {Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma},

author = {Grisendi G and Dall'Ora M and Casari G and Spattini G and Farshchian M and Melandri A and Masicale V and Lepore F and Banchelli F and Costantini RC and D'Esposito A and Chiavelli C and Spano C and Spallanzani A and Petrachi T and Veronesi E and Ferracin M and Roncarati R and Vinet J and Magistri P and Catellani B and Candini O and Marra C and Eccher A and Bonetti LR and Horwtiz EM and Di Benedetto F and Dominici M},

url = {https://www.sciencedirect.com/science/article/pii/S2666379124004063?via%3Dihub},

doi = {10.1016/j.xcrm.2024.101685},

year  = {2024},

date = {2024-09-02},

urldate = {2024-09-02},

journal = {Cell reports. Medicine.},

volume = {5},

issue = {8},

pages = {101685},

abstract = {Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_172,

title = {Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives},

author = {Carosi F and Broseghini E and Fabbri L and Corradi G and Gili R and Forte V and Roncarati R and Filippini DM and Ferracin M},

url = {https://www.mdpi.com/2072-6694/16/15/2752},

doi = {10.3390/cancers16152752},

year  = {2024},

date = {2024-09-02},

urldate = {2024-09-02},

journal = {Cancers},

volume = {16},

issue = {15},

pages = {2752},

abstract = {The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included},

keywords = {},

pubstate = {published},

tppubtype = {article}

}