1,355,079 research outputs found
Sulla lettura del Fedone nella ‘Quarta Accademia’ (con riflessioni sulla composizione dell’Assioco pseudoplatonico)
No full textFew years ago, William Stull has persuasively examined Cicero’s peculiar reading of Plato’s Phaedo in Tusculans i (Reading the Phaedo in Tusculan Disputations 1, «Classical Philology», cvii, pp. 38-52). This article aims to show that Stull’s results can be interpreted not as Cicero’s personal reading of Plato’s Phaedo, but as his personal reinterpretation of a certain ‘hermeneutic approach’ to the Phaedo, which had been probably developed in the Academy led by Philo of Larissa, Cicero’s Academic master. Besides other reasons, this hypothesis is supported by the impressive intertextual play existing between the pseudo-platonic Axiochus and Tusculans i, as well as between these two dialogues and the Phaedo. In the ‘Appendix’ the author discusses the recent article by Francesco Verde (Filone di Larissa e l’Assioco, «Elenchos», xlii.1, 2021, pp. 199-208) dealing with A. Beghini, [Platone], Assioco, saggio introduttivo, edizione critica, traduzione e commento, Baden-Baden, Academia Verlag, 2020
Molecular events in acute myeloid leukemogenesis: a model from core binding factor leukemia
No full textFZD4 (frizzled class receptor 4)
No full textFzd4 is a receptor for Wnt proteins, belonging to the frizzled receptors family. Its stimulation can activate both Wnt/β-catenin canonical and Wnt/Ca2+ non canonical pathways. This receptor plays an important role in the development processes, in particular in the retinal vascularization: it binds the Norrin ligand, a Wnt-unrelated growth factor, and activates β-catenin signalling pathway. Mutations of FZD4 gene are associated with Familial Exudative Vitreoretinopathy (FEVR). Recently dysregulation of FZD4 expression has been reported in different type of cancers, but FZD4 contribution in tumor pathogenesis and progression is still not entirely elucidated
Core Binding Factor Leukemia : Chromatin Remodeling Moves Towards Oncogenic Transcription
No full textAcute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous malignant clonal disorder arising from multipotent hematopoietic progenitor cells characterized by genetic and concerted epigenetic aberrations. Core binding factor-Leukemia (CBFL) is characterized by the recurrent reciprocal translocations t(8;21)(q22;q22) or inv(16)(p13;q22) that, expressing the distinctive RUNX1-RUNX1T1 (also known as Acute myeloid leukemia1-eight twenty-one, AML1-ETO or RUNX1/ETO) or CBFB-MYH11 (also known as CBFβ-SMMHC) translocation product respectively, disrupt the essential hematopoietic function of the CBF. In the past decade, remarkable progress has been achieved in understanding the structure, three-dimensional (3D) chromosomal topology, and disease-inducing genetic and epigenetic abnormalities of the fusion proteins that arise from disruption of the CBF subunit alpha and beta genes. Although CBFLs have a relatively good prognosis compared to other leukemia subtypes, 40-50% of patients still relapse, requiring intensive chemotherapy and allogenic hematopoietic cell transplantation (alloHCT). To provide a rationale for the CBFL-associated altered hematopoietic development, in this review, we summarize the current understanding on the various molecular mechanisms, including dysregulation of Wnt/β-catenin signaling as an early event that triggers the translocations, playing a pivotal role in the pathophysiology of CBFL. Translation of these findings into the clinical setting is just beginning by improvement in risk stratification, MRD assessment, and development of targeted therapies
Carbonic Anhydrase 9: mastering ferropoptosis resistance in cancer, protector or weak point?
No full textFerroptosis is a recently discovered form of iron-dependent programmed cell death, characterized by the toxic accumulation of lipid peroxides that disrupt cell membrane function. Cancer cells are particularly susceptible to ferroptosis due to their high iron requirements for growth and a metabolism that creates an intracellular environment conducive to triggering this death mechanism. However, cancer cells counteract this vulnerability through carbonic anhydrase 9 (CA9), a protein that regulates intracellular pH, ensuring conditions unfavorable for ferroptosis.\\nThis minireview explores the factors necessary to induce ferroptosis and examines how CA9 not only protects cancer cells but also facilitates their migration. The aim is to highlight potential therapeutic opportunities arising from disrupting the functionality of this protein
Beyond the Warburg Effect: KRAS/MAPK-Driven Uridine Utilization in Glucose-Deprived Pancreatic Ductal Adenocarcinoma
No full textCancer cells exhibit a significantly altered metabolic phenotype, characterized by a distinctive reliance on glucose to support their growth, survival, and proliferation through a unique energy extraction mechanism. This metabolic reprogramming is epitomized by an increased glucose demand and a preference for lactic fermentation, even in the presence of oxygen, rather than the conventional citric acid cycle utilized by non-cancerous cells. This phenomenon, known as the Warburg Effect, serves as a hallmark of cancer metabolism. The implications of this metabolic shift extend beyond cellular energy dynamics, as it initiates the development of a novel tumor microenvironment characterized by adverse conditions such as hypoxia and glucose scarcity, particularly pronounced in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDA), a notably therapy-resistant malignancy, exemplifies this metabolic adaptation. Under conditions of glucose limitation, PDA cells demonstrate a remarkable ability to utilize uridine as a primary energy substrate, a process regulated by uridine phosphorylase 1 (UPP1). UPP1 plays a central role in metabolizing uridine-derived ribose, thereby supporting central carbon metabolism, maintaining redox homeostasis, and promoting cell survival and proliferation under nutrient-restricted conditions. This metabolic pathway is under the regulatory control of KRAS–MAPK signaling, which is further amplified in response to nutrient deprivation. Consistent with these observations, tumor specimens show elevated UPP1 expression compared to normal tissues, correlating with poor clinical outcomes. The availability of uridine in the tumor microenvironment and its active catabolism within tumor cells underscore the clinical importance of these metabolic processes. Notably, genetic ablation of UPP1 disrupts uridine utilization and significantly suppresses PDA growth in murine models.
In summary, this review highlights uridine metabolism as a pivotal compensatory mechanism enabling PDA cells to adapt to nutrient-deprived environments. By influencing the Warburg Effect, uridine utilization integrates nucleotide metabolism with energy production, revealing critical molecular pathways that regulate glucose metabolism in tumor cells. These findings provide novel insights into the metabolic flexibility of PDA and identify potential therapeutic targets for its treatment
Affermare l'immortalità dell'anima: il testo dell'Assioco tra Academici e Platonici
No full textAt the end of the Axiochus Socrates vigorously states that the soul is immortal (τοῦτο μόνον ἐμπέδως οἶδα ὅτι ψυχὴ ἅπασα ἀθάνατος· ἡ δὲ ἐκ τοῦδε τοῦ χωρίου μετασταθεῖσα καὶ ἄλυπος). However, this statement is in contrast with Socrates’ previous profession of ignorance in such matters. This contradiction raises the suspicion that the text is corrupted and possibly interpolated by a dogmatic Platonist. For this reason the author attempts the correction τοῦτο μόνον ἐμπέδως οἶδα ὅτι, ψυχὴ ἅπασα ἀθάνατος, [ἡ δὲ] ἐκ τοῦδε τοῦ χωρίου μετασταθεῖσα καὶ ἄλυπος. The XVIth century case of Étienne Dolet is a clear example of the ideological tensions that this dialogue could give rise t
CSNK2A2 (casein kinase 2 alpha 2)
No full textCSNK2A2 gene, 16q21, has a role in regulating the phosphorylation and circulation of old proteasomes by encoding the catalytic α' subunit of casein kinase 2 (CK2α'). Casein kinase 2 is a serine/threonine protein kinase that phosphorylates acidic proteins. It can regulate Wnt signalling by phosphorylating CTNNB1 and the transcription factor LEF1 and for this reason, it is involved in some cellular key processes such as cell cycle progression, inhibition of apoptosis, DNA damage repair, differentiation and transcription but also viral infection. CSNK2A2 is a cancer-related gene and its upregulation has been detected is many cancers such as glioblastoma multiforme, colorectal cancer, breast cancer and ovarian cancer, and also in some diseases such as diabetes, theileriasis in cattle and distal muscular dystrophy with anterior tibial onset in mice are associated with CSNK2A2
Affermare l’immortalità dell’anima: il testo dell’Assioco tra Academici e Platonici
No full textAt the end of the Axiochus Socrates vigorously states that the soul is immortal (τοῦτο μόνον ἐμπέδως οἶδα ὅτι ψυχὴ ἅπασα ἀθάνατος· ἡ δὲ ἐκ τοῦδε τοῦ χωρίου μετασταθεῖσα καὶ ἄλυπος). However, this statement is in contrast with Socrates’ previous profession of ignorance in such matters. This contradiction raises the suspicion that the text is corrupted and possibly interpolated by a dogmatic Platonist. For this reason the author attempts the correction τοῦτο μόνον ἐμπέδως οἶδα ὅτι, <εἰ> ψυχὴ ἅπασα ἀθάνατος, [ἡ δὲ] ἐκ τοῦδε τοῦ χωρίου μετασταθεῖσα καὶ ἄλυπος. The XVIth century case of Étienne Dolet is a clear example of the ideological tensions that this dialogue could give rise to
- …
