94 research outputs found
Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia
During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of \u3b3H2A.X protein expression and by the activation of different apoptotic markers (Parp-1 and pro-Caspase3 cleavage). Furthermore, the inhibition of Chk1 changed the cell cycle profile. In order to evaluate the chemo-sensitizer activity of the compound, different cell lines were treated for 24 and 48 hours with prexasertib in combination with other drugs (imatinib, dasatinib and clofarabine). The results from cell line models were strengthened in primary leukemic blasts isolated from peripheral blood of adult acute lymphoblastic leukemia patients. In this study we highlighted the mechanism of action and the effectiveness of prexasertib as single agent or in combination with other conventional drugs like imatinib, dasatinib and clofarabine in the treatment of B-/T-ALL
Novel and rare fusion transcripts involving transcription factors and tumor suppressor genes in acute myeloid leukemia
Approximately 18% of acute myeloid leukemia (AML) cases express a fusion transcript. However, few fusions are recurrent across AML and the identification of these rare chimeras is of interest to characterize AML patients. Here, we studied the transcriptome of 8 adult AML patients with poorly described chromosomal translocation(s), with the aim of identifying novel and rare fusion transcripts. We integrated RNA-sequencing data with multiple approaches including computational analysis, Sanger sequencing, fluorescence in situ hybridization and in vitro studies to assess the oncogenic potential of the ZEB2-BCL11B chimera. We detected 7 different fusions with partner genes involving transcription factors (OAZ-MAFK, ZEB2-BCL11B), tumor suppressors (SAV1-GYPB, PUF60-TYW1, CNOT2-WT1) and rearrangements associated with the loss of NF1 (CPD-PXT1, UTP6-CRLF3). Notably, ZEB2-BCL11B rearrangements co-occurred with FLT3 mutations and were associated with a poorly differentiated or mixed phenotype leukemia. Although the fusion alone did not transform murine c-Kit+ bone marrow cells, 45.4% of 14q32 non-rearranged AML cases were also BCL11B-positive, suggesting a more general and complex mechanism of leukemogenesis associated with BCL11B expression. Overall, by combining different approaches, we described rare fusion events contributing to the complexity of AML and we linked the expression of some chimeras to genomic alterations hitting known genes in AML
Using Radon-222 as a Naturally Occurring Tracer to investigate the streamflow-groundwater interactions in a typical Mediterranean fluvial-karst landscape: the interdisciplinary case study of the Bussento river (Campania region, Southern Italy).
Valutazione delle “Radon-prone Areas” su scala regionale mediante un approccio interdisciplinare gerarchico multi-scalare per la valutazione della radioattività naturale e la pianificazione ambientale. Caso studio della Regione Campania.
Valutazione delle Radon-Prone Areas in Regione Campania: un nuovo campo per la ricerca geologico-applicativa e la pratica professionale interdisciplinare
Radon-prone Areas Assessment in Campania Region. Applications of a Hierarchical and Multi-scale Approach to the Environmental Planning
Investigation of groundwater-surface waters interactions in karst environments, using Radon as an environmental tracer through alpha-spectrometry measurements of its short-lived progenies.
Valutazione Speditiva della VulnerabilitĂ Sismica delle Chiese a Tre Navate della Diocesi di Alife-Caiazzo
Seismic Risk Assessment of One Nave Complex Churches in Alife-Caiazzo Diocese of Caserta
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