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showing 10 items of 2487 documents
Active Akt signaling triggers CLL toward Richter transformation via overactivation of Notch1
2021
Abstract Richter’s transformation (RT) is an aggressive lymphoma that occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL phase involving TP53, CDKN2A, MYC, and NOTCH1; however, a significant proportion of RT cases lack CLL phase–associated events. Here, we report that high levels of AKT phosphorylation occur both in high-risk CLL patients harboring TP53 and NOTCH1 mutations as well as in patients with RT. Genetic overactivation of Akt in the murine Eµ-TCL1 CLL mouse model resulted in CLL transformation to RT with significantly reduced survival and an aggressive lymphoma phenotype. In the absence of recurren…
Effect of Buthionine Sulfoximine on the Sensitivity to Doxorubicin of Parent and MDR Tumor Cell Lines
1994
We have studied the interaction of glutathione-depleting concentrations of buthionine sulfoximine (BSO) with the anti-proliferative activity of doxorubicin (DXR) in three tumor lines, the mouse B16 melanoma. Friend erythroleukemia and the human K562 leukemia, both as DXR-sensitive and-resistant (with typical multidrug resistance) variants. BSO significantly enhanced the DXR effects in the wild-type Friend and K562 leukemias, and especially in the drug-resistant subline of Friend leukemia. BSO did not modify DXR accumulation and retention in the latter clone. Moreover, neither BSO nor verapamil used alone completely reversed the resistance to DXR of this cell line; their combination was more…
High Nutrient Concentration Can Induce Virulence Factor Expression and Cause Higher Virulence in an Environmentally Transmitted Pathogen
2016
Environmentally transmitted opportunistic pathogens shuttle between two substantially different environments: outside-host and within-host habitats. These environments differ from each other especially with respect to nutrient availability. Consequently, the pathogens are required to regulate their behavior in response to environmental cues in order to survive, but how nutrients control the virulence in opportunistic pathogens is still poorly understood. In this study, we examined how nutrient level in the outside-host environment affects the gene expression of putative virulence factors of the opportunistic fish pathogen Flavobacterium columnare. The impact of environmental nutrient concen…
Deciphering human γδ T cell response in cancer: Lessons from tumor‐infiltrating γδ T cells
2020
The finding that γδ T cells are present among tumor-infiltrating lymphocytes in humans suggests they participate in tumor immune surveillance, but their relevance is unclear because the relative abundance of tumor-infiltrating γδ T cells correlates with positive or negative, or even do not correlate with prognosis. This likely depends on the fact that tumor-infiltrating γδ T cells may play substantially different effector or regulatory functions, and correlation with patient's prognosis relies on distinct γδ T cell subsets in the context of the tumor. There is interest to exploit γδ T cells in tumor immunotherapy, but to make this approach successful there is urgent need to fully understand…
Transcriptome analysis revealed that a quorum sensing system regulates the transfer of the pAt megaplasmid in Agrobacterium tumefaciens.
2016
Background Agrobacterium tumefaciens strain P4 is atypical, as the strain is not pathogenic and produces a for this species unusual quorum sensing signal, identified as N-(3-hydroxy-octanoyl)-homoserine lactone (3OH,C8-HSL). Results By sequence analysis and cloning, a functional luxI-like gene, named cinI, has been identified on the At plasmid of A. tumefaciens strain P4. Insertion mutagenesis in the cinI gene and transcriptome analyses permitted the identification of 32 cinI-regulated genes in this strain, most of them encoding proteins responsible for the conjugative transfer of pAtP4. Among these genes were the avhB genes that encode a type 4 secretion system (T4SS) involved in the forma…
Effects of Pimozide Derivatives on pSTAT5 in K562 Cells
2017
STAT5 is a transcription factor, a member of the STAT family of signaling proteins. STAT5 is involved in many types of cancer, including chronic myelogenous leukemia (CML), in which this protein is found constitutively activated as a consequence of BCR-ABL expression. The neuroleptic drug pimozide was recently reported to act as an inhibitor of STAT5 phosphorylation and is capable of inducing apoptosis in CML cells in vitro. Our research group has synthesized simple derivatives of pimozide with cytotoxic activity and that are able to decrease the levels of phosphorylated STAT5. In this work we continued the search for novel STAT5 inhibitors, synthesizing compounds in which the benzoimidazol…
Chronic Myelogenous Leukemia: Approaches to Pharmacological Resistance
2017
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the reciprocal t (9:22) chromosomal translocation. This rearrangement produces the socalled Philadelphia chromosome carrying the chimeric Bcr-Abl oncoprotein, p210, responsible of disease progression [1]. Because of its critical role in pathogenesis, the scientific community had focused on targeting Bcr–Abl for treatment of CML. For many years Imatinib (IM), as selective inhibitor of the Tyr-Kinase activity of the oncoprotein, was used to treat CML patients [2]. From 2000 some data relative to IM resistance were available. There are many mechanisms responsible of IM resistance, more often point mutat…
T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
2021
Simple Summary T-cells defend the human body from pathogenic invasion via specific recognition by T-cell receptors (TCRs). The TCR genes undergo recombination (rearrangement) in a myriad of possible ways to generate different TCRs that can recognize a wide diversity of foreign antigens. However, in patients with T-cell lymphoma (TCL), a particular T-cell becomes malignant and proliferates, resulting in a population of genetically identical cells with same TCR rearrangement pattern. To help diagnose patients with TCL, a polymerase chain reaction (PCR)-based assay is currently used to determine if neoplastic cells in patient samples are of T-cell origin and bear identical (monoclonal) TCR rea…
The severe phenotype of Diamond-Blackfan anemia is modulated by heat shock protein 70.
2017
International audience; Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome that exhibits an erythroid-specific phenotype. In at least 70% of cases, DBA is related to a haploinsufficient germ line mutation in a ribosomal protein (RP) gene. Additional cases have been associated with mutations in GATA1. We have previously established that the RPL11+/Mut phenotype is more severe than RPS19+/Mut phenotype because of delayed erythroid differentiation and increased apoptosis of RPL11+/Mut erythroid progenitors. The HSP70 protein is known to protect GATA1, the major erythroid transcription factor, from caspase-3 mediated cleavage during normal erythroid differentiation.…
Virological response and retention in care according to time of starting ART in Italy: data from the Icona Foundation Study cohort
2020
Abstract Objectives To describe: (i) factors associated with rapid and delayed ART initiation; (ii) rates of 12 week virological response; and (iii) virologically controlled retention in care by 1 year from ART initiation according to timing of start in a real-life setting. Methods All individuals in the Icona cohort diagnosed with HIV in 2016–17 who initiated ART were grouped according to the time between HIV diagnosis and ART initiation: Group 1, ≤7 days; Group 2, 8–14 days; Group 3, 15–30 days; Group 4, 31–120 days; and Group 5, >120 days. Multivariable logistic regression models were used to identify factors associated with: (i) the probability of rapid (Group 1) and very delayed…