evaluation of granules obtained from 3D sphene scaffolds and bovine bone grafts: chemical and biological assays.

Sphene is an innovative bone graft material. The aim of this study was to investigate and compare the physicochemical and biological properties of Bio-Oss® (BO) and in-lab synthesized and processed sphene granules. BO granules of 1000-2000 μm (BO-L), 250-1000 μm (BO-S) and 100-200 μm (BO-p) for derived granules, and corresponding groups of sphene granules obtained from 3D printed blocks (SB-L, SB-S, SB-p) and foams (SF-L, SF-S and SF-p) were investigated.

Vav1 is necessary for PU.1 mediated upmodulation of miR-29b in acute myeloid leukaemia-derived cells.

It has been recently demonstrated that high pre-treatment levels of miR-29b positively correlated with the response of patients with acute myeloid leukaemia (AML) to hypomethylating agents. Upmodulation of miR-29b by restoring its transcriptional machinery appears indeed a tool to improve therapeutic response in AML. In cells from acute promyelocytic leukaemia (APL), miR-29b is regulated by PU.

A network including PU.1, Vav1 and miR-142-3p sustains ATRA-induced differentiation of acute promyelocytic leukemia cells - a short report.

Purpose: Reduced expression of miR-142-3p has been found to be associated with the development of various subtypes of myeloid leukemia, including acute promyelocytic leukemia (APL). In APL-derived cells, miR-142-3p expression can be restored by all-trans retinoic acid (ATRA), which induces the completion of their maturation program. Here, we aimed to assess whether PU.

hnRNP K in PU.1-containing complexes recruited at the CD11b promoter: a distinct role in modulating granulocytic and monocytic differentiation of AML-derived cells.

PU.1 is essential for the differentiation of haemopoietic precursors and is strongly implicated in leukaemogenesis, yet the protein interactions that regulate its activity in different myeloid lineages are still largely unknown. In the present study, by combining fluorescent EMSA (electrophoretic mobility-shift assay) with MS, we reveal the presence of hnRNP K (heterogeneous nuclear ribonucleoprotein K) in molecular complexes that PU.

High nuclear level of Vav1 is a positive prognostic factor in early invasive breast tumors: a role in modulating genes related to the efficiency of metastatic process.

Vav1 is one of the signalling proteins normally restricted to hematopoietic cells that results ectopically expressed in solid tumors, including breast cancer. By immunohistochemical analysis on TMAs containing invasive breast tumor from patients without lymph node involvement, we have found that Vav1 is expressed in almost all investigated cancers and shows a peculiar localization inside the nucleus of tumor cells. High amounts of nuclear Vav1 are positively correlated with low incidence of relapse, regardless phenotype and molecular subtype of breast neoplasia.

In triple negative breast tumor cells, PLC-β2 promotes the conversion of CD133high to CD133low phenotype and reduces the CD133-related invasiveness.

Background: Beyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia.

Methods: To study the correlation between the levels of CD133 expression and the biology of breast-derived cells, CD133low and CD133high cell subpopulations isolated from triple negative MDA-MB-231 cells were compared in terms of malignant properties and protein expression.

Results: High expression of CD133 characterizes cells with larger adhesion area, lower proliferation rate and reduced migration speed, indicative of a less undifferentiated phenotype.

Vav1 in differentiation of tumoral promyelocytes.

The multidomain protein Vav1, in addition to promote the acquisition of maturation related properties by normal hematopoietic cells, is a key player in the ATRA- and PMA-induced completion of the differentiation program of tumoral myeloid precursors derived from APL. This review is focussed on the role of Vav1 in differentiating promyelocytes, as part of interconnected networks of functionally related proteins ended to regulate different aspects of myeloid maturation. The role of Vav1 in determining actin cytoskeleton reorganization alternative to the best known function as a GEF for small G proteins is discussed, as well as the binding of Vav1 with cytoplasmic and nuclear signaling molecules which provides a new perspective in the modulation of nuclear architecture and activity.

Nuclear proteome analysis reveals a role of Vav1 in modulating RNA processing during maturation of tumoral promyelocytes.

Vav1 is a key molecule in the ATRA-induced acquisition of a mature phenotype by tumoral myeloid precursors. Since ATRA acts throughout events that require extensive changes of nuclear architecture and activity and considering that Vav1 accumulates inside the nuclear compartment of differentiating APL-derived cells, the possible role of this protein in modulating the nuclear proteome was investigated. Membrane-depleted nuclei purified from NB4 cells induced to differentiate with ATRA in the presence of forcedly down-modulated Vav1 were subjected to 2D-DIGE followed by mass spectra analysis.

Vav1 is a crucial molecule in monocytic/macrophagic differentiation of myeloid leukemia-derived cells.

Vav1 is a critical signal transducer for both the development and function of normal hematopoietic cells, in which it regulates the acquisition of maturation-related properties, including adhesion, motility, and phagocytosis. Vav1 is also important for the agonist-induced maturation of acute promyelocytic leukemia (APL)-derived promyelocytes, in which it promotes the acquisition of a mature phenotype by playing multiple functions at both cytoplasmic and nuclear levels. We investigated the possible role of Vav1 in the differentiation of leukemic precursors to monocytes/macrophages.

Mass spectrometry-based identification of Y745 of Vav1 as a tyrosine residue crucial in maturation of acute promyelocytic leukemia-derived cells.

Vav1, whose physiological expression is restricted to hematopoietic system, is one of the signaling proteins up-regulated by all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL)-derived precursors, in which it promotes the overcoming of the differentiation blockade. High levels of tyrosine phosphorylated Vav1 accumulate in differentiating APL-derived cells, suggesting that one or more Vav1 tyrosine residues are involved in neutrophil differentiation of tumoral promyelocytes. Here, we have found that phosphorylation of Vav1 Y174, that is known to regulate Vav1 activity in mature neutrophils, is up-regulated by ATRA in NB4 cells.