The NF-κB1/p50 Subunit Influences the Notch/IL-6-Driven Expansion of Myeloid-Derived Suppressor Cells in Murine T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia is an aggressive neoplasia due to hyper-proliferation of lymphoid progenitors and lacking a definitive cure to date. Notch-activating mutations are the most common in driving disease onset and progression, often in combination with sustained activity of NF-κB. Myeloid-derived suppressor cells represent a mixed population of immature progenitors exerting suppression of anti-cancer immune responses in the tumor microenvironment of many malignancies.

Notch3-regulated microRNAs impair CXCR4-dependent maturation of thymocytes allowing maintenance and progression of T-ALL.

Malignant transformation of T-cell progenitors causes T-cell acute lymphoblastic leukemia (T-ALL), an aggressive childhood lymphoproliferative disorder. Activating mutations of Notch, Notch1 and Notch3, have been detected in T-ALL patients. In this study, we aimed to deeply characterize hyperactive Notch3-related pathways involved in T-cell dynamics within the thymus and bone marrow to propose these processes as an important step in facilitating the progression of T-ALL.

Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia.

Notch receptors deeply influence T-cell development and differentiation, and their dysregulation represents a frequent causative event in "T-cell acute lymphoblastic leukemia" (T-ALL). "Myeloid-derived suppressor cells" (MDSCs) inhibit host immune responses in the tumor environment, favoring cancer progression, as reported in solid and hematologic tumors, with the notable exception of T-ALL. Here, we prove that Notch-signaling deregulation in immature T cells promotes CD11bGr-1 MDSCs in the Notch3-transgenic murine model of T-ALL.

NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric malignancy that arises from the transformation of immature T-cell progenitors and has no definitive cure. Notch signaling governs many steps of T cell development and its dysregulation represents the most common causative event in the pathogenesis of T-ALL. The activation of canonical NF-κB pathway has been described as a critical downstream mediator of Notch oncogenic functions, through the sustaining of tumor cell survival and growth.

High-Precision In Situ Sr/Sr Analyses through Microsampling on Solid Samples: Applications to Earth and Life Sciences.

An analytical protocol for high-precision, in situ microscale isotopic investigations is presented here, which combines the use of a high-performing mechanical microsampling device and high-precision TIMS measurements on micro-Sr samples, allowing for excellent results both in accuracy and precision. The present paper is a detailed methodological description of the whole analytical procedure from sampling to elemental purification and Sr-isotope measurements. The method offers the potential to attain isotope data at the microscale on a wide range of solid materials with the use of minimally invasive sampling.

Perfusion MRI of the lung: preliminary results in twenty healthy volunteers.

Purpose: This study attempted to assess the feasibility and the accuracy of lung contrast enhanced magnetic resonance (MR) perfusion imaging in the evaluation of 20 healthy volunteers and to correlate the intensity/time (I/T) curves with the pulmonary physiological criteria.

Material And Methods: After an informed consensus, twenty no-smoker subjects, without any present or past pulmonary pathologies, were studied by means of an ultra-fast gradient echo sequence after a Gd-DTPA intravenous administration. The acquisitions were performed in coronal and sagittal planes, in supine and prone position, in breath holding.