TOP2A expression predicts responsiveness to carfilzomib in myeloma and informs novel combinatorial strategies for enhanced proteasome inhibitor cell killing.

Microarray was utilized to determine if a genetic signature associated with resistance to carfilzomib (CFZ) could be identified. Twelve human myeloma (MM) cell lines (HMCLs) were treated with CFZ and a cell-viability profile was assessed categorizing HMCLs as sensitive or resistant to CFZ. The gene expression profiles (GEP) of untreated resistant versus sensitive HMCLs revealed 29 differentially expressed genes.

Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma.

The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473.

Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques.

Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient's quality of life.

Autoimmune uveitis: a retrospective analysis of 104 patients from a tertiary reference center.

Background: The aim of this study was to identify the main features of a cohort of Caucasian patients with idiopathic (I) and systemic disease-associated (SDA) autoimmune uveitis (AU) who were followed up at a single tertiary reference center. The study consisted of a retrospective analysis of the demographic, clinical, and laboratory features and the response to treatment of 104 patients with AU evaluated between 2004 and 2013, with a median follow-up of 4.8 years.

Modulation of the Fcgamma receptors induced by anti-Ro and anti-La autoantibodies: observations in salivary gland cells.

Only few reports have shown protein expression of the Fcgamma receptors (FcgammaRs) molecules on human salivary gland cells. In this study we investigate a possible upregulation of FcgammaRs following anti-Ro and anti-La autoantibodies treatment. Anti-Ro and anti-La autoantibodies were purified from IgG fractions obtained from 14 patients with primary Sjögren's syndrome (SS), using Sepharose 4B-Ro and Sepharose 4B-La affinity columns.

KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.

Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.