COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: Seropositivity and safety. A prospective observational study in Italy.

Introduction: Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor.

Methods: An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study.

A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

Background: Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors.

Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying a high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma.

Methods: Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas.

Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients.

There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [occludin (OCLN), claudin-5 (CLN-5) and zonula occludens-1 (ZO-1)] levels, sphingosine-1 phosphate 1 (S1P) receptor expression on circulating leukocyte populations as well as in vitro PBMC migration were longitudinally assessed in 20 MS patients under 12-months fingolimod treatment and correlated with clinical and magnetic resonance imaging (MRI) parameters. After 12 months of treatment, a significant reduction of mean relapse rate as well as number of active lesions at MRI was found.

Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior.

Hairy cell leukemia (HCL) is generally responsive to single-agent cladribine, and only a minority of patients are refractory and with poor prognosis. HCLs generally express mutated (M) and, in a minority, unmutated (UM) IGHV. In a multicenter clinical trial in newly diagnosed HCL, we prospectively investigated clinical and molecular parameters predicting response and event-free survival after single-agent cladribine.

The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukaemia and is recapitulated by biological risk factors.

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic monoclonal expansion of <5.0 x 10(9)/l circulating CLL-phenotype B-cells. The relationship between MBL and Rai 0 CLL, as well as the impact of biological risk factors on MBL prognosis, are unknown.

Higher expression of BDNF receptor gp145trkB is associated with lower apoptosis intensity in T cell lines in multiple sclerosis.

Conflicting data exist on expression of gp145trkB, the high affinity receptor for brain-derived neurotrophic factor (BDNF), on peripheral blood immunocompetent cells in multiple sclerosis (MS). We analyzed expression of gp145trkB by western blotting and flow cytometry in myelin basic protein (MBP)- and ovalbumin (OVA)-T cell lines prepared from 12 patients with relapsing-remitting MS and 12 normal healthy subjects (NHS) and correlated it with activation-induced apoptosis. We found a higher percentage of gp145trkB-expressing MBP-T cells in MS patients than in NHS (p=0.

Low-dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic Leukaemia.

Fludarabine plus cyclophosphamide (FC) at conventional doses is an effective treatment for chronic lymphocytic leukaemia (CLL). However, FC at standard doses may give hematological and non-hematological toxicity, predominantly in the elderly. Intravenous or oral low-dose FC regimens remain highly effective in elderly patients with Low-Grade Lymphomas other than CLL and are well tolerated.

Physiological T cell activation starts and propagates in lipid rafts.

Lipid rafts are plasma membrane compartments enriched in key signaling molecules. We have previously shown that in T lymphocytes anti-CD3 stimulation is insensitive to cholesterol extraction by methyl-beta-cyclodextrin (MbetaCD), suggesting that anti-CD3 induced signal transduction is independent of raft integrity. Here we show that, in contrast to T cell stimulation by anti-CD3 antibodies, T cell activation by a physiological ligand is mediated by signaling events taking place in lipid raft.

T cell receptor can be recruited to a subset of plasma membrane rafts, independently of cell signaling and attendantly to raft clustering.

The constitutive/inducible association of the T cell receptor (TCR) with isolated detergent-resistant, lipid raft-derived membranes has been studied in Jurkat T lymphocytes. Membranes resistant to 1% Triton X-100 contained virtually no CD3epsilon, part of the TCR complex, irrespective of cell stimulation. On the other hand, membranes resistant either to a lower Triton X-100 concentration (i.

Lipid rafts and T cell receptor signaling: a critical re-evaluation.

The current model suggesting that raft integrity is required for T cell activation is mostly (but not exclusively) based on the use of drugs, such as methyl-beta-cyclodextrin (M beta CD), that disorganize rafts and inhibit T cell receptor (TCR)-induced Ca2+ influx. Here we show that conditions that disrupt lipid raft integrity do not inhibit TCR triggering in Jurkat cells and normal T lymphocytes. Indeed, we found that the reported inhibition of TCR-induced Ca2+ influx by M beta CD treatment is mainly due to (a) nonspecific depletion of intracellular Ca2+ stores and (b) plasma membrane depolarization of T cells.

Diacylglycerol activates the influx of extracellular cations in T-lymphocytes independently of intracellular calcium-store depletion and possibly involving endogenous TRP6 gene products.

In Jurkat and human peripheral blood T-lymphocytes, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeant analogue of diacylglycerol, activated the influx of Ca(2+), Ba(2+) and Sr(2+). OAG also caused plasma-membrane depolarization in Ca(2+)-free media that was recovered by the addition of bivalent cation, indicating the activation of Na(+) influx. OAG-induced cation influx was (i) mimicked by the natural dacylglycerol 1-stearoyl-2-arachidonyl-sn-glycerol, (ii) not blocked by inhibiting protein kinase C or in the absence of phospholipase C activity and (iii) blocked by La(3+) and Gd(3+).