Mara De Amici

Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib

To identify factors that might predict response to sunitinib in patients with renal cell carcinoma, we measured serum vascular endothelial growth factor (VEGF) and neutrophil gelatinase-associated lipocalin (NGAL) levels. A total of 85 patients were selected and, using the Motzer classification, 46 were assigned to the good- and 38 to the intermediate-risk groups. With univariate Cox analysis, both baseline serum VEGF and NGAL titers, determined by enzyme-linked immunosorbent assay, significantly predicted progression-free survival. For each biomarker, a threshold value was identified, which proved useful to classify patients into groups having titers above or below the thresholds. We then stratified patients according to the two dichotomous variables into good-, intermediate-, and poor-risk groups, and found significantly different progression-free survival rates ranging from 3.5 to 11.6 months. Both VEGF and NGAL maintained their predictive significance at bivariate analysis. Our study shows that serum levels of VEGF and NGAL are significant predictors of progression-free survival in patients with renal cell carcinoma treated with sunitinib.

Zoledronic acid down-regulates adhesion molecules of bone marrow stromal cells in multiple myeloma : A possible mechanism for its antitumor effect

Myeloma plasma cells interact with the bone marrow microenvironment which, in turn, supports their growth and protects them from apoptosis. In vitro studies have demonstrated the antitumor potential of zoledronic acid (ZOL) on myeloma cell lines, but few data are available on its effects on bone marrow stromal cells (BMSCs). The aim of the current study was to evaluate the antiproliferative and apoptotic effect of ZOL on BMSCs, as well as its effect on the expression of adhesion molecules.

Changes in circulating pro-angiogenic cytokines, other than VEGF, before progression to sunitinib therapy in advanced renal cell carcinoma patients.

Objectives: This study included a cohort of advanced renal cell carcinoma patients treated with sunitinib. Since resistance to sunitinib may be mediated through angiogenic cytokines other than VEGF, we measured the circulating levels of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin (IL)-6. Methods: Cytokines were measured at baseline and on the first day of each treatment cycle until progression in 85 advanced kidney cancer patients treated with sunitinib using a quantitative sandwich enzyme immunoassay (ELISA) technique. Results: Even though no statistically significant differences in the titers of the three cytokines were observed between baseline and the time of progression in the whole patient cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between baseline and the time of progression was shown in circulating IL-6, bFGF, and HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and 30.6% of the patients, respectively. We also demonstrated that, in these patients, cytokines tended to increase and to remain high immediately before progression. Conclusions: In a large percentage of kidney cancer patients, progression is preceded by a significant increase in pro-angiogenic cytokines other than VEGF.

Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin‐cell antibodies and markers of autoimmunity

Objectives  Autoimmune targeting of hypothalamic‐neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood.

Serum vascular endothelial growth factor in allergic rhinitis and systemic lupus erythematosus

Allergic rhinitis (AR) is characterized by an inflammatory reaction sustained by Th2 polarization, whereas systemic lupus erythematosus (SLE) is a typical autoimmune disorder. Vascular endothelial growth factor (VEGF) is a critical mediator of inflammation. The aim of this study was to compare serum VEGF levels in three groups of subjects: 40 normal subjects, 40 allergic patients, evaluated before and after specific immunotherapy, and 40 patients with inactive SLE. Patients who were allergic before immunotherapy had the lowest VEGF serum levels, which significantly increased after treatment; SLE patients had the highest VEGF serum levels. This comparative study provides evidence that serum VEGF levels depend on the type of immune response: they are high in autoimmune disease and low in Th2-polarized allergic reaction. The relevance of this phenomenon is further apparent, as it is also observed in patients with inactive disease.

Tryptophan metabolism in allergic rhinitis: The effect of pollen allergen exposure

This study evaluates serum tryptophan, kynurenine, kynurenine-to-tryptophan ratio, and neopterin levels in patients with pollen-induced allergic rhinitis (AR) during and outside of the pollen season, along with these values in healthy subjects. A total of 102 patients (56 female and 46 male, median age 28.7 years) were included in this study: 56 with seasonal AR evaluated outside of the pollen season and thus without allergic inflammation and symptoms, and 46 with seasonal AR evaluated during the pollen season with symptoms. A skin prick test and blood sampling for assessing serum concentrations of tryptophan and kynurenine and of immune activation marker neopterin were performed in all subjects. Tryptophan and kynurenine serum concentrations were higher in AR patients than in controls and were also higher out of pollen season than during this season. In conclusion, this preliminary study demonstrates that serum tryptophan metabolism could serve as a biomarker in patients with AR.

The Age Impact on Serum Total and Allergen-Specific IgE.

Aging is accompanied by a progressive decline in almost all functions of the immune system. To investigate a possible impact of age on IgE production, this study evaluated total and allergen-specific serum IgE levels in a large cohort of allergic patients. This study included 6,370 allergic patients (2,961 females, 3,409 males; mean age, 21.7 years; age range, 0-96 years). Total and allergen-specific serum IgE levels were measured by immunoenzymatic assay. The analysis of variance showed a significant difference (P<0.0001) in the mean value of total IgE among the different age groups of patients. Moreover, specific IgE levels for all allergens examined differed significantly among the age groups of patients (P<0.0001), with a specific trend pattern for each allergen. Total IgE increased with age, but allergen-specific IgE levels significantly decreased with age, with a trend specific for each allergen tested.

Flow cytometric analysis of peripheral blood dendritic cells in patients with severe sepsis.

Dendritic cells (DC) play a key role in cell‐mediated immunity. We aimed to analyse the number and function of peripheral blood (PB) myeloid and plasmacytoid DC (mDC/pDC) in patients with severe sepsis.

Effect of active and passive smoking during pregnancy on natural killer-cell activity in infants

Several studies have documented the short- and longterm adverse effects of maternal cigarette smoking during pregnancy on the fetus and neonate, such as low birth weight, behavior problems, intellectual impairment, and increased morbidity and mortality. 1 Furthermore, the following alterations of the immune system have been observed in infants with mothers who smoke compared with control subjects: increased uptake in PHA-stimulated culture of cord cells 2; higher cord serum levels of IgG, IgA, and IgM3; and decreased neutrophil counts 1 in cord blood. Cigarette smoking has been reported to reduce natural killer (NK)‐cell activity in adults; however, to our knowledge, no data are available on the effect of passive smoking on NK-cell activity in neonates. The aim of this study was to investigate whether maternal smoking may be correlated with an alteration of NK-cell activity in cord blood lymphocytes (CBLs) obtained from 3 groups of term newborns with mothers who had different levels of exposure to cigarette smoke.

Vascular endothelial growth factor promoted endothelial progenitor cell mobilization into the peripheral blood of a patient with POEMS syndrome

We assessed the percentage of endothelial progenitor cells (EPCs) in the peripheral blood of a patient with POEMS with elevated VEGF plasma levels. High VEGF plasma levels were associated with increased EPC concentration and treatment with an anti-VEGF antibody induced a consensual decrease of both parameters. In vitro cultures of the patient BM cells suggested that the stromal compartment could be responsible for VEGF overproduction.