A Multi-Center, Real-Life Experience on Liquid Biopsy Practice for EGFR Testing in Non-Small Cell Lung Cancer (NSCLC) Patients.

Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy.

HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2.

To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection.

Lack of expression of inhibitory KIR3DL1 receptor in patients with natural killer cell-type lymphoproliferative disease of granular lymphocytes.

Background: Natural killer cell-type lymphoproliferative disease of granular lymphocytes is a disorder characterized by chronic proliferation of CD3(-)CD16(+) granular lymphocytes. By flow cytometry analysis, we previously demonstrated a dysregulation in killer immunoglobulin-like receptor (KIR) expression in natural killer cells from patients with this lymphoproliferative disease, the activating KIR receptors being mostly expressed. We also found that patients with natural killer cell-type lymphoproliferative disease of granular lymphocytes usually had KIR genotypes characterized by multiple activating KIR genes.

Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity.

Chemokines and their receptors play a pivotal role in the regulation of B-lymphocyte trafficking. This study was aimed at investigating the pattern of chemokine receptor expression, including CCR1 to CCR3, CCR5 to CCR7, CXCR1 to CXCR5, and the migration ability of multiple myeloma (MM) plasma cells (PC). PC were recovered from the bone marrow (BM) of 29 MM patients, extramedullary sites of 10 patients and the BM of five controls.

Expression and role of CCR6/CCL20 chemokine axis in pulmonary sarcoidosis.

We have shown previously that the chemokine receptors CXCR3 and CXCR6 are coexpressed by Th1 cells infiltrating the lung and the granuloma of patients with sarcoidosis. In this study, we evaluated the role of CCL20/CCR6 interaction in the pathogenesis of acute and chronic pulmonary sarcoidosis. By flow cytometry and molecular analyses, we have demonstrated that Th1 cells isolated from the bronchoalveolar lavage (BAL) of patients with sarcoidosis and T cell alveolitis are equipped with CCR6.

T-cell type lymphoproliferative disease of granular lymphocytes (LDGL) is equipped with a phenotypic pattern typical of effector cytotoxic cells.

By analyzing the expression of several cytotoxic markers, killer-immunoglobulin-like receptors (KIRs), CD94/CD159, CD314 and natural cytotoxicity receptors (NCRs), in 22 CD3+ lymphoproliferative disease of granular lymphocyte (LDGL) patients we investigated whether granular lymphocytes (GLs) displayed the phenotype of fully differentiated cytotoxic cells. Our results demonstrate that GLs express a pattern consistent with fully differentiated CTLs. KIRs are expressed only in a fraction of patients (7/22), as is CD94/CD159 (5/22).

Circulating progenitor cells are reduced in patients with severe lung disease.

Patients with chronic severe lung disease are prone to develop pulmonary vascular remodeling, possibly through pulmonary endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are involved in maintenance of endothelial homeostasis. The aim of this study was to assess whether obstructive and restrictive lung diseases are associated with modification of EPC number in peripheral blood.

Epithelial CXCR3-B regulates chemokines bioavailability in normal, but not in Sjogren's syndrome, salivary glands.

Expression of CXCR3-targeting chemokines have been demonstrated in several diseases, suggesting a critical role for CXCR3 in recruiting activated T cells to sites of immune-mediated inflammation. Sjögren's syndrome (SS) is an autoimmune disease characterized by a mononuclear cell infiltrate of activated T cells around the duct in the salivary gland. Analysis of minor salivary gland biopsy specimens from 20 healthy subjects and 18 patients with primary SS demonstrated that CXCR3, in particular, the B form of this receptor, is constitutively expressed by human salivary gland epithelial cells.

Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis.

Rationale: Receptor expression dictates the spectrum of chemokine actions on immunocompetent cells. We have previously shown that the chemokine receptor CXCR3 is highly expressed by T-helper type 1 (Th1) cells infiltrating the lungs of patients with sarcoidosis.

Objectives: The evaluation of the role of Bonzo/CXCR6 and its ligand CXCL16 in the pathogenesis of sarcoidosis.

Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL).

We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL). The presence of in vivo circulating DCs was studied in 11 patients (5 CD3+ and 6 CD3- LDGL). Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs.

Arterio-venous gradient of endothelial progenitor cells across renal artery stenosis.

A role for circulating progenitor cells have been recently demonstrated in many pathological conditions. Endothelial progenitor cells (EPCs) localize at sites of ischemia and stimulate neovasculogenesis. This small study was carried out to assess whether selective blood sampling during renal angiography could demonstrate an arterio-venous gradient of EPCs in 5 patients with renal artery stenosis.

Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus.

Objectives: We sought to establish whether a reduction in endothelial progenitor cells (EPCs) has a putative role in peripheral vascular disease (PVD) of type 2 diabetic patients.

Background: Peripheral vascular disease is a common and severe complication of diabetes mellitus. Impaired collateralization of diabetic vasculopathy has been extensively shown, but causes leading to its pathogenesis are not fully understood.

CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined.

Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis.

B cell chronic lymphocytic leukemia (B-CLL) is a neoplastic disorder characterized by accumulation of B lymphocytes due to uncontrolled growth and resistance to apoptosis. Analysis of B cells freshly isolated from 40 patients with chronic lymphocytic leukemia demonstrated that the Src kinase Lyn, the switch molecule that couples the B cell receptor to downstream signaling, displays anomalous properties. Lyn is remarkably overexpressed at the protein level in leukemic cells as compared with normal B lymphocytes, with a substantial aliquot of the kinase anomalously present in the cytosol.

Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas.

This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells.

T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner.

Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8(+) T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8(+) T cells bearing (TCR)-beta variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP.

Gene expression profile analysis by DNA microarrays: a new approach to assess functional genomics in diseases.

A biologically based and potentially powerful way to characterize human diseases has arisen from the new science of genomics. One of the methodologies to provide a systematic way to observe and characterize gene expression programs is the DNA microarrays (also called gene chips). This modern genomic analysis tool shows the promise of providing an unbiased approach to detecting biologically relevant differences within clinically similar diseases.