Nummular eczema and contact allergy: a retrospective study.

Background: Etiopathogenesis of nummular eczema is obscure; many causative factors have been proposed. Only a few studies investigated the relevance of contact allergy.

Objective: This retrospective study aimed to investigate the role of contact allergy in the underlying mechanism of nummular eczema.

Novel lenalidomide-based combinations for treatment of multiple myeloma.

Lenalidomide (LEN) is an immunomodulatory drug (IMiD) which exerts tumoricidal effects and has immunomodulatory, anti-inflammatory and anti-angiogenic properties that synergistically keep the tumor in remission. It is currently approved as second-line therapy for multiple myeloma (MM) and for 5q defective myelodysplastic syndrome, while ongoing studies are at present evaluating its role in both solid and hematologic malignancies. Based on its high activity as an anti-myeloma drug with a good tolerability profile, LEN is currently gaining interest in both preclinical and clinical research for combinatory treatments with novel agents including monoclonal antibodies, immunotoxins, tyrosine kinase inhibitors, new proteasome inhibitors and epigenetic-interfering agents as well as with new compounds targeting the cancer stem cell niche.

Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy.

The goal of cancer pharmacogenomics is to obtain benefit from personalized approaches of cancer treatment and prevention. Recent advances in genomic research have shed light on the crucial role of genetic variants, mainly involving genes encoding drug-metabolizing enzymes, drug transporters and targets, in driving different treatment responses among individuals, in terms of therapeutic efficacy and safety. Although a considerable amount of new targeted agents have been designed based on a finely understanding of molecular alterations in cancer, a wide gap between pharmacogenomic knowledge and clinical application still persists.

Barrett's esophagus and esophageal cancer: an overview.

Although esophageal cancer (EC) is the eighth most common cancer in several European countries, it is one of deadliest worldwide. The most frequent predisposing factor implicated in its development is Barrett's esophagus (BE), an acquired metaplastic transformation of the esophageal lining cells from normal squamous epithelium into specialised or intestinal-like columnar epithelium. The major risk factor for BE is gastroesophageal reflux disease.

Therapeutic approaches to myeloma bone disease: an evolving story.

Bone disease is a major morbidity factor in patients with multiple myeloma and significantly affects their overall survival. A complex interplay between malignant plasma cells and other marrow cells results in the generation of a microenvironment capable of enhancing both tumor growth and bone destruction. Bisphosphonates have consistently reduced the incidence of skeletal-related events in patients with multiple myeloma and other osteotropic tumors as well.

Novel strategies in the treatment of castration-resistant prostate cancer (Review).

Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression.

Lenalidomide in multiple myeloma: current experimental and clinical data.

Lenalidomide (LEN) is a structural analogue of Thalidomide and is currently considered a promising compound among immunomodulatory drugs. Following the demonstration of its potent anti-angiogenic, anti-inflammatory, and antineoplastic effects in preclinical models, LEN has emerged as an interesting option for the management of selective hematologic malignancies and may also have a possible role in certain solid tumors as well. It is currently approved in the second-line therapy of multiple myeloma (MM) as well as in myelodysplastic syndrome characterized by 5q minus abnormalities.

Antibody V(h) repertoire differences between resolving and chronically evolving hepatitis C virus infections.

Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE.

Extra-articular manifestations of rheumatoid arthritis: An update.

Rheumatoid arthritis (RA) is an immune-mediated disease involving chronic low-grade inflammation that may progressively lead to joint destruction, deformity, disability and even death. Despite its predominant osteoarticular and periarticular manifestations, RA is a systemic disease often associated with cutaneous and organ-specific extra-articular manifestations (EAM). Despite the fact that EAM have been studied in numerous RA cohorts, there is no uniformity in their definition or classification.

A spatial view of the CD8+ T-cell response: the case of HCV.

In viral infections, a memory T-cell population comprises multiple subtypes of cells, distributed in diverse anatomic compartments and possibly re-circulating among them. Accordingly, memory T cells display distinct phenotypes and functions, depending on the nature of the infecting virus, the anatomic location of the infection, and the differences between the sites of active infection and T-cell collection. This paper explores the body compartments where virus-specific CD8(+) T cells have been found during chronic hepatitis C virus infection, describes the cells' memory qualities, and discusses how they are spatially regulated, in comparison with other human viral infections.

Dendritic cells and malignant plasma cells: an alliance in multiple myeloma tumor progression?

The crosstalk of myeloma cells with accessory cells drives the expansion of malignant plasma cell clones and the hyperactivation of osteoclastogenesis that occurs in multiple myeloma (MM). These reciprocal interactions promote defective dendritic cell (DC) function in terms of antigen processing, clearance of tumor cells, and efficacy of the immune response. Thus, myeloma cells exert immune suppression that explains, at least in part, the failure of therapeutic approaches, including DC vaccination.

Relationship between C3 levels and common carotid intima-media thickness in overweight and obese patients.

Objective: The study aim was to compare C3 levels with the common carotid artery intima-media thickness (CCAIMT) in subjects of both genders, with a wide range of BMI, independently of age, gender, and abdominal obesity.

Method: 140 euthyroid, mainly overweight/obese subjects (age 18-30 years) were examined. BMI, waist circumference, blood pressure, fasting insulin, glucose, lipids, C3 and C-reactive protein serum concentrations, and insulin resistance degree (estimated by homeostasis model assessment for insulin resistance (HOMAIR)) were measured.

Immature dendritic cells from patients with multiple myeloma are prone to osteoclast differentiation in vitro.

Objective: Recent studies demonstrated that the interactions of immature dendritic cells (iDCs) with myeloma cells enhance the clonogenic capacity of tumor cells while iDCs undergo osteoclast (OC) transformation. Here, we investigated these interactions as well as iDC behavior in terms of both migration and OC differentiation.

Materials And Methods: We studied 12 patients with multiple myeloma (MM) and 5 with monoclonal gammopathy of undetermined significance.

Angiogenesis and vasculogenesis in multiple myeloma: role of inflammatory cells.

Angiogenesis plays a central role in the progression of both solid and hematologic tumors. We have focused our attention on multiple myeloma (MM) and on bone marrow stromal cells. These, in fact, both support tumor cell survival and participate in angiogenesis by releasing a broad number of angiogenic cytokines.

Cell fusion and hyperactive osteoclastogenesis in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy whose progression may account for uncontrolled osteoclastogenesis promoted by the malignant plasma cells within the marrow microenvironment. Osteoclasts are multinucleated cells derived from the fusion of myeloid progenitors such as monocytes/macrophages, in response to specific differentiation factors released within the marrow niche, that are significantly deregulated in MM. In this malignancy DC-STAMP, a major fusogen protein enrolled by pre-osteoclasts, is highly expressed by peripheral macrophages, whereas dendritic cells and myeloma plasma cells show high fusogenic susceptibility and under specific conditions transdifferentiate to osteoclasts.

Arterial hypertension in obesity: relationships with hormone and anthropometric parameters.

Background: Obesity has been recognized as an independent risk factor for arterial hypertension.

Design: This study was addressed to identify parameters predictive of 24-h mean systolic and/or diastolic blood pressure levels in obesity.

Methods: A cohort of 180 euthyroid overweight and obese patients, 79 women and 101 men, aged 20-63 years, normotensive (n = 62) or with recently developed hypertension (n = 118), and never treated with antihypertensive drugs, was examined.

Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma.

Purpose: To determine the in vivo and in vitro antiangiogenic power of lenalidomide, a "lead compound" of IMiD immunomodulatory drugs in bone marrow (BM) endothelial cells (EC) of patients with multiple myeloma (MM) in active phase (MMEC).

Experimental Design: The antiangiogenic effect in vivo was studied using the chorioallantoic membrane (CAM) assay. Functional studies in vitro (angiogenesis, "wound" healing and chemotaxis, cell viability, adhesion, and apoptosis) were conducted in both primary MMECs and ECs of patients with monoclonal gammopathies (MGUS) of undetermined significance (MGEC) or healthy human umbilical vein endothelial cells (HUVEC).

Cytokine overproduction, T-cell activation, and defective T-regulatory functions promote nephritis in systemic lupus erythematosus.

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role.

Mesenchymal stem cells: a new promise in anticancer therapy.

Novel cell-based and gene therapies represent promising approaches for the treatment of incurable diseases, including cancer. Following the success of the hematopoietic stem cell-based transplantation, other populations of adult progenitor cells, including mesenchymal stem cells (MSCs), have been identified as powerful therapeutic tools in humans. The intrinsic capability of MSCs to migrate toward injured tissues emphasizes their suitability to deliver anticancer agents for new clinical applications in addition to the tissue repairing capacity.

The immunodominant epitope of centromere-associated protein A displays homology with the transcription factor forkhead box E3 (FOXE3).

Some patients with systemic sclerosis express autoantibodies to centromere-associated protein A (CENP-A), but the exact CENP-A epitope is unknown and it is possible that another protein primes these antibodies. This study aimed to define the amino acids recognized by these antibodies and discover other proteins that may be targeted by or may prime them. Peptide Ap(17-30), the immunodominant epitope of CENP-A, was used to purify anti-CENP-A Ig from sera of 8 patients.

CD20-depleting therapy in autoimmune diseases: from basic research to the clinic.

The B lymphocyte-associated antigen CD20 is becoming an important immunotherapy target for autoimmune diseases, although its biological function has not been defined. Besides rheumatoid arthritis, growing experience with B cell-depleting therapy indicates that it may be effective in Sjögren's syndrome, dermatomyositis-polymyositis, systemic lupus erythematosus and some types of vasculitides. However, controlled clinical trials are still lacking for some of these indications.

Targeted therapies in cancer.

Recent advances in understanding the biologic mechanisms underlying cancer development have driven the design of new therapeutic approaches, termed 'targeted therapies', that selectively interfere with molecules or pathways involved in tumor growth and progression. Inactivation of growth factors and their receptors on tumor cells as well as the inhibition of oncogenic tyrosine kinase pathways and the inhibition of molecules that control specific functions in cancer cells constitute the main rational bases of new cancer treatments tailored for individual patients. Small-molecule inhibitors and monoclonal antibodies are major components of these targeted approaches for a number of human malignancies.

Alterations in the antigen processing-presenting machinery of transformed plasma cells are associated with reduced recognition by CD8+ T cells and characterize the progression of MGUS to multiple myeloma.

We hypothesized that progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) reflects the escape of transformed plasma cells from T-cell recognition because of impaired antigen processing-presenting machinery (APM). We studied plasma cells and CD8(+) T cells from bone marrow of 20 MGUS patients, 20 MM patients, and 10 control patients. Immunofluorescence and flow cytometry revealed significantly different patterns of APM component expression in plasma cells from the 3 groups.

Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma.

Bone marrow neovascularisation supports plasma cell tumour progression in patients with multiple myeloma (MM), and is partially sustained by bone marrow macrophages through their angiogenic and vasculogenic activities. As such, macrophages may be a target for antivascular treatment in MM. Here, we show that bortezomib (BZ) and zoledronic acid (ZOL) display distinct and synergistic inhibitory effects on cell proliferation, adhesion, migration and expression of angiogenic cytokines (i.

Oversecretion of cytokines and chemokines in lupus nephritis is regulated by intraparenchymal dendritic cells: a review.

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is attributed to the glomerular deposition of immune complexes as well as to imbalance of the cytokine homeostasis. In this context, high production of cytokines and chemokines by dendritic cells (DCs) may concur to LN.