Anaplastic lymphoma kinase: a glimmer of hope in lung cancer treatment?

Anaplastic lymphoma kinase (ALK) rearrangements (ALK-Rs) have been identified in 3-7% of all non-small-cell lung cancers (NSCLCs) and represent an important molecular target for NSCLC treatment. The authors discuss the role of ALK-Rs in the prediction of clinical-pathological features of NSCLCs and the technical problems related to their determination in specimens. The authors also describe the preclinical and clinical results derived from the use of ALK inhibitors.

Gene expression of adhesion molecules in endothelial cells from patients with peripheral arterial disease is reduced after surgical revascularization and pharmacological treatment.

Atherosclerosis is an inflammatory disease characterized by immunological activity, in which endothelial dysfunction represents an early event leading to subsequent inflammatory vascular damage. We investigated gene expression of the adhesion molecules (AMs) ICAM-1, VCAM-1, and β1-integrin in endothelial cells (ECs) isolated from venous blood (circulating EC, cEC) and purified from femoral plaques (pEC) obtained from 9 patients with peripheral artery disease (PAD) submitted to femoral artery thrombendarterectomy (FEA). In addition, in peripheral blood mononuclear cells (PBMCs) of the same subjects, we investigated gene expression of IFN-γ, IL-4, TGF-β, and IL-10.

Universal quantitative kinase assay based on diagonal SCX chromatography and stable isotope dimethyl labeling provides high-definition kinase consensus motifs for PKA and human Mps1.

In order to understand cellular signaling, a clear understanding of kinase-substrate relationships is essential. Some of these relationships are defined by consensus recognition motifs present in substrates making them amendable for phosphorylation by designated kinases. Here, we explore a method that is based on two sequential steps of strong cation exchange chromatography combined with differential stable isotope labeling, to define kinase consensus motifs with high accuracy.

STAT3 activity is necessary and sufficient for the development of immune-mediated myocarditis in mice and promotes progression to dilated cardiomyopathy.

Myocarditis, often triggered by viral infection, may lead to heart auto-immunity and dilated cardiomyopathy. What determines the switch between disease resolution and progression is however incompletely understood. We show that pharmacological inhibition of STAT3, the main mediator of IL-6 signalling and of Th17-cell differentiation, protects mice from the development of Experimental Auto-immune Myocarditis reducing liver production of the complement component C3, and can act therapeutically when administered at disease peak.

Cold-water immersion decreases cerebral oxygenation but improves recovery after intermittent-sprint exercise in the heat.

This study examined the effects of post-exercise cooling on recovery of neuromuscular, physiological, and cerebral hemodynamic responses after intermittent-sprint exercise in the heat. Nine participants underwent three post-exercise recovery trials, including a control (CONT), mixed-method cooling (MIX), and cold-water immersion (10 °C; CWI). Voluntary force and activation were assessed simultaneously with cerebral oxygenation (near-infrared spectroscopy) pre- and post-exercise, post-intervention, and 1-h and 24-h post-exercise.

Multiple genetic alterations within the PI3K pathway are responsible for AKT activation in patients with ovarian carcinoma.

The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is activated in multiple cancers including ovarian carcinoma (OC). However, the relative contribution of the single components within the PI3K pathway to AKT activation in OC is still unclear. We examined 98 tumor samples from Italian OC patients for alterations in the members of the PI3K pathway.

Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition.

Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal through a process that requires poly(ADP-ribose) polymerase (PARP) activity. Whether regressed forks can efficiently restart and what factors are required to restart fork progression after fork reversal are still unknown.

Angiotensin II type 1 and type 2 receptor expression in circulating monocytes of diabetic and hypercholesterolemic patients over 3-month rosuvastatin treatment.

Background: In diabetes, a variety of pro-inflammatory cellular changes has been found in various cell types, including monocytes which are known to be involved in all the phases of atherogenesis. Angiotensin II (Ang II) type 1 receptor (AT1R) mediates the pro-atherogenic effects of Ang II whereas the type 2 receptor (AT2R) seems associated with atheroprotection. We sought to investigate the potential changes of AT1R-AT2R expression in human monocytes of type 2 diabetic- hypercholesterolemic patients and in hypercholesterolemic subjects, upon clinical treatment with rosuvastatin.

A rare case of deradelphus cephalo-thoracoomphalopagus in lamb.

Male cross-breed lamb conjoined twins were sent for examination. The twins came from a farm located in the outskirts of Palermo. The twins were spontaneously delivered and found dead by the farmer.

Activin-β(c) reduces reproductive tumour progression and abolishes cancer-associated cachexia in inhibin-deficient mice.

Activins are involved in the regulation of a diverse range of physiological processes including development, reproduction, and fertility, and have been implicated in the progression of cancers. Bioactivity is regulated by the inhibin α-subunit and by an activin-binding protein, follistatin. The activin-β(C) subunit was not considered functionally significant in this regard due to an absence of phenotype in knockout mice.

A new diagnosis of myelodysplastic syndrome in hemochromatosis in an elderly man.

Hemochromatosis is associated with increased risk of hematological neoplasias, but studies showing hemochromatosis gene mutations in myelodysplastic syndrome (MDS) are scanty, particularly in the elderly. The onset of MDS in hemochromatosis usually occurs between 60 and 70 years of age, while cases with advanced age are very rare. We report a case of a 78- year-old man with hemochromatosis who developed refractory anemia with excess of blasts.

Beta-catenin expression in pilomatrix carcinoma with multiple visceral metastases in a dog.

Beta-catenin is a protein initially identified as a submembrane component of the E-cadherin-mediated cell-to-cell adhesion system. It plays a role as a transcriptional factor in the wingless/Wnt signalling pathway. Beta-catenin has been associated with oncogenic activity in human benign and malignant pilomatrix neoplasms where the immunohistochemical profile of β-catenin expression displayed both nuclear and cytoplasmic staining in basaloid cells.

Detection of West Nile virus RNA (lineages 1 and 2) in an external quality assessment programme for laboratories screening blood and blood components for West Nile virus by nucleic acid amplification testing.

Background: A second Italian external quality assessment programme was run in 2011 to assess the performance of blood transfusion centres in detecting West Nile virus RNA in plasma.

Materials And Methods: Each participant received two panels containing negative samples and samples positive for West Nile virus lineages 1 and 2, some of which with a viral concentration close to or below the 95% limit of detection of the respective commercial nucleic acid amplification test assay: the PROCLEIX WNV assay or the Cobas TaqScreen West Nile virus test.

Results: Eleven laboratories took part in the external quality assessment programme.

Adrenergic and dopaminergic modulation of immunity in multiple sclerosis: teaching old drugs new tricks?

Multiple sclerosis (MS) is an autoimmune disorder of the CNS characterized by inflammation, demyelination and axonal loss. Classical evidence in experimental allergic encephalomyelitis, the animal model of MS, support the relevance of sympatoadrenergic as well as of dopaminergic mechanisms. In MS patients, dysregulation of adrenergic and dopaminergic pathways contribute to the disease in immune system cells as well as in glial cells.

Mortality and cardiovascular events are best predicted by low central/peripheral pulse pressure amplification but not by high blood pressure levels in elderly nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study.

Objectives: The aim of the longitudinal PARTAGE study was to determine the predictive value of blood pressure (BP) and pulse pressure amplification, a marker of arterial function, for overall mortality (primary endpoint) and major cardiovascular (CV) events, in subjects older than 80 years of age living in a nursing home.

Background: Assessment of pulse indexes may be important in the evaluation of the CV risk in very elderly frail subjects.

Methods: A total of 1,126 subjects (874 women) who were living in French and Italian nursing homes were enrolled (mean age, 88 ± 5 years).

Expression of p53 and Ki-67 as prognostic factors for survival of men with colorectal cancer.

In patients with colorectal cancer (CRC) several independent prognostic factors are well-supported in the literature, including TNM stage, histological type and grade, and serum levels of carcinoembryonic antigen (CEA). All cancer cells express high levels of tissue proliferation markers, such as Ki-67 and p53, which are currently considered prognostic markers for patients with several types of cancers. We retrospectively studied 31 men (median age 65, range 48-75 years) with confirmed Dukes' B colorectal adenocarcinoma.

Metal chelates anchored to poly-L-peptides and linear D,L-α-peptides with promising nanotechnological applications.

Regular configurationally alternating amino acid sequences generate cyclic and linear helical peptides with a local β-conformation able to self-assemble in nanowires and nanoscaffolds directed and stabilized by hydrogen bonds. The possibility of modulating the chemical profile of the various amino acid residues containing reactive side chains means that peptides could be flexible templates for creating various building blocks. A method for the design of molecules with potential spintronic properties is described.

The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell malignancies.

Diffuse large B-cell lymphoma (DLBCL) can present as de novo or can arise through the transformation of many indolent lymphomas, including follicular lymphoma (FL). The morphological differentiation between germinal center-DLBCL (GC-DLBCL) and high-grade (grade 3) FL could be challenging; the accurate sub-classification of large B-cell lymphomas is mandatory in order to select the most appropriate among the new-targeted therapies. Recent expression profiling studies reported microRNAs (miRNAs) (and miR-17-92 cluster, in particular) as useful tools in differentiating DLBCL and FL.

Association between CYP1A2 polymorphisms and clozapine-induced adverse reactions in patients with schizophrenia.

We investigated the relationships between common polymorphisms in CYP1A2 (CYP1A2(⁎)1C and (⁎)1F), CYP1A2-mRNA levels in circulating lymphocytes and clozapine(CLZ)-induced adverse drug reactions (ADRs) in 34 patients. Patients with ADRs had a higher frequency of CYP1A2 low activity allele combinations (8/12; 67%) and lower CYP1A2-mRNA levels than patients without ADRs (6/22; 27%, P=0.019).

Touch imprint cytology and frozen-section analysis for intraoperative evaluation of sentinel nodes in early breast cancer.

Sentinel lymph node biopsy (SLNB) is currently the suggested axillary staging procedure in patients with early-stage breast cancer (BC) and usually requires intraoperative frozen-section (FS) examination of the removed nodes. However, other techniques, such as touch imprint cytology (IC), real-time reverse transcriptase-polymerase chain reaction and rapid cytokeratin immunostaining on FS may be used. The aim of this preliminary study was to assess the usefulness of intraoperative IC and FS section analysis together in improving the accuracy of sentinel lymph node evaluation in patients with early BC, who underwent SLNB.

A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.

Diagnosis of essential thrombocythemia (ET) has been updated in the last World Health Organization (WHO) classification. We developed a prognostic model to predict survival at diagnosis, named IPSET (International Prognostic Score for ET), studying patients with WHO-defined ET. Age 60 years or older, leukocyte count ≥ 11 × 10(9)/L, and prior thrombosis significantly affected survival, by multivariable Cox regression.

Systemic candidiasis in farm-reared red-legged partridges (Alectoris rufa) caused by Leucosporidium spp.

Background: This report describes the results of radiological, histological and molecular examination of three farm-reared red-legged partridges (Alectoris rufa) affected by candidiasis.

Case Presentation: Three juvenile farm-reared red-legged partridges in a batch of 100 of the same species were sent for clinical and pathological investigations. The owner referred of a sudden isolation of the sick animals, with apathy, diarrhea, ruffled plumage and respiratory rattles.

Neoangiogenesis in temporal bone carcinoma: the prognostic role of CD105.

Objective: Temporal bone squamous cell carcinoma (SCC) accounts for less than 2% of all head and neck tumors. Its biologic parameters should be investigated because clinicopathologic factors are often inaccurate for the purposes of its prognosis. CD105 is a proliferation-associated protein expressed in angiogenic endothelial cells and a potential prognostic indicator for several solid malignancies.