Isolation and characterization of neural stem cells from dystrophic mdx mouse.

The blood-brain barrier (BBB) is altered in mdx mouse, an animal model to study Duchenne muscular dystrophy (DMD). Our previous work demonstrated that perivascular glial endfeet control the selective exchanges between blood and neuropil as well as the BBB development and integrity; the alterations of dystrophin and dystrophin-associated protein complex (DAPs) in the glial cells of mdx mouse, parallel damages of the BBB and increase in vascular permeability. The aim of this study was to improve our knowledge about brain cellular components in the mdx mouse through the isolation, for the first time, of the adult neural stem cells (ANSCs).

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX.

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression.

Patients And Methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab.

Integrating computational and chemical biology tools in the discovery of antiangiogenic small molecule ligands of FGF2 derived from endogenous inhibitors.

The FGFs/FGFRs system is a recognized actionable target for therapeutic approaches aimed at inhibiting tumor growth, angiogenesis, metastasis, and resistance to therapy. We previously identified a non-peptidic compound (SM27) that retains the structural and functional properties of the FGF2-binding sequence of thrombospondin-1 (TSP-1), a major endogenous inhibitor of angiogenesis. Here we identified new small molecule inhibitors of FGF2 based on the initial lead.

The development of human mast cells. An historical reappraisal.

The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34(+)/CD117(+)/CD13(+)multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation.

Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression.

Multiple myeloma (MM) pathogenesis and progression largely rely on the cells and extracellular factors in the bone marrow (BM) microenvironment. Compelling studies have identified tumour exosomes as key regulators in the maintenance and education of the BM microenvironment by targeting stromal cells, immune cells, and vascular cells. However, the role of MM exosomes in the modification of the BM microenvironment and MM progression remains unclear.

The failed attribution of the Nobel Prize for Medicine or Physiology to Viktor Hamburger for the discovery of Nerve Growth Factor.

The announcement in October 1986 that the Nobel Prize for Physiology or Medicine was to awarded to Rita Levi Montalcini and Stanley Cohen for the discovery of nerve growth factor (NGF) and epidermal growth factor, respectively, caused many to wonder why Viktor Hamburger in whose laboratory the initial work was done had not been included in the award. This article try to reconstruct the history of the discovery of NGF with the aim to re-establish a correct dynamic of the events.

Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients.

Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo and EpoR), unrelated to erythropoiesis, including angiogenesis. Here, we detected the expression of EpoR in bone marrow-derived endothelial cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients (MGECs and MMECs, respectively) and assessed whether Epo plays a role in MGECs- and MMECs-mediated angiogenesis. We show that EpoR is expressed by both MGECs and MMECs even though at a higher level in the first ones.

Mast cells positive to tryptase and tumour-associated macrophages correlate with angiogenesis in locally advanced colorectal cancer patients undergone to surgery.

Objective: The density of mast cells positive to tryptase (MCDPT) and tumor-associated macrophages (TAMs) were evaluated in a series of 87 patients with stage B and C colorectal cancer who had undergone radical surgery.

Methods: MCDPT, TAMs, microvascular density (MVD), endothelial area (EA) and CD8(+) tumor infiltrating lymphocytes (CD8(+) TILs) were evaluated in tumor tissue samples by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and with the main clinico-pathological features.

Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma.

Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).

Targeting B-cell non Hodgkin lymphoma: New and old tricks.

The management of B-cell malignancies continues to pose a clinical challenge. In the past years, rituximab (anti-CD20) emerged as the standard of care in the induction treatment of follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), as well as in other subsets. Since the benefits of immuno-chemotherapy have been clearly demonstrated in a whole range of lymphomas, several innovative approaches are being explored to achieve significant responses, particularly in refractory B-cell non-Hodgkin lymphoma (NHL) cases.

The discovery of immunoglobulin E.

The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers.

Cholangiocarcinoma: Current opinion on clinical practice diagnostic and therapeutic algorithms: A review of the literature and a long-standing experience of a referral center.

In the oncology landscape, cholangiocarcinoma is a challenging disease in terms of both diagnosis and treatment. Besides anamnesis and clinical examination, a definitive diagnosis of cholangiocarcinoma should be supported by imaging techniques (US, CT, MRI) and invasive investigations (ERC or EUS with brushing and FNA or US or CT-guided biopsy) followed by pathological confirmation. Surgery is the main curative option, so resectability of the tumour should be promptly assessed.

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

Background: After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far.

Methods: We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions.

The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

The discovery of the blood-thymus barrier.

The blood-thymus barrier is a functional and selective barrier separating T-lymphocytes from blood and cortical capillaries in the cortex of the thymus. The existence of this barrier was proposed for the first in time in 1961 by Marshall and White, and demonstrated in 1963 by Clark and Weiss. The most clear morphological evidence concerning the existence of the blood-thymus barrier may be attributed to the collaborative work published in 1972 by two scientists, Morris Karnovsky and Elio Raviola.

Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib.

Background And Objective: Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib.

Enhanced expression of CD31/platelet endothelial cell adhesion molecule 1 (PECAM1) correlates with hypoxia inducible factor-1 alpha (HIF-1α) in human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is characterized by numerous abnormal blood vessels, which rapidly proliferate and invade brain tissue and express different angiogenic factors. In this study we have investigated whether the expression levels of CD31/ PECAM1 are deregulated in human GBM tissue specimens and we have also correlated the expression levels of CD31/PECAM1 with those of HIF-1α. Finally, we have established a correlation between the expression levels of CD31/PECAM1 and HIF-1α, and those of two other biomarkers, namely N-cadherin and ADAM-10, of aggressiveness in the same tumors.

A fractal analysis of the spatial distribution of tumoral mast cells in lymph nodes and bone marrow.

The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells distribution through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. We have compared diffuse large B cells lymphoma (DLBCL) and systemic mastocytosis in two different anatomical localizations (lymph nodes for DLBCL and, respectively, bone marrow for mastocytosis).

Hemilipin, a novel Hemiscorpius lepturus venom heterodimeric phospholipase A2, which inhibits angiogenesis in vitro and in vivo.

Phospholipases A2 (PLA2) are enzymes which specifically hydrolyze the sn-2 acyl ester bond of phospholipids producing free fatty acids and lysophospholipids. The secreted PLA2 (sPLA2) are the most common types of PLA2 purified from the snake venom, mammalian pancreatic juice and other sources. They display a variety of toxic actions and biological activities, including antitumoral and antiangiogenic effects.

New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?

Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents.