Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease.

Defects of the angiogenic process occur in the brain of twitcher mouse, an authentic model of human Krabbe disease caused by genetic deficiency of lysosomal β-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and accumulation of neurotoxic psychosine in the central nervous system. Here, quantitative computational analysis was used to explore the alterations of brain angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were used to assess calibers, amounts, lengths and spatial dispersion of CD31(+) vessels in 3D volumes from the postnatal frontal cortex of twitcher animals.

Interval sentinel lymph nodes in melanoma: a digital pathology analysis of Ki67 expression and microvascular density.

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma.

Peter Brian Medawar and the discovery of acquired immunological tolerance.

The immunological tolerance was described for the first time with the seminal observations made in 1945 by R.D. Owen, demonstrating that cattle dizygotic twins display red cell chimerism in adult life.

Sorafenib: 10 years after the first pivotal trial.

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings.

Cancer survivorship: long-term side-effects of anticancer treatments of gastrointestinal cancer.

Purpose Of Review: Surveillance of patients with a history of cancer is a frequent practice in oncology. However, it is often aimed at the early diagnosis of relapse and tends to underestimate the evaluation and care of factors impairing quality of life (QoL). Among these, long-term toxicities of anticancer treatments are one of the major threats to a complete physical and psychosocial recovery.

MMPs and angiogenesis affect the metastatic potential of a human vulvar leiomyosarcoma cell line.

Gynaecological leiomyosarcoma (gLMS) represent a heterogeneous group of soft tissue sarcoma, characterized by rare incidence, high aggressiveness and propensity to infiltrate secondary organs, poor prognosis and lethality, because of the lack of biological mechanisms that underlying their progression and effective pharmaceutical treatments. This study was focused on some of the aspects of progression and dissemination of a subtype of gLMS namely vulvar LMS (vLMS). We therefore used a vulvar LMS-derived cell line namely SK-LMS-1, coupled with in vitro and in vivo assays.

The crucial role of mast cells in blood-brain barrier alterations.

Mast cells are critical regulators of the pathogenesis of the central nervous system diseases, including stroke, multiple sclerosis, and traumatic brain injury, and brain tumors. Here, we have summarized the literature data concerning the involvement of mast cells in blood-brain barrier alterations, and we have suggested a possible role of angiogenic mediators stored in mast cell granules in the vasoproliferative reactions occurring in these pathological conditions. It is conceivable to hypothesize that mast cells might be regarded in a future perspective as a new target for the adjuvant treatment of neurodegenerative diseases and brain tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, favoring the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.

T cells, mast cells and microvascular density in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is recognized as the most common form of non-Hodgkin lymphoma (NHL), accounting for about 40 % of all cases of NHL. Among the cellular components of the tumor inflammatory infiltrate, T cells and mast cells have been demonstrated to be correlated with tumor angiogenesis. In this report, we have investigated CD3 and tryptase expression and their relationship with microvascular density (MVD) in DLBCL patients.

Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma.

The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples.

Mast cells as therapeutic target in cancer.

Mast cells promote tumorigenesis and tumor progression, and have functions that favor the host. Increased mast cell number correlates with a poor prognosis in several human tumors. In different vascular tumors, as well as a number of hematological and solid tumors, mast cell accumulation correlate with increased neovascularization, tumor aggressiveness, and metastatic spread.

Marine compounds inhibit growth of multiple myeloma in vitro and in vivo.

Purpose: The prognosis of patients with multiple myeloma (MM) is still dismal despite recent improvements achieved by introducing new therapeutic agents. However, there remains an urgent need for progress in myeloma drug development. We here show that novel marine-derived compounds can exert potent anti-myeloma activity.

Edelman's view on the discovery of antibodies.

Gerald M. Edelman began working to the structure of antibodies when joined as graduate student the laboratory of Henry Kunkel in 1958 at the "Rockefeller University" in New York, obtaining his doctorate in 1960. Edelman's focus on the structure of antibodies led to the 1972 Nobel Prize in Physiology or Medicine along with Rodney R.

Multiple myeloma as a model for the role of bone marrow niches in the control of angiogenesis.

Bone marrow (BM) contains hematopoietic stem cells (HSCs) and nonhematopoietic cells. HSCs give rise to all types of mature blood cells, while the nonhematopoietic component includes osteoblasts/osteoclasts, endothelial cells (ECs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). These cells form specialized "niches" which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche").

Broad targeting of angiogenesis for cancer prevention and therapy.

Deregulation of angiogenesis--the growth of new blood vessels from an existing vasculature--is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development.

First evidence of in vivo pro-angiogenic activity of cerebrospinal fluid samples from multiple sclerosis patients.

Increased vascular density and endothelial cell proliferation have been demonstrated in multiple sclerosis (MS) white matter, as well as an elevated vascular endothelial growth factor expression was detected in reactive astrocytes of both active and inactive chronic demyelinated lesions and in sera of MS patients during clinical relapses. In this study, we have investigated the angiogenic activity of cerebrospinal fluid (CSF) samples from MS patients with different stages of disease by means of the chick embryo chorioallantoic membrane (CAM), a well-known assay to study angiogenesis in vivo. Results have shown that CSF samples from MS patients induced a significant (p < 0.

The EGFR pathway regulates BCRP expression in NSCLC cells: role of erlotinib.

While multidrug resistance (MDR) in cancer is well established, little is known about the cellular pathways regulating the expression and trafficking of the MDR efflux transporter like BCRP (ABCG2). Here we evaluated the role of signalling downstream of EGFR on BCRP expression and sub-cellular localization using lung cancer cells harboring BCRP but expressing various EGFR and Ras activating mutations; A549 (K-Ras-G12S), H292 wild-type EGFR and Ras, and H1650 (EGFR-DelE747-A750). Immunocytochemistry and immunofluorescence studies demonstrated that BCRP was predominantly intracellular but its expression was found also on the plasma membrane in A549 and H1650 cells with activated Ras and EGFR.

Tryptase, a novel angiogenic factor stored in mast cell granules.

Human mast cells (MCs) are a rich reservoir of neutral proteases, packed in large amounts in their granules and comprising a high fraction of all cellular proteins. Among these proteases, tryptase is involved in angiogenesis after its release from activated MC granules, as it has been demonstrated in different in vitro and in vivo assays. Moreover, tryptase-positive MCs increase in number and vascularization increases in a linear fashion in different solid and hematological tumors.

Cancer associated fibroblasts in hematological malignancies.

Tumor microenvironment plays an important role in cancer initiation and progression. In hematological malignancies, the bone marrow represents the paradigmatic anatomical site in which tumor microenvironment expresses its morphofunctional features. Among the cells participating in the composition of this microenvironment, cancer associated fibrobasts (CAFs) have received less attention in hematopoietic tumors compared to solid cancers.

Basal and bevacizumab-based therapy-induced changes of lactate dehydrogenases and fibrinogen levels and clinical outcome of previously untreated metastatic colorectal cancer patients: a multicentric retrospective analysis.

Background: To assess the predictive role of lactate dehydrogenases (LDH) and fibrinogen (FBG) serum levels in metastatic colorectal cancer (mCRC) patients receiving a first-line bevacizumab-based therapy.

Objectives: The aim of the present analysis was to retrospectively evaluate the role of basal and post-treatment LDH and FBG serum levels in predicting the clinical outcome of 139 mCRC patients receiving first-line chemotherapy in combination with bevacizumab.

Results: A statistically significant association between high pre-treatment LDH and FBG levels and progressive disease was observed with respect to low basal LDH and FBG patients.

Pharmacogenomics of cetuximab in metastatic colorectal carcinoma.

Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit.

Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting.

Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy.

Epithelial-mesenchymal interactions: a fundamental Developmental Biology mechanism.

Interactions between epithelium and mesenchyme are common features of early stages of morphogenesis in different organs. In this historical review article, we retrospectively analyze the most important contribution to the definition and characterization of these interactions in three different organogenetic systems, including kidney, lung and limb bud. Tubule formation in the kidney is an example of an organogenetic event which involves interaction between the ureteric epithelium and the underlying mesenchyme that, in turn, induces the branching of the ureteric epithelium.

Microvascular density, CD68 and tryptase expression in human diffuse large B-cell lymphoma.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma characterized by clinical and biological heterogeneity attributable both to the tumor cells and the complex tumor-microenvironment surrounding them. Tumor-associated macrophages (TAMs) and mast cells are two major components of the tumor inflammatory infiltrate with a definite role in enhancing tumor angiogenesis. In this study, we have investigated CD68 and tryptase expression and their relationship with microvascular density (MVD) in chemo-resistant and chemosensitive patients affected by DLBCL.

The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma.

Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma.

Max D. Cooper and the delineation of two lymphoid lineages in the adaptive immune system.

This article outlines the fundamental contribution of Max D. Cooper to the analysis of the role of the thymus and of the bursa of Fabricius in the development of immunologic competence both before and after birth, placing a new scientific paradigm in the definition of the ontogeny of the lymphoid tissues.