Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

Cancer-associated neo vessels’ formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines’ expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial–neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically

Long-Term Monitoring of a Surface Flow Constructed Wetland Treating Agricultural Drainage Water in Northern Italy

Agricultural drainage water that has seeped into tile drainage systems can cause nitrogen and phosphorus pollution of the surface water bodies. Constructed wetlands (CWs) can help mitigate the effects of agricultural non-point sources of pollution and remove different pollutants from tile drainage water. In this study, hydrological and water quality data of a Northern Italian CW that has been treating agricultural drainage water since 2000 were considered to assess its ability to mitigate nitrogen and phosphorus pollution. The effects of such long-term operation on the nutrients and heavy metals that eventually accumulate in CW plants and sediments were also analysed. Since 2003, the CW has received different inflows with different nutrient loads due to several operation modes. However, on average, the outflow load has been 50% lower than the inflow one; thus, it can be said that the system has proved itself to be a viable option for tile drainage water treatment. It was found that the concentration of nitrogen and phosphorus in the plant tissues varied, whereas the nitrogen content of the soil increased more than 2.5 times. Heavy metals were found accumulated in the plant root systems and uniformly distributed throughout a 60 cm soil profile at levels suitable for private and public green areas, according to the Italian la

New insights in Diffuse Large B Cell Lymphoma Pathobiology

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases of NHL. Analysis of the tumor microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we analyzed the role of different cellular components of the tumor microenvironment, including mast cells, macrophages, and lymphocytes, in the tumor progression of DLBCL. We examined several approaches to confront the available pieces of evidence, whereby three key points emerged. DLBCL is a disease of malignant B cells spreading and accumulating both at nodal and at extranodal sites. In patients with both nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. The DLBCL cell interaction with mature stromal cells and vessels confers tumor protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL-milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression

Modelling soil water conent in a tomato field: proximal gamma ray spectroscopy and soil-crop system models

Proximal soil sensors are taking hold in the understanding of soil hydrogeological processes involved in precision agriculture. In this context, permanently installed gamma ray spectroscopy stations represent one of the best space-time trade off methods at field scale. This study proved the feasibility and reliability of soil water content monitoring through a seven-month continuous acquisition of terrestrial gamma radiation in a tomato test field. By employing a 1 L sodium iodide detector placed at a height of 2.25 m, we investigated the gamma signal coming from an area having a ~25 m radius and from a depth of approximately 30 cm. Experimental values, inferred after a calibration measurement and corrected for the presence of biomass, were corroborated with gravimetric data acquired under different soil moisture conditions, giving an average absolute discrepancy of about 2%. A quantitative comparison was carried out with data simulated by AquaCrop, CRITeRIA, and IRRINET soil-crop system models. The different goodness of fit obtained in bare soil condition and during the vegetated period highlighted that CRITeRIA showed the best agreement with the experimental data over the entire data-taking period while, in presence of the tomato crop, IRRINET provided the best results.Comment: 18 pages, 9 Figures, 3 Table

Productivity of energy sorghum irrigated with reclaimed wastewaters

The sustainability of biomass sorghum ( Sorghum bicolor L. Moench.) in the Mediterranean environment is linked to the possibility of increasing crop productivity by using conventional clean water and wastewater irrigation. An experimental setup was arranged in Southern Italy during 2012 and 2013 seasons to determine the potential productivity of biomass sorghum irrigated with conventional water at different irrigation regimes (100 and 50% of calculated evapotranspiration) and different types of municipal wastewater. During the sorghum growing season, the crop development (biomass and leaf are index) and the soil water content were monitored for all irrigation treatments. The data obtained showed that the dry biomass of sorghum irrigated with the deficit treatment (17 t ha –1 ) was lower compared with conventionally irrigated sorghum. For both seasons and under full irrigated conditions, sorghum irrigated with wastewater produced on average more dry biomass (23 t ha –1 ) than the crop irrigated with conventional water (20.5 t ha –1 ), using the same irrigation volumes

circPVT1 and PVT1/AKT3 show a role in cell proliferation, apoptosis, and tumor subtype-definition in small cell lung cancer

Small cell lung cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsa_circ_0001821 (circPVT1) and PVT1/AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1/POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC; these entities may prove useful as novel biomarkers in MYC-amplified tumors.</p

A HGF/cMET Autocrine Loop Is Operative in Multiple Myeloma Bone Marrow Endothelial Cells and May Represent a Novel Therapeutic Target

Purpose: The aim of this study was to investigate the angiogenic role of the hepatocyte growth factor (HGF)/cMET pathway and its inhibition in bone marrow endothelial cells (EC) from patients with multiple myeloma versus from patients with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (control group). Experimental Design: The HGF/cMET pathway was evaluated in ECs from patients with multiple myeloma (multiple myeloma ECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies, or on refractory phase to these drugs; in ECs from patients with MGUS (MGECs); and in those patients from the control group. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on multiple myeloma ECs' angiogenic activities were studied in vitro and in vivo. Results: Multiple myeloma ECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNAand protein levels versus MGECs and control ECs. Multiple myeloma ECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, whereas treatment with anti-HGF and anti-cMET neutralizing antibodies (Ab) is able to inhibit cMET activation. The cMET pathway regulates several multiple myeloma EC activities, including chemotaxis, motility, adhesion, spreading, and whole angiogenesis. Its inhibition by SU11274 impairs these activities in a statistically significant fashion when combined with bortezomib or lenalidomide, both in vitro and in vivo. Conclusions: An autocrine HGF/cMET loop sustains multiple myeloma angiogenesis and represents an appealing new target to potentiate the antiangiogenic management of patients with multiple myeloma

Mast Cells and Interleukins

Mast cells play a critical role in inflammatory diseases and tumor growth. The versatility of mast cells is reflected in their ability to secrete a wide range of biologically active cytokines, including interleukins, chemokines, lipid mediators, proteases, and biogenic amines. The aim of this review article is to analyze the complex involvement of mast cells in the secretion of interleukins and the role of interleukins in the regulation of biological activities of mast cells

SARS-CoV-2 and Endothelial Cells: Vascular Changes, Intussusceptive Microvascular Growth and Novel Therapeutic Windows

Endothelial activation in infectious diseases plays a crucial role in understanding and predicting the outcomes and future treatments of several clinical conditions. COVID-19 is no exception. Moving from basic principles to novel approaches, an evolving view of endothelial activation provides insights into a better knowledge of the upstream actors in COVID-19 as a crucial future direction for managing SARS-CoV-2 and other infections. Assessing the function of resting and damaged endothelial cells in infection, particularly in COVID-19, five critical processes emerged controlling thrombo-resistance: vascular integrity, blood flow regulation, immune cell trafficking, angiogenesis and intussusceptive microvascular growth. Endothelial cell injury is associated with thrombosis, increased vessel contraction and a crucial phenomenon identified as intussusceptive microvascular growth, an unprecedented event of vessel splitting into two lumens through the integration of circulating pro-angiogenic cells. An essential awareness of endothelial cells and their phenotypic changes in COVID-19 inflammation is pivotal to understanding the vascular biology of infections and may offer crucial new therapeutic windows