Models and molecular mechanisms of blood vessel co-option by cancer cells
AbstractCancer cells have diverse mechanisms for utilizing the vasculature; they can initiate the formation of new blood vessels from preexisting ones (sprouting angiogenesis) or they can form cohesive interactions with the abluminal surface of preexisting vasculature in the absence of sprouting (co-option). The later process has received renewed attention due to the suggested role of blood vessel co-option in resistance to antiangiogenic therapies and the reported perivascular positioning and migratory patterns of cancer cells during tumor dormancy and invasion, respectively. However, only a few molecular mechanisms have ...
Source: Angiogenesis - October 18, 2019 Category: Molecular Biology Source Type: research
The tumor vasculature an attractive CAR T cell target in solid tumors
AbstractT cells armed with a chimeric antigen receptor, CAR T cells, have shown extraordinary activity against certain B lymphocyte malignancies, when targeted towards the CD19 B cell surface marker. These results have led to the regulatory approval of two CAR T cell approaches. Translation of this result to the solid tumor setting has been problematic until now. A number of differences between liquid and solid tumors are likely to cause this discrepancy. The main ones of these are undoubtedly the uncomplicated availability of the target cell within the blood compartment and the abundant expression of the target molecule o...
Source: Angiogenesis - October 18, 2019 Category: Molecular Biology Source Type: research
Highlights of the 13th International Hereditary Hemorrhagic Telangiectasia Scientific conference
Source: Angiogenesis - October 12, 2019 Category: Molecular Biology Source Type: research
The protein tyrosine phosphatase PTPRJ/DEP-1 contributes to the regulation of the Notch-signaling pathway and sprouting angiogenesis
AbstractThe Dll4-Notch-signaling pathway regulates capillary sprouting via the specification of endothelial tip cells. While VEGF is a potent inducer of Dll4 expression, the intracellular mediators that stimulate its expression remain poorly defined. The protein tyrosine phosphatase PTPRJ/DEP-1 is required for angiogenesis in normal or pathological contexts through its modulation of VEGF signaling. Here, we show that in DEP-1 KO mice, retinas at post-natal day 5 show enlarged blood vessels, as well as an increased number of tip cells and vessel branching points at the migrating front of the vascular plexus. Consistent with...
Source: Angiogenesis - October 9, 2019 Category: Molecular Biology Source Type: research
Stabilization of myeloid-derived HIFs promotes vascular regeneration in retinal ischemia
AbstractThe retinal vasculature is tightly organized in a structure that provides for the high metabolic demand of neurons while minimizing interference with incident light. The adverse impact of retinal vascular insufficiency is mitigated by adaptive vascular regeneration but exacerbated by pathological neovascularization. Aberrant growth of neovessels in the retina is responsible for impairment of sight in common blinding disorders including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration. Myeloid cells are key players in this process, with diverse roles that can eithe...
Source: Angiogenesis - October 3, 2019 Category: Molecular Biology Source Type: research
Glucose withdrawal induces Endothelin 1 release with significant angiogenic effect from first trimester (FTM), but not term human umbilical cord perivascular cells (HUCPVC)
ConclusionsFTM HUCPVC isolated from an early extraembryonic tissue show significant pro-angiogenic paracrine reaction in low-glucose conditions at least in part through the excess release of Endothelin 1. This can be a substantial advantage in cell therapy applications for ischemic injuries. (Source: Angiogenesis)
Source: Angiogenesis - October 1, 2019 Category: Molecular Biology Source Type: research
Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations
ConclusionsIHCT lesions are phenotypically similar to AVMs and contain the same somaticMAP2K1 orKRAS mutations, suggesting that IHCT is on the AVM spectrum. We propose calling this lesion “intramuscular fast-flow vascular anomaly.” (Source: Angiogenesis)
Source: Angiogenesis - September 5, 2019 Category: Molecular Biology Source Type: research
Revascularization after angiogenesis inhibition favors new sprouting over abandoned vessel reuse
AbstractInhibiting pathologic angiogenesis can halt disease progression, but such inhibition may offer only a temporary benefit, followed by tissue revascularization after treatment stoppage. This revascularization, however, occurs by largely unknown phenotypic changes in pathologic vessels. To investigate the dynamics of vessel reconfiguration during revascularization, we developed a model of reversible murine corneal angiogenesis permitting longitudinal examination of the same vasculature. Following 30 days of angiogenesis inhibition, two types of vascular structure were evident: partially regressed persistent vess...
Source: Angiogenesis - September 4, 2019 Category: Molecular Biology Source Type: research
Mitochondrial fission protein 1 up-regulation ameliorates senescence-related endothelial dysfunction of human endothelial progenitor cells
ConclusionIn human EPCs, down-regulation of Fis1 is involved in mitochondrial dysfunction and contributes to the impaired activity of EPCs during the senescence process. Enhanced expression of Fis1 in senescent EPCs restores the youthful phenotype. (Source: Angiogenesis)
Source: Angiogenesis - September 3, 2019 Category: Molecular Biology Source Type: research
Variable impact of three different antiangiogenic drugs alone or in combination with chemotherapy on multiple bone marrow-derived cell populations involved in angiogenesis and immunity
AbstractIn contrast to VEGF pathway-targeting antibodies, antiangiogenic tyrosine kinase inhibitors (TKIs) have failed to meet primary endpoints in almost all phase III clinical trials when combined with conventional chemotherapy. One exception is the combination of nintedanib and docetaxel as a second-line therapy for rapidly progressing advanced NSCLC. In addition to increased toxicity caused by this type of combination, thus necessitating drug dose reductions or treatment breaks, such phase III trial failures may also be related to the differential impact of host-mediated responses involving mobilization and tumor infil...
Source: Angiogenesis - August 28, 2019 Category: Molecular Biology Source Type: research
VEGFR2 activation mediates the pro-angiogenic activity of BMP4
AbstractThe Bone Morphogenetic Protein 4 (BMP4) regulates multiple biological processes, including vascular development and angiogenesis. Here, we investigated the role of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in mediating the angiogenic activity of BMP4. BMP4 induces a rapid relocation and phosphorylation of VEGFR2 on the endothelial cell membrane. These effects occur in the absence of a direct interaction of BMP4 and/or BMP receptors with VEGFR2. At variance, BMP4, by interacting with the BMPRI-II hetero-complex, induces c-Src phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic res...
Source: Angiogenesis - July 30, 2019 Category: Molecular Biology Source Type: research
Adgrf5 contributes to patterning of the endothelial deep layer in retina
AbstractNeovascularization of the inner retinal space is a major cause of vision loss. In retinal angiomatous proliferation (RAP) syndrome, newly formed vessels originate from the retinal plexus and invade the inner retinal space. However, the molecular pathways preventing subretinal vascularization remain largely unknown. In most murine models of RAP, pathological neovascularization occurs concomitantly with the development of the retinal vasculature. Here, we demonstrate that disturbing the sequence of morphogenetic events that shape the three-layered retinal vascular network leads to subretinal vascularization. Sprouts ...
Source: Angiogenesis - June 29, 2019 Category: Molecular Biology Source Type: research
PinX1 represses renal cancer angiogenesis via the mir-125a-3p/VEGF signaling pathway
ConclusionsPinX1 represses renal cancer angiogenesis through mir-125a-3p/VEGF signal pathway. The miR-125a-3p may be a candidate clinical prognostic marker and a novel therapeutic target in RCC. (Source: Angiogenesis)
Source: Angiogenesis - June 28, 2019 Category: Molecular Biology Source Type: research
Successful therapy with bevacizumab combined with corticosteroids for crizotinib-induced interstitial lung disease
We present the case of an old woman with ALK-rearranged stage IV lung adenocarcinoma who received crizotinib. She presented with severe dyspnea on the 34th day, and diffuse ground-glass opacifications in her chest. A diagnosis of crizotinib-induced ILD was confirmed. Corticosteroids were administered. However, the disease was still progressing rapidly. Therefore, as a monoclonal antibody against vascular endothelial growth factor, bevacizumab was administered in low doses (200 mg on days one and three). Her symptoms began to improve. Our clinical experience indicates that bevacizumab combined with corticosteroids mig...
Source: Angiogenesis - June 27, 2019 Category: Molecular Biology Source Type: research
The role of receptor MAS in microglia-driven retinal vascular development
AbstractObjectiveThe receptor MAS, encoded byMas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia.Approach and resultsTo assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and Mas1−/− mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced ( − 24%,p
Source: Angiogenesis - June 20, 2019 Category: Molecular Biology Source Type: research
Cancer stem cells contribute to angiogenesis and lymphangiogenesis in serous adenocarcinoma of the ovary
AbstractThe origin of blood and lymphatic vessels in high-grade serous adenocarcinoma of ovary (HGSOC) is uncertain. We evaluated the potential of cancer stem cells (CSCs) in HGSOC to contribute to their formation. Using spheroids as an in vitro model for CSCs, we have evaluated their role in primary malignant cells (PMCs) in ascites from previously untreated patients with HGSOC and cell lines. Spheroids from PMCs grown under specific conditions showed significantly higher expression of endothelial, pericyte and lymphatic endothelial markers. These endothelial and lymphatic cells formed tube-like structures, showed uptake ...
Source: Angiogenesis - June 3, 2019 Category: Molecular Biology Source Type: research
Monitoring tumour microenvironment changes during anti-angiogenesis therapy using functional MRI
This study aims to explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in assessing vessel function and tumour aggressiveness during anti-angiogenesis treatment.Materials and methodsA colon cancer xenograft model was established in BALB/C nude mice with the HCT116 cell line. Sixteen mice were randomly divided into Group A and Group B, which were treated with saline or bevacizumab by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th days and underwent DCE-MRI and BOLD-MRI examinations before and on the 3r...
Source: Angiogenesis - May 30, 2019 Category: Molecular Biology Source Type: research
Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma
ConclusionsOur results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression. (Source: Angiogenesis)
Source: Angiogenesis - April 15, 2019 Category: Molecular Biology Source Type: research
Prognostic effect of VEGF gene variants in metastatic non-small-cell lung cancer patients
ConclusionOur findings reinforce the potential clinical value of germline variants inVEGFA andVEGFR2 and show for the first time variants inITGAV andMAPK11 as promising prognostic markers in metastatic NSCLC patients receiving platinum-based chemotherapy. (Source: Angiogenesis)
Source: Angiogenesis - April 11, 2019 Category: Molecular Biology Source Type: research
The plaque-aortic ring assay: a new method to study human atherosclerosis-induced angiogenesis
We describe here a novel ex vivo model which fills this gap. Plaques obtained from 15 patients who underwent endarterectomy procedures were co-cultured in collagen gels with rat aorta rings which served as read-out of human plaque angiogenic activity. The majority of plaque fragments markedly stimulated angiogenic sprouting from the aortic rings while concurrently promoting the outgrowth of resident macrophages from the aortic adventitia. This stimulatory activity correlated with the presence of intraplaque macrophages. Proteomic analysis of plaque secretomes revealed heterogeneity of macrophage-stimulatory cytokine and an...
Source: Angiogenesis - April 9, 2019 Category: Molecular Biology Source Type: research
Exhaustion of the bone marrow progenitor cell reserve is associated with major events in severe limb ischemia
In this study, we examine if PB and BM PC numbers predict Amputation-Free Survival (AFS) in patients with Severe Limb Ischemia (SLI). We obtained PB and BM from 160 patients enrolled in a clinical trial investigating BM cell therapy for SLI. Samples were incubated with antibodies against CD34, KDR, CD133, CD184, CD14, CD105, CD140b, and CD31; PC populations were enumerated by flow cytometry. Higher PB CD34+ and CD133+ PC numbers were related to AFS (Both Hazard Ratio [HRevent] = 0.56,p = 0.003 andp = 0.0007, respectively). AFS was not associated with the other cell populati...
Source: Angiogenesis - March 30, 2019 Category: Molecular Biology Source Type: research
A new prognostic model for survival in second line for metastatic renal cell carcinoma: development and external validation
ConclusionA new prognostic model was developed and validated to estimate overall survival of patients with previously treated mRCC. This model is an easy-to-use tool that allows accurate estimation of patient survival to inform decision making and follow-up after first line for mRCC. (Source: Angiogenesis)
Source: Angiogenesis - February 9, 2019 Category: Molecular Biology Source Type: research
A ribosomal DNA-hosted microRNA regulates zebrafish embryonic angiogenesis
AbstractMicroRNAs (miRNAs) are single-stranded small non-coding RNAs, generally 18 –25 nucleotides in length, that act as repressors of gene expression. miRNAs are encoded by independent genes or processed from a variety of different RNA species. So far, there is no evidence showing that the ribosomal DNA-hosted microRNA is implicated in vertebrate development. Currently, we fou nd a highly expressed small RNA hosted in ribosomal DNA was predicted as a novel miRNA, named miR-ntu1, in zebrafish endothelial cells by deep sequencing analysis. The miRNA was validated by custom-designed Taqman PCR, Northern Blot, and in s...
Source: Angiogenesis - January 17, 2019 Category: Molecular Biology Source Type: research
Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety
AbstractRetinopathy of prematurity (ROP) with pathological retinal neovascularization is the most common cause of blindness in children. ROP is currently treated with laser therapy or cryotherapy, both of which may adversely affect the peripheral vision with limited efficacy. Owing to the susceptibility of the developing retina and vasculatures to pharmacological intervention, there is currently no approved drug therapy for ROP in preterm infants. Secretogranin III (Scg3) was recently discovered as a highly disease-restricted angiogenic factor, and a Scg3-neutralizing monoclonal antibody (mAb) was reported with high effica...
Source: Angiogenesis - January 14, 2019 Category: Molecular Biology Source Type: research
Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases
AbstractBackgroundIn patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values for the determination ...
Source: Angiogenesis - January 12, 2019 Category: Molecular Biology Source Type: research
Live imaging of angiogenesis during cutaneous wound healing in adult zebrafish
AbstractAngiogenesis, the growth of new blood vessels from pre-existing vessels, is critical for cutaneous wound healing. However, it remains elusive how endothelial cells (ECs) and pericytes (PCs) establish new blood vessels during cutaneous angiogenesis. We set up a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. First, we characterized basic structures of cutaneous vasculature. In normal skin tissues, ECs and PCs remained dormant to maintain quiescent blood vessels, whereas cutaneous injury immediately induced angiogenesis through the vascular endothelial growth factor signaling pathway. Tortuo...
Source: Angiogenesis - January 4, 2019 Category: Molecular Biology Source Type: research
Kruppel-like factor 4 regulates developmental angiogenesis through disruption of the RBP-J –NICD–MAML complex in intron 3 of Dll4
AbstractAngiogenesis is a multistep process that requires highly regulated endothelial cell (EC) behavior. The transcription factor Kr üppel-like factor 4 (KLF4) is a critical regulator of several basic EC functions; we have recently shown that KLF4 disturbs pathological (tumor) angiogenesis by mediating the expression of members of VEGF and Notch signaling pathways. Notch signaling is central to orchestration of sprouting angioge nesis but little is known about the upstream regulation of Notch itself. To determine the role of KLF4 in normal (developmental) angiogenesis, we used a mouse retinal angiogenesis model. We ...
Source: Angiogenesis - January 3, 2019 Category: Molecular Biology Source Type: research
Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity
ConclusionTo conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF. (Source: Angiogenesis)
Source: Angiogenesis - January 3, 2019 Category: Molecular Biology Source Type: research
Interleukin-22 promotes tumor angiogenesis
AbstractTH17 cells play important yet complex roles in cancer development and progression. We previously reported that TH17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by TH17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody,...
Source: Angiogenesis - December 11, 2018 Category: Molecular Biology Source Type: research
Mouse models of Alzheimer ’s disease cause rarefaction of pial collaterals and increased severity of ischemic stroke
AbstractVascular dysfunction contributes to the progression and severity of Alzheimer ’s disease (AD). Patients with AD also sustain larger infarctions after ischemic stroke; however, the responsible mechanisms are unknown. Pial collaterals are the primary source of protection in stroke. Unfortunately, natural aging and other vascular risk factors cause a decline in collateral numb er and diameter (rarefaction) and an increase in stroke severity. Herein, we tested the hypothesis that AD accelerates age-induced collateral rarefaction and examined potential underlying mechanisms. Triple and double transgenic mouse mode...
Source: Angiogenesis - December 5, 2018 Category: Molecular Biology Source Type: research
TSPYL5-mediated inhibition of p53 promotes human endothelial cell function
AbstractTestis-specific protein, Y-encoded like (TSPYL) family proteins (TSPYL1-6), which are members of the nucleosome assembly protein superfamily, have been determined to be involved in the regulation of various cellular functions. However, the potential role of TSPYL family proteins in endothelial cells (ECs) has not been determined. Here, we demonstrated that the expression of TSPYL5 is highly enriched in human ECs such as human umbilical vein endothelial cells (HUVECs) and human pluripotent stem cell-differentiated ECs (hPSC-ECs). Importantly, TSPYL5 overexpression was shown to promote EC proliferation and functions,...
Source: Angiogenesis - November 23, 2018 Category: Molecular Biology Source Type: research
The regulatory network of miR-141 in the inhibition of angiogenesis
In this study, we used several in vitro and in vivo models to demonstrate that miR-141 in endothelial cells inhibits angiogenesis. Additional mechanistic studies showed that miR-141 suppresses angiogenesis through multiple targets, includingNRP1, GAB1, CXCL12 β, TGFβ2, andGATA6, and bioinformatics analysis indicated that miR-141 and its targets comprise a powerful and precise regulatory network to modulate angiogenesis. Taken together, these data not only demonstrate an anti-angiogenic effect of miR-141, further strengthening the critical role of miR-200 family in the process of angiogenesis, but also provides a ...
Source: Angiogenesis - November 21, 2018 Category: Molecular Biology Source Type: research
ADAM10 controls the differentiation of the coronary arterial endothelium
AbstractThe coronary vasculature is crucial for normal heart function, yet much remains to be learned about its development, especially the maturation of coronary arterial endothelium. Here, we show that endothelial inactivation of ADAM10, a key regulator of Notch signaling, leads to defects in coronary arterial differentiation, as evidenced by dysregulated genes related to Notch signaling and arterial identity. Moreover, transcriptome analysis indicated reduced EGFR signaling inA10 ΔEC coronary endothelium. Further analysis revealed thatA10 ΔEC mice have enlarged dysfunctional hearts with abnormal myocardial c...
Source: Angiogenesis - November 16, 2018 Category: Molecular Biology Source Type: research
Extracellular vesicles of multiple myeloma cells utilize the proteasome inhibitor mechanism to moderate endothelial angiogenesis
AbstractBone marrow microenvironment is known to support angiogenesis, thus contributing to progression of multiple myeloma (MM). Bortezomib, a proteasome inhibitor (PI) widely used in MM treatment, has anti-angiogenic activity. Extracellular vesicles (EVs), shedding from cell surface, serve as mediators in cell-to-cell communication. We have hypothesized that MM cells (MMCs) treated with bortezomib generate EVs that could diminish angiogenesis, thus limiting MM progression. In the present study, EVs were obtained from MMCs (RPMI-8226), untreated (na ïve) or pre-treated with bortezomib. EVs were outlined using NanoSig...
Source: Angiogenesis - November 1, 2018 Category: Molecular Biology Source Type: research
AutoTube: a novel software for the automated morphometric analysis of vascular networks in tissues
AbstractDue to their involvement in many physiologic and pathologic processes, there is a great interest in identifying new molecular pathways that mediate the formation and function of blood and lymphatic vessels. Vascular research increasingly involves the image-based analysis and quantification of vessel networks in tissue whole-mounts or of tube-like structures formed by cultured endothelial cells in vitro. While both types of experiments deliver important mechanistic insights into (lymph)angiogenic processes, the manual analysis and quantification of such experiments are typically labour-intensive and affected by inte...
Source: Angiogenesis - October 28, 2018 Category: Molecular Biology Source Type: research
Platelets: the holy grail in cancer blood biomarker research?
AbstractWe would like to promote the fact that platelets are increasingly emerging as a rich source of potential biomarkers for cancer. Blood platelets contain vast amounts of bioactive proteins, such as growth factors, chemokines, and cytokines. These proteins are either synthesized by the megakaryocytes that produce the platelets or are sequestered by the circulating platelets from the blood, in which case these proteins may originate from the tumor. Recent studies in patients have demonstrated that the presence of cancer influences multiple platelet characteristics (e.g., platelet count, volume, activation status, prote...
Source: Angiogenesis - October 20, 2018 Category: Molecular Biology Source Type: research
Staphylococcus aureus alpha toxin activates Notch in vascular cells
AbstractStaphylococcus aureus infection is one of the leading causes of morbidity in hospitalized patients in the United States, an effect compounded by increasing antibiotic resistance. The secreted agent hemolysin alpha toxin (Hla) requires the receptor A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10) to mediate its toxic effects. We hypothesized that these effects are in part regulated by Notch signaling, for which ADAM10 activation is essential. Notch proteins function in developmental and pathological angiogenesis via the modulation of key pathways in endothelial and perivascular cells. Thus, ...
Source: Angiogenesis - October 15, 2018 Category: Molecular Biology Source Type: research
Excess vascular endothelial growth factor-A disrupts pericyte recruitment during blood vessel formation
AbstractPericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations. Pericytes had little to no expression of V...
Source: Angiogenesis - September 20, 2018 Category: Molecular Biology Source Type: research
Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia
In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted. (Source: Angiogenesis)
Source: Angiogenesis - September 6, 2018 Category: Molecular Biology Source Type: research
Perfused 3D angiogenic sprouting in a high-throughput in vitro platform
AbstractAngiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from within the cellular microenvironment, such as biochemical gradients and perfusion. However, many of these cues are missing in current in vitro models of angiogenic sprouting. We here describe an in vitro platform that integrates both perfusion and the generation of stable biomolecular gradients and demonstrate its potential to study more physiologically relevant angiogenic sprouting and microvascular stabilization. The platform consists of an array of 40 individually addressable microfluidic units that enab...
Source: Angiogenesis - August 31, 2018 Category: Molecular Biology Source Type: research
The calcium-binding type III repeats domain of thrombospondin-2 binds to fibroblast growth factor 2 (FGF2)
AbstractThrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2. The FGF2 binding properties of TSP-1 and TSP-2 and their recombinant domains were analyzed by solid...
Source: Angiogenesis - August 30, 2018 Category: Molecular Biology Source Type: research
Understanding the evolving phenotype of vascular complications in telomere biology disorders
AbstractVascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications...
Source: Angiogenesis - August 25, 2018 Category: Molecular Biology Source Type: research
Angiogenesis in pancreatic cancer: current research status and clinical implications
AbstractPancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of
Source: Angiogenesis - August 24, 2018 Category: Molecular Biology Source Type: research
Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer
AbstractCancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promising results in preclinical models, the benefits for patients proved to be limited. Inadequate efficacy similarly halted the development of agents impinging on the activity of the activin receptor-like kinase (ALK)1, a member of the transforming growth factor- β superfamily. Notwithstanding its char...
Source: Angiogenesis - August 21, 2018 Category: Molecular Biology Source Type: research