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Results for “angiogenesis”

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At least 19 recordsLinked to original sources

PubMed2022

WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy.

Lysine-deficient protein kinase-1 (WNK1) is critical for both embryonic angiogenesis and tumor-induced angiogenesis. However, the downstream effectors of WNK1 during these processes remain ambiguous. In this study, we identified that oxidative stress responsive 1b (osr1b) is upregulated in endothelial cells in both embryonic and tumor-induced angiogenesis in zebrafish, accompanied by downregulation of protein phosphatase 2A (pp2a) subunit ppp2r1bb. In addition, wnk1a and osr1b are upregulated in two liver cancer transgenic fish models: [tert x p53-/-] and [HBx,src,p53-/-,RPIA], while ppp2r1bb is downregulated in [tert x p53-/-]. Furthermore, using HUVEC endothelial cells co-cultured with HepG2 hepatoma cells, we confirmed that WNK1 plays a critical role in the induction of hepatoma cell migration in both endothelial cells and hepatoma cells. Moreover, overexpression of OSR1 can rescue the reduced cell migration caused by shWNK1 knockdown in HUVEC cells, indicating OSR1 is downstream of WNK1 in endothelial cells promoting hepatoma cell migration. Overexpression of PPP2R1A can rescue the increased cell migration caused by WNK1 overexpression in HepG2, indicating that PPP2R1A is a downstream effector in hepatoma. The combinatorial treatment with WNK1 inhibitor (WNK463) and OSR1 inhibitor (Rafoxanide) plus oligo-fucoidan via oral gavage to feed [HBx,src,p53-/-,RPIA] transgenic fish exhibits much more significant anticancer efficacy than Regorafenib for advanced HCC. Importantly, oligo-fucoidan can reduce the cell senescence marker-IL-1β expression. Furthermore, oligo-fucoidan reduces the increased cell senescence-associated β-galactosidase activity in tert transgenic fish treated with WNK1-OSR1 inhibitors. Our results reveal the WNK1-OSR1-PPP2R1A axis plays a critical role in both endothelial and hepatoma cells during tumor-induced angiogenesis promoting cancer cell migration. By in vitro and in vivo experiments, we further uncover the molecular mechanisms of WNK1 and its downstream effectors during tumor-induced angiogenesis. Targeting WNK1-OSR1-mediated anti-angiogenesis and anti-cancer activity, the undesired inflammation response caused by inhibiting WNK1-OSR1 can be attenuated by the combination therapy with oligo-fucoidan and may improve the efficacy.

Animals↗

PubMed2024

Comprehensive analysis of circRNA-miRNA-mRNA network related to angiogenesis in recurrent implantation failure.

BACKGROUND: Abnormal endometrial blood flow causes a decrease in endometrial receptivity and is considered a relatively independent risk factor for recurrent implantation failure (RIF). This study aimed to explore the potentially functional circRNA-miRNA-mRNA network in RIF, and further explore its mechanism. METHODS: Datasets were downloaded from the GEO database to identify differentially expressed circRNAs, miRNAs and mRNAs. The circRNA-miRNA-mRNA and PPI networks were constructed using Cytoscape 3.6.0 and the STRING database, the hub genes were identified with the cytoHubba plug-in, and a circRNA-miRNA-hub mRNA regulatory sub-network was constructed. Then, GO and KEGG pathway enrichment analyses of the hub genes were performed to comprehensively analyze the mechanism of hub mRNAs in RIF. Due to the results of circRNAs-miRNAs-hub mRNAs regulatory network, we verified the expression of circRNA_0001721, circRNA_0000714, miR-17-5p, miR-29b-3p, HIF1A and VEGFA in the RIF mouse model by qRT‒PCR and western blotting. RESULTS: We initially identified 175 DEmRNAs, 48 DEmiRNAs and 56 DEcircRNAs in RIF associated with angiogenesis and constructed a circRNA-miRNA‒mRNA network and PPI network. We further identified six hub genes in the acquired network. Based on these genes, functional enrichment analysis revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. In addition, the interaction networks of circRNA_0001721/miR-17-5p/HIF1A and the circRNA_0000714/miR-29b-3p/VEGFA axis were predicted. In the RIF mouse model, circRNA_0001721, circRNA_0000714, HIF1A and VEGFA were down-regulated, whereas miR-17-5p and miR-29b-3p were up-regulated according to qRT‒PCR and western blotting. CONCLUSION: This study revealed that the HIF-1 signaling pathway plays a vital role in endometrial angiogenesis in RIF. The circRNA_0001721/miR-17-5p/HIF1A and circRNA_0000714/miR-29b-3p/VEGFA axes might play a role in the pathogenesis of endometrial angiogenesis in RIF.

MicroRNAs↗

PubMed1978

[The tumor angiogenesis factor (TAF)].

The tumor Angiogenesis Factor (T.A.F.) isolated from several human and animal neoplasms by J. Folkman and S. Kumar is a factor that induces the appearance of neovessels in the tumors. After describing the methods of vasculor, physiological, experimental and in some cases pathological proliferation, the author has compared the Angiogenesis in both the natural and neoplastic tissues, then, he's studies the tumoral growth the rate of which regularized by the T.A.F. The proving, the extraction and chemical nature of this factor have been reviewed. Afterwards, the author has called to mind the notion of tumoral ecology and the various possibilities of inhibition of the tumoral growth, that is founded on the inhibition of the Angiogenesis and the therapeutical possibilities of the T.A.F. in the fight against cancer. To end up with his study, the author is now considering the possibility of using the T.A.F., extract of the sarcoma of sticker as a complement to the electontherapy in the treatment of this neoplasm.

Angiogenesis Inducing Agents↗

PubMed1976

Mast cells and tumor angiogenesis.

Tumor angiogenesis factor (TAF) elicits a strong vasoproliferative response when implanted upon the chorioallantoic membrane (CAM) of the chick embryo. This response is first observed stereomicroscopically 2-3 days after implantation. A 40-fold increase in mast cell density is observed within the vicinity of this implant by 24 h. Mast cells that have been isolated from retired breeder Sprague-Dawley rats fail to evoke a vascular reaction when implanted on the CAM. An intermediate role for the mast cell in tumor angiogenesis is suggested.

Angiogenesis Inducing Agents↗

PubMed1979

Tumour angiogenesis factor (TAF) and its neutralisation by a xenogeneic antiserum.

Tumour angiogenesis factor (TAF) has been extracted from a variety of animal and human tumours. Its ability to induce neovascularization in two bioassays, viz. rat air-sac and chick chorioallantoic membrane, is demonstrated. Similar extracts from normal tissues fail to induce angiogenesis. TAF extracts have been used to raise a xenogeneic antiserum, the specificity of which was investigated using classical immunological methods. Its ability to neutralize the biological activity of TAF using the two in vivo assays, was also demonstrated.

Allantois↗

PubMed1978

Inhibition of lymphocyte-induced angiogenesis by enzymatically isolated rabbit cornea cells.

Corneal and kidney cells were isolated from adult rabbits by enzymatic digestion. The were tested for anti-angiogeneic activity by the lymphocyte-induced angiogenesis assay. In this assay an intradermal injection of semi-allogeneic lymphocytes resulted in a new blood vessel formation visible after three days at the injection site. Isolated rabbit cells were mixed in 1:10 ratio with murine lymphocytes and injected into 600 R X-ray irradiated mice. Number of newly formed blood vessels evoked by lymphocytes injected alone or with rabbit cells added was counted. Corneal cells but not kidney cells decreased angiogenesis evoked by lymphocytes. This finding is discussed in view of corneal avascularity and pathological neo-vascularization.

Angiogenesis Inducing Agents↗

PubMed1979

Tumor angiogenesis activity in clonal cells transformed by bovine adenovirus type 3.

Four different sets of clonal cells transformed by bovine adenovirus type 3 and its oncogenic DNA fragments, and their clonal normal counterparts, were tested for tumor angiogenesis activity. The activity was assayed by measuring the host-mediated vascular response of a chorioallantoic membrane to the cell suspension separated from the vascular bed by a Millipore filter. Angiogenesis activity due to inflammation reaction was prevented by using corticosteroids. All of the transformed cells tested induced strong vascular responses as compared with their corresponding clonal normal cells. Cell dose and time dependency for the expression of the activity were also shown.

Adenoviridae↗

PubMed1975

Lymphocyte-induced angiogenesis: a quantitative and sensitive assay of the graft-vs.-host reaction.

A new and sensitive assay for the effect of intracutanous administration of immunocompentent lymphocytes into the skin of irradiated unimmunized mice is described. The assay, which we have termed lymphocyte-induced angiogenesis (LIA) involves enumeration of new vascular branches induced by the action of these competent cells. As is the case for the previously described normal lymphocyte transfer reaction, LIA is a manifestation of the graft-vs.-host reaction, as shown by experiments utilizing appropaiate genetic combinations. The reaction is dose-dependent, and within the dose range of 2 times 10 minus 5 -4 times 10-6 cells the mumber of vessels induced correlates with the mumber of immunocompetent cells injected. At these dose levels spleen, lumph node, and hydrocortisone-resistant thymocytes are effective; bone marrow and thymus cells are not. Spleen cells from nude mice are incapable of inducing LIA, while mitomycin-C and irradiated lymphocytes can initiate but not maintain the reaction. The relationship between lymphocyte-induced angiogenesis has been discussed as have the implications of these findings to delayed hypersensitivity, inflammation, and vascular pathology.

Age Factors↗

PubMed1979

Fibrin gel investment associated with line 1 and line 10 solid tumor growth, angiogenesis, and fibroplasia in guinea pigs. Role of cellular immunity, myofibroblasts, microvascular damage, and infarction in line 1 tumor regression.

Line 1 and line 10 tumors became invested in a fibrin-gel cocoon within hours after transplantation to the subcutaneous spaces of unsensitized syngeneic inbred Sewall Wright strain 2 guinea pigs. The fibrin gel comprised more than 80% of the line 1 tumor mass and, after day 3, became organized and was subsequently replaced by fibrous connective tissue, which gave the tumor the appearance of a scirrhous carcinoma. A cellular infiltrate of lymphocytes and basophils developed at the periphery of line 1 tumors after day 8, and tumors regressed by day 13. The fibrin gel investing the highly malignant line 10 tumors accounted for less than 10% of the tumor mass and persisted without fibrous organization as a tumor grew progressively and invaded adjacent tissues. These data provide new and potentially important insights into the biology of solid tumor growth and the mechanisms of immunologic tumor rejection. Envelopment of tumors in a fibrin gel created an anatomic barrier separating the tumors from the host. Neovascularization mimicking that about line 1 and line 10 tumors was induced by sc fibrin implants; these data suggest that activation of the clotting and/or fibrinolytic systems by tumor cells may itself provide sufficient stimulus for induction of tumor angiogenesis without requiring a separate tumor angiogenesis factor. The scirrhous pattern of growth characteristic of line 1 tumors apparently was achieved by organization of an abundant fibrin gel. Line 1 tumor regression did not for the most part involve direct contacts between tumor cells and any type of inflammatory cell, including macrophages; rather, tumor destruction was effected by ischemic necrosis secondary to widespread microvascular injury. The mechanisms of such injury are uncertain, but tumor rejection was correlated with evidence of developing cellular immunity and anatomic associations between lymphocytes and myofibroblasts. Further experiments will be necessary before these findings can be generalized to other tumor systems.

Animals↗

PubMed2026

Discovery of NAT-6-321056 as a novel modulator of VEGFR2 signaling to suppress tumor angiogenesis.

Vascular endothelial growth factor receptor 2 (VEGFR2) is a master regulator of angiogenesis and cancer progression. However, current VEGFR2 modulators face significant challenges, including off-target toxicity and acquired resistance, underscoring the urgent need for novel therapeutic agents with improved efficacy and safety profiles. Here, we reported that virtual screening of 39,442 natural products from the ZINC natural products-derived library, coupled with molecular docking and molecular dynamics (MD) simulations to evaluate the binding stability of candidate compounds, identified NAT-6-321056 as a highly promising modulator of VEGFR2 signaling. Biological evaluations demonstrated that NAT-6-321056 exerted potent inhibition on the growth of a broad spectrum of cancer cells, including both solid tumors and hematological malignancies. In EA.hy 926 endothelial cells and SK-N-DZ neuroblast cells, the compound significantly suppressed proliferation, migration, and invasion. Microscale thermophoresis (MST) confirmed direct binding of NAT-6-321056 to VEGFR2 with favorable affinity. Kinase profiling against a panel of 33 kinases indicated that NAT-6-321056 exhibited a multi-kinase modulation profile. Mechanistic studies revealed that NAT-6-321056 suppressed the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and was associated with reduced VEGFR2 phosphorylation and attenuation of the downstream ERK/JNK/AKT signaling pathways. Moreover, NAT-6-321056 exhibited robust in vivo anti-angiogenic effects in both the chick chorioallantoic membrane (CAM) assay and transgenic zebrafish vascular fluorescence imaging models. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction suggested acceptable drug-like properties. Collectively, these findings demonstrated that NAT-6-321056 is a promising modulator of VEGFR2 signaling with potent anti-angiogenic activity and represents a viable candidate for cancer therapy.

Vascular Endothelial Growth Factor Receptor-2↗

PubMed1976

Tumour angiogenesis factor (TAF) in human and animal tumours.

Extracts were made from Walker 256 carcinoma, spontaneous rat mammary adenocarcinoma, Wilms' tumour, human neuroblastoma and human haemangioma. Chromatography of the extracts on Sephadex G-100 yielded four fractions, A, B, C and D. Injection of fractions B and C resulted in the growth of new capillaries in the subcutaneous fascia or rats. Controls, e.g. similar extracts of rat liver or human kidney, did not induce neovascularisation. The endothelium of newly-formed blood vessels contained many mitotic figures. A limitation of this method is that it is qualitative only. In order to develop a quantitative in vitro assay for a tumour angiogenesis factor (TAF), short-term primary cultures were initiated from adult rat brain white matter, as cells from such cultures were shown to be vascular in origin. Addition of fractions containing TAF (B and C) which were active in vivo failed to stimulate thymidine uptake by the cells. The possible reasons for this failure and the therapeutic potential of TAF in cancer control are discussed.

Adenocarcinoma↗

PubMed1979

Importance of a collagen substratum for stimulation of capillary endothelial cell proliferation by tumour angiogenesis factor.

Tumour extracts were obtained from rat Walker 256 carcinoma and examined for the presence of tumour angiogenesis factor (TAF) in vivo before being used in tissue culture experiments. Capillary endothelial cells derived from cow brain white matter were used to study the effects of TAF-containing tumour extracts on cell proliferation in vitro. The cells were grown on two types of substrata: (1) plastic tissue culture dishes and (2) hydrated gels made of rat tail tendon type I collagen. Human platelets or platelet-released factors were introduced into the system because of the many inter-relationships known to exist between platelets, collagen and endothelial cells. If trypsin was used during the preparation of TAT, the resulting batches stimulated endothelial cell proliferation only when the cells were growing on a collagen substratum and either platelets or platelet-released factors were present in the growth medium. If incubation with trypsin was omitted from the TAF extraction procedure, the resulting batches stimulated cell growth both on plastic and on collagen. A synergistic interaction also occurred between these TAF-containing tumour extracts and platelet-released factors. This effect was always more marked when the cells were growing on collagen than when on plastic. These data suggest that the nature of the substratum affects the response of the endothelial cells to TAF and to platelet-released factors.

Angiogenesis Inducing Agents↗

PubMed1978

The chick embryo choriallantoic membrane as a bioassay for angiogenesis factors: reactions induced by carrier materials.

A variety of filter materials, sponges, and gels were placed on the chick chorioallantoic membrane (CAM), the reactions of it investigated and compared with those induced by natural egg materials (white eggshell membrane, coagulated albumen and yolk). Independently of the kind and nature of the naterials the CAM reacted nearly regularly underneath these diverse materials with a proliferation of ectodermal cells, fibroblasts, and blood vessels forming a highly capillarized granulation tissue. The area of the CAM surrounding the foreign materials frequently displayed an increase of small blood vessels macroscopically discernible and showing a radial arrangement (spoke-wheel-appearance according to FOLKMAN 1974). It is concluded that this type of vascular reaction cannot be considered as a characteristic feature for the action of a special tumour angiogenesis factor, since it can be induced by a variety of stimuli leading to an inflammatory reaction in the CAM. For the detection of special angiogenetic activities an objective quantification of the vessel reactions is necessary under consideration of the reactions induced by the mere presence of such foreign materials.

Allantois↗

PubMed2025

A model of Notch signalling control of angiogenesis: Evidence of a role for Notch ligand heterodimerization.

The ubiquitous Notch receptor signalling network is essential for tissue growth and maintenance. Operationally, receptor activity is regulated by two principal, counterposed mechanisms: intercellular Notch transactivation triggered by interactions between receptors and ligands expressed in neighbouring cells; intracellular cis inhibition mediated by ligands binding to receptors expressed in the same cell. Moreover, different Notch receptor/ligand combinations are known to elicit distinct molecular and cellular responses, and together, these phenomena determine the strength, the duration and the specificity of Notch receptor signalling. To date, it has been assumed that these processes involve discrete ligand homomers and not heteromeric complexes composed of more than one ligand species. In this study, we explore the molecular basis of the opposing actions of the Notch ligands, DLL4 and JAG1, which control angiogenic sprouting. Through a combination of experimental approaches and mathematical modelling, we provide evidence that two mechanisms could underpin this process: 1) DLL4 rather than JAG1 induces efficient Notch1 receptor transactivation; 2) JAG1 directly blocks DLL4-dependent cis-inhibition of Notch signalling through the formation of a JAG1/DLL4 complex. We propose a new model of Notch signalling that recapitulates the formation of tip and stalk cells, which is necessary for sprouting angiogenesis.

Signal Transduction↗

PubMed1978

Enhancing effect of X-ray irradiation on a new blood vessel formation in mice tested by lymphocyte induced angiogenesis assay.

X-irradiation enhanced a new blood vessel formation occurring in the course of a local GvH reaction in mice. Maximal enhancing effect was exerted by single total body irradiation doses ranging from 700 to 1050 R. Fractionation in daily doses smaller than 200 R did not exhibit enhancing effect. Proliferative ability of angiogenesis inducing cells is not necessary for enhancing effect of irradiation.

Angiogenesis Inducing Agents↗

PubMed2021

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

AGING↗

PubMed2026

Phosphoproteomic Profiling of Early-Stage Non-Small Cell Lung Cancer Provides Preliminary Evidence of Phosphorylation-Regulated Rho GTPase Signaling Driving Cytoskeletal Remodeling, Angiogenesis, and Cell Cycle Progression.

Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related deaths worldwide. This can be attributed to the difficulty in early detection and the limited efficacy of available treatments, partly due to an incomplete understanding of the disease biology. Identification of key proteins involved in early-stage progression and understanding the underlying mechanisms can greatly contribute to the development of diagnostic and treatment strategies for NSCLC. Quantitative phosphoproteomic analysis was done on paired tumor tissues and adjacent normal lung tissues from early-stage NSCLC adenocarcinoma (LUAD) patients to allow for the identification of proteins with differential phosphorylation and their associated pathways. A total of 6483 phosphoproteins were identified, with 1229 proteins having significantly higher phosphorylation and 701 proteins having significantly lower phosphorylation in the tumor tissues. All MS data were deposited in ProteomeXchange with the identifier PXD071583. Function enrichment analysis showed that the differentially phosphorylated proteins and phosphosites were primarily involved in Rho GTPase signaling and cytoskeleton remodeling. Analysis of protein interaction networks suggests that the predicted kinase activity likely drives malignant transformation in NSCLC LUAD, presumably through Rho GTPase-mediated angiogenesis and cell cycle progression. More importantly, this study identified several protein phosphosites with differential phosphorylation and inferred kinase-phosphosite activities that have not previously been reported in NSCLC LUAD.

Humans↗

PubMed1979

Angiogenesis in the mouse cornea.

We have developed a method that permits analysis of neovascular responses in the mouse cornea. Using this method we have demonstrated that both allogeneic lymphocytes and a variety of tumors can induce angiogenesis, but that only the latter appear capable of eliciting secondary capillary sprouting.

Animals↗