scholarly journals A Tunable Nanoplatform of Nanogold Functionalised with Angiogenin Peptides for Anti-Angiogenic Therapy of Brain Tumours

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1322 ◽  
Author(s):  
Naletova ◽  
Cucci ◽  
D’Angeli ◽  
Anfuso ◽  
Magrì ◽  
...  
Keyword(s):  
Physical Adsorption ◽  
Brain Cell ◽  
Metal Nanoparticle ◽  
Angiogenic Factor ◽  
Peptide Fragments ◽  
Growth And Survival ◽  
Angiogenic Therapy ◽  
Cellular Assays ◽  
Endogenous Protein ◽  
Cell Membrane Binding

Angiogenin (ANG), an endogenous protein that plays a key role in cell growth and survival, has been scrutinised here as promising nanomedicine tool for the modulation of pro-/anti-angiogenic processes in brain cancer therapy. Specifically, peptide fragments from the putative cell membrane binding domain (residues 60–68) of the protein were used in this study to obtain peptide-functionalised spherical gold nanoparticles (AuNPs) of about 10 nm and 30 nm in optical and hydrodynamic size, respectively. Different hybrid biointerfaces were fabricated by peptide physical adsorption (Ang60–68) or chemisorption (the cysteine analogous Ang60–68Cys) at the metal nanoparticle surface, and cellular assays were performed in the comparison with ANG-functionalised AuNPs. Cellular treatments were performed both in basal and in copper-supplemented cell culture medium, to scrutinise the synergic effect of the metal, which is another known angiogenic factor. Two brain cell lines were investigated in parallel, namely tumour glioblastoma (A172) and neuron-like differentiated neuroblastoma (d-SH-SY5Y). Results on cell viability/proliferation, cytoskeleton actin, angiogenin translocation and vascular endothelial growth factor (VEGF) release pointed to the promising potentialities of the developed systems as anti-angiogenic tunable nanoplaftforms in cancer cells treatment.

scholarly journals A Tunable Nanoplatform of Nanogold Functionalised With Angiogenin Peptides for Anti-angiogenic Therapy of Brain Tumours

2019 ◽  
Author(s):  
Irina Naletova ◽  
Lorena Maria Cucci ◽  
Floriana D'Angeli ◽  
Carmelina Daniela Anfuso ◽  
Antonio Magrì ◽  
...  
Keyword(s):  
Physical Adsorption ◽  
Brain Cell ◽  
Metal Nanoparticle ◽  
Angiogenic Factor ◽  
Peptide Fragments ◽  
Growth And Survival ◽  
Angiogenic Therapy ◽  
Cellular Assays ◽  
Endogenous Protein ◽  
Cell Membrane Binding

Angiogenin (ANG), an endogenous protein that plays a key role in cell growth and survival, has been scrutinised here as promising nanomedicine tool for the modulation of pro-/ anti-angiogenic processes in brain cancer therapy. Specifically, peptide fragments from the putative cell membrane binding domain (residues 60-68) of the protein were used in this study to obtain peptide-functionalised spherical gold nanoparticles (AuNPs) of about 10 nm and 30 nm in optical and hydrodynamic size, respectively. Different hybrid biointerfaces were fabricated by peptide physical adsorption (Ang60-68) or chemisorption (the cysteine analogous Ang60-68Cys) at the metal nanoparticle surface, and the cellular assays were performed in the comparison with ANG-functionalised AuNPs. Cellular treatments were performed both in basal and in copper-supplemented cell culture medium, to scrutinise the synergic effect of the metal, which is another known angiogenic factor. Two brain cell lines were investigated in parallel, namely tumour glioblastoma (A172) and neuron-like differentiated neuroblastoma (d-SH-SY5Y). Results on cell viability/proliferation, cytoskeleton actin, angiogenin translocation and VEGF release pointed to the promising potentialities of the developed systems as anti-angiogenic tunable nanoplaftforms in cancer cells treatment.

19. Anti-Angiogenic Therapy for Endometriosis

2018 ◽  
Author(s):  
Privia Randhawa
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Blood Supply ◽  
Uterine Cavity ◽  
Growth And Survival ◽  
Angiogenic Therapy ◽  
Lesion Growth ◽  
Gynecological Disease ◽  
Stromal Cell Derived Factor ◽  
Survival Studies

Endometriosis is a gynecological disease affecting 10 to 15% women. The disease is characterized by the growth of endometrium (lining of the uterus) outside of the uterine cavity. Women affected by this condition can experience symptoms that include pelvic pain, irregular bleeding, and infertility. One of the key requirements for endometriotic lesions to survive is to develop a blood supply to support their growth. Our laboratory is investigating mechanisms of how endometriotic lesions establish their blood supply and how neo-angiogenesis is regulated by endothelial and hematopoietic progenitor cells. Results from our laboratory showed that stromal cell derived factor-1 plays an important role in the recruitment of endothelial progenitor cells. Blocking of SDF-1 in a mouse model of endometriosis resulted in reduced lesion growth and survival. Studies are in progress to evaluate safety and efficacy of anti-angiogenic peptide, ABT-898, in an immunodeficient mouse model of endometriosis. 

scholarly journals Concurrent Physiological and Pathological Angiogenesis in Retinopathy of Prematurity and Emerging Therapies

2021 ◽  
Vol 22 (9) ◽  
pp. 4809
Author(s):  
Chang Dai ◽  
Keith A. Webster ◽  
Amit Bhatt ◽  
Hong Tian ◽  
Guanfang Su ◽  
...  
Keyword(s):  
Animal Models ◽  
Retinopathy Of Prematurity ◽  
Molecular Mechanisms ◽  
Retinal Vessel ◽  
Angiogenic Factor ◽  
Angiogenic Therapy ◽  
Pathological Angiogenesis ◽  
Emerging Therapies ◽  
Vessel Development ◽  
Novel Strategy

Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and tortuous retinal blood vessels, and retinal or vitreous hemorrhages that may lead to retinal detachment, vision impairment and blindness. Compared with other neovascular diseases, ROP is unique because of ongoing and concurrent physiological and pathological angiogenesis in the developing retina. While the disease is currently treated by laser or cryotherapy, anti-vascular endothelial growth factor (VEGF) agents have been extensively investigated but are not approved in the U.S. because of safety concerns that they negatively interfere with physiological angiogenesis of the developing retina. An ideal therapeutic strategy would selectively inhibit pathological but not physiological angiogenesis. Our group recently described a novel strategy that selectively and safely alleviates pathological RNV in animal models of ROP by targeting secretogranin III (Scg3), a disease-restricted angiogenic factor. The preclinical profile of anti-Scg3 therapy presents a high potential for next-generation disease-targeted anti-angiogenic therapy for the ROP indication. This review focuses on retinal vessel development in neonates, the pathogenesis of ROP and its underlying molecular mechanisms, including different animal models, and provides a summary of current and emerging therapies.

scholarly journals The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment

2017 ◽  
Author(s):  
Ding Li ◽  
Stacey D. Finley
Keyword(s):  
Combination Therapy ◽  
Cancer Patients ◽  
Receptor Expression ◽  
Angiogenic Factor ◽  
Whole Body ◽  
Cancer Therapies ◽  
Detailed Model ◽  
Angiogenic Therapy ◽  
Multiple Promoters ◽  
The Impact

AbstractMultiple promoters and inhibitors mediate angiogenesis, the formation of new blood vessels, and these factors represent potential targets for impeding vessel growth in tumors. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor targeted in anti-angiogenic cancer therapies. In addition, thrombospondin-1 (TSP1) is a major endogenous inhibitor of angiogenesis, and TSP1 mimetics are being developed as an alternative type of anti-angiogenic agent. The combination of bevacizumab, an anti-VEGF agent, and ABT-510, a TSP1 mimetic, has been tested in clinical trials to treat advanced solid tumors. However, the patients’ responses are highly variable and show disappointing outcomes. To obtain mechanistic insight into the effects of this combination anti-angiogenic therapy, we have constructed a novel whole-body systems biology model including the VEGF and TSP1 reaction networks. Using this molecular-detailed model, we investigated how the combination anti-angiogenic therapy changes the amounts of pro-angiogenic and anti-angiogenic complexes in cancer patients. We particularly focus on answering the question of how the effect of the combination therapy is influenced by tumor receptor expression, one aspect of patient-to-patient variability. Overall, this model complements the clinical administration of combination anti-angiogenic therapy, highlights the role of tumor receptor variability in the heterogeneous responses to anti-angiogenic therapy, and identifies the tumor receptor profiles that correlate with a high likelihood of a positive response to the combination therapy. Our model provides novel understanding of the VEGF-TSP1 balance in cancer patients at the systems-level and could be further used to optimize combination anti-angiogenic therapy.

BacMam-Enabled LanthaScreen® Cellular Assays for PI3K/Akt Pathway Compound Profiling in Disease-Relevant Cell Backgrounds

2010 ◽  
Vol 15 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Coby B. Carlson ◽  
Michael J. Mashock ◽  
Kun Bi
Keyword(s):  
Cell Growth ◽  
Gene Delivery ◽  
Cell Types ◽  
Genetic Alterations ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Signaling Cascade ◽  
Growth And Survival ◽  
Cellular Assays ◽  
Delivery Technology

The authors recently reported the development and application of multiple LanthaScreen® cellular assays to interrogate specific steps within the PI3K/Akt pathway. The importance of this signaling cascade in regulating fundamental aspects of cell growth and survival, as well as in the progression of cancer, underscores the need for portable cell-based assays for compound profiling in multiple disease-relevant cell backgrounds. To meet this need, the authors have now expanded their LanthaScreen® assay platform across a variety of cell types using a gene delivery technology known as BacMam. Here, they have demonstrated the successful detection of Akt-dependent phosphorylation of PRAS40 at Thr246 in 10 different cell lines harboring mutations known to activate the PI3K/Akt pathway. In addition, they generated inhibitory profiles of 17 known pathway inhibitors in these same cells to validate the approach of using the BacMam-enabled LanthaScreen® cellular assay format to rapidly profile compounds in disease-relevant cell types. Importantly, their results provide a broad illustration of how the genetic alterations that affect PI3K/Akt signaling can also influence the inhibitory profile of a given compound.

scholarly journals FTY720, a sphingosine analog, altered placentome histoarchitecture in ewes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kathrin A. Dunlap ◽  
Bryan G. White ◽  
David W. Erikson ◽  
M. Carey Satterfield ◽  
Christiane Pfarrer ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Fetal Growth ◽  
Morphological Changes ◽  
Allantoic Fluid ◽  
Angiogenic Factor ◽  
Length Of Day ◽  
Placental Development ◽  
Crown Rump Length ◽  
Growth And Survival ◽  
Sphingosine 1 Phosphate

Abstract Background The lysosphingolipid, sphingosine-1-phosphate, is a well-described and potent pro-angiogenic factor. Receptors, as well as the sphingosine phosphorylating enzyme sphingosine kinase 1, are expressed in the placentomes of sheep and the decidua of rodents; however, a function for this signaling pathway during pregnancy has not been established. The objective of this study was to investigate whether sphingosine-1-phosphate promoted angiogenesis within the placentomes of pregnant ewes. Ewes were given daily jugular injections of FTY720 (2-amino-2[2-(− 4-octylphenyl)ethyl]propate-1,3-diol hydrochloride), an S1P analog. Results FTY720 infusion from days 30 to 60 of pregnancy did not alter maternal organ weights nor total number or mass of placentomes, but did alter placentome histoarchitecture. Interdigitation of caruncular crypts and cotyledonary villi was decreased, as was the relative area of cotyledonary tissue within placentomes. Also, the percentage of area occupied by cotyledonary villi per unit of placentome was increased, while the thickness of the caruncular capsule was decreased in ewes treated with FTY720. Further, FTY720 infusion decreased the number and density of blood vessels within caruncular tissue near the placentome capsule where the crypts emerge from the capsule. Finally, FTY720 infusion decreased asparagine and glutamine in amniotic fluid and methionine in allantoic fluid, and decreased the crown rump length of day 60 fetuses. Conclusions While members of the sphingosine-1-phosphate signaling pathway have been characterized within the uteri and placentae of sheep and mice, the present study uses FTY720 to address the influence of S1P signaling on placental development. We present evidence that modulation of the S1P signaling pathway results in the alteration of caruncular vasculature, placentome architecture, abundance of amino acids in allantoic and amniotic fluids, and fetal growth during pregnancy in sheep. The marked morphological changes in placentome histoarchitecture, including alteration in the vasculature, may be relevant to fetal growth and survival. It is somewhat surprising that fetal length was reduced as early as day 60, because fetal growth in sheep is greatest after day 60. The subtle changes observed in the fetuses of ewes exposed to FTY720 may indicate an adaptive response of the fetuses to cope with altered placental morphology.

scholarly journals THREE-DIMENSIONAL MODEL OF METASTATIC TUMOR ANGIOGENESIS IN RESPONSE TO ANTI-ANGIOGENIC FACTOR ANGIOSTATIN

2017 ◽  
Vol 17 (06) ◽  
pp. 1750094 ◽  
Author(s):  
GAIPING ZHAO ◽  
ERYUN CHEN ◽  
XIAOLI YU ◽  
HAIPO CUI ◽  
JIE LV ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Experimental Tests ◽  
Metastatic Tumor ◽  
Theoretical Models ◽  
Inhibitory Effect ◽  
Angiogenic Factor ◽  
Three Dimensional Model ◽  
Primary Tumors ◽  
Angiogenic Therapy ◽  
Therapy Strategies

Surgeons observed that primary tumors are capable of suppressing the growth of their metastases by generating anti-angiogenic factor angiostatin. A three-dimensional (3D) mathematical model of development of the metastatic tumor vasculature is presented to simulate the morphology and construction of 3D microvascular networks under the inhibitory effect of anti-angiogenic factor angiostatin excreted by the primary tumor. The simulation results demonstrate that metastatic tumor microvascular density (MVD) decreases by about 60%, 58% and 52%, respectively, at [Formula: see text], 7 and 14 days under the effect of anti-angiogenic factor angiostatin. The abnormal geometric and morphological features of 3D microvasculature networks inside and outside the metastatic tumor improve in the presence of angiostatin. The present model may allow to simulate experimental tests and may provide theoretical models for clinical research of anti-angiogenic therapy strategies.

scholarly journals Exploring the extracellular regulation of the tumor angiogenic interaction network using a systems biology model

2019 ◽  
Author(s):  
Ding Li ◽  
Stacey D. Finley
Keyword(s):  
Growth Factor ◽  
Tumor Tissue ◽  
Interaction Network ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Detailed Knowledge ◽  
Cancer Treatments ◽  
Platelet Factor ◽  
Angiogenic Therapy ◽  
Counterintuitive Result

ABSTRACTTumor angiogenesis is regulated by pro- and anti-angiogenic factors. Anti-angiogenic agents target the interconnected network of angiogenic factors to inhibit neovascularization, which subsequently impedes tumor growth. Due to the complexity of this network, optimizing anti-angiogenic cancer treatments requires detailed knowledge at a systems level. In this study, we constructed a tumor tissue-based model to better understand how the angiogenic network is regulated by opposing mediators at the extracellular level. We consider the network comprised of two pro-angiogenic factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), and two anti-angiogenic factors: thrombospondin-1 (TSP1) and platelet factor 4 (PF4). The model’s prediction of angiogenic factors’ distribution in tumor tissue reveals the localization of different factors and indicates the angiogenic state of the tumor. We explored how the distributions are affected by the secretion of the pro- and anti-angiogenic factors, illustrating how the angiogenic network is regulated in the extracellular space. Interestingly, we identified a counterintuitive result that the secretion of the anti-angiogenic factor PF4 can enhance pro-angiogenic signaling by elevating the levels of the interstitial and sur-face-level pro-angiogenic species. This counterintuitive situation is pertinent to the clinical setting, such as the release of anti-angiogenic factors in platelet activation or the administration of exogenous PF4 for anti-angiogenic therapy. Our study provides mechanistic insights into this counterintuitive result and highlights the role of heparan sulfate proteoglycans in regulating the interactions between angiogenic factors. This work complements previous studies aimed at understanding formation of angiogenic complexes in tumor tissue and helps in the development of anti-cancer strategies targeting angiogenesis.

Sequential detection of mRNA for the chemokine IL-8 and macrophages (F4/80) in human melanoma

1995 ◽  
Vol 53 ◽  
pp. 1008-1009
Author(s):  
C.D. Bucana ◽  
R. Sanchez ◽  
R. Singh ◽  
I.J. Fidler
Keyword(s):  
Tumor Cells ◽  
Nude Mice ◽  
Constitutive Expression ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Angiogenic Factor ◽  
Infiltrating Cells ◽  
Immunoperoxidase Assay ◽  
Multifunctional Cytokine

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.

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