TY - JOUR. T1 - A catechin nanoformulation inhibits WM266 melanoma cell proliferation, migration and associated neo-angiogenesis. AU - di Leo, Nicoletta. AU - Battaglini, Matteo. AU - Berger, Liron. AU - Giannaccini, Martina. AU - Dente, Luciana. AU - Hampel, Silke. AU - Vittorio, Orazio. AU - Cirillo, Giuseppe. AU - Raffa, Vittoria. N1 - This work was supported by the EU (Marie Curie programme), by Fondazione Veronesi, by Fondazione Arpa, by Fondazione Pisa, and by the Italian Ministero dellIstruzione, dellUniversità e della Ricerca (PRA, progetti di ricerca di ateneo).. PY - 2017/5. Y1 - 2017/5. N2 - We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The ...

Regulation of Bone Marrow Angiogenesis by Osteoblasts during Bone Development and Homeostasiss profile, publications, research topics, and co-authors

TY - JOUR. T1 - Targeting tumor neoangiogenesis via targeted adenoviral vector to achieve effective cancer gene therapy for disseminated neoplastic disease. AU - Lee, Myungeun. AU - Lu, Zhi Hong. AU - Li, Jie. AU - Kashentseva, Elena A.. AU - Dmitriev, Igor P.. AU - Mendonca, Samir A.. AU - Curiel, David T.. PY - 2020/3. Y1 - 2020/3. N2 - The application of cancer gene therapy has heretofore been restricted to local, or locoregional, neoplastic disease contexts. This is owing to the lack of gene transfer vectors, which embody the requisite target cell selectivity in vivo required for metastatic disease applications. To this end, we have explored novel vector engineering paradigms to adapt adenovirus for this purpose. Our novel strategy exploits three distinct targeting modalities that operate in functional synergy. Transcriptional targeting is achieved via the hROBO4 promoter, which restricts transgene expression to proliferative vascular endothelium. Viral binding is modified by incorporation ...

The approval of the first antiangiogenic agent for clinical use in patients with colorectal carcinoma has taught us many lessons, the most important of which is that these agents must be used in combination with agents that target cancer cells to have an appreciable impact on patient survival. Increasing the dose of antiangiogenic agent may harm normal tissues and destroy too much of the tumor vasculature, leading to hypoxia and poor drug delivery in the tumor and to toxicity in normal tissues. However, optimal doses and schedules of these reagents tailored to the angiogenic profile of tumors can normalize tumor vasculature and microenvironment without harming normal tissue.. At least three major challenges must be met before therapies based on this vascular normalization model can be successfully translated to the clinic. The first challenge is to determine which other direct or indirect antiangiogenic therapies lead to vascular normalization. In principle, any therapy that restores the balance ...

The treatment of the most common cancers (colon, breast, lung, liver and kidney) has recently added a new therapeutic class known as the anti-angiogenic. It was born from a better understanding of tumor growth requires the development of neo-vessels. These new vessels are of major importance for the viability of the tumor but also the birth of metastases. This neo-angiogenesis is complex and results from an imbalance between pro-angiogenic factors and anti-angiogenic factors. Growth factor VEGF and its receptors (VEGFR-1, VEGFR-2 and VEGFR-3) are a way of survival of endothelial cells required for tumor neoangiogenesis. The anti-angiogenic drugs currently available on the market are bevacizumab (Avastin ®), sunitinib (Sutent ®) and sorafenib (Nexavar ®). The mechanism of anti-angiogenic action of these three main drugs are pharmacological inhibition of the VEGF pathway.. These new anti-angiogenic therapies, however, have significant adverse effects are common and some other more serious but ...

In the early 1970s (1) , Folkman hypothesized that solid tumor growth and metastasis are critically dependent on angiogenesis, the formation of new blood vessels from preexisting vasculature. Over the past few decades, many mediators of angiogenesis have been characterized, providing new and important targets for drug discovery research. Considerable effort has been directed toward the development of pharmacological agents that modulate specific pathways associated with angiogenesis.. Among the many known triggers of tumor angiogenesis, VEGF6 has emerged as a relatively specific effector (2 , 3) . In fact, VEGF expression has been observed in many human tumor types (4, 5, 6, 7, 8, 9, 10) , is up-regulated in response to hypoxia (11 , 12) , and has been specifically linked with tumor neovascularization (13, 14, 15) . Tumor cells engineered to express VEGF constitutively exhibit enhanced tumor growth and angiogenic phenotypes (16) . Conversely, treatments with anti-VEGF monoclonal antibodies have ...

Tumor-induced angiogenesis is of major interest for oncology research. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor characterized so far. VEGF blockade was shown to be sufficient for angiogenesis inhibition and subsequent tumor regression in several preclinical tumor models. Bevacizumab was the first treatment targeting specifically tumor-induced angiogenesis through VEGF blockade to be approved by the Food and Drugs Administration (FDA) for cancer treatment. However, after very promising results in preclinical evaluations, VEGF blockade did not show the expected success in patients. Some tumors became resistant to VEGF blockade. Several factors have been accounted responsible, the over-expression of other angiogenic factors, the noxious influence of VEFG blockade on normal tissues, the selection of hypoxia resistant neoplastic cells, the recruitment of hematopoietic progenitor cells and finally the transient nature of angiogenesis inhibition by VEGF blockade. ...

Nitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) and N-monomethyl-L-arginine (L-NMMA), are metabolized by dimethylarginine dimethylaminohydrolase (DDAH), and hence, DDAH is an intracellular factor that regulates NO. However, DDAH may also have an NO-independent action. We aimed to investigate whether DDAH I has any direct role in tumour vascular development and growth independent of its NO-mediated effects, in order to establish the future potential of DDAH inhibition as an anti-angiogenic treatment strategy. A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline. Xenografts derived from these cells were propagated in the presence or absence of doxycycline and susceptibility magnetic resonance imaging used to assess functional vasculature in vivo. ...

The Ohio State University College of Pharmacy Division of Pharmacology Assistant Professor Nam Lee has received a $1.6 million grant from the National Institute of Healths National Cancer Institute (NIH NCI) to study therapeutics that target pathways essential for tumor angiogenesis (i.e., how tumors recruit new blood vessels for growth). NIH NCIs grant will fund the project for five years.. While many strategies exist for inhibiting tumor angiogenesis, Food and Drug Administration approved drugs like Avastin (bevacizumab) have yielded mixed results. Lees project aims to understand the basic mechanisms by which another potential vascular target, endoglin (CD105), a protein located on cell surfaces, promotes tumor-associated angiogenesis.. My lab is going to look at several treatment options to better determine what ways we can improve and make current drugs more effective in fighting angiogenesis, said Lee. There is still so much we can learn about the subject.. Part of Lees study will ...

Definition of angiogenesis factor in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is angiogenesis factor? Meaning of angiogenesis factor as a legal term. What does angiogenesis factor mean in law?

Considerable interest is focusing on a treatment approach targeting inhibition of microvessel formation and/or function within atherosclerotic plaque. More than 300 potential inhibitors of angiogenesis have been identified, of which 80 are currently being tested in clinical trials (58). Their mechanisms of action are varied, affecting aspects of angiogenesis such as endothelial cell proliferation, the availability or production of endothelial cell growth factors, the signaling of tyrosine kinase receptors on endothelial cells, and the activity of metalloprotease enzymes. Although significant differences in efficacy between agents may not be apparent in a heterogeneous patient group, it is possible that subpopulations such as diabetics may ultimately benefit from tailored therapy that takes account of specific signaling or other molecular defects of angiogenesis known to be more prevalent in these patients (59). Combination therapy using 2 or more inhibitors with differing mechanisms of action ...

TY - JOUR. T1 - Angiogenesis as targeted breast cancer therapy. AU - Hayes, Daniel F.. AU - Miller, Kathy. AU - Sledge, George. PY - 2007. Y1 - 2007. N2 - Neo-angiogenesis appears to be a critical feature of tumor growth, migration, and metastasis. Therefore, inhibition of angiogenesis is an appealing strategy for treatment of cancer. Since angiogenesis is the result of several mechanistic processes, controlled by numerable pro- and anti-angiogenic factors and their receptors, multiple possibilities to prevent or reverse tumor-induced neo-vascularization have been proposed. Of these, currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Bevacizumab has been shown to be active in several malignancies, in particular colo-rectal cancer. Although early studies of bevacizumab in far-advanced metastatic breast cancer were disappointing, the results of a ...

A promising strategy to overcome the chemoresistance is the tumor blood vessel normalization, which restores the physiological perfusion and oxygenation of tumor vasculature. Thalidomide (Thal) has been shown to increase the anti-tumor effect of chemotherapy agents in solid tumors. However, it is not yet known whether the synergistic effect of Thal combined with other cytotoxic drugs is attributable to tumor vascular normalization. We used two homograft mice models (4 T1 breast tumor model and CT26 colorectal tumor model) to investigate the effect of Thal on tumor growth, microvessel density, vascular physiology, vascular maturity and function, drug delivery and chemosensitivity. Immunofluorescence, immunohistochemistry and scanning electron microscopy were performed to determine the vessel changes. Protein array assay, qPCR and western blotting were used to detect the molecular mechanism by which Thal regulates tumor vascular. Here we report that Thal potently suppressed tumor growth, angiogenesis,

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been

Our results demonstrate that the systemic administration of human IFN-α-2a to nude mice bearing bladder wall implants of human 253J B-V-IFNR bladder cancer cells inhibits angiogenesis and tumor growth. Altering the dose of IFN-α and schedule of administration profoundly influenced therapeutic outcome; daily administration of IFN-α-2a at far below maximal tolerated doses produced maximal antiangiogenic effects. Because the human bladder cancer cells we used are resistant to the antiproliferative effects of IFN-α, the data clearly show that the indirect antiangiogenic activity of IFN-α requires a different approach than that designed to inhibit tumor cell proliferation directly.. The progressive growth and metastasis of malignant neoplasms depend on adequate neovascularization, i.e., angiogenesis, the extent of which is determined by the balance between the proangiogenic and antiangiogenic molecules that are released by both the tumor cells and surrounding normal cells (36, 37, 38) . Among ...

Angiogenesis is defined as the formation of new blood vessels from pre-existing vasculature. Angiogenesis is relevant not just to disease tumors and to non-neoplastic diseases most notably macular degeneration, psoriasis, endometriosis, {and,as well as arthritis. The development {and,because well as metastasis of tumors tend to be really critically dependent upon angiogenesis. Therefore, the inhibition of angiogenesis grew to become {an,a particular,a few sort of,some of important therapeutic approach for cancer. Although the existing anti-angiogenesis options have been stated to have less toxicity than conventional chemo {or, alternatively perhaps radiotherapy, they are frequently connected with clinical side impacts, {and,since well also limited tumor regression. Therefore, there has become {an,a particular,a bunch of type of,a few of increased focus towards development of novel angiogenesis inhibitors {and,also as book approaches to improve the anti-angiogenic options .. Human apolipoprotein ...

Title:Cytokine Network: New Targeted Therapy for Pancreatic Cancer. VOLUME: 18 ISSUE: 17. Author(s):Yoichi Matsuo, Hiromitsu Takeyama and Sushovan Guha. Affiliation:Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 4678601, Japan.. Keywords:Pancreatic cancer, cytokine, angiogenesis, targeted therapy. Abstract:Increasing evidence has shown that cytokines have a role in tumor biology. The role of chemokines in tumor biology is important because these peptides may influence tumor growth, invasion, angiogenesis, and metastasis. In this review, we demonstrated the role of cytokines (Interleukin-1α, hepatocyte growth factor, Interleukin-8, stromal cell-derived factor-1 and CXC-chemokines/CXCR2 biological axis) in pancreatic cancer angiogenesis, especially from the standpoint of the interaction between tumor and its microenvironments. The cytokines are intimately related with cancer angiogenesis. Blocking ...

Synonyms for angiogenesis factor in Free Thesaurus. Antonyms for angiogenesis factor. 37 synonyms for factor: element, thing, point, part, cause, influence, item, aspect, circumstance, characteristic, consideration, component, determinant.... What are synonyms for angiogenesis factor?

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Metastatic potential. Tumor angiogenesis is closely related to lymphangiogenesis in the spread of cancer cells from the primary neoplasm to other tissues and organs and usually first occur via the sentinel lymph node.36 Nevertheless, melanoma tumor cells can bypass the lymph-node system and metastasize to distant organs by gaining direct access to blood circulation. Depending on the angiogenic potential of the tumor cells trapped in secondary organ capillary beds, metastatic tumor growth can be favored by increased induction of neovascularization.37 Some authors therefore suggest that tumor angiogenesis is associated with poor prognostic outcome and increased rate of relapse in melanoma.38-40 Pro-angiogenic factors such as VEGF-A, IL-8, PDEGF, bFGF, Ang-2 and MMP, necessary for tumor angiogenesis can be generated in part by melanoma cells.41,42 Therefore, the clinical utility of VEGF serum determination in melanoma patients has been under investigation as circulating serum levels of VEGF in some ...

Rheumatoid arthritis (RA) is an inflammatory disease associated with intense angiogenesis and vascular expression of integrin αvβ3. Intra-articular administration of a cyclic peptide antagonist of integrin αvβ3 to rabbits with antigen-induced arthritis early in disease resulted in inhibition of synovial angiogenesis and reduced synovial cell infiltrate, pannus formation, and cartilage erosions. These effects were not associated with lymphopenia or impairment of leukocyte function. Furthermore, when administered in chronic, preexisting disease, the αvβ3 antagonist effectively diminished arthritis severity and was associated with a quantitative increase in apoptosis of the angiogenic blood vessels. Therefore, angiogenesis appears to be a central factor in the initiation and persistence of arthritic disease, and antagonists of integrin αvβ3 may represent a novel therapeutic strategy for RA.. ...

Angiogenesis is a process of nascent blood vessel formation (1) and is critical for tumor growth and metastasis (2). When tumors reach approximately 1 mm in diameter, hypoxia develops and induces the secretion of vascular growth factor A (VEGFA, or VEGF) from cancer cells (3). VEGF recruits endothelial cells and stimulates new blood vessel formation (4) to ensure sufficient oxygen and nutrient supply for the proliferation of cancer cells. Inhibiting this process reduces tumor sizes and has been proposed as a nonconventional therapy for cancer treatment (5, 6). Various angiogenesis inhibitors have been developed and many of them show promising tumor inhibitory effects (7). However, adaptive responses to single antiangiogenic therapy, manifested as increased invasion and metastasis of cancer cells, have been observed both experimentally and clinically (8-10). The mechanisms for this adaptive response are not clear, but its occurrence strongly argues for combinations of antiangiogenic regimens to ...

Design:. This study is intended to obtain preliminary data on the uptake and retention of [18F]fluciclatide before and after anti-angiogenic therapy. This will enable optimization of the imaging protocol, identification of the most relevant imaging parameters, and allow for calculation of the number patients required to power a larger study to assess the utility of PET imaging with [18F]fluciclatide as a pharmacodynamic biomarker in the context of targeted anti-angiogenic therapies. We expect to enroll 30 evaluable patients in this single center study. Subjects will undergo at least two [18F]fluciclatide PET/CT imaging studies, one pre-therapy and one following completion of 1 cycle of chemotherapy. An optional early post-therapy (2-7 days post therapy commencement) [18F]fluciclatide PET/CT may be performed. The magnitude of [18F]fluciclatide uptake on the pre- and post- treatment PET/CT studies will be evaluated to determine if there is a measureable difference in uptake. Data from the ...

University of Pittsburgh scientists have shown that triggering an anti-tumor immune response significantly potentiates the effects of the anti-angiogenic drug endostatin in animal models, leading to permanent and complete regression...

TY - THES. T1 - Preclinical and clinical studies on the co-regulation of tumor-induced angiogenesis and dendritic cell suppression. AU - van Cruijsen, H.. N1 - Naam instelling promotie: S.l.. PY - 2009. Y1 - 2009. M3 - Research VU University Amsterdam, graduation VU University Amsterdam. SN - 9789090240251. PB - s.n.. CY - S.l.. ER - ...

The data of the present study demonstrate that S1P can induce eNOS phosphorylation and NO production by way of the PI3K/Akt pathway in cultured ECs and that NO plays a critical role in S1P-induced angiogenesis in vitro and in vivo. Platelets contain many angiogenic factors, and the angiogenic activity of those released by platelets plays an important role in initiating angiogenesis in injured tissue, especially in wound healing and tumor angiogenesis. It seems likely that S1P, which is known to be abundantly stored in platelets and released on their activation,17 may contribute to platelet-induced angiogenesis in wound repair, because it was demonstrated that S1P is the major EC chemoattractant released into serum by platelets during blood clotting.18 Therefore, it is suggested that the angiogenic activity of S1P may account for the important role of platelet interaction with ECs in angiogenesis at sites of injury. Interestingly, previous studies have demonstrated the crucial role of NO in wound ...

CANSSUFIVE is also based on the technology platform of angiogenesis screening assays. These unique assays screen for angiogenesis which is the process of new blood vessels formation from pre-existing blood vessels. Angiogenesis is an essential natural process in the body for healing and reproduction. The human body produces a precise balance of growth and inhibitory factors in healthy tissues to control angiogenesis. When this balance is altered, the result is either excessive or insufficient angiogenesis. The abnormal angiogenesis is a common denominator in many conditions including cancer, Alzheimers disease, diabetic blindness, wet age related macula degeneration, obesity and rheumatoid arthritis ...

Semaphorin 4D (SEMA4D; CD100) has been implicated in several key mechanisms of tumor progression, including neovascularization, tumor invasion, and metastasis. SEMA4D binding to its receptor plexin-B1 (PLXNB1) on endothelial cells transactivates MET and promotes formation of new blood vessels and tumor growth in vivo. SEMA4D is over-expressed in a wide array of tumor types, and is also produced by recruited inflammatory cells present in the tumor microenvironment. Several recent papers have shown that in an environment lacking SEMA4D, the ability of mouse cancer cells to originate tumor masses and metastases is severely impaired. Furthermore, SEMA4D produced by tumor-associated macrophages has been shown to support tumor angiogenesis and growth.. In addition to its effects on endothelial cells, SEMA4D has a direct effect on tumor invasive growth and migration. A recent clinical study in soft tissue sarcomas correlates strong SEMA4D expression in tumors with a higher mitotic count and poor ...

Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.

The sprouting and development of blood vessels affects numerous processes in the body, and excessive or insufficient angiogenesis can exacerbate a variety of disease states. Therefore, precise regulation of angiogenesis is crucial to an organisms survival. Studies knocking down Dicer and Drosha implicated miRNAs in regulation of angiogenesis, and subsequent studies revealed roles for miR-126, the miR17~92 cluster, miR378, miR-210, miR-296, and others in various settings such as neoangiogenesis in response to injury, developmental angiogenesis, and tumor angiogenesis. (1, 5). Over the past year, significant progress has been made in discovering which miRNAs drive this process in both normal physiology and in various disease states. Due to these studies and others, a clearer picture of the miRNA network governing angiogenesis is starting to emerge. This review spans some of the most significant recent discoveries that have contributed to our understanding of angiomiR function in vascular ...

TY - JOUR. T1 - Modeling three-dimensional invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. AU - Xie, Hang. AU - Jiao, Yang. AU - Fan, Qihui. AU - Hai, Miaomiao. AU - Yang, Jiaen. AU - Hu, Zhijian. AU - Yang, Yue. AU - Shuai, Jianwei. AU - Chen, Guo. AU - Liu, Ruchuan. AU - Liu, Liyu. PY - 2018/10. Y1 - 2018/10. N2 - A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We ...

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Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and ...

3 hours publish DMXAA remedy, ectopic MCA tumors showed 6 fold better induction of DPP-4 compared to orthotopic MCA tumors. No statistically significant distinction in intratumoral ranges of VEGF had been observed in between untreated ectopic and orthotopic MCA tumors.. Even so, higher levels of VEGF have been seen in orthotopic tumors than ectopic tumors following DMXAA treatment method. The host microenvironment is critically involved in tumor angiogenesis via a complex network of interactions in between tumor cells, endothelial cells and host cells. It is as a result important to assess and interpret the preclinical RAD001 activity of VDAs within the context of the tumor kind and its microenvironment. In the present examine, non invasive MMCM MRI was utilized to investigate the influence of the host microenvironment on tumor angiogenesis and response to DMXAA. The outcomes show the usefulness of MMCM MRI in characterizing vascular variations between ectopic and orthotopic tumors and offer ...

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-β inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-β-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of ...

Endometriosis, the presence of endometrium-like tissue outside of the uterine cavity, is a common disease among women of reproductive age. Typical symptoms include abdominal pain and painful menstruation. In addition, endometriosis is associated with reduced fertility. Current treatment modalities, the surgical removal of endometriotic lesions and the hormonal suppression of estrogen are associated with significant morbidity, side-effects and recurrence rates. Despite uncertainties about the pathophysiology of the disease it has recently become apparent that angiogenesis plays a pivotal role in endometriosis. This review focuses on a multitude of factors involved in the angiogenic phenotype of endometriosis demonstrating that many biological systems such as the immune system and steroid hormones are closely connected to angiogenic pathways in this disease. In addition, experimental and clinical data are discussed that concentrate on the inhibition of angiogenesis as a novel therapeutic approach for

Sigma-Aldrich offers abstracts and full-text articles by [Ngoc-Quynh-Nhu Nguyen, Karolien Castermans, Sarah Berndt, Stephanie Herkenne, Sebastien P Tabruyn, Silvia Blacher, Michelle Lion, Agnes Noel, Joseph A Martial, Ingrid Struman].

The angiogenic switch, a rate-limiting step in tumor progression, has already occurred by the time most human tumors are detectable. The angiogenic switch is not limited at earliest stages, but occurs also at different stages of tumor progression (2). Antiangiogenic therapy is a promising alternative for treatment of cancer, and may also be used as a maintenance therapy to prevent the metastasis or recurrence (4). Therapy with endogenous angiogenic inhibitors such as endostatin and angiostatin may reverse the angiogenic switch by preventing growth of tumor vasculature. Angiostatin can maintain metastases in a dormant state in laboratory animals when administered exogenously (34). In transgenic mice overexpressing endostatin, a small increase of circulating endostatin (approximately 1.6-fold) is sufficient to confer dramatic protection against tumor growth (11). In individuals with Down syndrome, a similar small increase of circulating endostatin is associated with a remarkably low incidence of ...

Treatment with certain anti-cancer agents, particularly taxanes and sunitinib, can lead to mobilization of pro-angiogenic factors and an acute mobilization of endothelial progenitor cells (EPCs) and other stromal cells, which migrate to the viable tumor rim where they can enhance tumor vascularization, invasion and metastasis. This phenomenon has been linked to rapid tumor regrowth following chemotherapy or treatment with specific angiogenesis inhibitors and may thus diminish the long-term efficacy of the treatment. Stromal cells like EPCs are mobilized in response to circulating growth factors and chemokines (VEGFR, FGF, G-CSF, IL-6, SDF1α, etc.) that are induced by the drug or the progressing tumor. Many of these factors contain heparin binding domains for their anchorage to proteoglycans on cell surfaces or the extracellular matrix. We tested a novel heparan sulfate mimetic, M402, for its ability to inhibit EPC mobilization as well as tumor vascularization and invasion. Mice bearing ...

Tumors are composed not only of malignant cells, but also of various types of normal cells, including vascular cells and infiltrating immune cells, which drive tumor development and progression. The tumor vasculature is abnormal and dysfunctional due to sustained tumor angiogenesis driven by high levels of pro-angiogenic factors. Proteins differentially expressed in tumor vessels affect vascular function and the tumor microenvironment and may serve as targets for therapy. The tumor is also a site of sustained chronic inflammation. The recruitment and activation of inflammatory cells significantly influence tumor progression and regression. Targeting molecules regulating tumor angiogenesis and inflammation in the tumor microenvironment is therefore a promising strategy for the treatment of cancer. This thesis is aiming to understand and investigate the molecular regulation of these two processes in tumors.. αB-crystallin is a heat shock protein previously proposed as a target for cancer therapy ...

TY - JOUR. T1 - A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. AU - Garlich, Joseph R.. AU - De, Pradip. AU - Dey, Nandini. AU - Jing, Dong Su. AU - Peng, Xiaodong. AU - Miller, Antoinette. AU - Murali, Ravoori. AU - Lu, Yiling. AU - Mills, Gordon B.. AU - Kundra, Vikas. AU - Shu, H. K.. AU - Peng, Qiong. AU - Durden, Donald L.. PY - 2008/1/1. Y1 - 2008/1/1. N2 - PTEN and the pan phosphoinositide 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1benzopyran-4-one (LY294002) exert significant control over tumor-induced angiogenesis and tumor growth in vivo. The LY294002 compound is not a viable drug candidate due to poor pharmacologic variables of insolubility and short half-life. Herein, we describe the development and antitumor activity of a novel RGDS-conjugated LY294002 prodrug, termed SF1126, which is designed to exhibit increased solubility and bind to specific integrins within the tumor compartment, resulting ...

Over the last few years the paradigm of how to approach cancer therapy has shifted from solely trying to mitigate cancer cell proliferation to incorporating targeting agents against the production of new vessels, which allow the cancerous cells to thrive. Current anti-angiogenic therapies focus on the earliest steps in these signaling cascades and try to prevent angiogenic molecules like vascular endothelial growth factor from reaching endothelial cells or hinder the activation of their endothelial cell receptors. One or more of the downstream signaling steps might be a signaling ...

Results: In vitro and in vivo angiogenesis assays showed inhibition of capillary-like network formation of microvascular endothelial cells and neovascularization under dorsal skin of nude mice, respectively. We observed inhibition of intracerebral tumorigenesis and s.c. solid tumor formation in nude mice after treatment with combination of hTERT siRNA and IFN-γ. Western blotting of solid tumor samples showed significant downregulation of the molecules that regulate cell invasion, angiogenesis, and tumor progression ...

Tumor angiogenesis is the process through which certain tumors stimulate the growth of the microvascular network in the surrounding tissue. This capillary network is remarkable in that the growth is...

Antibodies for proteins involved in regulation of sprouting angiogenesis pathways, according to their Panther/Gene Ontology Classification

TY - JOUR. T1 - Regulation of tumor angiogenesis by organ-specific cytokines. AU - Singh, R. K.. AU - Fidler, I. J.. PY - 1996/5/22. Y1 - 1996/5/22. UR - http://www.scopus.com/inward/record.url?scp=0029888971&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0029888971&partnerID=8YFLogxK. M3 - Review article. C2 - 9053286. AN - SCOPUS:0029888971. VL - 213 II. SP - 1. EP - 11. JO - Current Topics in Microbiology and Immunology. JF - Current Topics in Microbiology and Immunology. SN - 0070-217X. ER - ...

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Title: Imaging in the Age of Molecular Medicine: Monitoring of Anti-Angiogenic Treatments. VOLUME: 13 ISSUE: 4. Author(s):W. Lederle, M. Palmowski and F. Kiessling. Affiliation:Department of Experimental Molecular Imaging, University of Aachen (RWTH), Pauwelsstrasse 20, 52074 Aachen, Germany.. Keywords:Angiogenesis, imaging, CT, MRI, nuclear imaging, optical imaging, ultrasound, characterization of different angiogenic steps, numerous angiogenesis inhibitors, anti-angiogenic treatment, longitudinal treatment monitoring, molecular imaging, tumor vessels. Abstract: Angiogenesis is a complex multistep process and a crucial pre-requisite for tumor growth, invasion and metastasis. A profound knowledge of the mechanisms including the elucidation of markers for angiogenic vessels is essential for the generation of new anti-angiogenic chemotherapeutic agents and the improvement of specific imaging techniques. During the last decades, numerous angiogenesis inhibitors have been developed and some of them ...

Cancer growth, invasion and metastasis are highly related to tumor-associated neovasculature. The presence and progression of endothelial cells in cancer is chaotic, unorganized, and angiogenic vessels are less functional. Therefore, not all markers appearing on the chaotic endothelial cells are accessible if a drug is given through the vascular route. Identifying endothelial cell markers from functional cancer angiogenic vessels will indicate the accessibility and potential efficacy of vascular targeted therapies. In order to quickly and effectively identify endothelial cell markers on the functional and accessible tumor vessels, we developed a novel technique by which tumor angiogenic vessels are labeled in vivo followed by Laser Capture Microdissection of microscopically isolated endothelial cells for genomic screening. Female C3H mice (N = 5) with established SCCVII tumors were treated with Rhodamine-RCA lectin by tail vein injection, and after fluorescence microscopy showed a successful vasculature

Angiogenesis is an essential process whereby new blood vessels are formed from pre-existing vessels and occurs under both normal and pathophysiological conditions. growth element receptor 1 (sVEGFR-1). Therefore, FoxC1 appears to control angiogenesis by regulating two unique and opposing mechanisms; if so, vascular development could be identified, at least in part, Elvitegravir by a competitive balance between pro-angiogenic and anti-angiogenic FoxC1-controlled pathways. With this review, we describe the mechanisms by which FoxC1 regulates vessel growth and discuss how these observations could contribute to a more total understanding of the part of FoxC1 in pathological angiogenesis. Intro Under both physiological and pathological conditions, new blood vessels are created from pre-existing vessels through a process called angiogenesis, which is definitely exactly controlled by the balance between pro-angiogenic and anti-angiogenic factors. Vascular endothelial growth element (VEGF)-A is perhaps ...

TY - JOUR. T1 - Vascular Mimicry. T2 - A Novel Neovascularization Mechanism Driving Anti-Angiogenic Therapy (AAT) Resistance in Glioblastoma. AU - Angara, Kartik. AU - Borin, Thaiz Ferraz. AU - Arbab, Ali Syed. PY - 2017/8/1. Y1 - 2017/8/1. N2 - Glioblastoma (GBM) is a hypervascular neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation. The benefits of AAT have been transient and the tumors were shown to relapse faster and demonstrated particularly high rates of AAT therapy resistance. Alternative neovascularization mechanisms were shown to be at work in these resilient tumors to counter the AAT therapy insult. Vascular Mimicry (VM) is the uncanny ability of tumor cells to acquire endothelial-like properties and lay down vascular patterned networks reminiscent of host endothelial blood vessels. The VM channels ...

TY - JOUR. T1 - In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization. AU - Tamura, Michie. AU - Unno, Keiko. AU - Yonezawa, Sei. AU - Hattori, Kenji. AU - Nakashima, Emi. AU - Tsukada, Hideo. AU - Nakajima, Motowo. AU - Oku, Naoto. PY - 2004/6/18. Y1 - 2004/6/18. N2 - Circulating endothelial progenitor cell (EPCs) have been reported to contribute to vasculogenesis in adult organisms. To investigate the possible recruitment of EPCs and organization to form tumor vasculature, we investigated the in vivo real-time trafficking of EPCs non-invasively by using positron emission tomography (PET). A conditionally immortalized endothelial cell line derived from rat bone marrow (TR-BME1) was labeled with [2-18F] 2-fluoro-2-deoxy-D-glucose (FDG) and chased the accumulation in the rat tumor with PET. TR-BME1 cells were accumulated in the tumor tissues time-dependently. To investigate that the accumulation of the cells is specific or not, rats were ...

The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma MH134-induced angiogenesis when assessed by morphological and biochemical examinations. This finding suggested that the anti-metastatic effect of PSK is attributed to the suppression of tumor-induced angiogenesis.[...]

https://academic.oup.com/humupd/article/18/6/682/627018. Laschke, M. W., and M. D. Menger. Anti-angiogenic treatment strategies for the therapy of endometriosis. Human reproduction update 18.6 (2012): 682-702.. initiation of the disease by retrograde menstruation of highly angiogenic endometrial fragments into the peritoneal cavity. Based on these findings, endometriosis has been classified as a typical angiogenic disease, such as cancer, psoriasis or diabetic retinopathy (Healy et al., 1998).. Several studies report that COX-2 is also crucially involved in the pathogenesis of endometriosis. COX-2 over-expression is found in both endometriotic lesions and eutopic endometrium of patients with endometriosis when compared with controls. treatment with COX-2 inhibitors prevents the implantation of endometrium to ectopic sites and induces the regression of established endometriotic lesions. Dopamine agonists. A decade ago, Basu et al. (2001) made the interesting discovery that the neurotransmitter ...

From the Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City (K.L.T., S.P., X.C., Y.D., J.M., X.L., L.Y., S.H., B.C., Y.C., C.G., L.X., H.C.); Biochemistry and Molecular Biology Department (X.L., L.X., H.C.) and Cell Biology Department (C.G.), University of Oklahoma Health Sciences Center, Oklahoma City; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany (R.H.A.); and Faculty of Medicine, University of Münster, Münster, Germany (R.H.A.). ...

New blood vessel formation, or angiogenesis, is a critical hallmark of solid tumor growth and anti-angiogenic agents have become a vital component of current cancer treatment regimens. The appeal of anti-angiogenic therapy can be attributed to several advantages of targeting the endothelial cells that line blood vessels, rather than the tumor cells themselves. First, endothelial cells are directly exposed to circulating blood, facilitating drug delivery and enabling the use of high molecular weight therapeutics. Second, each vessel capillary supports hundreds of tumor cells. Third, endothelial cells are genetically stable and their ability to develop resistance may be limited. Finally, this type of therapy should be applicable to a wide variety of tumor types. Several anti-angiogenic agents that target the vascular endothelial growth factor (VEGF) pathway have been approved for the treatment of cancer. However, tumors can exploit alternative angiogenesis mechanisms when the VEGF pathway is ...

TY - JOUR. T1 - BMP9 counteracts the tumorigenic and pro-angiogenic potential of glioblastoma. AU - Porcù, Elena. AU - Maule, Francesca. AU - Boso, Daniele. AU - Rampazzo, Elena. AU - Barbieri, Vito. AU - Zuccolotto, Gaia. AU - Rosato, Antonio. AU - Frasson, Chiara. AU - Viola, Giampietro. AU - Della Puppa, Alessandro. AU - Basso, Giuseppe. AU - Persano, Luca. PY - 2018/11/1. Y1 - 2018/11/1. N2 - Glioblastoma multiforme (GBM) is a highly vascularized and aggressive brain tumor, with a strong ability to disseminate and invade the surrounding parenchyma. In addition, a subpopulation of GBM stem cells has been reported to possess the ability to transdifferentiate into tumor-derived endothelial cells (TDECs), supporting the resistance to anti-angiogenic treatments of newly formed blood vessels. Bone Morphogenetic Protein 9 (BMP9) is critically involved in the processes of cancer cell differentiation, invasion and metastasis, representing a potential tool in order to impair the intrinsic GBM ...

Purpose: The avascular cornea is predestined to study neovascular responses. First experiences with this model date back to 1972, when Gimbrone et al heterotopically implanted tumor fragments in rabbit corneal pockets. Different assays in rabbit, rat, and mouse corneas have since been published including placement of (anti-)angiogenic growth factor releasing pellets or proangiogenic corneal sutures. Using murine corneas is surgically more intricate but advantageous due to the well-defined genetic background and availability of genetically modified animals. In mice, so far tumor-associated angiogenesis has been studied by inserting pre-grown tumor fragments into corneal pockets. Here we describe an alternative approach, where a suspension of cultured tumor cells is directly injected into the corneal stroma.. Methods: One µl of B16F10 melanoma cells suspended in PBS (100.000 cells/µl) and pre-stained with FITC+ CellTracker Green was injected into the paracentral corneal stroma of C57Bl/6 mice ...

High levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in esophageal squamous carcinoma. and significantly decreased NF-B signaling pathway. This study suggests that CCR7 plays WZ8040 an important pro-angiogenic role in esophageal squamous carcinoma via a mechanism linked to activation of the NF-B pathway; CCR7 may represent a potential target for anti-angiogenic therapy in esophageal squamous carcinoma. Keywords: CCR7, esophageal squamous carcinoma, angiogenesis, VEGF Introduction Esophageal squamous cell carcinoma (ESCC) is usually one of the most aggressive tumors and is usually also the most common cause of esophagus malignancy deaths WZ8040 worldwide [1]. Most of individuals showing with ESCC are diagnosed with advanced disease, due to the late emergence of clinical symptoms. In particular, the presence of regional attack, distant metastasis and tumor-induced angiogenesis show highly malignant potential in esophageal carcinoma patients [2]. Although ...

1. Wolinsky JB, Colson YL, Grinstaff MW. Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J Control Release. 2012;159:14-26 2. Bellon JR, Come SE, Gelman RS. et al. Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial. J Clin Oncol. 2005;23:1934-40 3. Ghadjar P, Vock J, Vetterli D. et al. Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking. Radiat Oncol. 2008;3:35 4. Holohan C, Van Schaeybroeck S, Longley DB. et al. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13:714-26 5. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10:417-27 6. Heath VL, Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol. 2009;6:395-404 7. Ebos JM, Lee CR, Kerbel RS. ...

Both defective and persistent angiogenesis are linked to pathological situations in the adult. Compounds able to modulate angiogenesis have a potential value for the treatment of such pathologies. Several small molecules present in the diet have been shown to have modulatory effects on angiogenesis. This review presents the current state of knowledge on the potential modulatory roles of dietary proteins on angiogenesis. There is currently limited available information on the topic. Milk contains at least three proteins for which modulatory effects on angiogenesis have been previously demonstrated. On the other hand, there is some scarce information on the potential of dietary lectins, edible plant proteins and high protein diets to modulate angiogenesis.

Pericytes, surrounding the endothelium, fulfill diverse functions that are crucial for vascular homeostasis. The loss of pericytes is associated with pathologies, such as diabetic retinopathy and Alzheimers disease. Thus, there exists a need for an experimental system that combines pharmacologic manipulation and quantification of pericyte coverage during sprouting angiogenesis. Here, we describe an in vitro angiogenesis assay that develops lumenized vascular sprouts composed of endothelial cells enveloped by pericytes, with the additional ability to comparatively screen the effect of multiple small molecules simultaneously. For automated analysis, we also present an ImageJ plugin tool we developed to quantify sprout morphology and pericyte coverage. Human umbilical vein endothelial cells and human brain vascular pericytes were coated on microcarrier beads and embedded in fibrin gels in a 96-well plate to form lumenized vascular sprouts. After treatment with pharmacologic compounds, sprouts were fixed,

The central importance of angiogenesis and our understanding of how new blood vessels are formed have led to the development of novel antiangiogenic therapies. Although the number of agents in development has grown exponentially, only one phase III trial in breast cancer has been completed. In that study the addition of bevacizumab to capecitabine did not extend the progression-free survival of patients with refractory disease as compared with capecitabine monotherapy. Early enthusiasm for antiangiogenic therapy must give way to clinical reality. Our challenge now is to exploit better the activity of antiangiogenic agents seen in the early clinical studies.

BACKGROUND Endothelial cells (ECs) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (VEGF), Notch, transforming growth factor β, and other signals, but the detailed molecular mechanisms remain unclear. METHODS AND RESULTS Small RNA sequencing initially identified miR-342-5p as a novel downstream molecule of Notch signaling in ECs. Reporter assay, quantitative reverse transcription polymerase chain reaction and Western blot analysis indicated that miR-342-5p targeted endoglin and modulated transforming growth factor β signaling by repressing SMAD1/5 phosphorylation in ECs. Transfection of miR-342-5p inhibited EC proliferation and lumen formation and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin beads-based sprouting assay, mouse aortic ring culture, and intravitreal injection of miR-342-5p agomir in P3 pups. Moreover, miR-342-5p promoted the migration of ECs, accompanied by reduced endothelial markers and

Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and

Background: Scientific understanding of the role of VEGF-A in tumor angiogenesis has led to the development of antiangiogenic therapies, such as bevacizumab, that selectively target VEGF-A. However, clinical trials across multiple cancer types have resulted in limited positive outcomes. VEGF-C is thought to be a potent lymphangiogenic growth factor and plays a role in tumor angiogenesis through VEGFR3; it has also been shown to bind to VEGFR2, which is important in tumor angiogenesis. Nevertheless, a direct role of VEGF-C in driving tumor angiogenesis has not been established.. To explore the potential of VEGF-C as a driver of tumor angiogenesis and its implication in developing antiangiogenic therapies, we assessed the activity of tivozanib, a potent and selective TKI for VEGFR1, 2 and 3, and a VEGF-A targeted antibody in animal tumor models that exhibit distinct VEGF-C and VEGF-A expression.. Method: A total of 107 independently derived murine breast tumors were expanded in vivo to establish ...

The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect targeting by inhibiting the release of proangiogenic growth factors by cancer or stromal cells. Many patients benefit from antiangiogenic therapies; thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in their management. A number of non-invasive tools are described with their potential benefits and limitations. We review currently available candidate biomarkers of anti-angiogenic agent effect. Including these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, and prediction of individual response. This has important consequences for the clinical use of angiogenesis

Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of ...

Angiogenesis plays a key role in the carcinogenesis of HCC. HCC is characterized by an excess of angiogenic factors produced by tumor cells, vascular endothelial cells, immune cells, and surrounding TME. This creates a vascular network composed of leaky and abnormal vasculature resulting in hypovascular regions within the tumor, which promotes hypoxia and necrosis. Vascular endothelial growth factor (VEGF) is an important mediator in hepatocarcinogenesis and regulated by oncogenic gene mutations, hormones, and cytokines. Its overexpression results in leaky vessels and abnormal vascular structure and function. This creates a hypoxic and acidotic environment, which further stimulates VEGF overexpression. In addition, VEGF acts on the surrounding stromal environment consisting of hepatic stellate cells and Kupffer cells through VEGR receptors.[79] HIF-1α is stimulated by hypoxic conditions and play a synergistic role with other angiogenic factors, especially VEGF in counteracting apoptosis and ...

Angiogenesis, the growth of new blood vessels, is required for the growth of microscopic cancers into larger, clinically relevant tumors (1). The importance of angiogenesis specifically in prostate carcinogenesis is supported by a large body of research, including studies demonstrating altered expression of angiogenic factors in prostate cancer, inhibition of tumor growth in animal models after treatment with angiogenesis inhibitors, and correlations between tumor blood vessel density and both tumor characteristics and clinical outcome (2, 3). Proangiogenic factors important in prostate angiogenesis have been reviewed (2, 3). We selected nine candidate genes, described individually below, which are important in prostate angiogenesis. We then used cases and controls from a large cohort of U.S. men to examine associations between 58 polymorphisms in these genes and risk of advanced and overall prostate cancer.. Vascular endothelial growth factor (VEGF) plays a central role in prostate angiogenesis ...

High levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in esophageal squamous carcinoma. and significantly decreased NF-B signaling pathway. This study suggests that CCR7 plays WZ8040 an important pro-angiogenic role in esophageal squamous carcinoma via a mechanism linked to activation of the NF-B pathway; CCR7 may represent a potential target for anti-angiogenic therapy in esophageal squamous carcinoma. Keywords: CCR7, esophageal squamous carcinoma, angiogenesis, VEGF Introduction Esophageal squamous cell carcinoma (ESCC) is usually one of the most aggressive tumors and is usually also the most common cause of esophagus malignancy deaths WZ8040 worldwide [1]. Most of individuals showing with ESCC are diagnosed with advanced disease, due to the late emergence of clinical symptoms. In particular, the presence of regional attack, distant metastasis and tumor-induced angiogenesis show highly malignant potential in esophageal carcinoma patients [2]. Although ...

Abnormal angiogenesis is implicated in a number of human diseases and endothelial growth inhibition represents a common approach in tumor therapy. Recently itraconazole, frequently used in humans as antifungal drug, which blocks the biosynthesis of cholesterol, has been found to be antiangiogenic in primary umbilical vein endothelial cells. However, the exact antiangiogenic mechanisms remain largely unknown. In this paper, we studied the effect of itraconazole in human dermal microvascular endothelial cells (HMEC-1), an immortalized cell line to study adult angiogenesis. A 50% reduction of microtubule formation was observed after itraconazole treatment which was partially rescued by cholesterol addition. We found that itraconazole inhibits angiogenesis markers such as VEGF, AAMP and e-NOS. mTOR and ERK1/2 phosphorylation as well as the expression of Gli1, one of the main controllers of the Shh pathway, were also inhibited by itraconazole. Cholesterol addition did not completely rescue inhibition ...

HRC, start up grant - Linkages between angiogenesis and hemostasis in cancer. $54,000/year Department of Medicine Internal Award - Tissue factor as a putative regulator of VEGF expression. $15,000/year NCIC Terry Fox Grant for New Investigators - Tagreting oncogene driven tumor angiogenesis. Dissecting the role of angiogenesis inhibitors. Equipment grant- $70,000. Operating grant 100, 000/year NSERC - The role of solid stress in tumor angiogenesis. $25,000/year CIHR - co-applicant (PI Dr. Brenda Coomber University of Guelph) Vascular dependence, tumor angiogenesis and microenvironment. App. $40,000. Hamilton Health Foundation Research Grant - Atherosclerosis and tumor angiogenesis - $43,000 NCIC - Scientists Award - Career Award - Targeting oncogene-driven tumor angiogenesis - app. $71,000/year NCIC - co-applicant (PI Dr. Brenda Coomber, University of Guelph) Heterogeneous tumor vasculature: implications for therapy and consequences for cancer progression.-total of app $67,000 Hamilton Health ...

Angiogenesis, the process of new vessel formation or neovascularization, has aroused increasing interest over the last 25 years.1 2 3 4 5 Normal angiogenic activity is low in the adult organism but increases during injury and in diseases such as cancer, retinopathies, or arthritis, where it contributes to pathological changes. Conversely, in states of inadequate tissue perfusion such as myocardial or limb ischemia, enhanced angiogenesis is essential and beneficial. Inhibition or enhancement of angiogenesis may thus prove an attractive strategy for the treatment of several disorders. Although numerous growth factors stimulating vessel development are known (eg, bFGF or VEGF), the exact mechanisms controlling angiogenesis are poorly understood.5 The sympathetic nerves have long been known to have in vivo trophic effects on blood vessel growth. This process was believed to be mediated by catecholamines; at physiological plasma concentrations, however, catecholamines have weak growth-promoting ...

This study investigated the effects on the tumor microenvironment (TME) of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in two murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using three endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight ...

Coordination between the vascular system and forming organs is essential for proper embryonic development. The vasculature expands by sprouting angiogenesis, during which tip cells form filopodia that incorporate into capillary loops. Although several molecules, such as vascular endothelial growth factor A (Vegfa), are known to induce sprouting, the mechanism that terminates this process to ensure neovessel stability is still unknown. Sphingosine-1-phosphate receptor 1 (S1P1) has been shown to mediate interaction between endothelial and mural cells during vascular maturation. In vitro studies have identified S1P1 as a pro-angiogenic factor. Here, we show that S1P1 acts as an endothelial cell (EC)-autonomous negative regulator of sprouting angiogenesis during vascular development. Severe aberrations in vessel size and excessive sprouting found in limbs of S1P1-null mouse embryos before vessel maturation imply a previously unknown, mural cell-independent role for S1P1 as an anti-angiogenic factor. ...

The ANGPT-TIE2 pathway is important for angiogenesis, lymphangiogenesis and inflammation, and therefore has important roles in cancer. Given the context-dependent and opposing effects of the ANGPTs, how do we target this pathway? Angiopoietins (ANGPTs) are ligands of the endothelial cell receptor TIE2 and have crucial roles in the tumour angiogenic switch. Increased expression of ANGPT2 relative to ANGPT1 in tumours correlates with poor prognosis. The biological effects of the ANGPT-TIE system are context dependent, which brings into question what the best strategy is to target this pathway. This Review presents an encompassing picture of what we know about this important axis in tumour biology. The various options for

Abstract : Inefficient immune response is a major glitch during tumor growth and progression. Chaotic and leaky blood vessels created in the process of angiogenesis allow tumor cells to escape and extricate anti-cancer immunity. Proangiogenic characteristics of hypoxic tumor microenvironment maintained by low oxygen tension attract endothelial progenitor cells, drive expansion of cancer stem cells, and deviantly differentiate monocyte descendants. Such cellular milieu further boosts immune tolerance and eventually appoint immunity for cancer advantage. Blood vessel normalization strategies that equilibrate oxygen levels within tumor and fix abnormal vasculature bring exciting promises to future anticancer therapies especially when combined with conventional chemotherapy. Recently, a new group of microRNAs (miRs) engaged in angiogenesis, called angiomiRs and hypoxamiRs, emerged as new therapeutic targets in cancer. Some of those miRs were found to efficiently regulate cancer immunity and their ...

A required role for MT1-MMP in neovessel formation, endothelial cell invasion, and collagenolytic activity. (A) Aortic vessel explants isolated from MT1-MMP-

CCM3, a product of the cerebral cavernous malformation 3 or programmed cell death 10 gene (CCM3/PDCD10), is broadly expressed throughout development in both vertebrates and invertebrates. Increasing evidence indicates a crucial role of CCM3 in vascular development and in regulation of angiogenesis and apoptosis. Furthermore, loss of CCM3 causes inherited (familial) cerebral cavernous malformation (CCM), a common brain vascular anomaly involving aberrant angiogenesis. This study focused on signalling pathways underlying the angiogenic functions of CCM3. Silencing CCM3 by siRNA stimulated endothelial proliferation, migration and sprouting accompanied by significant downregulation of the core components of Notch signalling including DLL4, Notch4, HEY2 and HES1 and by activation of VEGF and Erk pathways. Treatment with recombinant DLL4 (rhDLL4) restored DLL4 expression and reversed CCM3-silence-mediated impairment of Notch signalling and reduced the ratio of VEGF-R2 to VEGF-R1 expression. ...

Excessive neovascularization of atherosclerotic lesions increases plaque vulnerability and the susceptibility to rupture. Semaphorin 7A (Sema7A), a semaphorin family member, was recently reported to promote atherosclerotic plaque formation by mediating d-flow-induced endothelial phenotypic change and leukocyte adhesion. To extend our understanding of the proatherogenic role of Sema7A, we investigated the role of endothelial Sema7A in angiogenesis and atherosclerotic neovascularization. Sema7A overexpression in human umbilical vein endothelial cells (HUVECs) significantly upregulated VEGFA/VEGFR2 and promoted cell migration and angiogenesis. This enhancing effect was eliminated by the blockage of Sema7A receptor, β1 integrin. Inhibition of FAK or ERK1/2 downstream of β1 integrin signaling significantly inhibited cell migration and angiogenesis via ROCK (Rho-associated coiled forming protein kinase) and MYPT (myosin phosphatase targeting subunit), which are responsible for actin polymerization.

RATIONALE: Genetic variation at the chromosome 9p21 cardiovascular risk locus has been associated with peripheral artery disease, but its mechanism remains unknown. OBJECTIVE: To determine whether this association is secondary to an increase in atherosclerosis, or it is the result of a separate angiogenesis-related mechanism. METHODS AND RESULTS: Quantitative evaluation of human vascular samples revealed that carriers of the 9p21 risk allele possess a significantly higher burden of immature intraplaque microvessels than carriers of the ancestral allele, irrespective of lesion size or patient comorbidity. To determine whether aberrant angiogenesis also occurs under nonatherosclerotic conditions, we performed femoral artery ligation surgery in mice lacking the 9p21 candidate gene, Cdkn2b. These animals developed advanced hindlimb ischemia and digital autoamputation, secondary to a defect in the capacity of the Cdkn2b-deficient smooth muscle cell to support the developing neovessel. Microarray ...

Results Lentiviral-mediated reduction of MIF in HMEC led to significantly decreased angiogenesis (p,0.01) which could be restored by adding extracellular rhMIF. Interestingly, reduction of MIF did not influence hypoxia-induced (i) protein-levels of HIF-1α and HIF-2α, respectively, and (ii) HIF-target gene expression of PGK1, GAPDH and VEGFA but (iii) induced secretion of pro-angiogenic VEGFA and IL8. Moreover, addition of 4-IPP also decreased angiogenic response of non-transduced HMECs but enhanced the hypoxia-induced HIF-target gene expression of PGK1 and VEGFA. Inhibiting MIF-signalling by the addition of extracellular anti-CD74-IgG also reduced angiogenic potential of HMEC (p,0.001), which was not restorable by the addition of extracellular rhMIF. Furthermore, lentiviral-mediated reduction of CD74 in HMEC also decreased angiogenesis (p,0.01) without influencing HIF-target gene expression of PGK1, GAPDH and VEGFA. ...

The evolving landscape of treatment for advanced gastric cancer and the role of anti-angiogenic therapy: implications from results of the INTEGRATE study

Tissue branching morphogenesis requires the hierarchical organization of sprouting cells into leading tip and trailing stalk cells [ [1] and [2]]. During new blood vessel branching (angiogenesis), endothelial tip cells (TCs) lead sprouting vessels, extend filopodia, and migrate in response to gradients of the secreted ligand, vascular endothelial growth factor (Vegf) [3]. In contrast, adjacent stalk cells (SCs) trail TCs, generate the trunk of new vessels, and critically maintain connectivity with parental vessels. Here, we establish that h2.0-like homeobox-1 (Hlx1) determines SC potential, which is critical for angiogenesis during zebrafish development. By combining a novel pharmacological strategy for the manipulation of angiogenic cell behavior in vivo with transcriptomic analyses of sprouting cells, we identify the uniquely sprouting-associated gene, hlx1. Expression of hlx1 is almost entirely restricted to sprouting endothelial cells and is excluded from adjacent nonangiogenic cells. ...

Pierce, A. D., Anglin, I. E., Vitolo, M. I., Mochin, M. T., Underwood, K. F., Goldblum, S. E., Kommineni, S. and Passaniti, A. (2012), Glucose-activated RUNX2 phosphorylation promotes endothelial cell proliferation and an angiogenic phenotype. J. Cell. Biochem., 113: 282-292. doi: 10.1002/jcb.23354 ...

New blood vessel growth, or angiogenesis, is critical for cancer to grow and spread throughout the body. Drugs that target vascular endothelial growth factor -- a key driver of angiogenesis -- are now approved for the treatment of several metastatic cancers. However, not all patients respond and many more eventually become resistant after initial treatment benefits.

Understanding of structural and functional characteristics of the vascular microenvironment in gliomas and the impact of antiangiogenic treatments is essential for developing better therapeutic strategies. Although a number of methods exist in which this process can be studied experimentally, no single noninvasive test has the capacity to provide information concerning both microvascular function and morphology. The purpose of present study is to demonstrate the feasibility of using a novel three-dimensional ?R2-based microscopic magnetic resonance angiography (3D ?R2-µMRA) technique for longitudinal imaging of tumor angiogenesis and monitoring the effects of antiangiogenic treatment in rodent brain tumor models. Using 3D ?R2-µMRA, a generally consistent early pattern of vascular development in gliomas was revealed, in which a single feeding vessel was visualized first (arteriogenesis), followed by sprouting angiogenesis. Considerable variability of the tumor-associated vasculature was then ...