Colorectal carcinoma growth and progression is dependent on the vasculature of the tumor microenvironment. Tumor-derived endothelial cells differ functionally from their normal counterpart. For this reason we isolated microvascular endothelial cells from human colon cancer tissue (HCTEC) and compared them with endothelial cells from normal colonic tissue (HCMEC) of the same donor. Since hypoxia is a universal hallmark of carcinomas, we examined its effects on HCTEC of five patients in comparison with the corresponding HCMEC, with respect to the secretion of the soluble form of the two important vascular endothelial growth factor (VEGF) receptors, VEGFR-1 and -2. After dissociation by dispase/collagenase of central non-necrotic tumor areas obtained from colon carcinomas, HCTEC were isolated using CD31-coated magnetic beads and cultivated as monolayers. Subsequent characterization studies demonstrated the endothelial phenotype, including VEGFR-1 and -2 mRNA and protein expression as well as E-selectin
Accumulating evidence shows the emerging roles of the S1P signaling pathway in the regulation of blood vessel functions, including vascular formation, vascular permeability, and the proliferative responses to injury (22, 32). Compared with S1P1, the roles of S1P2 in vascular pathophysiology are relatively poorly understood. In the present investigation, we studied the role of S1P2 in tumor angiogenesis. The present study showed that S1P2 is expressed in both ECs and VSMCs of tumor blood vessels and BMDCs infiltrating in the tumor stroma, as well as in normal blood vessels in a variety of organs. Deletion of host S1P2 resulted in stimulation of tumor angiogenesis with enhanced vascular mural cell recruitment and myeloid cell mobilization, leading to acceleration of tumor cell proliferation and tumor growth. These data collectively suggest that S1P2, which is expressed in ECs and BDMC, is involved in suppression of tumor angiogenesis. The action of S1P2 in tumor angiogenesis contrasts with ...
Expression of integrin αvβ3 is increased on endothelial cells after exposure to bFGF in vitro (Cheng and Kramer, 1989; Senger et al., 1996; Boudreau et al., 1997) and angiogenic blood vessels in vivo (Brooks et al., 1994a,b, 1995). In addition, integrin αvβ3 expression on chick CAM angiogenic blood vessels has been linked to the ability of bFGF to promote expression of the Hox D3 homeobox gene in these tissues (Boudreau et al., 1997). While αvβ3 was detectable on preexisting blood vessels in 10-d-old chick CAMs, αvβ3 levels were not significantly increased above this baseline level for at least 12 h after bFGF treatment. This suggests that the preexisting levels of αvβ3 are sufficient to initiate this sustained phase of MAP kinase activity in these blood vessels and that the requirement of αvβ3 ligation for the sustained MAP kinase activity in blood vessels within 4 h was independent of an increase in the total expression of αvβ3 protein. To support the model that integrin-mediated ...
Angiogenesis, the summation of multiple cellular and biologic processes culminating in the propagation of blood vessels, has been the subject of extensive examination in the context of tumor biology over the past 4 decades since it was first proposed by Judah Folkman in 1971 (1). Solid tumor growth and progression is dependent on tumor-associated angiogenesis. Tumor expression and circulating levels of angiogenic factors have been correlated with aggressive tumor growth, predilection for metastasis, and prognosis in a wide array of solid tumors, including lung cancer (2-4). Although many putative regulators of angiogenesis have been identified, 2 secreted factors, VEGF and basic fibroblast growth factor (bFGF), have been, in particular, strongly implicated in tumor-associated angiogenesis (5). VEGF and bFGF interact with distinct families of tyrosine kinase receptors (RTK) on the surface of endothelial cells and activate multiple downstream signaling pathways. Together, these pathways promote ...
License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php International Journal of Nanomedicine 2015:1
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 ...
Tumor neovascularization is highly dependent upon numerous cytokines and signaling events critical for the growth and organization of the vascular tree. A number of agents targeting tumor neovascularization and which interfere with one or several steps in this robust process have demonstrated significant clinical efficacy and have received FDA approval [24]. These include agents which block angiogenesis signaling events by inhibiting various growth factor receptor kinases [25]; interfere with VEGF physical interaction with its receptors such as anti-VEGF antibodies (bevacizumab and ranibizumab) and anti-receptor antibodies (IMC-1121B and DC101) [26, 27]; and strategies that trap growth factor ligands (VEGF-Trap) [28]. These have all shown antitumor efficacy alone and in combination with conventional antitumor modalities [29, 30].. VEGF-A has been shown to play an important role in tube formation of endothelial cells in vitro [31] and in angiogenesis [32]. In the present study, the effect of ...
There is a very strong link between the vascularization of a tumour and the spread of the disease, both locally and to distant sites (Gimbrone et al., 1974, J. Natl. Cancer Inst. 52, 413-27; Muthukkaruppan et al, 1982, J. Natl. Cancer Inst. 69, 699-704; Ellis & Fiddler, 1995, Lancet 346, 388-9). A tumour becomes vascularized by a process known as angiogenesis. Tumour angiogenesis is initiated by the release of diffusible substances by the tumour, whereby neighbouring capillary vessels are stimulated to grow and eventually penetrate the tumour. Anti-angiogenesis has been proposed as a potential strategy for the treatment of cancer (Folkman, 1995, Nature Med. 1, 21-31; Harris et al, 1996, Breast Cancer Res. Treat. 38, 97-108). In this paper, a mathematical model of the development of the tumour vasculature is presented. By suitable manipulation of the model parameters, we simulate various anti-angiogenesis strategies and we examine the roles that haptotaxis and chemotaxis may play during the ...
The present study demonstrated the validity and superiority of CD105 as a marker of angiogenesis in NSCLC; the CD105-IMVD was more closely correlated with the expression of VEGF than the CD34-IMVD. Kumar et al. (11 , 13 , 15, 16, 17, 18) and others have demonstrated that anti-CD105 antibodies preferentially react with activated ECs in tissues participating in angiogenesis, such as tumor tissues, and that antibodies against pan-ECs, such as anti-CD34 antibodies, react with normal vessels, as well as activated vessels. According to the hypothesis, we tried to define the CD34-IMVD-CD105-IMVD as the baseline IMVD. As a result, the baseline IMVD proved not at all to be correlated with VEGF expression, suggesting the baseline IMVD was not a measurement of angiogenesis but a measurement of vessels just trapped within tumor tissues. Of course, it should be noted that angiogenesis is not influenced only by VEGF but also other angiogenic factors and antiangiogenic factors, such as angiostatin. Comparative ...
Fluciclatide (GE Healthcare) (AH111585) is a small cyclic peptide containing the RGD tripeptide (figure 1), which preferentially binds with high affinity to α¬vβ3 integrins that are up-regulated in angiogenesis.. The IMP is supplied as a solution for injection, 400 MBq at the reference date and time. Participants will receive one injection of the imaging agent at this dose on 3 occasions ...
Fluciclatide (GE Healthcare) (AH111585) is a small cyclic peptide containing the RGD tripeptide (figure 1), which preferentially binds with high affinity to α¬vβ3 integrins that are up-regulated in angiogenesis.. The IMP is supplied as a solution for injection, 400 MBq at the reference date and time. Participants will receive one injection of the imaging agent at this dose on 3 occasions ...
Angiogenesis, the process of new blood vessel formation from existing vessels, plays an important role in normal physiology (Tonnesen et al., 2000), as well as in many pathological conditions including cancer (Folkman, 1971; Papetti and Herman, 2002), macular degeneration (Ahmad et al., 2011), and various vascular diseases (Khurana et al., 2005). Strikingly, increased angiogenesis is observed in many types of human cancers (Bergers and Benjamin, 2003; Dvorak, 2003), whereas angiogenesis is decreased in age-associated vascular diseases (Ungvari et al., 2010). Therefore, diseases that are associated with increased angiogenesis, such as human cancers, can be treated by inhibiting angiogenesis (Folkman, 2007). In contrast, stimulation of angiogenesis could be beneficial in the treatment of coronary artery disease and other vascular diseases characterized by insufficient blood flow to target organs as a result of blocked or damaged blood vessels (Khan et al., 2002; Al Sabti, 2007). Many factors that ...
Now, Barbara Ranscht, Ph.D., and Robert Oshima, Ph.D., at Burnham have led a team that developed the first living model to study this proteins effect on tumor angiogenesis by creating a strain of mice that develops spontaneous mammary gland tumors in the absence of T-cadherin. Their results appeared March 1 in Cancer Research.. "Evidence of T-cadherins role in vascularization has been somewhat controversial," explains Dr. Ranscht, senior author of the study, which includes Drs. Lionel Hebbard and Michèle Garlatti from the Burnham Institute as equally contributing first authors and Drs. Robert Cardiff and Lawrence Young as collaborators from the University of California, Davis. "But our knockout model clearly shows that T-cadherin plays a role in promoting tumor vascularization, with implications for tumor growth and animal survival.". The tumor model developed in Dr. Ranschts laboratory shows that loss of T-cadherin slows down tumor growth and improves survival compared to controls where ...
Topolovec, Zlatko and Ćorušić, Ante and Babić, Damir and Mrčela, Milanka and Šijanović, Siniša and Müller-Vranješ, Andrijana and Čuržik, Darko (2010) Vascular endothelial growth factor and intratumoral microvessel density as prognostic factors in endometrial cancer. Collegium Antropologicum, 34 (2). pp. 447-53. ISSN 0350-6134 ...
For the paper by Seiichiro Takahashi, Markus Moser, Eloi Montanez, Takanari Nakano, Makoto Seo, Steffen Backert, Ikuo Inoue, Takuya Awata, Sigehiro Katayama, Tsugikazu Komoda, and Reinhard Fässler (The fibronectin RGD motif is required for multiple angiogenic events during early embryonic development. Arterioscler Thromb Vasc Biol. 2009 August 27 [Epub ahead of print]; DOI: 10.1161/ATVBAHA.108.181164), after an investigation by the Saitama Medical University Internal Investigation Committee, the Committee concluded that it was unethical for Dr. Takahashi to publish this paper for the following reasons: ...
β3-Integrin-knockout mice exhibit a complex phenotype that includes enhanced pathological angiogenesis. However, as mentioned above, β3-integrin is expressed by a diverse set of cells, and the described phenotype must arise from the integration of its pattern of expression. Although interesting, this biological integration makes it difficult to distinguish cell autonomous effects of β3-integrin. Our studies have addressed, for the first time to our knowledge, the specific contribution that endothelial β3-integrin makes to tumor growth and angiogenesis. Our findings have profound implications for targeting the endothelial-specific expression of β3-integrin to inhibit tumor angiogenesis, a strategy that is growing in popularity with the maturation of nanotechnology.38. Consistent with our findings in β3-knockout animals,10 the depletion of endothelial β3-integrin did not alter the structure of established tumor vessels (Online Figure IA and Online Figure VIA). Sprouting angiogenesis ...
Significant advances have been made in understanding the role of tumor angiogenesis and its influence on tumor progression in cancer. Based on this knowledge, a series of inhibitors of angiogenesis have been developed and evaluated in preclinical and clinical trials. Since detailed information of tumor progression in response to therapy is important to assess the efficacy of anti-tumor treatment in vivo, noninvasive imaging techniques emerge more and more as important tools to monitor alterations in tumor growth and vessel recruitment, as well as metastatic spread over time. So far, remarkable efforts have been made to improve the technical capability of these imaging modalities based on better resolution, as well as to implement multimodal approaches combining molecular with anatomical information. Advanced imaging techniques not only allow the detection and monitoring of tumor development, but also facilitate a broad understanding of the cellular and molecular events that propagate tumor angiogenesis,
New blood vessels are formed from pre-existing capillaries during the development and particular circumstances of postnatal life, such as wound healing. This process, widely known as angiogenesis, sustains the progression of pathological conditions, including cancer and chronic inflammatory diseases. The molecules involved in pathological angiogenesis are potential biomarkers and targets of pharmacological intervention (Carmeliet, 2005). Proof of principle that validates the therapeutic value of antiangiogenic intervention is the anti-VEGF treatment used in patients with metastatic colon cancer (Hurwitz et al., 2004). The inhibition of VEGF-dependent angiogenesis, combined with chemotherapy, is clearly effective in some pathological conditions but is limited in others (Ebos et al., 2009), suggesting that the characterization of alternative molecular targets is essential for developing new therapeutic tools.. Endothelial cell migration is a critical step in VEGF and SDF-1/CXCL-12-dependent ...
BAY1143269 is an orally bioavailable inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKNK1), with potential antineoplastic activity. Upon oral administration, MKNK1 inhibitor BAY 1143269 binds to MKNK1, thereby preventing its activation and the downstream MKNK1-mediated phosphorylation and activation of eukaryotic translation initiation factor 4E (eIF4E). As eIF4E enhances the synthesis of oncogenic proteins, preventing eIF4E activity inhibits the synthesis of tumor angiogenic factors and leads to both the inhibition of cellular proliferation and apoptosis in susceptible tumor cells.
Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination ...
We investigated whether the angiogenic profile, which is based on the local expression and systemic levels of angiogenic growth factors (VEGF, Ang-1, Ang-2, and the corresponding receptors), differs between rheumatoid arthritis (RA) and osteoarthritis (OA) patients. We determined the expression of VEGF, Ang-1, and Ang-2 together with its receptors (VEGFR-1/-2 ...
The Dermaroller is a cylindrical shaped drum studded with very fine needles. It is a medical device used in micro needling to break down old scar tissue & to stimulate skin cells to proliferate. This cell multiplication results in the formation of new tissue layers of elastin and collagen fibres (neo-collagenesis) as well as in new capillaries for an improved blood supply (neo-angiogenesis). The procedures are called Scar Reduction Therapy (SRT) & Collagen Induction Therapy (CIT).. ...
Oral cancer is common among men in the developed world and among the most difficult neoplasms to treat. The growth and metastasis of all solid tumors requires i...
Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. Angiogenesis may take place in two ways - endothelial sprouting or non-sprouting (intussusceptive).
Angiogenesis (angiogenesis) -- the growth of new blood vessels -- is an important natural process occurring in the body, both in health and in disease. Angiogenesis occurs in the healthy body for healing wounds and for restoring blood flow to tissues after injury or insult. In females, angiogenesis also occurs during the monthly reproductive cycle (to rebuild the uterus lining, to mature the egg during ovulation) and during pregnancy (to build the placenta, the circulation between mother and fetus ...
Angiogenesis (also known as neovascularization) is the generation of new blood vessels from pre-existing vasculature. It is a normal process in growth and development and is required for the formation of arteries, veins, and capillaries in an embryo. Proliferation of new blood vessels also takes place in adults and is essential for the repair or regeneration of tissue during wound healing ...
BACKGROUND AND PURPOSE: Quantifying MVA rather than MVD provides better correlation with survival in HGG. This is attributed to a specific "glomeruloid" vascular pattern, which is better characterized by vessel area than number. Despite its prognostic value, MVA quantification is laborious and clinically impractical. The DSC-MR imaging measure of rCBV offers the advantages of speed and convenience to overcome these limitations; however, clinical use of this technique depends on establishing accurate correlations between rCBV, MVA, and MVD, particularly in the setting of heterogeneous vascular size inherent to human HGG. ...
Sigma-Aldrich offers abstracts and full-text articles by [Bing Yan, Long Liu, Ying Zhao, Li-Juan Xiu, Da-Zhi Sun, Xuan Liu, Ye Lu, Jun Shi, Yin-Cheng Zhang, Yong-Jin Li, Xiao-Wei Wang, Yu-Qi Zhou, Shou-Han Feng, Can Lv, Pin-Kang Wei, Zhi-Feng Qin].
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Regulation of Bone Marrow Angiogenesis by Osteoblasts during Bone Development and Homeostasiss profile, publications, research topics, and co-authors
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 ...
Abstract : Tumour microenvironment determines the fate of treatments. Reconstitution of tumour conditions is mandatory for alternative in vitro methods devoted to cancer development and the selection of therapeutic strategies. This work describes a 3D model of melanoma growth in its environment. Introducing means to mimic tumour angiogenesis, which turns on tumour progression, the model shows that melanoma tumour spheroids allow reconstitution of solid tumours with stromal cells. Angiogenesis evidenced the differential recruitment of endothelial cells (EC) from early progenitors (EEPCs) to mature ECs. Hypoxia was the key parameter that selected and stabilized melanoma cancer stem like cells (CSCs) phenotype based on aldehyde dehydrogenase expression as the best criterion. The 3D-tumour-model demonstrated the distinct reactivity of ECs toward tumour cells in terms of cellular cross-talk and humoral response. Intra-spheroid cell-to-cell membrane dye exchanges, mediated by intercellular ...
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 ...
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 ...
An atherosclerotic plaque begins to develop as a result of damage/insult/hypoxia to the endothelial cells of the vascular system (5,17). As atherosclerosis progresses, reduced oxygen diffusion diminishes the nutrient supply reaching the arterial wall, resulting in hypoxia. Reactive physiologic compensation causes a thickening of the intima-media complex exceeding the oxygen diffusion threshold (250 to 500 μm), inducing ischemia, which then triggers a continual release of angiogenic growth factors (vascular endothelial growth factor, tissue hypoxic factor, and so on). It is believed that the absence of pericytes in some angiogenic vessels causes these immature vessels to "leak" potentially noxious and inflammatory plasma components (hemoglobin, oxidized low-density lipoprotein cholesterol, lipoprotein[a], glucose, advanced glycation end products, and inflammatory cells) into the extracellular matrix of the media/intima, increasing plaque volume. The ongoing deposit of plasma components appears ...
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?
Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques
Health, ...The beneficial effects of anti-angiogenesis drugs in the treatment of ... Our findings suggest that antiangiogenesis therapy can increase patie...Cediranib inhibits the potent angiogenesis factor VEGF which is known... We frequently see beneficial effects from drugs in patients without f...,Angiogenesis,inhibitor,improves,brain,tumor,survival,by,reducing,edema,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
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 ...
Our findings demonstrate that a new isocoumarin, NM-3, increases the antitumor effects of various existing chemotherapeutic drugs in breast and prostate tumor model systems, as measured by TGI. The increase in the antitumor effects of chemotherapy in combination with NM-3 was accomplished without any apparent increase in toxicity. Although the mechanisms by which NM-3 exerts antitumor effects are not completely understood, this favorable therapeutic index is attributable to the selective effects of NM-3 on the tumor vasculature. Our data clearly demonstrates that NM-3 specifically inhibits several stages of angiogenesis, in vitro and in vivo, including endothelial cell proliferation, migration, tube formation, sprouting, and neovascularization in the Matrigel plug model. Although direct effects on tumor cells cannot be ruled out, this indicates that NM-3 acts indirectly on delaying tumor growth in vivo by inhibiting tumor angiogenesis.. Antiangiogenic therapy, although effective in inhibiting ...
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...
Looking for microvessel density? Find out information about microvessel density. ratio of the mass mass, in physics, the quantity of matter in a body regardless of its volume or of any forces acting on it. The term should not be confused... Explanation of microvessel density
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 ...
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 ...
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 ...
Blood vessel formation. Artwork showing malignant (cancerous) tumour cells promoting the formation of new blood vessels, a process known as angiogenesis. The tumour cells release angiogenic growth factor proteins that bind to endothelial cells in nearby blood vessels and encourage the growth of new blood vessels from the existing ones. These blood vessels provide the tumour with oxygen and nutrients. - Stock Image C026/8534
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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 ...
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 ...
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...
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 - ...
Advanced imaging techniques may be able to distinguish which patients tumors will respond to treatment with antiangiogenic drugs and which will not.
In the present work, we show that short-term cortisol exposure alters the expression of a number of cardiac remodelling markers in a time-dependent manner and in support of previous work (Johansen et al., 2017), we show that cortisol treatment increases RVM. Moreover, markers of pro-hypertrophic signalling (i.e. smlc2, vmhc, anp and bnp) were upregulated by the cortisol treatment in a time-dependent manner. Both the proliferation marker pcna and the angiogenesis marker vegf were downregulated during the course of cortisol treatment, indicating that cortisol suppresses myocardial cell proliferation and angiogenesis at an early stage of cortisol exposure. Further, there was a clear tendency for autoregulation of the cortisol receptor mr in the cardiac tissue early in the course of exposure, perhaps serving to reduce tissue responsiveness to excess cortisol. Since the observed downregulation of mr was not maintained throughout the treatment period, we speculate that such a potentially protective ...
Angiogenesis is the process of new blood vessel growth. In malignant tumors this process is essential for the delivery of needed nutrients and oxygen for the continued growth and survival of cancer cells. Thus the process of angiogenesis and the subsequent development of therapies that inhibit the process have generated great interest since Judah Folkmans original hypothesis
Hybrigenics was developing nanomolar selective compounds that target tumour angiogenesis for the treatment of cancer. Several antikinase inhibitor compounds
Tumors cells need a rich blood supply in order to grow and metastasize. Angiogenesis (Angio-blood, genesis-creation) is the process by which new blood vessels, called capillaries are formed. Capillaries are lined with endothelial cells. Normal angiogenesis occurs under very tight physiological regulation when stimulators and inhibitors work in balance with each other. Normally the proliferation…
Health, ...SAN FRANCISCO Studies presented at the AACR-NCI-EORTC International C...Among the studies presented include a pair of reports on two separate ... Efficacy safety and changes in angiogenic markers following sunit...Use of sunitinib designed to reduce tumor angiogenesis appears to of...,Clinical,studies,in,the,pipeline:,the,therapies,of,tomorrow,in,trials,today,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Angiogenesis is the creation of new blood vessels. The body creates small blood vessels called "collaterals" to help compensate for reduced blood flow.. ...
Blood vessel growth; Sprouting angiogenesis; Computational modeling; Particle-continuum coupling; 3D; Matrix-bound VEGF; Extracellular matrix; ...
A concoction that meddles with the signs to structure fresh recruits vessels is alluded to as an angiogenesis inhibitor. Researchers have examined the impa..
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 ...
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 ...
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. ...
Uncontrolled neovascularization occurs in several angiogenesis-dependent diseases, including cancer. Neovascularization is tightly controlled by the balance between angiogenic growth factors and antiangiogenic agents. The various natural angiogenesis inhibitors identified so far affect neovascularization by different mechanisms of action. Thrombospondin-1 (TSP-1) is a matricellular modular glycoprotein that acts as a powerful endogenous inhibitor of angiogenesis. It acts both indirectly, by sequestering angiogenic growth factors and effectors in the extracellular environment, and directly, by inducing an antiangiogenic program in endothelial cells following engagement of specific receptors including CD36, CD47, integrins and proteoglycans (all involved in angiogenesis ). In view of its central, multifaceted role in angiogenesis, TSP-1 has served as a source of antiangiogenic tools, including TSP-1 fragments, synthetic peptides and peptidomimetics, gene therapy strategies, and agents that up-regulate TSP
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 ...
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 ...
Akt signaling is involved in tumorigenesis via a number of different mechanisms that result in increased proliferation and decreased apoptosis. Previous data have demonstrated that Akt-mediated signaling is functionally involved in keratinocyte transformation. This work investigates the involvement of angiogenesis as a mediator of tumorigenesis in Akt-transformed keratinocytes. Tumors produced by subcutaneous injection of the latter showed increased angiogenic profiles associated with increased vascular endothelial growth factor (VEGF) protein levels. However, in contrast to v-rasHa-transformed keratinocytes, VEGF mRNA levels were not increased. The induction of VEGF protein by Akt is associated with increased phosphorylation and thus activation of p70S6K and eIF4E-binding protein 1, leading to increased VEGF translation. In addition, we observed increased metaloproteinases 2 and 9 expression, but not thrombospondin 1, in tumors derived from Akt-transformed keratinocytes. Collectively, these ...
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 ...
Tumor angiogenesis is an important factor in proliferation, metastasis, and drug sensitivity. Primary tumors without vasculature are small and dormant, while the growth of the tumor mass creates hypoxic conditions in the center of the tumor that induce expression of VEGF and subsequent tumor vascularization [75]. CAFs are also suggested to be an important source for growth factors and cytokines recruiting endothelial cells. These are involved in the establishment of the cancer stem cell niche and metastatic spread of tumor cells into distant organs [76]. Angiogenesis in malignant tumors, as measured by microvessel density correlates with clinicopathological factors or poor survival in many cancer types (reviewed in [77]). Tumor-endothelial cell interactions are mediated mostly by cell surface adhesion molecules (i.e. integrins, cadherins, immunoglobulins and selectins) [78, 79]. CD34, CD31, and factor-VIII-related antigen are commonly used as tumor endothelial cell markers and microvessel ...
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 ...
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. ...
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. ...
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. ...
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Although a number of growth factors and receptors are known to control tumor angiogenesis, relatively little is known about the mechanism by which these factors influence directional endothelial cell migration required for cancer microvessel formation. Recently, the focal adhesion protein, paxillin, was shown to be required for directional migration of fibroblasts in vitro. Here we show that paxillin knockdown enhances endothelial cell migration in vitro and stimulates angiogenesis during normal development and in response to tumor angiogenic factors in vivo. Paxillin produces these effects by decreasing expression of neuropilin 2 (NRP2). Moreover, soluble factors secreted by tumors that stimulate vascular ingrowth, including VEGF, also decrease endothelial cell expression of paxillin and NRP2, and over-expression of NRP2 reverses these effects. These results suggest that the VEGF-paxillin-NRP2 pathway could represent a new therapeutic target for cancer and other angiogenesis-related ...
Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TPase/PD-ECGF) is a catabolic enzyme that has been shown to be chemotactic for endothelial cells in vitro and angiogenic in vivo. TPase/PD-ECGF expression is increased in a variety of tumors. In the skin, TPase is active in normal keratinocytes in vitro and in vivo. Our objective was to study the expression and localization of TPase/PD-ECGF by immunohistochemical analysis in normal skin and cutaneous tumors and to correlate this information with enzymatic activity of TPase. TPase/PD-ECGF expression was observed in keratinocytes with intense staining of the infundibulum of hair follicles but no staining of hair bulbs. Expression localized primarily to the nucleus of keratinocytes in the basal layer but was more intense and cytoplasrmic in suprabasal keratinocytes. Increased expression of TPase/PD-ECGF in differentiated cells was confirmed by in vitro studies of TPase activity. In cutaneous tumors, there was positive staining ...
Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth
TY - JOUR. T1 - Angiogenic activity of multiple myeloma endothelial cells in vivo in the chick embryo chorioallantoic membrane assay is associated to a down-regulation in the expression of endogenous endostatin. AU - Mangieri, Domenica. AU - Nico, Beatrice. AU - Benagiano, Vincenzo. AU - De Giorgis, Michela. AU - Vacca, Angelo. AU - Ribatti, Domenico. PY - 2008/6. Y1 - 2008/6. N2 - We have attempted a fine characterization of the angiogenic response induced by multiple myeloma endothelial cells (MMEC) by using the chick embryo chorioallantoic membrane (CAM) assay and by reverse transcriptase-polymerase chain reaction (RT-PCR). Results showed that in the CAM assay MMEC induced an angiogenic response comparable to that of a well-known angiogenic cytokine, namely fibroblast growth factor-2 (FGF-2), while RT-PCR demonstrated that the expression of endostatin mRNA detected in MM treated CAM was significantly lower respect to control CAM. These data suggest that angiogenic switch in MM may involve ...
BioAssay record AID 52868 submitted by ChEMBL: Compound was tested for antiangiogenic activity in chick embryo chorioallantoic membrane (CAM) assay system at 10 ug/egg dose; No of CAM avascular/total=4/16(25%).
Title:Targeting Vascular Endothelial Growth Factor in Neuroblastoma. VOLUME: 2 ISSUE: 1. Author(s):Danielle Hsu, Jason M. Shohet and Eugene S. Kim. Affiliation:Division of Pediatric Surgery, Texas Childrens Hospital, CCC Building, Suite 1210, 6701 Fannin St, Houston, TX 77030, USA.. Keywords:Vascular endothelial growth factor, angiogenesis, clinical trials, neuroblastoma.. Abstract:Angiogenesis is critical to tumor growth and metastasis and is dependent on growth factors, such as vascular endothelial growth factor (VEGF). The most characterized angiogenic factor, VEGF is an endothelial cell mitogen and permeability factor that has been found to be overexpressed in almost all human cancers. In a number of tumor model systems, antagonism of the VEGF pathway results in inhibition of angiogenesis and tumor growth. Specifically, VEGF inhibition has been shown to suppress tumor growth, decrease microvasculature, and induce apoptosis of endothelial cells. This close relationship between hypoxia, ...
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