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Cancer Reports (Hoboken, N.J.) Dec 2022The concept that all the tumors need the formation of new vessels to grow inspired the hypothesis that inhibition of angiogenesis would have led to "cure" cancer. The... (Review)
Review
BACKGROUND
The concept that all the tumors need the formation of new vessels to grow inspired the hypothesis that inhibition of angiogenesis would have led to "cure" cancer. The expectancy that this type of therapy would have avoided the insurgence of resistance was based on the concept that targeting normal vessels, instead of the cancer cells which easily develop new mutations, would have allowed evasion of drug caused selection is, however, more complex as it was made apparent by the discovery of nonangiogenic tumors. At the same time an increasing number of trials with antiangiogenic drugs were coming out as not as successful as expected, mostly because of the appearance of unexpected resistance.
RECENT FINDINGS
Among the several different mechanisms of resistance to antiangiogenic treatment by now described, we review the evidences that vascular co-option and vasculogenic mimicry by nonangiogenic tumors are effectively two of such mechanisms. We focused on reviewing exclusively the study, both clinical and preclinical, that offer a demonstration that vascular co-option and vasculogenic mimicry are effectively two mechanisms of both intrinsic and acquired resistance.
CONCLUSION
The discovery that vascular co-opting and vasculogenic mimicry are two ways of escaping antiangiogenic treatment, prompts the need for a better understanding of this phenomenon in order to improve cancer treatment.
Topics: Humans; Neovascularization, Pathologic; Neoplasms
PubMed: 33295149
DOI: 10.1002/cnr2.1318 -
Postepy Higieny I Medycyny... Nov 2015Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most... (Review)
Review
Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments.
Topics: Cytokines; Humans; Intercellular Signaling Peptides and Proteins; Lymphangiogenesis; Lymphoma, T-Cell, Cutaneous; Neovascularization, Pathologic
PubMed: 26561847
DOI: 10.5604/17322693.1177170 -
Dental Materials Journal Oct 2016This review intended to provide an overview of the effects of dental materials, used in dentin-pulp complex and dental pulp regeneration, on angiogenesis processes... (Review)
Review
This review intended to provide an overview of the effects of dental materials, used in dentin-pulp complex and dental pulp regeneration, on angiogenesis processes during regenerative endodontic procedures. An electronic search was performed in PubMed and MEDLINE databases via OVID using the keywords mentioned in the PubMed and MeSH headings for English language published articles from January 2005-April 2014 that evaluated the angiogenic properties of different dental materials used in regenerative endodontic procedures. Of the articles identified in an initial search, only 40 articles met the inclusion criteria set for this review. Vital pulp therapy materials might have positive effects on angiogenesis events, while most of the canal irrigating solutions and antibiotic pastes have anti-angiogenic activity except for EDTA. Future clinical studies will be helpful in defining the mechanisms of action for dental materials that promote or inhibit angiogenesis events at applied areas.
Topics: Biocompatible Materials; Dental Materials; Dental Pulp; Dental Pulp Necrosis; Humans; Neovascularization, Physiologic; Regeneration
PubMed: 27546854
DOI: 10.4012/dmj.2015-332 -
Essential roles of EphB receptors and EphrinB ligands in endothelial cell function and angiogenesis.Advances in Cancer Research 2012Eph receptor tyrosine kinases and their Ephrin ligands represent an important signaling system with widespread roles in cell physiology and disease. Receptors and... (Review)
Review
Eph receptor tyrosine kinases and their Ephrin ligands represent an important signaling system with widespread roles in cell physiology and disease. Receptors and ligands in this family are anchored to the cell surface; thus Eph/Ephrin interactions mainly occur at sites of cell-to-cell contact. EphB4 and EphrinB2 are the Eph/Ephrin molecules that play essential roles in vascular development and postnatal angiogenesis. Analysis of expression patterns and function has linked EphB4/EphrinB2 to endothelial cell growth, survival, migration, assembly, and angiogenesis. Signaling from these molecules is complex, with the potential for being bidirectional, emanating both from the Eph receptors (forward signaling) and from the Ephrin ligands (reverse signaling). In this review, we describe recent advances on the roles of EphB/EphrinB protein family in endothelial cell function and outline potential approaches to inhibit pathological angiogenesis based on this understanding.
Topics: Animals; Endothelial Cells; Ephrins; Humans; Ligands; Neovascularization, Pathologic; Neovascularization, Physiologic; Receptors, Eph Family
PubMed: 22588055
DOI: 10.1016/B978-0-12-386503-8.00002-8 -
Biomedicine & Pharmacotherapy =... Jul 2023In 1971, Folkman proposed that tumors could be limited to very small sizes by blocking angiogenesis. Angiogenesis is the generation of new blood vessels from... (Review)
Review
In 1971, Folkman proposed that tumors could be limited to very small sizes by blocking angiogenesis. Angiogenesis is the generation of new blood vessels from pre-existing vessels, considered to be one of the important processes in tumor growth and metastasis. Angiogenesis is a complex process regulated by various factors and involves many secreted factors and signaling pathways. Angiogenesis is important in the transport of oxygen and nutrients to the tumor during tumor development. Therefore, inhibition of angiogenesis has become an important strategy in the clinical management of many solid tumors. Combination therapies of angiogenesis inhibitors with radiotherapy and chemotherapy are often used in clinical practice. In this article, we will review common targets against angiogenesis, the most common and up-to-date anti-angiogenic drugs and clinical treatments in recent years, including active ingredients from chemical and herbal medicines.
Topics: Humans; Antineoplastic Agents; Neovascularization, Pathologic; Neoplasms; Angiogenesis Inhibitors
PubMed: 37163782
DOI: 10.1016/j.biopha.2023.114806 -
Journal of Cancer Research and... 2019Cancer is one of the main causes of death worldwide. High mortality rates were reported among breast cancer patients which makes the development of new anticancer agents...
AIM
Cancer is one of the main causes of death worldwide. High mortality rates were reported among breast cancer patients which makes the development of new anticancer agents targeting breast cancer a priority. The synthesis of the compounds incorporating- N=N- group is an important field of research that may lead to the discovery of new anticancer drug.
MATERIALS AND METHODS
In this work, we report the synthesis of a compound has O and N centers with the incorporation of the arylazo group (4-BrC6H4-N=N-) into acetylacetone to synthesize 3-(4-Bromo phenylazo)-2,4-pentanedione. Physical characteristics of the newly synthesized compound were determined by measuring electronic absorption spectra, nuclear magnetic resonances, and the infrared absorption spectrum. The inhibitory effect of the compound against breast cancer cell lines was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Its effect on angiogenesis was evaluated by measuring vascular endothelial growth factor (VEGF) levels in treated cells. The ability of the compound to induce apoptosis in cancer cells was tested by measuring caspase-3 activity, and its capacity to stimulate the immune system was evaluated by measuring the levels of interferon gamma (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 cytokines in treated lymphocytes.
RESULTS
Significant antiproliferative activity against breast cancer cell lines was observed in treated cells. Low levels of VEGF and high caspase-3 activity were observed in treated cells. Levels of IFN-γ, IL-2, and IL-4 were increased after treating lymphocytes with this compound.
CONCLUSION
3-(4-Bromo phenylazo)-2,4-pentanedione is a promising anticancer agent that can inhibit breast cancer cells through apoptosis induction and angiogenesis inhibition. Further testing is needed to clearly determine the molecular mechanisms of the anticancer effect of this compound.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Death; Cell Line, Tumor; Cell Proliferation; Female; Humans; Interferon-gamma; Interleukin-2; Interleukin-4; MCF-7 Cells; Neovascularization, Pathologic; Pentanones; Vascular Endothelial Growth Factor A
PubMed: 31603124
DOI: 10.4103/jcrt.JCRT_948_17 -
American Journal of Physiology. Cell... Mar 2020Chemokines are a family of soluble cytokines that act as chemoattractants to guide the migration of cells, in particular of immune cells. However, chemokines are also... (Review)
Review
Chemokines are a family of soluble cytokines that act as chemoattractants to guide the migration of cells, in particular of immune cells. However, chemokines are also involved in cell proliferation, differentiation, and survival. Chemokines are associated with a variety of human diseases including chronic inflammation, immune dysfunction, cancer, and metastasis. This review discusses the expression of CC and CXC chemokines in the tumor microenvironment and their supportive and inhibitory roles in tumor progression, angiogenesis, metastasis, and tumor immunity. We also specially focus on the diverse roles of CXC chemokines (CXCL9-11, CXCL4 and its variant CXCL4L1) and their two chemokine receptor CXCR3 isoforms, CXCR3-A and CXCR3-B. These two distinct isoforms have divergent roles in tumors, either promoting (CXCR3-A) or inhibiting (CXCR3-B) tumor progression. Their effects are mediated not only directly in tumor cells but also indirectly via the regulation of angiogenesis and tumor immunity. A full comprehension of their mechanisms of action is critical to further validate these chemokines and their receptors as biomarkers or therapeutic targets in cancer.
Topics: Animals; Biomarkers, Tumor; Chemokine CXCL9; Disease Progression; Humans; Neoplasm Invasiveness; Neovascularization, Pathologic; Platelet Factor 4; Receptors, CXCR3; Tumor Microenvironment
PubMed: 31913695
DOI: 10.1152/ajpcell.00378.2019 -
Histology and Histopathology Feb 2012The Notch signaling pathway is critical for many developmental processes including physiologic angiogenesis. Notch is also implicated in having a key role in tumor... (Review)
Review
The Notch signaling pathway is critical for many developmental processes including physiologic angiogenesis. Notch is also implicated in having a key role in tumor angiogenesis. Preclinical and clinical experience with anti-angiogenic strategies indicates that they may be limited by tumor resistance and recurrence, which has led to the search for alternative angiogenic treatment strategies. Significant progress has been made in shedding light on the complex mechanisms by which Notch signaling can influence tumor growth by disrupting vasculature in an array of tumor models (Ridgway et al., 2006). These results have led to the consideration of Notch as an attractive target to block tumor angiogenesis and inhibit growth. However, studies of inhibition of Notch signaling in different tumor models have uncovered similarly variable results, and some unexpected adverse effects. The ability of Notch to function in a context-dependent manner as a determinant of cell fate, a tumor suppressor, and an oncogene may partially explain the complexity in interpreted the role of Notch signaling inhibitors in preclinical tumor studies. In addition, Notch may also play an important role in metastasis via its direct effects on the vasculature and by modulation of epithelial-mesenchymal transition in tumor cells. Here we present a current understanding of Notch signaling in tumor angiogenesis, and discuss recent work on the role of Notch in tumor metastatic progression.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Receptors, Notch; Signal Transduction
PubMed: 22207549
DOI: 10.14670/HH-27.151 -
International Journal of Molecular... Jul 2021Tissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit...
Tissue regeneration depends on the complex processes of angiogenesis, inflammation and wound healing. Regarding muscle tissue, glucocorticoids (GCs) inhibit pro-inflammatory signalling and angiogenesis and lead to muscle atrophy. Our hypothesis is that the synthetic GC dexamethasone (dex) impairs angiogenesis leading to muscle atrophy or inhibited muscle regeneration. Therefore, this study aims to elucidate the effect of dexamethasone on HUVECs under different conditions in mono- and co-culture with myoblasts to evaluate growth behavior and dex impact with regard to muscle atrophy and muscle regeneration. Viability assays, qPCR, immunofluorescence as well as ELISAs were performed on HUVECs, and human primary myoblasts seeded under different culture conditions. Our results show that dex had a higher impact on the tube formation when HUVECs were maintained with VEGF. Gene expression was not influenced by dex and was independent of cells growing in a 2D or 3D matrix. In co-culture CD31 expression was suppressed after incubation with dex and gene expression analysis revealed that dex enhanced expression of myogenic transcription factors, but repressed angiogenic factors. Moreover, dex inhibited the VEGF mediated pro angiogenic effect of myoblasts and inhibited expression of angiogenic inducers in the co-culture model. This is the first study describing a co-culture of human primary myoblast and HUVECs maintained under different conditions. Our results indicate that dex affects angiogenesis via inhibition of VEGF release at least in myoblasts, which could be responsible not only for the development of muscle atrophy after dex administration, but also for inhibition of muscle regeneration after vascular damage.
Topics: Coculture Techniques; Dexamethasone; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Myoblasts, Skeletal; Neovascularization, Physiologic; Vascular Endothelial Growth Factor A
PubMed: 34360750
DOI: 10.3390/ijms22157986 -
Asia Pacific Journal of Clinical... 2008Angiogenesis means the formation of new blood vessels from preexisting vascular, is of fundamental importance in several pathological states such as tumor growth,...
Angiogenesis means the formation of new blood vessels from preexisting vascular, is of fundamental importance in several pathological states such as tumor growth, rheumatoid arthritis, and diabetic retinopathy. Angiogenesis involves a set of steps, including activation and movement of endothelial cells and tube formation. Control of these steps by drugs or dietary food components is a hopeful approach for the prevention of angiogenic disorders. Based on these backgrounds, we searched the anti-angiogenic food components. As a result, we found that tocotrienol (T3), especially delta, beta, and gamma-T3 has the potent anti-angiogenic activity in vitro and in vivo experiments. T3, which is rich in rice bran and palm oil, inhibited growth factor-induced proliferation, migration and tube formation in human umbilical vein endothelial cells. T3 showed inhibition of tumor cell-induced angiogenesis in mouse dorsal air sac (DOS) assay. These results indicated that T3 is a potent anti-angiogenesis compound. Tocopherol (Toc) did not inhibit angiogenesis. The anti-angiogenic mechanism of T3 and Toc was evaluated by western blotting. T3 inhibited activation of growth factor-induced extracellular signal-regulated kinase, Akt (protein kinase B), and endothelial nitric oxide synthase (eNOS), which are located downstream of the various growth factor receptors. T3 suppressed phosphorylation of vascular endothelial growth factor (VEGF) receptor 2. These effects were dose-dependent manner. Anti-angiogenic mechanism of T3 mediates inhibition of growth factor induced survival, migration and angiogenesis signals. These findings suggested that T3 may have potential for preventing angiogenic disorders in humans.
Topics: Angiogenesis Inhibitors; Animals; Biological Assay; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Fibroblast Growth Factors; Humans; Male; Mice; Mice, Inbred ICR; Neovascularization, Pathologic; Neovascularization, Physiologic; Tocotrienols
PubMed: 18296349
DOI: No ID Found