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Broad targeting of angiogenesis for cancer prevention and therapy

Wang, Zongwei, (författare)
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Dabrosin, Charlotta, (författare)
Linköpings universitet, Avdelningen för kliniska vetenskaper, Linköpings universitet, Hälsouniversitetet, Östergötlands Läns Landsting, Onkologiska kliniken US
Yin, Xin, (författare)
Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, San Diego, CA, USA
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Fuster, Mark M, (författare)
Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, San Diego, CA, USA
Arreola, Alexandra, (författare)
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Rathmell, W Kimryn, (författare)
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Generali, Daniele, (författare)
Molecular Therapy and Pharmacogenomics Unit, AO Isituti Ospitalieri di Cremona, Cremona, Italy
Nagaraju, Ganji P, (författare)
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
El-Rayes, Bassel, (författare)
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Ribatti, Domenico, (författare)
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy, National Cancer Institute Giovanni Paolo II, Bari, Italy
Chen, Yi Charlie, (författare)
Department of Biology, Alderson Broaddus University, Philippi, WV, USA
Honoki, Kanya, (författare)
Department of Orthopedic Surgery, Arthroplasty and Regenerative Medicine, Nara Medical University, Nara, Japan
Fujii, Hiromasa, (författare)
Department of Orthopedic Surgery, Arthroplasty and Regenerative Medicine, Nara Medical University, Nara, Japan
Georgakilas, Alexandros G, (författare)
Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece
Nowsheen, Somaira, (författare)
Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA
Amedei, Amedeo, (författare)
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Niccolai, Elena, (författare)
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Amin, Amr, (författare)
Department of Biology, College of Science, United Arab Emirate University, United Arab EmiratesFaculty of Science, Cairo University, Cairo, Egypt
Ashraf, S Salman, (författare)
Department of Chemistry, College of Science, United Arab Emirate University, United Arab Emirates
Helferich, Bill, (författare)
University of Illinois at Urbana Champaign, Urbana, IL, USA
Yang, Xujuan, (författare)
University of Illinois at Urbana Champaign, Urbana, IL, USA
Guha, Gunjan, (författare)
School of Chemical and Bio Technology, SASTRA University, Thanjavur, India
Bhakta, Dipita, (författare)
School of Chemical and Bio Technology, SASTRA University, Thanjavur, India
Ciriolo, Maria Rosa, (författare)
Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
Aquilano, Katia, (författare)
Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
Chen, Sophie, (författare)
Ovarian and Prostate Cancer Research Trust Laboratory, Guilford, Surrey, UK
Halicka, Dorota, (författare)
New York Medical College, New York City, NY, USA
Mohammed, Sulma I, (författare)
Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, USA
Azmi, Asfar S, (författare)
School of Medicine, Wayne State University, Detroit, MI, USA
Bilsland, Alan, (författare)
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
Keith, W Nicol, (författare)
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
Jensen, Lasse D, (författare)
Linköpings universitet, Avdelningen för kardiovaskulär medicin, Linköpings universitet, Hälsouniversitetet, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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2015
Engelska.
Ingår i: Seminars in Cancer Biology. - Elsevier. - 1044-579X .- 1096-3650. ; S1044-579X:15, s. 00002-00004
  • Forskningsöversikt (refereegranskat)
Abstract Ämnesord
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  • <p>Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature - is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance over time. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of non-toxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies.</p>

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Angiogenesis Cancer Phytochemicals Treatment Anti-angiogenic

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