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  • 51.
    Wang, Zongwei
    et al.
    Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Yin, Xin
    Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, San Diego, CA, USA.
    Fuster, Mark M
    Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, San Diego, CA, USA.
    Arreola, Alexandra
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
    Rathmell, W Kimryn
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
    Generali, Daniele
    Molecular Therapy and Pharmacogenomics Unit, AO Isituti Ospitalieri di Cremona, Cremona, Italy.
    Nagaraju, Ganji P
    Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
    El-Rayes, Bassel
    Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
    Ribatti, Domenico
    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
    Department of Biology, Alderson Broaddus University, Philippi, WV, USA.
    Honoki, Kanya
    Department of Orthopedic Surgery, Arthroplasty and Regenerative Medicine, Nara Medical University, Nara, Japan.
    Fujii, Hiromasa
    Department of Orthopedic Surgery, Arthroplasty and Regenerative Medicine, Nara Medical University, Nara, Japan.
    Georgakilas, Alexandros G
    Physics Department, School of Applied Mathematics and Physical Sciences, National Technical University of Athens, Athens, Greece.
    Nowsheen, Somaira
    Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA.
    Amedei, Amedeo
    Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
    Niccolai, Elena
    Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
    Amin, Amr
    Department of Biology, College of Science, United Arab Emirate University, United Arab EmiratesFaculty of Science, Cairo University, Cairo, Egypt.
    Ashraf, S Salman
    Department of Chemistry, College of Science, United Arab Emirate University, United Arab Emirates.
    Helferich, Bill
    University of Illinois at Urbana Champaign, Urbana, IL, USA.
    Yang, Xujuan
    University of Illinois at Urbana Champaign, Urbana, IL, USA.
    Guha, Gunjan
    School of Chemical and Bio Technology, SASTRA University, Thanjavur, India.
    Bhakta, Dipita
    School of Chemical and Bio Technology, SASTRA University, Thanjavur, India.
    Ciriolo, Maria Rosa
    Department of Biology, University of Rome “Tor Vergata”, Rome, Italy.
    Aquilano, Katia
    Department of Biology, University of Rome “Tor Vergata”, Rome, Italy.
    Chen, Sophie
    Ovarian and Prostate Cancer Research Trust Laboratory, Guilford, Surrey, UK.
    Halicka, Dorota
    New York Medical College, New York City, NY, USA.
    Mohammed, Sulma I
    Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, USA.
    Azmi, Asfar S
    School of Medicine, Wayne State University, Detroit, MI, USA.
    Bilsland, Alan
    Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
    Keith, W Nicol
    Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
    Jensen, Lasse D
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Broad targeting of angiogenesis for cancer prevention and therapy2015Inngår i: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. S1044-579X, nr 15, s. 00002-00004Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    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.

    Fulltekst (pdf)
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