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  • 1.
    Block, Keith I.
    et al.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Gyllenhaal, Charlotte
    Block Centre Integrat Cancer Treatment, IL 60077 USA; National Cancer Centre, South Korea.
    Lowe, Leroy
    Getting Know Canc, Canada; University of Lancaster, England.
    Amedei, Amedeo
    University of Florence, Italy.
    Ruhul Amin, A. R. M.
    University of Florence, Italy.
    Amin, Amr
    University of Florence, Italy.
    Aquilano, Katia
    United Arab Emirates University, U Arab Emirates.
    Arbiser, Jack
    Atlanta Vet Adm Medical Centre, GA USA; Emory University, GA USA.
    Arreola, Alexandra
    University of Roma Tor Vergata, Italy.
    Arzumanyan, Alla
    University of N Carolina, NC 27599 USA.
    Salman Ashraf, S.
    Temple University, PA 19122 USA.
    Azmi, Asfar S.
    United Arab Emirates University, U Arab Emirates.
    Benencia, Fabian
    Wayne State University, MI USA.
    Bhakta, Dipita
    Ohio University, OH 45701 USA.
    Bilsland, Alan
    SASTRA University, India.
    Bishayeen, Anupam
    University of Glasgow, Scotland.
    Blain, Stacy W.
    Larkin Health Science Institute, FL USA.
    Block, Penny B.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Boosani, Chandra S.
    Suny Downstate Medical Centre, NY USA.
    Carey, Thomas E.
    Creighton University, NE 68178 USA.
    Carnero, Amancio
    University of Michigan, MI USA.
    Carotenuto, Marianeve
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Casey, Stephanie C.
    University of Naples Federico II, Italy.
    Chakrabarti, Mrinmay
    Stanford University, CA 94305 USA.
    Chaturvedi, Rupesh
    University of S Carolina, SC USA.
    Zhuo Chen, Georgia
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Chenx, Helen
    Jawaharlal Nehru University, India.
    Chen, Sophie
    University of British Columbia, Canada.
    Charlie Chen, Yi
    Ovarian and Prostate Cancer Research Lab, England; Alderson Broaddus University, PA USA.
    Choi, Beom K.
    National Cancer Centre, South Korea.
    Rosa Ciriolo, Maria
    United Arab Emirates University, U Arab Emirates.
    Coley, Helen M.
    University of Surrey, England.
    Collins, Andrew R.
    University of Oslo, Norway.
    Connell, Marisa
    Jawaharlal Nehru University, India.
    Crawford, Sarah
    So Connecticut State University, CT 06515 USA.
    Curran, Colleen S.
    University of Wisconsin, WI USA.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Damia, Giovanna
    Ist Ric Farmacol Mario Negri, Italy.
    Dasgupta, Santanu
    University of Texas Health Science Centre Tyler, TX USA.
    DeBerardinis, Ralph J.
    University of Texas SW Medical Centre Dallas, TX 75390 USA.
    Decker, William K.
    Baylor Coll Med, TX 77030 USA.
    Dhawan, Punita
    Vanderbilt University, TN 37212 USA.
    Diehl, Anna Mae E.
    Duke University, NC 27710 USA.
    Dong, Jin-Tang
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Ping Dou, Q.
    United Arab Emirates University, U Arab Emirates.
    Drew, Janice E.
    University of Aberdeen, Scotland.
    Elkord, Eyad
    United Arab Emirates University, U Arab Emirates.
    El-Rayes, Bassel
    Emory University, GA 30322 USA.
    Feitelson, Mark A.
    University of N Carolina, NC 27599 USA.
    Felsher, Dean W.
    University of Naples Federico II, Italy.
    Ferguson, Lynnette R.
    University of Auckland, New Zealand.
    Fimognari, Carmela
    University of Auckland, New Zealand.
    Firestone, Gary L.
    University of Bologna, Italy.
    Frezza, Christian
    University of Calif Berkeley, CA 94720 USA.
    Fujii, Hiromasa
    University of Cambridge, England.
    Fuster, Mark M.
    Nara Medical University, Japan.
    Generali, Daniele
    University of Calif San Diego, CA 92103 USA; University of Calif San Diego, CA 92103 USA.
    Georgakilas, Alexandros G.
    University of Trieste, Italy.
    Gieseler, Frank
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Gilbertson, Michael
    National Technical University of Athens, Greece.
    Green, Michelle F.
    University Hospital Schleswig Holstein, Germany.
    Grue, Brendan
    Getting Know Canc, Canada.
    Guha, Gunjan
    Ohio University, OH 45701 USA.
    Halicka, Dorota
    Duke University, NC USA.
    Helferich, William G.
    Dalhousie University, Canada.
    Heneberg, Petr
    New York Medical Coll, NY 10595 USA.
    Hentosh, Patricia
    University of Illinois, IL 61820 USA.
    Hirschey, Matthew D.
    University Hospital Schleswig Holstein, Germany.
    Hofseth, Lorne J.
    Charles University of Prague, Czech Republic.
    Holcombe, Randall F.
    Old Domin University, VA USA.
    Honoki, Kanya
    Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
    Hsu, Hsue-Yin
    University of S Carolina, SC 29208 USA.
    Huang, Gloria S.
    Mt Sinai School Med, NY USA.
    Jensen, Lasse D.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jiang, Wen G.
    Cardiff University, Wales.
    Jones, Lee W.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Karpowicz, Phillip A.
    University of Windsor, Canada.
    Nicol Keith, W.
    SASTRA University, India.
    Kerkar, Sid P.
    Mayo Clin, MN USA.
    Khan, Gazala N.
    Henry Ford Hospital, MI 48202 USA.
    Khatami, Mahin
    National Institute Heatlh, MD USA.
    Ko, Young H.
    University of Maryland BioPark, MD USA.
    Kucuk, Omer
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Kulathinal, Rob J.
    University of N Carolina, NC 27599 USA.
    Kumar, Nagi B.
    University of S Florida, FL USA.
    Kwon, Byoung S.
    National Cancer Centre, South Korea; Tulane University, LA 70118 USA.
    Le, Anne
    Johns Hopkins University, MD USA.
    Lea, Michael A.
    Rutgers State University, NJ USA.
    Lee, Ho-Young
    Seoul National University, South Korea.
    Lichtor, Terry
    Rush University, IL 60612 USA.
    Lin, Liang-Tzung
    Taipei Medical University, Taiwan.
    Locasale, Jason W.
    Cornell University, NY 14853 USA.
    Lokeshwar, Bal L.
    Georgia Regents University, GA USA.
    Longo, Valter D.
    University of So Calif, CA USA.
    Lyssiotis, Costas A.
    University of Michigan, MI USA; University of Michigan, MI USA.
    MacKenzie, Karen L.
    Childrens Cancer Institute Australia, Australia.
    Malhotra, Meenakshi
    McGill University, Canada.
    Marino, Maria
    University of Rome Tre, Italy.
    Martinez-Chantar, Maria L.
    Technology Pk Bizkaia, Spain.
    Matheu, Ander
    Biodonostia Institute, Spain.
    Maxwell, Christopher
    Jawaharlal Nehru University, India.
    McDonnell, Eoin
    University Hospital Schleswig Holstein, Germany.
    Meeker, Alan K.
    Johns Hopkins University, MD 21205 USA.
    Mehrmohamadi, Mahya
    Cornell University, NY USA.
    Mehta, Kapil
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Michelotti, Gregory A.
    Duke University, NC 27710 USA.
    Mohammad, Ramzi M.
    United Arab Emirates University, U Arab Emirates.
    Mohammed, Sulma I.
    Purdue University, IN 47907 USA.
    James Morre, D.
    Mor NuCo Inc, IN USA.
    Muqbil, Irfana
    United Arab Emirates University, U Arab Emirates.
    Muralidhar, Vinayak
    Harvard University, MA USA; MIT, MA 02139 USA.
    Murphy, Michael P.
    MRC Mitochondrial Biol Unit, England.
    Purnachandra Nagaraju, Ganji
    Emory University, GA 30322 USA.
    Nahta, Rita
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Niccolai, Elena
    University of Florence, Italy.
    Nowsheen, Somaira
    Mayo Clin, MN USA.
    Panis, Carolina
    State University of West Parana, Brazil.
    Pantano, Francesco
    University of Campus Bio Med, Italy.
    Parslow, Virginia R.
    University of Auckland, New Zealand.
    Pawelec, Graham
    University of Tubingen, Germany.
    Pedersen, Peter L.
    Johns Hopkins University, MD USA.
    Poore, Brad
    Johns Hopkins University, MD USA.
    Poudyal, Deepak
    Charles University of Prague, Czech Republic.
    Prakash, Satya
    McGill University, Canada.
    Prince, Mark
    University of Michigan, MI USA.
    Raffaghello, Lizzia
    Ist Giannina Gaslini, Italy.
    Rathmell, Jeffrey C.
    University Hospital Schleswig Holstein, Germany.
    Kimryn Rathmell, W.
    University of Roma Tor Vergata, Italy.
    Ray, Swapan K.
    Stanford University, CA 94305 USA.
    Reichrath, Joerg
    Saarland University Hospital, Germany.
    Rezazadeh, Sarallah
    University of Rochester, NY 14627 USA.
    Ribatti, Domenico
    University of Bari, Italy.
    Ricciardiello, Luigi
    National Cancer Institute Giovanni Paolo II, Italy.
    Brooks Robey, R.
    University of Bologna, Italy; White River Junct Vet Affairs Medical Centre, VT USA.
    Rodier, Francis
    Geisel School Medical Dartmouth, NH USA; University of Montreal, Canada.
    Vasantha Rupasinghe, H. P.
    Institute Cancer Montreal, Canada.
    Luigi Russo, Gian
    University of Montreal, Canada.
    Ryan, Elizabeth P.
    Dalhousie University, Canada.
    Samadi, Abbas K.
    Sanus Biosciences, San Diego, CA, United States.
    Sanchez-Garcia, Isidro
    CNR, Italy.
    Sanders, Andrew J.
    Cardiff University, Wales.
    Santini, Daniele
    University of Campus Bio Med, Italy.
    Sarkar, Malancha
    Colorado State University, CO 80523 USA.
    Sasada, Tetsuro
    Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
    Saxena, Neeraj K.
    University of Salamanca, Spain.
    Shackelford, Rodney E.
    University of Miami, FL USA.
    Shantha Kumara, H. M. C.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Sharma, Dipali
    Kurume University, Japan.
    Shin, Dong M.
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Sidransky, David
    University of Maryland, MD 21201 USA.
    David Siegelin, Markus
    Louisiana State University, LA 71105 USA.
    Signori, Emanuela
    Johns Hopkins University, MD 21205 USA; Johns Hopkins University, MD USA.
    Singh, Neetu
    Johns Hopkins University, MD USA; King Georges Medical University, India.
    Sivanand, Sharanya
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Sliva, Daniel
    Institute Translat Pharmacol, Italy; Purdue Research Pk, IN USA.
    Smythe, Carl
    University of Sheffield, England.
    Spagnuolo, Carmela
    University of Montreal, Canada.
    Stafforini, Diana M.
    University of Utah, UT USA.
    Stagg, John
    University of Utah, UT USA.
    Subbarayan, Pochi R.
    University of Montreal, Canada.
    Sundin, Tabetha
    University of Miami, FL USA.
    Talib, Wamidh H.
    Sentara Healthcare, VA USA.
    Thompson, Sarah K.
    Appl Science University, Jordan.
    Tran, Phuoc T.
    Royal Adelaide Hospital, Australia.
    Ungefroren, Hendrik
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Vander Heiden, Matthew G.
    MIT, MA 02139 USA.
    Venkateswaran, Vasundara
    Johns Hopkins University, MD USA; University of Toronto, Canada.
    Vinay, Dass S.
    Tulane University, LA USA.
    Vlachostergios, Panagiotis J.
    Johns Hopkins University, MD USA; New York University, NY USA.
    Wang, Zongwei
    Johns Hopkins University, MD USA; Harvard University, MA USA.
    Wellendx, Kathryn E.
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Whelan, Richard L.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Yang, Eddy S.
    University of Alabama Birmingham, AL USA.
    Yang, Huanjie
    Harbin Institute Technology, Peoples R China.
    Yang, Xujuan
    Dalhousie University, Canada.
    Yaswen, Paul
    Lawrence Berkeley National Lab, CA USA.
    Yedjou, Clement
    Jackson State University, MS USA.
    Yin, Xin
    Nara Medical University, Japan.
    Zhu, Jiyue
    Washington State University, WA USA.
    Zollo, Massimo
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Designing a broad-spectrum integrative approach for cancer prevention and treatment2015In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 35, p. S276-S304Article, review/survey (Refereed)
    Abstract [en]

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 2.
    Rosén, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Murray, F
    Uppsala University, Uppsala, Sweden.
    Evaldsson, Chamilly
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rosenquist, R
    Uppsala University, Uppsala, Sweden.
    Antigens in chronic lymphocytic leukemia—Implications for cell origin and leukemogenesis2010In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 20, no 6, p. 400-409Article, review/survey (Refereed)
    Abstract [en]

    Several types of B cell tumors, particularly MALT lymphomas, are known to have an antigen-driven component in tumor development. Over the past two decades substantial data have accumulated regarding the restricted immunoglobulin (IG) gene repertoire in chronic lymphocytic leukemia (CLL) and its potential implications for antigenic drive in the disease development and progression. Herein we discuss how evidence first illustrated a link between certain B cell receptor (BCR) specificities and disease outcome and the subsequent large-scale IG analyses which revealed the extent of “stereotyped” BCRs in CLL. More recent studies on CLL antibody reactivity have gradually provided clues as to which antigens may be involved in the tumor development. Significantly, CLL monoclonal antibodies have been shown to resemble natural antibodies recognizing molecular motifs both on apoptotic cells (e.g. modified cytoskeletal proteins and oxidation-specific epitopes), as well as exogenous bacteria, indicating that CLL clones possibly arise from B cells which have dual function as scavengers of apoptotic debris, while also having the ability to bind conserved bacterial cell structures. Such revelations have led us to re-evaluate both the phenotypic and functional characteristics of the tumor B cells and the pathway by which CLL arises and develops.

  • 3.
    Sandman, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. University of Borås, Sweden.
    Liliemark, Jan
    Swedish Agency Health Technology Assessment and Assessment, Sweden; Dent and Pharmaceut Benefits Agency, Sweden.
    From evidence-based to hope-based medicine? Ethical aspects on conditional market authorization of and early access to new cancer drugs2017In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 45, p. 58-63Article, review/survey (Refereed)
    Abstract [en]

    There is a strong patient demand for early access to potentially beneficial cancer drugs. In line with this authorization agencies like the European Medicines Agency are providing drugs with conditional market authorisation based on positive interim analyses. This implies that drugs are used with insecure evidence of efficacy and adverse side-effects. Several authors have pointed to ethical problems with such a system but up to date no indepth ethical analysis of this system is found which is the aim of this article. Drawing of the four generally accepted principles of medical ethics: beneficence, nonmaleficence, respect for autonomy and justice the ethical pros and cons of conditional market authorisation are analysed. From the perspective of beneficence and non maleficence it is found that the main problem is not risk of adverse side-effects to patients, but rather risk of less beneficial outcomes than what can be expected which could change incentives for patients choice of treatment. This is also related to the extent to which patients might make an autonomous choice, especially taking into account problematic psychological attitudes and biases in medical decision-making. However, the main problem is related to justice and an equitable distribution of scarce health-care resources given the opportunity cost of drugs treatment. When using resources on cancer treatments which later might be found to be less efficacious than was first expected, other patients (in and outside the cancer field) are deprived of potentially more beneficial treatments even though their needs might be equally or more severe. At the same time, demanding more evidence has an ethical cost to patients in terms of depriving them of potential benefits in terms of reduced mortality and morbidity. In order to handle these ethical conflicts further research and analyses are required and it is suggested that pricing strategies and information requirements are alternatives to be further explored.

  • 4.
    Wang, Zongwei
    et al.
    Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    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
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Broad targeting of angiogenesis for cancer prevention and therapy2015In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. S1044-579X, no 15, p. 00002-00004Article, review/survey (Refereed)
    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.

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  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf