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Designing a broad-spectrum integrative approach for cancer prevention and treatment
KI. Block, C. Gyllenhaal, L. Lowe, A. Amedei, AR. Amin, A. Amin, K. Aquilano, J. Arbiser, A. Arreola, A. Arzumanyan, SS. Ashraf, AS. Azmi, F. Benencia, D. Bhakta, A. Bilsland, A. Bishayee, SW. Blain, PB. Block, CS. Boosani, TE. Carey, A. Carnero,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S., přehledy
Grantová podpora
NV15-32432A
MZ0
CEP - Centrální evidence projektů
- MeSH
- chemorezistence genetika MeSH
- cílená molekulární terapie * MeSH
- fytogenní protinádorové látky terapeutické užití MeSH
- genetická heterogenita * MeSH
- individualizovaná medicína * MeSH
- lidé MeSH
- nádorové mikroprostředí genetika MeSH
- nádory genetika patologie prevence a kontrola terapie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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 "broad-spectrum" 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.
1st Department of Medicine University Hospital Schleswig Holstein Campus Lübeck Lübeck Germany
Albert Einstein College of Medicine and Montefiore Medical Center Bronx NY United States
Atlanta Veterans Administration Medical Center Atlanta GA United States
Biodonostia Institute Gipuzkoa Spain
Block Center for Integrative Cancer Treatment Skokie IL United States
Cancer Biology Research Laboratory Southern Connecticut State University New Haven CT United States
Cardiff University School of Medicine Heath Park Cardiff United Kingdom
Center for Medical Research University of Tübingen Tübingen Germany
Centro di Ingegneria Genetica e Biotecnologia Avanzate Naples Italy
Charles University Prague 3rd Faculty of Medicine Prague Czech Republic
Children's Cancer Institute Australia Kensington New South Wales Australia
College of Medicine and Health Sciences United Arab Emirates University Al Ain United Arab Emirates
College of Pharmacy Seoul National University South Korea
College of Pharmacy University of South Carolina Columbia SC United States
Department of Biology Alderson Broaddus University Philippi WV United States
Department of Biology College of Science United Arab Emirates University Al Ain United Arab Emirates
Department of Biology Jackson State University Jackson MS United States
Department of Biology Temple University Philadelphia PA United States
Department of Biology University of Miami Miami FL United States
Department of Biology University of Rochester Rochester NY United States
Department of Biology University of Rome Tor Vergata Rome Italy
Department of Biomedical Engineering McGill University Montréal Canada
Department of Biomedical Sciences Ohio University Athens OH United States
Department of BioMedical Sciences School of Medicine Creighton University Omaha NE United States
Department of Clinical Pharmacy and Therapeutics Applied Science University Amman Jordan
Department of Experimental and Clinical Medicine University of Florence Florence Italy
Department of Hematology and Medical Oncology Emory University Atlanta GA United States
Department of Immunology Kurume University School of Medicine Kurume Fukuoka Japan
Department of Life Sciences Tzu Chi University Hualien Taiwan
Department of Medical and Health Sciences Linköping University Linköping Sweden
Department of Medical and Surgical Sciences University of Bologna Bologna Italy
Department of Medical Surgery and Health Sciences University of Trieste Trieste Italy
Department of Medicine Duke University Medical Center Durham NC United States
Department of Medicine Georgia Regents University Cancer Center Augusta GA United States
Department of Medicine Memorial Sloan Kettering Cancer Center New York NY United States
Department of Medicine Tulane University Health Sciences Center New Orleans LA United States
Department of Medicine University of Maryland School of Medicine Baltimore MD United States
Department of Medicine University of Miami Miller School of Medicine Miami FL United States
Department of Microbiology Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
Department of Molecular and Cell Biology University of California Berkeley Berkeley CA United States
Department of Molecular Diagnostics Sentara Healthcare Norfolk VA United States
Department of Neurosurgery Rush University Medical Center Chicago IL United States
Department of Nutrition Faculty of Medicine University of Oslo Oslo Norway
Department of Oncology Karmanos Cancer Institute Wayne State University Detroit MI United States
Department of Orthopedic Surgery Nara Medical University Kashihara Nara Japan
Department of Pathology and Immunology Baylor College of Medicine Houston TX United States
Department of Pathology Johns Hopkins University School of Medicine Baltimore MD United States
Department of Pathology Louisiana State University Health Shreveport Shreveport LA United States
Department of Pathology New York Medical College Valhalla NY United States
Department of Science University Roma Tre Rome Italy
Department of Surgery Royal Adelaide Hospital Adelaide Australia
Department of Surgery St Luke's Roosevelt Hospital New York NY United States
Department of Urology Massachusetts General Hospital Harvard Medical School Boston MA United States
Division of Nutritional Sciences Cornell University Ithaca NY United States
DSTest Laboratories Purdue Research Park Indianapolis IN United States
Duke Molecular Physiology Institute Duke University Medical Center Durham NC United States
Faculty of Health and Medical Sciences University of Surrey Guildford Surrey United Kingdom
Geisel School of Medicine at Dartmouth Hanover NH United States
Getting to Know Cancer Guelph Canada
Getting to Know Cancer Truro Nova Scotia Canada
Head and Neck Cancer Biology Laboratory University of Michigan Ann Arbor MI United States
Henry Ford Hospital Detroit MI United States
Institute of Food Sciences National Research Council Avellino Italy
Instituto de Biomedicina de Sevilla Consejo Superior de Investigaciones Cientificas Seville Spain
Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States
Laboratory of Inflammatory Mediators State University of West Paraná UNIOESTE Paraná Brazil
Laboratory of Oncology Istituto Giannina Gaslini Genoa Italy
Lancaster Environment Centre Lancaster University Bailrigg Lancaster United Kingdom
Life Sciences Division Lawrence Berkeley National Lab Berkeley CA United States
Lineberger Comprehensive Cancer Center University of North Carolina Chapel Hill NC United States
Medical Oncology Department University Campus Bio Medico Rome Italy
Moffitt Cancer Center University of South Florida College of Medicine Tampa FL United States
Mor NuCo Inc Purdue Research Park West Lafayette IN United States
MRC Mitochondrial Biology Unit Wellcome Trust MRC Building Hills Road Cambridge United Kingdom
National Research Council Institute of Translational Pharmacology Rome Italy
New Jersey Medical School Rutgers University Newark NJ United States
Ovarian and Prostate Cancer Research Laboratory Guildford Surrey United Kingdom
Rowett Institute of Nutrition and Health University of Aberdeen Aberdeen Scotland United Kingdom
Sanus Biosciences San Diego CA United States
School of Biotechnology Jawaharlal Nehru University New Delhi India
School of Chemical and Bio Technology SASTRA University Thanjavur Tamil Nadu India
School of Medical Laboratory and Radiation Sciences Old Dominion University Norfolk VA United States
School of Medicine and Public Health University of Wisconsin Madison Madison WI United States
The School of Life Science and Technology Harbin Institute of Technology Harbin Heilongjiang China
Tisch Cancer Institute Mount Sinai School of Medicine New York NY United States
University of Florence Florence Italy
University of Glasgow Glasgow United Kingdom
University of Illinois at Urbana Champaign Champaign IL United States
University of Maryland BioPark Innovation Center KoDiscovery Baltimore MD United States
University of Windsor Windsor Ontario Canada
Washington State University College of Pharmacy Spokane WA United States
White River Junction Veterans Affairs Medical Center White River Junction VT United States
Winship Cancer Institute of Emory University Atlanta GA United States
Citace poskytuje Crossref.org
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- $a Block, Keith I $u Block Center for Integrative Cancer Treatment, Skokie, IL, United States. Electronic address: drblock@blockmedical.com.
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- $a Designing a broad-spectrum integrative approach for cancer prevention and treatment / $c KI. Block, C. Gyllenhaal, L. Lowe, A. Amedei, AR. Amin, A. Amin, K. Aquilano, J. Arbiser, A. Arreola, A. Arzumanyan, SS. Ashraf, AS. Azmi, F. Benencia, D. Bhakta, A. Bilsland, A. Bishayee, SW. Blain, PB. Block, CS. Boosani, TE. Carey, A. Carnero, M. Carotenuto, SC. Casey, M. Chakrabarti, R. Chaturvedi, GZ. Chen, H. Chen, S. Chen, YC. Chen, BK. Choi, MR. Ciriolo, HM. Coley, AR. Collins, M. Connell, S. Crawford, CS. Curran, C. Dabrosin, G. Damia, S. Dasgupta, RJ. DeBerardinis, WK. Decker, P. Dhawan, AM. Diehl, JT. Dong, QP. Dou, JE. Drew, E. Elkord, B. El-Rayes, MA. Feitelson, DW. Felsher, LR. Ferguson, C. Fimognari, GL. Firestone, C. Frezza, H. Fujii, MM. Fuster, D. Generali, AG. Georgakilas, F. Gieseler, M. Gilbertson, MF. Green, B. Grue, G. Guha, D. Halicka, WG. Helferich, P. Heneberg, P. Hentosh, MD. Hirschey, LJ. Hofseth, RF. Holcombe, K. Honoki, HY. Hsu, GS. Huang, LD. Jensen, WG. Jiang, LW. Jones, PA. Karpowicz, WN. Keith, SP. Kerkar, GN. Khan, M. Khatami, YH. Ko, O. Kucuk, RJ. Kulathinal, NB. Kumar, BS. Kwon, A. Le, MA. Lea, HY. Lee, T. Lichtor, LT. Lin, JW. Locasale, BL. Lokeshwar, VD. Longo, CA. Lyssiotis, KL. MacKenzie, M. Malhotra, M. Marino, ML. Martinez-Chantar, A. Matheu, C. Maxwell, E. McDonnell, AK. Meeker, M. Mehrmohamadi, K. Mehta, GA. Michelotti, RM. Mohammad, SI. Mohammed, DJ. Morre, V. Muralidhar, I. Muqbil, MP. Murphy, GP. Nagaraju, R. Nahta, E. Niccolai, S. Nowsheen, C. Panis, F. Pantano, VR. Parslow, G. Pawelec, PL. Pedersen, B. Poore, D. Poudyal, S. Prakash, M. Prince, L. Raffaghello, JC. Rathmell, WK. Rathmell, SK. Ray, J. Reichrath, S. Rezazadeh, D. Ribatti, L. Ricciardiello, RB. Robey, F. Rodier, HP. Rupasinghe, GL. Russo, EP. Ryan, AK. Samadi, I. Sanchez-Garcia, AJ. Sanders, D. Santini, M. Sarkar, T. Sasada, NK. Saxena, RE. Shackelford, HM. Shantha Kumara, D. Sharma, DM. Shin, D. Sidransky, MD. Siegelin, E. Signori, N. Singh, S. Sivanand, D. Sliva, C. Smythe, C. Spagnuolo, DM. Stafforini, J. Stagg, PR. Subbarayan, T. Sundin, WH. Talib, SK. Thompson, PT. Tran, H. Ungefroren, MG. Vander Heiden, V. Venkateswaran, DS. Vinay, PJ. Vlachostergios, Z. Wang, KE. Wellen, RL. Whelan, ES. Yang, H. Yang, X. Yang, P. Yaswen, C. Yedjou, X. Yin, J. Zhu, M. Zollo,
- 520 9_
- $a 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 "broad-spectrum" 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.
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- 700 1_
- $a Amin, A R M Ruhul $u Winship Cancer Institute of Emory University, Atlanta, GA, United States. $7 gn_A_00005570
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Bilsland, Alan $u University of Glasgow, Glasgow, United Kingdom.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Lin, Liang-Tzung $u Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
- 700 1_
- $a Locasale, Jason W $u Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
- 700 1_
- $a Lokeshwar, Bal L $u Department of Medicine, Georgia Regents University Cancer Center, Augusta, GA, United States.
- 700 1_
- $a Longo, Valter D $u Andrus Gerontology Center, Division of Biogerontology, University of Southern California, Los Angeles, CA, United States.
- 700 1_
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- 700 1_
- $a MacKenzie, Karen L $u Children's Cancer Institute Australia, Kensington, New South Wales, Australia.
- 700 1_
- $a Malhotra, Meenakshi $u Department of Biomedical Engineering, McGill University, Montréal, Canada.
- 700 1_
- $a Marino, Maria $u Department of Science, University Roma Tre, Rome, Italy.
- 700 1_
- $a Martinez-Chantar, Maria L $u Metabolomic Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Technology Park of Bizkaia, Bizkaia, Spain.
- 700 1_
- $a Matheu, Ander $u Biodonostia Institute, Gipuzkoa, Spain.
- 700 1_
- $a Maxwell, Christopher $u Department of Pediatrics, University of British Columbia, Michael Cuccione Childhood Cancer Research Program, Child and Family Research Institute, Vancouver, British Columbia, Canada.
- 700 1_
- $a McDonnell, Eoin $u Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, United States.
- 700 1_
- $a Meeker, Alan K $u Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
- 700 1_
- $a Mehrmohamadi, Mahya $u Field of Genetics, Genomics, and Development, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States.
- 700 1_
- $a Mehta, Kapil $u Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
- 700 1_
- $a Michelotti, Gregory A $u Department of Medicine, Duke University Medical Center, Durham, NC, United States.
- 700 1_
- $a Mohammad, Ramzi M $u Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
- 700 1_
- $a Mohammed, Sulma I $u Department of Comparative Pathobiology, Purdue University Center for Cancer Research, West Lafayette, IN, United States.
- 700 1_
- $a Morre, D James $u Mor-NuCo, Inc, Purdue Research Park, West Lafayette, IN, United States.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Nowsheen, Somaira $u Medical Scientist Training Program, Mayo Graduate School, Mayo Medical School, Mayo Clinic, Rochester, MN, United States.
- 700 1_
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- 700 1_
- $a Pantano, Francesco $u Medical Oncology Department, University Campus Bio-Medico, Rome, Italy.
- 700 1_
- $a Parslow, Virginia R $u Discipline of Nutrition and Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand.
- 700 1_
- $a Pawelec, Graham $u Center for Medical Research, University of Tübingen, Tübingen, Germany.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Russo, Gian Luigi $u Institute of Food Sciences National Research Council, Avellino, Italy.
- 700 1_
- $a Ryan, Elizabeth P $u Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, United States.
- 700 1_
- $a Samadi, Abbas K $u Sanus Biosciences, San Diego, CA, United States.
- 700 1_
- $a Sanchez-Garcia, Isidro $u Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain.
- 700 1_
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- 700 1_
- $a Santini, Daniele $u Medical Oncology Department, University Campus Bio-Medico, Rome, Italy.
- 700 1_
- $a Sarkar, Malancha $u Department of Biology, University of Miami, Miami, FL, United States.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Sliva, Daniel $u DSTest Laboratories, Purdue Research Park, Indianapolis, IN, United States.
- 700 1_
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- 700 1_
- $a Spagnuolo, Carmela $u Institute of Food Sciences National Research Council, Avellino, Italy.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Sundin, Tabetha $u Department of Molecular Diagnostics, Sentara Healthcare, Norfolk, VA, United States.
- 700 1_
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- 700 1_
- $a Thompson, Sarah K $u Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia.
- 700 1_
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- 700 1_
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- 700 1_
- $a Vander Heiden, Matthew G $u Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Yaswen, Paul $u Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, CA, United States.
- 700 1_
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- 700 1_
- $a Yin, Xin $u Medicine and Research Services, Veterans Affairs San Diego Healthcare System & University of California, San Diego, CA, United States.
- 700 1_
- $a Zhu, Jiyue $u Washington State University College of Pharmacy, Spokane, WA, United States.
- 700 1_
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