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      Warburg effect(s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism

      review-article
      Cancer & Metabolism
      BioMed Central
      Biography, Warburg effect, Glycolysis, Respiration, NAD(P)H, Tumor cells, Spectroscopy, Manometer, Hypothesis, Nobel prize

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          Abstract

          Virtually everyone working in cancer research is familiar with the “Warburg effect”, i.e., anaerobic glycolysis in the presence of oxygen in tumor cells. However, few people nowadays are aware of what lead Otto Warburg to the discovery of this observation and how his other scientific contributions are seminal to our present knowledge of metabolic and energetic processes in cells. Since science is a human endeavor, and a scientist is imbedded in a network of social and academic contacts, it is worth taking a glimpse into the biography of Otto Warburg to illustrate some of these influences and the historical landmarks in his life. His creative and innovative thinking and his experimental virtuosity set the framework for his scientific achievements, which were pioneering not only for cancer research. Here, I shall allude to the prestigious family background in imperial Germany; his relationships to Einstein, Meyerhof, Krebs, and other Nobel and notable scientists; his innovative technical developments and their applications in the advancement of biomedical sciences, including the manometer, tissue slicing, and cell cultivation. The latter were experimental prerequisites for the first metabolic measurements with tumor cells in the 1920s. In the 1930s–1940s, he improved spectrophotometry for chemical analysis and developed the optical tests for measuring activities of glycolytic enzymes. Warburg’s reputation brought him invitations to the USA and contacts with the Rockefeller Foundation; he received the Nobel Prize in 1931. World politics and world wars heavily affected Warburg’s scientific survival in Berlin. But, after his second postwar recovery, Warburg’s drive for unraveling the energetic processes of life, both in plants and in tumor cells, continued until his death in 1970. The legacy of Otto Warburg is not only the Warburg effect, but also the identification of the “respiratory ferment” and hydrogen-transferring cofactors and the isolation of glycolytic enzymes. His hypothesis of respiratory damage being the cause of cancer remains to be a provocative scientific issue, along with its implications for cancer treatment and prevention. Warburg is therefore still stimulating our thinking, as documented in a soaring increase in publications citing his name in the context of tumor metabolism.

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          Most cited references25

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Causes and consequences of increased glucose metabolism of cancers.

            In this review we examine the mechanisms (causes) underlying the increased glucose consumption observed in tumors within a teleological context (consequences). In other words, we will ask not only "How do cancers have high glycolysis?" but also, "Why?" We believe that the insights gained from answering the latter question support the conclusion that elevated glucose consumption is a necessary component of carcinogenesis. Specifically we propose that glycolysis is elevated because it produces acid, which provides an evolutionary advantage to cancer cells vis-à-vis normal parenchyma into which they invade.
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              Cancer metabolism: the Warburg effect today.

              One of the first studies on the energy metabolism of a tumour was carried out, in 1922, in the laboratory of Otto Warburg. He established that cancer cells exhibited a specific metabolic pattern, characterized by a shift from respiration to fermentation, which has been later named the Warburg effect. Considerable work has been done since then, deepening our understanding of the process, with consequences for diagnosis and therapy. This review presents facts and perspectives on the Warburg effect for the 21st century. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                +49 89 289-10806 , otto@tum.de , http://www.imetum.tum.de
                Journal
                Cancer Metab
                Cancer Metab
                Cancer & Metabolism
                BioMed Central (London )
                2049-3002
                8 March 2016
                8 March 2016
                2016
                : 4
                : 5
                Affiliations
                Institute of Medical Engineering (IMETUM), Technische Universitaet Muenchen, Boltzmannstr. 11, D-85748 Garching, Germany
                Article
                145
                10.1186/s40170-016-0145-9
                4784299
                26962452
                022e8636-e5dc-4023-930d-3fa03462c628
                © Otto. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 January 2016
                : 29 February 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                biography,warburg effect,glycolysis,respiration,nad(p)h,tumor cells,spectroscopy,manometer,hypothesis,nobel prize

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