WordNet

act so as to bring into existence; "effect a change"
a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of the anesthetic"
(of a law) having legal validity; "the law is still in effect" (同)force
the central meaning or theme of a speech or literary work (同)essence, burden, core, gist
an impression (especially one that is artificial or contrived); "he just did it for effect"
produce; "The scientists set up a shock wave" (同)effectuate, set_up
German art historian (1866-1929) (同)Aby Warburg, Aby Moritz Warburg
German biochemist who pioneered the use of chemical techniques in biological investigations; noted for studies of cellular respiration (1883-1970) (同)Otto Heinrich Warburg
property of a personal character that is portable but not used in business; "she left some of her personal effects in the house"; "I watched over their effects until they returned" (同)personal_effects

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〈C〉〈U〉『結果』 / 〈C〉〈U〉(…への)『効果』,効きめ,影響《+『on』(『upon』)+『名』》 / 〈C〉(色・音・形などの)印象,感銘 / 《複数形で》品物;身の回り品;動産,財産 / (結果として)…‘を'『もたらす』;〈目的など〉‘を'果たす,遂行する

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/30 20:55:19」(JST)

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The phrase "Warburg effect" is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.

Plant physiology

In plant physiology, the Warburg effect is the inhibition of carbon dioxide fixation, and subsequently of photosynthesis, by high oxygen concentrations. The oxygenase activity of RuBisCO, which initiates the process of photorespiration, largely accounts for this effect.

Oncology

Basis

In oncology, the Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria as in most normal cells.^[1]^[2] The latter process is aerobic (uses oxygen). Malignant, rapidly growing tumor cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful.

Otto Warburg postulated this change in metabolism is the fundamental cause of cancer,^[3] a claim now known as the Warburg hypothesis. Today, mutations in oncogenes and tumor suppressor genes are known to be responsible for malignant transformation.^[4]^[5]

Use in diagnosis

The Warburg effect has important medical applications, as high aerobic glycolysis by malignant tumors is used clinically to diagnose and monitor treatment responses of cancers by imaging uptake of 2-¹⁸F-2-deoxyglucose (FDG) (a radioactive modified hexokinase substrate) with positron emission tomography (PET).^[6]^[7]

Possible explanations of the effect

The Warburg effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumors, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's apoptosis program which would otherwise kill cancerous cells. It may also be an effect associated with cell proliferation. Since glycolysis provides most of the building blocks required for cell proliferation, cancer cells (and normal proliferating cells) have been proposed to need to activate glycolysis, despite the presence of oxygen, to proliferate .^[8] Evidence attributes some of the high aerobic glycolytic rates to an overexpressed form of mitochondrially bound hexokinase^[9] responsible for driving the high glycolytic activity.

In March 2008, Lewis C. Cantley and colleagues at the Harvard Medical School announced they had identified the enzyme that gave rise to the Warburg effect.^[10]^[11] The researchers stated tumor M2-PK, a form of the pyruvate kinase enzyme, is produced in all rapidly dividing cells, and is responsible for enabling cancer cells to consume glucose at an accelerated rate; on forcing the cells to switch to pyruvate kinase's alternative form by inhibiting the production of tumor M2-PK, their growth was curbed. The researchers acknowledged the fact that the exact chemistry of glucose metabolism was likely to vary across different forms of cancer; but PKM2 was identified in all of the cancer cells they had tested. This enzyme form is not usually found in healthy tissue, though it is apparently necessary when cells need to multiply quickly, e.g. in healing wounds or hematopoiesis.

Glycolytic inhibitors

Many substances have been developed which inhibit glycolysis, and such inhibitors are currently the subject of intense research as anticancer agents,^[12] including SB-204990, 2-deoxy-D-glucose (2DG), 3-bromopyruvate (3-BrPA, bromopyruvic acid, or bromopyruvate), 3-BrOP, 5-thioglucose and dichloroacetic acid (DCA). Clinical trials are ongoing for 2-DG and DCA.^[13]

DCA, a small-molecule inhibitor of mitochondrial pyruvate dehydrogenase kinase, "downregulates" glycolysis in vitro and in vivo. Researchers at the University of Alberta theorized in 2007 that DCA might have therapeutic benefits against many types of cancers.^[14]^[15]

Alternative models

A model called the reverse Warburg effect describes cells producing energy by glycolysis, but were not tumor cells, but stromal fibroblasts. Although the Warburg effect would exist in certain cancer types potentially, it highlighted the need for a closer look at tumor metabolism.^[16]^[17]

References

^ Gatenby RA; Gillies RJ (2004). "Why do cancers have high aerobic glycolysis?". Nature Reviews Cancer 4 (11). PMID 15516961.
^ Kim JW, Dang CV (2006). "Cancer's molecular sweet tooth and the Warburg effect". Cancer Res. 66 (18): 8927–8930. doi:10.1158/0008-5472.CAN-06-1501. PMID 16982728. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16982728.
^ Warburg O (1956). "On the origin of cancer cells". Science 123 (3191): 309–314. Bibcode 1956Sci...123..309W. doi:10.1126/science.123.3191.309. PMID 13298683.
^ Bertram JS (2000). "The molecular biology of cancer". Mol. Aspects Med. 21 (6): 167–223. doi:10.1016/S0098-2997(00)00007-8. PMID 11173079.
^ Grandér D (1998). "How do mutated oncogenes and tumor suppressor genes cause cancer?". Med. Oncol. 15 (1): 20–26. doi:10.1007/BF02787340. PMID 9643526.
^ "PET Scan: PET Scan Info Reveals ...". http://www.petscaninfo.com/. Retrieved December 5, 2005.
^ "4320139 549..559". http://biogenomica.com/PDFs/PauwelsPETandHexokinase.pdf. Retrieved December 5, 2005.
^ Lopez-Lazaro M (2008). "The Warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen?". Anticancer Agents Med. Chem. 8 (3): 305–312. doi:10.2174/187152008783961932. PMID 18393789.
^ Bustamante E, Pedersen PL (September 1977). "High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase". Proc. Natl. Acad. Sci. U.S.A. 74 (9): 3735–3739. Bibcode 1977PNAS...74.3735B. doi:10.1073/pnas.74.9.3735. PMC 431708. PMID 198801. http://www.pnas.org/cgi/reprint/74/9/3735.
^ Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC (2008). "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth". Nature 452 (7184): 230–233. Bibcode 2008Natur.452..230C. doi:10.1038/nature06734. PMID 18337823.
^ Pedersen PL (2007). "Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen". J. Bioenerg. Biomembr. 39 (3): 211–222. doi:10.1007/s10863-007-9094-x. PMID 17879147.
^ Pelicano H, Martin DS, Xu RH, Huang P (2006). "Glycolysis inhibition for anticancer treatment". Oncogene 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078.
^ See ClinicalTrials.gov.
^ Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED (2007). "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth". Cancer Cell 11 (1): 37–51. doi:10.1016/j.ccr.2006.10.020. PMID 17222789.
^ Pan JG, Mak TW (2007). "Metabolic targeting as an anticancer strategy: dawn of a new era?". Sci. STKE 2007 (381): pe14–pe14. doi:10.1126/stke.3812007pe14. PMID 17426345.
^ Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (December 2009). "The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma". Cell Cycle 8 (23): 3984–4001. doi:10.4161/cc.8.23.10238. PMID 19923890.
^ Alfarouk KO, Shayoub ME, Muddathir AK, Elhassan GO, Bashir AH. Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity). Cancers. 2011; 3(3):3002-3017.

UpToDate Contents

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English Journal

Glucose transporter-1 expression in CD133+ laryngeal carcinoma Hep-2 cells.

Chen XH, Bao YY, Zhou SH, Wang QY, Wei Y, Fan J.SourceDepartment of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Molecular medicine reports.Mol Med Rep.2013 Dec;8(6):1695-700. doi: 10.3892/mmr.2013.1740. Epub 2013 Oct 18.
CD133 is a useful putative marker of cancer stem cells (CSCs) in human laryngeal tumors. Numerous studies have demonstrated that CD133+ CSCs possess higher clonogenicity, invasiveness and tumorigenesis compared with CD133- cells. Recently, interest in the Warburg effect in the microenvironment of CS
PMID 24146103

Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells.

Zhai X, Yang Y, Wan J, Zhu R, Wu Y.SourceDepartment of Radiation Oncology, The First Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Oncology reports.Oncol Rep.2013 Dec;30(6):2983-91. doi: 10.3892/or.2013.2735. Epub 2013 Sep 19.
An elevated rate of glucose consumption and the dependency on aerobic glycolysis for ATP generation have long been observed in cancer cells, a phenomenon known as the Warburg effect. the altered energy metabolism in cancer cells provides an attractive opportunity for developing novel cancer therapeu
PMID 24064966

Characterizing the metabolic heterogeneity in human breast cancer xenografts by 3D high resolution fluorescence imaging.

Xu HN, Zheng G, Tchou J, Nioka S, Li LZ.SourceMolecular Imaging Laboratory, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA ; Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, USA.
SpringerPlus.Springerplus.2013 Dec;2(1):73. Epub 2013 Feb 28.
We previously reported that tumor mitochondrial redox state and its heterogeneity distinguished between the aggressive and the indolent breast cancer xenografts, suggesting novel metabolic indices as biomarkers for predicting tumor metastatic potential. Additionally, we reported that the identified
PMID 23543813