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tumour, mice, data, fig, cold, bat, cancer, exposure, growth, glucose, pubmed, group, tumours, extended, analysis, article, cells, scholar, google, crc, cell, uptake, tumourbearing, cas, temperature, suppression, performed, metabolism, ucp, activation, source, human, mouse, tissue, conditions, signals, metabolic, nature, glycolysis, central, tissues, feeding, subcutaneous, positive, ffdg, adipose, staining, scale, samples, findings,

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nature portfolio privacy policy siemens medical solutions advertising scandinavia-japan sasakawa foundation 18f-fluoro-2-deoxy-d-glucose brown-fat-mediated tumour suppression rabbit anti-mouse cleaved-caspase-3 cdna libraries mmtv-pymt tumour-bearing mice inveon animal-pet-ct system body mass index social media library construction cold-exposure-induced tumour suppression cold-mitigated 18f-fdg uptake feeding crc-tumour-bearing mice bat-removed mmtv-pymt mice species-matched secondary antibodies crc-tumour-bearing mice relative high-glucose–glut1 signalling axis reprints crc-tumour-bearing mice treated rabbit anti-mouse cd45 vegfr2-mediated vascular dilation ucp1−/− crc-tumour-bearing mice cold-induced antitumor activity fatty-acid-dependent ucp1 uncoupling nature 565 nature 572 nature 608 nature cold-exposed tumour-bearing mice cold-exposure tumour-bearing mice rabbit anti-ca9 antibodies rna-seq multi-omics analyses rabbit anti-mouse iba1 calcium overload-induced dysfunction rabbit anti-mouse ki-67 bat-activation-manipulated tumour growth rabbit anti-mouse ucp1 overseas research fellowships european research council proton-linked monocarboxylate transporter cold-induced tumour suppression swedish research council 30 °c-exposed tumour-bearing mice microvolume uv-vis spectrophotometer rabbit anti-mouse fsp1 cold-triggered tumour formation

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         headline:Brown-fat-mediated tumour suppression by cold-altered global metabolism
         description:Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1–6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1—the key mediator for BAT-thermogenesis—ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers. Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.
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      headline:Brown-fat-mediated tumour suppression by cold-altered global metabolism
      description:Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1–6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1—the key mediator for BAT-thermogenesis—ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers. Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.
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               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
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               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
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               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
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            address:
               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
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      name:Xu Jing
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            address:
               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
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            name:People’s Hospital of Hangzhou Medical College
            address:
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      name:Masahito Yoshihara
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      affiliation:
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            address:
               name:Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
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      name:Lili Qu
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      affiliation:
            name:Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University
            address:
               name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
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      affiliation:
            name:Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University
            address:
               name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
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            type:Organization
      name:Yuguo Chen
      url:http://orcid.org/0000-0001-9501-2546
      affiliation:
            name:Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University
            address:
               name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Yihai Cao
      url:http://orcid.org/0000-0003-1308-0065
      affiliation:
            name:Karolinska Institutet
            address:
               name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vison and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China
      name:Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
      name:Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
      name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
      name:Department of Nutrition and Metabolism, Tokushima University Graduate School, Tokushima, Japan
      name:Department of Nutrition and Metabolism, Tokushima University Graduate School, Tokushima, Japan
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
      name:Department of Head and Neck Surgery, Center of Otolaryngology-Head and Neck Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
      name:Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
      name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
      name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
      name:Department Nuclear Medicine, Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China
      name:Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden

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