Abstract
Cancer research relies heavily on murine models for evaluating the anti-tumour efficacy of therapies. Here we show that the sensitivity of several pancreatic tumour models to cytotoxic therapies is significantly increased when mice are housed at a thermoneutral ambient temperature of 30 °C compared with the standard temperature of 22 °C. Further, we find that baseline levels of norepinephrine as well as the levels of several anti-apoptotic molecules are elevated in tumours from mice housed at 22 °C. The sensitivity of tumours to cytotoxic therapies is also enhanced by administering a β-adrenergic receptor antagonist to mice housed at 22 °C. These data demonstrate that standard housing causes a degree of cold stress sufficient to impact the signalling pathways related to tumour-cell survival and affect the outcome of pre-clinical experiments. Furthermore, these data highlight the significant role of host physiological factors in regulating the sensitivity of tumours to therapy.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adrenergic beta-Agonists / pharmacology
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Albumins / pharmacology
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Line, Tumor
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Cisplatin / pharmacology
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Drug Resistance, Neoplasm / genetics*
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Gene Expression Regulation, Neoplastic*
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Humans
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Isoproterenol / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, SCID
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Paclitaxel / pharmacology
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Adrenergic, beta-2 / genetics*
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Receptors, Adrenergic, beta-2 / metabolism
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Signal Transduction
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Stress, Physiological
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TNF-Related Apoptosis-Inducing Ligand / pharmacology
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Temperature
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Xenograft Model Antitumor Assays
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bcl-X Protein / genetics
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bcl-X Protein / metabolism
Substances
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130-nm albumin-bound paclitaxel
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Adrenergic beta-Agonists
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Albumins
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Antineoplastic Agents
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Bcl2l1 protein, mouse
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Adrenergic, beta-2
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TNF-Related Apoptosis-Inducing Ligand
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bcl-X Protein
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Bcl2 protein, mouse
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Isoproterenol
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Paclitaxel
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Cisplatin