| Muscarinic receptor agonists and antagonists: effects on cancer. | |
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MedLine Citation:
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PMID: 22222710 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Many epithelial and endothelial cells express a cholinergic autocrine loop in which acetylcholine acts as a growth factor to stimulate cell growth. Cancers derived from these tissues similarly express a cholinergic autocrine loop and ACh secreted by the cancer or neighboring cells interacts with M3 muscarinic receptors expressed on the cancer cells to stimulate tumor growth. Primary proliferative pathways involve MAPK and Akt activation. The ability of muscarinic agonists to stimulate, and M3 antagonists to inhibit tumor growth has clearly been demonstrated for lung and colon cancer. The ability of muscarinic agonists to stimulate growth has been shown for melanoma, pancreatic, breast, ovarian, prostate and brain cancers, suggesting that M3 antagonists will also inhibit growth of these tumors as well. As yet no clinical trials have proven the efficacy of M3 antagonists as cancer therapeutics, though the widespread clinical use and low toxicity of M3 antagonists support the potential role of these drugs as adjuvants to current cancer therapies. |
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Authors:
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Eliot R Spindel |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Handbook of experimental pharmacology Volume: - ISSN: 0171-2004 ISO Abbreviation: Handb Exp Pharmacol Publication Date: 2012 |
Date Detail:
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Created Date: 2012-01-06 Completed Date: 2012-04-25 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 7902231 Medline TA: Handb Exp Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 451-68 Citation Subset: IM |
Affiliation:
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Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. Spindele@ohsu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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metabolism Animals Antineoplastic Agents / pharmacology* Autocrine Communication / drug effects Cell Proliferation / drug effects Chemotherapy, Adjuvant Humans Muscarinic Agonists / pharmacology* Muscarinic Antagonists / pharmacology* Neoplasms / drug therapy*, metabolism Receptors, Muscarinic / drug effects*, metabolism Signal Transduction / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL087710/HL/NHLBI NIH HHS; R01 CA151601/CA/NCI NIH HHS; R01 HL087710/HL/NHLBI NIH HHS; RR00163/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Muscarinic Agonists; 0/Muscarinic Antagonists; 0/Receptors, Muscarinic; 51-84-3/Acetylcholine |
| Comments/Corrections | |
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