| Development and characterization of a novel in vivo model of carcinoid syndrome. | |
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MedLine Citation:
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PMID: 19336516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Carcinoid syndrome, characterized by flushing, diarrhea, and valvular heart disease, can occur following carcinoid tumor metastasis to the liver and systemic release of bioactive hormones into the systemic circulation. Treatment of this devastating disease is hampered by the lack of an in vivo model that recapitulates the clinical syndrome. EXPERIMENTAL DESIGN: Here, we have injected BON cells, a novel human carcinoid cell line established in our laboratory, into the spleens of athymic nude mice to establish liver metastases. RESULTS: The majority of mice injected intrasplenically with BON cells developed significant increases in plasma serotonin and urine 5-hydroxyindoleacetic acid, and several mice exhibited mesenteric fibrosis, diarrhea, and fibrotic cardiac valvular disease reminiscent of carcinoid syndrome by both echocardiographic and histopathologic evaluation. Mice pretreated with octreotide, a long-acting somatostatin analogue, or bevacizumab, a vascular endothelial growth factor inhibitor, developed fewer liver metastases and manifestations of carcinoid syndrome, including valvular heart disease. CONCLUSION: We have provided an important in vivo model to further delineate novel treatment modalities for carcinoid syndrome that will also be useful to elucidate the factors contributing to the sequelae of carcinoid disease (e.g., mesenteric fibrosis and valvular heart disease). |
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Authors:
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Lindsey N Jackson; L Andy Chen; Shawn D Larson; Scott R Silva; Piotr G Rychahou; Paul J Boor; Jing Li; Gilberto Defreitas; W Lane Stafford; Courtney M Townsend; B Mark Evers |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-03-31 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 15 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-16 Completed Date: 2009-06-04 Revised Date: 2011-04-13 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 2747-55 Citation Subset: IM |
Affiliation:
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Department of Surgery and Pathology, The University of Texas Medical Branch, Galveston, Texas 77555-0536, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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therapeutic use Animals Antibodies, Monoclonal / therapeutic use Antineoplastic Agents, Hormonal / therapeutic use Carcinoid Heart Disease / pathology, prevention & control Cell Line, Tumor Disease Models, Animal Humans Hydroxyindoleacetic Acid / blood Liver Neoplasms / prevention & control, secondary* Male Malignant Carcinoid Syndrome / drug therapy, metabolism*, pathology* Mice Mice, Nude Octreotide / therapeutic use Serotonin / blood |
| Grant Support | |
ID/Acronym/Agency:
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P01 DK035608-220001/DK/NIDDK NIH HHS; P01 DK35608/DK/NIDDK NIH HHS; R01 CA104748/CA/NCI NIH HHS; R01 CA104748-05/CA/NCI NIH HHS; R01 DK048498-13/DK/NIDDK NIH HHS; R01 DK48489/DK/NIDDK NIH HHS; R37 AG010885-17/AG/NIA NIH HHS; R37 AG10885/AG/NIA NIH HHS; T32 DK007639-16/DK/NIDDK NIH HHS; T32DK07639/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antineoplastic Agents, Hormonal; 0/bevacizumab; 50-67-9/Serotonin; 54-16-0/Hydroxyindoleacetic Acid; 83150-76-9/Octreotide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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