Document Detail


Development and characterization of a novel in vivo model of carcinoid syndrome.
MedLine Citation:
PMID:  19336516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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).
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-31
Journal Detail:
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:
Created Date:  2009-04-16     Completed Date:  2009-06-04     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2747-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / therapeutic use
Animals
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
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:
P01 DK035608/DK/NIDDK NIH HHS; P01 DK035608-220001/DK/NIDDK NIH HHS; P01 DK35608/DK/NIDDK NIH HHS; R01 CA104748/CA/NCI NIH HHS; R01 CA104748/CA/NCI NIH HHS; R01 CA104748-05/CA/NCI NIH HHS; R01 DK048498/DK/NIDDK NIH HHS; R01 DK048498-13/DK/NIDDK NIH HHS; R01 DK48489/DK/NIDDK NIH HHS; R37 AG010885/AG/NIA NIH HHS; R37 AG010885-17/AG/NIA NIH HHS; R37 AG10885/AG/NIA NIH HHS; T32 DK007639/DK/NIDDK NIH HHS; T32 DK007639-16/DK/NIDDK NIH HHS; T32DK07639/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents, Hormonal; 2S9ZZM9Q9V/bevacizumab; 333DO1RDJY/Serotonin; 54-16-0/Hydroxyindoleacetic Acid; RWM8CCW8GP/Octreotide
Comments/Corrections

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