Source:http://linkedlifedata.com/resource/pubmed/id/10965887
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2000-9-21
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| pubmed:abstractText |
Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis, as they are often diagnosed late and are usually resistant to chemotherapy. The lack of a suitable animal model for these tumors has been a major obstacle to the evaluation of new therapeutic agents. The aim of this study was to establish and characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line as a model of adrenocortical carcinoma for future therapeutic trials. This cell line was sc injected (6 x 10(6) cells) into nude mice (n = 20). Solid tumors were locally measurable after 45 days at 90% of the inoculation sites. The xenografts were similar histologically to the original adrenocortical carcinoma from which the cell line was derived. The xenografts precisely reproduced the dysregulation of the insulin-like growth factor (IGF) system [overexpression of the IGF-II and IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma. Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was secreted in mouse plasma. We analyzed steroid production (cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, delta4-androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts produced all three class of steroids, with the preferential production of androgens of the delta4 pathway. The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors. It also produces IGFBP-2 and steroids that can be used as tumor markers. This model may therefore be useful for evaluating therapeutic agents.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Somatomedins,
http://linkedlifedata.com/resource/pubmed/chemical/Steroids
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
141
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3165-71
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10965887-Adrenal Cortex Neoplasms,
pubmed-meshheading:10965887-Animals,
pubmed-meshheading:10965887-Antineoplastic Agents,
pubmed-meshheading:10965887-Blotting, Northern,
pubmed-meshheading:10965887-Blotting, Western,
pubmed-meshheading:10965887-Female,
pubmed-meshheading:10965887-Humans,
pubmed-meshheading:10965887-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:10965887-Mice,
pubmed-meshheading:10965887-Mice, Nude,
pubmed-meshheading:10965887-Neoplasm Proteins,
pubmed-meshheading:10965887-Neoplasm Transplantation,
pubmed-meshheading:10965887-RNA, Neoplasm,
pubmed-meshheading:10965887-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10965887-Somatomedins,
pubmed-meshheading:10965887-Steroids,
pubmed-meshheading:10965887-Transplantation, Heterologous,
pubmed-meshheading:10965887-Tumor Cells, Cultured
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| pubmed:year |
2000
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| pubmed:articleTitle |
Establishment and characterization of a human adrenocortical carcinoma xenograft model.
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| pubmed:affiliation |
Laboratoire d'Explorations Fonctionnelles Endocriniennes, INSERM U-515, Hôpital d'Enfants Armand Trousseau, Paris, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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