The DOI matches its Crossref record; 46 of the 49 references it cites were found in a registry or an index.
Expression of Insulin-Like Growth Factor-II and Its Receptor in Pediatric and Adult Adrenocortical Tumors
Abstract
BACKGROUND: Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas. OBJECTIVES: The objective of the study was to analyze expression of IGF-II and its receptor (IGF-IR) in pediatric and adult adrenocortical tumors and the effects of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenocortical tumor cells. PATIENTS: Fifty-seven adrenocortical tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were studied. METHODS: Gene expression was determined by quantitative real-time PCR. Cell proliferation and apoptosis were analyzed in NCI H295 cells and a new cell line established from a pediatric adrenocortical adenoma. RESULTS: IGF-II transcripts were overexpressed in both pediatric adrenocortical carcinomas and adenomas. Otherwise, IGF-II was mainly overexpressed in adult adrenocortical carcinomas (270.5 +/- 130.2 vs. 16.1 +/- 13.3; P = 0.0001). IGF-IR expression was significantly higher in pediatric adrenocortical carcinomas than adenomas (9.1 +/- 3.1 vs. 2.6 +/- 0.3; P = 0.0001), whereas its expression was similar in adult adrenocortical carcinomas and adenomas. IGF-IR expression was a predictor of metastases in pediatric adrenocortical tumors in univariate analysis (hazard ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01). Furthermore, NVP-AEW541 blocked cell proliferation in a dose- and time-dependent manner in both cell lines through a significant increase of apoptosis. CONCLUSION: IGF-IR overexpression was a biomarker of pediatric adrenocortical carcinomas. Additionally, a selective IGF-IR kinase inhibitor had antitumor effects in adult and pediatric adrenocortical tumor cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenocortical carcinoma.
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“In an NCI-H295 xenograft mouse model, IGF pathway inhibition by the small-molecule inhibitor NVP-AEW541 and the monoclonal IGF-1R antibody IMCA12 showed an antitumor effect.”
From Adrenocortical carcinoma (2014) · cites this paper as [223]
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“Furthermore, the combined treatment of NCI-H295 cells with IGF-1R antagonists and mitotane resulted in a synergistic antiproliferative effect in vitro and in vivo in tumor xenografts (223, 227).”
From Adrenocortical carcinoma (2014) · cites this paper as [223]
Citations
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Metadata
- Authors
- Almeida, M. Q., Fragoso, M. C. B. V., Lotfi, C. F. P., Santos, M. G., Nishi, M. Y., Costa, M. H. S., Lerario, A. M., Maciel, C. C., Mattos, G. E., Jorge, A. A. L., Mendonca, B. B., & Latronico, A. C.
- Affiliations
- Universidade de São Paulo (BR)
- Unidade de Endocrinologia do Desenvolvimento (M.Q.A., M.C.B.V.F., M.G.S., M.Y.N., M.H.S.C., A.M.L., A.A.L.J., B.B.M., A.C.L.), Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05403-900 São Paulo, Brazil
- Corresponding author
- Almeida, Madson Q.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-09-01
- Volume
- 93
- Issue
- 9
- Pages
- 3524-3531
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2095417135
- Cited by
- 176
- References
- 49
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 13 · 2019: 6 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 7 · 2012: 17
- FWCI
- 16.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- insulin-like growth factor II, IGF-II receptor, adrenocortical tumors, pediatric adrenocortical carcinoma, adrenal adenoma, NVP-AEW541, metastasis biomarkers, cell proliferation, apoptosis, cancer therapy
- MeSH terms
- Adenoma, Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Carcinoma, Child, Child, Preschool, Female, Humans, Infant, Insulin-Like Growth Factor II, Male, Middle Aged, Neoplasm Metastasis, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Receptor, IGF Type 2
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