Tags

Type your tag names separated by a space and hit enter

Preclinical in vivo study of new insulin-like growth factor-I receptor--specific inhibitor in Ewing's sarcoma.
Clin Cancer Res. 2007 Feb 15; 13(4):1322-30.CC

Abstract

PURPOSE

Small-molecule insulin-like growth factor-I receptor (IGF-IR)-specific tyrosine kinase inhibitors have been recently proposed as clinically viable approaches to impair IGF-IR functions. NVP-AEW541 seems one of the most promising agents. In this article, we point out its effects against migration, metastasis, vasculogenicity, and angiogenesis of Ewing's sarcoma cells.

EXPERIMENTAL DESIGN

In vivo NVP-AEW541 effectiveness was analyzed against TC-71 Ewing's sarcoma growth and bone metastasis after cell inoculation in athymic mice. Activity of the compound against angiogenesis as well as vasculogenesis properties was also considered both in vitro and in xenografts. Serum glucose, urea, transaminase levels, as well as other signs of distress were checked in mice treated with the IGF-IR inhibitor.

RESULTS

Significant inhibition of migration, metastasis, vasculogenicity, and angiogenesis was recorded after treatment of Ewing's sarcoma cells with NVP-AEW541. In view of its application and the similarity of insulin receptor and IGF-IR, diabetogenic side effects were considered. We observed a significant decrease of glucose blood serum due to increased glucose uptake at cellular level and an increase in urea concentration. Moreover, an initial weight loss was observed in mice bearing tumors. All these side effects were similarly detected in mice treated with vincristine. After the first days of treatment, all the animals started to grow again.

CONCLUSIONS

Our results globally reinforce the idea that IGF-IR inhibitor NVP-AEW541 could have a role in future combined therapies and suggest to pursue a thorough molecular analysis of the metabolic activity of IGF-IR to avoid possible side effects of these inhibitors.

Authors+Show Affiliations

Laboratory of Oncologic Research, Istituti Ortopedici Rizzoli, Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17317844

Citation

Manara, Maria C., et al. "Preclinical in Vivo Study of New Insulin-like Growth factor-I Receptor--specific Inhibitor in Ewing's Sarcoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 13, no. 4, 2007, pp. 1322-30.
Manara MC, Landuzzi L, Nanni P, et al. Preclinical in vivo study of new insulin-like growth factor-I receptor--specific inhibitor in Ewing's sarcoma. Clin Cancer Res. 2007;13(4):1322-30.
Manara, M. C., Landuzzi, L., Nanni, P., Nicoletti, G., Zambelli, D., Lollini, P. L., Nanni, C., Hofmann, F., García-Echeverría, C., Picci, P., & Scotlandi, K. (2007). Preclinical in vivo study of new insulin-like growth factor-I receptor--specific inhibitor in Ewing's sarcoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 13(4), 1322-30.
Manara MC, et al. Preclinical in Vivo Study of New Insulin-like Growth factor-I Receptor--specific Inhibitor in Ewing's Sarcoma. Clin Cancer Res. 2007 Feb 15;13(4):1322-30. PubMed PMID: 17317844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preclinical in vivo study of new insulin-like growth factor-I receptor--specific inhibitor in Ewing's sarcoma. AU - Manara,Maria C, AU - Landuzzi,Lorena, AU - Nanni,Patrizia, AU - Nicoletti,Giordano, AU - Zambelli,Diana, AU - Lollini,Pier Luigi, AU - Nanni,Cristina, AU - Hofmann,Francesco, AU - García-Echeverría,Carlos, AU - Picci,Piero, AU - Scotlandi,Katia, PY - 2007/2/24/pubmed PY - 2007/7/19/medline PY - 2007/2/24/entrez SP - 1322 EP - 30 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 13 IS - 4 N2 - PURPOSE: Small-molecule insulin-like growth factor-I receptor (IGF-IR)-specific tyrosine kinase inhibitors have been recently proposed as clinically viable approaches to impair IGF-IR functions. NVP-AEW541 seems one of the most promising agents. In this article, we point out its effects against migration, metastasis, vasculogenicity, and angiogenesis of Ewing's sarcoma cells. EXPERIMENTAL DESIGN: In vivo NVP-AEW541 effectiveness was analyzed against TC-71 Ewing's sarcoma growth and bone metastasis after cell inoculation in athymic mice. Activity of the compound against angiogenesis as well as vasculogenesis properties was also considered both in vitro and in xenografts. Serum glucose, urea, transaminase levels, as well as other signs of distress were checked in mice treated with the IGF-IR inhibitor. RESULTS: Significant inhibition of migration, metastasis, vasculogenicity, and angiogenesis was recorded after treatment of Ewing's sarcoma cells with NVP-AEW541. In view of its application and the similarity of insulin receptor and IGF-IR, diabetogenic side effects were considered. We observed a significant decrease of glucose blood serum due to increased glucose uptake at cellular level and an increase in urea concentration. Moreover, an initial weight loss was observed in mice bearing tumors. All these side effects were similarly detected in mice treated with vincristine. After the first days of treatment, all the animals started to grow again. CONCLUSIONS: Our results globally reinforce the idea that IGF-IR inhibitor NVP-AEW541 could have a role in future combined therapies and suggest to pursue a thorough molecular analysis of the metabolic activity of IGF-IR to avoid possible side effects of these inhibitors. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17317844/Preclinical_in_vivo_study_of_new_insulin_like_growth_factor_I_receptor__specific_inhibitor_in_Ewing's_sarcoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17317844 DB - PRIME DP - Unbound Medicine ER -