Tags

Type your tag names separated by a space and hit enter

Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.
Cancer Res. 2005 Mar 01; 65(5):1897-903.CR

Abstract

Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

Authors+Show Affiliations

Department of Medical Physiopathology, Policlinico Umberto I, University of Rome "La Sapienza", Rome, 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 available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15753388

Citation

Basciani, Sabrina, et al. "Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for in Vitro and in Vivo Activity." Cancer Research, vol. 65, no. 5, 2005, pp. 1897-903.
Basciani S, Brama M, Mariani S, et al. Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Res. 2005;65(5):1897-903.
Basciani, S., Brama, M., Mariani, S., De Luca, G., Arizzi, M., Vesci, L., Pisano, C., Dolci, S., Spera, G., & Gnessi, L. (2005). Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Research, 65(5), 1897-903.
Basciani S, et al. Imatinib Mesylate Inhibits Leydig Cell Tumor Growth: Evidence for in Vitro and in Vivo Activity. Cancer Res. 2005 Mar 1;65(5):1897-903. PubMed PMID: 15753388.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. AU - Basciani,Sabrina, AU - Brama,Marina, AU - Mariani,Stefania, AU - De Luca,Gabriele, AU - Arizzi,Mario, AU - Vesci,Loredana, AU - Pisano,Claudio, AU - Dolci,Susanna, AU - Spera,Giovanni, AU - Gnessi,Lucio, PY - 2005/3/9/pubmed PY - 2005/4/20/medline PY - 2005/3/9/entrez SP - 1897 EP - 903 JF - Cancer research JO - Cancer Res. VL - 65 IS - 5 N2 - Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15753388/Imatinib_mesylate_inhibits_Leydig_cell_tumor_growth:_evidence_for_in_vitro_and_in_vivo_activity_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15753388 DB - PRIME DP - Unbound Medicine ER -