Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells

被引:28
|
作者
Lawrence, J. [1 ,2 ]
Saba, C. [1 ]
Gogal, R., Jr. [2 ]
Lamberth, O. [2 ]
Vandenplas, M. L. [3 ]
Hurley, D. J. [4 ]
Dubreuil, P. [5 ]
Hermine, O. [6 ]
Dobbin, K. [7 ]
Turek, M. [1 ,2 ]
机构
[1] Univ Georgia, Dept Small Anim Med & Surg, Coll Vet Med, Athens, GA 30602 USA
[2] Univ Georgia, Dept Anat & Radiol, Coll Vet Med, Athens, GA 30602 USA
[3] Univ Georgia, Dept Large Anim Med & Surg, Coll Vet Med, Athens, GA 30602 USA
[4] Univ Georgia, Dept Populat Hlth, Coll Vet Med, Athens, GA 30602 USA
[5] AB Sci SA, Paris, France
[6] Univ Paris 05, Serv Hematol Adulte, Hop Necker, AP HP, Paris, France
[7] Univ Georgia, Dept Epidemiol & Biostat, Coll Publ Hlth, Athens, GA 30602 USA
关键词
cat; injection-site sarcoma; masitinib; platelet-derived growth factor receptor; tyrosine kinase inhibitor; vaccine-associated sarcoma; VACCINE-ASSOCIATED SARCOMAS; TYROSINE KINASE INHIBITOR; SOFT-TISSUE SARCOMAS; POSTVACCINAL SARCOMAS; IMMUNOHISTOCHEMICAL EXPRESSION; RADIATION-THERAPY; CATS; SURGERY; FIBROSARCOMAS; CHEMOTHERAPY;
D O I
10.1111/j.1476-5829.2011.00291.x
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.
引用
收藏
页码:143 / 154
页数:12
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