Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferation of spindle-shaped cells predominantly of endothelial cell origin, neoangiogenesis, inflammatory cell infiltration, and edema. At least in early stage, KS behaves as a reactive lesion sustained by the action of inflammatory cytokines and growth factors, has a polyclonal nature, and can regress. However, in time it can become monoclonal, especially in the nodular stage, evolving into a true sarcoma, likely in association with the increased expression of antiapoptotic oncogenes. We have recently demonstrated by immunohistochemical analysis that Bcl-2, a proto-oncogene known to prolong cellular viability and to antagonize apoptosis, is highly expressed in spindle cells and vessels of both AIDS-KS and classical KS lesions and that its expression increases with lesion stage. Paclitaxel, a microtubule-stabilizing drug known to inhibit Bcl-2 antiapoptotic activity and to be highly effective in the treatment of certain neoplasms, has recently been found to be active also in patients with advanced HIV-associated KS. In this report we investigated the mechanism(s) of paclitaxel activity in KS. By using a model of experimental KS induced by the inoculation of KS-derived spindle cells in nude mice and primary cultures of KS spindle cells, we found that paclitaxel promotes regression of KS lesions in vivo and that it blocks the growth, migration, and invasion of KS cells in vitro. Furthermore, paclitaxel treatment promoted apoptosis and down-regulated Bcl-2 protein expression in KS cells in vitro and in KS-like lesions in mice. Our results suggest that paclitaxel interferes with KS by down-regulating Bcl-2 antiapoptotic effect.
Sgadari, C., Toschi, E., Palladino, C., Barillari, G., Carlei, D., Cereseto, A., et al. (2000). Mechanism of paclitaxel activity in Kaposi's sarcoma. JOURNAL OF IMMUNOLOGY, 165(1), 509-517.
|Tipologia:||Articolo su rivista|
|Citazione:||Sgadari, C., Toschi, E., Palladino, C., Barillari, G., Carlei, D., Cereseto, A., et al. (2000). Mechanism of paclitaxel activity in Kaposi's sarcoma. JOURNAL OF IMMUNOLOGY, 165(1), 509-517.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/05 - Patologia Clinica|
|Revisione (peer review):||Esperti anonimi|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||1-lug-2000|
|Titolo:||Mechanism of paclitaxel activity in Kaposi's sarcoma|
|Autori:||Sgadari, C; Toschi, E; Palladino, C; Barillari, G; Carlei, D; Cereseto, A; Ciccolella, C; Yarchoan, R; Monini, P; Stürzl, M; Ensoli, B|
|Appare nelle tipologie:||01 - Articolo su rivista|