title: Antiglioma effects of a new, low molecular mass, inhibitor of fibroblast growth factor.
abstract: Despite the deployment of multimodal therapies involving neurosurgical resection, radio- and polychemotherapy, the prognosis for glioblastoma patients remains poor. These tumors are pathologically characterized by their associated angiogenesis and diffuse brain invasion, processes that are probably closely linked to the unfavorable prognosis of this disease. Accordingly, pharmacological inhibition of glioblastoma invasion and approaches that impede angiogenesis are considered to be promising therapeutic strategies to combat these tumors. Nevertheless, the anti-angiogenic therapies for glioblastoma currently available are transient and palliative at best. Blocking the effects of fibroblast growth factor (FGF) may represent a novel mean of inhibiting the angiogenesis associated with glioblastoma, as it mediates the angiogenesis induced by other factors and it is an angiogenic factor by itself. In addition, the survival of glioma cells and their resistance to chemotherapeutic agents are highly FGF-dependent. We show here that a recently described inhibitor of FGF, 2,5-dihydroxyphenyl-sulfonate (2,5DHPS, dobesilate), stimulates the apoptosis of tumor cells, inhibits glioblastoma invasion and suppresses its associated angiogenesis. Moreover, this agent augments the efficiency of chemotherapeutic agents in a rat model of orthotopic brain tumor. These results suggest that 2,5DHPS treatment may represent a promising therapy for malignant glioma.
authors.affiliation: Servicio de Histología, IRYCIS, E-28034 Madrid, Spain. pedro.cuevas@hrc.es
authors.forename: Pedro
authors.initials: P
authors.lastname: Cuevas
authors.forename: Fernando
authors.initials: F
authors.lastname: Carceller
authors.forename: Javier
authors.initials: J
authors.lastname: Angulo
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Corrochano
authors.forename: Adrián
authors.initials: A
authors.lastname: Cuevas-Bourdier
authors.forename: Guillermo
authors.initials: G
authors.lastname: Giménez-Gallego
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D002123:Calcium Dobesilate / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D002123:Calcium Dobesilate; D005346:Fibroblast Growth Factors