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Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.
Wang L., Shi W.-Y., Yang F., Tang W., Gapihan G., Varna M., Shen Z.-X., Chen S.-J., Leboeuf C., Janin A. et al
Haematologica 96, 6 (2011) 927-31 - http://www.hal.inserm.fr/inserm-00741102
Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.
Li Wang1, 2, Wen-Yu Shi1, Fan Yang1, 2, Wei Tang1, Guillaume Gapihan2, 3, 4, Mariana Varna2, 3, 4, Zhi-Xiang Shen1, Sai-Juan Chen1, 2, Christophe Leboeuf2, 3, 4, Anne Janin () 2, 3, 4, Wei-Li Zhao () 1, 2
1 :  Laboratory of Pathogenesis of Leukemia
Shanghai Rui Jin Hospital – Shanghai Jiao Tong University School of Medicine – Shanghai Institute for Biological Sciences Chinese Academy of Sciences
225 South Chongqing Road - Shanghai 200025
2 :  Pôle Sino-Français de Recherches en Sciences du Vivant et Génomique
Shanghai Institute for Biological Sciences – Chinese National Human Genome Center – Ruijin Hospital – Shanghai Jiaotong University School of Medicine – CNRS : - INSERM - INSTITUT PASTEUR
Ruijin Science and Education Plaza (bâtiment 11), 11e étage - Rue Ruijin Er N°197 - 200025 Shanghai
3 :  Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique
INSERM : U728 – Université Paris VII - Paris Diderot
Hopital Saint-Louis - Centre Hayem PARIS VII 1, Avenue Claude Vellefaux 75475 PARIS CEDEX 10
4 :  Service d'anatomo-pathologie
Assistance publique - Hôpitaux de Paris (AP-HP) – Hôpital Saint-Louis – Université Paris VII - Paris Diderot
1 avenue Claude Vellefaux 75475 Paris cedex 10
Vascular endothelial growth factor-A, an angiogenesis stimulator expressed on both tumor endothelial and malignant T cells, is involved in tumor progression in T-leukemia/lymphoma. Here, we assessed the impact of therapeutic vascular endothelial growth factor-A blockade on tumor-endothelial cell interaction and on tumor progression. In a murine xenograft T-leukemia/lymphoma model, combined bevacizumab (monoclonal antibody against vascular endothelial growth factor-A) with doxorubicin, compared with doxorubicin alone, significantly delayed tumor growth and induced prevalence of tumor cell apoptosis over mitosis. More importantly, the combined treatment induced endothelial cell swelling, microvessel occlusions, and tumor necrosis. In vitro, co-culture of endothelial cells with T-leukemia/lymphoma cells showed that doxorubicin induced expression of intracellular cell adhesion molecule-1, provided endothelial and malignant T cells were in direct contact. This was abrogated by bevacizumab treatment with doxorubicin. Taken together, bevacizumab enhances the chemotherapeutic effect on T-leukemia/lymphoma cells. Directly targeting tumor endothelial cells might be a promising therapeutic strategy to counteract tumor progression in T-cell malignancies.
Sciences du Vivant/Cancérologie

Articles dans des revues avec comité de lecture
Haematologica (Haematologica)
Publisher Ferrata Storti Foundation
ISSN 0390-6078 (eISSN : 1592-8721)

T-cell leukemia/lymphoma – bevacizumab – endothelial cells
Angiogenesis Inhibitors – Animals – Antibodies – Monoclonal – Humanized – Antineoplastic Agents – Apoptosis – Cell Line – Tumor – Down-Regulation – Endothelial Cells – Humans – Intercellular Adhesion Molecule-1 – Jurkat Cells – Leukemia – T-Cell – Lymphoma – Mice – Nude – Neovascularization – Pathologic – Tumor Burden – Vascular Endothelial Growth Factor A – Xenograft Model Antitumor Assays
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