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Antivascular Therapy of Oral Tongue Squamous Cell Carcinoma with PTK787
Author(s) -
Yazici Yasemin D.,
Kim Seungwon,
Jasser Samar A.,
Wang Zhuoying,
Carter Kenny B.,
Bucana Corazan D.,
Myers Jeffrey N.
Publication year - 2005
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/01.mlg.0000183861.53765.77
Subject(s) - medicine , angiogenesis , tongue , vascular endothelial growth factor , pathology , cancer research , tyrosine kinase inhibitor , epidermoid carcinoma , carcinoma , cancer , vegf receptors
Objectives/Hypothesis: Vascular endothelial growth factor (VEGF) is an important mediator in tumor vascularization, growth, and metastasis. We investigated whether blockade of the VEGF receptor (VEGF‐R) signaling pathway by the tyrosine kinase inhibitor PTK787 combined with CPT‐11, a semisynthetic camptothecin analogue, can inhibit the tumor growth and angiogenesis of squamous cell carcinoma of the oral tongue in an orthotopic nude mouse model. Methods: JMAR human oral squamous cell carcinoma cells were injected into the tongues of nude mice. Seven days later, the mice were randomized to receive a placebo, daily oral PTK787, weekly CPT‐11 injection, or PTK787 plus CPT‐11. After 4 weeks of treatment, the mice underwent necropsy, and the tongue tumors, cervical lymph nodes, and lungs were removed for immunohistochemical analyses. Results: CPT‐11, PTK787, and PTK787 plus CPT‐11 significantly decreased tumor volumes and prolonged survival. The combination treatment group had the most significant decrease in volume and increase in survival. PTK787 alone or in combination with CPT‐11 reduced the phosphorylation of VEGF‐R in tumor cells and tumor‐associated endothelial cells, was associated with decreased microvessel density, a decreased proliferative index, and an increased apoptotic index. PTK787 alone or the combination therapy resulted in apoptosis of both tumor cells and tumor‐associated endothelial cells. Conclusions: These results suggest that targeting VEGF‐R tyrosine kinase activity can be an effective therapeutic approach in squamous cell carcinoma of the oral tongue.