title: Blockade of vascular endothelial growth factor sensitizes tumor-associated vasculatures to angiolytic therapy with a high-frequency ultrashort pulsed laser.
abstract: Because of high spatial resolution and superior tissue penetration, a femtosecond laser of the near-infrared spectrum has great potential to improve the efficacy of conventional photodynamic therapy; however, the lack of suitable photosensitizers has so far limited its bedside applications. Recently, our group reported that a brief irradiation by femtosecond lasers in the absence of exogenous probes can modulate various cellular behaviors in vitro and in vivo. Here, we demonstrate that targeted irradiation by a femtosecond laser disrupted tumor-associated blood vessels, and the inhibition of vascular endothelial growth factor signaling augmented the efficacy of laser-induced angiolysis. Further, we show that reactive oxygen species (ROS) are generated in response to laser irradiation, and reducing the intracellular levels of ROS rendered endothelial cells resistant to laser-induced cytotoxicity. Collectively, these results indicate that a femtosecond laser can be used as a vascular-disrupting therapeutic modality for cancer treatment, especially when used in combination with conventional anti-angiogenic therapies.
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, 301-705, Republic of Korea.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Choi
authors.forename: Myunghwan
authors.initials: M
authors.lastname: Choi
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007834:Lasers; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry; D017382:Reactive Oxygen Species; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A