Cytotoxicity and antiangiogenesis by fibroblast growth factor 2–targeted Ad‐TK cancer gene therapy

Abstract

These data suggest that FGF2-retargeted Ad-TK produces a combination of expected direct antitumor cytotoxicity and a newly reported antiangiogenesis effect that could prove promising as a novel therapeutic approach in the treatment of FGF receptor-expressing cancers.

Molecular disruption of NBS1 with targeted gene delivery enhances chemosensitisation in head and neck cancer

“…To overcome these issues, the FGF2-targeted adenoviral system will be the most efficacious when applied to cells that have low CAR and high FGFRs expression. In our previous study, FGFR1 and FGFR2 expression was widely observed in both tumour cells and ECs of the human HNSCC xenograft model (Saito et al , 2009). Several studies have described a two- to 34-fold increase in intratumoral transduction efficiency (Rancourt et al , 1998; Doukas et al , 1999; Qin et al , 2005) and a two-fold increased transduction efficiency of adenoviral TK gene was observed for human HNSCC (Saito et al , 2009).…”

“…The FGF2-targeted system has been shown to induce highly efficient transduction in ECs that express relatively low levels of CAR receptor (Gupta et al , 2006; Saito et al , 2009). It has been reported that angiogenesis is enhanced and the expression levels of FGFR1 and FGFR2 are upregulated in cancer cells and ECs in HNSCC (Dellacono et al , 1997; Riedel et al , 2000).…”

“…Fibroblast growth factor 2 (FGF2)-targeted adenoviral conjugates (FGF2-Ad) utilises FGF2 as the targeting ligand. This FGF2-targeted adenoviral system has achieved efficient gene transfer in previously reported ovarian, pancreatic, skin and lung cancer models, as well as in HNSCC and in endothelial cells (ECs) (Rogers et al , 1997; Rancourt et al , 1998; Kleeff et al , 2002; Qin et al , 2005; Saito et al , 2009). Fibroblast growth factor 2 exhibits its biological activities by high affinity binding to FGFRs (particularly FGFR1 and FGFR2).…”

Biliverdin’s regulation of reactive oxygen species signalling leads to potent inhibition of proliferative and angiogenic pathways in head and neck cancer

“…Subsequently, sections were incubated with 3,30-diaminobenzidine tetrahydrochloride (DAB)–H 2 O 2 solution for visualisation and were counterstained with haematoxylin. To assess the grade of microvessel growth within the tumour, three views ( × 20) were digitally recorded for each tumour to cover the greatest anti-CD31 staining area for estimation of microvessel development (Mavria et al , 2005; Saito et al , 2009). The relative percentage of CD31-positive area, represented by the microvessel density (MVD) within each high power field, was measured for three separate images with the assistance of ImmunoRatio, an application reviewed in detail by Tuominen et al (2010).…”

Phase I/II clinical study on safety and antivascular effects of paclitaxel encapsulated in cationic liposomes for targeted therapy in advanced head and neck cancer

“…Consequently, both compartments (tumor cells as well as tumor‐associated microvessels) seem to be promising targets in head and neck cancer. In this line, currently, dual targeting antibodies against EGFR and VEGF and fibroblast growth factor‐2‐targeted gene therapy approaches are proposed preclinically with the intent to interfere with both target compartments in HNSCC. Interestingly, VEGF receptor antibodies were shown to overcome resistance to EGFR inhibitors .…”