Effects of an antibody to vascular endothelial growth factor receptor-2 on survival, tumor vascularity, and apoptosis in a murine model of colon carcinomatosis

Shaheen, Raymond M.; Tseng, William W.; Vellagas, Roberto; Liu, Wenbiao; Ahmad, Syed A.; Jung, Young Do; Reinmuth, Niels; Drazan, Kenneth E.; Bucana, Corazon D.; Hicklin, Daniel J.; Ellis, Lee M.

doi:10.3892/ijo.18.2.221

Cited by 39 publications

(41 citation statements)

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“…Studies have also shown that maximal inhibition of tumor growth can be achieved by completely blocking circulating VEGF (35). Similarly, preclinical studies have reported decreased angiogenesis and decreased primary and metastatic growth when the angiogenic signaling pathway is inhibited with anti-VEGFR monoclonal antibodies and tyrosine kinase inhibitors of the VEGFR (39)(40)(41)(42)(43)(44)(45). Furthermore, there is an emerging body of preclinical data that show improved antitumor activity when VEGF pathway inhibitors are combined with conventional cytotoxic agents (38,(44)(45)(46)(47)(48)(49)(50)(51).…”

Section: Vegf Inhibitionmentioning

confidence: 99%

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

Tabernero

2007

Molecular Cancer Research

375

266

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Section: Vegf Inhibitionmentioning

confidence: 99%

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

Tabernero

2007

Molecular Cancer Research

375

266

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“…Antiangiogenic therapy (AAT) inhibits new blood vessel formation and decreases vessel density (VD) and tumour growth in several tumour models (Kim et al, 1993;Borgstrom et al, 1998;Kamiya et al, 1999;Lee et al, 2000;Soh et al, 2000;Beecken et al, 2001;Shaheen et al, 2001). As a consequence, one would expect that tumour blood flow and tumour oxygenation also decrease during AAT.…”

mentioning

confidence: 99%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

298

150

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Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P ¼ 0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.

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“…In endothelial cells, VEGF activates standard signaling pathways such as the phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase (MAPK) pathways (Gerber et al, 1998;Takahashi et al, 1999). Intracellular signaling leads to endothelial cell activation, including upregulation of degradative enzymes, induction of vascular permeability, and enhanced survival mechanisms (Shaheen et al, 2001;Chen et al, 2002;Patel et al, 2003). VEGFR-1 has been associated with cell migration (Barleon et al, 1996), whereas VEGFR-3 is typically associated with lymphangiogenesis in adults (Irrthum et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

et al. 2005

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Effects of an antibody to vascular endothelial growth factor receptor-2 on survival, tumor vascularity, and apoptosis in a murine model of colon carcinomatosis

Cited by 39 publications

References 0 publications

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

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