First published November 1, 2006 - More info
Various conventional chemotherapeutic drugs can block angiogenesis or even kill activated, dividing endothelial cells. Such effects may contribute to the antitumor efficacy of chemotherapy in vivo and may delay or prevent the acquisition of drug-resistance by cancer cells. We have implemented a treatment regimen that augments the potential antivascular effects of chemotherapy, that is devoid of obvious toxic side effects, and that obstructs the development of drug resistance by tumor cells. Xenografts of 2 independent neuroblastoma cell lines were subjected to either continuous treatment with low doses of vinblastine, a monoclonal neutralizing antibody (DC101) targeting the flk-1/KDR (type 2) receptor for VEGF, or both agents together. The rationale for this combination was that any antivascular effects of the low-dose chemotherapy would be selectively enhanced in cells of newly formed vessels when survival signals mediated by VEGF are blocked. Both DC101 and low-dose vinblastine treatment individually resulted in significant but transient xenograft regression, diminished tumor vascularity, and direct inhibition of angiogenesis. Remarkably, the combination therapy resulted in full and sustained regressions of large established tumors, without an ensuing increase in host toxicity or any signs of acquired drug resistance during the course of treatment, which lasted for >6 months.
Giannoula Klement, Sylvain Baruchel, Janusz Rak, Shan Man, Katherine Clark, Daniel J. Hicklin, Peter Bohlen, Robert S. Kerbel
Original Citation: J. Clin. Invest.105:R15–R24 (2000).
Citation for this corrigendum: J. Clin. Invest.116:2827 (2006). doi:10.1172/JCI8829C1.
Note: This Corrigendum duplicates the October 2009 Corrigendum and was published in error.
The fluorescent image in Figure 3 that depicts TUNEL assay in vinblastine-treated tumors was incorrect. It was a rotated duplication of the depiction of the DC101 anti-VEGFR-2 antibody–treated group that appeared in the panel immediately above.
The vinblastine fluorescence panel has therefore been eliminated in the corrected figure below. The text of the legend should read as follows: “In both single-treatment groups (vinblastine [data not shown] and DC101), widening of the apoptotic rims and extension of the apoptotic figures into the cuff was observed after 35 and 50 days of treatment, respectively.” The corrected figure appears below.
The authors regret this error.
We also wish to make clear the legend of Figure 4 with respect to the source of the images to avoid any possibility of misleading readers. Specifically, parts A, C, and E are enlarged, and parts A and C are rotated versions of the respective H&E panels in Figure 3. The second sentence of the legend should read as follows: “H&E stain of formalin-fixed, paraffin-embedded sections of human neuroepithelioma SK-N-MC images from Figure 3 were magnified and complemented with an additional 3 panels to demonstrate more clearly the progressive damage to endothelial cells caused by the respective therapy treatments.”
The authors regret any inconvenience this may have caused.