Endostatin therapy reveals a U-shaped curve for antitumor activity

Harvard University, Cambridge, Massachusetts, United States
Cancer Gene Therapy (Impact Factor: 2.42). 07/2006; 13(6):619-27. DOI: 10.1038/sj.cgt.7700938
Source: PubMed


Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.

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Available from: David Zurakowski, May 19, 2014
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    • "Interestingly, endostatin has a tumour-specific optimal inhibition concentration, higher and lower dosages having less inhibitory effect (Celik et al, 2005; Tjin Tham Sjin et al, 2006). All in all, endostatin is associated with several fundamental aspects of cancer including tumour cell differentiation, cancer angiogenesis and lymphangiogenesis, and inflammatory cell infiltration (Brideau et al, 2007; Seppinen and Pihlajaniemi, 2011). "
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    • "Considering that BPA has been described as a xenoestrogen, it is interesting to note that Vandenberg et al. (2006) found that mice exposed to estradiol exhibited a non monotonic dose response for mammary gland morphology. Other classes of compounds, most notably the angiogenesis inhibitors, have also reported nonmonotonic therapeutic dose responses (Benelli et al. 2003; Bruns et al. 2004; Celik et al. 2005; Humar et al. 2002; Lalani et al. 2004; Motegi et al. 2002; Panigrahy et al. 2002; Slaton et al. 1999; Tjin Tham Sjin et al. 2005, 2006; Trinh et al. 2000; Yamaguchi et al. 1999). Given that our data suggest a potential role for BPA in tumor angiogenesis because of the significant increases in tumor volume and the incidence of metastasis, future research efforts focusing on this connection are warranted. "
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    • "Nowadays, animal experiments in vivo have been carried out. The clinical evaluation, however, calls for more deep research about the gene transduction system with better efficiency, specificity and safety (Tjin et al, 2006). The comprehensive therapy involving muti-genes transduction can inhibit the tumor in different stages, which may result in more conspicuous curative effect (Liu et al, 2009). "
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