Vivo tumor models

Another important factor associated with an accurate in vivo tumor model is the number of days separating cancer cell inoculation and the initiation of the anticancer conjugate treatment. For example, if the inoculation of the cancer cells and the start of treatment are on the same day, it is likely that the tumor model will not be accurate since the cancer cells would not be established in the host, i.e., the cancer is easily eradicated. However, if treatment with the anticancer conjugate begins many days following inoculation of the cancer cells into the host, the cancer will be well established and the efficacy of the model greatly enhanced. 

Dolastatin 10 has been evaluated with promising results in a phase I clinical study in patients with solid tumors. Subsequently, its noticeable antitumor activity was well documented in various in vitro and in vivo tumor models (Madden et al., 2000). More than a dozen dolastatin peptides have been isolated to date. Recent studies have shown, for example, that the depsipeptide dolastatin 11 arrests cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network and induces the hyperpolymerization of purified actin (Bai et al., 2001). The effects of dolastatin 11 were similar to those of the sponge-derived depsipeptide jasplakinolide however, dolastatin 11 exhibited threefold more cytotoxicity than jasplakinolide in the cells studied. 

The Combretastatin A-4 analogues, containing a variety of heterocyclic moieties, such as imidazoles, thiazoles and tetrazoles, not only display efficient inhibition of tubulin polymerization but also exert potent cellular growth inhibition in different cancer lines including MDR cancer cells. It is worthy to note that some of Combretastatin A-4 analogues, such as imidazole-based Combretastatin A-4 exhibited oral availability leading to solid tumor regression in vivo tumor models. 

Nisslein, T., and J. Freudenstein. 2004. Concomitant administration of an isopropanoUc extract of black cohosh and tamoxifen in the in vivo tumor model of implanted RUCA-I rat endometrial adenocarcinoma cells. Toxicol. Lett. 150(3) 271-275. 

The nucleic acid delivery efQcacy of decorated cationic polymer-pDNA (or siRNA) polyplexes has also been demonstrated in several in vivo tumor models. After intravenous administration, these targeted polyplexes were taken up specifically by tumor cells and showed tumor inhibition via knockdown of mRNA or increased expression of tumor suppressor genes. Currently, one siRNA-based polyplex formulation for the treatment of solid tumors in humans has reached phase I clinical trials. ... 

Recently, Lee et al. showed highly efficient PDT with an in vivo tumor model using chitosan-based nanoparticles (Fig. 6) [78]. They prepared self-assembled amphiphilic glycol chitosan-5p-cholanic acid conjugates and encapsulated the hydrophobic photosensitizer, PpIX, with a high dmg-loading efficiency of over... 

Yin, M.B., Li, Z.R., Toth, K., et al. (2006). Potentiation of irinotecan sensitivity by Se-methylselenocysteine in an in vivo tumor model is associated with downregulation of cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia-inducible factor lalpha expression, resulting in reduced angiogenesis. Oncogene 25(17), 2509-2519. 

Buchegger F, Halpem SE, Sutherland RM, Schreyer M, Mach J-P. In vitro and in vivo tumor models for studies of distribution of radiolabeUed monoclonal antibodies and fragments. Nuklearmedizin 1986 25 207-209. 

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