Cisplatin animal models

Finally, replication-competent viral vector systems have been combined with standard cancer therapy in animal models, resulting in synergistic effects. This has, for example, been shown for ONYX-015 plus cisplatin or ionizing radiation [108,112] and for an AdElB 55k-deleted virus expressing HSV-tk (plus ganciclovir) in combination with the topoisomerase inhibitor topotecan [114]. 

Authier, N., Gillet, J. P., Fialip, J., Eschalier, A., and Coudore, F. (2003). An animal model of nociceptive peripheral neuropathy following repeated cisplatin injections. Exp. Neurol 182, 12-20. 

HER2-overexpressing breast cancer xenografts in vivo (243). Furthermore, trastuzumab enhanced the antitumor efficacy of multiple chemotherapeutic agents, including cisplatin, paclitaxel, and doxorubicin, in animal models (244-246). 

Finally, the ability of aprepitant to block emesis, a therapeutically relevant endpoint for the ultimate clinical application of the drug, as discussed below, was tested in the presence of several emetogens in the ferret. This species is believed to be a valid animal model for cancer chemotherapy-induced emesis in humans. Aprepitant (1) effectively blocked retching and vomiting due to cisplatin, apomorphine, and morphine at a dose of 3.0 mg/kg p.o. and 0.3 mg/kg i.v. (in the case of cisplatin).8... 

IL-18 is a proinflammatory cytokine involved in mediating inflammation in many organs (Jordan et al., 2001 Gracie et al., 2003). Recent studies have shown that renal IL-18 mRNA levels are significantly upregulated, cleaved in the proximal tubules, and detected in the urine following ischemia-reperfusion AKI and cisplatin-induced nephrotoxicity animal models (Melnikov et al., 2001 Leslie and... 

The key step will now be to estabhsh whether complexes of this type, which exhibit a reasonable spectrum of antitumour activity in animal models, attack DNA, and if so, by what mechanism. Perhaps copper could play an important role in this. Cu(II) potentiates the cytotoxicity of dppe and [Au(dppe)2]Cl is reactive towards Cu(II) ions. There is a potential wealth of Cu(I)phosphine chemistry (particularly aqueous) involving chelate ring opening, halide (Cl ) competition and free radical reactions which could be explored. The mechanism of cytotoxicity of metal diphosphine complexes seems likely to be different from that of cisplatin. This could be a promising sign for possible combination chemotherapy. 

Nitroglycerin injection twice a week (0.02 mg/kg or 0.2 mg/kg/per injection) combined with cisplalin significantly inhibited tnmor growth compared with cisplatin alone in an animal model of mnrine colon cancer (colon-26) inocnlated into B ALB/c mice (Yasnda et al. 2007b). 

Very few other cannabinoids have been tested (or at least reported) in animals. A-Methyllevonantradol (cf. 9) and nabilone (39) have been compared in the cat model [151]. Both cannabinoids showed dose-dependent antiemetic activity at the 20-100 mg/kg dose levels, A-methyllevonantradol being ca. 5-times more active than nabilone. The latter drug had previously been shown to suppress in the cat emesis induced by apomorphine, deslanoside and the anticancer drugs l,3-bis(2-chlorethyl)-l-nitrosourea (BCNU) and cisplatin, but not nicotine. At the doses tested (25-100/ig/kg), nabilone produced behavioural disturbances, from mild ataxia and display of pleasure at 25 /ig/kg to severe locomotor disturbance, catatonic behaviour and vocalization at 100 /ig/kg. 

Also the renal 3D models, which have been described recently, have been tested with <10 compounds and their predictivity is unclear. One of these renal 3D models is based on hydrogel-embedded PT isolated from murine kidneys (Astashkina et al., 2012a). Thus, two of the main potential advantages of in vitro models do not apply here, which are (1) use of human cells and (2) avoidance of animal experiments. The four compounds tested with this model included doxorubicin, which gave in addition to cisplatin the most consistent positive resnlts (cytokine release was measured as endpoint). However, in humans doxorubicin toxicity usually does not affect the PT. Doxorubicin has substantial hepato- and cardiotoxicity, but only ntinor toxic effects on the kidney, which are mainly limited to the glomerulus (Tacar et al., 2013). 

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