Interestingly, when parental and CDV-resistant cells produced an

Interestingly, when parental and CDV-resistant cells produced an equivalent size of xenografts (i.e. 3 and 5 weeks post cell-inoculation),

the amount of neutrophils, macrophages, NK cells and inflammatory cytokines was significantly higher in the animals inoculated with the parental cells compared to those that received the CDV-resistant cells. Our data obtained by whole genome gene expression profiling of normal versus immortalized cells exposed to CDV supports the use of CDV for the treatment of non-viral induced neoplasias. Furthermore, a few reports sustain this hypothesis. For instance, CDV proved effective in reducing the growth of melanoma B16 in an experimental model in mice ( Redondo et al., 2000). The most effective treatment in this model was subcutaneous administration of 67 mg/kg on alternative days three times weekly that resulted in 90% inhibition selleck inhibitor of tumor growth. When CDV antiproliferative effects were evaluated against a series of nine HPV-negative cells, the 50% cytostatic concentrations of the drug following

7 days of incubation varied between 1.4 μg/ml (for the cervical carcinoma cell line C33A) and 43 μg/ml (for the breast carcinoma cell line BT-20) compared to 0.7–2.0 μg/ml for four different HPV-positive cell lines [SiHa and CaSki (HPV-16), HeLa (HPV-18) and CK-1 (HPV-33) (Andrei et al., 1998a). When ODE-CDV was compared to CDV, ODE-CDV proved more potent than the parent compound against the HPV-positive PD0332991 cell carcinoma cell lines HeLa, CaSki, Me-180 (HPV-68) and the C33A cervical carcinoma cells lacking HPV (Hostetler et al., 2006). Liekens et al. have demonstrated the inhibitory effects of CDV on the development of virus-independent vascular tumors originated by basic fibroblast growth factor (FGF2)-overexpressing endothelial cells (FGF2-T-MAE). The in vivo antitumor efficacy of CDV was attributed to specific induction of apoptosis in this model ( Liekens et al., 2007). next In addition, CDV treatment of FGF2-T-MAE cells resulted in a pronounced up-regulation of the tumor suppressor protein p53. However, the expression of

Bax (pro-apoptotic) and Bcl-2 (anti-apoptotic) proteins remained unchanged, and CDV did not induce the release of cytochrome c from the mitochondria. Therefore CDV appeared to inhibit the growth of FGF2-T-MAE cells via inhibition of FGF2 expression and signalling ( Liekens et al., 2007). Recently, it was shown that CDV possesses potent antineoplastic activity against both HCMV positive and negative glioblastomas (Hadaczek et al., 2013). While this activity was associated with inhibition of HCMV expression and with activation of cellular apoptosis in HCMV-positive glioblastomas, CDV was also demonstrated to induce cell death in the absence of HCMV. CDV incorporated into tumor cell DNA promoting double-strand DNA breaks and apoptosis.

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