Background:A fibroblast growth factor 2 (FGF2)-targeted adenoviral system can alter viral tropism and allow for improved transduction and reduced systemic toxicity. This study is to investigate if the FGF2-targeted adenoviral mutant Nijmegen breakage syndrome 1 (FGF2-Ad-NBS1) gene transfer can enhance cisplatin chemosensitisation not only by targeting DNA repair, but also through the induction of antiangiogenesis, whereas at the same time reducing toxicities in treating head and neck squamous cell carcinoma (HNSCC).Methods:The human HNSCC cell line was treated in vitro and in a nude mouse xenograft model. We conducted verification of binding ability of mutant NBS1 and downregulation of MRN complex, evaluation of transduction efficiency and combined antitumour activities. The antiangiogenesis mechanism was also investigated. Finally, we estimated the distribution of adenoviral vector in the liver.Results:The mutant NBS1 protein retains the binding ability and effectively suppresses the expression level of the MRN in infected cells. Transduction efficiency in vitro and cisplatin chemosensitisation were upregulated. The FGF2-Ad-NBS1 also showed detargeting the viral vectors away from the liver. The downregulation of NF-κB expression was supposed to correlate with increased antiangiogenesis.Conclusions:FGF2-targeted adenoviral system enhances the cisplatin chemosensitisation of mutant NBS1 and may avoid viral-associated liver toxicities.

C-PC (C-phycocyanin) is a water-soluble biliprotein from the filamentous cyanobacterium Spirulina platensis with potent antioxidant, anti-inflammatory and anticancerous properties. In the present study, the effect of C-PC was tested on the proliferation of doxorubicin-sensitive (S-HepG2) and -resistant (R-HepG2) HCC (hepatocellular carcinoma) cell lines. These studies indicate a 50% decrease in the proliferation of S- and R-HepG2 cells treated with 40 and 50 microM C-PC for 24 h respectively. C-PC also enhanced the sensitivity of R-HepG2 cells to doxorubicin. R-HepG2 cells treated with C-PC showed typical apoptotic features such as membrane blebbing and DNA fragmentation. Flow-cytometric analysis of R-HepG2 cells treated with 10, 25 and 50 microM C-PC for 24 h showed 18.8, 39.72 and 65.64% cells in sub-G(0)/G(1)-phase respectively. Cytochrome c release, decrease in membrane potential, caspase 3 activation and PARP [poly(ADP-ribose) polymerase] cleavage were observed in C-PC-treated R-HepG2 cells. These studies also showed down-regulation of the anti-apoptotic protein Bcl-2 and up-regulation of the pro-apoptotic Bax (Bcl2-associated X-protein) protein in the R-HepG2 cells treated with C-PC. The present study thus demonstrates that C-PC induces apoptosis in R-HepG2 cells and its potential as an anti-HCC agent.

Surgery plays an important role in the treatment of head and neck cancer (HNC), and surgical margin status is a key prognostic factor. Molecular imaging (MI) can be applied to identify tumor extensions intraoperatively. We applied this technique in a murine HNC model to determine whether it improves outcomes from surgical intervention. An orthotopic murine model with HNC was established with SCC VII cells expressing a green fluorescent protein. To determine the diagnostic accuracy of MI, 20 murine models undergoing standard surgical resection were assessed with MI to identify residual tumor, which was compared to histology as the gold standard. Then, to assess the effect of MI as a therapeutic intervention for survival, 65 mice were randomly divided into standard surgical resection, MI-assisted surgical resection, and control groups. In the MI-assisted surgery group, residual signals identified by MI underwent further tissue excision to eliminate the signal positivity. In diagnostic accuracy analysis, sensitivity and specificity of intraoperative MI in the HNC murine model were 86% and 100%, respectively. The mice undergoing MI-assisted surgery showed a significantly improved 60-day survival rate compared to standard surgery, 37% versus 5%, respectively. Intraoperative MI guidance is a promising technique in oncologic surgery, which could increase the efficacy of tumor resection and the survival of patients with HNC. The hurdles in applying this technique in clinical practice are still considerable, and further research and development is warranted.

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This novel animal model represents an orthotopic human HNC model. The tumor can be detected earlier with molecular imaging than by conventional external caliper measurement. Unlike surgical measurement, the tumor can be quantified without disturbing the tumor environment. This model has significant potential for HNC oncologic research.