Molecular imaging assisted surgery improves survival in a murine head and neck cancer model.

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.

A novel orthotopic mouse model of head and neck cancer with molecular imaging.

OBJECTIVES/HYPOTHESIS: Our goal was to develop a noninvasive, dynamic imaging method that would further the understanding of head and neck cancer (HNC) tumor growth and local spreading. We developed a novel orthotopic mouse model of HNC with a stable cell line expressing a red fluorescent protein gene to compare a molecular imaging tumor quantification with traditional caliper measurement. METHODS: An HNC-tdT stable cell line expressing the tdTomato gene was established, which were injected into the floor of the mouth of nude mice. Tumor growth was constantly monitored using molecular imaging for up to 35 days. The tumors were further evaluated by histologic examination. RESULTS: Established tumors consistently expressed fluorescent signals that were successfully imaged by molecular imaging during the study. Initial tumor development was detected earlier than caliper measurement would allow. The fluorescent signal quantities of tumors detected by the imaging correlated with the tumor sizes measured by calipers. CONCLUSIONS: 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.

Alteration of mitochondrial membrane potential by Spirulina platensis C-phycocyanin induces apoptosis in the doxorubicinresistant human hepatocellular-carcinoma cell line HepG2.

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.