Imaging the efficacy of UVC irradiation on superficial brain tumors and metastasis in live mice at the subcellular level.

The effect of UVC irradiation was investigated on a model of brain cancer and a model of experimental brain metastasis. For the brain cancer model, brain cancer cells were injected stereotactically into the brain. For the brain metastasis model, lung cancer cells were injected intra-carotidally or stereotactically. The U87 human glioma cell line was used for the brain cancer model, and the Lewis lung carcinoma (LLC) was used for the experimental brain metastasis model. Both cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was used to image single cancer cells in the brain. This double labeling of the cancer cells with GFP and RFP enabled apoptosis of single cells to be imaged at the subcellular level through the craniotomy open window. UVC irradiation, beamed through the craniotomy open window, induced apoptosis in the cancer cells. UVC irradiation was effective on LLC and significantly extended survival of the mice with experimental brain metastasis. In contrast, the U87 glioma was relatively resistant to UVC irradiation. The results of this study suggest the use of UVC for treatment of superficial brain cancer or metastasis.

Matrilysin (MMP-7) degrades VE-cadherin and accelerates accumulation of beta-catenin in the nucleus of human umbilical vein endothelial cells.

Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.

Fluorescent proteins enhance UVC PDT of cancer cells.

Cancer cells, with and without fluorescent protein expression, were irradiated with various doses of UVC (100, 400, and 600 J/m(2)). Dual-color Lewis lung carcinoma cells (LLC) and U87 human glioma cells, expressing GFP in the nucleus and RFP in the cytoplasm and non-colored LLC and U87 cells were cultured in 96-well plates. Eight hours after seeding, the cells were irradiated with the various doses of UVC. The resulting cell number was determined after 24 hours. Compared to non-colored LLC cells, the number of dual-color LLC cells decreased significantly due to UVC irradiation with 100 J/m(2) (p=0.003). Although there was no significant difference in the number of dual-color and non-colored U87 cells after 100 J/m(2) UVC irradiation (p=0.852), the number of dual-color U87 cells decreased significantly with respect to non-colored cells due to UVC irradiation with 400 J/m(2) and 600 J/m(2) (p=0.011 and p=0.009, respectively). Thus, both dual-color LLC and dual-color U87 cells were more sensitive to UVC light than non-colored LLC and U87 cells. These results suggest that the expression of fluorescent proteins in cancer cells can enhance photodynamic therapy (PDT) using UVC and possibly with other wavelengths of light as well.