Briefly, after OGD treatment, the supernatant of the cell culture was harvested

vehicle control. All treatment arms demonstrated efficacy compared to control treatment with increased quadrupling times of 9.9 days for sorafenib alone, 15.3 days for radiation alone, 15.4 days for concurrent sorafenib-radiation, and 22.2 days for sequential radiation followed by sorafenib. No significant difference in quadrupling time was observed between treatment with concurrent sorafenib-radiation and radiation alone. However, sequential treatment with radiation-sorafenib resulted in a quadrupling time that was significantly longer than that for concurrent sorafenib-radiation or radiation alone. To show the behavior of all tumors used in the analysis over time, the data are also represented using Kaplan-Meier statistics with quadrupling time as an event. All relationships noted above to be significant by the Mann-Whitney U-test were found to be similarly significant with Kaplan-Meier statistics compared by the log-rank test. HCC tumors treated with sequential radiation-sorafenib required an Lysine vasopressin average of 16.2 days more to quadruple compared to untreated tumors. This is similar to the sum of increases in HCC tumor growth delay seen with sorafenib alone and radiation alone, which suggests that sequential treatment additively delays tumor growth. No weight loss, diarrhea, dermatitis, ulceration, or other observable toxicity was noted due to sorafenib, radiation, or either schedule of combined radiation-sorafenib treatment throughout these experiments. radiation on days 2 and 3; sequential arm after 2 consecutive daily fractions of 3 Gy followed by 3 consecutive daily injections of sorafenib. In this way, animals in the concurrent and sequential arms received equal numbers of sorafenib and radiation doses. Treatment with sorafenib alone markedly reduced the average number of blood vessels per high power field from 23.6 for vehicle control to 5.8 . Treatment with radiation alone likewise reduced the average number of blood vessels per HPF, though to a lesser degree at 10.8. Concurrent sorafenib-radiation decreased the number of blood vessels per HPF to 5.2, a similar reduction to that observed with sorafenib alone. Therefore, concurrent sorafenib-radiation 15864271 does not appear to significantly augment the reduction in vascularity beyond that achieved with sorafenib alone. However, sequential radiation-sorafenib significantly reduced tumor vascularity compared to all other arms at 2.9 CD31 foci per HPF. This evidence suggests that a sequential radiationsorafenib schedule may additively enhance the anti-angiogenic effects of either radiation or sorafenib given alone, while a concurrent schedule may not. Mitotic index as measured by Ki-67 was slightly lower for tumors treated with sorafenib alone or concurrent sorafenib-radiation compared to untreated controls, whereas tumors treated with radiation alone showed no significant difference from untreated controls . The mitotic index of tumors treated with sequential radiation- sorafenib was significantly lower than that for all other arms, including sorafenib alone and concurrent sorafenib-radiation-. Concurrent treatment with sorafenib-radiation resulted in reduced persistence of double-strand breaks compared to treatment with sequential radiationsorafenib or radiation alone in vivo Immunofluorescence staining for c-H2AX foci was assessed quantitatively and revealed that tumors treated concurrently with sorafenib-radiation 18004284 displayed a lesser proportion of nuclei with high and moderate numbers of fo