Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.

1-(2-Deoxy-2-[18F]fluoro-β-D-arabinofuranosyl)-5-bromouracil ([18F]FBAU), a substitute for thymine, has been reported as an effective reporter probe by which to trace cellular metabolism with its positron emission. In the present study, a rat xenograft model bearing F98 glioma transfected with dual reporter genes, herpes simplex virus type 1 thymidine kinase (HSV1-tk) and firefly luciferase (luc) was used for monitoring tumor progression by multimodalities of molecular imaging using [18F]FBAU and D-luciferase as probes. Rat F98 glioma cells were transfected with the pC1-tk-IRES-luc vectors. The selected stable clone was renamed as the F98/tk-luc cell line. Fischer 344 male rats bearing orthotropic F98/tk-luc gliomas in the left brain were used. On day 13 post tumor inoculation, biodistribution, positron emission tomography (PET), magnetic resonance imaging (MRI) and ex vivo autoradiography were performed. The surviving fraction of F98/tk-luc cells treated with 15 µM ganciclovir (GCV) was 15.9%, and the uptake of [131I]FIAU in these cells was significantly enhanced when compared with F98 cells. The correlation coefficient of tumor volume vs. the bioluminescence in the F98/tk-luc glioma-bearing rats was 0.90. The biodistribution showed that the accumulation ratios of [18F]FBAU for glioma-to-normal brain were 9.16, 14.24, 5.7 and 13.7 at 30, 60, 90 and 120 min post i.v. injection, respectively. Consistent tumor enhancement of [18F]FBAU/PET imaging was also noted from 30-90 min post injection. Ex vivo autoradiography also confirmed significant [18F]FBAU uptake in tumors. In conclusion, [18F]FBAU may be used as a PET probe for monitoring glioma progression in animal models and may have potential for clinical use as well.

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Background/Aim: In precision therapy, liposomal encapsulated chemotherapeutic drugs have been developed to treat cancers by achieving higher drug accumulation in the tumor compared to normal tissues/organs. Materials and Methods: We developed a novel chemoradiotherapeutic approach via nanoliposomes conjugated with vinorelbine (VNB) and 111 In (111 In-VNB-liposome) and examined their pharmacokinetics, biodistribution, maximum tolerance dose, and toxicity in a NOD/SCID mouse model. Results: Pharmacokinetic results showed that the area under the curve (AUC) of PEGylated liposomes was about 17-fold higher than that of the free radioisotope. Tumor growth inhibition by 111 In-VNB-liposome was significantly higher than that of the control (p<0.05). Conclusion: The tumors in NOD/SCID mice bearing HT-29/tk-luc xenografts were significantly suppressed by 111 In-VNB-liposomes. The study proposed repeated treatments with a novel liposome-mediated radiochemotherapy and validation of therapeutic efficacy via imaging. Colorectal cancer is a common malignant tumor in industrialized countries (1-3). From an epidemiological viewpoint, family inheritance, ageing and diabetes may all contribute to a higher risk of colorectal cancer (4-6). Clinically, colorectal cancer has a high mortality rate due to the fact that it remains undetected until later stages of the disease (7). The average five-year overall survival rate for all stages is about 65% based on surgery, adjuvant chemotherapy and radiotherapy (8). Vinorelbine (5'-noranhydrovinblastine, VNB) is a drug widely used in cancer therapy (9, 10). It acts through microtubule disruption, thereby arresting cell division in mitosis. Also, it is less toxicity than the naturally occurring 61 This article is freely accessible online.