This study had several limitations. First, we used an overdose of doxorubicin for facilitating the detection of the drug-specific inflorescence, especially in tumor receiving doxorubicin intravenous injection, which could overestimate the effect of transcatheter intraarterial techniques on drug penetration. The distribution of doxorubicin given in a routine dose via transcatheter intraarterial route needs to be further investigated. Second, we selected 10 minutes and 4 hours after doxorubicin administration as the sacrifice time points to ensure AbMole Clofentezine effective drug penetration. Given the fact that drug delivery in tumor is a dynamic process, it is possible that more time points of measurements might provide additional information about doxorubicin penetration in tumor. AbMole Folinic acid calcium salt pentahydrate Finally, we used a sample of the tumor to assess doxorubicin distribution throughout the tumor. The penetration length in twodimensional images could overestimate the real distance of a doxorubicin fluorescent spot to its nearest vessel since the nearest vessel might be out of the section. Future studies using immunofluorescence technique should aim to quantify staining throughout the entire tumor. In summary, this study provides evidence that hepatic artery chemotherapeutic infusion, especially when combined with embolization, improves drug penetration as well as drug concentration in liver cancer. This could, at least in part, account for the mechanism by which transcatheter intraarterial techniques are effective therapies for liver cancer. On the other hand, our results suggest that the effect of these techniques on drug distribution is somewhat limited in spite of the overdose of doxorubicin. Further studies are necessary to develop additional strategies for improve the distribution of doxorubicin. Importantly, UII and UT are abundant in the skeletal muscle of mouse and monkey, and radio-ligand binding assay has shown that UT binds UII with high affinity in skeletal muscle. Besides its important role in the cardiovascular system, UII also participates in metabolic regulation and plays a significant role in diabetes and its complications. We speculated that skeletal muscle-derived UII might be involved as an autocrine/paracrine factor in the pathogenesis of skeletal muscle insulin resistance, although the mechanism remains unclear. IR, the major defect of T2DM, is a common pathophysiological state in which higher than normal concentrations of insulin are required to exert its biological effect in target tissues such as the skeletal muscle, adipose tissue and liver. Considering the skeletal muscle accounts for the majority of insulin-mediated glucose disposal in the post-prandial state, skeletal muscle IR contributes significantly 
to the metabolic derangements seen in T2DM patients.