Ovide informations on combination strategies. In fact, these data by performing sequential biopsies from patients treated with AZD1480, to determine its in vivo effect on JAK2, ERK, p38 and Aurora A, and AS-604850 to correlate the phosphorylation status of these proteins with the response to AZD1480 therapy. Finally, these data provide a mechanistic rationale for combination strategies aiming at blocking the AZD1480 induced activation of ERK and p38. Hepatocellular carcinoma, the major form of primary liver cancer, is one of the most deadly human cancers. The pathogenesis of HCC is frequently linked with continuous hepatocyte death, inflammatory cell infiltration and compensatory liver regeneration.
Understanding the molecular signaling pathways driving or mediating these processes during liver tumorigenesis is important for the identification of novel therapeutic targets for this dreadful Baicalein disease. The classical IKK dependent NF ?B signaling pathway has been shown to promote hepatocyte survival in both developing and adult livers. In addition, it also plays a crucial role in liver inflammatory responses by controlling the expression of an array of growth factors and cytokines. One of these cytokines is IL 6, which is best known for its role in the liver acute phase response. IL 6 exerts many of its functions via activation of STAT3, a transcription factor found to be important for HCC development. This review will focus on recent studies on the roles of NF ?B and STAT3 in liver cancer. Interactions between the two pathways and their potential as therapeutic targets will also be discussed.
Introduction Nearly 25 years ago, Dvorak recognized that the composition of the tumor stroma is very similar to that of granulation tissue of healing skin wounds. He therefore suggests that tumors are wounds that do not heal. Careful examination of the many phases of wound healing and tumorigenesis reveals even more extensive similarities between these two processes. Importantly, the human body mounts inflammatory responses in both situations aiming to clear dead cells and restore the tissue integrity. However, unlike the normal wound healing process that is tightly regulated both in extent and in duration, the inflammatory response during cancer development is not self limited. It is estimated that about 15% of human cancers are associated with chronic infections and inflammation.
The best examples of inflammation and infection associated cancers include colon cancer and inflammatory bowel diseases, gastric cancer and chronic Helicobacter pylori infection, and hepatocellular carcinoma following chronic hepatitis virus infection. Persistent infections and inflammation in these organs lead to continuous cell death and long lasting local infiltration of inflammatory cells. Even those cancers, whose development is not associated with pre existing infection or inflammation, are accompanied by massive inflammatory cell recruitment into the tumor, a phenomenon which led Virchow to his original suggestion that inflammation and cancer are linked. This inflammatory response is likely caused by necrotic cell death in the core of rapidly growing tumor mass due to lack of oxygen and nutrients. Continuous cell death and inflammatory cell i