Disufenton sodium NXY-059 directly activated miR 21 in NSCLC cells. These results suggest that, in lung cancer, miR 21 affects the response to enzastaurin through the JAK/STAT signalling pathway. In conclusion, we have identified unique molecules, genes, RTKs and miRNAs that are correlated with sensitivity to enzastaurin and have constructed an eight gene signature to distinguish the sensitive cells from the resistant cells. Furthermore, we demonstrate that JAK1 is the most significant factor concerned in response to enzastaurin. Patient selection based on the JAK expression might be useful for future clinical development of enzastaurin therapy in NSCLC. ACKNOWLEDGEMENTS This study was supported in part by a Grant in Aid from the Ministry of rhein inhibitor Education, Culture, Sports, Science and Technology of Japan, and Basic and Clinical Studies on Functional RNA Molecules for Advanced Medical Technologies. Wound healing is a complex process that is characterized by three orderly but overlapping phases: the inflammation phase, the cell proliferation phase and the remodeling phase. In each stage, various cells are activated and orchestrated to contribute to the repair of injury.
As the major cell type in the epidermis, the keratinocyte has critical high throughput chemical screening roles in wound healing. Functions of keratinocytes are involved in every stage of the wound healing process. Upon the occurrence of a wound, keratinocytes produce and secrete a number of chemokines such as CCL and CXCL super families under the stimulation of the change in potential difference between the epidermal and dermal layers and other micro environment factors through receptors. Through these factors, keratinocytes contribute to the recruitment of neutrophils and macrophages to the wound site to remove foreign material, bacteria and non functional host cells and damaged matrix components. During cellular proliferation, keratinocytes express and secrete numerous growth factors and cytokines that contribute to the integrated action of a number of cell types, cytokines and the extracellular matrix. Moreover, keratinocytes play a very important role in wound closure by expressing keratins and influencing recentin wound contraction. Currently, the cultured keratinocytes have already been used in the therapy of chronic ulcers and wound healing disorders. Moreover, it was also reported that promoted keratinocyte proliferation could lead to enhanced wound healing.
The proliferation of keratinocytes can be regulated by various factors. It was found that UV irradiation and small molecules such as estrodiol, purines, pyrimidines and calcitonin gene related peptide can stimulate the growth of keratinocytes. More importantly, keratinocyte cisplatin proliferation is influenced by a number of biological growth factors such as keratinocyte growth factor, epidermal growth factor, IL 6, granulocyte macrophage colony stimulating factor, hepatocyte growth factor, transforming growth factor a and b that form the molecular basis of the interaction between keratinocytes and other cells during wound healing. The molecular mechanism of the regulation of keratinocyte proliferation has also been investigated intensively and it has been found that protein kinases contribute significantly in the regulation. Herbal products are used intensively for wound healing in tradition.