Epithelial mesenchymal transition (EMT) is a well conserved process by which polarized, immotile epithelial cells transition into motile mesenchymal cells. EMT plays an important role during normal biological processes such as embryogenesis and wound healing. More recently, EMT has been studied for its role in cancer progression and metastasis. Understanding the molecular mechanisms that regulate EMT are key to developing novel therapeutic interventions for cancer. Dysregulated or uncontrolled activation of the Wnt/Î²-catenin signaling pathway promotes tumor progression and metastasis. The Wnt/Î²-catenin signaling pathway is one of the signaling pathways that has been implicated in EMT. In this review, major Wnt target genes that promote EMT as well as the various antagonists and microRNAs that regulate the Wnt/Î²-catenin pathway to influence EMT during cancer progression will be discussed.
Diabetes is a long-standing disease that leads to secondary complications of capillaries such as retinopathy, nephropathy and neuropathy. Emerging evidence suggests that diabetes may also affect the cerebromicrovasculature, the blood-brain barrier (BBB), and lead to changes in the brain that affect cognition and mood. Therefore, it is important to identify natural compounds that may have therapeutic benefit for reducing BBB dysfunction and improve patient quality of life. Preclinical evidence suggests that sesamol, a natural antioxidant in sesame seed oil, could have therapeutic benefit for treating BBB dysfunction during diabetes. Similarly, paroxetine, which shares a methylenedioxy moiety with sesamol shows clinical benefit for treating neuropathic pain associated with diabetes. This review emphasizes BBB dysfunction as a treatable secondary complication associated with diabetes and examines the evidence for the use of natural compounds like sesamol or existing therapies like paroxetine to help restore BBB function.
In this tutorial review, the machinery of optical (visible and infrared) two-dimensional coherent spectroscopy has been discussed from a conceptual point of view, emphasizing the necessity along with few practical applications of this state-of the art spectroscopic technique.
Cancer and aging, despite seemingly opposite characteristics, are tightly linked. Indeed, cancer incidence and mortality dramatically increases with age. This review discusses some of the hallmarks of the two processes and tries to offer an explanation on why the degenerative pathology of aging is at least partly linked to the hyperplastic diseases of cancer.
Phosphatase and tensin homolog detected on chromosome ten (PTEN) is a tumor suppressor gene protecting cells from developing cancer and forming tumors (Leslie and den Hertog). In addition, PTEN mediates cell cycle arrest, adhesion, migration, and apoptosis(Sun, Lesche et al. 1999). The complete loss or mutations in the PTEN gene has been implicated in many human cancers from mammary carcinoma to developmental abnormalities and autism. It is in fact the most common mutation in human cancers and are inherited in an autosomal dominant manner (Yamada and Araki 2001). In their recent Cell paper, Papa et al (Papa, Wan et al. 2014) shows a novel homodimerization characteristic of PTEN that renders it active. Mechanistically, the homodimerized active conformation exerts its phosphatase activity on downstream targets such as AKT, PIP3, and PI3K and decreases their oncogenic activity. The two mutated PTEN isoforms characterized in this study have a reversed functionality compared to wild-type protein. These findings have great implications in developing drug agents that target PI3K pathway and sensitive to PTEN mutations.
The development of leadership and project management skills is increasingly important to the evolution of translational science and team-based endeavors. Team science is dependent upon individuals at various stages in their careers, inclusive of postdocs. Data from case histories, as well as from interviews with current and former postdocs, and those supervising postdocs, indicate six essential tasks required of project managers in multidisciplinary translational teams, along with eight skill-related themes critical to their success. To optimize the opportunities available and to ensure sequential development of team project management skills, a life cycle model for the development of translational team skills is proposed, ranging from graduate trainees, postdocs, assistant professors, and finally to mature scientists. Specific goals, challenges and project management roles and tasks are recommended for each stage for the life cycle.
IL2-inducible T-cell kinase (ITK), a member of the Tec family tyrosine kinases, is the predominant Tec kinase in T cells and natural killer (NK) cells mediating T cell receptor (TCR) and Fc receptor (Fc R) initiated signal transduction. ITK deficiency results in impaired T and NK cell functions, leading to various disorders including malignancies, inflammation, and autoimmune diseases. In this mini-review, the role of ITK in Tcell signaling and the development of small molecule inhibitors of ITK for the treatment of T-cell related disorders is examined.