Entamoeba histolytica is an intestinal protozoan parasite that causes amoebic dysentery and liver abscess. Phagocytosis by the parasite is a critical virulence process, since it is a prerequisite for tissue invasion and establishment of chronic infection. While the roles of many of the proteins that regulate phagocytosis-related signaling events in E. histolytica have been characterized, the functions of lipids in this cellular process remain largely unknown in this parasite. In other systems, phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ), a major product of phosphoinositide 3 kinase (PI3-kinase) activity, is essential for phagocytosis. Pleckstrin homology (PH) domains are protein domains that specifically bind to PIP 3 . In this study, we utilized glutathione S-transferase (GST)-and green fluorescent protein (GFP)-labeled PH domains as lipid biosensors to characterize the spatiotemporal aspects of PIP 3 distribution during various endocytic processes in E. histolytica. PIP 3 -specific biosensors accumulated at extending pseudopodia and in phagosomal cups in trophozoites exposed to erythrocytes but did not localize to pinocytic compartments during the uptake of a fluid-phase marker, dextran. Our results suggest that PIP 3 is involved in the early stages of phagosome formation in E. histolytica. In addition, we demonstrated that PIP 3 exists at high steady-state levels in the plasma membrane of E. histolytica and that these levels, unlike those in mammalian cells, are not abolished by serum withdrawal. Finally, expression of a PH domain in trophozoites inhibited erythrophagocytosis and enhanced motility, providing genetic evidence supporting the role of PI3-kinase signaling in these processes in E. histolytica.Entamoeba histolytica is an intestinal protozoan parasite that causes amoebic dysentery and liver abscess. A high incidence of E. histolytica infection is found in developing countries and is associated with low basic hygiene standards and a lack of water sanitation (reviewed in reference 20). Since E. histolytica is mainly a human parasite (40), improvements in sanitation may help prevent the fecal-oral spread of this pathogen; however, overpopulation, scarcity of clean water, and socioeconomic shortcomings impede the progress of such improvements in developing countries (36). This lack of progress supports an elevated need for the development of improved prevention, diagnosis, and treatment for dysentery caused by E. histolytica. This requires a better understanding of the basic biology of this parasite.

LKB1 acts as a master kinase, with its major protein targets being the family of AMPKs. Through activation of multiple signaling pathways, LKB1's main physiologic functions involve regulating cellular growth, metabolism, and polarity. Germline mutations in LKB1 result in Peutz-Jeghers Syndrome, a rare cancer susceptibility syndrome. In addition, multiple LKB1 mutations have been identified in sporadic cancers, especially those of the lung. Recent studies from a variety of murine models have helped characterize LKB1's role in the pathogenesis of epithelial cancers. In some tumor types, LKB1 might function chiefly to suppress cell growth or invasion, while in other cases, it may serve to prevent metastasis. Moreover, molecular signatures of individual tumors likely influence LKB1's operational role, as multiple studies have shown that LKB1 can synergize with other tumor suppressors and/or oncogenes to accelerate tumorigenesis. To date, LKB1 has been considered mainly a tumor suppressor; however, some studies have suggested its potential oncogenic role, mainly through the suppression of apoptosis. In short, LKB1 is a tissue and context-specific kinase. This review aims to summarize our current understanding of its role in the pathogenesis of epithelial cancers.

Our case series is only the second report in the literature demonstrating complete resolution of MF tumors with topical imiquimod. An additional therapeutic option for tumor-stage MF, imiquimod may represent an effective alternative to localized radiation for isolated MF tumors and warrants further investigation in the treatment of various stages of MF.

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