Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system.
View Article and Find Full Text PDFSuccessful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) "shielding" of residual tumor cells from promising chemotherapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell-killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 10-fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically-driven organic ion pump ("GemIP") to achieve controlled, targeted Gem delivery to GBM cells.
View Article and Find Full Text PDFThe Ca sensor STIM1 and the Ca channel Orai1 that form the store-operated Ca (SOC) channel complex are key targets for drug development. Selective SOC inhibitors are currently undergoing clinical evaluation for the treatment of auto-immune and inflammatory responses and are also deemed promising anti-neoplastic agents since SOC channels are linked with enhanced cancer cell progression. Here, we describe an investigation of the site of binding of the selective inhibitor Synta66 to the SOC channel Orai1 using docking and molecular dynamics simulations, and live cell recordings.
View Article and Find Full Text PDFBackground: Toxoplasmosis endangers the unborn child if its infectious agent--toxoplasma gondii--is transmitted transplacentally during pregnancy. Although this condition occurs in all parts of the world and represents a major public health burden, no detailed knowledge on the global research architecture of congenital toxoplasmosis is available thus far. Hence, it was the aim of this study to assess the related global research activity over the past 110 years.
View Article and Find Full Text PDFPaper presents current opinions on the definition, causes, classification, diagnosis and treatment of the compartment syndrome (CS). The development of CS after the long-bone fractures of the lower extremity and also after the limb operations or trauma without fracture is discussed. The importance of early and correct diagnostics and treatment is also revealed.
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