Overall, the data presented reveal that erufosine could have potential as an antimyeloma drug and deserves further development.

The ether lipid analog erufosine (erucylphospho-N,N,N,-trimethylpropylammonium, ErPC3) has high activity against leukemic cells without affecting the normal hematopoiesis. It belongs to the group of alkylphosphocholines (APC) that are inhibitors of protein kinase C and phospholipase C. However, the mechanism of action of erufosine remains rather unclear. We focused on combination effects with the tyrosine kinase inhibitor imatinib mesylate (gleevec, former STI-571 or CGP-57148) against two chronic myeloid leukemia (CML)-derived cell lines (K-562 and BV-173). The influence of erufosine on proteins involved in the phosphatidylinositol-3-phosphate pathway and on expression of the retinoblastoma protein Rb was studied, the latter being a key component for cell cycle entry and progression in mammalian cells. The consecutive treatment of K-562 and BV-173 cells with erufosine (2.5, 5, 15, 30 microM) and imatinib mesylate (0.05, 0.1 microM) led to synergism as measured by the MTT-dye reduction assay and this is reason to hypothesize that such combinations could be beneficial for relapsed patients with drug-resistant disease. Whole cell lysates from K-562 and BV-173 were investigated for the expression of Rb, PKB/Akt, pAkt, and p27 by Western blot. Erufosine caused decreases of pAkt and CML fusion protein p210 (BCR-ABL) protein expression, but induced the Rb protein expression in K-562 cells. A parallel increase in p27 level was observed after 24 and 48 h treatment. These alterations in signal transduction could be an explanation for the drug interaction found. Furthermore, Rb is a substrate of caspases and is cleaved during apoptosis as already evidenced for BV-173 cells. Our experimental findings suggest that erufosine acts through induction of changes in protein signaling and especially through Rb induction. This unique mode of action makes it an attractive partner for combination therapies, for example, in combination with imatinib mesylate for treatment of CML.

Despite the progress made in the fight against the COVID-19 pandemic, it still poses dramatic challenges for scientists around the world. Various approaches are applied, including repurposed medications and alternative routes for administration. Several vaccines have been approved, and many more are under clinical and preclinical investigation. This review aims to systemize the available information and to outline the key therapeutic strategies for COVID-19, based on the nasal route of administration.

Neurodegenerative disorders (NDs) have become a serious health problem worldwide due to the rapid increase in the number of people that are affected and the constantly aging population. Among all NDs, Alzheimer’s and Parkinson’s disease are the most common, and many efforts have been made in the development of effective and reliable therapeutic strategies. The intranasal route of drug administration offers numerous advantages, such as bypassing the blood–brain barrier and providing a direct entrance to the brain through the olfactory and trigeminal neurons. The present review summarizes the available information on recent advances in micro- and nanoscale nose-to-brain drug-delivery systems as a novel strategy for the treatment of Alzheimer’s and Parkinson’s disease. Specifically, polymer- and lipid-base micro- and nanoparticles have been studied as a feasible approach to increase the brain bioavailability of certain drugs. Furthermore, nanocomposites are discussed as a suitable formulation for administration into the nasal cavity.

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