The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a na...

The relationship between Hamlet and Gertrude seems to be the exception to the rule regarding parent-child connections. Although Hamlet shows clear distress about his mother's marriage to Claudius, his relationship with her is positive. Even though his mother's actions lead Hamlet to frequently criticize women in general, in obvious allusion to Gertrude's marriage, and even though Claudius' marr...

BACKGROUND Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. OBJECTIVE To investigate if HAMLET can be used for colon cancer treatment and pre...

Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed...

The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedent...

The purpose of this article is to present a multi-strategy approach to learn heuristics for planning. This multi-strategy system, called HAMLET-EVOCK, combines a learning algorithm specialized in planning (HAMLET) and a genetic programming (GP) based system (EVOCK: Evolution of Control Knowledge). Both systems are able to learn heuristics for planning on their own, but both of them have weaknes...

Human α-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, function...

BACKGROUND Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded alpha-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or s...

Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current...

Shakespeare’s Hamlet ominously begins with Horatio and Marcellus discussing the appearance of a ghostly apparition that strangely resembles the King of Denmark. As the play unfolds, we learn that it is, in fact, the ghost of Hamlet Sr., the King of Denmark. Immediately, the play begins with a sense of foreboding danger for all of those involved who have a direct connection with his son Hamlet, ...