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...

Hamlet: Has this fellow no feelings of his business, that he sings at grave-making? Horatio: Custom hath made it in him a property of easiness. (Hamlet Act V, scene i) Hamlet is appalled by the gravedigger's insensitivity towards death and corpses. Horatio explains that the gravedigger is so accustomed to such things that he no longer shares Hamlet's seriousness. We contend that human dissectio...

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, ...

T he events narrated by Shakespeare in his tragedy Hamlet 1 are the following: King Hamlet of Denmark dies suddenly and his brother Claudius a few weeks later marries the widow, his sister-in-law, Queen Gertrude; according to the official explanation, a snakebite was the cause of his death. The ghost of the king appears before his son, Prince Hamlet, and tells him that his own brother, now his ...