Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects

There is an ongoing need for effective and targeted cancer treatments that can overcome the detrimental side effects presented by current treatment options. One class of novel anticancer molecules with therapeutic potential currently under investigation are cationic antimicrobial peptides (CAPs). CAPs are small innate immunity peptides found ubiquitously throughout nature that are typically membrane-active against a wide range of pathogenic microbes. A number of CAPs can also target mammalian cells and often display selective activity towards tumor cells, making them attractive candidates as novel anticancer agents warranting further investigation. This current and comprehensive review describes key examples of naturally occurring membrane-targeting CAPs and their modified derivatives that have demonstrated anticancer activity, across multiple species of origin and structural subfamilies. In addition, we address recent advances made in the field and the ongoing challenges faced in translating experimental findings into clinically relevant treatments.     

Releasement and Nihilism in the Art of Living with Technology

In this contribution the author tries to formulate an approach to the art of living with technology based on Heidegger’s The Principle of Reason, a work often overlooked by contemporary commentators in the philosophy of technology. This approach couples the concept of releasement to insights hailing from Wolfgang Schirmacher concerning Heidegger’s nihilism.     

Detectable clonal mosaicism from birth to old age and its relationship to cancer

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).     

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer

PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.     

The Documentary Real and the Shoah

Without the support of imagination, one would not have the slightest idea of the cruel ‘real’ that has occurred in the Nazi extermination camps. Yet, in documentaries imaging the events of the Shoah, one runs the risk of missing their most basic property, namely their unimaginability. The mere idea that one is able to imagine the unimaginable comes down to a denial of the Shoah’s status as an event that defies our understanding. The unimaginable ‘real’ of the Shoah, however, is not simply located in its object, in the cruelty of what happened in the camp. The Shoah makes us at the same time facing the unimaginable ‘real’ of the modern subject—the blind spot in our own identity. If we need imagination to deal with the Shoah, it is also because of an ungraspable ‘real’ in ourselves. This is why adequate Shoah representations, acknowledging their object as being beyond representation, include the same ‘beyond’ concerning the subject of the Holocaust memory. The essay makes this clear in an elaborated comparison of Claude Lanzmann’s 1985 film, Shoah, with some conceptual works of art from the late nineties—all of this ‘fine-tuned’ in a reflection upon Ingmar Bergman’s Persona.