The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

Transparente leitfähige Nitride

Transparent conductive nitrides – New perspectives in device design More than 20 years after the pioneer of the GaN LED Nobel laureate Shuji Nakamura published that germanium is an inferior dopand for GaN when compared to silicon we showed that the opposite is true in regard of achievable n-type doping concentration. With Ge-doped GaN now device performance can be improved and new device structures realized. As transparent highly conductive nitride (TCN) new application fields emerge for GaN, in particular the replacement of ITO. Besides many potential applications Ge-doped GaN layers also show interesting physics as a new quasiparticle, the Collexon.     

Mechanism of cytotoxicity and cellular uptake of lipophilic inert dinuclear polypyridylruthenium(II) complexes

The accumulation, uptake mechanism, cytotoxicity, cellular localisation of—and mode of cell death induced by—dinuclear ruthenium(II) complexes ΔΔ/ΛΛ‐[{Ru(phen)₂}₂{μ‐bb_n}]⁴⁺ (Rubb_n), where phen is 1,10‐phenanthroline, bb_n is bis[4(4′‐methyl‐2,2′‐bipyridyl)]‐1,n‐alkane (n=2, 5, 7, 10, 12 or 16), and the corresponding mononuclear complexes containing the bb_n ligands, were studied in L1210 murine leukaemia cells. Cytotoxicity increased with linker chain length, and the ΔΔ‐Rubb₁₆ complex displayed the highest cytotoxicity of the series, with an IC₅₀ value of 5 μM , similar to that of carboplatin in the L1210 murine leukaemia cell line. Confocal microscopy and flow cytometry studies indicated that the complexes accumulate in the mitochondria of L1210 cells, with the magnitude of cellular uptake and accumulation increasing with linking chain length in the bb_n bridge of the metal complex. ΔΔ‐Rubb₁₆ entered the L1210 cells by passive diffusion (with a minor contribution from protein‐mediated active transport), inducing cell death via apoptosis. Additionally, metal‐complex uptake in leukaemia cells was approximately 16‐times that observed in healthy B cells highlighting that the bb_n series of complexes may have potential as selective anticancer drugs.     

A Natural Algacide from Soft Coral Sinularia flexibilis (Coelenterata, Octocorallia, Alcyonacea)

A crude lipophilic extract and specific pure metabolites of the soft coral Sinularia flexibilis have been examined for algacidal properties both in laboratory and field experiments. Laboratory algal bioassays, in which cultures of the common fouling alga Ceramium codii were incubated with six different diterpenes isolated from S. flexibilisrevealed that 11-episinulariolide exhibits strong algacidal properties. Field experiments carried out with treated settlement tiles confirmed the laboratory findings and provided evidence for the algacidal properties of 11-episinulariolide against several other common reef algae. Sinulariolide, which had previously been reported to inhibit the growth of unicellular algae, was approximately one third as effective as its stereoisomer 11-episinulariolide in the laboratory growth inhibition bioassay and showed no significant algacidal properties at the concentrations used in the field experiments.     

Novel Furin Inhibitors with Potent Anti‐infectious Activity

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a K_i value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases.     

Innovative Diagnostic Peptide-Based Technologies for Cancer Diagnosis: Focus on EGFR-Targeting Peptides

Active targeting using biological ligands has emerged as a novel strategy for the targeted delivery of diagnostic agents to tumor cells. Conjugating functional targeting moieties with diagnostic probes can increase their accumulation in tumor cells and tissues, enhancing signal detection and, thus, the sensitivity of diagnosis. Due to their small size, ease of chemical synthesis and site-specific modification, high tissue penetration, low immunogenicity, rapid blood clearance, low cost, and biosafety, peptides offer several advantages over antibodies and proteins in diagnostic applications. Epidermal growth factor receptor (EGFR) is one of the most promising cancer biomarkers for actively targeting diagnostic and therapeutic agents to tumor cells due to its active involvement and overexpression in various cancers. Several peptides for EGFR-targeting have been identified in the last decades, which have been obtained by multiple means including derivation from natural proteins, phage display screening, positional scanning synthetic combinatorial library, and in silico screening. Many studies have used these peptides as a targeting moiety for diagnosing different cancers in vitro, in vivo, and in clinical trials. This review summarizes the progress of EGFR-targeting peptide-based assays in the molecular diagnosis of cancer.