Dendritic Cells and Cancer Immunotherapy: The Adjuvant Effect

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.     

NMR study on reaction processes from aluminum chloride hydroxides to alpha alumina powders

Starting from gelatinous aluminum chloride hydroxide, the transformation process toward α-Al₂O₃ was examined using ²⁷Al NMR, both in the liquid and solid states, as a main analytical tool. By increasing the hydrolysis ratio (h, defined as [OH⁻]/[Al³⁺]) of the starting aqueous precursor up to h = 2.5, the transition temperature to the final product, α-Al₂O₃, decreased to as low as 500°C. In this case, the structural change from amorphous alumina to α-Al₂O₃ took place without intermediate transition Al₂O₃ phases. Examining the process of networking during the transition from aqueous sol–through the state of xerogel–to final anhydrous oxide by nuclear magnetic resonance (NMR) revealed the presence of highly polymeric species mainly ascribed to δ-[Al₂O₈Al₂₈(OH)₅₆(H₂O)₂₄]¹⁸⁺ (δ-Al₃₀). δ-Al₃₀ species were found in the solution phase and became predominant after drying. We conclude that the lower temperature synthesis of α-Al₂O₃ became possible due to preformation of polymerized AlO₆ construction units in the precursor, reducing the energy barrier for the nucleation of the final α-Al₂O₃ phase.     

Wear resistance glass-ceramics with a gahnite phase obtained in CaO-MgO-ZnO-Al2O3-B2O3-SiO2 system

The thermal conditions for obtaining the glass-ceramic material of Al_0.107B_0.374Mg_0.043Zn_0.282Ca_0.100Si_0.927O₃ with a crystalline phase in the form of gahnite (ZnAl₂O₄) were specified. The activation energy E_a and the Avrami parameter n for the crystallisation process were determined with the non-isothermal DTA procedure. The maximum temperatures of crystallisation of phases, depending on the rate of heating, ranged between 800-840 °C for willemite and 870-915 °C for gahnite. The homogeneous crystalline spinel phase was obtained by heat treatment above 1000 °C. Precipitation solely of a ghanite phase from glass-ceramic causes a relative increase in its fracture toughness and wear resistance compared to the two-phase materials, i.e., K_IC = 2.12-1.65 MPam^1/2 and w_s = 0.21 × 10⁻⁴ mm³/Nm to w_s = 1.43 × 10⁻⁴ mm³/Nm.     

Chain packing versus chain mobility in semialiphatic BTDA-based copolyimides

A series of partially aliphatic copolyimides derived from 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA), 4,4′-diaminodiphenylmethane (DDM) and 1,6-diaminohexane (DAH) was synthesized. Solubility tests and structural characteristics, evaluated by wide-angle X-ray diffraction measurements (WAXD) did not vary steadily with the content of the flexible segment. On the dynamic mechanical analysis (DMA) the evolution of the secondary relaxations (γ and β) suggested an increased chain tightness as more aliphatic component is included. The onset temperature of α-relaxation decreased regularly with the content of aliphatic sequence. During the α-relaxation the trend of E′, E″ and tan δ with temperature, and at multiple frequencies, evidenced the overlapping of phenomena. The increased mobility determines the formation of oriented structures that behave as constraints. Simultaneously, as the flexible content (DAH segment) is more important, orientation relaxations take place with increasing temperature. The equilibrium between stiffening and flowing makes the polyimides with high aliphatic content behave like elastomers.     

Host Sex Discrimination by an Egg Parasitoid on Brassica Leaves

Egg parasitoids are able to find their hosts by exploiting their chemical footprints as host location cues. In nature, the apolar epicuticular wax layer of plants that consists of several classes of hydrocarbons serves as the substrate that retains these contact kairomones. However, experiments on chemical footprints generally have used filter paper as substrate to study insect behavior. Here, we explored the ability of Trissolcus basalis (Scelionidae) females to discriminate between footprint cues left by male and female Nezara viridula (Pentatomidae) on leaves of their host plant Brassica oleracea (broccoli). Furthermore, we analyzed the chemical composition of the outermost wax layer of broccoli leaves to evaluate the degree of overlap in insect and plant cuticular hydrocarbons that could lead to masking effects in the detection of footprint cues. Our results showed that B. oleracea epicuticular wax retains the chemical footprints of adult bugs and allows T. basalis females to differentiate hosts of different sex. Traces of female bugs elicited more extensive searching behavior in egg parasitoids than traces of males. The application of n-nonadecane, a compound specific to male N. viridula, on the tarsi of female bugs prevented parasitoid females from distinguishing between host male and host female footprints. Analyses of B. oleracea leaves revealed that epicuticular waxes were mainly composed of linear alkanes, ketones, and secondary alcohols. Alkanes were dominated by n-nonacosane (nC29) and n-hentriacontane (nC31), while male-specific n-nonadecane (nC19) was absent. The ecological significance of these results for parasitoid host location behavior is discussed.     

Peptide‐Based Fluorescent Probes for Deacetylase and Decrotonylase Activity: Toward a General Platform for Real‐Time Detection of Lysine Deacylation

Histone deacetylases regulate the acetylation levels of numerous proteins and play key roles in physiological processes and disease states. In addition to acetyl groups, deacetylases can remove other acyl modifications on lysines, the roles and regulation of which are far less understood. A peptide‐based fluorescent probe for single‐reagent, real‐time detection of deacetylase activity that can be readily adapted for probing broader lysine deacylation, including decrotonylation, is reported. Following cleavage of the lysine modification, the probe undergoes rapid intramolecular imine formation that results in marked optical changes, thus enabling convenient detection of deacylase activity with good statistical Z′ factors for both absorption and fluorescence modalities. The peptide‐based design offers broader isozyme scope than that of small‐molecule analogues, and is suitable for probing both metal‐ and nicotinamide adenine dinucleotide (NAD⁺)‐dependent deacetylases. With an effective sirtuin activity assay in hand, it is demonstrated that iron chelation by Sirtinol, a commonly employed sirtuin inhibitor, results in an enhancement in the inhibitory activity of the compound that may affect its performance in vivo.     

Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins

Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds.     

Multilayer biopolymer/poly(ε-caprolactone)/polycation nanoparticles

Combining two or more materials for carrier construction is one of the topical approaches to avoid/diminish deficiencies and to increase functionality in delivery systems for bioactive compounds. In this context, here, multilayered nanoparticles comprising both natural (atelocollagen—AteCol; hyaluronic acid derivative—HA) and synthetic [poly(ε-caprolactone)—PCL; polyethylenimine—PEI; poly(l-lysine)—PLL] polymers were prepared and characterized. The combination of a modified double-emulsion method with polymer modification reactions allowed improvement of the polymer particle’s functionality. Fourier transform infrared spectroscopy (FTIR), UV–Vis spectroscopy, fluorescence spectroscopy, dynamic light scattering, transmission/scanning electron microscopy and fluorescence microscopy investigations confirmed the obtention of the envisaged nanomaterials with the expected composition and structure. The double-layered biopolymer/PCL-based nanoparticles formed in a first synthesis step could be successfully coated with PEI and PLL. The gel electrophoresis assay attested the DNA packing ability of the formed nano-vehicles involving surface grafting of the former biopolymer/PCL-based nanoparticles in the case of both cationic polymers, for N/P ratios of 10 (PEI coating) and 3.5 (PLL coating), respectively. According to the FTIR registration, the protein’s native form was preserved. Considering the advantage of biocompatibility and high versatility (controlled size, tuned chemistry and biodegradation rate) some of the resulted nanomaterials may appear as potential candidates for biomedical uses (i.e., drug/gene delivery and tissue engineering).