Cell Therapies in Bladder Cancer Management

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.     

Detection of the First Epoxyalcohol Synthase/Allene Oxide Synthase (CYP74 Clan) in the Lancelet (Branchiostoma belcheri,Chordata)

The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity.     

Online Coloring of Bipartite Graphs with and without Advice

In the online version of the well-known graph coloring problem, the vertices appear one after the other together with the edges to the already known vertices and have to be irrevocably colored immediately after their appearance. We consider this problem on bipartite, i.e., two-colorable graphs. We prove that at least ?1.13746?log₂(n)?0.49887? colors are necessary for any deterministic online algorithm to be able to color any given bipartite graph on n vertices, thus improving on the previously known lower bound of ?log₂ n?+1 for sufficiently large n. Recently, the advice complexity was introduced as a method for a fine-grained analysis of the hardness of online problems. We apply this method to the online coloring problem and prove (almost) tight linear upper and lower bounds on the advice complexity of coloring a bipartite graph online optimally or using 3 colors. Moreover, we prove that \(O(\sqrt{n})\) advice bits are sufficient for coloring any bipartite graph on n vertices with at most ?log₂ n? colors.     

Behavioral Changes in Workers of the Leaf-Cutting Ant Atta sexdens rubropilosa Induced by Chemical Components of Eucalyptus maculata Leaves

The response of Atta sexdens rubropilosa Forel workers to essential oils, epicuticular wax and hexane, dichloromethane, ethyl acetate, and methanol extracts of Eucalyptus maculata was evaluated. Hexane extracts of E. maculata interfered with the recognition mechanism among workers. The main active compounds identified from this plant were the sesquiterpenes elemol and beta-eudesmol. These compounds may be responsible for the resistance of this species to ant attack.     

Diffusional kinetics of metalliding zinc into solid copper

The process of incorporation of zinc into a copper cathode has been experimentally studied in a molten salt system at 381±2° C and at various current densities. The process is shown to be kinetically controlled by the diffusion of Zn into the solid matrix. A galvanostatic pulse titration technique has been used to determine the chemical diffusion coefficient at various alloy compositions, and an exponential relationship has been found between the diffusivity and the third power of the zinc concentration in the alloy. This relationship was then used in the diffusion equation within the solid matrix and a numerical integration was performed. Very good agreement was found between the calculated and experimental data for Zn interfacial concentration versus time. The same calculation procedure was used to determine zinc concentration profiles in the alloys.Nomenclature c _A concentration of the diffusing metal (mol cm^–3) - D _AB chemical diffusion coefficient of A into B (cm² s^–1) - E cell e.m.f. (mV) - F Faraday number - i current density (A cm^–2) - t time (s) - V _M alloy molar volume (cm³ mol^–1) - x linear dimension in the diffusion direction (cm) - X zinc mass fraction in the alloy - z ionic valence of Zn - stoichiometric ratio Zn/Cu     

Morphology and thermomechanical properties of recycled PET–organoclay nanocomposites

Recycled PET/organoclay nanocomposites were prepared by melt intercalation process with several amounts (1, 3, and 5 wt %) of clay modified with quaternary ammonium salt (DELLITE 67G) dispersed in a recycled poly(ethylene terephthalate) (rPET) matrix. The resultant mechanical properties (modulus and yield strength) of the nanocomposites were found to be different from those of rPET. Wide angle X‐ray scattering (WAXS) and Transmission Electron Microscopy (TEM) measurements have shown that although complete exfoliation was not achieved, delaminated clay platelets could be observed. Thermal analysis did not show significant changes in the thermal properties from those of recycled PET. Mechanical testing showed that nanocomposite properties were superior to the recycled PET in terms of strength and elasticity modulus. This improvement was attributed to nanoscale effects and strong interaction between the rPET matrix and the clay interface, as revealed by WAXS and TEM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1839–1844, 2007     

Effect of olive paste kneading process time on the overall quality of virgin olive oil

The influence of the olive paste malaxation time on the composition and the industrial output of oil was investigated. To this purpose, three Italian olive varieties (Leccino, Dritta, Caroleo) were processed with a centrifugal system for six malaxation periods (0, 15, 30, 45, 60 and 75 min). The concentrations of the majority of the oil constituents changed during the malaxation. However, these changes were not significant for all of them: the contents of β‐carotene, the major xanthophylls, chlorophylls a and b, pheophytins a and b in the oils increased progressively with increasing malaxing times, whereas the contents of simple and hydrolysable phenols (secoiridoid derivatives), o‐diphenols and total phenols decreased. A significant increase in total volatiles and green volatiles of the lipoxygenase cascade (C₆ aldehydes, C₆ alcohols, C₅ alcohols and C₅ carbonyls) was detected. An opposite trend was observed for the green C₆ esters. As a result, the global analytical quality, flavour, aroma and shelf‐life of the oils were negatively affected. The oil yield increased substantially up to 45 min of paste malaxation times. Beyond 60 min, the yields tended to decrease.