AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.     

Role of Epithelial–Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments

The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial–mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal–epithelial transition, MET), now collectively called epithelial–mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial–mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.     

Photosynthetic membranes, 21. Immobilization of catalase by photochemically grafted ultrafiltration membranes

Catalase has been immobilized in membranes prepared by photoinduced grafting onto microporous polymeric supports and its catalytic activity on hydrogen peroxide decomposition has been studied under ultrafiltration conditions by means of a recirculation apparatus. The membranes showed a very good catalytic performance and the enzyme reaction took place exclusively within the membrane structure. Initial reaction rates measured in the temperature range 5 – 35°C as a function of both substrate concentration and enzyme amount immobilized per unit membrane surface indicate that the mechanism of action of catalase is not altered after immobilization.     

Dispersing Behavior of Hydroxyapatite Powders Produced by Wet-Chemical Synthesis

Three hydroxyapatite powders with different surface properties were produced by wet-chemical synthesis and characterized. The electrokinetic properties of powders dispersed in water were investigated by electroacoustic spectroscopy measurements. The different surface reactivity (pH_iep and ζ potential versus pH curves) was related to the interplay of dissolution and adsorption of Ca²⁺ ions. With a view toward the preparation of porous bodies by sponge impregnation, the behavior of powder suspensions was studied. Four deflocculants were tested, and the optimum dispersing conditions for each powder were found. Anionic polyelectrolytes resulted in the best effective dispersing agent, with different optimum amounts added to the suspensions.     

Nonhypothesis Analysis of a Mutagenic Soybean (Glycine max [L.]) Population for Protein and Fatty‐Acid Composition

Soybean is a major source of oil for food, feed, and biofuel production. Mutagenesis is a tool for creating unique traits useful in breeding programs. The aim of this study is to use nonhypothesis statistical testing methods to make decisions about a mutagenic population. To this end, a total of 1037 mutation lines and 28 wild‐type lines were analyzed for fatty‐acid composition and protein content. Principal component analysis (PCA) was used to analyze the fatty acid profile, multivariate analysis of variance (MANOVA) to build a selection model for seed weight per plant and weight per 10 seeds, and clustering in conjunction with power analysis to determine the minimum number of individuals needed to create a MANOVA selection model for the oil to protein content. Five of the 35 possible entries were identified by PCA analysis for stearic acid and four of 16 possible entries for oleic acid. Interestingly, most of the selected mutants were validated genetically. In fact, selected mutants with high seed stearic acid or high seed oleic acid contents were verified to carry mutations on GmFAD2‐1A, GmFAD2‐1B, and GmSACPD‐C genes. This shows a promising method of identifying smaller portion of the population to screen for desired mutations.     

Thermal and UV degradation of polypropylene with pro‐oxidant. Abiotic characterization

The oxodegradation of an injection molding grade polypropylene (PP), formulated with 0%, 1.5%, and 3% w/w of a pro‐oxidant additive, was studied. The degradation was conducted in a weathering tester at 60 °C for 40 h. The process was monitored by Fourier transform infrared spectroscopy, standard differential scanning calorimetry, and successive self‐nucleation and annealing. Neat PP samples did not exhibit significant changes during the exposure time employed. PP samples with oxo‐additive presented similar changes independently of the amount of oxo‐degradative additive employed; however, the changes manifested more rapidly in the formulation with higher pro‐oxidant content. Fourier transform infrared spectroscopy studies revealed the presence of hydroxyl and carbonyl functional groups whereas differential scanning calorimetry tests showed the decrease in the melting and crystallization temperatures as a consequence of the chain scission and oxidation reactions taking place during exposure. In addition, the induction time (t_id) of the oxo‐degradative process was determined for each technique employed and successive self‐nucleation and annealing was found to be the most sensitive characterization technique to reveal structural modifications in PP samples. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46088.     

Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I

The structure and biological activities of two disulphide isomersof a C-region deletion mutant of insulin-like growth factor-I(IGF-I) which has an Asn–Gly link engineered at the junctionof the A- and B-regions were studied before and after chemicalcleavage. Circular dichroism (CD) spectra and binding affinityto IGF binding protein 3 (IGFBP3) indicated that the treatmentwith hydroxylamine did not disrupt the overall tertiary foldof the hormones. Cleavage restored some binding affinity forthe IGF-I receptor in both isomers and weakly restored the abilityto stimulate incorporation of tritiated thymidine into DNA inNIH 3T3 fibroblasts transfected with the human IGF-I receptor.Cleavage also restored metabolic capacity, as measured by theability of the isomers to promote lipogenesis in isolated ratadipocytes through the insulin receptor. These results are consistentwith the theory that binding of IGF-I to the IGF-I receptorrequires a conformational change similar to that involved ininsulin binding the insulin receptor. The weak affinity forthe IGF-I receptor after cleavage is consistent with the beliefthat residues in the C-region interact with the IGF-I receptor.This structural difference between insulin and IGF-I gives eacha higher binding affinity for its own receptor.     

Selection of catalytically active biotin ligase and trypsin mutants by phage display

Phage display has been shown to facilitate greatly the selectionof polypeptides with desired properties by establishing a directlink between the polypeptide and the gene that encodes it. However,selection for catalytic activities displayed on phage remainsa challenge, since reaction products diffuse away from the enzymeand make it difficult to recover catalytically active phage–enzymes.We have recently described a selection methodology in whichthe reaction substrate (and eventually the reaction product)is anchored on calmodulin-tagged phage–enzymes by meansof a calmodulin binding peptide. Phage displaying a catalyticactivity are physically isolated by means of affinity reagentsspecific for the product of reaction. In this study, we investigatedthe efficiency of selection for catalysis by phage display,using a ligase (the Escherichia coli biotin ligase BirA) andan endopeptidase (the rat trypsin His57     

Design,Synthesis, and Biological Evaluation of Unconventional Aminopyrimidine,Aminopurine, and Amino‐1,3,5‐triazine Methyloxynucleosides

Herein we describe a class of unconventional nucleosides (methyloxynucleosides) that combine unconventional nucleobases such as substituted aminopyrimidines, aminopurines, or aminotriazines with unusual sugars in their structures. The allitollyl or altritollyl derivatives were pursued as ribonucleoside mimics, whereas the tetrahydrofuran analogues were pursued as their dideoxynucleoside analogues. The compounds showed poor, if any, activity against a broad range of RNA and DNA viruses, including human immunodeficiency virus (HIV). This inactivity may be due to lack of an efficient metabolic conversion into their corresponding 5′‐triphosphates and poor affinity for their target enzymes (DNA/RNA polymerases). Several compounds showed cytostatic activity against proliferating human CD4⁺ T‐lymphocyte CEM cells and against several other tumor cell lines, including murine leukemia L1210 and human prostate PC3, kidney CAKI‐1, and cervical carcinoma HeLa cells. A few compounds were inhibitory to Moloney murine sarcoma virus (MSV) in C3H/3T3 cell cultures, with the 2,6‐diaminotri‐O‐benzyl‐D ‐allitolyl‐ and ‐D ‐altritolyl pyrimidine analogues being the most potent among them. This series of unconventional nucleosides may represent a novel family of potential antiproliferative agents.