Novel Inhibitor-Based Therapies for Thyroid Cancer—An Update

Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.     

Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response,Cancer, and Differentiation

G protein-coupled receptor 55 (GPR55) is a recently deorphanized lipid- and peptide-sensing receptor. Its lipidic endogenous agonists belong to lysoglycerophospholipids, with lysophosphatidylinositol (LPI) being the most studied. Peptide agonists derive from fragmentation of pituitary adenylate cyclase-activating polypeptide (PACAP). Although GPR55 and its ligands were implicated in several physiological and pathological conditions, their biological function remains unclear. Thus, the aim of the study was to conduct a large-scale re-analysis of publicly available gene expression datasets to identify physiological and pathological conditions affecting the expression of GPR55 and the production of its ligands. The study revealed that regulation of GPR55 occurs predominantly in the context of immune activation pointing towards the role of the receptor in response to pathogens and in immune cell lineage determination. Additionally, it was revealed that there is almost no overlap between the experimental conditions affecting the expression of GPR55 and those modulating agonist production. The capacity to synthesize LPI was enhanced in various types of tumors, indicating that cancer cells can hijack the motility-related activity of GPR55 to increase aggressiveness. Conditions favoring accumulation of PACAP-derived peptides were different than those for LPI and were mainly related to differentiation. This indicates a different function of the two agonist classes and possibly the existence of a signaling bias.     

Stochastic finite element method for elasto‐plastic body

This paper proposes a Stochastic Finite Element Method (SFEM) for non‐linear elasto‐plastic bodies, as a generalization of the SFEM for linear elastic bodies developed by Ghanem and Spanos who applied the Karhunen–Loeve expansion and the polynomial chaos expansion for stochastic material properties and field variables, respectively. The key feature of the proposed SFEM is the introduction of two fictitious bodies whose behaviours provide upper and lower bounds for the mean of field variables. The two bounding bodies are rigorously obtained from a given distribution of material properties. The deformation of an ideal elasto‐plastic body of the Huber–von Mises type is computed as an illustrative example. The results are compared with Monte‐Carlo simulation. It is shown that the proposed SFEM can satisfactorily estimate means, variances and other probabilistic characteristics of field variables even when the body has a larger variance of the material properties. Copyright © 1999 John Wiley & Sons, Ltd.     

Association studies on the porcine RETN, UCP1, UCP3 and ADRB3 genes polymorphism with fatness traits

Searching for effects of candidate gene polymorphisms on fatness traits is an important goal for pig industry. In this study we evaluated polymorphism of four porcine genes involved in energy metabolism (RETN, UCP1, UCP3 and ADRB3). Moreover, their association with fat deposition traits was analyzed in two breeds (Polish Landrace, Polish Large White) and a Polish synthetic line (L990). Altogether, five SNPs were identified, including two novel ones in the 5′-flanking region of the RETN gene and a novel missense substitution in the UCP3. Distribution of these polymorphisms in the studied five breeds and the synthetic line was not uniform. Two of the analyzed SNPs: g.−178G > A in the RETN and g.946C > T in the UCP3 gene revealed a significant association with abdominal fat weight or backfat thickness. Such associations were not observed for the UCP1 or ADRB3 gene polymorphisms. Our study showed that polymorphisms of the UCP3 and RETN genes are potentially associated with porcine fatness traits.     

Iron transport in cancer cell culture suspensions measured by cell magnetophoresis

Cell motion in a magnetic field reveals the presence of intracellular paramagnetic elements, such as iron or manganese. Under controlled field and liquid media composition, such motion previously allowed us to compare the paramagnetic contribution to cell magnetic susceptibility in erythrocytes differing in the spin state of heme associated with hemoglobin. The method is now tested on cells with less obvious paramagnetic properties: cell cultures derived from human cancers to determine if the magnetophoretic mobility (MM) measurement is sufficiently sensitive to the dysregulation of the intracellular iron metabolism as suggested by reports on loss of iron homeostasis in cancer. The cell lines included hepatocellular carcinoma (Hep 3B 2.1-7 and Hep G2), promyelocytic (HL-60) and chronic myelogenous (K-562) leukemias, histiocytic lymphoma (U-937), tongue (CAL 27) and pharyngeal (Detroit 562) carcinomas, and epitheloid carcinoma (HeLa), whose MM was measured in complete media with standard and elevated soluble iron (ferric nitrate and ferric ammonium citrate), against oxy- and met-hemoglobin erythrocytes used as controls. Different cell lines responded differently to the magnetic field and the soluble iron concentrations in culture media establishing the possibility of single cell elemental analysis by magnetophoresis and magnetic cell separation based upon differences in intracellular iron concentration.     

The effects of atmospheric aging on a hybrid polymer matrix composite

The effect of thermal exposure in an atmospheric environment for up to 1 year on the flexural performance, under both static and fatigue loading, of a glass fiber/carbon fiber hybrid polymer matrix composite material was evaluated. It was found that exposure to a temperature near, but below, the glass transition temperature resulted in diminished flexure strength as well as reduced fatigue performance. The magnitude of property reduction was, in general, proportional to the amount of aging time, and was found to be dictated by the dominant aging mechanism. Scanning electron microscopy revealed that the modest reduction in mechanical properties at intermediate aging times was predominantly attributed to thermal oxidation, while for longer aging times thermal aging (dimensional relaxation) was the primary cause for the substantial reduction. Dimensional relaxation of the composite was measured at several isothermal aging temperatures, from which, the activation energy of the aging process was determined. This work provides insight into the evolution of mechanical properties as a function of aging time in an atmospheric environment for a hybrid polymer matrix composite.