„America First”. Relacje administracji Trumpa z Unią Europejską

The article presents the actions of the Trump administration towards the European Union. By analyzing the problem, they tried to find out the causes of tensions between Washington and Brussels and to outline the main axis of the dispute. It was the strained trade relations, which even entered the phase of an undeclared trade war between the US and the EU. It has been shown that the essence of the problem was that Trump used higher tariffs on goods imported from Europe as an instrument of exerting pressure and implementing policies aimed at the EU. As a result, the cohesion of the transatlantic alliance was weakened.W artykule przedstawiono działania administracji Trumpa wobec Unii Europejskiej. Analizując problem, starano się dociec przyczyn napięć na linii Waszyngton–Bruksela oraz zarysować główną oś sporu. Były nią napięte relacje handlowe, które weszły nawet w fazę niewypowiedzianej wojny handlowej między USA a UE. Wykazano, że istotą problemu było to, że Trump używał wyższych ceł na towary sprowadzane z Europy jako instrumentu wywierania nacisku oraz realizowania polityki wymierzonej w UE. Wspólnota zaś reagowała cłami odwetowymi. W efekcie osłabiano spoistość sojuszu transatlantyckiego

Od asymetrii do zrównoważonego partnerstwa: relacje Stany Zjednoczone-Republika Federalna Niemiec

Throughout the Cold War, US-German relations were characterized by a clear asymmetry. This resulted not only from the imbalance between those countries’ potentials, but also from formula of the West German dependence on the American patron: the FRG relied heavily on the support and guarantees provided byWashington. In 1990, the unification of Germany introduced new elements to the relationship. New Germany became a sovereign and „normal” state, at the same time their rank and position in Europe was on the rise accompanied by a gradual weakening of the sense of dependence on the American patron. As a result, at the turn of the century US-German relations have entered a phase of mitigating the asymmetry. This process was accompanied by an unprecedented downturn in mutual relations: Germany became more assertive with respect to the Washington expectations and demands; they also became able to attitudes contrary to the American policy agenda. The United States understood that they are now dealing with a more difficult partner: one conscious of its rank, and strongly articulating its own interestsand expectations.Washington – Berlin relations have thus entered the phase of a more balanced partnership.Throughout the Cold War, US-German relations were characterized by a clear asymmetry. This resulted not only from the imbalance between those countries’ potentials, but also from formula of the West German dependence on the American patron: the FRG relied heavily on the support and guarantees provided byWashington. In 1990, the unification of Germany introduced new elements to the relationship. New Germany became a sovereign and „normal” state, at the same time their rank and position in Europe was on the rise accompanied by a gradual weakening of the sense of dependence on the American patron. As a result, at the turn of the century US-German relations have entered a phase of mitigating the asymmetry. This process was accompanied by an unprecedented downturn in mutual relations: Germany became more assertive with respect to the Washington expectations and demands; they also became able to attitudes contrary to the American policy agenda. The United States understood that they are now dealing with a more difficult partner: one conscious of its rank, and strongly articulating its own interestsand expectations.Washington – Berlin relations have thus entered the phase of a more balanced partnership

USA–Unia Europejska. Stan i perspektywy relacji transatlantyckich

USA – European Union. Condition and Prospects of Trans-Atlantic RelationsUSA–Unia Europejska. Stan i perspektywy relacji transatlantyckic

Ukraina i stosunki transatlantyckie

Europe/the European Union, with its obvious trump cards, should be an active and efficient player on the international arena. Such are the expectations of the United States, formulated especially by the administration of Barack Obama. However, from the American perspective, the EU has not proved successful as an important international actor, engaged in resolving global problems and prepared to assume greater responsibility for the course of events in the world. This inertia of the EU resulted in the marginalisation of Europe in American politics, as manifested by the latter’s pivot to the Pacific Rim. It was only after the developments in the Ukraine, which resulted from Russia’s imperial tendencies, that a greater activity and coherence in American and European politics was triggered, having a positive influence also on transatlantic relations.Europe/the European Union, with its obvious trump cards, should be an active and efficient player on the international arena. Such are the expectations of the United States, formulated especially by the administration of Barack Obama. However, from the American perspective, the EU has not proved successful as an important international actor, engaged in resolving global problems and prepared to assume greater responsibility for the course of events in the world. This inertia of the EU resulted in the marginalisation of Europe in American politics, as manifested by the latter’s pivot to the Pacific Rim. It was only after the developments in the Ukraine, which resulted from Russia’s imperial tendencies, that a greater activity and coherence in American and European politics was triggered, having a positive influence also on transatlantic relations

Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas

Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients.Methylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level.The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients.Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling.The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas

Single nucleotide polymorphism rs11614913 associated with CC genotype in miR-196a2 is overrepresented in laryngeal squamous cell carcinoma, but not salivary gland tumors in Polish population

The miRNA-196a2 has shown significance in the development of various neoplasms, including head and neck squamous cell carcinoma (HNSCC). The oncogenic functionality of this miRNA is mediated via its potential to target annexin A1 mRNA, a tumor suppressor gene involved in inhibition of the NF-kappa B pathway. Interestingly, recent data indicate a susceptibility for aforementioned neoplasms in patients with the CC genotype vs the CT and TT genotypes of the rs11614913 SNP located within the DNA sequence of the miR-196a2 that results in elevated expression of the gene. To further investigate this phenomenon, we genotyped this SNP in 40 patients with laryngeal squamous cell carcinoma (LSCC), the most common tumor of the head and neck region and 60 patients with salivary gland tumors (SGT) that show a yet unexplained incidence increase in the last two decades. In agreement with previous reports, we have identified a statistically significant (p < 0.05) overrepresentation of the CC genotype in LSCC patients and demonstrated in LSCC cell lines that it results in elevated expression of miR-196a2 as compared to cell lines with the TT genotype of the respective SNP. Importantly, none of these correlations was found in patients with SGT. These findings underline the importance of the SNP rs11614913 for LSCC development in the Polish population and moreover highlight the different genetic background of the two studied neoplasms of the head and neck region

Polymorphisms of the DNA repair genes XRCC1 and ERCC4 are not associated with smoking- and drinking-dependent larynx cancer in a polish population

Aim of this article is to investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415Gln (rs1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population

Laryngeal squamous cell carcinoma cell lines show high tolerance for siRNA-mediated CDK1 knockdown

Alterations of the cell cycle checkpoints lead to uncontrolled cell growth and result in tumorigenesis. One of the genes essential for cell proliferation and cell cycle regulation is CDK1. This makes it a potential target in cancer therapy. In our previous study we have shown upregulation of this gene in laryngeal squamous cell carcinoma (LSCC). Here we analyze the impact of siRNA-mediated CDK1 knockdown on cell proliferation and viability, measured with cell growth monitoring and colorimetric test (CCK8 assay), respectively. We proved that a reduction of CDK1 expression by more than 50% has no effect on these cellular processes in LSCC cell lines (n=2). Moreover, using microarrays, we analyzed global gene expression deregulation in these cell lines after CDK1 knockdown. We searched for enriched ontologies in the group of identified 137 differentially expressed genes (>2-fold change). Within this group we found 3 enriched pathways: protein binding (GO:0005515), mitotic nuclear division (GO:0007067) and transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169) and a group of 11 genes encoding proteins for which interaction with CDK1 was indicated with the use of bioinformatic tools. Among these genes we propose three: CDK6, CALD1 and FYN as potentially dependent on CDK1

Copy Number Gains of the Putative CRKL Oncogene in Laryngeal Squamous Cell Carcinoma Result in Strong Nuclear Expression of the Protein and Influence Cell Proliferation and Migration

Laryngeal squamous cell carcinoma is a major medical problem worldwide. Although our understanding of genetic changes and their consequences in laryngeal cancer has opened new therapeutic pathways over the years, the diagnostic as well as treatment options still need to be improved. In our previous study, we identifed CRKL (22q11) as a novel putative oncogene overexpressed and amplifed in a subset of LSCC tumors and cell lines. Here we analyze to what extent CRKL DNA copy number gains correlate with the higher expression of CRKL protein by performing IHC staining of the respective protein in LSCC cell lines (n=3) and primary tumors (n=40). Moreover, the importance of CRKL gene in regard to proliferation and motility of LSCC cells was analyzed with the application of RNA interference (siRNA). Beside the physiological cytoplasmic expression, the analysis of LSCC tumor samples revealed also nuclear expression of CRKL protein in 10/40 (25%) cases, of which three (7.5%), presented moderate or strong nuclear expression. Similarly, we observed a shift towards aberrantly strong nuclear abundance of the CRKL protein in LSCC cell lines with gene copy number amplifcations. Moreover, siRNA mediated silencing of CRKL gene in the cell lines showing its overexpression, signifcantly reduced proliferation (p<0.01) as well as cell migration (p<0.05) rates. Altogether, these results show that the aberrantly strong nuclear localization of CRKL is a seldom but recurrent phenomenon in LSCC resulting from the increased DNA copy number and overexpression of the gene. Moreover, functional analyses suggest that proliferation and migration of the tumor cells depend on CRKL expression.</p

Loss of the MAF Transcription Factor in Laryngeal Squamous Cell Carcinoma

MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this study, we shed further light on the interaction between miR-1290 and MAF, as well as on cellular MAF protein localization in LSCC. We confirmed the direct interaction between miR-1290 and MAF 3'UTR by a dual-luciferase reporter assay. In addition, we used immunohistochemistry staining to analyze MAF protein distribution and observed loss of MAF nuclear expression in 58% LSCC samples, of which 10% showed complete absence of MAF, compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility that loss-of-function mutations, promoter region DNA methylation or CNV are responsible for MAF loss in LSCC. Finally, we identified genes involved in the regulation of apoptosis harboring the MAF binding motif in their promoter region by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor by regulating apoptosis.</p