Recurrent and multiple bladder tumors show conserved expression profiles

<p>Abstract</p> <p>Background</p> <p>Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors.</p> <p>Methods</p> <p>Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses.</p> <p>Results</p> <p>We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles.</p> <p>Conclusion</p> <p>Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.</p

Convergence versus Divergence: Testing Varieties of Capitalism Perspective on the Globalization of Business Practices

This paper analyses links between intra-organizational adaptation and institutional variation across countries. Using the varieties of capitalism viewpoint, we examine strategic options open to multinational firms operating simultaneously in liberal market economies and coordinated market economies. A holistic perspective is achieved by implementing an original ‘index of institutional impact.’ Data are drawn from a survey of the subsidiaries of German firms in the UK in 2007. The results suggest that pressure towards accepting local practices for multinational firms varies across the dimensions in which firms resolve coordination problems, inciting speedy convergence in some, but allowing for maintaining distinctive practices in other

Capitalist Convergence? European (dis?)Integration and the Post-crash Restructuring of French and European Capitalisms

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. This article critiques and builds upon first-wave (Höpner and Schäfer 2010. A new phase of European integration: organised capitalisms in post-Ricardian Europe. West European Politics, 33 (2), 344–368) and second-wave (Johnston and Regan 2018. Introduction: is the European Union capable of integrating diverse models of capitalism? New Political Economy, 23 (2), 145–159) European Integration and comparative capitalisms literatures which posit convergence towards a single model of capitalism or growth. It utilises the case study of France to explore the impact of European integration and disintegration on national models of capitalism in the post-crisis era. The article focuses on the impact of integrative and disintegrative dynamics on France’s ‘state-industry-finance nexus’, putting forward three core claims. First, French capitalism is not accurately captured by the above frameworks and remains better characterised by the concept of post-dirigisme. Indeed, comparative capitalisms debates must move beyond a simple bifurcation of capitalist types. Second, European integrative pressures must be viewed as fragmented, differentiating, mediated by domestic state actors and producing capitalist variegation and hybridisation. Countering functionalist tendencies within this literature, it shows how different conceptions of state-market relations crucially mediate the relationship between national capitalisms and European integration. Finally, in the context of Brexit, the dynamics of European disintegration–an issue not discussed so far in these debates–is contributing to a variegated and multi-directional process of capitalist restructuring in post-crisis France

Rethinking European integration history in light of capitalism: the case of the long 1970s

This introduction outlines the possibilities and perspectives of an intertwining between European integration history and the history of capitalism. Although debates on capitalism have been making a comeback since the 2008 crisis, to date the concept of capitalism remains almost completely avoided by historians of European integration. This introduction thus conceptualizes ‘capitalism’ as a useful analytical tool that should be used by historians of European integration and proposes three major approaches for them to do so: first, by bringing the question of social conflict, integral to the concept of capitalism, into European integration history; second, by better conceptualizing the link between European governance, Europeanization and the globalization of capitalism; and thirdly by investigating the economic, political and ideological models or doctrines that underlie European cooperation, integration, policies and institutions. Finally, the introduction addresses the question of the analytical benefits of an encounter between capitalism and European integration history, focusing on the case of the 1970s. This allows us to qualify the idea of a clear-cut rupture, and better highlight how the shift of these years resulted from a complex bargaining that took place in part at the European level

Cytogenetic polyclonality in hematologic malignancies

The present study was undertaken to ascertain the frequency of cytogenetic polyclonality in various hematologic malignancies and to investigate whether morphologic subgroup, age, gender, or previous genotoxic exposure influences the incidence. Among 2,243 cytogenetically investigated hematologic malignancies, 10 acute myeloid leukemias (AML), 5 myelodysplastic syndromes (MDS), 2 acute lymphoblastic leukemias (ALL), 1 acute undifferentiated leukemia (AUL), 1 atypical Philadelphia chromosome-negative (Ph-) chronic myeloid leukemia (CML), 1 chronic myeloproliferative disorder (CMD), and 1 chronic lymphoproliferative disorder (CLD) with karyotypically unrelated clones were identified, constituting 2.6% of AML, 1.6% of MDS, 0.8% of ALL, 13% of AUL, 9.1% of Ph- CML, 1.5% of CMD, and 2.8% of CLD with chromosomal abnormalities. In contrast to the cytogenetic features, the X-inactivation pattern was monoclonal in the two informative female patients that could be investigated. Among 17,733 karyotypically aberrant published cases surveyed, significant frequency differences (P < 0.001) were discerned: 1.7% of 6,526 AML, 3.4% of 2,391 MDS, 0.4% of 1,920 Ph+ CML, 2.9% of 856 CMD, 0.9% of 4,226 ALL, and 5.8% of 1,814 CLD displayed unrelated clones. The incidence of cytogenetic polyclonality did not differ significantly among the MDS, CMD, or ALL subgroups, between males and females, between children (< 16 years) and adults, or between B- and T-cell ALL, whereas the frequencies varied among the AML FAB types (P < 0.05), among the different CLD entities (P < 0.001), and between B- and T-cell CLD (P < 0.001). Furthermore, the incidence was higher in therapy-related AML and MDS than in de novo AML and MDS (P < 0.001 and P < 0.01, respectively)

Fusion Gene Microarray Reveals Cancer Type-Specificity Among Fusion Genes

Detection of fusion genes for diagnostic purposes and as a guide to treatment is well-established in hematological malignancies, and the prevalence of fusion genes in epithelial cancers is also increasingly appreciated. To study whether established fusion genes are present within additional cancer types, we have used an updated version of our fusion gene microarray in a systematic survey of reported fusion genes in multiple cancer types. We assembled a comprehensive database of published fusion genes, including those reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 599,839 oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines representing 15 different cancer types. Data from ten leukemia cell lines with known fusion gene status were used to develop an automated scoring algorithm, and in five cell lines the correct fusion gene was the top scoring hit, and one came second. Two additional fusion genes, BCAS4-BCAS3 in the MCF-7 breast cancer cell line and CCDC6-RET in the TPC-1 thyroid cancer cell line were validated as true positive fusion transcripts. However, these fusion genes were not new to these cancer types, and none of 548 fusion genes were identified from a novel cancer type. We therefore find it unlikely that the assayed fusion genes are commonly present across multiple cancer types. (C) 2011 Wiley-Liss, Inc

N-terminus DUX4-immunohistochemistry is a reliable methodology for the diagnosis of DUX4-fused B-lymphoblastic leukemia/lymphoma (N-terminus DUX4 IHC for DUX4-fused B-ALL)

B-lymphoblastic leukemia/lymphoma (B-ALL) is the most common pediatric malignancy and the most commonly diagnosed adult lymphoblastic leukemia. Recent advances have broadened the spectrum of B-ALL, with DUX4 gene fusions implicated in a subclass occurring in adolescents and young adults and harboring a favorable prognosis. DUX4 fusions have been challenging to identify. We aimed to determine whether expression of the DUX4 oncoprotein, as detected by targeted immunohistochemistry, might serve as a surrogate for molecular detection of DUX4 fusions in B-ALL. A cohort of investigational B-ALLs was generated with enrichment for DUX4 fusions by the inclusion of cases with characteristic demographic features and immunophenotypic properties. B-ALLs with mutually exclusive cytogenetics were collected. Immunohistochemical staining by a monoclonal antibody raised against the N-terminus of the DUX4 protein was performed. N-DUX4 immunohistochemistry demonstrated strong, crisp nuclear staining in blasts of seven investigational cases, six of which had nucleic acid material available for molecular evaluation. Five of these cases demonstrated RNA-seq DUX4-fusion positivity. One N-DUX4 immunohistochemistry positive case lacked a definitive DUX4-fusion by RNA-seq, though demonstrated a gene expression profile characteristic of DUX4-rearranged B-ALLs, a CD2+ immunophenotype, and a lack of staining by C-terminus DUX4 antibody immunohistochemistry. At least 83.3% [5/6] positive predictive value. N-DUX4 immunohistochemistry was negative in blasts of three RNA-seq DUX4-fusion-negative cases (3/3; 100% negative predictive value). B-ALLs with mutually exclusive cytogenetic profiles were all N-DUX4 negative (0/10, specificity 100%). N-DUX4 immunohistochemistry is reliable for the distinction of DUX4-rearranged B-ALLs from other B-ALLs. We recommend its use for subclassification of B-ALLs in adolescents and young adults and in B-ALLs that remain “not otherwise specified.”

Rising powers and IMF governance reform

The International Monetary Fund (IMF) has long been under fire for not adapting its governance and quota structure to the growing economic weight of emerging and developing countries in the world order. Starting from the preferences of the main players (BRICS, US and advanced European countries), this chapter discusses the 2010 quota and governance reform package to address this problem and advances explanations for its modest outcome. It is argued that the US and the European countries enjoyed substantial ‘structural’ and ‘institutional’ power in ways that reduced the influence of the BRICS to impose a more generous reshuffling of voting power within the IMF. Furthermore, we assess the current state of implementation of the 2010 reforms and discuss its follow-up, namely the debate on the new quota formula and the next quota review. While large emerging and developing countries might develop alternative options to reduce their dependency on the IMF, they have definitely not turned their back on the IMF in the face of lack of progress in the reform process