Prognostic and Therapeutic Potential of Nuclear Receptors in Head and Neck Squamous Cell Carcinomas

Head and neck squamous cell carcinomas are among the most common neoplasms worldwide and characterized by local tumor aggressiveness, high rate of early recurrences, development of metastasis, and second primary cancers. Despite modern therapeutic strategies and sophisticated surgical management, overall survival-rates remained largely unchanged over the last decades. Thus, the need for novel treatment options for this tumor entity is undeniable. A key event in carcinogenesis is the uncontrolled modulation of genetic programs. Nuclear receptors belong to a large superfamily of transcription factors implicated in a broad spectrum of physiological and pathophysiological processes, including cancer. Several nuclear receptors have also been associated with head and neck cancer. This review will summarize their mode of action, prognostic/therapeutic relevance, as well as preclinical and clinical studies currently targeting nuclear receptors in this tumor entity

Gender Matters: Making the Case for Trans Inclusion

[Excerpt] “The transgender communities are producing an important and nuanced critique of our gender system. For community members, the project is self-constitutive and, therefore, has an immediacy that also marks the efforts of other marginalized groups who have attempted to make sense of the world through description, interrogation, and ultimately a program for transformation. The transgender project also has universalizing elements because, existing within the gender system, each one of us embodies a particular gender articulation. It is through this articulation that we define ourselves in relation to the gender we were assigned at birth, the gender we choose, the gender we create, the gender we reject, the gender we are, and the gender we are assumed to be. […]This article, written largely for an audience who does not identify as transgender, makes the case for greater inclusion of transgender issues by identifying and examining various points of resistance, outlining commonalities, and proposing action steps. […

Fibrinolysis and Beyond: Bridging the Gap between Local and Systemic Clot Removal

Recanalization methods in ischemic stroke have been progressively expanded over the past years. In addition the continuous development of specialized mechanical devices for thrombectomy a broad spectrum of new drugs has been tested: Both options, novel drugs as well as new devices, can be employed independently of each other, but in most cases a combination of the two with the standard treatment of intravenous fibrinolysis is applied. Until recently, a large number of case series have been performed to investigate the effects of various drugs and interventions, but only a few trials have been conducted to determine the optimal conditions for combining both procedures. This review surveys the different systemic and endovascular vessel reopening practices and their major bridging techniques

Calcitonin receptor-like receptor is expressed on gastrointestinal immune cells

Background/Aims: Pharmacological and morphological studies suggest that the gut mucosal immune system and local neuropeptide-containing neurones interact. We aimed to determine whether gut immune cells are targets for calcitonin gene-related peptide (CGRP), which has potent immune regulatory properties. Methods: Using density gradient centrifugation, rat lamina propria mononuclear cells (LP-MNCs) and intra-epithelial lymphocytes (IELs) were isolated. RT-PCR was employed for the detection of mRNA of rat calcitonin receptor-like receptor (CRLR), which is considered to represent the pharmacologically defined CGRP receptor-1 subtype, as well as mRNA of the receptor activity-modifying proteins, which are essential for CRLR function and determine ligand specificity. A radioreceptor assay was employed for the detection of specific CGRP binding sites. Results: RT-PCR and DNA sequencing showed that LP-MNCs and IELs express CRLR. Incubation of isolated LP-MNCs with radiolabelled alphaCGRP revealed the existence of specific binding sites for CGRP. Conclusion: These novel data indicate that mucosal immune cells of the rat gut are a target for CGRP and provide significant evidence that CGRP functions as an immune regulator in the gut mucosa. Copyright (C) 2002 S. Karger AG, Basel

Development of a harmonized risk mitigation toolbox dedicated to environmental risks of pesticides in farmland in Europe: outcome of the MAgPIE workshop

Risk mitigation measures are a key component in designing conditions of use of pesticides in crop protection. A 2-step workshop was organized under the auspices of SETAC and the European Commission and gathered risk assessors and risk managers of 21 European countries, industry, academia and agronomical advisors/extension services, in order to provide European regulatory authorities with a toolbox of risk mitigation measures designed to reduce environmental risks of pesticides used in agriculture, and thus contribute to a better harmonization within Europe in the area.The workshop gathered an inventory of the risk mitigation tools for pesticides being implemented or in development in European countries. The inventory was discussed in order to identify the most promising tools for a harmonized toolbox in the European area. The discussions concerned the level of confidence in the technical data on which the tools identified rely, possible regulatory hurdles, expectations as regards the implementation of these tools by farmers and links with risk assessment. Finally, this workshop was a first step towards a network gathering all stakeholders, i.e. experts from national authorities, research sector, industry and farmers, to share information and further develop this toolbox. This paper presents an outline of the content of the toolbox with an emphasis on spray drift reducing techniques, in line with the discussions ongoing in the SPISE workshop

Abelian doppelsemigroups

A doppelsemigroup is an algebraic system consisting of a set with two binary associative operations satisfying certain identities. Doppelsemigroups are a generalization of semigroups and they have relationships with such algebraic structures as doppelalgebras, duplexes, interassociative semigroups, restrictive bisemigroups, dimonoids and trioids. This paper is devoted to the study of abelian doppelsemigroups. We show that every abelian doppelsemigroup can be constructed from a left and right commutative semigroup and describe the free abelian doppelsemigroup. We also characterize the least abelian congruence on the free doppel-semigroup, give examples of abelian doppelsemigroups and find conditions under which the operations of an abelian doppelsemi-group coincide

A Laboratory Investigation of Supersonic Clumpy Flows: Experimental Design and Theoretical Analysis

We present a design for high energy density laboratory experiments studying the interaction of hypersonic shocks with a large number of inhomogeneities. These ``clumpy'' flows are relevant to a wide variety of astrophysical environments including the evolution of molecular clouds, outflows from young stars, Planetary Nebulae and Active Galactic Nuclei. The experiment consists of a strong shock (driven by a pulsed power machine or a high intensity laser) impinging on a region of randomly placed plastic rods. We discuss the goals of the specific design and how they are met by specific choices of target components. An adaptive mesh refinement hydrodynamic code is used to analyze the design and establish a predictive baseline for the experiments. The simulations confirm the effectiveness of the design in terms of articulating the differences between shocks propagating through smooth and clumpy environments. In particular, we find significant differences between the shock propagation speeds in a clumpy medium compared to a smooth one with the same average density. The simulation results are of general interest for foams in both inertial confinement fusion and laboratory astrophysics studies. Our results highlight the danger of using average properties of inhomogeneous astrophysical environments when comparing timescales for critical processes such as shock crossing and gravitational collapse times.Comment: 7 pages, 6 figures. Submitted to the Astrophysical Journal. For additional information, including simulation animations and the pdf and ps files of the paper with embedded high-quality images, see http://pas.rochester.edu/~wm

Novel strategies to target the survivin pathway in cancer – interference with nuclear export prevents the tumor promoting activites of survivin : meeting abstract

Survivin functions as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Since survivin is a highly relevant target for tumor therapy, we investigated whether interference with it’s dynamic cellular localization represents a novel strategy to inhibit survivin’s cancer promoting functions. We confirmed survivin overexpression in head and neck as well as in colorectal cancers and identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. Importantly, nuclear export was required for survivin mediated protection against chemo- and radiotherapy-induced apoptosis by securing efficient interference with cytoplasmic caspases. In dividing cells, the NES was required for tethering of survivin and of the survivin/Aurora-B kinase complex to the mitotic machinery, which was inevitable for proper cell division. The clinical relevance of our findings was supported by showing that preferential nuclear localization of survivin correlated with enhanced survival in a cohort of colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We here show that nuclear export is essential for the tumor promoting activities of survivin and encourage the identification of chemical inhibitors to specifically interfere with survivin’s nuclear export as a novel class of anticancer therapeutics