66 research outputs found
Discovery of Novel, Potent, and Specific Cell-Death Inducers in the Jurkat Acute Lymphoblastic Leukemia Cell Line
No full textThe limited clinical efficacy of many cancer therapeutics has initiated intense research efforts toward the discovery of novel chemical entities in this field. In this study, 31 hit candidates were selected from nearly 800000 database compounds in a ligand-based virtual screening campaign. In turn, three of these hits were found to have (sub)micromolar potencies in proliferation assays with the Jurkat acute lymphatic leukemic cell line. In this assay, the three hits were found to exhibit higher potency than clinically tested cell-death inducers (GDC-0152, AT-406, and birinapant). Importantly, antiproliferative activity toward non-cancer peripheral blood mononuclear cells (PBMCs) was found to be marginal. Further biological characterization demonstrated the cell-death-inducing properties of these compounds. Biological testing of hit congeners excluded a nonspecific, toxic effect of the novel structures. Altogether, these findings may have profound relevance for the development of clinical candidates in tumor therapy
EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1
No full textEBV-Infection in Cardiac and Non-Cardiac Gastric Adenocarcinomas is Associated with Promoter Methylation of p16, p14 and APC, but not hMLH1
No full textBackground: Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV
The Lymphotoxin β Receptor Is Essential for Upregulation of IFN-Induced Guanylate-Binding Proteins and Survival after Toxoplasma gondii Infection
No full textLymphotoxin β receptor (LTβR) signaling plays an important role in efficient initiation of host responses to a variety of pathogens, encompassing viruses, bacteria, and protozoans via induction of the type I interferon response. The present study reveals that after Toxoplasma gondii infection, LTβR−/− mice show a substantially reduced survival rate when compared to wild-type mice. LTβR−/− mice exhibit an increased parasite load and a more pronounced organ pathology. Also, a delayed increase of serum IL-12p40 and a failure of the protective IFNγ response in LTβR−/− mice were observed. Serum NO levels in LTβR−/− animals rose later and were markedly decreased compared to wild-type animals. At the transcriptional level, LTβR−/− animals exhibited a deregulated expression profile of several cytokines known to play a role in activation of innate immunity in T. gondii infection. Importantly, expression of the IFNγ-regulated murine guanylate-binding protein (mGBP) genes was virtually absent in the lungs of LTβR−/− mice. This demonstrates clearly that the LTβR is essential for the induction of a type II IFN-mediated immune response against T. gondii. The pronounced inability to effectively upregulate host defense effector molecules such as GBPs explains the high mortality rates of LTβR−/− animals after T. gondii infection
Expression of cyclin B1 in the metaplasia-dysplasia-carcinoma sequence of Barrett esophagus
No full textDiscourses on violence in Costa Rica, El Salvador and Nicaragua: Social Perceptions in Everyday Life
No full textHuhn S. Discourses on violence in Costa Rica, El Salvador and Nicaragua: Social Perceptions in Everyday Life. GIGA Working Papers. Vol 81. Hamburg: GIGA; 2008.Central America has the reputation of being a violent region with high crime rates, youth
gangs, drug traffic, and ubiquitous insecurity. Politicians, the media, and social scientists
in and outside the region often claim that the societies are in complete agreement with
their judgment of the situation and that all society members are calling for law and order
and social segregation. Focusing on Costa Rica, El Salvador, and Nicaragua, the paper analyzes
the social perception of violence and crime. On the basis of essays written by secondary
school students and interviews with citizens from all walks of life in the three countries,
the paper points out how elite arguments on violence and crime are translated into
everyday life, and what society members suggest be done to deal with these problems.
The sources prove that there are noticeable hegemonic discourses on violence and crime in
Costa Rica, El Salvador, and Nicaragua. Simultaneously, a majority of the respondents call
for social and integrative solutions rather than the so-called “iron fist.” The repressive
trend in Central American policies therefore does not necessarily receive the presumed affirmation
asserted by many authorities on and in the region
HER2 Expression in Gastric Cancer: Rare, Heterogeneous and of No Prognostic Value – Conclusions from 924 Cases of Two Independent Series
No full textBackground: Patients with gastric cancer (GC) have a poor survival and biologicals such as Trastuzumab have not been used routinely in these patients. Existing data on HER2 expression and its clinical relevance in GC are still limited and controversial
Immunohistochemical Colocalization of the Terminal Complex of Human Complement and Smooth Muscle Cell α-Actin in Early Atherosclerotic Lesions
No full text
Abstract
There is substantial evidence that activated components of the complement cascade are present in atherosclerotic lesions, and it was suggested some years ago that smooth muscle cells may be an important target of complement attack by the terminal components of the cascade, C5b-9, also called the membrane attack complex. Recent in vitro studies have shown that assembly of membrane attack complex on smooth muscle cells leads to the release of monocyte chemotactic protein-1, and, if this were to occur in vivo, then it could be responsible for the recruitment of monocytes into the lesion. In this study we have investigated the localization of C5b-9 in early atherosclerotic lesions of human coronary arteries, collected from autopsies, by immunohistochemical staining. C5b-9 was found to colocalize widely with smooth muscle cell α-actin, but not with intact macrophages, thus supporting the hypothesis that interaction of complement with smooth muscle cells may indeed be important in atherogenesis.
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Analysis for potential publication bias.
No full text<p>Funnel plots were prepared to assess publication bias with respect to the analyzed variable <b>(A)</b> sex, <b>(B)</b> depth of invasion (T-stage), <b>(C)</b> lymph node metastasis (N-status), <b>(D)</b> UICC tumor stage and <b>(E)</b> grade of differentiation. Y-axis represents the standard error (SE), x-axis represents the study's result.</p
Association between CXCR4 and clinicopathological variables.
No full text<p>The Forest plot reflects the individual and pooled OR with CI for the relationship between expression of CXCR4 and <b>(A)</b> sex, <b>(B)</b> depth of invasion (T-stage), <b>(C)</b> lymph node metastasis (N-status), <b>(D)</b> UICC tumor stage or <b>(E)</b> grade of differentiation. Heterogeneity was verified by the Cochrane Q test (Chi-squared test; Chi<sup>2</sup>) and inconsistency (I<sup>2</sup>).</p
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