High Progesterone Receptor Expression in Prostate Cancer Is Associated with Clinical Failure

BackgroundProstate cancer is a highly heterogeneous disease and one of the leading causes of mortality in developed countries. Specific prognostic and predictive markers for prostate cancer patients are still lacking. A causal relationship between androgens and the development of prostate cancer is generally considered biologically plausible, but androgens are not the sole effector in the complexity of prostate carcinogenesis. The aim of this study was to evaluate the prognostic significance of progesterone receptor in tumor tissue of T1-3N0 prostate cancer patients undergoing prostatectomy.MethodsTissue microarrays from 535 patients with prostate cancer were constructed. Duplicate cores of tumor cells and tumor stromal tissue from each resected specimen were extracted. Immunohistochemistry was used to evaluate the in-situ expression of progesterone receptor.ResultsIn univariate analyses, high tumor cell density (p = 0.006) and high tumor stromal cell density level (p = 0.045) of progesterone receptor were both significantly associated with tumor progression and clinical failure. In multivariate analysis, progesterone receptor expression in tumor cells was an independent negative prognostic factor for clinical failure (HR: 2.5, 95% CI: 1.2–5.2, p = 0.012).ConclusionHigh progesterone receptor density in tumor cells of the prostate cancer tumor is an independent negative prognostic factor for clinical failure.     

Production of target-specific recombinant human polyclonal antibodies in mammalian cells

We describe the expression and consistent production of a first target-specific recombinant human polyclonal antibody. An anti-Rhesus D recombinant polyclonal antibody, Sym001, comprised of 25 unique human IgG1 antibodies, was produced by the novel Sympress expression technology. This strategy is based on site-specific integration of antibody genes in CHO cells, using the FRT/Flp-In recombinase system. This allows integration of the expression construct at the same genomic site in the host cells, thereby reducing genomic position effects. Different bioreactor batches of Sym001 displayed highly consistent manufacturing yield, antibody composition, binding potency, and functional activity. The results demonstrate that diverse recombinant human polyclonal antibody compositions can be reproducibly generated under conditions directly applicable to industrial manufacturing settings and present a first recombinant polyclonal antibody which could be used for treatment of hemolytic disease of the newborn and/or idiopathic thrombocytopenic purpura.     

Maternal obesity reprograms offspring's executive brain centers in a sex‐specific manner?

This editorial highlights an article by McKee and colleagues in the current issue of Journal of Neurochemistry, in which the authors report epigenetic changes linked to one‐carbon metabolism in prefrontal cortex (PFC) of murine offspring from dams fed high‐fat diet to mimic maternal obesity. The group found that high‐fat diet feeding in utero increases weight gain in offspring and dynamically alters DNA methylation in the PFC of male but not female brains. These epigenetic marks were associated with a shift in brain one‐carbon metabolism (folate and methionine) intermediates and were normalized by early‐life methyl‐donor supplementation in a sex‐specific manner.

     

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations.