Evaluation of a Novel Anti-Mucin 1 (MUC1) Antibody (PankoMab) as a Potential Diagnostic Tool in Human Ductal Breast Cancer; Comparison with Two Established Antibodies

Aim: PankoMab is a novel antibody that recognizes a tumor-specific epitope of Mucin 1 (MUC1). The aim of this study was the evaluation of PankoMab as a potential diagnostic tool and its comparison with two established antibodies against MUC1 in human ductal breast cancer. Materials and Methods: Breast carcinomas were obtained from 82 patients. MUC1 expression and hormone receptor status were determined by immunohistochemistry of paraffin-embedded material. Results: PankoMab revealed strong correlation to hormone receptor expression. DF3 showed no correlation with grading, lymph node involvement and/or estrogen receptor (ER) expression. In the subgroup of lymph node-positive and ER-negative tumors, we saw a significantly reduced DF3 staining in G3 tumors compared to G2 tumors. VU-4-H5 showed increased staining intensity in correlation with increased grading. In addition, we also identified a significantly higher expression of the VU-4-H5 epitope in lymph node-positive carcinomas compared to carcinomas without lymph node involvement. Conclusion: PankoMab revealed strong correlation to hormone receptor expression in ductal carcinoma of the breast. VU-4-H5 showed increased staining intensity in correlation with increased grading and lymph node involvement. PankoMab and VU-4-H5 staining could be a useful combination in ductal breast cancer prognosis by immunohistochemistry

LDOC1 as negative prognostic marker for vulvar cancer patients

So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients’ survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-κB signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-κB inhibitor C-DIM 12 (3,3′-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough

Tectonomorphic evolution of Marie Byrd Land - Implications for Cenozoic rifting activity and onset of West Antarctic glaciation

The West Antarctic Rift System is one of the largest continental rifts on Earth. Because it is obscured by the West Antarctic Ice Sheet, its evolution is still poorly understood. Here we present the first low-temperature thermochronology data from eastern Marie Byrd Land, an area that stretches ~ 1000 km along the rift system, in order to shed light on its development. Furthermore, we petrographically analysed glacially transported detritus deposited in the marine realm, offshore Marie Byrd Land, to augment the data available from the limited terrestrial exposures. Our data provide information about the subglacial geology, and the tectonic and morphologic history of the rift system. Dominant lithologies of coastal Marie Byrd Land are igneous rocks that intruded (presumably early Paleozoic) low-grade meta-sedimentary rocks. No evidence was found for un-metamorphosed sedimentary rocks exposed beneath the ice. According to the thermochronology data, rifting occurred in two episodes. The earlier occurred between ~ 100 and 60 Ma and led to widespread tectonic denudation and block faulting over large areas of Marie Byrd Land. The later episode started during the Early Oligocene and was confined to western Pine Island Bay area. This Oligocene tectonic activity may be linked kinematically to previously described rift structures reaching into Bellingshausen Sea and beneath Pine Island Glacier, all assumed to be of Cenozoic age. However, our data provide the first direct evidence for Cenozoic tectonic activity along the rift system outside the Ross Sea area. Furthermore, we tentatively suggest that uplift of the Marie Byrd Land dome only started at ~ 20 Ma; that is, nearly 10 Ma later than previously assumed. The Marie Byrd Land dome is the only extensive part of continental West Antarctica elevated above sea level. Since the formation of a continental ice sheet requires a significant area of emergent land, our data, although only based on few samples, imply that extensive glaciation of this part of West Antarctica may have only started since the early Miocene

Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity. Here we characterized the polyenoic fatty acid metabolism of these mice in more detail and tested the animals in three different experimental inflammation models. In experimental autoimmune encephalomyelitis (EAE), Alox5-KI mice displayed an earlier disease onset and a significantly higher cumulative incidence rate than wildtype controls but the clinical score kinetics were not significantly different. In dextran sodium sulfate-induced colitis (DSS) and in the chronic constriction nerve injury model (CCI), Alox5-KI mice performed like wildtype controls with similar genetic background. These results were somewhat surprising since in previous loss-of-function studies targeting leukotriene biosynthesis (Alox5(-/-) mice, inhibitor studies), more severe inflammatory symptoms were observed in the EAE model but the degree of inflammation in DSS colitis was attenuated. Taken together, our data indicate that these mutant Alox5-KI mice respond differently in two models of experimental inflammation than Alox5(-/-) animals tested previously in similar experimental setups

Flow and retreat of the Late Quaternary Pine Island-Thwaites palaeo-ice stream, West Antarctica

Multibeam swath bathymetry and sub-bottom profiler data are used to establish constraints on the flow and retreat history of a major palaeo-ice stream that carried the combined discharge from the parts of the West Antarctic Ice Sheet now occupied by the Pine Island and Thwaites glacier basins. Sets of highly elongated bedforms show that, at the last glacial maximum, the route of the Pine Island-Thwaites palaeo-ice stream arced north-northeast following a prominent cross-shelf trough. In this area, the grounding line advanced to within similar to 68 km of, and probably reached, the shelf edge. Minimum ice thickness is estimated at 715 m on the outer shelf, and we estimate a minimum ice discharge of similar to 108 km(3) yr(-1) assuming velocities similar to today's Pine Island glacier (similar to 2.5 km yr(-1)). Additional bed forms observed in a trough northwest of Pine Island Bay likely formed via diachronous ice flows across the outer shelf and demonstrate switching ice stream behavior. The "style" of ice retreat is also evident in five grounding zone wedges, which suggest episodic deglaciation characterized by halts in grounding line migration up-trough. Stillstands occurred in association with changes in ice bed gradient, and phases of inferred rapid retreat correlate to higher bed slopes, supporting theoretical studies that show bed geometry as a control on ice margin recession. However, estimates that individual wedges could have formed within several centuries still imply a relatively rapid overall retreat. Our findings show that the ice stream channeled a substantial fraction of West Antarctica's discharge in the past, just as the Pine Island and Thwaites glaciers do today

NiO/YSZ Reduction for SOFC/SOEC Studied In Situ by Environmental Transmission Electron Microscopy

A typical anode for solid oxide fuel cells (SOFC) or cathode for solid oxide electrolysis cells (SOEC) is a complex porous structure of Ni and yttria-stabilized zirconia (YSZ). The porous Ni/YSZ is usually prepared from powder mixtures of NiO and YSZ, tape casted and sintered into a dense structure and finally reduced during start-up of the SOFC/SOEC in H2 at the operating temperature of the cell (ca. 800 °C). This contribution presents environmental transmission electron microscopy (ETEM) nanoscale observations of the reduction process of a NiO/YSZ powder in H2 at temperatures up to almost 1000 °C. The study focusses on the temperature dependent dynamical morphology of the NiO/YSZ and on the possible influence of YSZ on the NiO reduction.</jats:p

A large-scale transcontinental river system crossed West Antarctica during the Eocene

Extensive ice coverage largely prevents investigations of Antarctica’s unglaciated past. Knowledge about environmental and tectonic development before large-scale glaciation, however, is important for understanding the transition into the modern icehouse world. We report geochronological and sedimentological data from a drill core from the Amundsen Sea shelf, providing insights into tectonic and topographic conditions during the Eocene (~44 to 34 million years ago), shortly before major ice sheet buildup. Our findings reveal the Eocene as a transition period from &gt;40 million years of relative tectonic quiescence toward reactivation of the West Antarctic Rift System, coinciding with incipient volcanism, rise of the Transantarctic Mountains, and renewed sedimentation under temperate climate conditions. The recovered sediments were deposited in a coastal-estuarine swamp environment at the outlet of a &gt;1500-km-long transcontinental river system, draining from the rising Transantarctic Mountains into the Amundsen Sea. Much of West Antarctica hence lied above sea level, but low topographic relief combined with low elevation inhibited widespread ice sheet formation.</jats:p