CD15 is a risk predictor and a novel target in clear cell renal cell carcinoma.

INTRODUCTION: Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis. METHODS: A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration examined. RESULTS: ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p<0.01) and low-grade tumor differentiation (p<0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p<0.001) or with metachronous metastasis (p<0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on activating pathways of AP-1. CONCLUSION: CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicates a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely.

Multi-Disciplinary Monitoring Networks for Mesoscale Underground Experiments: Advances in the Bedretto Reservoir Project.

The Bedretto Underground Laboratory for Geosciences and Geoenergies (BULGG) allows the implementation of hectometer (>100 m) scale in situ experiments to study ambitious research questions. The first experiment on hectometer scale is the Bedretto Reservoir Project (BRP), which studies geothermal exploration. Compared with decameter scale experiments, the financial and organizational costs are significantly increased in hectometer scale experiments and the implementation of high-resolution monitoring comes with considerable risks. We discuss in detail risks for monitoring equipment in hectometer scale experiments and introduce the BRP monitoring network, a multi-component monitoring system combining sensors from seismology, applied geophysics, hydrology, and geomechanics. The multi-sensor network is installed inside long boreholes (up to 300 m length), drilled from the Bedretto tunnel. Boreholes are sealed with a purpose-made cementing system to reach (as far as possible) rock integrity within the experiment volume. The approach incorporates different sensor types, namely, piezoelectric accelerometers, in situ acoustic emission (AE) sensors, fiber-optic cables for distributed acoustic sensing (DAS), distributed strain sensing (DSS) and distributed temperature sensing (DTS), fiber Bragg grating (FBG) sensors, geophones, ultrasonic transmitters, and pore pressure sensors. The network was realized after intense technical development, including the development of the following key elements: rotatable centralizer with integrated cable clamp, multi-sensor in situ AE sensor chain, and cementable tube pore pressure sensor.