Thrombocytosis and Effects of IL-6 Knock-Out in a Colitis-Associated Cancer Model.

There is an increasing number of studies showing that thrombocytosis-accompanying a variety of solid tumors including colorectal cancer (CRC)-is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR/cas9 IL-6 knockout (KO) strain. Adult male FB/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions.

In vivo localization of chronically implanted electrodes and optic fibers in mice.

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges for operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to gold standard histology. Adjustment of the recording depth with micro-drives or early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional feedback helps surgeons avoid systematic errors. Increased aiming precision enables more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical or hippocampal layers.