44 research outputs found

    In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

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    <p>Abstract</p> <p>Background</p> <p>Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer.</p> <p>Methods</p> <p>Anaesthetized CD rats were mechanically ventilated and 10<sup>6 </sup>human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection.</p> <p>Results</p> <p>After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against ÎČ1-, ÎČ4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p < 0.05). The same degree of impairment was achieved by inhibition of P- and L-selectins via animal treatment with fucoidan (p < 0.05) and also by inhibition of the Thomson-Friedenreich (TF)-antigen (p < 0.05).</p> <p>Conclusions</p> <p>These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.</p

    Mechanics, malignancy, and metastasis: The force journey of a tumor cell

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    Focusing on membranes

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    Focusing on membranes

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    Heterogeneity of access to diabetes technology depending on area deprivation and demographics between 2016 and 2019 in Germany.

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    BACKGROUND: Despite increasing use of technology in type 1 diabetes, persistent ethnic and socio-economic disparities have been reported. We analyzed how the use of insulin pump therapy and continuous glucose monitoring (CGM) evolved over the years in Germany depending on demographics and area deprivation. METHOD: We investigated the use of insulin pump and CGM between 2016 and 2019 in 37,798 patients with type 1 diabetes aged &lt; 26 years from the German Prospective Follow-up Registry (DPV). Associations with federal state, area-deprivation quintile (German Index of Multiple Deprivation 2010 on district level), gender, and migration background were investigated over time using multiple logistic regression. RESULTS: Between 2016 and 2019, the regional distribution of insulin pump use did not change substantially and the association with area deprivation remained non-linear and statistically non-significant. The effect of area deprivation on CGM use decreased continuously and disappeared in 2019 (OR [95%-CI] Q1 vs Q5: 1.85 [1.63-2.10] in 2016; 0.97 [0.88-1.08] in 2019). The effect of migration background on the use of either technology decreased over the years but remained significant in 2019. Girls had constantly higher odds of using an insulin pump than boys (OR: 1.25 [1.18-1.31] in 2019), whereas no gender difference was identified for CGM use. CONCLUSIONS: Although disparities decreased in Germany, access to diabetes technology still depends on migration background in 2019, and gender differences in pump use persist. As technological advances are made, further research is needed to understand the reasons for these persistent disparities
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