an-unbiased-approach-of-sampling-tem-sections-in-neuroscience

An Unbiased Approach of Sampling TEM Sections in Neuroscience

Investigations of the ultrastructural features of neurons and their synapses are only possible with electron microscopy. Especially for comparative ...

Medical University of Graz

Chordoma, slow growing bone tumours originating from remnants of the notochord, leave affected patients with a median survival of six years. The high recurrence rate of chordoma, together with limited treatment options and bad overall prognosis, make the development of new treatment options urgently necessary.

Influence of silibinin and β-β-dimethylacrylshikonin on chordoma cells.

Biliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, "IL-6 classic signaling") or via soluble forms (sIL-6R, "IL-6 trans-signaling"). However, little is known about the impact on cellular responses of IL-6 trans-signaling on BTC. We analyzed primary tumors as whole sections and as tissue microarrays, and also searched The Cancer Genome Atlas database. Compared to non-neoplastic, non-inflamed gallbladder tissue, IL-6Rα was downregulated in GBC, and this correlated with the patients' overall survival. Furthermore, different CCA cell lines and compounds for activation (IL-6 and Hyper-IL-6) or inhibition (Tocilizumab and sgp130Fc) of IL-6 classic signaling and trans-signaling were used to determine their effects on cellular processes between the two modes of IL-6 signaling. Inhibition of IL-6 trans-signaling by sgp130Fc reduced CCA cell line viability and apoptosis, whereas migration and proliferation were increased. We conclude that IL-6Rα expression is a good prognostic marker for GBC, and that the blocking of IL-6 trans-signaling and activation of IL-6 classic signaling have tumor promoting activity. These findings warrant the exclusion of patients with GBC or other malignancies associated with bile metabolism from IL-6R inhibitor therapy.

Article	Year
Influence of silibinin and β-β-dimethylacrylshikonin on chordoma cells. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 30217260	2018
Pharmacologic IL-6Rα inhibition in cholangiocarcinoma promotes cancer cell growth and survival. Biochimica et biophysica acta. Molecular basis of disease\| PubMed ID: 30419338	2019

Florian Kleinegger

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