University of Kiel

About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.

IL-6 Trans-Signaling via the Soluble IL-6 Receptor: Importance for the Pro-Inflammatory Activities of IL-6

Abstract: Interleukin-6 (IL-6) is a cytokine with many activities. It has functions in the regulation of the immune system and the nervous system. Furthermore, IL-6 is involved in liver regeneration and in the metabolic control of the body. On target cells, IL-6 binds to an 80 kDa IL-6 receptor (IL-6R). The complex of IL-6 and IL-6R associates with a second protein, gp130, which thereupon dimerizes and initiates intracellular signaling. Whereas gp130 is expressed on all cells, IL-6R is only present on few cells in the body including hepatocytes and some leukocytes. Cells, which do not express IL-6R cannot respond to the cytokine, since gp130 alone has no measurable affinity for IL-6. Interestingly, a soluble form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL-6 and sIL-6R can bind to gp130 on cells, which do not express the IL-6R, and which are unresponsive to IL-6. This process has been called trans-signaling. Here I will review published evidence that IL-6 trans-signaling is pro-inflammatory whereas classic IL-6 signaling via the membrane bound IL-6R is needed for regenerative or anti-inflammatory activities of the cytokine. Furthermore, the detailed knowledge of IL-6 biology has important consequences for therapeutic strategies aimed at the blockade of the cytokine IL-6.

Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial

Abstract: Objective The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor a (TNF), for the induction of clinical remission in anti-TNF nao¨ve patients with moderately to severely active ulcerative colitis. Methods This 8-week, multicentre, randomised, doubleblind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of $6 points and endoscopic subscore of $2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1:1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score #2 with no individual subscore >1) at week 8, assessed in 390 patients randomised (1:1:1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment. Results At week 8, 18.5% of patients in the ADA160/80 group (p¼0.031 vs placebo) and 10.0% in the ADA80/40 group (p¼0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths. Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants. Clinical trial NCT00385736.

Recent Research on Selective Exposure to Information

Abstract: Publisher Summary This chapter highlights the recent research on the selective exposure to information. The term “selective exposure” implies several assumptions concerning the decision-making process. It assumes that the seeking out of decision relevant information does not cease once a decision is made. This notion also implies that this post-decisional information seeking and evaluation is not impartial but, rather, is biased by certain factors activated during the decision-making process. This chapter discusses the fundamental theses of dissonance theory as it relates to selective exposure and gives a short overview of the early research. This chapter describes new research, including the experiments designed to specify those factors most important in influencing informational selectivity: the effects of choice and commitment on selective information seeking, selectivity and refutability of arguments, the amount of available information and its usefulness, the usefulness of decision reversibility, as well as the intensity of dissonance. This chapter reports the results on some additional variables-cost of information, the reliability of dissonant information, and the effects of personality.

Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial

Abstract: Summary Background Preclinical data suggest that triple-negative breast cancers are sensitive to interstrand crosslinking agents, and that synergy may exist for the combination of a taxane, trastuzumab, and a platinum salt for HER2-positive breast cancer. We therefore aimed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer. Methods Patients with previously untreated, non-metastatic, stage II–III, triple-negative breast cancer and HER2-positive breast cancer were enrolled. Patients were treated for 18 weeks with paclitaxel (80 mg/m 2 once a week) and non-pegylated liposomal doxorubicin (20 mg/m 2 once a week). Patients with triple-negative breast cancer received simultaneous bevacizumab (15 mg/kg intravenously every 3 weeks). Patients with HER2-positive disease received simultaneous trastuzumab (8 mg/kg initial dose with subsequent doses of 6 mg/kg intravenously every 3 weeks) and lapatinib (750 mg daily). Patients were randomly assigned in a 1:1 ratio with dynamic allocation and minimisation, stratified by biological subtype and Ki-67 level to receive, at the same time as the backbone regimens, either carboplatin (AUC 1·5 [2·0 for the first 329 patients] once a week) or no carboplatin. The primary endpoint the proportion of patients who achieved a pathological complete response (defined as ypT0 ypN0), analysed for all patients who started treatment; a p value of less than 0·2 was deemed significant for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01426880. Findings 296 patients were randomly assigned to receive carboplatin and 299 to no additional carboplatin, of whom 295 and 293 started treatment, respectively. In this final analysis, 129 patients (43·7%, 95% CI 38·1–49·4) in the carboplatin group achieved a pathological complete response, compared with 108 patients (36·9%, 31·3–42·4) without carboplatin (odds ratio 1·33, 95% CI 0·96–1·85; p=0·107). Of the patients with triple-negative breast cancer, 84 (53·2%, 54·4–60·9) of 158 patients achieved a pathological complete response with carboplatin, compared with 58 (36·9%, 29·4–44·5) of 157 without (p=0·005). Of the patients with HER2-positive tumours, 45 (32·8%, 25·0–40·7) of 137 patients achieved a pathological complete response with carboplatin compared with 50 (36·8%, 28·7–44·9) of 136 without (p=0·581; test for interaction p=0·015). Haematological and non-haematological toxic effects that were significantly more common in the carboplatin group than in the no-carboplatin group included grade 3 or 4 neutropenia (192 [65%] vs 79 [27%]), grade 3 or 4 anaemia (45 [15%] vs one [ vs one [ vs 32 [11%]); carboplatin was more often associated with dose discontinuations (141 [48%] with carboplatin and 114 [39%] without carboplatin; p=0·031). The frequency of grade 3 or 4 haematological events decreased from 82% (n=135) to 70% (n=92) and grade 3 or 4 non-haematological events from 78% (n=128) to 59% (n=77) in the carboplatin arm when the dose of carboplatin was reduced from AUC 2·0 to 1·5. Interpretation The addition of neoadjuvant carboplatin to a regimen of a taxane, an anthracycline, and targeted therapy significantly increases the proportion of patients achieving a pathological complete response. This regimen seems to increase responses in patients with triple-negative breast cancer, but not in those with HER2-positive breast cancer. Funding GlaxoSmithKline, Roche, and Teva.