37 research outputs found
The Doctrine of the Sacraments in the Apostolic Fathers
What is the teaching of the Apostolic Fathers concerning the sacraments? What do they teach of Baptism and of the Lordâs Supper? Is the number of sacraments restricted to two or is there reason to believe that the Romish Church finds in these writings ground for its teaching of seven sacraments? In treating first on Baptism and then on the Lordâs Supper these questions will be taken care of
Midostaurin does not prolong cardiac repolarization defined in a thorough electrocardiogram trial in healthy volunteers
Mechanisms of resistance against PKC412 in resistant FLT3-ITD positive human acute myeloid leukemia cells
Use of Studded Polyflexâą Stents in Patients with Neoplastic Obstructions of the Central Airways
Background: The Polyflex⹠is a commercially available silastic airway stent with proven efficacy. Due to a smooth outer surface its anchorage in the airway wall is superficial which may lead to stent migration. Objective: To study the performance of an newer version of the Polyflex stent with a studded outer surface, which should improve anchorage. Methods: In a 5-centre international study the new stent was prospectively tested in symptomatic patients with neoplastic central airway stenosis of more that 50% of normal diameter. Insertion technique, efficacy of stent placement and stent-related complications were recorded before, 1 month and 3 months post stent placement. Results: Under general anaesthesia and rigid bronchoscopy 27 stents were inserted in 26 patients, mean age: 62 years (range: 37-83), 16 men. Diagnoses were 18 bronchogenic carcinoma, 4 oesophageal carcinoma, 2 metastases, 1 tracheal carcinoma, and 1 schwannoma. The stents were inserted in the following locations: 10 right main bronchus, 8 left main bronchus, 7 trachea, and 2 tracheo-bronchial. There was significant improvement in all functional parameters assessed from before (A), to 1 month (B) and 3 months (C) after stent placement. The measured values (mean ± SD) were for the WHO scale: A: 2.7 (0.8), B: 1.5 (0.9), C: 1.6 (1.0); for the Karnofsky scale: A: 44 (19), B: 72 (18), C: 71 (21); for the Dyspnoea Index: A: 3.3 (0.7), B: 1.5 (0.8), C: 1.9 (1.2); for FEV1: A: 1.2 (0.5), B: 1.9 (0.6), C: 1.5 (0.5), and for FVC: A: 2.1 (0.7), B: 2.8 (0.7), C: 2.5 (1.0). Stent-related complications were 4 reversible stent obstructions by secretions, 1 migration. The observation period was mean 4.3 months (range 2 days to 23 months). Conclusion: The studded Polyflex showed excellent efficacy, was very well tolerated, and had a very low migration rate. It presents an improvement over the older smooth model and can be considered a true alternative to the most widely used silastic stent, the Dumon stent. Copyright © 2004 S. Karger AG, Basel.Articl
Simultaneous protection against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR-signaling blockade by oncogenic RAS.
Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS muntant cancers
One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAFV600 mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of RAS mutant cancers
Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS muntant cancers
One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAFV600 mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of RAS mutant cancers