Increased levels of choline metabolites are an early marker of docetaxel treatment response in BRCA1-mutated mouse mammary tumors: an assessment by ex vivo proton magnetic resonance spectroscopy.

BACKGROUND Docetaxel is one of the most frequently used drugs to treat breast cancer. However, resistance or incomplete response to docetaxel is a major challenge. The aim of this study was to utilize MR metabolomics to identify potential biomarkers of docetaxel resistance in a mouse model for BRCA1-mutated breast cancer. METHODOLOGY High resolution magic angle spinning (HRMAS) (1)H MR spectroscopy was performed on tissue samples obtained from docetaxel-sensitive or -resistant BRCA1-mutated mammary tumors in mice. Measurements were performed on samples obtained before treatment and at 1-2, 3-5 and 6-7 days after a 25 mg/kg dose of docetaxel. The MR spectra were analyzed by multivariate analysis, followed by analysis of the signals of individual compounds by peak fitting and integration with normalization to the integral of the creatine signal and of all signals between 2.9 and 3.6 ppm. RESULTS The HRMAS spectra revealed significant metabolic differences between sensitive and resistant tissue samples. In particular choline metabolites were higher in resistant tumors by more than 50% with respect to creatine and by more than 30% with respect to all signals between 2.9 and 3.6 ppm. Shortly after treatment (1-2 days) the normalized choline metabolite levels were significantly increased by more than 30% in the sensitive group coinciding with the time of highest apoptotic activity induced by docetaxel. Thereafter, choline metabolites in these tumors returned towards pre-treatment levels. No change in choline compounds was observed in the resistant tumors over the whole time of investigation. CONCLUSIONS Relative tissue concentrations of choline compounds are higher in docetaxel resistant than in sensitive BRCA1-mutated mouse mammary tumors, but in the first days after docetaxel treatment only in the sensitive tumors an increase of these compounds is observed. Thus both pre- and post-treatment tissue levels of choline compounds have potential to predict response to docetaxel treatment.

Evaluation of a Novel Screw Position in a Type III Distal Phalanx Fracture Model: An Ex Vivo Study

OBJECTIVE: Mechanical evaluation of a novel screw position used for repair in a type III distal phalanx fracture model and assessment of solar canal penetration (SCP). STUDY DESIGN: Experimental study. SAMPLE POPULATION: Disarticulated equine hooves (n = 24) and 24 isolated distal phalanges. METHODS: Hooves/distal phalanges cut in a sagittal plane were repaired with 1 of 2 different cortical screw placements in lag fashion. In group 1 (conventional screw placement), the screw was inserted halfway between the proximal border of the solar canal (SC) and the subchondral bone surface on a line parallel to the dorsal cortex, whereas in group 2, the screw was inserted more palmar/plantar, where a perpendicular line drawn from the group 1 position reached the palmar/plantar cortex. Construct strength was evaluated by 3-point bending to failure. SCP was assessed by CT imaging and macroscopically. RESULTS: Screws were significantly longer in group 2 and in forelimbs. Group 2 isolated distal phalanges had a significantly more rigid fixation compared with the conventional screw position (maximum point at failure 31%, bending stiffness 41% higher). Lumen reduction of the SC was observed in 13/52 specimens (all from group 2), of which 9 were forelimbs. CONCLUSIONS: More distal screw positioning compared with the conventionally recommended screw position for internal fixation of type III distal phalangeal fractures allows placement of a longer screw and renders a more rigid fracture fixation. The novel screw position, however, carries a higher risk of SCP

Sendschreiben eines verdeibelten Reharbeiters an den Arbeits-Minister Milde: Ex-Silenz-ia! Da't nanu nich anders is, das des Volk sufferen wurde, wie uns die Rehberger-Nazional-Zeitung gemöldet hat ...

Welsch (Projektbearbeiter): Heftige Kritik an der Politik des preußischen Arbeits- und Handelsministers Milde

Philosophia cabbalistica : Ex fontibus primariis adumbravit atque inter se comparavit

Freystadt

Ex Libris A. S. Winter [Illustration]

J. Stark

Zwei neue Lilien'sche Ex-Libris

M. Hirschfelder

Ex-Libris Dr. E. Simonson [Illustration]

Ephraim Mose Lilien

Ex Libris Ruben Brainin [Illustration]

Ephraim Mose Lilien

Ex libris Leo Winz [Illustration]

Ephraim Mose Lilien

Ex libris Anna Freifrau von Münchhausen [Illustration]

Ephraim Mose Lilien

Ex-Oberrabbiner Professor Dr. Simonsen in Kopenhagen [Illustration] : (Porträt)

Scan von Monochrom-Mikroform

Ex-Oberrabbiner Professor Dr. Wolff in Kopenhagen [Illustration] : (Porträt)

Scan von Monochrom-Mikroform

Ex libris [Illustration] : (nach einer Radierung)

Hugo Krayn

Ex-Libris [Illustration] : eigenes Ex-Libris des Künstlers

Ephraim Mose Lilien

Ex Libris des Reichstagsabgeordneten R. Fischer [Illustration]

Ephraim Mose Lilien