A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results in tumour shrinkage in highly proliferating CCND1 -driven PDX, including different RB-positive PDX with acquired palbociclib resistance. Mechanistic studies in endocrine resistant cell lines, suggest an ER-independent function of PLK1 in regulating cell proliferation. Finally, in two independent clinical cohorts of ER positive BC, we find a strong association between high expression of PLK1 and a shorter metastases-free survival and poor response to anastrozole. In conclusion, our findings support clinical development of PLK1 inhibitors in patients with advanced CCND1 -driven BC, including patients progressing on palbociclib treatment.

Static and dynamic imaging without blood sampling can discriminate between LG and HG for both newly diagnosed and recurrent gliomas. In dynamic imaging, excellent discrimination was obtained by considering the transport rate constant k1 of tumors. In static imaging, the best discrimination based on SUV was obtained for SUV(mean) calculated from a 5-minute acquisition started at 38 minutes after injection.

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The cerebral venous system is poorly understood, and best appreciated under macroscopic anatomical considerations. We present an anatomical and immunohistochemical studies to better define the morphological characteristics of the junction between the great cerebral vein and the straight sinus. Twenty-five cadaveric specimens from the anatomy laboratory of the University Victor Segalen of Bordeaux were studied. The observation of the venous junctions with the straight sinus was performed under an operating microscope. The smooth muscular actin immunohistochemical staining was performed for 18 veno-sinosal junctions. Five venous junctions were observed using an electron microscope. We observed 3 different anatomic aspects: type 1 was a junction with a small elevation in its floor and a posterior thickening (14 cases); type 2 was a junction with an outgrowth on the floor like a cornice (7 cases); and type 3 was a junction presenting a nodule. Microscopic study of type 1 and 2 junctions showed a positive coloration to orceine attesting the presence of elastic fibers. Immunohistochemistry revealed the presence of smooth muscular actin and S 100 protein attesting the presence of smooth muscular fibers and nervous fibers. We observed in the ultrastructural study, a morphological progression of the endothelium. The venous orifice of the great cerebral vein into the straight sinus could be anatomically assimilated as a true "sphincter." Its function in the regulation of the cerebral blood flow needs further exploration.

The authors present the French concept of a mobile neurosurgical unit (MNSU) as used to provide specific support to remote military medicosurgical units deployed in Africa, South America, Central Europe, and Afghanistan. From 2001 to 2009, 15 missions were performed, for 16 patients. All but 3 of these missions (those in Kosovo, French Guyana, and Afghanistan) concerned Africa. Eleven patients were French soldiers, 3 were civilians, and 2 were Djiboutian soldiers. The conditions that MNSUs were requested for included craniocerebral wounds (2 cases), closed head trauma (7 cases), spinal trauma (5 cases), and spontaneous intracranial hemorrhage (2 cases). In 5 of the 16 cases, neurosurgical treatment was provided on site. All French soldiers and 2 civilians were evacuated to France. The MNSU can be deployed for timely treatment when some delay in neurosurgical management is acceptable.