Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson's disease features.

The netrin-1/DCC ligand/receptor pair has key roles in central nervous system (CNS) development, mediating axonal, and neuronal navigation. Although expression of netrin-1 and DCC is maintained in the adult brain, little is known about their role in mature neurons. Notably, netrin-1 is highly expressed in the adult substantia nigra, leading us to investigate a role of the netrin-1/DCC pair in adult nigral neuron fate.

The continuum of ovarian response leading to BIRTH, a real world study of ART in Spain.

Background: The first biosimilar of recombinant follicle stimulating hormone (rFSH) launched in Europe was Bemfola® in 2014 following a clinical development programme demonstrating efficacy and safety to the satisfaction of the European Medicines Agency. Since then the increasing use of biosimilar rFSH has provided the opportunity to study both effectiveness across the whole population and the variation of rFSH use during routine clinical care in a real-world setting in Spain.

Methods: This is a real-world study of 1222 women treated in 26 assisted reproduction treatment centres throughout Spain providing experience of the use of a biosimilar recombinant follicle stimulating hormone in four distinct populations.

Prognostic value of a three-scale grading system based on combining molecular imaging with Ga-DOTATATE and F-FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias.

We investigated on the added prognostic value of a three-scale combined molecular imaging with Ga-DOTATATE and F-FDG PET/CT, (compared to Ki-67 based histological grading), in gastroenteropancreatic neuroendocrine neoplasia patients. 85 patients with histologically proven metastatic gastroenteropancreatic neuroendocrine neoplasias, who underwent combined PET/CT imaging were retrospectively evaluated. Highest Ki-67 value available at time of F-FDG PET/CT was recorded.

Blocking SHH/Patched Interaction Triggers Tumor Growth Inhibition through Patched-Induced Apoptosis.

The Sonic Hedgehog (SHH) pathway plays a key role in cancer. Alterations of SHH canonical signaling, causally linked to tumor progression, have become rational targets for cancer therapy. However, Smoothened (SMO) inhibitors have failed to show clinical benefit in patients with cancers displaying SHH autocrine/paracrine expression.

Patched-1 proapoptotic activity is downregulated by modification of K1413 by the E3 ubiquitin-protein ligase Itchy homolog.

The Hedgehog (Hh) receptor Patched-1 (PTCH1) opposes the activation of Gli transcription factors and induces cell death through a Gli-independent pathway. Here, we report that the C-terminal domain (CTD) of PTCH1 interacts with and is ubiquitylated on K1413 by the E3 ubiquitin-protein ligase Itchy homolog (Itch), a Nedd4 family member. Itch induces the ubiquitylation of K1413, the reduction of PTCH1 levels at the plasma membrane, and degradation, activating Gli transcriptional activity in the absence of Hh ligands.