Netrin signaling mediates survival of dormant epithelial ovarian cancer cells.

Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context.

Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor.

Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers.

From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors.

Targeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on the use of vectors to deliver radionuclides to tumor cells, targeting membrane-bound cancer-specific moieties. Here, we report the embryonic navigation cue netrin-1 as an unanticipated target for vectorized radiotherapy.

Hepatic inflammation elicits production of proinflammatory netrin-1 through exclusive activation of translation.

Background And Aims: Netrin-1 displays protumoral properties, though the pathological contexts and processes involved in its induction remain understudied. The liver is a major model of inflammation-associated cancer development, leading to HCC.

Approach And Results: A panel of cell biology and biochemistry approaches (reverse transcription quantitative polymerase chain reaction, reporter assays, run-on, polysome fractionation, cross linking immunoprecipitation, filter binding assay, subcellular fractionation, western blotting, immunoprecipitation, stable isotope labeling by amino acids in cell culture) on in vitro-grown primary hepatocytes, human liver cell lines, mouse samples and clinical samples was used.

Targeting netrin-3 in small cell lung cancer and neuroblastoma.

The navigation cue netrin-1 is well-documented for its key role in cancer development and represents a promising therapeutic target currently under clinical investigation. Phase 1 and 2 clinical trials are ongoing with NP137, a humanized monoclonal antibody against netrin-1. Interestingly, the epitope recognized by NP137 in netrin-1 shares 90% homology with its counterpart in netrin-3, the closest member to netrin-1 in humans, for which little is known in the field of cancer.

Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges.

Umbilical cord blood (UCB) is an attractive alternative to bone marrow for isolation of mesenchymal stem cells (MSCs) to treat articular cartilage defects. Here, we set out to determine the growth factors (bone morphogenetic protein 2 (BMP-2) and transforming growth factor-β (TGF-β1)) and oxygen tension effects during chondrogenesis of human UCB-MSCs for cartilage engineering. Chondrogenic differentiation was induced using 3D cultures in type I/III collagen sponges with chondrogenic factors in normoxia (21% O₂) or hypoxia (<5% O₂) for 7, 14 and 21 days.

RNA Interference and BMP-2 Stimulation Allows Equine Chondrocytes Redifferentiation in 3D-Hypoxia Cell Culture Model: Application for Matrix-Induced Autologous Chondrocyte Implantation.

As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM).

Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs.

Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages.

Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering.

Umbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors.

Sr₂₁Bi₈Cu₂(CO₃)₂O₄₁, a Bi⁵⁺ oxycarbonate with an original 10L structure.

The layered structure of Sr21Bi8Cu2(CO3)2O41 (Z = 2) was determined by transmission electron microscopy, infrared spectroscopy, and powder X-ray diffraction refinement in space group P6₃/mcm (No. 194), with a = 10.0966(3)Å and c = 26.

Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction.

Background: Articular cartilage defects are a veritable therapeutic problem because therapeutic options are very scarce. Due to the poor self-regeneration capacity of cartilage, minor cartilage defects often lead to osteoarthritis. Several surgical strategies have been developed to repair damaged cartilage.

Vascular aphasia outcome after intravenous recombinant tissue plasminogen activator thrombolysis for ischemic stroke.

Introduction: No data about the specific outcome of aphasia after thrombolysis are available. Our aim was to describe the severity and type of aphasia after stroke thrombolysis.

Methods: This retrospective cohort study included consecutive aphasic patients hospitalized in the Stroke Unit of Dijon (University Hospital, France) between 2004 and 2009 for a first-ever ischemic stroke of the left middle cerebral artery.

Oxygen storage capacity and structural flexibility of LuFe2O4+x (0≤x≤0.5).

Combining functionalities in devices with high performances is a great challenge that rests on the discovery and optimization of materials. In this framework, layered oxides are attractive for numerous purposes, from energy conversion and storage to magnetic and electric properties. We demonstrate here the oxygen storage ability of ferroelectric LuFe2O4+x within a large x range (from 0 to 0.

Sr7Co4(CO3)O(13-δ) (δ = 1.64), an original cobaltite derivative of the Ruddlesden-Popper series.

The oxycarbonate Sr7Co4(CO3)O11.36 exhibits a peculiar structure that has been characterized by combining transmission electron microscopy analyses and neutron diffraction. It consists of a regular intergrowth between the m = 2 and carbonated m = 3 members of the Sr(m+1)Co(m)O3(m+1) Ruddlesden-Popper (RP) series, Sr3Co2O5.

Stroke care organization overcomes the deleterious 'weekend effect' on 1-month stroke mortality: a population-based study.

Background And Purpose: Suffering a stroke during the weekend is associated with a poorer prognosis. The impact of implementing a dedicated stroke care network in Dijon, France, in 2003 on 30-day mortality in strokes/transient ischaemic attacks (TIA) occurring during weekends/bank holidays was evaluated.

Methods: All cases of stroke and TIA from 1985 to 2010 were identified from a population-based registry, using multiple overlapping sources of information.

Prestroke antiplatelet therapy and early prognosis in stroke patients: the Dijon Stroke Registry.

Background And Purpose: Previous antiplatelet therapy (APT) in cardiovascular prevention is common in patients with first-ever stroke. We aimed to evaluate the prognostic value of APT on early outcome in stroke patients.

Methods: All first-ever strokes from 1985 to 2011 were identified from the population-based Stroke Registry of Dijon, France.

Enhanced hyaline cartilage matrix synthesis in collagen sponge scaffolds by using siRNA to stabilize chondrocytes phenotype cultured with bone morphogenetic protein-2 under hypoxia.

Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI).

Diagnostic procedures in ischaemic stroke patients with dementia. a population-based study.

Background: Dementia is a frequent condition in stroke patients.

Aims: To investigate the effect of dementia on access to diagnostic procedures in ischaemic stroke patients.

Methods: All cases of ischaemic stroke from 2006 to 2010 were identified from the population-based Stroke Registry of Dijon, France.

Comparative effect of treadmill exercise on mature BDNF production in control versus stroke rats.

Physical exercise constitutes an innovative strategy to treat deficits associated with stroke through the promotion of BDNF-dependent neuroplasticity. However, there is no consensus on the optimal intensity/duration of exercise. In addition, whether previous stroke changes the effect of exercise on the brain is not known.

Effect of previous statin therapy on severity and outcome in ischemic stroke patients: a population-based study.

Although statin therapy has been shown to be effective in the prevention of ischemic stroke, its effect on stroke severity and early outcome is still controversial. We aimed to evaluate the association between statin use before onset and both initial severity and functional outcome in ischemic stroke patients. All cases of first-ever ischemic stroke that occurred in Dijon, France (151,000 inhabitants) between 2006 and 2011 were prospectively identified from the Dijon Stroke Registry.

NF-κB accumulation associated with COL1A1 transactivators defects during chronological aging represses type I collagen expression through a -112/-61-bp region of the COL1A1 promoter in human skin fibroblasts.

The aging process, especially of the skin, is governed by changes in the epidermal, dermo-epidermal, and dermal compartments. Type I collagen, which is the major component of dermis extracellular matrix (ECM), constitutes a prime target for intrinsic and extrinsic aging-related alterations. In addition, under the aging process, pro-inflammatory signals are involved and collagens are fragmented owing to enhanced matrix metalloproteinase activities, and fibroblasts are no longer able to properly synthesize collagen fibrils.

Serum 25-hydroxyvitamin D predicts severity and prognosis in stroke patients.

Background And Purpose: We aimed to evaluate the association between 25-hydroxyvitamin D (25(OH)D) levels and both clinical severity at admission and outcome at discharge in stroke patients.

Methods: From February 2010 to December 2010, consecutive stroke patients admitted to the Department of Neurology of Dijon, France, were identified. Clinical information was collected.

One-year survival of demented stroke patients: data from the Dijon Stroke Registry, France (1985-2008).

Background And Purpose:   Dementia is a frequent condition after stroke that may affect the prognosis of patients. Our aim was to determine whether post-stroke dementia was a predictor of 1-year case-fatality and to evaluate factors that could influence survival in demented stroke patients.

Methods: From 1985 to 2008, all first-ever strokes were recorded in the population-based stroke registry of Dijon, France (150, 000 inhabitants).