Intraprostatic hormone dosage: Validation of a novel prostate biopsy technique.

Background: Advances in chromatography and mass spectrometry have allowed us to develop a novel technique for measuring intraprostatic hormone concentrations directly on prostate needle biopsies, rather than using traditional punch excision. This has significant clinical implications as intraprostatic dihydrotestosterone and testosterone levels could help monitor prostate growth, neoplasia and castration resistance.

Methods: Patients undergoing radical cystoprostatectomy for bladder cancer were prospectively included.

Sex steroids in serum and prostatic tissue of human cancerous prostate (STERKPROSER trial).

Background: Currently, there is no consensus regarding the expected concentration levels of intra-prostatic sex steroids in patients with Prostate Cancer (PCa). Our objective was to assess the concentration levels of sex steroids in prostatic tissue and serum, in two cohorts of patients with localized PCa or benign prostatic hyperplasia (BPH).

Methods: Between September 2014 and January 2017, men selected for radical cystectomy (for bladder cancer) or open prostatectomy (for BPH), and men selected for radical prostatectomy for localized PCa were included.

Catheter Injected Bone Marrow Mesenchymal Stem Cells Induce Efficacious Occlusion of Arteriovenous Nidus in a Swine Model.

Objectives: Arteriovenous malformations (AVMs) are complex vascular lesions. Surgical excision is the treatment of choice, but is often not achievable. Embolo-sclerotherapy alone is associated with high recurrence rates.

Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

Background: The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume.

Methods: Monocentric prospective study performed between September 2014 and January 2017.

Diameter and thickness-related variations in mechanical properties of degraded arterial wall in the rat xenograft model.

The purpose of this study was to evaluate the diameter and thickness-related variations in mechanical properties of degraded arterial wall. To this end, ring tests were performed on 31 samples from the rat xenograft model of abdominal aortic aneurysm (AAA) and failure properties were determined. An inverse finite element method was then employed to identify the material parameters of a hyperelastic and incompressible strain energy function.

Influence of viscoelastic properties of an hyaluronic acid-based hydrogel on viability of mesenchymal stem cells.

Background: The present research is involved in the framework of the biotherapy using mesenchymal stem cells (MSCs). Here, MSC encapsulation in a hydrogel based on hyaluronic acid (HA) is investigated to optimize the composition of the biomaterial.

Methods: Several formulations candidates of the hydrogel (9 in total) are postulated as a scaffold for the 3D MSC culture in order to investigate their potential to mimic the in vivo cellular environment.

Sex steroids, precursors, and metabolite deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism: a GCMS-based comparative study.

Context: Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism or Kallmann syndrome.

Objective: The objective of the study was to compare the serum levels of sex steroids, precursors, and metabolites between men with complete IHH and those with Hypo-Pit.

Patients: We studied 42 healthy men, 16 untreated men with IHH (normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxine, and GH replacement therapy but not T.

Chemokine (C-X-C motif) receptor 4 blockade by AMD3100 inhibits experimental abdominal aortic aneurysm expansion through anti-inflammatory effects.

Objective: Inflammation plays a critical role in the development of abdominal aortic aneurysms (AAAs). Because stromal cell-derived factor 1 (SDF-1) is known for its ability to attract inflammatory cells, we investigated whether SDF-1/chemokine (C-X-C motif) receptor 4 (CXCR4) axis is expressed in aneurysmal aortic wall and plays a role in AAA physiopathology and asked whether its blockade modulates AAA formation and expansion.

Approach And Results: Quantitative real-time polymerase chain reaction analysis showed that SDF-1α and CXCR4 mRNA levels are increased in both human and CaCl2-induced mouse AAA wall and are positively correlated to the aortic diameter in mice.

Mechanical behavior of abdominal aorta aneurysm in rat model treated by cell therapy using mesenchymal stem cells.

Regenerative medicine to substitute conventional surgery or an endovascular stent constitutes currently a challenge to treat abdominal aneurysm artery (AAA). The present paper addresses the following question: Can a cellular therapy from mesenchymal stem cells reestablish the mechanical properties of damaged abdominal aorta? For that, the xenograft rat model that mimics arterial dilatation due to aneurysmal disease is used to study the effects of the proposed cellular therapy. To investigate the changes in the mechanical behavior of the arterial wall, the artery is assumed to be made of a hyperelastic and incompressible material characterized by a strain energy function fitted to the average data set of uniaxial tests of AAA tissue samples.

Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.

Purpose: Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs.

Optimized hyaluronic acid-hydrogel design and culture conditions for preservation of mesenchymal stem cell properties.

A novel approach that preserved most mesenchymal stem cell (MSC) characteristics was developed using MSC encapsulation in a hydrogel based on hyaluronic acid (HA). An optimized HA-hydrogel composition, whose characteristics were assessed by scanning electron microscopy and viscoelastic property analyses, as well as the more favorable MSC seeding density, was established. These optimal three-dimensional MSC culture conditions allowed morphological cell remodeling, maintained the expression of stem cell markers over 28 days of culture, and preserved MSC differentiation plasticity.

Stochastic modelling of wall stresses in abdominal aortic aneurysms treated by a gene therapy.

A stochastic mechanical model using the membrane theory was used to simulate the in vivo mechanical behaviour of abdominal aortic aneurysms (AAAs) in order to compute the wall stresses after stabilisation by gene therapy. For that, both length and diameter of AAAs rats were measured during their expansion. Four groups of animals, control and treated by an endovascular gene therapy during 3 or 28 days were included.

Carotid artery mechanical properties and stresses quantified using in vivo data from normotensive and hypertensive humans.

The goal of this study was to model the in vivo non-linear mechanical behavior of human common carotid arteries (CCAs) and then to compare wall stresses and associated contributions of micro-constituents in normotensive (NT) and treated hypertensive (HT) subjects. We used an established theoretical model of 3D arterial mechanics that assumes a hyperelastic, anisotropic, active-passive, and residually stressed wall. In vivo data were obtained non-invasively from CCAs in 16 NT (21-64 years old) and 25 treated HT (44-69 years old) subjects.

Aortic length changes during abdominal aortic aneurysm formation, expansion and stabilisation in a rat model.

Background: Determinants of extracellular matrix (ECM) destruction/reconstruction balance influencing abdominal aortic aneurysm (AAA) diameter may impact length.

Objective: Document aortic lengthening, its correlation to diameter, and determine how treatments that impact diameter also affect length.

Methods: Three hundred and fifty-five diameter and length measurements were performed in 308 rats during AAA formation, expansion and stabilisation in guinea pig aortas xenografted in rats.

[Pathobiology of idiopathic ascending aortic aneurysms].

Background: The majority of ascending aortic aneurysms cannot be related to any specific etiology and should be qualified as idiopathic. The incidence of this disease is increasing in the population of the developed countries but its pathobiology is poorly understood.

Aim: This article is reviewing the publications concerning the pathobiology of idiopathic ascending aortic aneurysms.

Intraurethral transfer of satellite cells by myofiber implants results in the formation of innervated myotubes exerting tonic contractions.

Purpose: We investigated a new method of muscle precursor cell transfer in the urethra for the treatment of urinary incontinence, consisting of implanting myofibers with their satellite cells.

Materials And Methods: In preliminary experiments to test the regenerative capacities of satellite cells histological analysis was performed on days 7 and 30 after the implantation of myofiber cores in the urethra of 6 female pigs. In the main experiments 11 pigs underwent baseline urodynamics, followed by endoscopic destruction of the striated urethral sphincter located around the distal urethra (day 0).

Multifaceted interaction between the androgen and Wnt signaling pathways and the implication for prostate cancer.

Androgen action in prostate and prostate cancer cells is dependent upon the androgen receptor (AR) protein that transcriptionally regulates the expression of androgen-dependent genes in the presence of a steroid ligand. Whereas the overall schema of androgen action mediated by this receptor protein appears to be relatively simple, androgen signaling is now known to be influenced by several other cell signal transduction pathways and here we review the evidence that the canonical Wnt signaling pathway also modulates androgen signaling at multiple levels. Wnt is a complex signaling pathway whose endpoint involves activation of transcription from LEF-1/TCF transcription factors and it is known to be involved in the development and progression of numerous human epithelial tumors including prostate cancer.

Protocadherin-PC promotes androgen-independent prostate cancer cell growth.

Background: Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues.

Methods: LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions.

Serum bioavailable testosterone: assayed or calculated?

Background: Bioavailable testosterone (BT), circulating testosterone not bound to sex hormone-binding globulin (SHBG), is thought to easily penetrate cells. We compared BT measurements obtained by assays with those obtained by calculation with different testosterone association constants.

Methods: We obtained sera from 2 groups of hypogonadal men [group 1 (G1), 1421 samples; group 2 (G2), 170 samples] and a group of healthy men [group 3 (G3), 109 samples].

Overexpression of transforming growth factor-beta1 stabilizes already-formed aortic aneurysms: a first approach to induction of functional healing by endovascular gene therapy.

Background: The cell response to transforming growth factor-beta1 (TGF-beta1), a multipotent cytokine with healing potential, varies according to tissue context. We have evaluated the ability of TGF-beta1 overexpression by endovascular gene therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by inflammation and proteolysis.

Methods And Results: Active TGF-beta1 overexpression was obtained in already-developed experimental AAAs in rats after endovascular delivery of an adenoviral construct encoding for a mutated form of active simian TGF-beta1 and in an explant model using human atherosclerotic AAA fragments incubated with recombinant active TGF-beta1.

Local endovascular treatment of aortic aneurysms. From operating theater to lab bench.

Current treatment of aortic abdominal aneurysms by conventional surgery or endoprosthesis is flawed by high post-operative mortality and unpredictable durability of haemodynamic exclusion, respectively. We have developed endovascular approaches with cell and gene transfer, aimed at controlling further diameter expansion in an animal model of already-developed aneurysms in rats. Preliminary results suggest that both cell and gene endovascular therapy can be used to control expansion of aneurysms generated by inflammation and proteolytic destruction of the aortic wall.

[Cell therapy for urethral sphincter incompetence by muscle precursor cell autograft].

This article reviews cell therapy for muscle diseases and describes the development of a treatment for urethral sphincter insufficiency by muscle precursor cell (MPC) autograft. These studies were conducted in several successive steps, comprising: 1) comparative study of the cellular mechanisms of regeneration of skeletal striated muscle and urethral striated sphincter and development of a method of extraction of MPC; 2) creation of an animal model of sphincter injury reproducing chronic denervation lesions and fibrosis responsible for sphincter insufficiency in human; 3) study of the biology of intrasphincteric transplantation of MPC extracted from peripheral muscle, taking into account the interactions between these cells and the peripheral nervous system.