Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

<p>Abstract</p> <p>Background</p> <p>New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process.</p> <p>Results</p> <p>We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under <it>in vitro </it>conditions and recruited to bind with blood vessels on gel-foam under <it>in vivo </it>conditions. The degree of recruitment of pericytes into <it>in vitro </it>neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells.</p> <p>Conclusion</p> <p>These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.</p

Amorphous carbon film deposition on inner surface of tubes using atmospheric pressure pulsed filamentary plasma source

Uniform amorphous carbon film is deposited on the inner surface of quartz tube having the inner diameter of 6 mm and the outer diameter of 8 mm. A pulsed filamentary plasma source is used for the deposition. Long plasma filaments (~ 140 mm) as a positive discharge are generated inside the tube in argon with methane admixture. FTIR-ATR, XRD, SEM, LSM and XPS analyses give the conclusion that deposited film is amorphous composed of non-hydrogenated sp2 carbon and hydrogenated sp3 carbon. Plasma is characterized using optical emission spectroscopy, voltage-current measurement, microphotography and numerical simulation. On the basis of observed plasma parameters, the kinetics of the film deposition process is discussed

A Second Generation 2-Methoxyestradiol Prodrug Is Effective Against Barrett's Adenocarcinoma in a Mouse Xenograft Model

This is the author's accepted manuscript. The original is available at http://mct.aacrjournals.org/content/12/3/2552-Methoxyestradiol (2-ME2) is an endogenous metabolite of estradiol. In preclinical models, 2-ME2 is effective against different types of tumors. Unfortunately, only low systemic concentrations of 2-ME2 can be achieved following oral administration, even after very high doses are administered to patients. In an effort to solve this problem we have now synthesized and tested a new prodrug of 2-ME2 that is water soluble due to a bio-reversible hydrophilic group added at the 3-position and more effectively resists metabolic inactivation due to an ester moiety added to mask the 17-position alcohol. We are reporting here for the first time that this double prodrug of 2-ME2 is effective as an antiproliferative and anti-cancer agent for both in vitro and in vivo studies against Barrett's esophageal adenocarcinoma (BEAC), and provided greater potency than 2-ME2 in inhibiting the growth of BEAC xenografts. Finally, studies indicate that, like 2-ME2, the 2-ME2-PD1 exhibits anticancer effect through possible disruption of microtubule-network

Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

<p>Abstract</p> <p>Background</p> <p>Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe.</p> <p>Methods</p> <p>Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated.</p> <p>Results</p> <p>Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain.</p> <p>Conclusions</p> <p>Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.</p> <p>Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.</p

Reproducibility of Standing Posture for X-Ray Radiography: A Feasibility Study of the BalancAid with Healthy Young Subjects

Unreliable spinal X-ray radiography measurement due to standing postural variability can be minimized by using positional supports. In this study, we introduce a balancing device, named BalancAid, to position the patients in a reproducible position during spinal X-ray radiography. This study aimed to investigate the performance of healthy young subjects’ standing posture on the BalancAid compared to standing on the ground mimicking the standard X-rays posture in producing a reproducible posture for the spinal X-ray radiography. A study on the posture reproducibility measurement was performed by taking photographs of 20 healthy young subjects with good balance control standing on the BalancAid and the ground repeatedly within two consecutive days. We analyzed nine posterior–anterior (PA) and three lateral (LA) angles between lines through body marks placed in the positions of T3, T7, T12, L4 of the spine to confirm any translocations and movements between the first and second day measurements. No body marks repositioning was performed to avoid any error. Lin’s CCC test on all angles comparing both standing postures demonstrated that seven out of nine angles in PA view, and two out of three angles in LA view gave better reproducibility for standing on the BalancAid compared to standing on the ground. The PA angles concordance is on average better than that of the LA angles

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans