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Sample records for share angiogenic characteristics

  1. Knowledge Sharing in Public Sector Organizations: The Effect of Organizational Characteristics on Interdepartmental Knowledge Sharing.

    OpenAIRE

    A. WILLEM; M. BUELENS

    2005-01-01

    Public sector organizations are mainly knowledge-intensive organizations and to exploit their knowledge, effective knowledge sharing among the different departments is required. We focus on specific characteristics of public sector organizations that increase or limit interdepartmental knowledge sharing. Three types of organization-specific coordination mechanisms directly influence knowledge sharing between units. Organizations are also characterized by members’ social identification and tru...

  2. Angiogenic biomarkers in pregnancy

    DEFF Research Database (Denmark)

    Rasmussen, Lene G; Lykke, Jacob A; Staff, Anne C

    2015-01-01

    We review diagnostic and predictive roles of the angiogenic proteins placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin in preeclampsia, and their association with future cardiovascular disease, diabetes, and breast cancer. Specific patterns of these proteins repres...... are correlated to HbA1c and fasting glucose. Hence dysregulation in angiogenic proteins may link preeclampsia and cardiovascular diseases, targeting women who could in future benefit from prophylactic programs to possibly prevent, delay or reduce cardiovascular disease.......We review diagnostic and predictive roles of the angiogenic proteins placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin in preeclampsia, and their association with future cardiovascular disease, diabetes, and breast cancer. Specific patterns of these proteins...... represent preeclamptic prediction markers and combined with maternal and clinical characteristics, the predictive values increase. Women experiencing preeclampsia have increased risks of developing cardiovascular diseases and diabetes, and a decreased risk of breast cancer. High placental growth factor...

  3. The characteristics to consider in municipal shared spaces

    DEFF Research Database (Denmark)

    Brinkoe, Rikke; Nielsen, Susanne Balslev

    2017-01-01

    to establishing a shared space in a municipal real-estate portfolio, created in collaboration between researchers and practitioners. It provides an introduction to the topic and outlines a number of tasks that must be completed in different parts of a project, thereby providing a tool which practitioners can use......Purpose The purpose of this study is through collaboration with practitioners to identify key characteristics of municipal shared spaces and, based on these, developing a guide for establishing a shared space in a municipal real-estate portfolio. Design/methodology/approach This paper builds...... on existing theory on the subject of shared space as well as the practical experience of professionals within the fields of property management, space management and facilities management. The guide presented is the result of data collected through case studies, interviews, surveys and literature reviews...

  4. What are the characteristics of repatriation knowledge sharing practices? : Exploring the barriers and opportunities for sharing knowledge

    OpenAIRE

    Stensholt, Jan Peter; Ingebo, Dag Anders

    2017-01-01

    Masteroppgave(MSc) in Master of Science in Leadership and Organizational Psychology - Handelshøyskolen BI, 2017 This thesis explores the characteristics of repatriation knowledge sharing, focusing on identifying the barriers and opportunities for sharing knowledge in a repatriation context. The findings presented is based on qualitative interviews of eight former expatriates in a Norwegian company within the defense industry operating in more than 25 different countries. Our st...

  5. Characterization and angiogenic potential of human neonatal and infant thymus mesenchymal stromal cells.

    Science.gov (United States)

    Wang, Shuyun; Mundada, Lakshmi; Johnson, Sean; Wong, Joshua; Witt, Russell; Ohye, Richard G; Si, Ming-Sing

    2015-04-01

    Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro. ©AlphaMed Press.

  6. Characteristics of file sharing and peer to peer networking | Opara ...

    African Journals Online (AJOL)

    A peer-to-peer (p2p) network allows computer hardware and software to function without the need for special server devices. While file sharing is the practice of distributing or providing access to digitally stored information, such as computer programs, multi-media (audio, video) resources, documents, or electronic books.

  7. Angiogenic Factors and Renal Disease in Pregnancy

    Directory of Open Access Journals (Sweden)

    Julie S. Rhee

    2011-01-01

    Full Text Available Background. Preeclampsia is difficult to diagnose in patients with underlying renal disease and proteinuria. Prior studies show that there is an angiogenic factor imbalance with elevated levels of antiangiogenic proteins soluble fms-like tyrosine kinase 1 (sFlt1 and soluble endoglin (sEng and reduced levels of the proangiogenic protein, placental growth factor (PlGF in women with preeclampsia. These angiogenic biomarkers may be useful in distinguishing preeclampsia from other conditions of pregnancy, which may present with overlapping clinical characteristics. Cases. Case 1: A multiparous woman at 18 weeks gestation with nephrotic syndrome presented with hypertensive emergency and worsening renal insufficiency. She underwent induction of labor for severe preeclampsia. Her sFlt1 and sEng levels were at the 97 percentile while her PlGF level was undetectable (less than the 1st percentile. Case 2: A nulliparous woman with lupus nephritis at 22 weeks gestation presented with fetal demise and heart failure. Three weeks previously, the patient had developed thrombocytopenia and hypertensive urgency. She underwent dilation and evacuation. Her angiogenic profile was consistent with severe preeclampsia. Conclusion. Angiogenic factors may provide evidence to support a diagnosis of preeclampsia in patients with preexisting renal disease and proteinuria, conditions in which the classical definition of hypertension and proteinuria cannot be used.

  8. Improving Service Delivery: Investigating the Role of Information Sharing, Job Characteristics, and Employee Satisfaction

    Science.gov (United States)

    Bontis, Nick; Richards, David; Serenko, Alexander

    2011-01-01

    Purpose: The purpose of this study is to propose and test a model designed to investigate the impact of job characteristics, employee satisfaction, and information sharing on two key indicators of quality service delivery, such as worker perceptions of their efficiency and customer focus. Design/methodology/approach: During the project, 9,060…

  9. The prevalence and characteristics associated with mother-infant bed-sharing in Klang district, Malaysia.

    Science.gov (United States)

    Tan, K L; Ghani, S N; Moy, F M

    2009-12-01

    This was a cross-sectional study to determine the prevalence and characteristics of mother-infant bed-sharing practice in Klang district, Malaysia. Data was collected by face-to-face interview using a structured questionnaire for a four month period in 2006. A total of 682 mother-infant pairs attending government health clinics were included in the study. Data regarding socio-demographic characteristics of the mothers, information on the infants, bed-sharing and breastfeeding practices were collected. The mean maternal age was 28.4 +/- 5.1 years while the mean infant gestational age was 38.8 +/- 1.8 weeks. The study showed the prevalence of bed-sharing was 73.5% (95% CI: 70.0, 76.7). In multivariate analysis; area of interview, maternal occupation, family income, breastfeeding and infant birth weight were associated with bed-sharing after adjusted for maternal ethnicity, age, marital status, educational level, parity, infant gender and infant gestational age. In conclusion, bed-sharing is a common practice in Klang district, Malaysia, not specific to ethnicity, but strongly associated with low family income and breastfeeding.

  10. Determinants of success in Shared Savings Programs: An analysis of ACO and market characteristics.

    Science.gov (United States)

    Ouayogodé, Mariétou H; Colla, Carrie H; Lewis, Valerie A

    2017-03-01

    Medicare's Accountable Care Organization (ACO) programs introduced shared savings to traditional Medicare, which allow providers who reduce health care costs for their patients to retain a percentage of the savings they generate. To examine ACO and market factors associated with superior financial performance in Medicare ACO programs. We obtained financial performance data from the Centers for Medicare and Medicaid Services (CMS); we derived market-level characteristics from Medicare claims; and we collected ACO characteristics from the National Survey of ACOs for 215 ACOs. We examined the association between ACO financial performance and ACO provider composition, leadership structure, beneficiary characteristics, risk bearing experience, quality and process improvement capabilities, physician performance management, market competition, CMS-assigned financial benchmark, and ACO contract start date. We examined two outcomes from Medicare ACOs' first performance year: savings per Medicare beneficiary and earning shared savings payments (a dichotomous variable). When modeling the ACO ability to save and earn shared savings payments, we estimated positive regression coefficients for a greater proportion of primary care providers in the ACO, more practicing physicians on the governing board, physician leadership, active engagement in reducing hospital re-admissions, a greater proportion of disabled Medicare beneficiaries assigned to the ACO, financial incentives offered to physicians, a larger financial benchmark, and greater ACO market penetration. No characteristic of organizational structure was significantly associated with both outcomes of savings per beneficiary and likelihood of achieving shared savings. ACO prior experience with risk-bearing contracts was positively correlated with savings and significantly increased the likelihood of receiving shared savings payments. In the first year, performance is quite heterogeneous, yet organizational structure does not

  11. Financial and Legal Characteristics of Cross-Jurisdictional Shared Service Agreements Between Local Public Health Agencies.

    Science.gov (United States)

    Watts, Theresa; Zahner, Susan; Mrochek, Tracy

    Cross-jurisdictional sharing is a resource management strategy increasingly being used by local health departments to provide essential and mandated public health services. Cross-jurisdictional shared service agreements (CJSSAs) are the legal documents that govern cross-jurisdictional sharing arrangements. Information on the financial and legal characteristics of CJSSAs is limited. This study described the financial and legal elements of a set of formal, written CJSSAs in one state to offer guidance to practitioners on how to structure the financial and legal elements in CJSSAs. CJSSAs, which included a written statement about the financial commitment governed by the agreement (n = 63), were analyzed. Data collection occurred through 2 structured data extraction tools and structured telephone interviews conducted with local and tribal health department directors. Descriptive statistics of all variables and a single predictor linear regression were performed. The higher population partner to the CJSSA more often provided the public health service and received payment (n = 41; 65%). Financial statements were found to vary by CJSSA characteristic. CJSSAs were more likely to be legally complete when a legal counsel was involved in creating them (odds ratio = 2.74; 95% confidence interval, 2.19-3.29; P ≤ .001). Yet, only 2 (3%) of the CJSSAs described all the legal elements and were considered legally complete. Clearly identifying and including necessary fiscal and legal elements when creating and managing CJSSAs may strengthen agreements and reduce local health department legal and fiscal vulnerabilities. Local health department capacity for planning, coordination, budgeting, management, and evaluation is essential when creating CJSSA. Careful consideration of cost-sharing and consulting with legal counsel could strengthen the CJSSA.

  12. The role of networks in firms' multi-characteristics competition and market-share inequality

    CERN Document Server

    Garas, Antonios

    2016-01-01

    We develop a location analysis spatial model of firms' competition in multi-characteristics space, where consumers' opinions about the firms' products are distributed on multilayered networks. Firms do not compete on price but only on location upon the products' multi-characteristics space, and they aim to attract the maximum number of consumers. Boundedly rational consumers have distinct ideal points/tastes over the possible available firm locations but, crucially, they are affected by the opinions of their neighbors. Our central argument is that the consolidation of a dense underlying consumers' opinion network is the key for the firm to enlarge its market-share. Proposing a dynamic agent-based analysis on firms' location choice we characterize multi-dimensional product differentiation competition as adaptive learning by firms' managers and we argue that such a complex systems approach advances the analysis in alternative ways, beyond game-theoretic calculations.

  13. Graphene Oxides Show Angiogenic Properties.

    Science.gov (United States)

    Mukherjee, Sudip; Sriram, Pavithra; Barui, Ayan Kumar; Nethi, Susheel Kumar; Veeriah, Vimal; Chatterjee, Suvro; Suresh, Kattimuttathu Ittara; Patra, Chitta Ranjan

    2015-08-05

    Angiogenesis, a process resulting in the formation of new capillaries from the pre-existing vasculature plays vital role for the development of therapeutic approaches for cancer, atherosclerosis, wound healing, and cardiovascular diseases. In this report, the synthesis, characterization, and angiogenic properties of graphene oxide (GO) and reduced graphene oxide (rGO) have been demonstrated, observed through several in vitro and in vivo angiogenesis assays. The results here demonstrate that the intracellular formation of reactive oxygen species and reactive nitrogen species as well as activation of phospho-eNOS and phospho-Akt might be the plausible mechanisms for GO and rGO induced angiogenesis. The results altogether suggest the possibilities for the development of alternative angiogenic therapeutic approach for the treatment of cardiovascular related diseases where angiogenesis plays a significant role. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Decisional Involvement: Differences Related to Nurse Characteristics, Role, and Shared Leadership Participation.

    Science.gov (United States)

    Fischer, Shelly A; Horak, Dawn; Kelly, Lesly A

    2017-12-18

    A sample of 1933 registered nurses working in 24 hospitals with shared leadership was surveyed to examine perceptions of nurse decisional involvement. Council participation was associated with higher decisional involvement scores (P = .03), and nurse experience was a statistically significant predictor of decisional involvement (P < .01). Nurse manager and staff registered nurse scores were significantly different (P < .01). Shared leadership may promote staff nurse perceptions of involvement in decision-making.

  15. Characteristics of parents with shared residence and father sole custody. Evidence from Norway 2012

    OpenAIRE

    Ragni Hege Kitterød; Jan Lyngstad

    2014-01-01

    Shared residence for children has increased considerably in recent years among parents living apart in Norway, while mother sole custody is less common than before and father sole custody is still practiced by a minority. A similar pattern is observed in many other countries as well. In Norway, 25 prcent of the parents with separate homes now practice shared residence for their children, compared to only 10 percent in 2004. Such an arrangement is most common among highly educated parents, tho...

  16. Understanding the Characteristics of Internet Short Video Sharing: YouTube as a Case Study

    OpenAIRE

    Cheng, Xu; Dale, Cameron; Liu, Jiangchuan

    2007-01-01

    Established in 2005, YouTube has become the most successful Internet site providing a new generation of short video sharing service. Today, YouTube alone comprises approximately 20% of all HTTP traffic, or nearly 10% of all traffic on the Internet. Understanding the features of YouTube and similar video sharing sites is thus crucial to their sustainable development and to network traffic engineering. In this paper, using traces crawled in a 3-month period, we present an in-depth and systemati...

  17. A summary of design, policies and operational characteristics for shared bicycle/bus lanes.

    Science.gov (United States)

    2012-07-01

    This report contains the results of an investigation of the design and operation of shared bicycle/bus lanes in municipalities in the United States and other countries. These lanes are designated for use by public transit buses, bicycles, and usually...

  18. A common carp (Cyprinus carpio L.) leucocyte cell line shares morphological and functional characteristics with macrophages.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Rombout, J.H.W.M.; Flik, G.; Verburg-van Kemenade, B.M.L.

    1997-01-01

    A carp leucocyte cell line (CLC), originating from peripheral blood, was characterised to assess its suitability for studies into carp macrophage functions. The cells reacted with a monoclonal antibody raised against carp head kidney macrophages. Other macrophage characteristics observed were:

  19. The association between kinematic risky driving among parents and their teenage children: Moderation by shared personality characteristics

    Science.gov (United States)

    Ehsani, Johnathon P.; Simons-Morton, Bruce; Xie, Yunlong; Klauer, Sheila G.; Albert, Paul S.

    2014-01-01

    This study examined the driving behavior of 42 parent–teenager dyads for 18 months, under naturalistic driving conditions. At baseline participants’ personality characteristics were assessed. Objective risky driving measures (kinematic risky driving) were captured by accelerometers for the duration of the study. To estimate teenage and parent correlations in kinematic risky driving, separate Poisson regression models were fit for teenagers and parents. Standardized residuals were computed for each trip for each individual. Correlations were obtained by estimating the Spearman rank correlations of the individual average residuals across teenagers and parents. The bootstrap technique was used to estimate the standard errors associated with the parent–teenager correlations. The overall correlation between teenage and parent kinematic risky driving for the 18-month study period was positive, but weak (r = 0.18). When the association between parent and teenagers’ risky driving was adjusted for shared personality characteristics, the correlation reduced to 0.09. Although interesting, the 95% confidence intervals on the difference between these two estimates overlapped zero. We conclude that the weak similarity in parent–teen kinematic risky driving was partly explained by shared personality characteristics. PMID:24745931

  20. Is human fracture hematoma inherently angiogenic?

    LENUS (Irish Health Repository)

    Street, J

    2012-02-03

    This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.

  1. Low back pain patients in Sweden, Denmark and the UK share similar characteristics and outcomes

    DEFF Research Database (Denmark)

    Kongsted, Alice; Davies, Laura; Axén, Iben

    2015-01-01

    observed. The clinical course followed almost identical patterns across nations and small observed differences were not present after adjusting for baseline factors. The associations of LBP intensity and episode duration with outcome differed in strength between countries. CONCLUSIONS: Chiropractic...... were LBP intensity (0-10 scales) and LBP frequency (0-7 days the previous week). Cohort differences were tested in mixed models accounting for repeated measures. It was investigated if any differences were explained by different baseline characteristics, and interaction terms between baseline factors...... patients with low back pain had similar characteristics and clinical course across three Northern European countries. It is unlikely that culture have substantially different impacts on the course of LBP in these countries and the results support knowledge transfer between the investigated countries....

  2. Comparison of anti-angiogenic properties of pristine carbon nanoparticles

    DEFF Research Database (Denmark)

    Wierzbicki, Mateusz; Sawosz, Ewa; Grodzik, Marta

    2013-01-01

    showed the greatest anti-angiogenic properties. Interestingly, fullerene exhibited the opposite effect, increasing blood vessel development, while graphite nanoparticles and graphene had no effect. Subsequently, protein levels of pro-angiogenic growth factor receptors were analysed, showing that diamond...

  3. Does hemiplegic shoulder pain share clinical and sensory characteristics with central neuropathic pain? A comparative study.

    Science.gov (United States)

    Zeilig, Gabi; Rivel, Michal; Doron, Dana; Defrin, Ruth

    2016-10-01

    Hemiplegic shoulder pain (HSP) is a common poststroke complication and is considered to be a chronic pain syndrome. It is negatively correlated with the functional recovery of the affected arm and the quality of life of the individual. It also leads to a longer length of stay in rehabilitation. Today, there is no consensus as to the underlying mechanism causing HSP, making the syndrome difficult to treat. The aim of this study was to compare the clinical and sensory profile of individuals with HSP to that of individuals with established central neuropathic pain (CNP) in order to identify common features and the presence of neuropathic components in HSP. Cross sectional controlled study. Outpatient rehabilitation clinics. Sixteen chronic HSP patients and 18 chronic CNP patients with spinal cord injury (SCI-CNP). The chronic pain characteristics, thresholds of thermal and tactile sensations and presence of pathological sensations were compared between groups, and between painful and pain free body regions within groups. Correlations were calculated between HSP intensity and sensory and musculoskeletal characteristics. Patients with HSP and patients with SCI-CNP had similar decrease of thermal sensibility in the painful compared to intact body regions and both groups presented similar rates of pathological sensations in painful regions. HSP and SCI-CNP differed however, in the quality of pain and aggravating factors. Significant correlations were found between HSP intensity and heat-pain threshold, presence of subluxation and spasticity. The similarities between HSP and SCI-CNP and the altered spinothalamic function and sensitization suggest that HSP has neuropathic components in its mechanism. Nevertheless, the unique features of HSP point towards additional possible mechanisms. The use of specific therapy options for neuropathic pain should be considered when treating patients with HSP.

  4. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

    2007-03-15

    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  5. Identification of a potent endothelium-derived angiogenic factor

    DEFF Research Database (Denmark)

    Jankowski, Vera; Tölle, Markus; Tran, Thi Nguyet Anh

    2013-01-01

    The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelia...

  6. Referred pain from trapezius muscle trigger points shares similar characteristics with chronic tension type headache.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Ge, Hong-You; Arendt-Nielsen, Lars; Cuadrado, Maria Luz; Pareja, Juan A

    2007-05-01

    Referred pain and pain characteristics evoked from the upper trapezius muscle was investigated in 20 patients with chronic tension-type headache (CTTH) and 20 age- and gender-matched controls. A headache diary was kept for 4 weeks in order to confirm the diagnosis and record the pain history. Both upper trapezius muscles were examined for the presence of myofascial trigger points (TrPs) in a blinded fashion. The local and referred pain intensities, referred pain pattern, and pressure pain threshold (PPT) were recorded. The results show that referred pain was evoked in 85% and 50% on the dominant and non-dominant sides in CTTH patients, much higher than 55% and 25% in controls (Pactive TrPs. CTTH patients with active TrPs in the right upper trapezius muscle showed greater headache intensity and frequency, and longer headache duration than those with latent TrPs. CTTH patients with bilateral TrPs reported significantly decreased PPT than those with unilateral TrP (Pactive TrPs. Our results suggest that spatial summation of perceived pain and mechanical pain sensitivity exists in CTTH patients.

  7. Are similar ones different? Determinant characteristics of management tool usage within companies sharing the same institutional environment

    Directory of Open Access Journals (Sweden)

    Franciele do Prado Daciê

    Full Text Available Abstract Technical literature describes local productive arrangements (LPAs as an institution. It also states that existing interaction links within their members foster them to act quite similarly. However, entrepreneurs and their characteristic attributes tend to distinguish their decisions. Therefore, according to such, this research examined if entrepreneur psychological characteristics would be able to influence management practices and the performance of companies sharing the same institutional environment. This study follows such objectives via an epistemologically positivist approach – quantitative view – and data gathering through forms used in 121 firms from clothing industry LPA in Parana Northwest. The research model has been tested through structural equation modelling techniques. Amongst findings, it may be observed management control practices have a 46.42% positive effect on company performance. Characteristics of entrepreneurial orientation have been able to positively influence the usage of management controls in 38.38%, and company performance in 14.90%. However, no statistical inferences regarding the individual's metacognitive ability of predicting the variables of entrepreneurial orientation, management controls and company performance have been carried out.

  8. The tetraspanin TSP3 of Neurospora crassa is a vacuolar membrane protein and shares characteristics with IDI proteins.

    Science.gov (United States)

    Heine, Daniela; Petereit, Linda; Schumann, Marcel R; Patzelt, Diana; Rachid, Leila; Brandt, Ulrike; Werner, Antonia; Pöggeler, Stefanie; Fleißner, André

    2016-01-01

    The fungal vacuole is an organelle, which adopts pleiotropic morphologies and functions. In aging and starving hyphae it is the compartment of degradation and recycling of cellular constituents. Here we identified TSP3, one of three tetraspanins present in the filamentous ascomycete fungus Neurospora crassa, as a vacuolar membrane protein. The protein is detected only in aging and starving cultures and under other conditions, which induce autophagy, such as vegetative incompatibility or the presence of the macrolide antibiotic rapamycin. Mutant analysis revealed that TSP3 is dispensable for growth and development of the fungus under laboratory conditions. Together these findings indicate that tsp3 shares characteristics with idi (induced during incompatibility) genes and might promote vacuolar functions related to autophagy. © 2016 by The Mycological Society of America.

  9. Shared psychological characteristics that are linked to aggression between patients with Internet addiction and those with alcohol dependence.

    Science.gov (United States)

    Hwang, Jae Yeon; Choi, Jung-Seok; Gwak, Ah Reum; Jung, Dawn; Choi, Sam-Wook; Lee, Jaewon; Lee, Jun-Young; Jung, Hee Yeon; Kim, Dai Jin

    2014-02-21

    Internet addiction (IA) is considered as one of behavioral addictions. Although common neurobiological mechanisms have been suggested to underlie behavioral addiction and substance dependence, few studies have directly compared IA with substance dependence, such as alcohol dependence (AD). We compared patients with IA, AD, and healthy controls (HC) in terms of the Five Factor Model of personality and with regard to impulsiveness, anger expression, and mood to explore psychological factors that are linked to aggression. All patients were treatment-seeking and had moderate-to-severe symptoms. The IA and AD groups showed a lower level of agreeableness and higher levels of neuroticism, impulsivity, and anger expression compared with the HC group, which are characteristics related to aggression. The addiction groups showed lower levels of extraversion, openness to experience, and conscientiousness and were more depressive and anxious than the HCs, and the severity of IA and AD symptoms was positively correlated with these types of psychopathology. IA and AD are similar in terms of personality, temperament, and emotion, and they share common characteristics that may lead to aggression. Our findings suggest that strategies to reduce aggression in patients with IA are necessary and that IA and AD are closely related and should be dealt with as having a close nosological relationship.

  10. Angiogenic Potential of Vitreous from Proliferative Diabetic Retinopathy and Eales' Disease Patients

    Science.gov (United States)

    Murugeswari, Ponnalagu; Shukla, Dhananjay; Kim, Ramasamy; Namperumalsamy, Perumalsamy; Stitt, Alan W.; Muthukkaruppan, Veerappan

    2014-01-01

    Purpose Proliferative Diabetic Retinopathy (PDR) and Eales' Disease (ED) have different aetiologies although they share certain common clinical symptoms including pre-retinal neovascularization. Since there is a need to understand if the shared end-stage angiogenic pathology of PDR and ED is driven by common stimulating factors, we have studied the cytokines contained in vitreous from both patient groups and analyzed the angiogenic potential of these samples in vitro. Material and Methods Vitreous samples from patients with PDR (n = 13) and ED (n = 5) were quantified for various cytokines using a cytokine biochip array and sandwich ELISA. An additional group of patients (n = 5) with macular hole (MH) was also studied for comparison. To determine the angiogenic potential of these vitreous samples, they were analyzed for their ability to induce tubulogenesis in human microvascular endothelial cells. Further, the effect of anti-VEGF (Ranibizumab) and anti-IL-6 antibodies were studied on vitreous-mediated vascular tube formation. Results Elevated levels of IL-6, IL-8, MCP-1 and VEGF were observed in vitreous of both PDR and ED when compared to MH. PDR and ED vitreous induced greater levels of endothelial cell tube formation compared to controls without vitreous (Pvitreous was neutralized by clinically-relevant concentrations of Ranibizumab, tube length was reduced significantly in 5 of 6 PDR and 3 of 5 ED samples. Moreover, when treated with IL-6 neutralizing antibody, apparent reduction (71.4%) was observed in PDR vitreous samples. Conclusions We have demonstrated that vitreous specimens from PDR and ED patients share common elevations of pro-inflammatory and pro-angiogenic cytokines. This suggests that common cytokine profiles link these two conditions. PMID:25310689

  11. Anti-angiogenic therapy: concept to clinic.

    Science.gov (United States)

    Young, Robin J; Reed, Malcolm W R

    2012-02-01

    It has been 40 years since Folkman hypothesized the use of anti-angiogenic therapy as a strategy in the treatment of cancer. Since then, vascular endothelial growth factor (VEGF) has been identified as the most potent cytokine to induce angiogenesis and drugs targeting VEGF, principally the humanized monoclonal antibody bevacizumab and the tyrosine kinase inhibitors sunitinib and sorafenib, have proven therapeutic benefit. The initial high expectations of tumor vascular targeting agents, however, have yet to be fulfilled. In unselected patient populations, the benefits of these agents is often marginal, they cause harmful side effects, and drug resistance is quickly established. Biomarkers to identify patients suitable for anti-angiogenic therapy will be key to the future development of these drugs. © 2012 John Wiley & Sons Ltd.

  12. Angiogenesis and Anti-Angiogenic Treatments

    Directory of Open Access Journals (Sweden)

    Ersin Demirer

    2013-10-01

    Full Text Available Blood vessels in our body is developed by vasculogenesis and angiogenesis. There have been new advances in molecular pathology and tumor biology areas in recent years. Angiogenesis is modulated by the balance between angiogenic and anti-angiogenic factors. Angiogenesis plays a key role in tumor growth. Drugs inhibiting angiogenesis have been in use in various malign or non-malign diseases. Inhibition of angiogenesis in malign diseases is a very attractive subject in medicine and studies are going on about long term affects and toxicities. Inhibition of angiogenesis is not an only treatment choice alone. It is a supplemental treatment option applied with conventional chemotherapy, radiotherapy, surgery, immunotherapy and hormonal therapy. It has been used in colorectal carcinoma, renal cell carcinoma, non-small cell lung cancer, glioblastoma, heoatocellular carcinoma, pancreatic neuroendocrine tumor, tyroid medullary cancer.

  13. Tumor angiogenic factor and human skin tumors.

    Science.gov (United States)

    Wolf, J E; Hubler, W R

    1975-03-01

    A transparent acrylic hamster cheek-pouch chamber was used to investigate the elaboration of a tumor angiogenic factor (TAF) by human cutaneous neoplasms; direct tumor implantations, transfilter diffusion, and soluble tumor extracts were used in the study. A diffusible and filterable TAF was extracted from cutaneous tumors and produced distinctive patterns of sequential vasodilatation, tortuosity, and neovascular proliferation in the cheek-pouch membrane. Malignant human neoplasms (eg, melanoma, basal cell epithelioma, squamous cell carcinoma, lymphoma) produced striking neovascularization; vascular tumors (eg, Kaposi sarcoma, pyogenic granuloma, vascular histiocytoma) stimulated dramatic hyperemia and ectasia. Angiogenesis was conspicuously absent after implantation of control materials and nevoid or normal cutaneous components (with the exception of epidermis). Tumor angiogenic factor appears to induce direct stimulation of endothelial cell mitosis and may be essential for survival of nutritionally ravenous neoplastic tissues. The interference with TAF has therapeutic implications.

  14. hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

    Science.gov (United States)

    Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

    2015-08-01

    Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

  15. Bacterial Toxins: A Hope Towards Angiogenic Ailments.

    Science.gov (United States)

    Khandia, Rekha; Munjal, Ashok; Dhama, Kuldeep; Malik, Yashpal Singh

    2017-01-01

    Angiogenesis is an essential physiological process for growth and maintenance of the body. Especially its role becomes indispendable during the embryonic development stage but lacks in adults with some exceptions like while wound repair and menstrual cycle. It is a tightly regulated process and relies on the cascade of several molecular signaling pathways with the involvement of many effectors like vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) etc. Related literature/ information were retrieved, analyzed and compiled from the online published resources available in Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases. Excessive angiogenesis leads to disorders like tumor, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, endometriosis, psoriasis, and adiposity. While, reduced angiogenesis also results in several ailments like cardiac ischemia, low capillary density in brain of Alzheimer's patients and delayed wound healing. Therefore, both angio-proliferative and anti-angiogenic approaches may be of use in developing novel therapeutics. Bacterial toxins are known for modulating the process of angiogenesis by mimicking pro-angiogenic factors and/ or competing with them. Furthermore, they inactivate the receptors or keep them in ON status, hence can be used to treat angiogenic disorders. The ease in handling, cultivation and manipulating the toxins structure has enabled the use of bacteria as an ideal choice for novel therapeutic developments. This review intends to elucidate the molecular mechanisms through which certain bacteria may alter the level of angiogenesis and consequently can work as therapeutics against angiogenic disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Quality of Care Improves for Patients with Diabetes in Medicare Shared Savings Accountable Care Organizations: Organizational Characteristics Associated with Performance.

    Science.gov (United States)

    Fraze, Taressa K; Lewis, Valerie A; Tierney, Emily; Colla, Carrie H

    2017-12-06

    Accountable care organizations (ACOs), a primary care-centric delivery and payment model, aim to promote integrated population health, which may improve care for those with chronic conditions such as diabetes. Research has shown that, overall, the ACO model is effective at reducing costs, but there is substantial variation in how effective different types of ACOs are at impacting costs and improving care delivery. This study examines how ACO organizational characteristics - such as composition, staffing, care management, and experiences with health reform - were associated with quality of care delivered to patients with diabetes. Secondary data were analyzed retrospectively to examine Medicare Shared Savings Program (MSSP) ACOs' performance on diabetes metrics in the first 2 years of ACO contracts. Ordinary least squares was used to analyze 162 MSSP ACOs with publicly available performance data and the National Survey of ACOs. ACOs improved performance significantly for patients with diabetes between contract years 1 and 2. In year 1, also having a private payer contract and an increased number of services within the ACO were positively associated with performance, while having a community health center or a hospital were negatively associated with performance. Better performance in year 1 was negatively associated with improved performance in year 2. This study found that ACOs substantively improved diabetes management within initial contract years. ACOs may need different types of support throughout their contracts to ensure continued improvements in performance.

  17. ASL, Total Communication and Oralism: Identifying Shared Characteristics of School-Based Writing Intervention Programs for Deaf and Hard-of-Hearing Students, K-6

    Science.gov (United States)

    Reed, Carolyn Mascia

    2009-01-01

    To be effective in providing a writing literacy program, regardless of communication approaches, educators should establish program-wide conditions that promote English writing literacy over time. The researcher's purpose for this study was to identify shared characteristics of writing intervention programs in three different communication school…

  18. Effects of Information Technologies, Department Characteristics and Individual Roles on Improving Knowledge Sharing Visibility: A Qualitative Case Study

    Science.gov (United States)

    Zhang, Xi; Vogel, Douglas R.; Zhou, Zhongyun

    2012-01-01

    Knowledge sharing visibility (KSV) is a critical environmental factor which can reduce social loafing in knowledge sharing (KS). This is especially true in ICT [information and communication technology]-based KS in learning organisations. As such, it is imperative that we better understand how to design technology enabled knowledge management…

  19. Pro-angiogenic properties of orosomucoid (ORM).

    Science.gov (United States)

    Irmak, Ster; Oliveira-Ferrer, Leticia; Singer, Bernhard B; Ergün, Süleyman; Tilki, Derya

    2009-11-01

    The acute phase protein orosomucoid (ORM), also known as alpha1-acid glycoprotein (AGP), is found to be increased in infection, inflammation and cancer. Recently, we demonstrated that ORM is produced by endothelial cells and detectable in urine samples of patients with bladder cancer. However, it was not clarified yet whether ORM plays a role in new vessel formation. To this aim we performed overexpression and gene silencing for ORM in human microvascular endothelial cells (HDMECs). ORM purified from human plasma was used individually or in combination with VEGF-A in endothelial tube formation, migration and proliferation assay. The in vivo effect of ORM in angiogenesis was studied using the chicken chorionallantois membrane (CAM) with subsequent counting of blood vessels on histological sections from the stimulated areas of CAM tissue. Our data show that ORM alone enhances migration but not proliferation of HDMECs. ORM alone does not induce endothelial tubes in vitro but simultaneous application of ORM with VEGF-A increases the number and the network of VEGF-A-induced endothelial tubes. Remarkably, ORM alone induces new vessel formation in vivo using CAM assay and supports the VEGF-A-induced new vessel formation in this assay. Taken together, our results let assume that ORM has pro-angiogenic properties and supports the angiogenic effect of VEGF-A. Thus, ORM seems to be involved in the regulation of angiogenesis.

  20. Tumour biology: Herceptin acts as an anti-angiogenic cocktail

    Science.gov (United States)

    Izumi, Yotaro; Xu, Lei; di Tomaso, Emmanuelle; Fukumura, Dai; Jain, Rakesh K.

    2002-03-01

    Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.

  1. Research on Multiple-Split Load Sharing Characteristics of 2-Stage External Meshing Star Gear System in Consideration of Displacement Compatibility

    Directory of Open Access Journals (Sweden)

    Shuai Mo

    2017-01-01

    Full Text Available This paper studies the multiple-split load sharing mechanism of gears in two-stage external meshing planetary transmission system of aeroengine. According to the eccentric error, gear tooth thickness error, pitch error, installation error, and bearing manufacturing error, we performed the meshing error analysis of equivalent angles, respectively, and we also considered the floating meshing error caused by the variation of the meshing backlash, which is from the floating of all gears at the same time. Finally, we obtained the comprehensive angle meshing error of the two-stage meshing line, established a refined mathematical computational model of 2-stage external 3-split loading sharing coefficient in consideration of displacement compatibility, got the regular curves of the load sharing coefficient and load sharing characteristic curve of full floating multiple-split and multiple-stage system, and took the variation law of the floating track and the floating quantity of the center wheel. These provide a scientific theory to determine the load sharing coefficient, reasonable load distribution, and control tolerances in aviation design and manufacturing.

  2. Distributed Primary and Secondary Power Sharing in a Droop-Controlled LVDC Microgrid with Merged AC and DC Characteristics

    DEFF Research Database (Denmark)

    Peyghami, Saeed; Mokhtari, Hossein; Loh, Poh Chiang

    2017-01-01

    sharing and secondary voltage regulation merged. The main idea is to introduce a non-zero unifying frequency and a second power term to each dc source by modulating its converter with both a dc and a small ac signal. Two droop expressions can then be written for the proposed scheme, instead of the single...... expression found in the conventional droop scheme. The first expression is for regulating the ac frequency and active power generated, while the second is for relating the dc voltage to the second power term. The outcomes are better active power sharing and average voltage regulation in the dc microgrid...

  3. Exploring the central characteristics of HR shared services: evidence from a critical case study in the Netherlands

    NARCIS (Netherlands)

    Meijerink, Jeroen Gerard; Bondarouk, Tatiana

    2012-01-01

    Human resource shared service centers (HR SSCs) are foreseen as improving HR service delivery for their end-users: employees, line managers and decentralized HR professionals. Although the concept expects the benefits of HR SSCs to come from centralizing knowledge and decentralizing the control

  4. Early pregnancy angiogenic markers and spontaneous abortion

    DEFF Research Database (Denmark)

    Andersen, Louise B; Dechend, Ralf; Karumanchi, S Ananth

    2016-01-01

    BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between...... maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week ..., interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum

  5. Anti-angiogenic peptides for cancer therapeutics.

    Science.gov (United States)

    Rosca, Elena V; Koskimaki, Jacob E; Rivera, Corban G; Pandey, Niranjan B; Tamiz, Amir P; Popel, Aleksander S

    2011-08-01

    Peptides have emerged as important therapeutics that are being rigorously tested in angiogenesis-dependent diseases due to their low toxicity and high specificity. Since the discovery of endogenous proteins and protein fragments that inhibit microvessel formation (thrombospondin, endostatin) several peptides have shown promise in pre-clinical and clinical studies for cancer. Peptides have been derived from thrombospondin, collagens, chemokines, coagulation cascade proteins, growth factors, and other classes of proteins and target different receptors. Here we survey recent developments for anti-angiogenic peptides with length not exceeding 50 amino acid residues that have shown activity in pre-clinical models of cancer or have been tested in clinical trials; some of the peptides have been modified and optimized, e.g., through L-to-D and non-natural amino acid substitutions. We highlight technological advances in peptide discovery and optimization including computational and bioinformatics tools and novel experimental techniques.

  6. Angiogenic Profiling of Synthesized Carbon Quantum Dots.

    Science.gov (United States)

    Shereema, R M; Sruthi, T V; Kumar, V B Sameer; Rao, T P; Shankar, S Sharath

    2015-10-20

    A simple method was employed for the synthesis of green luminescent carbon quantum dots (CQDs) from styrene soot. The CQDs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared, and Raman spectroscopy. The prepared carbon quantum dots did not show cellular toxicity and could successfully be used for labeling cells. We also evaluated the effects of carbon quantum dots on the process of angiogenesis. Results of a chorioallantoic membrane (CAM) assay revealed the significant decrease in the density of branched vessels after their treatment with CQDs. Further application of CQDs significantly downregulated the expression levels of pro-angiogenic growth factors like VEGF and FGF. Expression of VEGFR2 and levels of hemoglobin were also significantly lower in CAMs treated with CQDs, indicating that the CQDs inhibit angiogenesis. Data presented here also show that CQDs can selectively target cancer cells and therefore hold potential in the field of cancer therapy.

  7. Fluid shear stress threshold regulates angiogenic sprouting.

    Science.gov (United States)

    Galie, Peter A; Nguyen, Duc-Huy T; Choi, Colin K; Cohen, Daniel M; Janmey, Paul A; Chen, Christopher S

    2014-06-03

    The density and architecture of capillary beds that form within a tissue depend on many factors, including local metabolic demand and blood flow. Here, using microfluidic control of local fluid mechanics, we show the existence of a previously unappreciated flow-induced shear stress threshold that triggers angiogenic sprouting. Both intraluminal shear stress over the endothelium and transmural flow through the endothelium above 10 dyn/cm(2) triggered endothelial cells to sprout and invade into the underlying matrix, and this threshold is not impacted by the maturation of cell-cell junctions or pressure gradient across the monolayer. Antagonizing VE-cadherin widened cell-cell junctions and reduced the applied shear stress for a given transmural flow rate, but did not affect the shear threshold for sprouting. Furthermore, both transmural and luminal flow induced expression of matrix metalloproteinase 1, and this up-regulation was required for the flow-induced sprouting. Once sprouting was initiated, continuous flow was needed to both sustain sprouting and prevent retraction. To explore the potential ramifications of a shear threshold on the spatial patterning of new sprouts, we used finite-element modeling to predict fluid shear in a variety of geometric settings and then experimentally demonstrated that transmural flow guided preferential sprouting toward paths of draining interstitial fluid flow as might occur to connect capillary beds to venules or lymphatics. In addition, we show that luminal shear increases in local narrowings of vessels to trigger sprouting, perhaps ultimately to normalize shear stress across the vasculature. Together, these studies highlight the role of shear stress in controlling angiogenic sprouting and offer a potential homeostatic mechanism for regulating vascular density.

  8. A Phenomenology of Teacher and Parent Perceptions of the Characteristics of Effective Schools: Working toward a Shared Vision

    Science.gov (United States)

    Sroufe, William David

    2013-01-01

    Research conducted at schools that have outperformed their counterparts points to specific characteristics that make them successful. These characteristics brought about the development of the effective schools correlates by Ronald Edmonds (1979). Various people from across the United States and in various occupations perceive these correlates…

  9. Angiogenic activity of Calendula officinalis flowers L. in rats.

    Science.gov (United States)

    Parente, Leila Maria Leal; Andrade, Maria Auxiliadora; Brito, Luiz Augusto Batista; Moura, Veridiana Maria Brianezi Dignani de; Miguel, Marina Pacheco; Lino-Júnior, Ruy de Souza; Tresvenzol, Leonice Faustino Manrique; Paula, José Realino de; Paulo, Neusa Margarida

    2011-02-01

    In this work, angiogenic activity of Calendula officinalis L. (Asteraceae) ethanolic extract and dichloromethane and hexanic fractions were evaluated, considering medicinal properties, especially healing activity, are attributed to this plant. Models using 36 rats and 90 embryonated eggs were used to evaluate healing and angiogenic activities of extracts and fractions of the plant, through the induction of skin wounds and the chorioallantoic membrane, respectively. The effect of vascular proliferation was also tested from the study to verify the intensity of expression of vascular endothelial growth factor (VEGF) in cutaneous wounds in rats. The angiogenic activity of the extract and the fractions was evidenced in both experimental models. It was verified that this effect is not directly related to the expression of VEGF and it could be associated to other pro-angiogenic factors. The healing activity referred to C. officinalis is related, among other factors, to its positive effect on angiogenesis, characterized by the induction of neovascularization.

  10. Anti-Angiogenic Therapeutic Indictors in Breast Cancer

    National Research Council Canada - National Science Library

    Su, Min-Ying

    2003-01-01

    This project studies the therapeutic indicators in ant-angiogenic therapy. Every animal with mammary tumor was scheduled to receive a baseline MRI, core biopsy, then followed by 4 treatments with weekly MRI follow...

  11. Angiogenic factors in preeclampsia: potential for diagnosis and treatment.

    Science.gov (United States)

    Goel, Arvind; Rana, Sarosh

    2013-11-01

    The review summarizes new observations of key roles for circulating angiogenic factors in diagnosing, managing, and treating preeclampsia. Alterations in circulating angiogenic factors (soluble fms-like tyrosine kinase-1 and placental growth factor) in preeclampsia correlate with the diagnosis and adverse outcomes, particularly when the disease presents prematurely (preeclampsia and its complications from other disorders that present with similar clinical profiles. A ratio of soluble fms-like tyrosine kinase-1/placental growth factor greater than 85 appears ideal as the cut-off for both diagnosis and prognosis. There is also evidence that modulating these factors has therapeutic effects, suggesting a future role for angiogenic factors in treatment and prevention of preeclampsia. Circulating angiogenic biomarkers help in diagnostic and prognostic profiling of preeclampsia and may facilitate better management of these patients.

  12. Can the Lung Cancer Pie Be Divided into Angiogenic Slices?

    Science.gov (United States)

    Cascone, Tina; Heymach, John V

    2015-12-01

    There are no validated markers for predicting benefit from angiogenesis inhibitors or classifying tumors with distinct angiogenic phenotypes. In patients with non-small cell lung cancer treated with bevacizumab and erlotinib, Franzini and colleagues find that angiogenesis- and hypoxia-associated gene expression signatures predict tumor response and/or clinical outcome, and may define distinct angiogenic patterns. ©2015 American Association for Cancer Research.

  13. Search for Anti-angiogenic Substances from Natural Sources.

    Science.gov (United States)

    Kotoku, Naoyuki; Arai, Masayoshi; Kobayashi, Motomasa

    2016-01-01

    As angiogenesis is critical for tumor growth and metastasis, potent and selective anti-angiogenic agents with novel modes of action are highly needed for anti-cancer drug discovery. In this review, our studies focusing on the search for anti-angiogenic substances from natural sources, such as bastadins, globostellatic acid X methyl esters and cortistatins from marine sponges, and pyripyropenes from marine-derived fungus, together with senegasaponins from medicinal plant, are summarized.

  14. Identification of a potent endothelium-derived angiogenic factor.

    Directory of Open Access Journals (Sweden)

    Vera Jankowski

    Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

  15. Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade.

    Directory of Open Access Journals (Sweden)

    Xiangying Kong

    Full Text Available Rheumatoid arthritis (RA is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11-45 µg/kg/day starting on the day 1 after first immunization. The arthritis scores (P<0.05 and the arthritis incidence (P<0.05 of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11~45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05. Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS-RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-β-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the

  16. Acute pyelonephritis during pregnancy changes the balance of angiogenic and anti-angiogenic factors in maternal plasma.

    Science.gov (United States)

    Chaiworapongsa, Tinnakorn; Romero, Roberto; Gotsch, Francesca; Kusanovic, Juan Pedro; Mittal, Pooja; Kim, Sun Kwon; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Kim, Chong Jai; Dong, Zhong; Yeo, Lami; Hassan, Sonia S

    2010-02-01

    Angiogenic factors have been implicated in the pathophysiology of sepsis. In experimental models of sepsis (endotoxemia and/or cecal ligation puncture), there is increased expression of vascular endothelial growth factors (VEGF) and the administration of exogenous soluble VEGF receptor (sVEGFR)-1, an antagonist to VEGF, reduces morbidity and mortality. Moreover, a dramatic elevation in sVEGFR-1 has been demonstrated in human sepsis. Although a balance between angiogenic and anti-angiogenic factors is essential for feto-placental development, the changes of angiogenic factors during pregnancy in the context of infection have never been explored. Angiogenic factors also play crucial roles in the pathophysiology of preeclampsia (PE). This study was conducted to determine if maternal plasma concentrations of placental growth factor (PlGF), sVEGFR-2, and soluble endoglin (sEng) change in pregnancies complicated by acute pyelonephritis (AP) compared with normal pregnancy and PE. A case-control study was conducted in patients with AP, normal pregnant (NP) women, and patients with PE (n=36 for each group) matched for gestational age. AP was diagnosed in the presence of fever (temperature >or=38 degrees C), clinical signs of infection, and a positive urine culture for microorganisms. Plasma concentrations of PlGF, sVEGFR-2, and sEng were determined by ELISA. The results of plasma sVEGFR-1 concentrations have previously been reported, but were included in this study to provide a complete picture of the angiogenic/anti-angiogenic profiles. Serum concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-gamma, granulocyte macrophage colony stimulating factor, and tumor necrosis factor (TNF) were also determined using high sensitivity multiplexed immunoassays in patients with AP and NP. AP was associated with a lower median plasma concentration of PlGF and sVEGFR-2 than NP (both pIL-7, IL-8, IL-10, IFN-gamma, and TNF

  17. Angiogenic Factors and Cytokines in Diabetic Retinopathy

    Science.gov (United States)

    Abcouwer, Steven F.

    2013-01-01

    Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DR-associated vascular dysfunction, edema and angiogenesis. This has stimulated research of alternative therapeutic targets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored. PMID:24319628

  18. Limited Evidence Suggests That Symptomatic Cracked Teeth Share Characteristics Such as Clenching, Grinding, and Molars With Distal Cracks.

    Science.gov (United States)

    Chogle, Sami; Miller, Andrew; Saadoun, Manal

    2017-09-01

    Correlation between symptoms and external characteristics of cracked teeth. Hilton TJ, Funkhouser E, Ferracane JL, Gilbert GH, Baltuck C, Benjamin P, Louis D, Mungia R, Meyerowitz. JADA 2017; 148(4):246-56.e1. National Institutes of Health grant U19-DE-22516 TYPE OF STUDY/DESIGN: Cross-sectional study. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis

    Directory of Open Access Journals (Sweden)

    Pratiek N. Matkar

    2017-10-01

    Full Text Available Angiogenesis, the formation of new blood vessels from pre-existing ones is a biological process that ensures an adequate blood flow is maintained to provide the cells with a sufficient supply of nutrients and oxygen within the body. Numerous soluble growth factors and inhibitors, cytokines, proteases as well as extracellular matrix proteins and adhesion molecules stringently regulate the multi-factorial process of angiogenesis. The properties and interactions of key angiogenic molecules such as vascular endothelial growth factors (VEGFs, fibroblast growth factors (FGFs and angiopoietins have been investigated in great detail with respect to their molecular impact on angiogenesis. Since the discovery of angiogenic growth factors, much research has been focused on their biological actions and their potential use as therapeutic targets for angiogenic or anti-angiogenic strategies in a context-dependent manner depending on the pathologies. It is generally accepted that these factors play an indispensable role in angiogenesis. However, it is becoming increasingly evident that this is not their only role and it is likely that the angiogenic factors have important functions in a wider range of biological and pathological processes. The additional roles played by these molecules in numerous pathologies and biological processes beyond angiogenesis are discussed in this review.

  20. A novel nucleic acid analogue shows strong angiogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Ikuko, E-mail: tukamoto@med.kagawa-u.ac.jp [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Sakakibara, Norikazu; Maruyama, Tokumi [Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193 (Japan); Igarashi, Junsuke; Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Kubota, Yasuo [Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan); Ashino, Hiromi [The Tokyo Metropolitan Institute of Medical Science, 1-6 Kamikitazawa2-chome, Setagaya-ku, Tokyo 156-8506 (Japan); Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro [Teikoku Seiyaku Co., Ltd., Sanbonmatsu, Higashikagawa, Kagawa 769-2695 (Japan); Konishi, Ryoji [Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793 (Japan)

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  1. Leptin’s Pro-Angiogenic Signature in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Perez, Ruben Rene, E-mail: rgonzalez@msm.edu; Lanier, Viola; Newman, Gale [Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW., Atlanta, GA 30310 (United States)

    2013-09-06

    Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis.

  2. Progastrin a new pro-angiogenic factor in colorectal cancer.

    Science.gov (United States)

    Najib, S; Kowalski-Chauvel, A; Do, C; Roche, S; Cohen-Jonathan-Moyal, E; Seva, C

    2015-06-11

    Angiogenesis is essential in tumor progression and metastatic process, and increased angiogenesis has been associated with poor prognosis and relapse of colorectal cancer (CRC). VEGF has become the main target of anti-angiogenic therapy. However, most patients relapse after an initial response or present a resistance to the treatment. Identification of new pro-angiogenic factors may help to improve anti-angiogenic therapy. In this study, we demonstrated that the pro-hormone progastrin (PG), over-expressed in CRC, recognized as a growth factor, is a potent pro-angiogenic factor. In transgenic mice and human colorectal HPs producing high levels of PG, we correlated PG overexpression with an increased vascularization. In vitro, exogenous PG and conditioned media (CM) from CRC cells producing PG increased endothelial cell proliferation and migration. We also showed that treatment with exogenous PG can increase the ability of endothelial cells to form capillary-like structures. Moreover, we demonstrated that PG enhanced endothelial permeability. The finding that PG stimulated the phosphorylation of vascular endothelial (VE)-cadherin, p125-FAK, paxillin and induced actin remodelling was consistent with a role of these components in PG-stimulated endothelial cell migration and permeability. The pro-angiogenic effects observed with CM were significantly inhibited when CRC cells expressed a PG shRNA. In vivo, we found an important decrease in tumor growth and neovascularization when the CRC cells expressing the PG shRNA were xenografted in mice or in the chick chorioallantoic membrane model. We also observed an increase in the coverage of blood vessels by pericytes and a decrease in endothelial permeability when PG expression was blocked. Our results demonstrate that PG is a new pro-angiogenic factor in CRC and an attractive therapeutic target.

  3. Galkinius Perreault, 2014 or Darwiniella (Anderson, 1992? A new coral-associated barnacle sharing characteristics of these two genera in Pacific waters (Crustacea, Cirripedia, Thoracica, Pyrgomatidae

    Directory of Open Access Journals (Sweden)

    Benny Kwok Kan Chan

    2017-12-01

    Full Text Available A new species of coral associated barnacle (Balanomorpha: Pyrgomatidae sharing morphological features of Darwiniella (Anderson, 1992 and Galkinius Perreault, 2014 is described. It has a fused shell and opercular plates, characteristic of Darwiniella. However, the morphology of the tergum and somatic body are closer to Galkinius. Sequence divergence of mitochondrial DNA 12S rDNA and COI reveals this new species clusters with the Galkinius clade. Therefore this new form is assigned to the genus Galkinius, as G. maculosus sp. n. Concomitantly the diagnosis of Galkinius is emended to include species with fused or four- plated shells and fused opercular plates. The new species is distinct from all Galkinius species in having a fused shell. It inhabits the corals Lobophyllia spp. and is distributed from the Dongsha Atoll in the South China Sea, Orchid Island of Taiwan in the Pacific Ocean, to Madang in Papua New Guinea waters.

  4. Definition of the "Drug-Angiogenic-Activity-Index" that allows the quantification of the positive and negative angiogenic active drugs: a study based on the chorioallantoic membrane model.

    Science.gov (United States)

    Demir, Resit; Peros, Georgios; Hohenberger, Werner

    2011-06-01

    Since the introduction of the angiogenic therapy by Folkman et al. in the 1970'ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the "Drug-Angiogenic-Activity-Index" of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the "Drug Angiogenic Activity Index" by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {ΔVIS[Drug]-ΔVIS[Control]} / Δ VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a -1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the "Drug-Angiogenic-Activity-Index" in the preclinical phase will give us an impact of effectiveness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family.

  5. Diversity of the angiogenic phenotype in non-small cell lung cancer.

    Science.gov (United States)

    McClelland, Marc R; Carskadon, Shannon L; Zhao, Liujian; White, Eric S; Beer, David G; Orringer, Mark B; Pickens, Allan; Chang, Andrew C; Arenberg, Douglas A

    2007-03-01

    Angiogenesis is crucial for tumor biology. There are many mechanisms by which tumors induce angiogenesis. We hypothesize that each individual tumor develops a unique mechanism to induce angiogenesis, and that activation of a particular angiogenic pathway suppresses the evolution of alternative pathways. We characterized 168 human non-small cell lung cancer (NSCLC) specimens for levels of angiogenic factors (angiogenic CXC chemokines, basic fibroblast growth factor, and vascular endothelial growth factor). We also induced lung tumor formation in A/J mice by injecting the tobacco carcinogen NNK. We dissected individual lung tumors and measured expression of angiogenic factors from three distinct families using real-time PCR. Finally, we controlled the angiogenic milieu using in vivo models to determine the resultant phenotype of the angiogenic factors expressed by NSCLC cells. Human tumors displayed marked variation in the expression of angiogenic factors. Individual mouse tumors, even from within the same mouse, displayed variability in their pattern of expression of angiogenic factors. In a sponge model of angiogenesis using murine lung cancer cells, implanting LLC cells with an angiogenic factor suppressed the expression of other angiogenic factors in implanted sponges. This suppressive effect was not seen in vitro. We conclude that lung cancer tumors evolve a unique and dominant angiogenic phenotype. Once an angiogenic pathway is activated, it may allow for tumor growth to proceed in the absence of a selection pressure to activate a second pathway.

  6. PWI-MRI and contrast extravasation in brain AVM help to estimate angiogenic activity.

    Science.gov (United States)

    Saliou, Guillaume; Krings, Timo; Rutgers, Dik R; Toulgoat, Frederique; Ozanne, Augustin; Lasjaunias, Pierre; Ducreux, Denis

    2011-10-01

    The aim of this study is to investigate perfusion characteristics of brain arteriovenous malformation (AVM) by means of MRI perfusion-weighted imaging (PWI). Forty-three patients with brain AVM were prospectively included and investigated by PWI-MRI. Diagnosis of type of disease was made by angiogram. According to angiographic features, the study group was classified in three groups: two groups of patients with classical AVM (group 1 with few or no angiogenic feature (13 patients) and group 2 with many angiogenic features (18 patients)) and one group (group 3) which included patients with cerebral proliferative angiopathy (CPA; 12 patients). Twenty-one patients had never been treated endovascularly for their AVM and 22 patients received partial treatment by endovascular embolisation. Through PWI, corrected cerebral blood volume (CBVc), mean transit time (MTT), and percentage of microvascular leakage (MVL) as an indirect measure of permeability were assessed. The three patient groups did not differ significantly in baseline and clinical parameters. CBVc, MTT, and MVL differed significantly between the three groups (p = 0.003, p = 0.04, p = 0.01, respectively), with the lowest mean values found in group 1 and the highest in group 3. Mean MVL was 11.4 in group 1, 18.6 in group 2, and 21.9 in group 3. MRI can demonstrate differences in PWI parameters among patients with classical AVM and CPA, which are related to angiographic features of these AVMs. Through PWI, the level of angiogenic activity in AVMs may be monitored.

  7. PWI-MRI and contrast extravasation in brain AVM help to estimate angiogenic activity

    Energy Technology Data Exchange (ETDEWEB)

    Saliou, Guillaume; Toulgoat, Frederique; Ozanne, Augustin; Lasjaunias, Pierre; Ducreux, Denis [Hopital de Bicetre, Service de Neuroradiologie, Kremlin Bicetre cedex (France); Krings, Timo [Hopital de Bicetre, Service de Neuroradiologie, Kremlin Bicetre cedex (France); University of Toronto, Division of Neuroradiology, Department of Medical Imaging, Toronto Western Hospital, UHN, Toronto, ON (Canada); Rutgers, Dik R. [Hopital de Bicetre, Service de Neuroradiologie, Kremlin Bicetre cedex (France); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2011-10-15

    The aim of this study is to investigate perfusion characteristics of brain arteriovenous malformation (AVM) by means of MRI perfusion-weighted imaging (PWI). Forty-three patients with brain AVM were prospectively included and investigated by PWI-MRI. Diagnosis of type of disease was made by angiogram. According to angiographic features, the study group was classified in three groups: two groups of patients with classical AVM (group 1 with few or no angiogenic feature (13 patients) and group 2 with many angiogenic features (18 patients)) and one group (group 3) which included patients with cerebral proliferative angiopathy (CPA; 12 patients). Twenty-one patients had never been treated endovascularly for their AVM and 22 patients received partial treatment by endovascular embolisation. Through PWI, corrected cerebral blood volume (CBVc), mean transit time (MTT), and percentage of microvascular leakage (MVL) as an indirect measure of permeability were assessed. The three patient groups did not differ significantly in baseline and clinical parameters. CBVc, MTT, and MVL differed significantly between the three groups (p = 0.003, p = 0.04, p = 0.01, respectively), with the lowest mean values found in group 1 and the highest in group 3. Mean MVL was 11.4 in group 1, 18.6 in group 2, and 21.9 in group 3. MRI can demonstrate differences in PWI parameters among patients with classical AVM and CPA, which are related to angiographic features of these AVMs. Through PWI, the level of angiogenic activity in AVMs may be monitored. (orig.)

  8. Angiogenic factors stimulate growth of adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    2010-02-01

    Full Text Available The ability to grow a uniform cell type from the adult central nervous system (CNS is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools.Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4 and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2. These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes.We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

  9. Angiogenic monocytes: another colorful blow to endothelial progenitors

    NARCIS (Netherlands)

    Horrevoets, Anton J. G.

    2009-01-01

    This Commentary provides perspective on a related article by Sun-Jin Kim and coworkers (Am J Pathol: 172 AJP08-0819), who assess the contribution of bone marrow-derived cells to tumor angiogenesis in a physiologic, non-myeloablative setting and conclude that the actual angiogenic cell type

  10. Cord blood angiogenic profile in normotensive pregnancies | Simmi ...

    African Journals Online (AJOL)

    ... normotensive pregnancy and dysbalance might occur during pathological pregnancy. These markers of angiogenic balance may serve as diagnostic marker and may help in explaining future risk of cardiovascular disease in these women. Keywords: Vasculogenesis; Proangiogenic and antiangiogenic factors; Pregnancy ...

  11. Sharing Economy

    DEFF Research Database (Denmark)

    Marton, Attila; Constantiou, Ioanna; Thoma, Antonela

    De spite the hype the notion of the sharing economy is surrounded by, our understanding of sharing is surprisingly undertheorized. In this paper, we make a first step towards rem edying this state of affairs by analy sing sharing as a s ocial practice. Based on a multi ple - case study, we analyse...

  12. The imbalance in expression of angiogenic and anti-angiogenic factors as candidate predictive biomarker in preeclampsia

    Directory of Open Access Journals (Sweden)

    Pooneh Nikuei

    2015-07-01

    Full Text Available Preeclampsia is an important pregnancy disorder with serious maternal and fetal complications which its etiology has not been completely understood yet. Early diagnosis and management of disease could reduce its potential side effects. The vascular endothelial growth factor (VEGF family including VEGF-A is the most potent endothelial growth factor which induces angiogenesis and endothelial cell proliferation and has basic role in vasculogenesis. VEGF and its tyrosine kinase receptors (Flt1 and KDR are major factors for fetal and placental angiogenic development. Finding mechanisms involved in expression of angiogenic factors may lead to new prognostic and therapeutic points in management of preeclampsia. Recent researches, has shown capability of some anti-angiogenic factors as potential candidate to be used as early predictors for preeclampsia. Soluble fms-like tyrosin kinase-1 (sFlt1 is a truncated splice variant of the membrane-bound VEGF receptor Flt1, that is produced by the placenta and it can bind to angiogenic growth factors and neutraliz, their effects. It is also observed that the ratio of sFlt1 to placental growth factor is valuable as prognostic marker. In this review, VEGF family member’s role in angiogenesis is evaluated as biomarkers to be used for prediction of preeclampsia.

  13. Sharing City

    DEFF Research Database (Denmark)

    This magazine offers an insight into the growing commercial innovation, civic movements, and political narratives surrounding sharing economy services, solutions and organisational types. It presents a cross-section of the manifold sharing economy services and solutions that can be found in Denmark....... Solutions of sharing that seeks to improve our cities and local communities in both urban and rural environments. 24 sharing economy organisations and businesses addressing urban and rural issues are being portrayed and seven Danish municipalities that have explored the potentials of sharing economy....... Moreover, 15 thought leading experts - professionals and academic - have been invited to give their perspective on sharing economy for cities. This magazine touches upon aspects of the sharing economy as mobility, communities, sustainability, business development, mobility, and urban-rural relation....

  14. Sharing code.

    Science.gov (United States)

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  15. Sharing City

    DEFF Research Database (Denmark)

    This magazine offers an insight into the growing commercial innovation, civic movements, and political narratives surrounding sharing economy services, solutions and organisational types. It presents a cross-section of the manifold sharing economy services and solutions that can be found in Denmark....... Moreover, 15 thought leading experts - professionals and academic - have been invited to give their perspective on sharing economy for cities. This magazine touches upon aspects of the sharing economy as mobility, communities, sustainability, business development, mobility, and urban-rural relation....

  16. Prevention of the Angiogenic Switch in Human Breast Cancer

    Science.gov (United States)

    2009-03-01

    conventional dosing of chemotherapy. New pharmacology : oral drugs that increase endogenous angiogenesis inhibitors. The clinical finding that...angiogenic proteins, opening the way for a new field of pharmacology (FIG.7). Endostatin is increased by tamoxifen136, celecoxib137 and (in joint...thrombospondin-1 (clone A6.1, Lab Vision, Fremont, CA) staining, sections were pretreated with pepsin for 15 minutes at 37uC (Biomeda, Foster City, CA

  17. Platelet lysate-based pro-angiogenic nanocoatings.

    Science.gov (United States)

    Oliveira, Sara M; Pirraco, Rogério P; Marques, Alexandra P; Santo, Vítor E; Gomes, Manuela E; Reis, Rui L; Mano, João F

    2016-03-01

    Human platelet lysate (PL) is a cost-effective and human source of autologous multiple and potent pro-angiogenic factors, such as vascular endothelial growth factor A (VEGF A), fibroblast growth factor b (FGF b) and angiopoietin-1. Nanocoatings previously characterized were prepared by layer-by-layer assembling incorporating PL with marine-origin polysaccharides and were shown to activate human umbilical vein endothelial cells (HUVECs). Within 20 h of incubation, the more sulfated coatings induced the HUVECS to the form tube-like structures accompanied by an increased expression of angiogenic-associated genes, such as angiopoietin-1 and VEGF A. This may be a cost-effective approach to modify 2D/3D constructs to instruct angiogenic cells towards the formation of neo-vascularization, driven by multiple and synergistic stimulations from the PL combined with sulfated polysaccharides. The presence, or fast induction, of a stable and mature vasculature inside 3D constructs is crucial for new tissue formation and its viability. This has been one of the major tissue engineering challenges, limiting the dimensions of efficient tissue constructs. Many approaches based on cells, growth factors, 3D bioprinting and channel incorporation have been proposed. Herein, we explored a versatile technique, layer-by-layer assembling in combination with platelet lysate (PL), that is a cost-effective source of many potent pro-angiogenic proteins and growth factors. Results suggest that the combination of PL with sulfated polyelectrolytes might be used to introduce interfaces onto 2D/3D constructs with potential to induce the formation of cell-based tubular structures. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. The angiogenic potential of leukocyte- and platelet-rich fibrin

    OpenAIRE

    Berkmans, Kirsten

    2016-01-01

    Introduction: L-PRF promotes tissue healing in clinical applications such as dental surgery. However, little is known about the mechanisms of action. Angiogenesis is a key process in tissue regeneration. Growth factors, fibrin and leukocytes, as present in L-PRF, are known to be important in angiogenesis. The goal of this study was to investigate whether L-PRF induces blood vessel formation. Materials and methods: The angiogenic cytokine profile of L-PRF CM and exudate was determined by an...

  19. The classical pink-eyed dilution mutation affects angiogenic responsiveness.

    Science.gov (United States)

    Rogers, Michael S; Boyartchuk, Victor; Rohan, Richard M; Birsner, Amy E; Dietrich, William F; D'Amato, Robert J

    2012-01-01

    Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations, including humans and mice, harbor genetic variations that alter angiogenesis. Angiogenesis-regulating gene variants can result in increased susceptibility to multiple angiogenesis-dependent diseases in humans. Our efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Using the murine corneal micropocket assay, we have observed more than ten-fold difference in angiogenic responsiveness among various mouse strains. This degree of difference is observed with either bFGF or VEGF induced corneal neovascularization. Ongoing mapping studies have identified multiple loci that affect angiogenic responsiveness in several mouse models. In this study, we used F2 intercrosses between C57BL/6J and the 129 substrains 129P1/ReJ and 129P3/J, as well as the SJL/J strain, where we have identified new QTLs that affect angiogenic responsiveness. In the case of AngFq5, on chromosome 7, congenic animals were used to confirm the existence of this locus and subcongenic animals, combined with a haplotype-based mapping approach that identified the pink-eyed dilution mutation as a candidate polymorphism to explain AngFq5. The ability of mutations in the pink-eyed dilution gene to affect angiogenic response was demonstrated using the p-J allele at the same locus. Using this allele, we demonstrate that pink-eyed dilution mutations in Oca2 can affect both bFGF and VEGF-induced corneal angiogenesis.

  20. CXC and CC Chemokines as Angiogenic Modulators in Nonhaematological Tumors

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2014-01-01

    Full Text Available Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors.

  1. Biomarkers in Tumor Angiogenesis and Anti-Angiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2011-10-01

    Full Text Available Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies.

  2. File sharing

    NARCIS (Netherlands)

    van Eijk, N.

    2011-01-01

    ‘File sharing’ has become generally accepted on the Internet. Users share files for downloading music, films, games, software etc. In this note, we have a closer look at the definition of file sharing, the legal and policy-based context as well as enforcement issues. The economic and cultural

  3. Shared leadership

    DEFF Research Database (Denmark)

    Ulhøi, John Parm; Müller, Sabine

    2012-01-01

    The aim of this paper is twofold. First, this paper comprehensively will review the conceptual and empirical literature to identify such critical underlying mechanisms which enable shared or collective leadership. Second, this article identifies the antecedents and outcomes of shared leadership...... according to the literature review to develop a re-conceptualised and synthesized framework for managing the organizational issues associated with shared leadership on various organizational levels. The paper rectifies this by identifying the critical factors and mechanisms which enable shared leadership...... and its antecedents and outcomes, and to develop a re-conceptualized and synthesized framework of shared leadership. The paper closes with a brief discussion of avenues for future research and implications for managers....

  4. Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    The concept of knowledge management has, indeed, become a buzzword that every single organization is expected to practice and live by. Knowledge management is about managing the organization's knowledge for the common good of the organization -but practicing knowledge management is not as simple...... as that. This article focuses on knowledge sharing as the process seeking to reduce the resources spent on reinventing the wheel.The article introduces the concept of time sensitiveness; i.e. that knowledge is either urgently needed, or not that urgently needed. Furthermore, knowledge sharing...... is considered as either a push or pull system. Four strategies for sharing knowledge - help, post-it, manuals and meeting, and advice are introduced. Each strategy requires different channels for sharing knowledge. An empirical analysis in a production facility highlights how the strategies can be practiced....

  5. Determinants of injection drug user (IDU) syringe sharing: the relationship between availability of syringes and risk network member characteristics in Winnipeg, Canada.

    Science.gov (United States)

    Shaw, Souradet Y; Shah, Lena; Jolly, Ann M; Wylie, John L

    2007-10-01

    Despite the establishment of syringe exchange programmes, syringe-sharing behaviour remains common among some injection drug users (IDU). Previous studies have identified several individual- and social network-level variables associated with syringe sharing. We examine the extent to which each of these variables is related independently to this behaviour within a diverse study population. A cross-sectional survey of 435 IDU conducted between December 2003 and September 2004 in Winnipeg, Canada. Individual and social-network variables were obtained from a survey instrument administered through a personal interview. Syringe sharing was defined as receptive syringe sharing in the last 6 months. Logistic regression analysis with generalized estimating equations was used to determine simultaneously the role of individual-level and risk network member-level variables on the odds of syringe sharing. Individuals' relationship to a risk network member (sex partner, OR: 15.3 95% CI: 7.6-30.8; family member, OR: 3.4 95% CI: 1.3-9.0) and difficulty of access to syringes (OR: 3.6 95% CI: 1.3-9.9) were predictive of syringe sharing. Dyads who 'often' pooled resources to obtain drugs were at 4.9 times (95% CI: 2.1-11.6) the odds of syringe sharing, while those who 'sometimes' pooled resources were at 2.8 times (95% CI: 1.1-6.7) the odds, compared to those who 'never' pooled resources together. Syringe sharing in this population depended on both the availability of clean syringes and social network relationships. Adopting interventions that take into account relationships and behaviours that shape social norms present in networks/dyads would be a necessary prevention strategy alongside the provision of clean syringes.

  6. Perforated Gastric Ulcer Associated with Anti-Angiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Diogo Libânio

    2017-08-01

    Full Text Available Anti-angiogenic therapy with bevacizumab, an inhibitor of vascular endothelial growth factor, is commonly used in metastatic colorectal cancer and is rarely associated with gastrointestinal perforation, perforation being more frequent in the primary tumor site or at the anastomotic level. We present the case of a 64-year-old male with stage IV rectal adenocarcinoma who was on palliative chemotherapy with FOLFOX and bevacizumab. After the 4th chemotherapy cycle, our patient started fever and epigastric pain. He was hemodynamically stable, and signs of peritoneal irritation were absent. There were no alterations in the abdominal X-ray, and C-reactive protein was markedly elevated. A CT scan revealed a de novo thickness in the gastric antrum. Upper digestive endoscopy showed an ulcerated 40-mm lesion in the angulus, with a 20-mm orifice communicating with an exsudative cavity revested by the omentum. A conservative approach was decided including fasting, broad-spectrum intravenous antibiotics, and proton-pump inhibitors. Subsequent gastroduodenal series showed no contrast extravasation, allowing the resumption of oral nutrition. Esophagogastroduodenoscopy after 8 weeks showed perforation closure. Biopsies did not show neoplastic cells or Heliobacter pylori infection. Although the success in the conservative management of perforation allowing the maintenance of palliative chemotherapy (without bevacizumab, the patient died after 4 months due to liver failure. The reported case shows an uncommon endoscopic finding due to a rare complication of anti-angiogenic therapy. Additionally, it reminds clinicians that a history of gastroduodenal ulcers should be actively sought before starting anti-angiogenic treatment and that suspicion for perforation should be high in these cases.

  7. Hypoxia enhances the angiogenic potential of human dental pulp cells.

    Science.gov (United States)

    Aranha, Andreza M F; Zhang, Zhaocheng; Neiva, Kathleen G; Costa, Carlos A S; Hebling, Josimeri; Nör, Jacques E

    2010-10-01

    Trauma can result in the severing of the dental pulp vessels, leading to hypoxia and ultimately to pulp necrosis. Improved understanding of mechanisms underlying the response of dental pulp cells to hypoxic conditions might lead to better therapeutic alternatives for patients with dental trauma. The purpose of this study was to evaluate the effect of hypoxia on the angiogenic response mediated by human dental pulp stem cells (DPSCs) and human dental pulp fibroblasts (HDPFs). DPSCs and HDPFs were exposed to experimental hypoxic conditions. Hypoxia-inducible transcription factor-1alpha (HIF-1alpha) was evaluated by Western blot and immunocytochemistry, whereas vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression was evaluated by enzyme-linked immunosorbent assay. YC-1, an inhibitor of HIF-1alpha, was used to evaluate the functional effect of this transcriptional factor on hypoxia-induced VEGF expression. Conditioned medium from hypoxic and normoxic pulp cells was used to stimulate human dermal microvascular endothelial cells (HDMECs). HDMEC proliferation was measured by WST-1 assay, and angiogenic potential was evaluated by a capillary sprouting assay in 3-dimensional collagen matrices. Hypoxia enhanced HIF-1alpha and VEGF expression in DPSCs and HDPFs. In contrast, hypoxia did not induce bFGF expression in pulp cells. YC-1 partially inhibited hypoxia-induced HIF-1alpha and VEGF in these cells. The growth factor milieu of hypoxic HDPFs (but not hypoxic DPSCs) induced endothelial cell proliferation and sprouting as compared with medium from normoxic cells. Collectively, these data demonstrate that hypoxia induces complex and cell type-specific pro-angiogenic responses and suggest that VEGF (but not bFGF) participates in the revascularization of hypoxic dental pulps. Copyright © 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  8. Myocardial hypertrophy overrides the angiogenic response to hypoxia.

    Directory of Open Access Journals (Sweden)

    Yeong-Hoon Choi

    Full Text Available Cyanosis and myocardial hypertrophy frequently occur in combination. Hypoxia or cyanosis can be potent inducers of angiogenesis, regulating the expression of hypoxia-inducible factors (HIF, vascular endothelial growth factors (VEGF, and VEGF receptors (VEGFR-1 and 2; in contrast, pressure overload hypertrophy is often associated with impaired pro-angiogenic signaling and decreased myocardial capillary density. We hypothesized that the physiological pro-angiogenic response to cyanosis in the hypertrophied myocardium is blunted through differential HIF and VEGF-associated signaling.Newborn rabbits underwent aortic banding and, together with sham-operated littermates, were transferred into a hypoxic chamber (FiO(2 = 0.12 at 3 weeks of age. Control banded or sham-operated rabbits were housed in normoxia. Systemic cyanosis was confirmed (hematocrit, arterial oxygen saturation, and serum erythropoietin. Myocardial tissue was assayed for low oxygen concentrations using a pimonidazole adduct. At 4 weeks of age, HIF-1alpha and HIF-2alpha protein levels, HIF-1alpha DNA-binding activity, and expression of VEGFR-1, VEGFR-2, and VEGF were determined in hypoxic and normoxic rabbits. At 6 weeks of age, left-ventricular capillary density was assessed by immunohistochemistry. Under normoxia, capillary density was decreased in the banded rabbits compared to non-banded littermates. As expected, non-hypertrophied hearts responded to hypoxia with increased capillary density; however, banded hypoxic rabbits demonstrated no increase in angiogenesis. This blunted pro-angiogenic response to hypoxia in the hypertrophied myocardium was associated with lower HIF-2alpha and VEGFR-2 levels and increased HIF-1alpha activity and VEGFR-1 expression. In contrast, non-hypertrophied hearts responded to hypoxia with increased HIF-2alpha and VEGFR-2 expression with lower VEGFR-1 expression.The participation of HIF-2alpha and VEGFR-2 appear to be required for hypoxia

  9. Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

    Science.gov (United States)

    Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Berg, Anders H; Geahchan, Carl; Wenger, Julia B; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2016-07-01

    Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine

  10. Sharing Death

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Refslund Christensen, Dorthe

    (s) displaying photographs, poetry, stories and expressions of grief and longing. They take part in expressions of empathy for others by lighting candles for other people's loved ones, they share their personal experiences in different chatrooms and the site offers services as a calendar displaying anniversaries...... allowing creating unique and editable profiles, adding personal content and sharing it with other people in your network(s) AND systems for publishing your own life: becoming visible to others, being connected and being observed. More and more sites turn up on the Internet that facilitates the process...

  11. The role of angiogenic markers in adverse perinatal outcomes: fresh versus frozen embryo transfers.

    Science.gov (United States)

    Woo, Irene; Chan, Yen; Sriprasert, Intira; Louie, Kristin; Ingles, Sue; Stanczyk, Frank; McGinnis, Lynda K; Chung, Karine

    2017-12-01

    We aimed to investigate the angiogenic balance in fresh compared to frozen embryo transfers, and among neonates with adverse perinatal outcomes. This was a retrospective cohort study. All IVF cycles resulting in a singleton live birth at a university academic fertility center from January 1, 2011, to December 31, 2013, were examined. Concentrations of sFLT-1 and PlGF were measured in previously frozen serum specimens collected during early gestation at approximately 5 weeks gestation. Patients completed an electronic survey to detail perinatal outcome. We identified 152 singleton live births (103 fresh, 49 frozen). Demographic characteristics were similar between the two groups. Ratios of sFlt-1:PlGF were not different between fresh and frozen transfers. Neonates from fresh cycles had a mean birth weight 202 g lighter (p = 0.01) than frozen cycles, after adjusting for gestational age. Among babies born with poor perinatal outcomes, there was a difference in sFlt-1:PlGF ratios after adjusting for race. In non-Asians, infants born small for gestational age (SGA) (< 10th percentile) had significantly higher sFLT-1:PLGF ratio, median ratio (0.21 vs 0.12, p = 0.016). Fresh transfers were associated with lower birth weight infants compared to frozen transfers. While there was no difference in sFlt-1:PlGF ratios between fresh and frozen transfers, these ratios were significantly lower in SGA infants, suggesting an imbalance in angiogenic markers during placentation.

  12. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins

    KAUST Repository

    Chan, Yuk-kit

    2015-04-01

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.

  13. Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting neuropilin-1 for anticancer application.

    Science.gov (United States)

    Kamarulzaman, Ezatul E; Vanderesse, Régis; Gazzali, Amirah M; Barberi-Heyob, Muriel; Boura, Cédric; Frochot, Céline; Shawkataly, Omar; Aubry, André; Wahab, Habibah A

    2017-01-01

    Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) are important targets of many pro-angiogenic factors. In this study, nine peptides were synthesized and evaluated for their molecular interaction with NRP-1 and compared to our previous peptide ATWLPPR. Docking study showed that the investigated peptides shared the same binding region as shown by tuftsin known to bind selectively to NRP-1. Four pentapeptides (DKPPR, DKPRR, TKPPR and TKPRR) and a hexapeptide CDKPRR demonstrated good inhibitory activity against NRP-1. In contrast, peptides having arginine residue at sites other than the C-terminus exhibited low activity towards NRP-1 and this is confirmed by their inability to displace the VEGF165 binding to NRP-1. Docking study also revealed that replacement of carboxyl to amide group at the C-terminal arginine of the peptide did not affect significantly the binding interaction to NRP-1. However, the molecular affinity study showed that these peptides have marked reduction in the activity against NRP-1. Pentapeptides having C-terminal arginine showed strong interaction and good inhibitory activity with NRP thus may be a good template for anti-angiogenic targeting agent.

  14. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

    NARCIS (Netherlands)

    Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

    2010-01-01

    Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

  15. Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics.

    Science.gov (United States)

    Abdalla, Ahmed M E; Xiao, Lin; Ullah, Muhammad Wajid; Yu, Miao; Ouyang, Chenxi; Yang, Guang

    2018-01-01

    With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.

  16. Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics

    Science.gov (United States)

    Abdalla, Ahmed M.E.; Xiao, Lin; Ullah, Muhammad Wajid; Yu, Miao; Ouyang, Chenxi; Yang, Guang

    2018-01-01

    With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels. PMID:29290825

  17. Shared Language

    Science.gov (United States)

    Bochicchio, Daniel; Cole, Shelbi; Ostien, Deborah; Rodriguez, Vanessa; Staples, Megan; Susla, Patricia; Truxaw, Mary

    2009-01-01

    This article describes a process by which seven educators collaboratively engaged in developing a shared language to describe the mathematics pedagogy used to guide whole-class discussions as well as the products of their work. Suggestions are made for how others might engage in similarly productive professional development activities. (Contains 3…

  18. The impact of laser surgery on angiogenic and anti-angiogenic factors in twin-twin transfusion syndrome: a prospective study.

    Science.gov (United States)

    Chon, Andrew H; Chavira, Emiliano R; Wilson, Melissa L; Ingles, Sue A; Llanes, Arlyn; Chmait, Ramen H

    2018-04-01

    To examine the effect of laser surgery on angiogenic and anti-angiogenic factors in patients with twin-twin transfusion syndrome (TTTS). Cases of TTTS and uncomplicated monochorionic diamniotic twin pregnancies between 16 and 26 weeks' gestation were prospectively enrolled into the study. Maternal blood samples were obtained to measure angiogenic factors (vascular endothelial growth factor-A [VEGF], placental-derived growth factor [PlGF], and endothelin) and anti-angiogenic factors (soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sEng), and sFlt-1/PlGF ratio). For cases, these factors were measured at visit 1 (pre-operatively), visit 2 (postoperative day one), and visit 3 (at least 3 weeks after surgery). In controls, the factors were measured at visit 1 (enrollment) and visit 2 (at least 3 weeks later). Levels of angiogenic and anti-angiogenic factors between cases and controls were compared. At enrollment, the TTTS cases demonstrated an anti-angiogenic state with significantly higher sFlt-1, sEng, sFlt-1/PlGF ratio, and lower PlGF. Laser surgery, comparing visit 1-3, had a partial corrective effect on TTTS cases. sFlt-1 significantly decreased several weeks after surgery. The other factors (PlGF, endothelin, sFlt-1, sEng, and sFlt-1/PlGF ratio) were not statistically significantly different by visit 3. Laser surgery partially corrected the angiogenic profile in patients with TTTS.

  19. Disrupted Balance of Angiogenic and Antiangiogenic Signalings in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Mitsuko Furuya

    2011-01-01

    Full Text Available The placenta plays a central role in governing local circulatory system that mediates maternal condition and fetal growth. In early gestational phases, the placenta exerts properties of invasion and neovascularization for successful placentation. Extravillous invasive trophoblasts replace uterine endometrial vasculature and establish local blood pathway to obtain oxygen and nutrients from the mother. In later phases, the placenta promotes villous angiogenesis and vascular maturation that are finely controlled by angiogenic and antiangiogenic molecules. Among various molecules involved in placental neovascularization, vascular endothelial growth factor receptors (VEGFRs and angiotensin II receptor type 1 (AT1 mediate important signaling pathways for maternal circulatory system and fetal growth. VEGFR1 and VEGFR2 are functional receptors for placental growth factor (PlGF and VEGF, respectively, and PlGF-VEGFR1 and VEGF-VEGFR2 interactions are disturbed in many preeclamptic patients by excess amount of soluble form of VEGFR1 (also named sFlt1, a natural PlGF/VEGF antagonist. Recent studies have disclosed that excessive sFlt1 production in the placenta and aberrant AT1 signaling in the mother are closely associated with the pathology of preeclampsia and intrauterine growth restriction (IUGR. In this paper, neovascularization of the placenta and pathological events associated with disrupted balance between angiogenic and antiangiogenic signaling in preeclampsia are discussed.

  20. Food Sharing: An Evolutionary Perspective.

    Science.gov (United States)

    Feinman, Saul

    Food altruism and the consumption of food are examined from a sociological perspective which assumes that humans share food as inclusive fitness actors. Inclusive fitness implies the representation of an individual's genes in future generations through his own or others' offspring. The discussion includes characteristics of food sharing among kin…

  1. Resistance exercise increases endothelial progenitor cells and angiogenic factors.

    Science.gov (United States)

    Ross, Mark D; Wekesa, Antony L; Phelan, John P; Harrison, Michael

    2014-01-01

    Bone marrow-derived endothelial progenitor cells (EPC) are involved in vascular growth and repair. They increase in the circulation after a single bout of aerobic exercise, potentially related to muscle ischemia. Muscular endurance resistance exercise (MERE) bouts also have the potential to induce muscle ischemia if appropriately structured. The objective of this study is to determine the influence of a single bout of MERE on circulating EPC and related angiogenic factors. Thirteen trained men age 22.4 ± 0.5 yr (mean ± SEM) performed a bout of MERE consisting of three sets of six exercises at participants' 15-repetition maximum without resting between repetitions or exercises. The MERE bout duration was 12.1 ± 0.6 min. Blood lactate and HR were 11.9 ± 0.9 mmol·L and 142 ± 5 bpm, respectively, at the end of MERE. Blood was sampled preexercise and at 10 min, 2 h, and 24 h postexercise. Circulating EPC and serum concentrations of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D), granulocyte colony stimulating factor, soluble Tie-2, soluble fms-like tyrosine kinase-1, and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-9) were higher (P < 0.05) in the postexercise period. Circulating EPC levels were unchanged at 10 min postexercise but higher at 2 h postexercise (P < 0.05). The concentration of most angiogenic factors and metalloproteinases were higher at 10 min postexercise (VEGF-A, +38%; VEGF-C, +40%; VEGF-D, +9%; soluble Tie-2, +15%; soluble fms-like tyrosine kinase-1, +24%; MMP-1, +62%; MMP-2, +3%; MMP-3, +54%; and MMP-9, +45%; all P < 0.05). Soluble E-selectin was lower (P < 0.05) at 2 and 24 h postexercise, with endothelial microparticles and thrombomodulin unchanged. Short intense bouts of MERE can trigger increases in circulating EPC and related angiogenic factors, potentially contributing to vascular adaptation and vasculoprotection.

  2. Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice

    DEFF Research Database (Denmark)

    Kragh, M; Spang-Thomsen, M; Kristjansen, P E

    1999-01-01

    We examined the effect of the anti-angiogenic compound TNP-470 on early tumor growth characteristics following subcutaneous implantation of 1 mm3 tissue blocks of human glioblastoma U87, in nude mice. The mice received daily injections with TNP-470, 7 mg/kg, from one day before until either 3, 7......, 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i....... These findings demonstrate that the in vivo effect of TNP-470 on tumor growth is tumor inhibitory rather than cytotoxic. The lack of effect of the anti-angiogenic compound, TNP-470, in the early 3-day schedule is consistent with the existence of an early avascular phase which precede the angiogenesis...

  3. Shared care (comanagement).

    Science.gov (United States)

    Montero Ruiz, E

    2016-01-01

    Surgical departments have increasing difficulties in caring for their hospitalised patients due to the patients' advanced age and comorbidity, the growing specialisation in medical training and the strong political-healthcare pressure that a healthcare organisation places on them, where surgical acts take precedence over other activities. The pressure exerted by these departments on the medical area and the deficient response by the interconsultation system have led to the development of a different healthcare organisation model: Shared care, which includes perioperative medicine. In this model, 2 different specialists share the responsibility and authority in caring for hospitalised surgical patients. Internal Medicine is the most appropriate specialty for shared care. Internists who exercise this responsibility should have certain characteristics and must overcome a number of concerns from the surgeon and anaesthesiologist. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  4. Obesity and Cancer: An Angiogenic and Inflammatory Link.

    Science.gov (United States)

    Fukumura, Dai; Incio, Joao; Shankaraiah, Ram C; Jain, Rakesh K

    2016-04-01

    With the current epidemic of obesity, a large number of patients diagnosed with cancer are overweight or obese. Importantly, this excess body weight is associated with tumor progression and poor prognosis. The mechanisms for this worse outcome, however, remain poorly understood. We review here the epidemiological evidence for the association between obesity and cancer, and discuss potential mechanisms focusing on angiogenesis and inflammation. In particular, we will discuss how the dysfunctional angiogenesis and inflammation occurring in adipose tissue in obesity may promote tumor progression, resistance to chemotherapy, and targeted therapies such as anti-angiogenic and immune therapies. Better understanding of how obesity fuels tumor progression and therapy resistance is essential to improve the current standard of care and the clinical outcome of cancer patients. To this end, we will discuss how an anti-diabetic drug such as metformin can overcome these adverse effects of obesity on the progression and treatment resistance of tumors. © 2016 John Wiley & Sons Ltd.

  5. [Anti-angiogenic therapies: from theory to practice].

    Science.gov (United States)

    Bidart, Marie; Berger, François; Pelletier, Laurent

    2013-01-01

    During recent years clear progress has been made in support of tumor pathology. However, the treatment of metastatic disease is now a real therapeutic challenge. Among the new therapeutic strategies, blocking angiogenesis has been the subject of numerous clinical trials. However, if this approach was validated in 2004 by the approval of the first humanized anti-VEGF antibody (bevacizumab or Avastin(®), Roche, 2004), the pre-clinical and clinical studies conducted in the last 5 years have moderated the enthusiasm that these therapies had led in the early 2000s. In November 2011, the US Food and drug administration (FDA) revoke the agency's approval of the breast cancer indication for Avastin(®) because of benefit-risk balance appears negative. This review describes successively the mechanisms of action of antiangiogenic agents, the main anti-angiogenic drugs and the theoretical advantages and practical limitations of these therapies.

  6. Computer-aided Image Processing of Angiogenic Histological.

    Science.gov (United States)

    Sprindzuk, Matvey; Dmitruk, Alexander; Kovalev, Vassili; Bogush, Armen; Tuzikov, Alexander; Liakhovski, Victor; Fridman, Mikhail

    2009-12-01

    This article reviews the questions regarding the image evaluation of angiogeneic histological samples, particularly the ovarian epithelial cancer. Review is focused on the principles of image analysis in the field of histology and pathology. The definition, classification, pathogenesis and angiogenesis regulation in the ovaries are also briefly discussed. It is hoped that the complex image analysis together with the patient's clinical parameters will allow an acquiring of a clear pathogenic picture of the disease, extension of the differential diagnosis and become a useful tool for the evaluation of drug effects. The challenge of the assessment of angiogenesis activity is the heterogeneity of several objects: parameters derived from patient's anamnesis as well as of pathology samples. The other unresolved problems are the subjectivity of the region of interest selection and performance of the whole slide scanning. Angiogenesis; Image processing; Microvessel density; Cancer; Pathology.

  7. Ovarian function following targeted anti-angiogenic therapy with bevacizumab.

    Science.gov (United States)

    Imai, Atsushi; Ichigo, Satoshi; Matsunami, Kazutoshi; Takagi, Hiroshi; Kawabata, Ichiro

    2017-06-01

    Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.

  8. Hypoxia-inducible factor as an angiogenic master switch

    Directory of Open Access Journals (Sweden)

    Takuya eHashimoto

    2015-04-01

    Full Text Available Hypoxia-inducible factors (HIFs regulate the transcription of genes that mediate the response to hypoxia. HIFs are constantly expressed and degraded under normoxia, but stabilized under hypoxia. HIFs have been widely studied in physiological and pathological conditions and have been shown to contribute to the pathogenesis of various vascular diseases. In clinical settings, the HIF pathway has been studied for its role in inhibiting carcinogenesis. HIFs might also play a protective role in the pathology of ischemic diseases. Clinical trials of therapeutic angiogenesis after the administration of a single growth factor have yielded unsatisfactory or controversial results, possibly because the coordinated activity of different HIF-induced factors is necessary to induce mature vessel formation. Thus, manipulation of HIF activity to simultaneously induce a spectrum of angiogenic factors offers a superior strategy for therapeutic angiogenesis. Because HIF-2α plays an essential role in vascular remodeling, manipulation of HIF-2α is a promising approach to the treatment of ischemic diseases caused by arterial obstruction, where insufficient development of collateral vessels impedes effective therapy. eIF3e/INT6 interacts specifically with HIF-2α and induces the proteasome inhibitor-sensitive degradation of HIF-2α, independent of hypoxia and VHL. Treatment with eIF3e/INT6 siRNA stabilizes HIF-2α activity even under normoxic conditions and induces the expression of several angiogenic factors, at levels sufficient to produce functional arteries and veins in vivo. We have demonstrated that administration of eIF3e/INT6 siRNA to ischemic limbs or cold-injured brains reduces ischemic damage in animal models. This review summarizes the current understanding of the relationship between HIFs and vascular diseases. We also discuss novel oxygen-independent regulatory proteins that bind HIF-α and the implications of a new method for therapeutic angiogenesis

  9. Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Laura Pisarsky

    2016-05-01

    Full Text Available Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.

  10. Stromal-Epithelial Interactions and the Angiogenic Phenotype of Breast Cancer

    National Research Council Canada - National Science Library

    Rozenberg, Gabriela I

    2005-01-01

    ... upregulation, and a pro-angiogenic phenotype in culture and in vivo. However, only inhibiting alpha5beta1 activity could phenotypically revert these tumors, reduce invasion and impair angiogenesis in culture...

  11. Clinical outcome, proteome kinetics and angiogenic factors in serum after thermoablation of colorectal liver metastases

    NARCIS (Netherlands)

    Wertenbroek, Marieke W. J. L. A. E.; Schepers, Marianne; Kamminga-Rasker, Hannetta J.; Bottema, Jan T.; Kobold, Anneke C. Muller; Roelofsen, Han; de Jong, Koert P.

    2013-01-01

    Background: Thermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). Methods: 205 patients underwent CSA (n

  12. In vitro and in vivo anti-angiogenic activity of girinimbine isolated from Murraya koenigii.

    Science.gov (United States)

    Iman, Venoos; Karimian, Hamed; Mohan, Syam; Hobani, Yahya Hasan; Noordin, Mohamed Ibrahim; Mustafa, Mohd Rais; Noor, Suzita Mohd

    2015-01-01

    Girinimbine is a carbazole alkaloid isolated from the stem bark and root of Murraya koenigii. Here we report that girinimbine is an inhibitor of angiogenic activity both in vitro and in vivo. MTT results showed that girinimbine inhibited proliferation of human umbilical vein endothelial cells, while results from endothelial cell invasion, migration, tube formation, and wound healing assays demonstrated significant time- and dose-dependent inhibition by girinimbine. A proteome profiler array done on girinimbine-treated human umbilical vein endothelial cells showed that girinimbine had mediated regulation of pro-angiogenic and anti-angiogenic proteins. The anti-angiogenic potential of girinimbine was also evidenced in vivo in the zebrafish embryo model wherein girinimbine inhibited neo vessel formation in zebrafish embryos following 24 hours of exposure. Together, these results showed that girinimbine could effectively suppress angiogenesis, suggestive of its therapeutic potential as a novel angiogenesis inhibitor.

  13. Angiogenic endothelium shows lactadherin-dependent phagocytosis of aged erythrocytes and apoptotic cells

    NARCIS (Netherlands)

    Fens, Marcel H. A. M.; Mastrobattista, Enrico; De Graaff, Anko M.; Flesch, Frits M.; Ultee, Anton; Rasmussen, Jan T.; Molema, Grietje; Storm, Gert; Schiffelers, Raymond M.

    2008-01-01

    Angiogenic endothelium plays a crucial role in tumor growth. During angiogenesis, complex alterations in the microenvironment occur. In response, the endothelium undergoes phenotypic changes, for example overexpression of alpha(v)-integrins. Here, we show that the overexpression of

  14. Regulation of angiogenesis in human skeletal muscle with specific focus on pro- angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Høier, Birgitte

    It is well established that acute exercise promotes an angiogenic response and that a period of exercise training results in capillary growth. Skeletal muscle angiogenesis is a complex process that requires a coordinated interplay of multiple factors and compounds to ensure proper vascular function...... to exercise in skeletal muscle cells whereas disease is a more determining factor for the capillary network. In conclusion, the findings in the six studies that the PhD thesis is based on provide valuable information to further the understanding of the regulation of human skeletal muscle angiogenesis......, the findings of simultaneously enhanced pro-angiogenic and angiostatic factors in response to acute exercise before training points to that the angiogenic process is highly regulated even when capillary growth is required. The attenuated response in some of the pro-angiogenic factors after training...

  15. Angiogenic factors in chronic lymphocytic leukaemia (CLL): Where do we stand?

    Science.gov (United States)

    Aguirre Palma, Luis Mario; Gehrke, Iris; Kreuzer, Karl-Anton

    2015-03-01

    The role of angiogenesis in haematological malignancies such as chronic lymphocytic leukaemia (CLL) is difficult to envision, because leukaemia cells are not dependent on a network of blood vessels to support basic physiological requirements. Regardless, CLL cells secrete high levels of major angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF). Nonetheless, it remains unclear how most angiogenic factors regulate accumulation and delayed apoptosis of CLL cells. Angiogenic factors such as leptin, granulocyte colony-stimulating factor (G-CSF), follistatin, angiopoietin-1 (Ang1), angiogenin (ANG), midkine (MK), pleiotrophin (PTN), progranulin (PGRN), proliferin (PLF), placental growth factor (PIGF), and endothelial locus-1 (Del-1), represent novel therapeutic targets of future CLL research but have remained widely overlooked. This review aims to outline our current understanding of angiogenic growth factors and their relationship with CLL, a still uncured haematopoietic malignancy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Cells and Angiogenic Cytokines in Therapeutic Angiogenesis for Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Luo, Yu; Zhang, Dai-Fu; Liang, Bo

    2005-01-01

    In the past 20 to 30 years,great developments had been achieved in the applying of cells and angiogenic cytokines for ischemic heart disease.The thesis reviews latest studies of mechanism and clinic application of this novel therapy.......In the past 20 to 30 years,great developments had been achieved in the applying of cells and angiogenic cytokines for ischemic heart disease.The thesis reviews latest studies of mechanism and clinic application of this novel therapy....

  17. Sharing values, sharing a vision

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    Teamwork, partnership and shared values emerged as recurring themes at the Third Technology Transfer/Communications Conference. The program drew about 100 participants who sat through a packed two days to find ways for their laboratories and facilities to better help American business and the economy. Co-hosts were the Lawrence Livermore National Laboratory and the Lawrence Berkeley Laboratory, where most meetings took place. The conference followed traditions established at the First Technology Transfer/Communications Conference, conceived of and hosted by the Pacific Northwest Laboratory in May 1992 in Richmond, Washington, and the second conference, hosted by the National Renewable Energy Laboratory in January 1993 in Golden, Colorado. As at the other conferences, participants at the third session represented the fields of technology transfer, public affairs and communications. They came from Department of Energy headquarters and DOE offices, laboratories and production facilities. Continued in this report are keynote address; panel discussion; workshops; and presentations in technology transfer.

  18. Early pregnancy maternal and fetal angiogenic factors and fetal and childhood growth: the Generation R Study.

    Science.gov (United States)

    Bergen, N E; Bouwland-Both, M I; Steegers-Theunissen, R P M; Hofman, A; Russcher, H; Lindemans, J; Jaddoe, V W V; Steegers, E A P

    2015-06-01

    What are the effects of maternal and fetal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) concentrations on fetal and childhood growth patterns? An angiogenic profile that is characterized by both low early pregnancy maternal sFlt-1 and PlGF concentrations and higher sFlt-1 concentrations, lower PlGF concentrations or a higher sFlt-1:PlGF ratio in umbilical cord blood is associated with a reduced fetal and childhood growth. An imbalance in maternal and fetal sFlt-1 and PlGF concentrations has been suggested to affect pregnancy outcomes. However, their effects on longitudinal fetal and childhood growth remain largely unknown. This study was performed in 5980 mothers and 4108 of their children, participating in the Generation R Study; a population-based prospective cohort study from fetal life onwards in Rotterdam, the Netherlands (2001-2005). Blood samples were obtained from mothers in early and mid-pregnancy and from the umbilical vein at delivery. Fetal and childhood growth characteristics (weight and length) were measured repeatedly by ultrasound and physical examinations until the age of 6 years. We assessed the associations of maternal and fetal angiogenic factors with fetal and childhood growth using repeated measurement regression models. Logistic regression models were used to determine associations between angiogenic factors and small for gestational age at birth (SGA). Compared with early pregnancy maternal sFlt-1 concentrations in the lowest quintile, early pregnancy maternal sFlt-1 concentrations in the highest quintile were associated with a higher fetal weight growth resulting in a higher birthweight (difference in birthweight 0.33 standard deviation score (SDS); 95% Confidence Interval (CI) 0.25-0.41), a lower risk of SGA (Odds Ratio (OR) 0.36; 95% CI 0.27-0.48) and a subsequent higher weight growth until the age of 6 years. Early pregnancy maternal PlGF concentrations in the lowest quintile were associated with a

  19. Low back pain patients in Sweden, Denmark and the UK share similar characteristics and outcomes: a cross-national comparison of prospective cohort studies.

    Science.gov (United States)

    Kongsted, Alice; Davies, Laura; Axen, Iben

    2015-11-26

    Low back pain (LBP) is the world's leading cause of disability and yet poorly understood. Cross-national comparisons may motivate hypotheses about outcomes being condition-specific or related to cultural differences and can inform whether observations from one country may be generalised to another. This analysis of data from three cohort studies explored whether characteristics and outcomes differed between LBP patients visiting chiropractors in Sweden, Denmark and the UK. LBP patients completed a baseline questionnaire and were followed up after 3, 5, 12 and 26 weeks. Outcomes were LBP intensity (0-10 scales) and LBP frequency (0-7 days the previous week). Cohort differences were tested in mixed models accounting for repeated measures. It was investigated if any differences were explained by different baseline characteristics, and interaction terms between baseline factors and nations tested if strength of prognostic factors differed across countries. The study sample consisted of 262, 947 and 453 patients from Sweden, Denmark and the UK respectively. Patient characteristics were largely similar across cohorts although some statistically significant differences were observed. The clinical course followed almost identical patterns across nations and small observed differences were not present after adjusting for baseline factors. The associations of LBP intensity and episode duration with outcome differed in strength between countries. Chiropractic patients with low back pain had similar characteristics and clinical course across three Northern European countries. It is unlikely that culture have substantially different impacts on the course of LBP in these countries and the results support knowledge transfer between the investigated countries.

  20. Angiogenic squamous dysplasia-like phenomenon in oral epithelial precursor lesions

    Directory of Open Access Journals (Sweden)

    Siar CH

    2009-07-01

    Full Text Available Abstract Statement of the problem Dysplasia, the morphological yardstick of epithelial precursor lesions, is the collective term for a variety of architectural and cytological changes within the altered oral epithelium. Angiogenic squamous dysplasia (ASD, a distinct morphological characteristic in pre-invasive bronchial lesions, describes the presence of capillary tufts that are closely juxtaposed to and projecting into the dysplastic bronchial epithelium. Objective To determine whether ASD-like phenomenon occurs in oral epithelial precursor lesions, and to speculate on its relevance. Methods Twenty cases each of mild, moderate and severe oral dysplasia (inclusive of carcinoma-in-situ, and 10 normal oral mucosa (normal controls were serial sectioned for H and E staining, and for microvessel density (MVD scoring with CD31, CD34 and CD105. Microcapillary pattern images were digitally captured for 3-D reconstruction. Results Oral ASD foci consisting of CD31-and CD34-positive capillary loops abutting onto the overlying dysplastic oral epithelium (and causing it to assume an irregular or papillary surface configuration were identified in moderate (3/20; 15% and severe dysplasia (13/20; 65%, but not in normal oral mucosa and mild dysplasia. MVD score demonstrated increasing vascularity as epithelium progressed from normal to severe dysplasia (p Conclusions These preliminary findings taken together suggest that: 1. ASD-like phenomenon may be an important intermediary biomarker in oral precursor lesions; and 2. architectural alterations of the entire disturbed mucosa may be a more useful pre-malignancy index.

  1. Anti-Angiogenic Tyrosine Kinase Inhibitors and Reversible Posterior Leukoencephalopathy Syndrome: Could Hypomagnesaemia Be the Trigger?

    Science.gov (United States)

    Shah, Rashmi R

    2017-05-01

    Reversible posterior leukoencephalopathy syndrome (RPLS), also known frequently as posterior reversible encephalopathy syndrome (PRES), is a characteristic acute neuro-radiology syndrome with clinical presentation that typically includes acute hypertension, seizures and other neurological symptoms and signs. Many patients with RPLS have (a history of) pre-existing hypertension and in receipt of diuretics. It is being diagnosed more frequently and in association with an increasing number of morbidities and medications. Drugs most frequently implicated are immunosuppressant drugs and anticancer agents, including a number of anti-angiogenic tyrosine kinase inhibitors (TKIs). Hypomagnesaemia is a frequent finding at presentation in RPLS patients, which is known to lead to or aggravate hypertension. Pre-eclampsia, a variant of RPLS, responds effectively to intravenous magnesium. Cyclosporin, tacrolimus and some TKIs that induce RPLS are also known to give rise to both hypertension and hypomagnesaemia. This raises an interesting hypothesis that hypomagnesaemia may play a contributory role in triggering RPLS in some patients by acutely raising the blood pressure further. Additional systematic studies are required to test this hypothesis. If the hypothesis is confirmed, hypomagnesaemia offers an effective target for risk mitigation and prevention of RPLS in patients identified at risk.

  2. Effects of hypergravity on the angiogenic potential of endothelial cells.

    Science.gov (United States)

    Costa-Almeida, Raquel; Carvalho, Daniel T O; Ferreira, Miguel J S; Aresta, Guilherme; Gomes, Manuela E; van Loon, Jack J W A; Van der Heiden, Kim; Granja, Pedro L

    2016-11-01

    Angiogenesis, the formation of blood vessels from pre-existing ones, is a key event in pathology, including cancer progression, but also in homeostasis and regeneration. As the phenotype of endothelial cells (ECs) is continuously regulated by local biomechanical forces, studying endothelial behaviour in altered gravity might contribute to new insights towards angiogenesis modulation. This study aimed at characterizing EC behaviour after hypergravity exposure (more than 1g), with special focus on cytoskeleton architecture and capillary-like structure formation. Herein, human umbilical vein ECs (HUVECs) were cultured under two-dimensional and three-dimensional conditions at 3g and 10g for 4 and 16 h inside the large diameter centrifuge at the European Space Research and Technology Centre (ESTEC) of the European Space Agency. Although no significant tendency regarding cytoskeleton organization was observed for cells exposed to high g's, a slight loss of the perinuclear localization of β-tubulin was observed for cells exposed to 3g with less pronounced peripheral bodies of actin when compared with 1g control cells. Additionally, hypergravity exposure decreased the assembly of HUVECs into capillary-like structures, with a 10g level significantly reducing their organization capacity. In conclusion, short-term hypergravity seems to affect EC phenotype and their angiogenic potential in a time and g-level-dependent manner. © 2016 The Author(s).

  3. Cutaneous lesions of secondary syphilis are highly angiogenic.

    Science.gov (United States)

    Macaron, Nada C; Cohen, Cynthia; Chen, Suephy C; Arbiser, Jack L

    2003-06-01

    The role of angiogenesis in infectious processes is poorly studied. Some viruses have been linked to angiogenesis, but the role of bacteria and protozoa in inducing angiogenesis in chronic infections is poorly understood. We examined the role of angiogenesis in syphilis, a common and often difficult-to-treat infectious disease, especially in the setting of HIV/AIDS. Microvessel counts were performed on 27 paraffin-fixed sections of secondary syphilis by staining with monoclonal antibodies against CD31. In addition, immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF) to determine whether increased angiogenesis may be mediated, in part, through increased production of VEGF. The CD31 mean microvessel count in secondary syphilis sections was significantly higher than in normal control sections. VEGF intensity appeared increased in the patients with secondary syphilis. Infection with Treponema pallidum results in increased angiogenesis in secondary syphilis. The mechanism for increased angiogenesis may involve elaboration of angiogenic cytokines, such as VEGF and epidermal growth factor.

  4. Cell viability and angiogenic potential of a bioartificial adipose substitute.

    Science.gov (United States)

    Panneerselvan, Anitha; Nguyen, Luong T H; Su, Yan; Teo, Wee Eong; Liao, Susan; Ramakrishna, Seeram; Chan, Ching Wan

    2015-06-01

    An implantable scaffold pre-seeded with cells needs to remain viable and encourage rapid angiogenesis in order to replace injured tissues, especially for tissue defect repairs. We created a bioartificial adipose graft composed of an electrospun 3D nanofibrous scaffold and fat tissue excised from New Zealand white rabbits. Cell viability and angiogenesis potential of the bioartificial substitute were examined during four weeks of culture in Dulbecco's Modified Eagle Medium by immunohistochemical staining with LIVE/DEAD® cell kit and PECAM-1 antibody, respectively. In addition, a Matrigel® assay was performed to examine the possibility of blood vessels sprouting from the bioartificial graft. Our results showed that cells within the graft were viable and vascular tubes were present at week 4, while cells in a fat tissue block were dead in vitro. In addition, capillaries were observed sprouting from the graft into the Matrigel, demonstrating its angiogenic potential. We expect that improved cell viability and angiogenesis in the bioartificial substitute, compared to intact autologous graft, could potentially contribute to its survival following implantation. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Exogenous and endogenous angiogenic stimuli do not augment splenic autotransplantation.

    Science.gov (United States)

    Power, Richard E; Kay, Elaine W; Bouchier-Hayes, David

    2002-01-01

    To find out if angiogenic stimulation improves the ability of the spleen to regenerate. Experimental study. Teaching hospital, Republic of Ireland. 27 male Sprague-Dawley rats. Each spleen was removed and half was reimplanted in the greater omentum. The rats were randomised into three groups of 9 each: the first (control) group was given no stimulation; the second had the implanted spleen sutured into the omentum with 6/0 polypropylene; and in the third group the implanted spleen was injected with human recombinant vascular endothelial growth factor (VEGF) 500 microg. Clearance of Howell-Jolly bodies, and the weight and histological appearance of the splenic remnant at 3 months. The splenic remnant was significantly larger at 3 months in the control group (p = 0.0006). Histological examination of the tissue from the control group showed that it was architecturally similar to that of normal functioning spleen, whereas the tissue from the two treated groups contained less lymphoid tissue and showed widespread acute and chronic inflammatory changes. There was a significantly greater clearance of Howell-Jolly bodies (an index of splenic function) from the peripheral blood of the control group (p = 0.0009). The excellent recovery of the splenic remnant in the control group suggests that the procedure of splenic autotransplantation might warrant further consideration and study.

  6. Early pregnancy angiogenic proteins levels and pregnancy related hypertensive disorders.

    Science.gov (United States)

    Jakovljevic, Ana; Bogavac, Mirjana; Lozanov-Crvenkovic, Zagorka; Milosević-Tosic, Mirjana; Nikolic, Aleksandra; Mitic, Gorana

    2017-03-01

    Normal placental vascular development depends on multiple interactions of many regulatory molecules including pro and antiangiogenic proteins. It is considered that these vascular modulators might be one of the factors responsible for development hypertensive disorders in pregnancy. To evaluate and compare the early pregnancy (11-14 week of gestation) serum level of angiogenic proteins sFlt1, VEGF i PIGF between different types of pregnancy related hypertensive disorders. The study included 177 pregnant women between 11 and 14 weeks of gestation, divided into four study subgroups (preeclampsia group-41, gestational hypertension group-31, chronic hypertension group-32 and miscarriage group-19) and control group-54. Blood samples (serum) were taken for measuring sFlt1, VEGF i PIGF by a quantitative ELISA technique and measuring other biochemical and hematological parameters. Significantly higher levels of sFlt1 were in the subgroups with preeclampsia and miscarriages, significantly lower level of VEGF in the all study subgroups and lover level of PIGF were in miscarriage group. In the groups with chronic and gestational hypertension there were higher level of sFlt1 and lover level of VEGF than in the control group, but the differences did not reach statistical significance. Early pregnancy imbalance between antiangiogenic protein sFlt1 and proangiogenic molecules VEGF and PIGF could have impact on pathophysiology of placental disorders which leads to development of pregnancy related hypertensive disorders.

  7. Testing for Unit Roots in Market Shares

    NARCIS (Netherlands)

    Franses, P.H.B.F.; Srinivasan, S.; Boswijk, H.P.

    2001-01-01

    A unique characteristic of marketing data sets is the logical consistency requirement in market share models that market shares are bounded by 0 and 1, and they sum to unity. To take account of this logical consistency requirement, we propose to test for unit roots in individual market share series

  8. Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki.

    Science.gov (United States)

    Lecht, Shimon; Chiaverelli, Rachel A; Gerstenhaber, Jonathan; Calvete, Juan J; Lazarovici, Philip; Casewell, Nicholas R; Harrison, Robert; Lelkes, Peter I; Marcinkiewicz, Cezary

    2015-06-01

    Cysteine-rich secretory protein (CRISP) is present in majority of vertebrate including human. The physiological role of this protein is not characterized. We report that a CRISP isolated from Echis carinatus sochureki venom (ES-CRISP) inhibits angiogenesis. The anti-angiogenic activity of purified ES-CRISP from snake venom was investigated in vitro using endothelial cells assays such as proliferation, migration and tube formation in Matrigel, as well as in vivo in quail embryonic CAM system. The modulatory effect of ES-CRISP on the expression of major angiogenesis factors and activation of angiogenesis pathways was tested by qRT-PCR and Western blot. The amino acid sequence of ES-CRISP was found highly similar to other members of this snake venom protein family, and shares over 50% identity with human CRISP-3. ES-CRISP supported adhesion to endothelial cells, although it was also internalized into the cytoplasm in a granule-like manner. It blocked EC proliferation, migration and tube formation in Matrigel. In the embryonic quail CAM system, ES-CRISP abolished neovascularization process induced by exogenous growth factors (bFGF, vpVEGF) and by developing gliomas. CRISP modulates the expression of several factors at the mRNA level, which were characterized as regulators of angiogenesis and blocked activation of MAPK Erk1/2 induced by VEGF. ES-CRISP was characterized as a negative regulator of the angiogenesis, by direct interaction with endothelial cells. The presented work may lead to the development of novel angiostatic therapy, as well as contribute to the identification of the physiological relevance of this functionally uncharacterized protein. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel

    DEFF Research Database (Denmark)

    Reck, Martin; Mellemgaard, Anders; von Pawel, Joachim

    2015-01-01

    +docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. MATERIALS AND METHODS: The incidence and intensity of AEs......, hypertension, bleeding, thromboembolic events, and skin disorders. RESULTS AND CONCLUSION: The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib......+docetaxel versus 0.2% with placebo+docetaxel. The incidence of some events was higher with nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1-2 with both...

  10. Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors.

    Directory of Open Access Journals (Sweden)

    Eléonore Otjacques

    Full Text Available Mithramycin (MTM, a cytotoxic compound, is currently being investigated for its anti-angiogenic activity that seems to be mediated through an inhibition of the transcription factor SP1. In this study we evaluated its anti-myeloma effects in the syngenic 5TGM1 model in vitro as well as in vivo. In vitro, MTM inhibited DNA synthesis of 5TGM1 cells with an IC50 of 400 nM and induced an arrest in cell cycle progression at the G1/S transition point. Western-blot revealed an up-regulation of p53, p21 and p27 and an inhibition of c-Myc, while SP1 remained unaffected. In rat aortic ring assays, a strong anti-angiogenic effect was seen, which could be explained by a decrease of VEGF production and an up-regulation of anti-angiogenic proteins such as IP10 after MTM treatment. The administration of MTM to mice injected with 5TGM1 decreased 5TGM1 cell invasion into bone marrow and myeloma neovascularisation. These data suggest that MTM displays anti-myeloma and anti-angiogenic effects that are not mediated by an inhibition of SP1 but rather through c-Myc inhibition and p53 activation.

  11. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxi...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

  12. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

  13. Combining angiogenic gene and stem cell therapies for myocardial infarction.

    Science.gov (United States)

    Pons, Jennifer; Huang, Yu; Takagawa, Junya; Arakawa-Hoyt, Janice; Ye, Jianqin; Grossman, William; Kan, Yuet Wai; Su, Hua

    2009-09-01

    Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

  14. Automated quantification reveals hyperglycemia inhibits endothelial angiogenic function.

    Directory of Open Access Journals (Sweden)

    Anthony R Prisco

    Full Text Available Diabetes Mellitus (DM has reached epidemic levels globally. A contributing factor to the development of DM is high blood glucose (hyperglycemia. One complication associated with DM is a decreased angiogenesis. The Matrigel tube formation assay (TFA is the most widely utilized in vitro assay designed to assess angiogenic factors and conditions. In spite of the widespread use of Matrigel TFAs, quantification is labor-intensive and subjective, often limiting experiential design and interpretation of results. This study describes the development and validation of an open source software tool for high throughput, morphometric analysis of TFA images and the validation of an in vitro hyperglycemic model of DM.Endothelial cells mimic angiogenesis when placed onto a Matrigel coated surface by forming tube-like structures. The goal of this study was to develop an open-source software algorithm requiring minimal user input (Pipeline v1.3 to automatically quantify tubular metrics from TFA images. Using Pipeline, the ability of endothelial cells to form tubes was assessed after culture in normal or high glucose for 1 or 2 weeks. A significant decrease in the total tube length and number of branch points was found when comparing groups treated with high glucose for 2 weeks versus normal glucose or 1 week of high glucose.Using Pipeline, it was determined that hyperglycemia inhibits formation of endothelial tubes in vitro. Analysis using Pipeline was more accurate and significantly faster than manual analysis. The Pipeline algorithm was shown to have additional applications, such as detection of retinal vasculature.

  15. Anti-angiogenic activity of inositol hexaphosphate (IP6).

    Science.gov (United States)

    Vucenik, Ivana; Passaniti, Antonino; Vitolo, Michele I; Tantivejkul, Kwanchanit; Eggleton, Paul; Shamsuddin, Abulkalam M

    2004-11-01

    A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.

  16. Maternal plasma angiogenic and inflammatory factor profiling in foetal Down syndrome.

    Directory of Open Access Journals (Sweden)

    Monika Zbucka-Kretowska

    Full Text Available Angiogenic factors are proteins that are related to certain foetal chromosomal abnormalities. The aim of this study was to determine the concentration of 60 angiogenic factors in the plasma of women with offspring possessing trisomy 21/Down syndrome (DS.After analysing karyotyping results, we selected 20 patients with foetuses possessing DS, and for the control group, we selected 28 healthy patients with uncomplicated pregnancies who delivered healthy newborns at term (i.e., 15-18 weeks of gestation. To assess the concentration of proteins in the blood plasma, we used a protein macroarray which enabled simultaneous determination of 60 angiogenic factors per sample.We observed a statistically significant increase in the concentration of these five angiogenic and inflammatory factors: TGFb1 (p = 0.039, angiostatin (p = 0.0142, I-309 (p = 0.0476, TGFb3 (p = 0.0395, and VEGF-D (p = 0.0173-compared to concentrations in patients with healthy foetuses.Our findings suggest that angiogenic factors may play role in DS pathogenesis.

  17. Assessment of anti-angiogenic and anti-tumoral potentials of Origanum onites L. essential oil.

    Science.gov (United States)

    Bostancıoğlu, Rakibe Beklem; Kürkçüoğlu, Mine; Başer, Kemal Hüsnü Can; Koparal, Ayşe Tansu

    2012-06-01

    Medicinal plants and culinary herbs with anti-angiogenic and little toxicity properties have gained importance. Non-toxic anti-angiogenic phytochemicals are useful in combating cancer by preventing the formation of new blood vessels to support the tumor growth. We have investigated the essential oil of Origanum onites L. (OOEO), for a possible anti-angiogenic activity. OOEO was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The anti-proliferative activities (by MTT assay, 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide), anti-angiogenic activities (by tube formation assay), cell migration inhibiting capability (migration assay) and apoptotic potential (DAPI staining) of OOEO were evaluated on rat adipose tissue endothelial cells (RATECs) and 5RP7 (c-H-ras transformed rat embryonic fibroblasts) cells. Our results revealed that OOEO could markedly inhibit cell viability and induced apoptosis of 5RP7 cells and also could block in vitro tube formation and migration of RATEC. These results imply that OOEO having anti-angiogenic activity might be useful in preventing angiogenesis-related diseases and in combating cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Cathepsin B-mediated CD18 shedding regulates leukocyte recruitment from angiogenic vessels.

    Science.gov (United States)

    Nakao, Shintaro; Zandi, Souska; Sun, Dawei; Hafezi-Moghadam, Ali

    2018-01-01

    Cathepsin B (CtsB) contributes to atherosclerosis and cancer progression by processing the extracellular matrix and promoting angiogenesis. Although CtsB was reported to promote and reduce angiogenesis, there is no mechanistic explanation that reconciles this apparent discrepancy. CtsB cleaves CD18 from the surface of immune cells, but its contribution to angiogenesis has not been studied. We developed an in vivo technique for visualization of immune cell transmigration from corneal vessels toward implanted cytokines. Wild-type (WT) leukocytes extravasated from limbal vessels, angiogenic stalks, and growing tip vessels and migrated toward the cytokines, indicating immune competence of angiogenic vessels. Compared to WT leukocytes, CtsB-/- leukocytes accumulated in a higher number in angiogenic vessels, but extravasated less toward the implanted cytokine. The accumulated CtsB-/- leukocytes in angiogenic vessels expressed more CD18. CD18-/- leukocytes extravasated later than WT leukocytes. However, once extravasated, CD18-/- leukocytes transmigrated more rapidly than their WT counterparts. These results suggest that, although CD18 facilitates efficient extravasation, outside of the vessel CD18 interaction with the extracellular matrix, it reduced transmigration velocity. Our results reveal an unexpected role for CtsB in leukocyte extravasation and transmigration, which advances our understanding of the complex contribution of CtsB to angiogenesis.-Nakao, S., Zandi, S., Sun, D., Hafezi-Moghadam, A. Cathepsin B-mediated CD18 shedding regulates leukocyte recruitment from angiogenic vessels. © FASEB.

  19. Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

    Directory of Open Access Journals (Sweden)

    Nicolas Guex

    2015-03-01

    Full Text Available Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an

  20. Angiogenic microspheres promote neural regeneration and motor function recovery after spinal cord injury in rats

    Science.gov (United States)

    Yu, Shukui; Yao, Shenglian; Wen, Yujun; Wang, Ying; Wang, Hao; Xu, Qunyuan

    2016-01-01

    This study examined sustained co-delivery of vascular endothelial growth factor (VEGF), angiopoietin-1 and basic fibroblast growth factor (bFGF) encapsulated in angiogenic microspheres. These spheres were delivered to sites of spinal cord contusion injury in rats, and their ability to induce vessel formation, neural regeneration and improve hindlimb motor function was assessed. At 2–8 weeks after spinal cord injury, ELISA-determined levels of VEGF, angiopoietin-1, and bFGF were significantly higher in spinal cord tissues in rats that received angiogenic microspheres than in those that received empty microspheres. Sites of injury in animals that received angiogenic microspheres also contained greater numbers of isolectin B4-binding vessels and cells positive for nestin or β III-tubulin (P spinal cord injury and markedly stimulate angiogenesis and neurogenesis, accelerating recovery of neurologic function. PMID:27641997

  1. On dynamic tumor eradication conditions under combined chemical/anti-angiogenic therapies

    Science.gov (United States)

    Starkov, Konstantin E.

    2018-02-01

    In this paper ultimate dynamics of the five-dimensional cancer tumor growth model at the angiogenesis phase is studied. This model elaborated by Pinho et al. in 2014 describes interactions between normal/cancer/endothelial cells under chemotherapy/anti-angiogenic agents in tumor growth process. The author derives ultimate upper bounds for normal/tumor/endothelial cells concentrations and ultimate upper and lower bounds for chemical/anti-angiogenic concentrations. Global asymptotic tumor clearance conditions are obtained for two versions: the use of only chemotherapy and the combined application of chemotherapy and anti-angiogenic therapy. These conditions are established as the attraction conditions to the maximum invariant set in the tumor free plane, and furthermore, the case is examined when this set consists only of tumor free equilibrium points.

  2. Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type.

    Directory of Open Access Journals (Sweden)

    Mariena J A van der Plas

    Full Text Available BACKGROUND: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MØ-1 and anti-inflammatory/pro-angiogenic macrophages (MØ-2 as these cells play a central role in wound healing. METHODOLOGY/PRINCIPAL FINDINGS: Freshly isolated monocytes were incubated with secretions and GM-CSF or M-CSF for 6 days and then stimulated with LPS or LTA for 18 h. The expression of cell surface molecules and the levels of cytokines, chemokines and growth factors in supernatants were measured. Our results showed secretions to affect monocyte-macrophage differentiation leading to MØ-1 with a partial MØ-2-like morphology but lacking CD163, which is characteristic for MØ-2. In response to LPS or LTA, secretions-differentiated MØ-1 produced less pro-inflammatory cytokines (TNF-alpha, IL-12p40 and MIF than control cells. Similar results were observed for MØ-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MØ-1 and MØ-2 characterized by an altered chemokine production. Secretions led to MØ-2, but not MØ-1, producing enhanced levels of the growth factors bFGF and VEGF, as compared to control cells. The expression of cell-surface receptors involved in LPS/LTA was enhanced by secretions, that of CD86 and HLA-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected. CONCLUSIONS: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

  3. [VEGF as an angiogenic, neurotrophic, and neuroprotective factor].

    Science.gov (United States)

    Namiecińska, Magdalena; Marciniak, Katarzyna; Nowak, Jerzy Z

    2005-01-01

    Vascular endothelial growth factor (VEGF, occurring in several isoforms: VEGF-A, -B, -C, -D) is a well-known endothelial cell mitogen and vascular growth and permeability factor. Recent work done over the last few years has elucidated the important role of VEGF, which participates in the regulation of normal (physiological or therapeutic) and pathological angiogenesis (VEGF-A, VEGF-B) and lymphangiogenesis (VEGF-C, VEGF-D). VEGF has also been implicated in practically every stage of angiogenesis, yet its role in the initiation of new blood vessel creation appears to be the most important. In addition to its role as a key angiogenic factor, VEGF also possesses neurotrophic and neuroprotective activity both in the peripheral and in the central nervous system, exerting a direct action on neurons, Schwann cells, astrocytes, neural stem cells, and microglia. VEGF interacts with three subtypes of VEGF receptors occurring on the cellular membrane known as VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR), and VEGFR-3 (Flt-4). All these receptor types possess an internal tyrosin kinase domain. Interaction of VEGF with particular subtypes of receptors activates a circuit of signaling pathways, e.g. PI3K/Akt, Ras/Raf-MEK/Erk, eNOS/NO, and IP3/Ca2+. These participate in the generation of specific biological responses connected with proliferation, migration, increasing vascular permeability, or promoting endothelial cell survival. Recent findings from experiments performed on animals with experimentally evoked focal cerebral ischemia suggest that the neuroprotective activity of VEGF runs in parallel with its ability to promote neurogenesis and angiogenesis and that these effects may operate independently through multiple mechanisms. The above-mentioned three major features characterizing the neurobiological activity of VEGF, i.e. neuroprotection, neurogenesis, and angiogenesis, together with their possible functional link(s), provide the rationale for considering VEGF-based therapy as a

  4. Augmented Angiogenic Factors Expression via FP Signaling Pathways in Peritoneal Endometriosis.

    Science.gov (United States)

    Rakhila, Halima; Al-Akoum, Mahera; Doillon, Charles; Lacroix-Pépin, Nicolas; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali; Pouliot, Marc

    2016-12-01

    Angiogenesis is required for ectopic endometrial tissue growth. Our previous studies showed that prostaglandin F2α (PGF2α) biosynthetic enzymes and receptor were markedly elevated in endometriotic lesions and that PGF2α is a potent angiogenic factor in endothelial cells. We sought to determine whether or not the F-prostanoid receptor modulates angiogenesis in ectopic stromal cells. Release of angiogenic factors by ectopic endometrial stromal cell primary cultures stimulated with PGF2αand exposed to agents that target PGF2α signaling was assessed. The study was conducted in an immunology laboratory at the Centre Hospitalier Universitaire (Québec City) medical research center. Women found to have peritoneal endometriosis during laparoscopy were included in this study. Prostaglandin E2, PGF2α, vascular endothelial cell growth factor, and CXC chemokine ligand 8 mRNA and protein; FP prostanoid receptor expression. PGF2α markedly up-regulated prostaglandin E2, CXC chemokine ligand 8 and vascular endothelial cell growth factor secretion in endometriotic cells. This effect was suppressed in the presence of a specific F-prostanoid antagonist (AL8810) and its signaling pathway was dependent on F-prostanoid receptor variant. PGF2α can exert its proliferative and angiogenic activities either directly by stimulating endothelial cell proliferation, migration and angiogenesis through F-prostanoid receptor, or indirectly, by stimulating endometriotic stromal cells to produce potent angiogenic factors through either receptor variant. These results show for the first time that PGF2α exerts an angiogenic effect on ectopic stromal cells, inducing the secretion of major angiogenic factors via different F-prostanoid signaling pathways. This study suggests a new interpretation of the mechanism underlying endometriosis development involving PGF2α in endometriosis-associated angio-inflammatory changes.

  5. Differential angiogenic gene expression in TP53 wild-type and mutant ovarian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Brittany Anne Davidson

    2014-06-01

    Full Text Available Objectives: Underlying mechanisms regulating angiogenesis in ovarian cancer have not been completely elucidated. Evidence suggests that the TP53 tumor suppressor pathway and tumor microenvironment play integral roles. We utilized microarray technology to study the interaction between TP53 mutational status & hypoxia on angiogenic gene expression.Methods: Affymetrix U133A arrays were analyzed for angiogenic gene expression in 19 ovarian cancer cell lines stratified both by TP53 mutation status and A2780 wild-type (wt TP53 vs. mutated (m TP53 cell lines after treatment under hypoxic conditions or with ionizing radiation. Results: Twenty-eight differentially expressed angiogenic genes were identified in the mTP53 cell lines compared to wtTP53 lines. Five genes were upregulated in mTP53 cells: 40% involved in extracellular matrix (ECM degradation (MMP10/15 and 60% in angiogenesis (FGFR3/VEGFA/EPHB4. Twenty-three genes were upregulated in wtTP53: nearly 22% were ECM constituents or involved in ECM degradation; over 40% were growth factors or mediators of angiogenesis. Five genes were upregulated in the A2780mTP53 cells: 40% involved in ECM remodeling (MMP10, ADAMTS1, 40% with pro-angiogenic activity (EFNB2, F2R, and 20% with anti-angiogenic properties (ADAMTS1. Three genes were upregulated in hypoxia treated cells compared to controls: 1 with anti-angiogenic activity (ANGPTL4 and 2 with pro-angiogenic activity (VEGFA, EFNA3. No significant gene fold changes were noted after exposure to radiation.Four genes continued to demonstrate significant differential expression (p≤0.05 after adjusting for multiple comparisons. These genes included ENG upregulation in wild-type lines and upregulation of FGF-20, ADAMTS1 & MMP10 in mTP53 lines.Conclusions: Our exploratory findings indicate that non-overlapping angiogenic pathways may be altered by TP53 mutations and hypoxic conditions in ththe tumor microenvironment. Further evaluation is needed for confirmation.

  6. Tumor-targeting templated silica nanoparticles as a dual-drug delivery system for anti-angiogenic ovarian cancer therapy

    Science.gov (United States)

    Zheng, Tianying; Wang, Aijun; Hu, Dongyan; Wang, Yonggang

    2017-01-01

    The present study indicated the successful construction of a silica nanoparticle (SLN)-based drug delivery system (DDS) for the tumor-targeted co-delivery of two anti-angiogenic drugs, candesartan (CD) and trastuzumab (Tra), for ovarian cancer therapy via different anti-angiogenic mechanisms using hyaluronic acid (HA)/Tra/CD/SLNs. In vitro and in vivo anti-angiogenic assays indicated that CD and Tra exert beneficial functions on suppressing cancer angiogenesis, and exhibited significantly enhanced effects compared with the angiotensin stimulated group (PTra co-delivery also significantly increased the anti-angiogenic effect compared with applying either drug alone (PTra/CD/SLNs may be a preferable formulation for anti-angiogenic ovarian cancer therapy. PMID:28962137

  7. Comprehensive review of the evidence regarding the effectiveness of community-based primary health care in improving maternal, neonatal and child health: 7. shared characteristics of projects with evidence of long-term mortality impact.

    Science.gov (United States)

    Perry, Henry B; Rassekh, Bahie M; Gupta, Sundeep; Freeman, Paul A

    2017-06-01

    There is limited evidence about the long-term effectiveness of integrated community-based primary health care (CBPHC) in improving maternal, neonatal and child health. However, the interventions implemented and the approaches used by projects with such evidence can provide guidance for ending preventable child and maternal deaths by the year 2030. A database of 700 assessments of the effectiveness of CBPHC in improving maternal, neonatal and child health has been assembled, as described elsewhere in this series. A search was undertaken of these assessments of research studies, field project and programs (hereafter referred to as projects) with more than a single intervention that had evidence of mortality impact for a period of at least 10 years. Four projects qualified for this analysis: the Matlab Maternal Child Health and Family Planning (MCH-FP) P in Bangladesh; the Hôpital Albert Schweitzer in Deschapelles, Haiti; the Comprehensive Rural Health Project (CRHP) in Jamkhed, India; and the Society for Education, Action and Research in Community Health (SEARCH) in Gadchiroli, India. These four projects have all been operating for more than 30 years, and they all have demonstrated reductions in infant mortality, 1- to 4-year mortality, or under-5 mortality for at least 10 years. They share a number of characteristics. Among the most notable of these are: they provide comprehensive maternal, child health and family planning services, they have strong community-based programs that utilize community health workers who maintain regular contact with all households, they have develop strong collaborations with the communities they serve, and they all have strong referral capabilities and provide first-level hospital care. The shared features of these projects provide guidance for how health systems around the world might improve their effectiveness in improving maternal, neonatal and child health. Strengthening these features will contribute to achieving the goal of

  8. Share your Sweets

    DEFF Research Database (Denmark)

    Byrnit, Jill; Høgh-Olesen, Henrik; Makransky, Guido

    2015-01-01

    All over the world, humans (Homo sapiens) display resource-sharing behavior, and common patterns of sharing seem to exist across cultures. Humans are not the only primates to share, and observations from the wild have long documented food sharing behavior in our closest phylogenetic relatives...

  9. Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study

    NARCIS (Netherlands)

    P.K. Bautista-Niño (Paula K.); M.J. Tielemans (Myrte); S. Schalekamp-Timmermans (Sarah); J.C.J. Steenweg-de Graaff (Jolien); A. Hofman (Albert); H.W. Tiemeier (Henning); V.W.V. Jaddoe (Vincent); E.A.P. Steegers (Eric); J.F. Felix (Janine); O.H. Franco (Oscar)

    2015-01-01

    textabstractIntroduction Angiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish

  10. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival

    DEFF Research Database (Denmark)

    Andersen, Niels Frost; Standal, Therese; Nielsen, Johan Lanng

    2005-01-01

    Angiogenesis is a complex process involved in the proliferation and metastasis of malignant tumours, and partly triggered by the secretion of various angiogenic factors by tumour cells or cells in the stromal environment. We investigated the correlation between bone marrow angiogenesis, estimated...

  11. Anti-angiogenic activity of Morinda citrifolia extracts and its chemical constituents.

    Science.gov (United States)

    Beh, Hooi-Kheng; Seow, Lay-Jing; Asmawi, Mohd Zaini; Abdul Majid, Amin Malik Shah; Murugaiyah, Vikneswaran; Ismail, Norhayati; Ismail, Zhari

    2012-01-01

    Morinda citrifolia L. has been used for the treatment of a wide variety of diseases, including cancer. This study was undertaken to evaluate the anti-angiogenic effect of M. citrifolia fruits and leaves. Anti-angiogenic activity was evaluated in vivo using the chick chorioallantoic membrane assay. Bioactivity-guided fractionation and isolation were performed to identify the active constituent, and high-performance liquid chromatography analysis was then used to quantify the amount of this active constituent in the active extracts and fraction. The methanol extracts of fruits and leaves of M. citrifolia and the subsequent chloroform fraction of the fruit methanolic extract were found to have potential anti-angiogenic activity and were more potent compared to suramin. Scopoletin was identified as one of the chemical constituents that may be partly responsible for the anti-angiogenic activity of M. citrifolia fruits. The present findings further support the use of M. citrifolia in cancer or other pathological conditions related to angiogenesis.

  12. In vitro and in vivo anti-angiogenic activity of girinimbine isolated from Murraya koenigii

    Directory of Open Access Journals (Sweden)

    Iman V

    2015-03-01

    Full Text Available Venoos Iman,1 Hamed Karimian,1 Syam Mohan,2 Yahya Hasan Hobani,2 Mohamed Ibrahim Noordin,1 Mohd Rais Mustafa,3 Suzita Mohd Noor41Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Center, University of Jazan, Jazan, Saudi Arabia; 3Department of Pharmacology, Centre for Natural Products and Drug Discovery (CENAR, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Girinimbine is a carbazole alkaloid isolated from the stem bark and root of Murraya koenigii. Here we report that girinimbine is an inhibitor of angiogenic activity both in vitro and in vivo. MTT results showed that girinimbine inhibited proliferation of human umbilical vein endothelial cells, while results from endothelial cell invasion, migration, tube formation, and wound healing assays demonstrated significant time- and dose-dependent inhibition by girinimbine. A proteome profiler array done on girinimbine-treated human umbilical vein endothelial cells showed that girinimbine had mediated regulation of pro-angiogenic and anti-angiogenic proteins. The anti-angiogenic potential of girinimbine was also evidenced in vivo in the zebrafish embryo model wherein girinimbine inhibited neo vessel formation in zebrafish embryos following 24 hours of exposure. Together, these results showed that girinimbine could effectively suppress angiogenesis, suggestive of its therapeutic potential as a novel angiogenesis inhibitor. Keywords: angiogenesis, inhibitor, carbazole alkaloid, zebrafish

  13. Pericardial fat pad tissue produces angiogenic factors for healing the bronchial stump.

    Science.gov (United States)

    Shoji, Fumihiro; Yano, Tokujiro; Miura, Naoko; Morodomi, Yosuke; Yoshida, Tsukihisa; Onimaru, Mitsuho; Maehara, Yoshihiko

    2011-09-01

    Maintaining blood flow in and supplying various anti-inflammatory or angiogenic cytokines to the bronchial stump are very important factors involved in its healing. Pericardial fat pad tissue samples surgically obtained from 20 patients were assessed, and their angiogenic ability was investigated. The messenger RNA level of all angiogenic cytokines, including vascular endothelial growth factor, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-A (PDGF-A), angiopoietin-1 (Ang-1), Ang-2 and hepatocyte growth factor (HGF) were detected in the pericardial fat pad tissue. The protein levels of all cytokines except PDGF-A increased with time from day one to day seven after primary culture of the pericardial fat pad tissue. In particular, both HGF and Ang-2 protein levels on day seven were significantly higher than those on day one (P=0.0475 and P=0.0417, respectively). On the other hand, the protein level of FGF-2 decreased in time and was significantly lower on day seven than on day one (P=0.0296). The present study demonstrated the angiogenic ability of the pericardial fat pad. These results suggest that reinforcement of the bronchial stump by the pericardial fat pad is a worthwhile and justified procedure, and may prevent bronchopleural fistula after pulmonary resections.

  14. Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors.

    Directory of Open Access Journals (Sweden)

    Devandir Antonio de Souza Junior

    Full Text Available Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7 in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.

  15. The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

    Science.gov (United States)

    Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

    2015-04-01

    Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

  16. Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences.

    NARCIS (Netherlands)

    Broxterman, H.J.; Lankelma, J.; Hoekman, K.

    2003-01-01

    Intrinsic resistance to anticancer drugs, or resistance developed during chemotherapy, remains a major obstacle to successful treatment. This is the case both for resistance to cytotoxic agents, directed at malignant cells, and for resistance to anti-angiogenic agents, directed at non-malignant

  17. Peptide-targeted PEG-liposomes in anti-angiogenic therapy

    NARCIS (Netherlands)

    Janssen, A.P.C.A.; Schiffelers, R.M.; ten Hagen, T.L.M.; Koning, G.A; Leegte - Schraa, Astrid; Kok, R.J; Storm, G.; Molema, Ingrid

    2003-01-01

    Peptides with the RGD amino acid sequence show affinity for the alpha(v)beta(3) integrin, an integrin which is over-expressed on angiogenic endothelium and involved in cell adhesion. A peptide with the sequence ATWLPPR has been demonstrated to show affinity for the vascular endothelial growth factor

  18. The anti-angiogenic and antibacterial effect of Tinomiscium philippinense Miers. (Menispermaceae leaf extract

    Directory of Open Access Journals (Sweden)

    Sheryl Rena-Aguila

    2016-01-01

    Full Text Available Objective: To determine the toxicity profile, anti-angiogenic and antibacterial activity of the crude and semi-crude leaf extracts of Tinomiscium philippinense (T. philippinense. Methods: The leaves of T. philippinense were extracted with methanol and partitioned with solvents of different polarities, namely, hexane, dichloromethane and butanol. The extracts were subjected to duck chorioallantoic membrane assay to establish its anti-angiogenic property. Microwell assay was utilized to determine the minimum inhibitory concentration and minimum bactericidal concentration of the different extracts of the plant. Results: The dichloromethane leaf extract of T. philippinense at 1 000 µg/disc showed the highest anti-angiogenic activity with 37.46% inhibition. All the fractions exhibited a bacteriostatic and bactericidal effect on the three bacterial strains with Pseudomonas aeruginosa, a Gram negative lactose fermenter exhibiting a higher sensitivity to dichloromethane semi-crude extract among the treatment groups. For the toxicity test, no mortality and no change in behavior were observed in the Sprague-Dawley rats 14 days after the oral administration of the plant extracts. The methanolic leaf extract of T. philippinense is non-toxic at a maximum dose of 5000 mg/kg. Conclusions: The dichloromethane leaf extract of T. philippinense is a potential antiangiogenic endemic plant species. This plant extract is also a potential antibacterial candidate as determined by microwell assay. The anti-angiogenic and antibacterial activity of the plant may be attributed to the essential oil, steroid, flavonoid, sterol and triterpene content of the plant.

  19. Investigation of In-Vitro Biological Behavior and Pro-Angiogenic ...

    African Journals Online (AJOL)

    Prof. Ogunji

    Investigation of In-Vitro Biological Behavior and Pro-Angiogenic. Potential of Baicalein as ... Current research is tackling the problem of vascularization with four distinct strategies, all of which have demonstrated ... To overcome this problem a lot of research effort has gone into the search for hypoxia mimics. (Xia et al., 2009, ...

  20. The Anti-Proliferative and Anti-Angiogenic Effect of the Methanol Extract from Brittle Star

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2015-05-01

    Full Text Available Background: Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. Methods: The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 μg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (p<0.05. Results: Results illustrated that the brittle star extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (p<0.05. Conclusion: These finding revealed the anti-angiogenic effects of brittle star methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

  1. Anti-angiogenic Activity and Mechanism of Sesquiterpene Lactones from Centipeda minima.

    Science.gov (United States)

    Huang, Weihuan; Yu, Xiaobin; Liang, Ning; Ge, Wei; Kwok, Hin Fai; Lau, Clara Bik-San; Li, Yaolan; Chung, Hau Yin

    2016-04-01

    Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti-angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti-angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1-15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1-8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9-15) showed little effect. Among the active ones, 6-O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 µM. Further study using the Tg (fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6-O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6-O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent.

  2. Angiogenic factors are increased in circulating granulocytes and CD34+ cells of myeloproliferative neoplasms.

    Science.gov (United States)

    Subotički, Tijana; Mitrović Ajtić, Olivera; Beleslin-Čokić, Bojana B; Nienhold, Ronny; Diklić, Miloš; Djikić, Dragoslava; Leković, Danijela; Bulat, Tanja; Marković, Dragana; Gotić, Mirjana; Noguchi, Constance T; Schechter, Alan N; Skoda, Radek C; Čokić, Vladan P

    2017-02-01

    It has been shown that angiogenesis and inflammation play an important role in development of most hematological malignancies including the myeloproliferative neoplasm (MPN). The aim of this study was to investigate and correlate the levels of key angiogenic molecules such as hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral blood and bone marrow cells of MPN patients, along with JAK2V617F mutation allele burden and effects of therapy. HIF-1α and VEGF gene expression were decreased, while eNOS mRNA levels were increased in granulocytes of MPN patients. Furthermore, positively correlated and increased VEGF and eNOS protein levels were in negative correlation with HIF-1α levels in granulocytes of MPN patients. According to immunoblotting, the generally augmented angiogenic factors demonstrated JAK2V617F allele burden dependence only in granulocytes of PMF. The angiogenic factors were largely reduced after hydroxyurea therapy in granulocytes of MPN patients. Levels of eNOS protein expression were stimulated by Calreticulin mutations in granulocytes of essential thrombocythemia. Immunocytochemical analyses of CD34+ cells showed a more pronounced enhancement of angiogenic factors than in granulocytes. Increased gene expression linked to the proinflammatory TGFβ and MAPK signaling pathways were detected in CD34+ cells of MPN patients. In conclusion, the angiogenesis is increased in several cell types of MPN patients supported by the transcriptional activation of inflammation-related target genes, and is not limited to bone marrow stroma cells. It also appears that some of the benefit of hydroxyurea therapy of the MPN is mediated by effects on angiogenic factors. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  4. Using the angiogenic factors sFlt-1 and PlGF with Doppler ultrasound of the uterine artery for confirming preeclampsia.

    Science.gov (United States)

    Bahlmann, Franz; Al Naimi, Ammar

    2016-11-01

    The aim of this study is to assess the value of the angiogenic factors for diagnosing preeclampsia and predicting the severity of manifestation. A secondary aim is assessing the combination of the uterine artery Doppler with the angiogenic factors for improving the diagnostic power. This is a prospective single center study in a tertiary referral hospital. This study includes 728 individual patients. Inclusion criteria were singleton pregnancies, a referral to the hospital with suspicion of preeclampsia and any one or combination of the following symptoms: headache, upper abdominal pain, edema, and hypertension. Patients with complications that would affect the course of the pregnancy, such as placenta praevia, premature preterm rupture of membranes, breech presentation, and fetal chromosomal or structural anomalies, were excluded from the study. Blood samples collection and uterine artery Doppler ultrasound were performed at time of recruitment. The differences in sFlt-1, PlGF, and their quotient among normal collective and patients with preeclampsia were analyzed. Doppler ultrasound was performed by one of four highly qualified sonographers. Wilcoxon-Mann-Whitney U test, Spearman's rank correlation, receiver operating characteristic curves, Chi-square test, and logistic regression were used in the analysis. A total of 1003 individual samples for the angiogenic factors were included in the analysis. 584 out of the recruited 728 patients had follow-up data with delivery information at the study hospital. Patients with preeclampsia show a significant increase in sFlt-1, which directly correlate with the increased severity of manifestation (Spearman's ρ 0.49). The sFlt-1 cut-off value of 5424 pg/ml confirms preeclampsia with 83.7 % sensitivity, 68.1 % specificity, and 24 % misclassification rate. Preeclampsia patients also show a significant decrease in PlGF, which negatively correlates with the increased severity of manifestation (Spearman's ρ -0.39). A Pl

  5. Relating Shared Vision Components To Thai Public School Performance

    National Research Council Canada - National Science Library

    Sooksan Kantabutra

    2012-01-01

      While shared vision is core to the prevailing vision-based leadership theories, little is known about the relationship between performance and the characteristics of visions shared between leader and followers...

  6. Share Your Values

    Science.gov (United States)

    ... Español Text Size Email Print Share Share Your Values Page Content Article Body Today, teenagers are bombarded ... mid-twenties. The Most Effective Way to Instill Values? By Example Your words will carry more weight ...

  7. Sharing is sparing

    NARCIS (Netherlands)

    P.Y. Kocher; U. Gaudenz; P. Troxler; Dr. P. Troxler; P. Wolf

    2014-01-01

    The commitment of the Fab Lab community to participate in processes of commons-based knowledge production thus also includes global knowledge sharing. For sharing back into the global commons, new knowledge needs however to be documented in a way that allows to share it by the means of information

  8. Gene expression analysis of angiogenic markers Robo1, Robo4 and the Slit2 in colorectal cancer

    OpenAIRE

    Döbler, Oliver

    2011-01-01

    Introduction: Colorectal cancer is one of the most common malignant tumors and in Germany the second most common cause of cancer death. A key factor in the progression of malignant neoplasms is the supply of oxygen and nutrients by connecting to the body's vascular system. The activation of angiogenesis by toggling the "angiogenic switch"is controlled by different signal transduction pathways. Monoclonal antibodies against pro-angiogenic factors are used already in the treatment of colorec...

  9. Protein kinase D1 signaling in angiogenic gene expression and VEGF-mediated angiogenesis

    Directory of Open Access Journals (Sweden)

    Bin eRen MD, Phd, FAHA

    2016-05-01

    Full Text Available Protein kinase D 1 (PKD-1 is a signaling kinase important in fundamental cell functions including migration, proliferation and differentiation. PKD-1 is also a key regulator of gene expression and angiogenesis that is essential for cardiovascular development and tumor progression. Further understanding molecular aspects of PKD-1 signaling in the regulation of angiogenesis may have translational implications in obesity, cardiovascular disease and cancer. The author will summarize and provide the insights into molecular mechanisms by which PKD-1 regulates transcriptional expression of angiogenic genes, focusing on the transcriptional regulation of CD36 by PKD-1-FoxO1 signaling axis along with the potential implications of this axis in arterial differentiation and morphogenesis. He will also discuss a new concept of dynamic balance between proangiogenic and antiangiogenic signaling in determining angiogenic switch, and stress how PKD-1 signaling regulates VEGF signaling-mediated angiogenesis.

  10. Physicochemical/photophysical characterization and angiogenic properties of Curcuma longa essential oil.

    Science.gov (United States)

    Araújo, Lilhian A; Araújo, Rafael G M; Gomes, Flávia O; Lemes, Susy R; Almeida, Luciane M; Maia, Lauro J Q; Gonçalves, Pablo J; Mrué, Fátima; Silva-Junior, Nelson J; Melo-Reis, Paulo R DE

    2016-01-01

    This study analyzed the physicochemical and photophysical properties of essential oil of Curcuma longa and its angiogenic potential. The results showed that curcumin is the main fluorescent component present in the oil, although the amount is relatively small. The experimental chorioallantoic membrane model was used to evaluate angiogenic activity, showing a significant increase in the vascular network of Curcuma longa and positive control groups when compared to the neutral and inhibitor controls (P Curcuma longa essential oil and the positive control (P >0.05). Histological analysis showed extensive neovascularization, hyperemia and inflammation in the positive control group and Curcuma longa when compared to other controls (P Curcuma longa oil showed considerable proangiogenic activity and could be a potential compound in medical applications.

  11. Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling

    Directory of Open Access Journals (Sweden)

    Kei Sugihara

    2015-12-01

    Full Text Available Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.

  12. Urban sharing culture

    DEFF Research Database (Denmark)

    Fjalland, Emmy Laura Perez

    In urban areas sharing cultures, services and economies are rising. People share, rent and recycle their homes, cars, bikes, rides, tools, cloths, working space, knowhow and so on. The sharing culture can be understood as mobilities (Kesselring and Vogl 2013) of goods, values and ideas reshaping...... problems and side effects from concentration of consumption and contamination; and due to the shift from ownership to access it change our basic social cultural norms (Sayer 2005; Sayer 2011) about the ‘good’ life and social status (Freudendal-Pedersen 2007), commons and individuality, responsibility...... and trust. (Thomsen 2013; Bauman 2000; Beck 1992; Giddens 1991). The sharing economy is currently hyper trendy but before claiming capitalism as dead we need to understand the basics of the sharing economies and cultures asking who can share and what will we share. Furthermore it is crucial to study what...

  13. Influence of Echinacea purpurea intake during pregnancy on fetal growth and tissue angiogenic activity.

    Directory of Open Access Journals (Sweden)

    Joanna Chorostowska-Wynimko

    2008-04-01

    Full Text Available The process of angiogenesis and control of blood vessels sprouting are fundamental to human health, as they play key roles in many physiological and pathological conditions. Intake of different pharmaceuticals with antiangiogenic activity by pregnant women may lead to severe developmental disturbances as it was described in case of thalidomide. It may also cause immunomodulatory effects as it was shown for antibiotics, theobromine, caffeic acid or catechins on the pregnant mice model. At present, Echinacea purpurea-based phytoceuticals are among the most popular herbals in the marketplace. Many compounds of Echinacea extracts (polysaccharides, alkamides, polyphenols, glycoproteins exert immunomodulatory, anti-oxidative and anti-inflammatory activity. Echinacea is one of the most powerful and effective remedies against many kinds of bacterial and viral infections. In previous studies we shown significant inhibitory effect of the Echinacea purpurea based remedy on tumour angiogenic activity using cutaneous angiogenesis test, and an inhibitory effect on L-1 sarcoma growth was observed . The aim of the present study was to establish whether pharmaceuticals containing alcoholic extracts of Echinacea purpurea given to pregnant mice influence angiogenic activity and tissue VEGF and bFGF production of their fetuses. We showed that angiogenic activity of tissue homogenates was increased in Esberitox group and diminished in case of Immunal forte as compared to standard diet group. In case of Echinapur group we did not find significant differences in angiogenic activity. VEGF and bFGF concentration were lower in all groups compared to the control. In the case of Echinapur and Esberitox number of fetuses in one litter were slightly lower as compared to control group, but the difference is on the border of statistical significance. In conclusion, there is some possibility that pharmaceuticals containing Echinacea purpurea might influence fetal development in

  14. In vitro and in vivo anti-angiogenic activities of Panduratin A.

    Directory of Open Access Journals (Sweden)

    Siew-Li Lai

    Full Text Available BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA, a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays. METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs with IC(50 value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2 secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.

  15. Osteogenic and Angiogenic Response to Calcium Silicate-based Endodontic Sealers.

    Science.gov (United States)

    Costa, Fábio; Sousa Gomes, Pedro; Fernandes, Maria Helena

    2016-01-01

    Calcium silicate-based endodontic sealers are reported to favor the regeneration of periradicular tissues, a process requiring concerted osteogenic and angiogenic events. This study compared 4 calcium silicate-based sealers for the effects of their extracts on osteogenic and angiogenic cell behavior. Extracts from ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), MTA Plus (Prevest Denpro Limited, Jammu City, India), MTA Fillapex (Angelus, Londrina, PR, Brazil), and Biodentine (Septodont, Saint-Maur-des-Fosses, France) were prepared from freshly mixed sealers (0.1 g/cm(2)/mL extraction medium) and diluted (1:2-1:20). The sealers were compared for the dose- and time-dependent effects on the proliferation and differentiation of human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs). An ex vivo osteogenic assay (regeneration of neonatal mice parietal bone defects) and an in vivo angiogenesis assay (chorioallantoic membrane assay) were performed. Diluted extracts from MTA ProRoot and MTA Plus had evident stimulatory effects on the proliferation of hMSCs, alkaline phosphatase activity, and ex vivo regeneration of bone defects. They also increased HUVEC growth; allowed normal tubularlike network organization; and, in vivo, did not affect angiogenesis. Comparatively, Biodentine also elicited a favorable response on hMSCs and HUVECs, but the overall osteogenic and angiogenic outcome was slightly lower. MTA Fillapex exhibited the highest toxicity in hMSCs and HUVECs and, unlike the other sealers, only allowed a partial regeneration of bone defects. The sealers caused dose- and time-dependent effects on the osteoblastic and endothelial response, eliciting similar cytocompatibility profiles. Results suggest that the induction of both osteogenic and angiogenic events may contribute to the sealers' regenerative outcome. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues.

    Science.gov (United States)

    Lambeng, Nathalie; Wallez, Yann; Rampon, Christine; Cand, Francine; Christé, Georges; Gulino-Debrac, Danielle; Vilgrain, Isabelle; Huber, Philippe

    2005-02-18

    Vascular endothelial-cadherin (VE-cadherin) plays a key role in angiogenesis and in vascular permeability. The regulation of its biological activity may be a central mechanism in normal or pathological angiogenesis. VE-cadherin has been shown to be phosphorylated on tyrosine in vitro under various conditions, including stimulation by VEGF. In the present study, we addressed the question of the existence of a tyrosine phosphorylated form of VE-cadherin in vivo, in correlation with the quiescent versus angiogenic state of adult tissues. Phosphorylated VE-cadherin was detected in mouse lung, uterus, and ovary but not in other tissues unless mice were injected with peroxovanadate to block protein phosphatases. Remarkably, VE-cadherin tyrosine phosphorylation was dramatically increased in uterus and ovary, and not in other organs, during PMSG/hCG-induced angiogenesis. In parallel, we observed an increased association of VE-cadherin with Flk1 (VEGF receptor 2) during hormonal angiogenesis. Additionally, Src kinase was constitutively associated with VE-cadherin in both quiescent and angiogenic tissues and increased phosphorylation of VE-cadherin-associated Src was detected in uterus and ovary after hormonal treatment. Src-VE-cadherin association was detected in cultured endothelial cells, independent of VE-cadherin phosphorylation state and Src activation level. In this model, Src inhibition impaired VEGF-induced VE-cadherin phosphorylation, indicating that VE-cadherin phosphorylation was dependent on Src activation. We conclude that VE-cadherin is a substrate for tyrosine kinases in vivo and that its phosphorylation, together with that of associated Src, is increased by angiogenic stimulation. Physical association between Flk1, Src, and VE-cadherin may thus provide an efficient mechanism for amplification and perpetuation of VEGF-stimulated angiogenic processes.

  17. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Evaluation of the in vitro and in vivo angiogenic effects of exendin-4

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hye-Min [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Kang, Yujung; Chun, Hyung J. [Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT (United States); Jeong, Joo-Won [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Park, Chan, E-mail: psychan@khu.ac.kr [Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2013-04-26

    Highlights: •We investigated the effects of exendin-4 on the angiogenic process. •Exendin-4 increased migration, sprouting, and tube formation by HUVECs in in vitro. •Exendin-4 increased sprouts in aortic rings and induced new vessels in Matrigel in in vivo. •Exendin-4 may be of potential use for the treatment of vascular complications of diabetes. -- Abstract: Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was reported to induce the proliferation of endothelial cells. However, its angiogenic effect on endothelial cells has not been clearly evaluated. Therefore, we investigated the effects of exendin-4 on the angiogenic process with respect to migration, sprouting, and neovascularization using in vitro and in vivo assays. Treatment with exendin-4 increased the migration of human umbilical vein endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays. These responses were abolished by co-treatment with exendin (9–39), a GLP-1 receptor antagonist, which suggests that exendin-4 regulates endothelial cell migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo assay, treatment of aortic rings with exendin-4 increased the sprouting of endothelial cells. Exendin-4 also significantly increased the number of new vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in vivo assays and provide a mechanism underlying the cardioprotective effects of exendin-4.

  19. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents. Copyright © 2014. Published by Elsevier B.V.

  20. Gestation dependant changes in angiogenic factors and their associations with fetal growth measures in normotensive pregnancy.

    Directory of Open Access Journals (Sweden)

    Deepali Sundrani

    Full Text Available BACKGROUND: Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight. METHOD: Ninety two pregnant women were followed at three different time points: 16-20 weeks, 26-30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA kits. RESULTS: Maternal plasma VEGF levels increased (p<0.01 till the second time point and decreased (p<0.05 up to delivery while plasma sFlt-1 levels increased (p<0.01 at delivery. PlGF levels peaked (p<0.01 at second time point and decreased (p<0.01 at delivery. Cord plasma VEGF levels were higher (p<0.01 and sFlt-1 levels were lower (p<0.01 as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively, while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05 with birth weight. CONCLUSION: Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16-20 weeks may be predictive of birth weight in healthy term pregnancies.

  1. An in vitro cord formation assay identifies unique vascular phenotypes associated with angiogenic growth factors.

    Directory of Open Access Journals (Sweden)

    Beverly L Falcon

    Full Text Available Vascular endothelial growth factor (VEGF plays a dominant role in angiogenesis. While inhibitors of the VEGF pathway are approved for the treatment of a number of tumor types, the effectiveness is limited and evasive resistance is common. One mechanism of evasive resistance to inhibition of the VEGF pathway is upregulation of other pro-angiogenic factors such as fibroblast growth factor (FGF and epidermal growth factor (EGF. Numerous in vitro assays examine angiogenesis, but many of these assays are performed in media or matrix with multiple growth factors or are driven by VEGF. In order to study angiogenesis driven by other growth factors, we developed a basal medium to use on a co-culture cord formation system of adipose derived stem cells (ADSCs and endothelial colony forming cells (ECFCs. We found that cord formation driven by different angiogenic factors led to unique phenotypes that could be differentiated and combination studies indicate dominant phenotypes elicited by some growth factors. VEGF-driven cords were highly covered by smooth muscle actin, and bFGF-driven cords had thicker nodes, while EGF-driven cords were highly branched. Multiparametric analysis indicated that when combined EGF has a dominant phenotype. In addition, because this assay system is run in minimal medium, potential proangiogenic molecules can be screened. Using this assay we identified an inhibitor that promoted cord formation, which was translated into in vivo tumor models. Together this study illustrates the unique roles of multiple anti-angiogenic agents, which may lead to improvements in therapeutic angiogenesis efforts and better rational for anti-angiogenic therapy.

  2. Imaging Tumor Vascularity and Response to Anti-Angiogenic Therapy Using Gaussia Luciferase.

    Science.gov (United States)

    Kantar, Rami S; Lashgari, Ghazal; Tabet, Elie I; Lewandrowski, Grant K; Carvalho, Litia A; Tannous, Bakhos A

    2016-05-20

    We developed a novel approach to assess tumor vascularity using recombinant Gaussia luciferase (rGluc) protein and bioluminescence imaging. Upon intravenous injection of rGluc followed by its substrate coelenterazine, non-invasive visualization of tumor vascularity by bioluminescence imaging was possible. We applied this method for longitudinal monitoring of tumor vascularity in response to the anti-angiogenic drug tivozanib. This simple and sensitive method could be extended to image blood vessels/vasculature in many different fields.

  3. Angiogenic effect of platelet-rich plasma combined with gelatin hydrogel granules injected into murine subcutis.

    Science.gov (United States)

    Kakudo, Natsuko; Morimoto, Naoki; Ogawa, Takeshi; Hihara, Masakatsu; Notodihardjo, Priscilla Valentin; Matsui, Makoto; Tabata, Yasuhiko; Kusumoto, Kenji

    2017-07-01

    Platelet-rich plasma (PRP), which contains highly concentrated platelets, is produced by centrifuging whole blood. It is a safe and readily available source of a wide range of growth factors necessary for angiogenesis. Gelatin hydrogel granules have been designed and prepared for the controlled release of many growth factors. The angiogenic effect of human PRP was examined in vitro, and the effect of its subcutaneous injection with gelatin hydrogel granules into murine subcutis was evaluated. Human PRP was prepared using a double-spin method. The concentration of growth factors and the platelet count were examined in PRP and in vitro, and the angiogenic activity of human umbilical vein endothelial cells (HUVECs) in co-culture with human dermal fibroblast cells (NHDFs) in the presence and absence of PRP was evaluated. Then, in vivo, PRP, either free or with gelatin hydrogel granules, was injected subcutaneously into tiebacks on mice. Using a microscope and Kurabo angiogenesis image analyser software, the area containing newly formed capillaries was evaluated histologically and the microvascular network score was calculated. PRP was shown to contain high concentrations of PDGF, VEGF and TGFβ and had an angiogenic effect on the co-culture system. PRP with gelatin hydrogel granules significantly enlarged the area containing newly formed capillaries and promoted the microvascular network in murine subcutaneous tissue. PRP encapsulated in gelatin hydrogel microspheres shows promise for enhancing angiogenic effects in murine subcutis and could represent a potential therapeutic combination for the treatment of ischaemic disorders. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Angiogenic response to passive movement and active exercise in individuals with peripheral arterial disease

    DEFF Research Database (Denmark)

    Høier, Birgitte; Walker, Meegan; Passos, Madla

    2013-01-01

    Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared to healthy control subjects. Twen...... increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor trombospondin-1 protein (TSP-1) was markedly higher (P...

  5. Induction of Pro-Angiogenic Factors by Pregnancy-Specific Glycoproteins and Studies on Receptor Usage

    Science.gov (United States)

    2008-01-01

    the surface of EVTs [183]. In normal 126 pregnancy, the KIR—HLA interaction is thought to prevent uNK cells from becoming cytotoxic against the...trophoblasts may prevent optimal trophoblast invasion [183]. Currently, it is unknown if PSGs exert effects on uNK cells; however, we can...Karumanchi, Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia . Hypertension, 2005. 46(5): p. 1077-85. 10. Carter

  6. Angiogenesis and Diabetes: Different Responses to Pro-Angiogenic Factors in the Chorioallantoic Membrane Assay

    OpenAIRE

    Di Marco, Giovana S; Alam, Antoine; Dol, Frédéric; Corvol, Pierre; Gasc, Jean-Marie; Larger, Etienne

    2008-01-01

    Hyperglycemia induces defects in angiogenesis without alteration in the expression of major vascular growth factors in the chicken chorioallantoic membrane (CAM) model. A direct negative effect of hyperglycemia on angiogenesis may participate in failures of “therapeutic angiogenesis” trials. Here, we tested the hypothesis that the response to pro-angiogenic molecules such as angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), and vascular endothelial growth factor-A (VEGF) is altered by...

  7. Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer.

    Science.gov (United States)

    Shanmugam, Muthu K; Warrier, Sudha; Kumar, Alan P; Sethi, Gautam; Arfuso, Frank

    2017-01-01

    Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed to the tumor cells migrating to distal site organs and forming colonies. In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies. Several growth factors and their receptors such as vascular endothelial growth factor and receptor (VEGF/VEGFR), basic fibroblast growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia inducible factors facilitate the development of angiogenesis and are attractive anti-cancer targets. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis. Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel.

    Science.gov (United States)

    Reck, Martin; Mellemgaard, Anders; von Pawel, Joachim; Gottfried, Maya; Bondarenko, Igor; Cheng, Ying; Zarogoulidis, Kostas; Luft, Alexander; Bennouna, Jaafar; Barrueco, José; Aboshady, Hesham; Hocke, Julia; Kaiser, Rolf; Douillard, Jean-Yves

    2015-11-01

    LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib+docetaxel versus placebo+docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib+docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. The incidence and intensity of AEs were evaluated in all patients who received at least one dose of study medication (N=1307) and for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma (SCC; n=553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation, hypertension, bleeding, thromboembolic events, and skin disorders. The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib+docetaxel versus 0.2% with placebo+docetaxel. The incidence of some events was higher with nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash (11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and cutaneous adverse reactions were predominantly Grade 1-2 with both treatments. The incidence of all-grade bleeding was also slightly higher in nintedanib+docetaxel-treated patients (14.1% vs 11.6%) driven by between-treatment differences in the SCC subpopulation; most events were Grade 1-2. The proportion of patients with a thromboembolic event was low and comparable between arms for all grades (5.1% vs 4.6%) and Grade ≥3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with

  9. Angiogenic potential of endothelial and tumor cells seeded on gelatin-based hydrogels in response to electrical stimulations.

    Science.gov (United States)

    Tzoneva, Rumiana; Uzunova, Veselina; Apostolova, Sonia; Krüger-Genge, Anne; Neffe, Axel T; Jung, Friedrich; Lendlein, Andreas

    2016-01-01

    contrast, for MDA-MB-231 the production of MMPs on gelatin materials was lower compared to control materials. With the application of EF the levels of MMP-9 decreased but MMP-2 expression raised significantly for gelatin materials. Overall, the results showed that studied gelatin materials suppressed attachment of cancerous cells, as well as suppressed their angiogenic potential revealed by decreased VEGF and MMP production. Thus, this study approved gelatin-based hydrogels with proper elasticity characteristics and different degradation behavior as useful matrices for use in vascular tissue regeneration or in restriction of tumor growth after tumor resection.

  10. Malignant Transformation in Glioma Steered by an Angiogenic Switch: Defining a Role for Bone Marrow-Derived Cells.

    Science.gov (United States)

    Xu, Raymond; Pisapia, David; Greenfield, Jeffrey P

    2016-01-27

    Low-grade gliomas, such as pilocytic astrocytoma and subependymoma, are often characterized as benign tumors due to their relative circumscription radiologically and typically non-aggressive biologic behavior. In contrast, low-grades that are by their nature diffusely infiltrative, such as diffuse astrocytomas and oligodendrogliomas, have the potential to transform into malignant high-grade counterparts and, given sufficient time, invariably do so. These high-grade gliomas carry very poor prognoses and are largely incurable, warranting a closer look at what causes this adverse transition. A key characteristic that distinguishes low- and high-grade gliomas is neovascularization: it is absent in low-grade gliomas, but prolific in high-grade gliomas, providing the tumor with ample blood supply for exponential growth. It has been well described in the literature that bone marrow-derived cells (BMDCs) may contribute to the angiogenic switch that is responsible for malignant transformation of low-grade gliomas. In this review, we will summarize the current literature on BMDCs and their known contribution to angiogenesis-associated tumor growth in gliomas.

  11. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

    Science.gov (United States)

    Rhode, Jennifer; Fogoros, Sarah; Zick, Suzanna; Wahl, Heather; Griffith, Kent A; Huang, Jennifer; Liu, J Rebecca

    2007-01-01

    Background Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. Methods The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. Results Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. Conclusion Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer. PMID:18096028

  12. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Jennifer

    2007-12-01

    Full Text Available Abstract Background Ginger (Zingiber officinale Rosc is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. Methods The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. Results Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. Conclusion Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.

  13. Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Melissa I March

    Full Text Available Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1 and proangiogenic placental growth factor (PlGF levels in women with PE (n=35 compared to controls with no hypertensive disorders (NHD (n=43 among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks and late onset (>34 weeks and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight 34 weeks with no adverse outcome.PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

  14. Effect of nano-sized bioactive glass particles on the angiogenic properties of collagen based composites.

    Science.gov (United States)

    Vargas, Gabriela E; Haro Durand, Luis A; Cadena, Vanesa; Romero, Marcela; Mesones, Rosa Vera; Mačković, Mirza; Spallek, Stefanie; Spiecker, Erdmann; Boccaccini, Aldo R; Gorustovich, Alejandro A

    2013-05-01

    Angiogenesis is essential for tissue regeneration and repair. A growing body of evidence shows that the use of bioactive glasses (BG) in biomaterial-based tissue engineering (TE) strategies may improve angiogenesis and induce increased vascularization in TE constructs. This work investigated the effect of adding nano-sized BG particles (n-BG) on the angiogenic properties of bovine type I collagen/n-BG composites. Nano-sized (20-30 nm) BG particles of nominally 45S5 Bioglass® composition were used to prepare composite films, which were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The in vivo angiogenic response was evaluated using the quail chorioallantoic membrane (CAM) as an model of angiogenesis. At 24 h post-implantation, 10 wt% n-BG containing collagen films stimulated angiogenesis by increasing by 41 % the number of blood vessels branch points. In contrast, composite films containing 20 wt% n-BG were found to inhibit angiogenesis. This experimental study provides the first evidence that addition of a limited concentration of n-BG (10 wt%) to collagen films induces an early angiogenic response making selected collagen/n-BG composites attractive matrices for tissue engineering and regenerative medicine.

  15. Structure-activity relationship study of collagen-derived anti-angiogenic biomimetic peptides.

    Science.gov (United States)

    Rosca, Elena V; Koskimaki, Jacob E; Pandey, Niranjan B; Tamiz, Amir P; Popel, Aleksander S

    2012-07-01

    Structure-activity relationship (SAR) studies are essential in the generation of peptides with enhanced activity and efficacy as therapeutic agents. In this study, we report a Structure-activity relationship study for a family of mimetic peptides derived from type IV collagen with potent anti-angiogenic properties. The Structure-activity relationship study was conducted using a number of validated in vitro assays including cell proliferation, adhesion, migration, and tubule formation. We report a critical sequence (NINNV) within this peptide series, which is required for the potent anti-angiogenic activity. Detailed amino acid substitutions resulted in peptides with superior efficacy. Specifically, substitutions with isoleucine at positions 12 and 18 along with the substitution of the methionine at position 10 with the non-natural amino acid D-alanine led to an increase in potency by two orders of magnitude over the parent peptide. Several mimetic peptides in this series exhibit a significant improvement of activity over the parent peptide. This improved in vitro activity is expected to correlate with an increase in in vivo activity leading to effective peptides for anti-angiogenic therapy for different disease applications including cancer and age-related macular degeneration. © 2012 John Wiley & Sons A/S.

  16. Structure-activity relationship study of collagen derived anti-angiogenic biomimetic peptides

    Science.gov (United States)

    Rosca, Elena V.; Koskimaki, Jacob E.; Pandey, Niranjan B.; Tamiz, Amir P.; Popel, Aleksander S.

    2012-01-01

    Structure-activity relationship (SAR) studies are essential in the generation of peptides with enhanced activity and efficacy as therapeutic agents. In this study we report a SAR study for a family of mimetic peptides derived from type IV collagen with potent anti-angiogenic properties. The SAR study was conducted using a number of validated in vitro assays including cell proliferation, adhesion, migration and tubule formation. We report a critical sequence (NINNV) within this peptide series which is required for the potent anti-angiogenic activity. Detailed amino acid substitutions resulted in peptides with superior efficacy. Specifically, substitutions with Isoleucine at positions twelve and eighteen along with the substitution of the Methionine at position ten with the non-natural amino acid d-Alanine led to an increase in potency by two orders of magnitude over the parent peptide. Several mimetic peptides in this series exhibit a significant improvement of activity over the parent peptide. This improved in vitro activity is expected to correlate with an increase in in vivo activity leading to effective peptides for anti-angiogenic therapy for different disease applications including cancer and age-related macular degeneration. PMID:22405100

  17. Immune-Mediated and Hypoxia-Regulated Programs: Accomplices in Resistance to Anti-angiogenic Therapies.

    Science.gov (United States)

    Croci, Diego O; Mendez-Huergo, Santiago P; Cerliani, Juan P; Rabinovich, Gabriel A

    2017-04-13

    In contrast to mechanisms taking place during resistance to chemotherapies or other targeted therapies, compensatory adaptation to angiogenesis blockade does not imply a mutational alteration of genes encoding drug targets or multidrug resistance mechanisms but instead involves intrinsic or acquired activation of compensatory angiogenic pathways. In this article we highlight hypoxia-regulated and immune-mediated mechanisms that converge in endothelial cell programs and preserve angiogenesis in settings of vascular endothelial growth factor (VEGF) blockade. These mechanisms involve mobilization of myeloid cell populations and activation of cytokine- and chemokine-driven circuits operating during intrinsic and acquired resistance to anti-angiogenic therapies. Particularly, we focus on findings underscoring a role for galectins and glycosylated ligands in promoting resistance to anti-VEGF therapies and discuss possible strategies to overcome or attenuate this compensatory pathway. Finally, we highlight emerging evidence demonstrating the interplay between immunosuppressive and pro-angiogenic programs in the tumor microenvironment (TME) and discuss emerging combinatorial anticancer strategies aimed at simultaneously potentiating antitumor immune responses and counteracting aberrant angiogenesis.

  18. Anti-angiogenic drugs currently in Phase II clinical trials for gynecological cancer treatment.

    Science.gov (United States)

    Wei, Xia-wei; Zhang, Zhi-rong; Wei, Yu-Quan

    2013-09-01

    Numerous female patients suffer from gynecological cancers every year. When it comes to recurrent or chemoresistant cancers, there are limited treatment options. For decades, much enthusiasm has been shown for novel therapeutic strategies for cancers, and anti-angiogenesis agents appear to be a potential option. Since several promising angiogenesis inhibitors for certain cancers have been approved by Food and Drug Administration, more and more anti-angiogenic drugs are put into clinical trials. In this review, the anti-angiogenic agents in Phase II clinical trials for gynecological cancer treatment are highlighted. This review mainly focuses on 5-year reports on angiogenesis inhibitors concerning ovarian cancer, cervical cancer, uterine leiomysarcoma and endometrial cancer. Inhibitors reviewed in this paper include bevacizumab, volociximab, aflibercept, temsirolimus, enzastaurin, trebananib, sunitinib, imatinib, pazopanib, sorafenib and nintedanib. These anti-angiogenic drugs while used either alone or in combination with chemotherapy, presented mixed results in treating gynecological cancers. The real challenge is how to take best advantage of the anti-angiogenesis hypothesis for therapeutic benefit. Much remains to be done before these molecules work efficaciously in treating gynecological cancer.

  19. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors.

    Science.gov (United States)

    Bai, Huai; Forrester, John V; Zhao, Min

    2011-07-01

    Small direct current (DC) electric fields direct some important angiogenic responses of vascular endothelial cells. Those responses indicate promising use of electric fields to modulate angiogenesis. We sought to determine the regulation of electric fields on transcription and expression of a serial of import angiogenic factors by endothelial cells themselves. Using semi-quantitative PCR and ELISA we found that electric stimulation upregulates the levels of mRNAs and proteins of a number of angiogenic proteins, most importantly VEGF165, VEGF121 and IL-8 in human endothelial cells. The up-regulation of mRNA levels might be specific, as the mRNA encoding bFGF, TGF-beta and eNOS are not affected by DC electric stimulation at 24h time-point. Inhibition of VEGF receptor (VEGFR1 or VEGFR2) signaling significantly decreased VEGF production and completely abolished IL-8 production. DC electric stimulation selectively regulates production of some growth factors and cytokines important for angiogenesis through a feed-back loop mediated by VEGF receptors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro.

    Science.gov (United States)

    Harp, Djana; Driss, Adel; Mehrabi, Sharifeh; Chowdhury, Indrajit; Xu, Wei; Liu, Dong; Garcia-Barrio, Minerva; Taylor, Robert N; Gold, Bert; Jefferson, Samantha; Sidell, Neil; Thompson, Winston

    2016-07-01

    Our objective has been to establish a pro-angiogenic role for exosomes in endometriosis and to determine whether a differential expression profile of cellular and exosomal microRNAs (miRNAs) exists in endometriosis. We performed an in vitro study of human primary endometrial stromal cells (ESCs) and human umbilical vein endothelial cells (HUVECs). We isolated and characterized exosomes from ESCs from five endometriosis patients and five phase-matched controls. Exosomes were characterized by transmission electron microscopy and NanoSight technology. MiRNA was assessed by deep sequencing and reverse transcription with quantitative polymerase chain reaction. Exosome uptake studies were achieved by means of confocal microscopy. The pro-angiogenic experiments were executed by treating HUVECs with ESC-derived exosomes. We observed differential profiles of exosomal miRNA expression between exosomes derived from endometriosis lesion cells and diseased eutopic stromal cells compared with exosomes derived from control ESCs. We also demonstrated autocrine cellular uptake of exosomes and paracrine functional angiogenic effects of exosomes on HUVECs. The results of this study support the hypothesis that exosomes derived from ESCs play autocrine/paracrine roles in the development of endometriosis, potentially modulating angiogenesis. The broader clinical implications are that Sampson's theory of retrograde menstruation possibly encompasses the finding that exosomes work as intercellular communication modulators in endometriosis.

  1. Impaired Circulating Angiogenic Cells Mobilization and Metalloproteinase-9 Activity after Dynamic Exercise in Early Metabolic Syndrome

    Science.gov (United States)

    Rocha, Natalia G.; Sales, Allan R. K.; Penedo, Leticia A.; Pereira, Felipe S.; Silva, Mayra S.; Miranda, Renan L.; Silva, Jemima F. R.; Silva, Bruno M.; Santos, Aline A.; Nobrega, Antonio C. L.

    2015-01-01

    Increased levels of adhesion molecules or metalloproteinases (MMPs) may indicate endothelial dysfunction. Exercise mobilizes circulating angiogenic cells (CACs) from bone marrow in healthy subjects, improving vascular function. However, it is unclear whether this mechanism is preserved in the early stages of metabolic syndrome (early MetS). We aimed to evaluate the acute effects of exercise on adhesion molecules, angiogenic factors, MMPs, and CACs in early MetS. Fifteen subjects with early MetS and nine healthy controls underwent an exercise session and a nonexercise session, randomly. Adhesion molecules, angiogenic factors, CACs, and MMPs were evaluated before and after exercise or nonexercise sessions. At baseline, levels of sE-selectin, sICAM-1, and MMP-9 were higher in early MetS than in controls (P ≤ 0.03). After exercise, sE-selectin, sICAM-1, and MMP-9 levels were still higher in early MetS (P exercise. There was no difference between moments in nonexercise session (P > 0.05). In conclusion, subjects with early MetS already presented impaired endothelial function at rest along with a decrease in CACs and an increase in MMP-9 activity in response to exercise. PMID:26557715

  2. Tenascin-C Orchestrates Glioblastoma Angiogenesis by Modulation of Pro- and Anti-angiogenic Signaling.

    Science.gov (United States)

    Rupp, Tristan; Langlois, Benoit; Koczorowska, Maria M; Radwanska, Agata; Sun, Zhen; Hussenet, Thomas; Lefebvre, Olivier; Murdamoothoo, Devadarssen; Arnold, Christiane; Klein, Annick; Biniossek, Martin L; Hyenne, Vincent; Naudin, Elise; Velazquez-Quesada, Ines; Schilling, Oliver; Van Obberghen-Schilling, Ellen; Orend, Gertraud

    2016-12-06

    High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis. Glioblastoma cells exposed to tenascin-C secrete pro-angiogenic factors that promote endothelial cell survival and tubulogenesis. Proteomic analysis of their secretome reveals a signature, including ephrin-B2, that predicts decreased survival of glioma patients. We find that ephrin-B2 is an important pro-angiogenic tenascin-C effector. Thus, we demonstrate dual activities for tenascin-C in glioblastoma angiogenesis and uncover potential targeting and prediction opportunities. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Hancornia speciosa latex for biomedical applications: physical and chemical properties, biocompatibility assessment and angiogenic activity.

    Science.gov (United States)

    Almeida, Luciane Madureira; Floriano, Juliana Ferreira; Ribeiro, Thuanne Pires; Magno, Lais Nogueira; da Mota, Lígia Souza Lima Silveira; Peixoto, Nei; Mrué, Fátima; Melo-Reis, Paulo; Lino Junior, Ruy de Souza; Graeff, Carlos Frederico de Oliveira; Gonçalves, Pablo José

    2014-09-01

    The latex obtained from Hancornia speciosa is used in folk medicine for treatment of several diseases, such as acne, warts, diabetes, gastritis and inflammation. In this work, we describe the biocompatibility assessment and angiogenic properties of H. speciosa latex and its potential application in medicine. The physical-chemical characterization was carried out following different methodologies (CHN elemental analyses; thermogravimetric analyses and Fourier transform infrared spectroscopy). The biocompatibility was evaluated through cytotoxicity and genotoxicity tests in fibroblast mouse cells and the angiogenic properties were evaluated using the chick chorioallantoic membrane (CAM) assay model. The physical-chemical results showed that the structure of Hancornia speciosa latex biomembrane is very similar to that of Hevea brasiliensis (commercially available product). Moreover, the cytotoxicity and genotoxicity assays showed that H. speciosa latex is biocompatible with life systems and can be a good biomaterial for medical applications. The CAM test showed the efficient ability of H. speciosa latex in neovascularization of tissues. The histological analysis was in accordance with the results obtained in the CAM assay. Our data indicate that the latex obtained from H. speciosa and eluted in water showed significant angiogenic activity without any cytotoxic or genotoxic effects on life systems. The same did not occur with H. speciosa latex stabilized with ammonia. Addition of ammonia does not have significant effects on the structure of biomembranes, but showed a smaller cell survival and a significant genotoxicity effect. This study contributes to the understanding of the potentialities of H. speciosa latex as a source of new phytomedicines.

  4. Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines.

    Science.gov (United States)

    Atmaca, Harika; Bozkurt, Emir

    2016-03-01

    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.

  5. Tumor Vesicle—Associated CD147 Modulates the Angiogenic Capability of Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Danilo Millimaggi

    2007-04-01

    Full Text Available Matrix metalloproteinase (MMP degradation of extracellular matrix is thought to play an important role in invasion, angiogenesis, tumor growth, and metastasis. Several studies have demonstrated that CD147/ extracellular MMP inducer, a membrane-spanning molecule highly expressed in tumor cells, may be involved in the progression of malignancies by regulating expression of MMP in peritumoral stromal cells. In the present study we show that CD147 is expressed in microvesicles derived from epithelial ovarian cancer cells and that CD147-positive vesicles may promote an angiogenic phenotype in endothelial cells in vitro. Vesicles shed by human ovarian carcinoma cell lines OVCAR3, SKOV3, and A2780 expressed different levels of CD147 and stimulated proangiogenic activities of human umbilical vein endothelial cells (HUVECs in a CD147-dependent fashion (OVCAR3 > SKOV3 > A2780. Moreover, vesicles shed by ovarian carcinoma cell line CABA I with low CD147 expression had no significant effect on the development of angiogenic phenotype in HUVECs. The treatment of OVCAR3 cells with small interfering RNA against CD147 suppressed the angiogenic potential of OVCAR3-derived microvesicles. However, transfection of CD147 cDNA into the CABA I cell line enabled CABA I-derived vesicles to induce angiogenesis and to promote MMP genes expression in HUVECs. We therefore conclude that vesicles shed by ovarian cancer cells may induce proangiogenic activities of HUVECs by a CD147-mediated mechanism.

  6. The Sharing Economy

    DEFF Research Database (Denmark)

    Avital, Michel; Carroll, John M.; Hjalmarsson, Anders

    2015-01-01

    the ongoing debate about the sharing economy and contribute to the discourse with insights about how digital technologies are critical in shaping this turbulent ecosystem. Furthermore, we will define an agenda for future research on the sharing economy as it becomes part of the mainstream society as well......The sharing economy is spreading rapidly worldwide in a number of industries and markets. The disruptive nature of this phenomenon has drawn mixed responses ranging from active conflict to adoption and assimilation. Yet, in spite of the growing attention to the sharing economy, we still do not know...... much about it. With the abundant enthusiasm about the benefits that the sharing economy can unleash and the weekly reminders about its dark side, further examination is required to determine the potential of the sharing economy while mitigating its undesirable side effects. The panel will join...

  7. Shared governance. Sharing power and opportunity.

    Science.gov (United States)

    Prince, S B

    1997-03-01

    Responding to an enlarged span of control and an ever changing health care environment, the author describes the implementation of a unit-based shared governance model. Through study,literature review, and team consensus, a new management style emerged. Using Rosabeth Kanter's framework for work effectiveness, the unit governance structure was transformed. The process, progress, and outcomes are described, analyzed, and celebrated.

  8. Secure association rule sharing

    OpenAIRE

    Oliveira,Stanley R. de M.; Zaïane, Osmar R.; Saygın, Yücel; Saygin, Yucel

    2004-01-01

    The sharing of association rules is often beneficial in industry, but requires privacy safeguards. One may decide to disclose only part of the knowledge and conceal strategic patterns which we call restrictive rules. These restrictive rules must be protected before sharing since they are paramount for strategic decisions and need to remain private. To address this challenging problem, we propose a unified framework for protecting sensitive knowledge before sharing. This framework encompasses:...

  9. Efficiency in Shared Services

    OpenAIRE

    Prachýl, Lukáš

    2010-01-01

    The thesis describes and analyzes shared services organizations as a management tool to achieve efficiency in the organizations' processes. Paper builds on established theoretical principles, enhance them with up-to-date insights on the current situation and development and create a valuable knowledge base on shared services organizations. Strong emphasis is put on concrete means on how exactly efficiency could be achieved. Major relevant topics such as reasons for shared services, people man...

  10. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  11. A Data Sharing Story

    Directory of Open Access Journals (Sweden)

    Mercè Crosas

    2012-01-01

    Full Text Available From the early days of modern science through this century of Big Data, data sharing has enabled some of the greatest advances in science. In the digital age, technology can facilitate more effective and efficient data sharing and preservation practices, and provide incentives for making data easily accessible among researchers. At the Institute for Quantitative Social Science at Harvard University, we have developed an open-source software to share, cite, preserve, discover and analyze data, named the Dataverse Network. We share here the project’s motivation, its growth and successes, and likely evolution.

  12. Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors.

    Directory of Open Access Journals (Sweden)

    Chenlei Shi

    Full Text Available To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC for surgery by comparing the difference between PTMC and larger papillary thyroid carcinoma (LPTC.We analyzed the differences in the clinicopathological characteristics, prognosis, B-type RAF kinase (BRAFV600E mutational status and expression of angiogenic factors, including pigment epithelium-derived factor (PEDF, Vascular Endothelial Growth Factor (VEGF, and hypoxia-inducible factor alpha subunit (HIF-1α, between PTMC and LPTC by retrospectively reviewing the records of 251 patients with papillary thyroid carcinoma, 169 with PTMC, and 82 with LPTC (diameter >1 cm.There were no significant differences in the gender, age, multifocality, Hashimoto's thyroiditis, TNM stage, PEDF protein expression, rate of recurrence, or mean follow-up duration between patients with PTMC or LPTC. The prevalence of extrathyroidal invasion (EI, lymph node metastasis (LNM, and BRAF mutation in patients with PTMC was significantly lower than in patients with LPTC. In addition, in PTMC patients with EI and/or LNM and/or positive BRAF (high-risk PTMC patients, the prevalence of extrathyroidal invasion, Hashimoto's disease, lymph node metastasis, tumor TNM stage, PEDF positive protein expression, the rate of recurrent disease, and the mRNA expression of anti-angiogenic factors was almost as high as in patients with larger PTC, but with no significant difference.Extrathyroid invasion, lymph node metastases, and BRAFV600E mutation were the high risk factors of PTMC. PTMC should be considered for the same treatment strategy as LPTC when any of these factors is found. Particularly, PTMC with BRAFV600E gene mutations needed earlier surgical treatment. In addition, the high cell subtype of PTMC with BRAFV600E gene mutation is recommended for total thyroidectomy in primary surgery to reduce the risk of recurrence.

  13. Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC).

    Science.gov (United States)

    Zavala, Gabriela; Prieto, Catalina P; Villanueva, Andrea A; Palma, Verónica

    2017-09-29

    Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of these specific factors are still mostly unknown. Emerging evidence suggests that Sonic hedgehog (SHH) plays a central role in angiogenesis and tissue maintenance. However, its contribution to the angiogenic potential of MSC has not been fully addressed. The aim of this work was to characterize the expression of the SHH pathway components in WJ-MSC primary cultures and to evaluate their angiogenic responsiveness to SHH signaling. Primary cell cultures obtained from human umbilical cords were treated with pharmacological modulators of the SHH pathway. We evaluated the modulation of diverse trophic factors in cell lysates, conditioned medium, and functional in vitro assays. In addition, we determined the angiogenic potential of the SHH pathway in the chicken chorioallantoic membrane, an in vivo model. Our results show that WJ-MSC express components of the canonical SHH pathway and are activated by its signaling. In fact, we provide evidence of basal autocrine/paracrine SHH signaling in WJ-MSC. SHH pathway stimulation promotes the secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase -9, and urokinase-type plasminogen activator, enhancing the pro-angiogenic capabilities of WJ-MSC both in vitro and in vivo. WJ-MSC are a cell population responsive to SHH pathway stimulation. Basal SHH signaling is in part responsible for the angiogenic inductive properties of WJ-MSC. Overall, exogenous activation of the SHH pathway enhances the angiogenic properties of WJ-MSC, making this cell population an ideal target for treating tissue injury.

  14. Pancreatic-carcinoma-cell-derived pro-angiogenic factors can induce endothelial-cell differentiation of a subset of circulating CD34+ progenitors

    National Research Council Canada - National Science Library

    Vizio, Barbara; Biasi, Fiorella; Scirelli, Tiziana; Novarino, Anna; Prati, Adriana; Ciuffreda, Libero; Montrucchio, Giuseppe; Poli, Giuseppe; Bellone, Graziella

    2013-01-01

    .... Recent studies suggest that circulating endothelial progenitor cells are recruited into the angiogenic vascular system of several cancers, including pancreatic carcinoma, and that they correlate with clinical progress...

  15. Millennials and the Sharing Economy

    DEFF Research Database (Denmark)

    Ranzini, Giulia; Newlands, Gemma; Anselmi, Guido

    Report from the EU H2020 Research Project Ps2Share: Participation, Privacy, and Power in the Sharing Economy......Report from the EU H2020 Research Project Ps2Share: Participation, Privacy, and Power in the Sharing Economy...

  16. 5G Spectrum Sharing

    OpenAIRE

    Nekovee, Maziar; Rudd, Richard

    2017-01-01

    In this paper an overview is given of the current status of 5G industry standards, spectrum allocation and use cases, followed by initial investigations of new opportunities for spectrum sharing in 5G using cognitive radio techniques, considering both licensed and unlicensed scenarios. A particular attention is given to sharing millimeter-wave frequencies, which are of prominent importance for 5G.

  17. Phenomenology of experiential sharing

    DEFF Research Database (Denmark)

    León, Felipe; Zahavi, Dan

    2016-01-01

    The chapter explores the topic of experiential sharing by drawing on the early contributions of the phenomenologists Alfred Schutz and Gerda Walther. It is argued that both Schutz and Walther support, from complementary perspectives, an approach to experiential sharing that has tended to be overl...

  18. Satisfaction and 'comparison sharing'

    DEFF Research Database (Denmark)

    Amilon, Anna

    2009-01-01

    Despite the high degree of flexibility and generosity in Sweden’s parental leave program, one fifth of parents are not satisfied with the sharing of parental leave. This paper investigates whether ‘comparison sharing’, the sharing of parental leave by other comparable couples, influences the prob...

  19. Mobile energy sharing futures

    DEFF Research Database (Denmark)

    Worgan, Paul; Knibbe, Jarrod; Plasencia, Diego Martinez

    2016-01-01

    We foresee a future where energy in our mobile devices can be shared and redistributed to suit our current task needs. Many of us are beginning to carry multiple mobile devices and we seek to re-evaluate the traditional view of a mobile device as only accepting energy. In our vision, we can...... sharing futures....

  20. Radical uncertainty, non-predictability, antifragility and risk-sharing Islamic finance

    National Research Council Canada - National Science Library

    Umar Rafi; Abbas Mirakhor; Hossein Askari

    2016-01-01

    .... The goal in this introductory paper is to show that risk-sharing Islamic finance shares the characteristics of an antifragile system by mapping some characteristics of antifragility onto those...

  1. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating...... knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organizational settings, the paper explores how knowledge exchange can be conceptualized as going on in four...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  2. Exploring the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    Despite the growing interest on the part of proponents and opponents - ranging from business, civil society, media, to policy-makers alike - there is still limited knowledge about the working mechanisms of the sharing economy. The thesis is dedicated to explore this understudied phenomenon...... and to provide a more nuanced understanding of the micro- and macro-level tensions that characterize the sharing economy. This thesis consists of four research papers, each using different literature, methodology, and data sets. The first paper investigates how the sharing economy is diffused and is ‘talked......-level tensions experience by sharing platforms by looking at the case of mobile fashion reselling and swapping markets. The final paper combines the perspectives of different sharing economy stakeholders and outlines some of the micro and macro tensions arising in and influencing the organization of these multi...

  3. Oxidative stress-mediated thrombospondin-2 upregulation impairs bone marrow-derived angiogenic cell function in diabetes mellitus.

    Science.gov (United States)

    Bae, Ok-Nam; Wang, Jie-Mei; Baek, Seung-Hoon; Wang, Qingde; Yuan, Hong; Chen, Alex F

    2013-08-01

    Circulating angiogenic cells play an essential role in angiogenesis but are dysfunctional in diabetes mellitus characterized by excessive oxidative stress. We hypothesize that oxidative stress-mediated upregulation of thrombospondin-2 (TSP-2), a potent antiangiogenic protein, contributes to diabetic bone marrow-derived angiogenic cell (BMAC) dysfunction. BMACs were isolated from adult male type 2 diabetic db/db mice and control db/+ (C57BLKS/J) mice. In Matrigel tube formation assay, angiogenic function was impaired in diabetic BMACs, accompanied by increased oxidative stress and nicotinamide adenine dinucleotide phosphate oxidase activity. BMAC angiogenic function was restored by overexpression of dominant negative Rac1 or by overexpression of manganese superoxide dismutase. TSP-2 mRNA and protein were both significantly upregulated in diabetic BMACs, mediated by increased oxidative stress as shown by a decrease in TSP-2 level after overexpression of dominant negative Rac1 or manganese superoxide dismutase. Silencing TSP-2 by its small interfering RNA in diabetic BMACs improved BMAC function in tube formation, adhesion, and migration assays. Notably, the upregulation of TSP-2 was also found in BMACs from streptozotocin-induced type 1 diabetic mice, and normal BMACs with high glucose treatment. let-7f, a microRNA which has been related to endothelial angiogenic function, is found to play key role in TSP-2 increase, but let-7f did not directly interact with TSP-2 mRNA. The upregulation of TSP-2 mediated by increased oxidative stress contributes to angiogenesis dysfunction in diabetic BMACs.

  4. Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yeyin Liang

    2017-01-01

    Full Text Available Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2 has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs. Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments.

  5. Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors

    Directory of Open Access Journals (Sweden)

    Rafaella Bastos LEITE

    2017-04-01

    Full Text Available Abstract The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1 and 3 (GLUT-3 in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs and non-syndromic keratocystic odontogenic tumors (NSKOTs, and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman’s correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360. There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778. GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05. The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.

  6. Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors.

    Science.gov (United States)

    Leite, Rafaella Bastos; Cavalcante, Roberta Barroso; Nogueira, Renato Luiz Maia; Souza, Lélia Batista de; Pereira Pinto, Leão; Nonaka, Cassiano Francisco Weege

    2017-04-27

    The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman's correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778). GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05). The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.

  7. High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy in pregnancy in the Mma Bana study, Botswana.

    Science.gov (United States)

    Powis, Kathleen M; McElrath, Thomas F; Hughes, Michael D; Ogwu, Anthony; Souda, Sajini; Datwyler, Saul A; von Widenfelt, Erik; Moyo, Sikhulile; Nádas, Marisa; Makhema, Joseph; Machakaire, Esther; Lockman, Shahin; Essex, Max; Shapiro, Roger L

    2013-04-15

    Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after highly active antiretroviral therapy (HAART) initiation have not been studied. The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts ≥ 200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression. Plasma samples drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1). Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia (odds ratio: 5.8, 95% confidence interval: 1.8 to 19.4, P = 0.004). Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not (130 vs 992 pg/mL, P = 0.001; 17.5 vs 9.4 pg/mL, P = 0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women. Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment.

  8. Employee share ownership in Germany

    DEFF Research Database (Denmark)

    Ortlieb, Renate; Matiaske, Wenzel; Fietze, Simon

    2016-01-01

    on an institutional theoretical framework, this article examines what aims firms pursue through the provision of ESO. The data originate from a survey of firms in Germany. The cluster analytic findings indicate distinctive patterns of relationships between aims and firm characteristics. Aims related to employee...... performance are most important to foreign-owned firms, financial aims are most important to non-public small and medium-sized firms and aims related to corporate image are most important to big firms and to firms that do not provide profit sharing. Aims related to employee attraction and retention are almost...

  9. Chronic hypoxia attenuates VEGF signaling and angiogenic responses by downregulation of KDR in human endothelial cells.

    Science.gov (United States)

    Olszewska-Pazdrak, Barbara; Hein, Travis W; Olszewska, Paulina; Carney, Darrell H

    2009-05-01

    Coronary artery disease results in progressive vascular stenosis associated with chronic myocardial ischemia. Vascular endothelial growth factor (VEGF) stimulates endothelial cell angiogenic responses to revascularize ischemic tissues; however, the effect of chronic hypoxia on the responsiveness of endothelial cells to VEGF remains unclear. We, therefore, investigated whether hypoxia alters VEGF-stimulated signaling and angiogenic responses in primary human coronary artery endothelial (HCAE) cells. Exposure of HCAE cells to hypoxia (1% O(2)) for 24 h decreased VEGF-stimulated endothelial cell migration ( approximately 82%), proliferation ( approximately 30%), and tube formation. Hypoxia attenuated VEGF-stimulated activation of endothelial nitric oxide (NO) synthase (eNOS) ( approximately 72%) and reduced NO production in VEGF-stimulated cells from 237 +/- 38.8 to 61.3 +/- 28.4 nmol/l. Moreover, hypoxia also decreased the ratio of phosphorylated eNOS to total eNOS in VEGF-stimulated cells by approximately 50%. This effect was not observed in thrombin-stimulated cells, suggesting that hypoxia specifically inhibited VEGF signaling upstream of eNOS phosphorylation. VEGF-induced activation of Akt, ERK1/2, p38, p70S6 kinases, and S6 ribosomal protein was also attenuated in hypoxic cells. Moreover, VEGF-stimulated phosphorylation of VEGF receptor-2 (KDR) at Y996 and Y1175 was decreased by hypoxia. This decrease correlated with a 70 +/- 12% decrease in KDR protein expression. Analysis of mRNA from these cells showed that hypoxia reduced steady-state levels of KDR mRNA by 52 +/- 16% and decreased mRNA stability relative to normoxic cells. Our findings demonstrate that chronic hypoxia attenuates VEGF-stimulated signaling in HCAE cells by specific downregulation of KDR expression. These data provide a novel explanation for the impaired angiogenic responses to VEGF in endothelial cells exposed to chronic hypoxia.

  10. Plant proteolytic enzyme papain abrogates angiogenic activation of human umbilical vein endothelial cells (HUVEC) in vitro

    Science.gov (United States)

    2013-01-01

    Background Vascular endothelial growth factor (VEGF) is a key regulator of physiologic and pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. It is known that cysteine proteases from plants, like bromelain and papain are capable to suppress inflammatory activation. Recent studies have demonstrated that they may interfere with angiogenesis related pathways as well. The aim of this study was to investigate the anti-angiogenic effects of papain on human umbilical vein endothelial cells (HUVEC) in vitro. Methods Cell viability after prolonged treatment with papain was investigated by life cell staining and lactate dehydrogenase release assay. Angiogenic activation was assessed by ELISA against phosphorylated proteins AKT, MEK1/2, ERK1/2, SAPK/JNK and p38-MAPK. Growth inhibition was determined by means of an MTT-assay and cell migration by means of a scratch assay. Capability to form a capillary network was investigated using a tube formation assay. Results Papain did not induce proteolysis or cell detachment of HUVEC in a concentration range between 0 and 25 μg/mL. Four hours treatment with 10 μg/mL papain resulted in a reduced susceptibility of endothelial cells to activation by VEGF as determined by phosphorylation levels of Akt, MEK1/2, SAPK/JNK. Papain exerted a distinct inhibitory effect on cell growth, cell migration and tube formation with inhibition of tube formation detectable at concentrations as low as 1 μg/mL. Bromelain and ficin displayed similar effects with regard to cell growth and tube formation. Conclusion Papain showed a strong anti-angiogenic effect in VEGF activated HUVEC. This effect may be due to interference with AKT, MEK1/2 and SAPK/JNK phosphorylation. Two other plant derived cysteine proteases displayed similar inhibition of HUVEC cell growth and tube formation. These findings indicate that plant proteolytic enzymes may have potential as preventive and therapeutic agents against angiogenesis related human diseases

  11. Interleukin-3 greatly expands non-adherent endothelial forming cells with pro-angiogenic properties

    Directory of Open Access Journals (Sweden)

    Lachlan M. Moldenhauer

    2015-05-01

    Full Text Available Circulating endothelial progenitor cells (EPCs provide revascularisation for cardiovascular disease and the expansion of these cells opens up the possibility of their use as a cell therapy. Herein we show that interleukin-3 (IL3 strongly expands a population of human non-adherent endothelial forming cells (EXnaEFCs with low immunogenicity as well as pro-angiogenic capabilities in vivo, making their therapeutic utilisation a realistic option. Non-adherent CD133+ EFCs isolated from human umbilical cord blood and cultured under different conditions were maximally expanded by day 12 in the presence of IL3 at which time a 350-fold increase in cell number was obtained. Cell surface marker phenotyping confirmed expression of the hematopoietic progenitor cell markers CD133, CD117 and CD34, vascular cell markers VEGFR2 and CD31, dim expression of CD45 and absence of myeloid markers CD14 and CD11b. Functional experiments revealed that EXnaEFCs exhibited classical properties of endothelial cells (ECs, namely binding of Ulex europaeus lectin, up-take of acetylated-low density lipoprotein and contribution to EC tube formation in vitro. These EXnaEFCs demonstrated a pro-angiogenic phenotype within two independent in vivo rodent models. Firstly, a Matrigel plug assay showed increased vascularisation in mice. Secondly, a rat model of acute myocardial infarction demonstrated reduced heart damage as determined by lower levels of serum creatinine and a modest increase in heart functionality. Taken together, these studies show IL3 as a potent growth factor for human CD133+ cell expansion with clear pro-angiogenic properties (in vitro and in vivo and thus may provide clinical utility for humans in the future.

  12. Anti-angiogenic activity of water extract from Euphorbia pekinensis Rupr.

    Science.gov (United States)

    Zhang, Wenting; Liu, Bin; Feng, Yaru; Liu, Jie; Ma, Zhiqiang; Zheng, Jian; Xia, Qing; Ni, Yuanyuan; Li, Farong; Lin, Ruichao

    2017-07-12

    Euphorbia pekinensis Rupr. (EP) is a Euphorbia species of Euphorbiaceae, which is widely used in traditional Chinese medicine. It has been reported to exhibit therapeutic effects on solid tumors, leukemias, and malignant ascites although underlying molecular mechanisms are poorly delineated. Anti-angiogenic therapy is a recognized strategy for treating cancer-based solid tumors, and is also associated with malignant ascites treatment. To study the anti-angiogenic properties of the water extract of EP vinegar preparation (WEVEP). Following WEVEP treatment, intersegmental blood vessels were assessed during the development of transgenic Tg (flk: mCherry) zebrafish as was the proliferation, migration and network formation of HUVECs in vitro. mRNA expression of specific angiogenic-related genes including VEGF family members, Met, and NRP2 was also measured using quantitative real-time PCR (Q-PCR). Data demonstrated that angiogenesis was inhibited by the WEVEP in zebrafish (from 100µg/mL to 250µg/mL, p numbers of administered groups were 26.00 ± 1.29 (100µg/mL), 24.54 ± 2.20 (150µg/mL), 22.66 ± 2.68 (200µg/mL), 20.80 ± 1.75 (250µg/mL), compared to 27.67 ± 0.96 of control group. Relative quantitative gene expression in zebrafish treated with WEVEP demonstrated that only VEGFR3 was significantly increased and other 23 genes including Met, VEGFA, Flt-1 were significantly decreased. WEVEP can positively modulate angiogenesis via multiple targeting mechanisms. Our novel results contribute towards the discovery of a possible mechanism(s) of the traditional use of EP in the treatment of cancer and malignant ascites. Copyright © 2017. Published by Elsevier B.V.

  13. Fibroblasts derived from human pluripotent stem cells activate angiogenic responses in vitro and in vivo.

    Science.gov (United States)

    Shamis, Yulia; Silva, Eduardo A; Hewitt, Kyle J; Brudno, Yevgeny; Levenberg, Shulamit; Mooney, David J; Garlick, Jonathan A

    2013-01-01

    Human embryonic and induced pluripotent stem cells (hESC/hiPSC) are promising cell sources for the derivation of large numbers of specific cell types for tissue engineering and cell therapy applications. We have describe a directed differentiation protocol that generates fibroblasts from both hESC and hiPSC (EDK/iPDK) that support the repair and regeneration of epithelial tissue in engineered, 3D skin equivalents. In the current study, we analyzed the secretory profiles of EDK and iPDK cells to investigate the production of factors that activate and promote angiogenesis. Analysis of in vitro secretion profiles from EDK and iPDK cells demonstrated the elevated secretion of pro-angiogenic soluble mediators, including VEGF, HGF, IL-8, PDGF-AA, and Ang-1, that stimulated endothelial cell sprouting in a 3D model of angiogenesis in vitro. Phenotypic analysis of EDK and iPDK cells during the course of differentiation from hESCs and iPSCs revealed that both cell types progressively acquired pericyte lineage markers NG2, PDGFRβ, CD105, and CD73 and demonstrated transient induction of pericyte progenitor markers CD31, CD34, and Flk1/VEGFR2. Furthermore, when co-cultured with endothelial cells in 3D fibrin-based constructs, EDK and iPDK cells promoted self-assembly of vascular networks and vascular basement membrane deposition. Finally, transplantation of EDK cells into mice with hindlimb ischemia significantly reduced tissue necrosis and improved blood perfusion, demonstrating the potential of these cells to stimulate angiogenic responses in vivo. These findings demonstrate that stable populations of pericyte-like angiogenic cells can be generated with high efficiency from hESC and hiPSC using a directed differentiation approach. This provides new cell sources and opportunities for vascular tissue engineering and for the development of novel strategies in regenerative medicine.

  14. Fibroblasts derived from human pluripotent stem cells activate angiogenic responses in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yulia Shamis

    Full Text Available Human embryonic and induced pluripotent stem cells (hESC/hiPSC are promising cell sources for the derivation of large numbers of specific cell types for tissue engineering and cell therapy applications. We have describe a directed differentiation protocol that generates fibroblasts from both hESC and hiPSC (EDK/iPDK that support the repair and regeneration of epithelial tissue in engineered, 3D skin equivalents. In the current study, we analyzed the secretory profiles of EDK and iPDK cells to investigate the production of factors that activate and promote angiogenesis. Analysis of in vitro secretion profiles from EDK and iPDK cells demonstrated the elevated secretion of pro-angiogenic soluble mediators, including VEGF, HGF, IL-8, PDGF-AA, and Ang-1, that stimulated endothelial cell sprouting in a 3D model of angiogenesis in vitro. Phenotypic analysis of EDK and iPDK cells during the course of differentiation from hESCs and iPSCs revealed that both cell types progressively acquired pericyte lineage markers NG2, PDGFRβ, CD105, and CD73 and demonstrated transient induction of pericyte progenitor markers CD31, CD34, and Flk1/VEGFR2. Furthermore, when co-cultured with endothelial cells in 3D fibrin-based constructs, EDK and iPDK cells promoted self-assembly of vascular networks and vascular basement membrane deposition. Finally, transplantation of EDK cells into mice with hindlimb ischemia significantly reduced tissue necrosis and improved blood perfusion, demonstrating the potential of these cells to stimulate angiogenic responses in vivo. These findings demonstrate that stable populations of pericyte-like angiogenic cells can be generated with high efficiency from hESC and hiPSC using a directed differentiation approach. This provides new cell sources and opportunities for vascular tissue engineering and for the development of novel strategies in regenerative medicine.

  15. Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene.

    Directory of Open Access Journals (Sweden)

    Casimiro Cárdenas

    Full Text Available BACKGROUND: Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules. METHODOLOGY/PRINCIPAL FINDINGS: The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish, the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells. CONCLUSION/SIGNIFICANCE: Taken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers.

  16. Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma.

    Science.gov (United States)

    Skuletic, Vesna; Radosavljevic, Gordana D; Pantic, Jelena; Markovic, Bojana Simovic; Jovanovic, Ivan; Jankovic, Nikola; Petrovic, Dusica; Jevtovic, Andra; Dzodic, Radan; Arsenijevic, Nebojsa

    2017-06-30

    INTRODUCTION    Papillary thyroid carcinoma (PTC) is a well‑differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear. Angiogenesis and lymphangiogenesis are critical processes that enable tumor progression. OBJECTIVES    The aim of this study was to evaluate the angiogenic and lymphangiogenic phenotypes of PTC, considering the differences between histological variants. PATIENTS AND METHODS    Angiogenic and lymphangiogenic profiles were analyzed by determining microvascular density (MVD) and lymphatic vessel density (LVD) in 73 cases of PTC, using immunohistochemistry. To assess the biological markers involved in blood and lymph vessel formation, the expression of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX‑2), and p27kip1 (p27) was determined. RESULTS    MVD was significantly higher in patients with high‑risk PTC and in those with local extrathyroidal and vascular invasion. Positive VEGF expression was strongly associated with high MVD and age‑related tumor enlargement. The presence of lymph vessel invasion was associated with the expression of either VEGF or COX‑2. The analysis of angiogenesis and lymphangiogenesis in different histological variants of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV‑PTC).Lower MVD was observed in FV‑PTC relative to the classic variant of PTC (CV‑PTC). The frequency of VEGF‑positive tumors was higher in CV‑PTC than in FV‑PTC. A significant association between COX‑2 and p27 expression was observed in FV‑PTC but not in CV‑PTC.  CONCLUSIONS    These results suggest that VEGF, COX‑2, and p27 may be important biological markers that determine the angiogenic and lymphangiogenic potentials of PTC, particularly between the follicular and classic variants.

  17. Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Nambiar, Dhanya K. [Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi (India); School of Environmental Sciences, Jawaharlal Nehru University, New Delhi (India); Rajamani, Paulraj [School of Environmental Sciences, Jawaharlal Nehru University, New Delhi (India); Singh, Rana P., E-mail: rana_singh@mail.jnu.ac.in [Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi (India); School of Life Sciences, Central University of Gujarat, Gandhinagar (India)

    2015-01-02

    Graphical abstract: Potential model showing mechanism of silibinin-mediated attenuation of IR-induced angiogenic phenotype and EMT in tumor cells. Silibinin counters radiation induced invasive and migratory phenotype of cancer cells by down-regulating mitogenic pathways activated by IR, leading to inhibition of molecules including VEGF, iNOS, MMPs and N-cadherin. Silibinin also reverses IR mediated E-cadherin down-regulation, inhibiting EMT in tumor cells. Silibinin also radiosensitizes endothelial cells, reduces capillary tube formation by targeting various pro-angiogenic molecules. Further, silibinin may inhibit autocrine and paracrine signaling between tumor and endothelial cells by decreasing the levels of VEGF and other signaling molecules activated in response to IR. - Highlights: • Silibinin radiosensitizes endothelial cells. • Silibinin targets ionization radiation (IR)-induced EMT in PCa cells. • Silibinin is in phase II clinical trial in PCa patients, hence clinically relevant. - Abstract: Radiotherapy of is well established and frequently utilized in prostate cancer (PCa) patients. However, recurrence following therapy and distant metastases are commonly encountered problems. Previous studies underline that, in addition to its therapeutic effects, ionizing radiation (IR) increases the vascularity and invasiveness of surviving radioresistant cancer cells. This invasive phenotype of radioresistant cells is an upshot of IR-induced pro-survival and mitogenic signaling in cancer as well as endothelial cells. Here, we demonstrate that a plant flavonoid, silibinin can radiosensitize endothelial cells by inhibiting expression of pro-angiogenic factors. Combining silibinin with IR not only strongly down-regulated endothelial cell proliferation, clonogenicity and tube formation ability rather it strongly (p < 0.001) reduced migratory and invasive properties of PCa cells which were otherwise marginally affected by IR treatment alone. Most of the pro-angiogenic

  18. VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A

    Directory of Open Access Journals (Sweden)

    Pio Ruben

    2010-12-01

    Full Text Available Abstract Background Different isoforms of VEGF-A (mainly VEGF121, VEGF165 and VEGF189 have been shown to display particular angiogenic properties in the generation of a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms, designated as VEGFxxxb, generated through alternative splicing, have been described. Previous studies have suggested that these isoforms may inhibit angiogenesis. In the present work we have produced recombinant VEGF121/165b proteins in the yeast Pichia pastoris and constructed vectors to overexpress these isoforms and assess their angiogenic potential. Results Recombinant VEGF121/165b proteins generated either in yeasts or mammalian cells activated VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than VEGF165. Furthermore, treatment of endothelial cells with VEGF121/165b increased cell proliferation compared to untreated cells, although such stimulation was lower than that induced by VEGF165. Moreover, in vivo angiogenesis assays confirmed angiogenesis stimulation by VEGF121/165b isoforms. A549 and PC-3 cells overexpressing VEGF121b or VEGF165b (or carrying the PCDNA3.1 empty vector, as control and xenotransplanted into nude mice showed increased tumor volume and angiogenesis compared to controls. To assess whether the VEGFxxxb isoforms are differentially expressed in tumors compared to healthy tissues, immunohistochemical analysis was conducted on a breast cancer tissue microarray. A significant increase (p xxxb and total VEGF-A protein expression in infiltrating ductal carcinomas compared to normal breasts was observed. A positive significant correlation (r = 0.404, p = 0.033 between VEGFxxxb and total VEGF-A was found. Conclusions Our results demonstrate that VEGF121/165b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A. In addition, VEGFxxxb isoforms are up-regulated in breast cancer in comparison with non malignant breast tissues. These results are to be taken

  19. Cathelicidins: peptides with antimicrobial, immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer activities.

    Science.gov (United States)

    Wong, Jack Ho; Ye, Xiu Juan; Ng, Tzi Bun

    2013-09-01

    The family of peptides designated as cathelicidins was identified over a decade ago. Cathelicidins have since gained increasing recognition, both as endogenous antibiotics and as effector molecules of the innate immune system. The human cathelicidin LL-37 is widely expressed in human tissues and plays diverse biological roles. It contributes substantially to host defense and impacts multiple aspects of immunity. In view of the escalating importance of cathelicidins, the activities of LL-37 with an emphasis on antimicrobial, immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer effects are discussed in this review article.

  20. Synthesis and biological evaluation of novel indolocarbazoles with anti-angiogenic activity.

    Science.gov (United States)

    Acero, Nuria; Braña, Miguel F; Añorbe, Loreto; Domínguez, Gema; Muñoz-Mingarro, Dolores; Mitjans, Francesc; Piulats, Jaume

    2012-02-01

    A novel series of indolocarbazoles were synthesized and their antiproliferative activity against HUVEC, LoVo, DLD-1 and ST-486 cell lines, was investigated. Those staurosporine analogs in which a substituted dimethylaminoalkoxy chain was attached to the indolic nitrogen showed interesting activity and selectivity with respect to HUVEC proliferation. The effect on capillary tube formation in 3-dimensional matrigel matrix was studied using the most active compounds. Evaluation of their in vivo anti-angiogenic activity in a murine Lewis lung cancer model was also analyzed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. Effect of smoking on circulating angiogenic factors in high risk pregnancies.

    Directory of Open Access Journals (Sweden)

    Arun Jeyabalan

    Full Text Available OBJECTIVE: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1 and soluble endoglin (sEng, and the pro-angiogenic placental growth factor (PlGF precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng in women at high risk for developing preeclampsia. STUDY DESIGN: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']. Smoking status was determined by self-report. RESULTS: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005 and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001. sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002 and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05. Smoking was not associated with a lower incidence of preeclampsia in any of these groups. CONCLUSIONS: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort.

  2. Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties.

    Science.gov (United States)

    Kasiotis, Konstantinos M; Pratsinis, Harris; Kletsas, Dimitris; Haroutounian, Serkos A

    2013-11-01

    Dietary stilbenes comprise a class of natural compounds that display significant biological activities of medicinal interest. Among them, their antioxidant, anti-aging and anti-angiogenesic properties are well established and subjects of numerous research endeavors. This mini-review aspires to account and present the literature reports published on research concerning various natural and synthetic stilbenes, such as trans-resveratrol. Special focus was given to most recent research findings, while the mechanisms underlying their anti-aging and anti-angiogenic effects as well as the respective signaling pathways involved were also presented and discussed. Copyright © 2013. Published by Elsevier Ltd.

  3. Global resource sharing

    CERN Document Server

    Frederiksen, Linda; Nance, Heidi

    2011-01-01

    Written from a global perspective, this book reviews sharing of library resources on a global scale. With expanded discovery tools and massive digitization projects, the rich and extensive holdings of the world's libraries are more visible now than at any time in the past. Advanced communication and transmission technologies, along with improved international standards, present a means for the sharing of library resources around the globe. Despite these significant improvements, a number of challenges remain. Global Resource Sharing provides librarians and library managers with a comprehensive

  4. Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study.

    Science.gov (United States)

    Widmer, Mariana; Cuesta, Cristina; Khan, Khalid S; Conde-Agudelo, Agustin; Carroli, Guillermo; Fusey, Shalini; Karumanchi, S Ananth; Lapaire, Olav; Lumbiganon, Pisake; Sequeira, Evan; Zavaleta, Nelly; Frusca, Tiziana; Gülmezoglu, A Metin; Lindheimer, Marshall D

    2015-10-01

    To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation. Pre-eclampsia. Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability. Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia. Copyright © 2015. Published by Elsevier B.V.

  5. Sharing resources@CERN

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    The library is launching a 'sharing resources@CERN' campaign, aiming to increase the library's utility by including the thousands of books bought by individual groups at CERN. This will improve sharing of information among CERN staff and users. Photo 01: L. to r. Eduardo Aldaz, from the PS division, Corrado Pettenati, Head Librarian, and Isabel Bejar, from the ST division, read their divisional copies of the same book.

  6. The Spanish Sharing Rule

    OpenAIRE

    Bernarda Zamora

    2003-01-01

    In this paper we estimate the intrahousehold distribution of household's private expenditures between men and women (the sharing rule) in two types of Spanish households: those in which the woman works and those in which the woman does not work. The results for working women are parallel to those obtained for other countries which indicate a proportionally higher transfer from the woman to the man than from the man to the woman, such that the proportion of the woman's share decreases both wit...

  7. Bonobos Share with Strangers

    OpenAIRE

    Jingzhi Tan; Brian Hare

    2013-01-01

    Humans are thought to possess a unique proclivity to share with others ? including strangers. This puzzling phenomenon has led many to suggest that sharing with strangers originates from human-unique language, social norms, warfare and/or cooperative breeding. However, bonobos, our closest living relative, are highly tolerant and, in the wild, are capable of having affiliative interactions with strangers. In four experiments, we therefore examined whether bonobos will voluntarily donate food ...

  8. [The shared nursing function].

    Science.gov (United States)

    Fleury, Cynthia

    The Chair of Philosophy at Hôtel-Dieu hospital in Paris, is a place for the sharing of knowledge and recognition. It provides a place where the subjective, institutional and political dimension of care can be considered, by all stakeholders: patients, nurses, families and citizens. The aim is to invent a shared nursing function. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Sharing big biomedical data

    OpenAIRE

    Toga, Arthur W.; Ivo D Dinov

    2015-01-01

    Background The promise of Big Biomedical Data may be offset by the enormous challenges in handling, analyzing, and sharing it. In this paper, we provide a framework for developing practical and reasonable data sharing policies that incorporate the sociological, financial, technical and scientific requirements of a sustainable Big Data dependent scientific community. Findings Many biomedical and healthcare studies may be significantly impacted by using large, heterogeneous and incongruent data...

  10. Information partnerships--shared data, shared scale.

    Science.gov (United States)

    Konsynski, B R; McFarlan, F W

    1990-01-01

    How can one company gain access to another's resources or customers without merging ownership, management, or plotting a takeover? The answer is found in new information partnerships, enabling diverse companies to develop strategic coalitions through the sharing of data. The key to cooperation is a quantum improvement in the hardware and software supporting relational databases: new computer speeds, cheaper mass-storage devices, the proliferation of fiber-optic networks, and networking architectures. Information partnerships mean that companies can distribute the technological and financial exposure that comes with huge investments. For the customer's part, partnerships inevitably lead to greater simplification on the desktop and more common standards around which vendors have to compete. The most common types of partnership are: joint marketing partnerships, such as American Airline's award of frequent flyer miles to customers who use Citibank's credit card; intraindustry partnerships, such as the insurance value-added network service (which links insurance and casualty companies to independent agents); customer-supplier partnerships, such as Baxter Healthcare's electronic channel to hospitals for medical and other equipment; and IT vendor-driven partnerships, exemplified by ESAB (a European welding supplies and equipment company), whose expansion strategy was premised on a technology platform offered by an IT vendor. Partnerships that succeed have shared vision at the top, reciprocal skills in information technology, concrete plans for an early success, persistence in the development of usable information for all partners, coordination on business policy, and a new and imaginative business architecture.

  11. Circulating angiogenic biomolecules at rest and in response to upper-limb exercise in individuals with spinal cord injury.

    Science.gov (United States)

    Vasiliadis, Angelo V; Zafeiridis, Andreas; Dipla, Konstantina; Galanis, Nikiforos; Chatzidimitriou, Dimitrios; Kyparos, Antonios; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2014-03-01

    Individuals with spinal cord injury (SCI) show structural and functional vascular maladaptations and muscle loss in their lower limbs. Angiogenic biomolecules play important roles in physiological and pathological angiogenesis, and are implicated in the maintenance of muscle mass. This study examined the responses of angiogenic molecules during upper-limb aerobic exercise in patients with SCI and in able-bodied (AB) individuals. Eight SCI patients with thoracic lesions (T6-T12, ASIA A) and eight AB individuals performed an arm-cranking exercise for 30 minutes at 60% of their VO2max. Plasma concentrations of vascular endothelial growth factor (VEGF-A165), VEGF receptor 1 (sVEGFr-1), VEGF receptor 2 (sVEGFr-2), metalloproteinase 2 (MMP-2), and endostatin were measured at rest, after exercise, and at 1.5 and 3.0 hours during recovery. The two-way analysis of variance showed non-significant main effects of "group" and significant main effects of "time/exercise" for all angiogenic biomolecules examined (P < 0.01-0.001). The arm-cranking exercise significantly increased plasma concentrations of VEGF, sVEGFr-1, sVEGFr-2, MMP-2, and endostatin in both groups (P < 0.001-0.01). The magnitude of the increase was similar in both patients with SCI and AB individuals, as shown by the non-significant group × time interaction for all angiogenic parameters. Upper-limb exercise (arm-cranking for 30 minutes at 60% of VO2max) is a sufficient stimulus to trigger a coordinated circulating angiogenic response in patients with SCI. The response of angiogenic molecules to upper-limb aerobic exercise in SCI appears relatively similar to that observed in AB individuals.

  12. Inflammation and N-formyl peptide receptors mediate the angiogenic activity of human vitreous humour in proliferative diabetic retinopathy.

    Science.gov (United States)

    Rezzola, Sara; Corsini, Michela; Chiodelli, Paola; Cancarini, Anna; Nawaz, Imtiaz M; Coltrini, Daniela; Mitola, Stefania; Ronca, Roberto; Belleri, Mirella; Lista, Liliana; Rusciano, Dario; De Rosa, Mario; Pavone, Vincenzo; Semeraro, Francesco; Presta, Marco

    2017-04-01

    Angiogenesis and inflammation characterise proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus. However, the impact of inflammation on the pathogenesis of PDR neovascularisation has not been elucidated. Here, we assessed the capacity of PDR vitreous fluid to induce pro-angiogenic/proinflammatory responses in endothelium and the contribution of the inflammation-related pattern recognition N-formyl peptide receptors (FPRs) in mediating these responses. Pooled and individual pars plana vitrectomy-derived PDR vitreous fluid ('PDR vitreous') samples were assessed in endothelial cell proliferation, motility, sprouting and morphogenesis assays, and for the capacity to induce proinflammatory transcription factor activation, reactive oxygen species production, intercellular junction disruption and leucocyte-adhesion molecule upregulation in these cells. In vivo, the pro-angiogenic/proinflammatory activity of PDR vitreous was tested in murine Matrigel plug and chick embryo chorioallantoic membrane (CAM) assays. Finally, the FPR inhibitors Boc-Phe-Leu-Phe-Leu-Phe (Boc-FLFLF) and Ac-L-Arg-Aib-L-Arg-L-Cα(Me)Phe-NH2 tetrapeptide (UPARANT) were evaluated for their capacity to affect the biological responses elicited by PDR vitreous. PDR vitreous activates a pro-angiogenic/proinflammatory phenotype in endothelial cells. Accordingly, PDR vitreous triggers a potent angiogenic/inflammatory response in vivo. Notably, the different capacity of individual PDR vitreous samples to induce neovessel formation in the CAM correlates with their ability to recruit infiltrating CD45+ cells. Finally, the FPR inhibitor Boc-FLFLF and the novel FPR antagonist UPARANT inhibit neovessel formation and inflammatory responses triggered by PDR vitreous in the CAM assay. This study provides evidence that inflammation mediates the angiogenic activity of PDR vitreous and paves the way for the development of FPR-targeting anti-inflammatory/anti-angiogenic approaches for PDR

  13. Regulating the sharing economy

    Directory of Open Access Journals (Sweden)

    Kristofer Erickson

    2016-06-01

    Full Text Available In this introductory essay, we explore definitions of the ‘sharing economy’, a concept indicating both social (relational, communitarian and economic (allocative, profit-seeking aspects which appear to be in tension. We suggest combining the social and economic logics of the sharing economy to focus on the central features of network enabled, aggregated membership in a pool of offers and demands (for goods, services, creative expressions. This definition of the sharing economy distinguishes it from other related peer-to-peer and collaborative forms of production. Understanding the social and economic motivations for and implications of participating in the sharing economy is important to its regulation. Each of the papers in this special issue contributes to knowledge by linking the social and economic aspects of sharing economy practices to regulatory norms and mechanisms. We conclude this essay by suggesting future research to further clarify and render intelligible the sharing economy, not as a contradiction in terms but as an empirically observable realm of socio-economic activity.

  14. The pro-angiogenic properties of multi-functional bioactive glass composite scaffolds

    KAUST Repository

    Gerhardt, Lutz Christian

    2011-06-01

    The angiogenic properties of micron-sized (m-BG) and nano-sized (n-BG) bioactive glass (BG) filled poly(D,L lactide) (PDLLA) composites were investigated. On the basis of cell culture work investigating the secretion of vascular endothelial growth factor (VEGF) by human fibroblasts in contact with composite films (0, 5, 10, 20 wt %), porous 3D composite scaffolds, optimised with respect to the BG filler content capable of inducing angiogenic response, were produced. The in vivo vascularisation of the scaffolds was studied in a rat animal model and quantified using stereological analyses. The prepared scaffolds had high porosities (81-93%), permeability (k = 5.4-8.6 × 10-9 m2) and compressive strength values (0.4-1.6 MPa) all in the range of trabecular bone. On composite films containing 20 wt % m-BG or n-BG, human fibroblasts produced 5 times higher VEGF than on pure PDLLA films. After 8 weeks of implantation, m-BG and n-BG containing scaffolds were well-infiltrated with newly formed tissue and demonstrated higher vascularisation and percentage blood vessel to tissue (11.6-15.1%) than PDLLA scaffolds (8.5%). This work thus shows potential for the regeneration of hard-soft tissue defects and increased bone formation arising from enhanced vascularisation of the construct. © 2011 Elsevier Ltd.

  15. Impact of alginate concentration on the viability, cryostorage, and angiogenic activity of encapsulated fibroblasts.

    Science.gov (United States)

    Mohanty, Swetaparna; Wu, Yang; Chakraborty, Nilay; Mohanty, Pravansu; Ghosh, Gargi

    2016-08-01

    Cryopreservation or cryostorage of tissue engineered constructs can enhance the off-the shelf availability of these products and thus can potentially facilitate the commercialization or clinical translation of tissue engineered products. Encapsulation of cells within hydrogel matrices, in particular alginate, is widely used for fabrication of tissue engineered constructs. While previous studies have explored the cryopreservation response of cells encapsulated within alginate matrices, systematic investigation of the impact of alginate concentration on the metabolic activity and functionality of cryopreserved cells is lacking. The objective of the present work is to determine the metabolic and angiogenic activity of cryopreserved human dermal fibroblasts encapsulated within 1.0%, 1.5% and 2.0% (w/v) alginate matrices. In addition, the goal is to compare the efficacy of dimethyl sulfoxide (DMSO) and trehalose as cryoprotectant. Our study revealed that the concentration of alginate plays a significant role in the cryopreservation response of encapsulated cells. The lowest metabolic activity of the cryopreserved cells was observed in 1% alginate microspheres. When higher concentration of alginate was utilized for cell encapsulation, the metabolic and angiogenic activity of the cells frozen in the absence of cryoprotectants was comparable to that observed in the presence of DMSO or trehalose. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells.

    Science.gov (United States)

    Cerino, Giulia; Gaudiello, Emanuele; Muraro, Manuele Giuseppe; Eckstein, Friedrich; Martin, Ivan; Scherberich, Arnaud; Marsano, Anna

    2017-10-27

    In vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promoted in vitro the early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells upon in vivo ectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as an angiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.

  17. The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration

    Directory of Open Access Journals (Sweden)

    Petra Hilkens

    2017-01-01

    Full Text Available Adequate vascularization, a restricting factor for the survival of engineered tissues, is often promoted by the addition of stem cells or the appropriate angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs and stem cells from the apical papilla (SCAPs were applied in an in vivo model of dental pulp regeneration in order to compare their regenerative potential and confirm their previously demonstrated paracrine angiogenic properties. 3D-printed hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously transplanted into immunocompromised mice. After twelve weeks, histological and ultrastructural analysis demonstrated the regeneration of vascularized pulp-like tissue as well as mineralized tissue formation in all stem cell constructs. Despite the secretion of vascular endothelial growth factor in vitro, the stem cell constructs did not display a higher vascularization rate in comparison to control conditions. Similar results were found after eight weeks, which suggests both osteogenic/odontogenic differentiation of the transplanted stem cells and the promotion of angiogenesis in this particular setting. In conclusion, this is the first study to demonstrate the successful formation of vascularized pulp-like tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the promising role of this approach in dental tissue engineering.

  18. Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

    Directory of Open Access Journals (Sweden)

    Aline Lopes Ribeiro

    2017-01-01

    Full Text Available Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ. Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitor β-aminopropionitrile (βAPN significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity with βAPN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents.

  19. Anti-angiogenic activity in metastasis of human breast cancer cells irradiated by a proton beam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu-Shik; Shin, Jin-Sun; Nam, Kyung-Soo [Dongguk University, Gyeongju (Korea, Republic of); Shon, Yun-Hee [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2012-07-15

    Angiogenesis is an essential process of metastasis in human breast cancer. We investigated the effects of proton beam irradiation on angiogenic enzyme activities and their expressions in MCF-7 human breast cancer cells. The regulation of angiogenic regulating factors, of transforming growth factor-β (TGF-β) and of vesicular endothelial growth factor (VEGF) expression in breast cancer cells irradiated with a proton beam was studied. Aromatase activity and mRNA expression, which is correlated with metastasis, were significantly decreased by irradiation with a proton beam in a dose-dependent manner. TGF-β and VEGF transcriptions were also diminished by proton beam irradiation. In contrast, transcription of tissue inhibitors of matrix metalloproteinases (TIMPs), also known as biological inhibitors of matrix metalloproteinases (MMPs), was dose-dependently enhanced. Furthermore, an increase in the expression of TIMPs caused the MMP-9 activity to be diminished and the MMP-9 and the MMP-2 expressions to be decreased. These results suggest that inhibition of angiogenesis by proton beam irradiation in breast cancer cells is closely related to inhibitions of aromatase activity and transcription and to down-regulation of TGF-β and VEGF transcription.

  20. Mechanistic, technical, and clinical perspectives in therapeutic stimulation of coronary collateral development by angiogenic growth factors.

    Science.gov (United States)

    Rubanyi, Gabor M

    2013-04-01

    Stimulation of collateral vessel development in the heart by angiogenic growth factor therapy has been tested in animals and humans for almost two decades. Discordance between the outcome of preclinical studies and clinical trials pointed to the difficulties of translation from animal models to patients. Lessons learned in this process identified specific mechanistic, technical, and clinical hurdles, which need to be overcome. This review summarizes current understanding of the mechanisms leading to the establishment of a functional coronary collateral network and the biological processes growth factor therapies should stimulate even under conditions of impaired natural adaptive vascular response. Vector delivery methods are recommended to maximize angiogenic gene therapy efficiency and reduce side effects. Optimization of clinical trial design should include the choice of clinical end points which provide mechanistic proof-of-concept and also reflect clinical benefits (e.g., surrogates to assess increased collateral flow reserve, such as myocardial perfusion imaging). Guidelines are proposed to select patients who may respond to the therapy with high(er) probability. Both short and longer term strategies are outlined which may help to make therapeutic angiogenesis (TA) work in the future.

  1. Sensitive, quantitative, and high-throughput detection of angiogenic markers using shape-coded hydrogel microparticles.

    Science.gov (United States)

    Al-Ameen, Mohammad Ali; Li, Ji; Beer, David G; Ghosh, Gargi

    2015-07-07

    Elevated serum concentrations of angiogenic markers including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) have been correlated with various clinical disorders including cancer, cardiovascular diseases, diabetes mellitus, and liver fibrosis. In addition, the correlation between the serum concentrations of these factors, clinical diagnosis, prognosis, and response to therapeutic agents is significant. Thereby suggesting high-throughput detection of serum levels of angiogenic markers has important implications in early detection of different clinical disorders as well as for subsequent therapy monitoring. Here, we demonstrate the feasibility of utilization of shape-coded hydrogel microparticle based suspension arrays for quantitative and reproducible measurement of VEGF, FGF, and PDGF in single and multiplexed assays. Bio-inert PEG hydrogel attenuated the background signal thereby improving the sensitivity of the detection method as well as eliminating the need for blocking the proteins. In the singleplexed assay, the detection limits of 1.7 pg ml(-1), 1.4 pg ml(-1), and 1.5 pg ml(-1) for VEGF, FGF, and PDGF respectively indicated that the sensitivity of the developed method exceeds that of the conventional technologies. We also demonstrated that in the multiplexed assays, recovery of the proteins was within 20% of the expected values. The practical applicability of the hydrogel microparticle based detection system was established by demonstrating the ability of the system to quantify the production of VEGF, FGF, and PDGF by breast cancer cells (MDA-MB-231).

  2. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

    Energy Technology Data Exchange (ETDEWEB)

    Baer, Caroline; Squadrito, Mario Leonardo [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Iruela-Arispe, M. Luisa, E-mail: arispe@mcdb.ucla.edu [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland); Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles 90095, CA (United States); De Palma, Michele, E-mail: michele.depalma@epfl.ch [The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne (Switzerland)

    2013-07-01

    The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis. -- Highlights: • Macrophages promote angiogenesis by secreting proangiogenic factors. • Macrophages modulate angiogenesis via cell-to-cell contacts with endothelial cells. • Endothelial cells promote the differentiation of proangiogenic macrophages. • Macrophages and endothelial cells may cooperate to form angiogenic vascular niches.

  3. Anti-angiogenic activity in metastasis of human breast cancer cells irradiated by a proton beam

    Science.gov (United States)

    Lee, Kyu-Shik; Shin, Jin-Sun; Nam, Kyung-Soo; Shon, Yun-Hee

    2012-07-01

    Angiogenesis is an essential process of metastasis in human breast cancer. We investigated the effects of proton beam irradiation on angiogenic enzyme activities and their expressions in MCF-7 human breast cancer cells. The regulation of angiogenic regulating factors, of transforming growth factor- β (TGF- β) and of vesicular endothelial growth factor (VEGF) expression in breast cancer cells irradiated with a proton beam was studied. Aromatase activity and mRNA expression, which is correlated with metastasis, were significantly decreased by irradiation with a proton beam in a dose-dependent manner. TGF- β and VEGF transcriptions were also diminished by proton beam irradiation. In contrast, transcription of tissue inhibitors of matrix metalloproteinases (TIMPs), also known as biological inhibitors of matrix metalloproteinases (MMPs), was dose-dependently enhanced. Furthermore, an increase in the expression of TIMPs caused th MMP-9 activity to be diminished and the MMP-9 and the MMP-2 expressions to be decreased. These results suggest that inhibition of angiogenesis by proton beam irradiation in breast cancer cells is closely related to inhibitions of aromatase activity and transcription and to down-regulation of TGF- β and VEGF transcription.

  4. Antibacterial ability and angiogenic activity of Cu-Ti-O nanotube arrays.

    Science.gov (United States)

    Zong, Mingxiang; Bai, Long; Liu, Yanlian; Wang, Xin; Zhang, Xiangyu; Huang, Xiaobo; Hang, Ruiqiang; Tang, Bin

    2017-02-01

    Bacterial infection and loosening of orthopedic implants remain two disastrously postoperative complications. Angiogenesis is critical important to facilitate implant osseointegration in vivo. TiO2 nanotubes arrays (NTAs) with proper dimensions possess good osseointegration ability. Accordingly, the present work incorporated copper (Cu) into TiO2 NTAs (Cu-Ti-O NTAs) to enhance their antibacterial ability and angiogenesis activity, which was realized through anodizing magnetron-sputtered TiCu coatings with different Cu contents on pure titanium (Ti). Our results show ordered Cu-Ti-O NTAs can be produced under proper Cu content (coatings. The NTAs possess excellent long-term antibacterial ability against Staphylococcus aureus (S. aureus), which may be ascribed to sustained release of Cu(2+). The cytotoxicity of Cu-Ti-O NTAs to endothelial cells (ECs) could be negligible and can even promote cell proliferation as revealed by live/dead staining and MTT. Meanwhile, Cu-Ti-O NTAs can up-regulate nitric oxide (NO) synthesis and vascular endothelial growth factors (VEGF) secretion of ECs on the sample surfaces compared with that of pure TiO2 NTAs (control). Furthermore, the angiogenic activity is also enhanced in ionic extracts of Cu-Ti-O NTAs compared with the control. The excellent long-term antibacterial ability and favorable angiogenic activity render Cu-Ti-O NTAs to be promising implant coatings. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Coordinating Shared Activities

    Science.gov (United States)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  6. Sharing big biomedical data.

    Science.gov (United States)

    Toga, Arthur W; Dinov, Ivo D

    The promise of Big Biomedical Data may be offset by the enormous challenges in handling, analyzing, and sharing it. In this paper, we provide a framework for developing practical and reasonable data sharing policies that incorporate the sociological, financial, technical and scientific requirements of a sustainable Big Data dependent scientific community. Many biomedical and healthcare studies may be significantly impacted by using large, heterogeneous and incongruent datasets; however there are significant technical, social, regulatory, and institutional barriers that need to be overcome to ensure the power of Big Data overcomes these detrimental factors. Pragmatic policies that demand extensive sharing of data, promotion of data fusion, provenance, interoperability and balance security and protection of personal information are critical for the long term impact of translational Big Data analytics.

  7. Sharing the dance -

    DEFF Research Database (Denmark)

    He, Jing; Ravn, Susanne

    2017-01-01

    to the highly specialized field of elite sports dance, we aim at exploring the way in which reciprocity unfolds in intensive deliberate practices of movement. In our analysis, we specifically argue that the ongoing dynamics of two separate flows of movement constitute a shared experience of dancing together....... In this sense, moving together, in sports dance, is a practical way of understanding each other. In agreement with Zahavi, our analysis emphasizes the bi-directed nature of sharing. However, at the same time, we contribute to Zahavi’s ongoing endeavour as the special case of sports dance reveals how reciprocity...

  8. Rethinking the Sharing Economy

    DEFF Research Database (Denmark)

    Kornberger, Martin; Leixnering, Stephan; Meyer, Renate

    2017-01-01

    -governmental organization Train of Hope – labeled as a ‘citizen start-up’ by City of Vienna officials – played an outstanding role in mastering the crisis. In a blog post during his visit in Vienna at the time, and experiencing the refugee crisis first-hand, it was actually Henry Mintzberg who suggested reading...... arguments. Second, we hold that a particular form of organizing facilitates the sharing economy: the sharing economy organization. This particular organizational form is distinctive – at the same time selectively borrowing and skillfully combining features from platform organizations (e.g., use...

  9. Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil.

    Science.gov (United States)

    Carneiro, Cristiene Costa; da Costa Santos, Suzana; de Souza Lino, Ruy; Bara, Maria Teresa Freitas; Chaibub, Beatriz Abdallah; de Melo Reis, Paulo Roberto; Chaves, Dwight Assis; da Silva, Antônio Jorge Ribeiro; Silva, Luana Santos; de Melo E Silva, Daniela; Chen-Chen, Lee

    2016-11-01

    Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5μg/μL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Discordant clinical presentations of preeclampsia and intrauterine fetal growth restriction with similar pro- and anti-angiogenic profiles.

    Science.gov (United States)

    Alahakoon, Thushari I; Zhang, Weiyi; Trudinger, Brian J; Lee, Vincent W

    2014-12-01

    To evaluate the plasma levels of angiogenic factors in preeclampsia (PE) and intrauterine fetal growth restriction (IUGR) and their potential as biomarkers to distinguish normal from pathologic pregnancies. Case control study included singleton pregnancies in four categories: (i) normal (n = 29), (ii) PE (n = 15), (iii) PE and IUGR (n = 16) and (iv) IUGR (n = 24). The classification of IUGR included umbilical artery Doppler resistance. Maternal plasma placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble kinase domain receptor (sKDR) and soluble endoglin (sEng) as well as fetal umbilical artery sFlt-1 levels were determined. Each individual marker and their ratios were assessed for their potential to distinguish normal pregnancy from pregnancies affected by PE and/or IUGR. We found (i) elevated plasma sFlt-1, sEng and reduced PlGF, sKDR in PE and IUGR; (ii) similar angiogenic profiles in PE and IUGR and (iii) sEng and sFlt-1*sEng/PlGF performed best as biomarkers in identifying pathologic pregnancies. PE and IUGR have similar angiogenic profiles, suggesting that angiogenic marker profiles lack specificity in identifying PE and that other factors are required for the development of PE instead of IUGR. sEng should be included in a biomarker profile for predicting PE or IUGR.

  11. Are MSCs Angiogenic Cells?New Insights on Human Nestin-positive Bone Marrow-derived Multipotent Cells

    Directory of Open Access Journals (Sweden)

    Simone ePacini

    2014-05-01

    Full Text Available Recent investigations have made considerable progress in the understanding of tissue regeneration driven by mesenchymal stromal cells (MSCs. Data indicate the anatomical location of MSC as residing in the perivascular space of blood vessels dispersed across the whole body. This histological localization suggests that MSCs contribute to the formation of new blood vessels in vivo. Indeed, MSCs can release angiogenic factors and protease to facilitate blood vessel formation and in vitro are able to promote/support angiogenesis. However, the direct differentiation of MCSs into endothelial cells is still matter of debate. Most of the conflicting data might arise from the presence of multiple subtypes of cells with heterogeneous morph-functional features within the MSC cultures. According to this scenario, we hypothesize that the presence of the recently described Mesodermal Progenitor Cells (MPCs within the MSCs cultures is responsible for their variable angiogenic potential. Indeed, MPCs are Nestin-positive CD31-positive cells exhibiting angiogenic potential that differentiate in MSC upon proper stimuli. The ISCT criteria do not account for the presence of MPC within MSC culture generating confusion in the interpretation of MSC angiogenic potential. In conclusion, the discovery of MPC gives new insight in defining MSC ancestors in human bone marrow, and indicates the tunica intima as a further, and previously overlooked, possible additional source of MSC.

  12. Synthesis and anti-angiogenic effect of conjugates between serum albumin and non-steroidal anti-inflammatory drugs

    DEFF Research Database (Denmark)

    Kjaer, B; Struve, C; Friis, T

    2010-01-01

    of investigating the anti-angiogenic efficiency of NSAID-HSA conjugates in vitro, three NSAIDs, aspirin, ibuprofen, and naproxen were conjugated to HSA using different concentrations of their N-hydroxysuccinimide esters. Conjugation ratios from 10 to 50 were achieved and the conjugates retained a growth inhibitory...

  13. Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFκB activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhuoli; Gan, Xueqi [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Fan, Hongyi [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Applied Mechanics, College of Architecture and Environment, Sichuan University, Chengdu 610065 (China); Yu, Haiyang, E-mail: yhyang6812@foxmail.com [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China)

    2015-12-25

    Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFκB activity p65 increased upon mechanical stretch. Inhibition of NFκB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells. - Highlights: • Mechanical stretch increases the angiogenic capacity via VEGFA induction in MSCs. • Mechanical stretch increases the survival rate of MSCs under nutrients deprivation. • Mechanical stretch manipulates MSCs via the activation of NFκB.

  14. Soluble CD40 ligand impairs the function of peripheral blood angiogenic outgrowth cells and increases neointimal formation after arterial injury

    NARCIS (Netherlands)

    Hristov, Mihail; Gümbel, Denis; Lutgens, Esther; Zernecke, Alma; Weber, Christian

    2010-01-01

    Recent work has revealed an essential involvement of soluble CD40 ligand (sCD40L) in inflammation and atherosclerosis. We investigated whether sCD40L functionally affects peripheral blood-derived angiogenic early outgrowth cells (EOCs) and neointimal remodeling after arterial injury. Besides myeloid

  15. Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate-containing RGD peptide liposomes inhibits experimental arthritis

    NARCIS (Netherlands)

    Koning, Gerben A.; Wauben, MHM; Kok, Robert J.; Mastrobattista, E; Molema, Grietje; ten Hagen, TLM; Storm, G

    Objective. To investigate whether RGD peptide-exposing long circulating polyethylene glycol (PEG) liposomes (RGD-PEG-L) targeted to alpha v beta 3 integrins expressed on angiogenic vascular endothelial cells (VECs) are able to bind VECs at sites of inflammation and whether such liposomes containing

  16. Capillary growth in human skeletal muscle: physiological factors and the balance between pro-angiogenic and angiostatic factors.

    Science.gov (United States)

    Hellsten, Ylva; Hoier, Birgitte

    2014-12-01

    In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either by mechanical or by chemical signalling. Mechanical signals originate from shear stress forces on the endothelial cell layer induced by the blood flowing through the vessel, but include also mechanical stretch and compression of the vascular structures and the surrounding tissue, as the muscle contracts. Depending on the mechanical signal provided, capillary growth may occur either by longitudinal splitting (shear stress) or by sprouting (passive stretch). The mechanical signals initiate angiogenic processes by up-regulation or release of angioregulatory proteins that either promote, modulate or inhibit angiogenesis. A number of such regulatory proteins have been described in skeletal muscle in animal and cell models but also in human skeletal muscle. Important pro-angiogenic factors in skeletal muscle are vascular endothelial growth factor, endothelial nitric oxide synthase and angiopoietin 2, whereas angiostatic factors include thrombospondin-1 and tissue inhibitor of matrix metalloproteinase. Which of these angiogenic factors are up-regulated in the muscle tissue depends on the mechanical and chemical stimulus provided and, consequently, the process by which capillary growth occurs. The present review addresses physiological signals and angiogenic factors in skeletal muscle with a focus on human data.

  17. The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization

    NARCIS (Netherlands)

    Zeng, Wenjiao; Gouw, Annette S. H.; van den Heuvel, Marius C.; Zwiers, Peter J.; Zondervan, Pieter E.; Poppema, Sibrand; Zhang, Nong; Platteel, Inge; de Jong, Koert P.; Molema, Grietje

    2008-01-01

    Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein

  18. Immunoexpression of GLUT-1 and angiogenic index in pleomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas of the salivary glands.

    Science.gov (United States)

    de Souza, Lélia Batista; de Oliveira, Lucileide Castro; Nonaka, Cassiano Francisco Weege; Lopes, Maria Luiza Diniz de Sousa; Pinto, Leão Pereira; Queiroz, Lélia Maria Guedes

    2017-06-01

    This study aimed to evaluate and compare the immunoexpression of glucose transporter-1 (GLUT-1) and angiogenic index between pleomorphic adenomas (PAs), adenoid cystic carcinomas (ACCs), and mucoepidermoid carcinomas (MECs) of the salivary glands, and establish associations with the respective subtype/histological grade. Twenty PAs, 20 ACCs, and 10 MECs were submitted to morphological and immunohistochemical analysis. GLUT-1 expression was semi-quantitatively evaluated and angiogenic index was assessed by microvessel counts using anti-CD34 antibody. Higher GLUT-1 immunoexpression was observed in the MECs compared to PAs and ACCs (p = 0.022). Mean number of microvessels was 66.5 in MECs, 40.4 in PAs, and 21.2 in ACCs (p GLUT-1 expression and angiogenic index showed no significant correlation in the tumors studied. Results suggest that differences in biological behavior of the studied tumors are related to GLUT-1. Benign and malignant salivary gland tumors differ in the angiogenic index; however, angiogenesis may be independent of the tumor cell's metabolic demand.

  19. P53 mutation analysis of colorectal liver metastases : Relation to actual survival, angiogenic status, and p53 overexpression

    NARCIS (Netherlands)

    de Jong, KP; Gouw, ASH; Peeters, PMJG; Bulthuis, M; Menkema, L; Porte, RJ; Slooff, MJH; van Goor, H; van den Berg, Anke

    2005-01-01

    Purpose: To correlate TP53 mutations with angiogenic status of the tumor and prognosis after liver surgery in patients with colorectal liver metastases and to correlate immunohistochemical staining of p53 protein with TP53 gene mutations. Experimental Design: Tumors of 44 patients with surgically

  20. VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment

    Directory of Open Access Journals (Sweden)

    Skowronski Karolina

    2010-12-01

    Full Text Available Abstract Background Targeting tumor vasculature is a strategy with great promise in the treatment of many cancers. However, anti-angiogenic reagents that target VEGF/VEGFR2 signaling have met with variable results clinically. Among the possible reasons for this may be heterogeneous expression of the target protein. Methods Double immunofluorescent staining was performed on formalin-fixed paraffin embedded sections of treated and control SW480 (colorectal and WM239 (melanoma xenografts, and tissue microarrays of human colorectal carcinoma and melanoma. Xenografts were developed using RAG1-/- mice by injection with WM239 or SW480 cells and mice were treated with 20 mg/kg/day of cyclophosphamide in their drinking water for up to 18 days. Treated and control tissues were characterized by double immunofluorescence using the mural cell marker α-SMA and CD31, while the ratio of desmin/CD31 was also determined by western blot. Hypoxia in treated and control tissues were quantified using both western blotting for HIF-1α and immunohistochemistry of CA-IX. Results VEGFR2 is heterogeneously expressed in tumor vasculature in both malignant melanoma and colorectal carcinoma. We observed a significant decrease in microvascular density (MVD in response to low dose metronomic cyclophosphamide chemotherapy in both malignant melanoma (with higher proportion VEGFR2 positive blood vessels; 93% and colorectal carcinoma (with lower proportion VEGFR2 positive blood vessels; 60% xenografts. This reduction in MVD occurred in the absence of a significant anti-tumor effect. We also observed less hypoxia in treated melanoma xenografts, despite successful anti-angiogenic blockade, but no change in hypoxia of colorectal xenografts, suggesting that decreases in tumor hypoxia reflect a complex relationship with vascular density. Based on α-SMA staining and the ratio of desmin to CD31 expression as markers of tumor blood vessel functionality, we found evidence for increased

  1. Angiogenic Mechanisms of Human CD34+ Stem Cell Exosomes in the Repair of Ischemic Hindlimb.

    Science.gov (United States)

    Mathiyalagan, Prabhu; Liang, Yaxuan; Kim, David; Misener, Sol; Thorne, Tina; Kamide, Christine E; Klyachko, Ekaterina; Losordo, Douglas W; Hajjar, Roger J; Sahoo, Susmita

    2017-04-28

    Paracrine secretions seem to mediate therapeutic effects of human CD34+ stem cells locally transplanted in patients with myocardial and critical limb ischemia and in animal models. Earlier, we had discovered that paracrine secretion from human CD34+ cells contains proangiogenic, membrane-bound nanovesicles called exosomes (CD34Exo). Here, we investigated the mechanisms of CD34Exo-mediated ischemic tissue repair and therapeutic angiogenesis by studying their miRNA content and uptake. When injected into mouse ischemic hindlimb tissue, CD34Exo, but not the CD34Exo-depleted conditioned media, mimicked the beneficial activity of their parent cells by improving ischemic limb perfusion, capillary density, motor function, and their amputation. CD34Exo were found to be enriched with proangiogenic miRNAs such as miR-126-3p. Knocking down miR-126-3p from CD34Exo abolished their angiogenic activity and beneficial function both in vitro and in vivo. Interestingly, injection of CD34Exo increased miR-126-3p levels in mouse ischemic limb but did not affect the endogenous synthesis of miR-126-3p, suggesting a direct transfer of stable and functional exosomal miR-126-3p. miR-126-3p enhanced angiogenesis by suppressing the expression of its known target, SPRED1, simultaneously modulating the expression of genes involved in angiogenic pathways such as VEGF (vascular endothelial growth factor), ANG1 (angiopoietin 1), ANG2 (angiopoietin 2), MMP9 (matrix metallopeptidase 9), TSP1 (thrombospondin 1), etc. Interestingly, CD34Exo, when treated to ischemic hindlimbs, were most efficiently internalized by endothelial cells relative to smooth muscle cells and fibroblasts, demonstrating a direct role of stem cell-derived exosomes on mouse endothelium at the cellular level. Collectively, our results have demonstrated a novel mechanism by which cell-free CD34Exo mediates ischemic tissue repair via beneficial angiogenesis. Exosome-shuttled proangiogenic miRNAs may signify amplification of stem

  2. Information Sharing and Knowledge Sharing as Communicative Activities

    Science.gov (United States)

    Savolainen, Reijo

    2017-01-01

    Introduction: This paper elaborates the picture of information sharing and knowledge sharing as forms of communicative activity. Method: A conceptual analysis was made to find out how researchers have approached information sharing and knowledge sharing from the perspectives of transmission and ritual. The findings are based on the analysis of one…

  3. Computing on quantum shared secrets

    Science.gov (United States)

    Ouyang, Yingkai; Tan, Si-Hui; Zhao, Liming; Fitzsimons, Joseph F.

    2017-11-01

    A (k ,n )-threshold secret-sharing scheme allows for a string to be split into n shares in such a way that any subset of at least k shares suffices to recover the secret string, but such that any subset of at most k -1 shares contains no information about the secret. Quantum secret-sharing schemes extend this idea to the sharing of quantum states. Here we propose a method of performing computation securely on quantum shared secrets. We introduce a (n ,n )-quantum secret sharing scheme together with a set of algorithms that allow quantum circuits to be evaluated securely on the shared secret without the need to decode the secret. We consider a multipartite setting, with each participant holding a share of the secret. We show that if there exists at least one honest participant, no group of dishonest participants can recover any information about the shared secret, independent of their deviations from the algorithm.

  4. Shared Care in Diabetes?

    DEFF Research Database (Denmark)

    Bødker, Keld

    2006-01-01

    The Danish National Board of Health has recently released a report that is intended to mark the start of a new project to establish it support for shared care in diabetes. In this paper I raise a number of concerns where lack of attention towards participation from prospective users constitute...

  5. A shared vision.

    Science.gov (United States)

    Hogan, Brigid

    2007-12-01

    One of today's most powerful technologies in biomedical research--the creation of mutant mice by gene targeting in embryonic stem (ES) cells--was finally celebrated in this year's Nobel Prize in Medicine. The history of how ES cells were first discovered and genetically manipulated highlights the importance of collaboration among scientists from different backgrounds with a shared vision.

  6. Beyond processor sharing

    NARCIS (Netherlands)

    S. Aalto; U. Ayesta (Urtzi); S.C. Borst (Sem); V. Misra; R. Núñez Queija (Rudesindo (Sindo))

    2007-01-01

    textabstractWhile the (Egalitarian) Processor-Sharing (PS) discipline offers crucial insights in the performance of fair resource allocation mechanisms, it is inherently limited in analyzing and designing differentiated scheduling algorithms such as Weighted Fair Queueing and Weighted Round-Robin.

  7. Too Much Information Sharing?

    DEFF Research Database (Denmark)

    Ganuza, Juan José; Jansen, Jos

    2013-01-01

    parameters gives the following trade-off in Cournot oligopoly. On the one hand, it decreases the expected consumer surplus for a given information precision, as the literature shows. On the other hand, information sharing increases the firms’ incentives to acquire information, and the consumer surplus...

  8. Promoting teachers’ knowledge sharing

    NARCIS (Netherlands)

    Runhaar, P.R.; Sanders, K.

    2016-01-01

    Teachers’ professional development is nowadays seen as key in efforts to improve education. Knowledge sharing is a learning activity with which teachers not only professionalize themselves, but contribute to the professional development of their colleagues as well. This paper presents two studies,

  9. The Sharing Economy

    DEFF Research Database (Denmark)

    Hamari, Juho; Sjöklint, Mimmi; Ukkonen, Antti

    2016-01-01

    Information and communications technologies (ICTs) have enabled the rise of so-called “Collaborative Consumption” (CC): the peer-to-peer-based activity of obtaining, giving, or sharing the access to goods and services, coordinated through community-based online services. CC has been expected to a...

  10. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...

  11. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...

  12. SharedSpaces mingle

    NARCIS (Netherlands)

    Handberg, L.; Gullström, C.; Kort, J.; Nyström, J.

    2016-01-01

    SharedSpaces is a WebRTC design prototype that creates a virtual media space where people can mingle and interact. Although you are in different locations, you appear side by side in front of a chosen backdrop. This interactive installation addresses spatial and social connectedness, stressing the

  13. Evaluation of a collagen-chitosan hydrogel for potential use as a pro-angiogenic site for islet transplantation.

    Directory of Open Access Journals (Sweden)

    Joanne E McBane

    Full Text Available Islet transplantation to treat type 1 diabetes (T1D has shown varied long-term success, due in part to insufficient blood supply to maintain the islets. In the current study, collagen and collagen:chitosan (10:1 hydrogels, +/- circulating angiogenic cells (CACs, were compared for their ability to produce a pro-angiogenic environment in a streptozotocin-induced mouse model of T1D. Initial characterization showed that collagen-chitosan gels were mechanically stronger than the collagen gels (0.7 kPa vs. 0.4 kPa elastic modulus, respectively, had more cross-links (9.2 vs. 7.4/µm(2, and were degraded more slowly by collagenase. After gelation with CACs, live/dead staining showed greater CAC viability in the collagen-chitosan gels after 18 h compared to collagen (79% vs. 69%. In vivo, collagen-chitosan gels, subcutaneously implanted for up to 6 weeks in a T1D mouse, showed increased levels of pro-angiogenic cytokines over time. By 6 weeks, anti-islet cytokine levels were decreased in all matrix formulations ± CACs. The 6-week implants demonstrated increased expression of VCAM-1 in collagen-chitosan implants. Despite this, infiltrating vWF(+ and CXCR4(+ angiogenic cell numbers were not different between the implant types, which may be due to a delayed and reduced cytokine response in a T1D versus non-diabetic setting. The mechanical, degradation and cytokine data all suggest that the collagen-chitosan gel may be a suitable candidate for use as a pro-angiogenic ectopic islet transplant site.

  14. Modeling tumor-associated edema in gliomas during anti-angiogenic therapy and its impact on imageable tumor

    Directory of Open Access Journals (Sweden)

    Andrea eHawkins-Daarud

    2013-04-01

    Full Text Available Glioblastoma, the most aggressive form of primary brain tumor is predominantly assessed with gadolinium-enhanced T1-weighted (T1Gd and T2-weighted magnetic resonance imaging (MRI. Pixel intensity enhancement on the T1Gd image is understood to correspond to the gadolinium contrast agent leaking from the tumor-induced neovasculature, while hyperintensity on the T2/FLAIR images corresponds with edema and infiltrated tumor cells. None of these modalities directly show tumor cells; rather, they capture abnormalities in the microenvironment caused by the presence of tumor cells. Thus, assessing disease response after treatments impacting the microenvironment remains challenging through the obscuring lens of MR imaging. Anti-angiogenic therapies have been used in the treatment of gliomas with spurious results ranging from no apparent response to significant imaging improvement with the potential for extremely diffuse patterns of tumor recurrence on imaging and autopsy. Anti-angiogenic treatment normalizes the vasculature, effectively decreasing vessel permeability and thus reducing tumor-induced edema, drastically altering T2-weighted MRI. We extend a previously developed mathematical model of glioma growth to explicitly incorporate edema formation allowing us to directly characterize and potentially predict the effects of anti-angiogenics on imageable tumor growth. A comparison of simulated glioma growth and imaging enhancement with and without bevacizumab supports the current understanding that anti-angiogenic treatment can serve as a surrogate for steroids and the clinically-driven hypothesis that anti-angiogenic treatment may not have any significant effect on the growth dynamics of the overall tumor-cell populations. However, the simulations do illustrate a potentially large impact on the level of edematous extracellular fluid, and thus on what would be imageable on T2/FLAIR MR for tumors with lower proliferation rates.

  15. MicroRNA-20a constrains p300-driven myocardial angiogenic transcription by direct targeting of p300.

    Directory of Open Access Journals (Sweden)

    Lina A Shehadeh

    Full Text Available To characterize downstream effectors of p300 acetyltransferase in the myocardium.Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known.Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17∼92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17∼92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3'UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts.p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a.

  16. Evaluation of a Collagen-Chitosan Hydrogel for Potential Use as a Pro-Angiogenic Site for Islet Transplantation

    Science.gov (United States)

    McBane, Joanne E.; Vulesevic, Branka; Padavan, Donna T.; McEwan, Kimberly A.; Korbutt, Gregory S.; Suuronen, Erik J.

    2013-01-01

    Islet transplantation to treat type 1 diabetes (T1D) has shown varied long-term success, due in part to insufficient blood supply to maintain the islets. In the current study, collagen and collagen:chitosan (10:1) hydrogels, +/- circulating angiogenic cells (CACs), were compared for their ability to produce a pro-angiogenic environment in a streptozotocin-induced mouse model of T1D. Initial characterization showed that collagen-chitosan gels were mechanically stronger than the collagen gels (0.7kPa vs. 0.4kPa elastic modulus, respectively), had more cross-links (9.2 vs. 7.4/µm2), and were degraded more slowly by collagenase. After gelation with CACs, live/dead staining showed greater CAC viability in the collagen-chitosan gels after 18h compared to collagen (79% vs. 69%). In vivo, collagen-chitosan gels, subcutaneously implanted for up to 6 weeks in a T1D mouse, showed increased levels of pro-angiogenic cytokines over time. By 6 weeks, anti-islet cytokine levels were decreased in all matrix formulations ± CACs. The 6-week implants demonstrated increased expression of VCAM-1 in collagen-chitosan implants. Despite this, infiltrating vWF+ and CXCR4+ angiogenic cell numbers were not different between the implant types, which may be due to a delayed and reduced cytokine response in a T1D versus non-diabetic setting. The mechanical, degradation and cytokine data all suggest that the collagen-chitosan gel may be a suitable candidate for use as a pro-angiogenic ectopic islet transplant site. PMID:24204863

  17. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Elena V Rosca

    Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  18. Aminopeptidase N inhibition could be involved in the anti-angiogenic effect of dobesilates

    Directory of Open Access Journals (Sweden)

    Farsa Oldřich

    2015-01-01

    Full Text Available Calcium, magnesium and zinc 2,5-dihydroxybenzenesulfonates (dobesilates were synthesized by sulfonation of hydroquinone with sulfuric acid under mild conditions. To form the salts, neutralization with calcium carbonate followed by cation exchange by means of magnesium or zinc sulfates was performed. The dobesilates were characterized by standard spectral methods and by AAS for metal content and then tested for inhibitory activity against aminopeptidase N. Calcium and magnesium 2,5-dihydroxybenzene sulfonates exhibited rather weak inhibitory activity to aminopeptidase N as demonstrated by IC50 values of 978.0 and 832.1 mmol l-1 respectively while zinc 2,5-dihydroxybenzene sulfonate reached the more significant inhibitory activity characterized by IC50 77.4 mmol l-1. The inhibitory activity results suggest that the inhibition of aminopeptidase N could play a role in the anti-angiogenic activity of 2,5-dihydroxybenzenesulfonates.

  19. Resveratrol modulates the angiogenic response to exercise training in skeletal muscle of aged men

    DEFF Research Database (Denmark)

    Gliemann Hybholt, Lasse; Olesen, Jesper; Biensø, Rasmus S

    2014-01-01

    Aim: The polyphenol resveratrol has in animal studies been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Methods: Forty-three healthy...... physically inactive aged men (65±1 years) were divided into A) a training group that conducted 8 weeks of intense exercise training where half of the subjects received a daily intake of either 250 mg trans resveratrol (n=14) and the other half received placebo (n=13); and B) a non-training group...... that received either 250 mg trans resveratrol (n=9) or placebo (n=7). Results: The group that trained with placebo showed a ~20% increase in capillary to fiber (C:F) ratio, an increase in the muscle protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2, and tissue inhibitor of matrix...

  20. Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells

    Science.gov (United States)

    Ma, Jin-Ling; van den Beucken, Jeroen J. J. P.; Pan, Ju-Li; Cui, Fu-Zhai; Chen, Su

    2014-03-01

    Cellular strategies remain a crucial component in bone tissue engineering (BTE). So far, the outcome of cell-based strategies from initial clinical trials is far behind compared to animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the tissue-engineered constructs. Cocultures, by introducing angiogenic cells into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, pre-clinical studies demonstrated that cocultures enhance vascularization and bone formation compared to monocultures. However, there has been no report on the application of cocultures in clinics. Therefore, this mini-review aims to provide an overview regarding (i) critical parameters in cocultures and the outcomes of cocultures compared to monocultures in the currently available pre-clinical studies using human mesenchymal stem cells implanted in orthotopic animal models; and (ii) the usage of monocultures in clinical application in BTE.

  1. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Science.gov (United States)

    Rosca, Elena V; Penet, Marie-France; Mori, Noriko; Koskimaki, Jacob E; Lee, Esak; Pandey, Niranjan B; Bhujwalla, Zaver M; Popel, Aleksander S

    2014-01-01

    We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  2. Single-step synthesis of heparin-doped polypyrrole nanoparticles for delivery of angiogenic factor.

    Science.gov (United States)

    Xiong, Gordon M; Yap, Yi Zhen; Choong, Cleo

    2016-04-01

    To perform one-pot synthesis of heparin-immobilized polypyrrole (PPy) nanoparticles and evaluate the use of these nanoparticles for the delivery of VEGF. Heparin-stabilized synthesis of PPy nanoparticles was performed via oxidative polymerization. VEGF-bound PPy-heparin nanoparticles were delivered to endothelial cells and bioactivity of VEGF was assessed by Matrigel tube formation. Size-controllable synthesis of heparin-doped PPy nanoparticles was achieved, and heparin promoted the conjugation of VEGF. Angiogenic activity of the VEGF-conjugated PPy nanoparticles was verified. Heparin-doped PPy nanoparticles can be synthesized using one-pot reaction and provide a delivery platform by which VEGF can be conjugated onto.

  3. Bisphosphonate-related osteonecrosis of jaw (BRONJ: an anti-angiogenic side-effect?

    Directory of Open Access Journals (Sweden)

    Petcu Eugen B

    2012-07-01

    Full Text Available Abstract Bisphosphonates are recommended in the treatment of osteoporosis and some cancers, in which case they prevent the appearance of bone metastasis. The patients taking bisphosphonates are at increased risk of developing bisphosphonate-related osteonecrosis of jaw (BRONJ which is characterised by the presence of an un-healing wound after dental surgery. BRONJ might represent an anti-angiogenic side effect. However, the real number of patients with BRONJ might be higher than currently recorded. Considering the differential diagnosis which includes various primary and secondary cancers, a correct histopathological diagnosis is very important. The morphological criteria for diagnosis of BRONJ are highlighted in this material. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1813972972323288

  4. Pericyte plasticity - comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues.

    Science.gov (United States)

    Herrmann, M; Bara, J J; Sprecher, C M; Menzel, U; Jalowiec, J M; Osinga, R; Scherberich, A; Alini, M; Verrier, S

    2016-04-10

    Pericyte recruitment is essential for the stability of newly formed vessels. It was also suggested that pericytes represent common ancestor cells giving rise to mesenchymal stem cells (MSCs) in the adult. Here, we systematically investigated pericytes and MSCs from different human tissues in terms of their angiogenic and multilineage differentiation potential in vitro in order to assess the suitability of the different cell types for the regeneration of vascularised tissues. Magnetic-activated cell sorting (MACS®) was used to enrich CD34-CD146+ pericytes from adipose tissue (AT) and bone marrow (BM). The multilineage potential of pericytes was assessed by testing their capability to differentiate towards osteogenic, adipogenic and chondrogenic lineage in vitro. Pericytes and endothelial cells were co-seeded on Matrigel™ and the formation of tube-like structures was examined to study the angiogenic potential of pericytes. MSCs from AT and BM were used as controls. CD34-CD146+ cells were successfully enriched from AT and BM. Only BM-derived cells exhibited trilineage differentiation potential. AT-derived cells displayed poor chondrogenic differentiation upon stimulation with transforming growth factor-β1. Interestingly, osteogenic differentiation was more efficient in AT-PC and BM-PC compared to the respective full MSC population. Matrigel™ assays revealed that pericytes from all tissues integrated into tube-like structures. We show that MACS®-enriched pericytes from BM and AT have the potential to regenerate tissues of different mesenchymal lineages and support neovascularisation. MACS® represents a simple enrichment strategy of cells, which is of particular interest for clinical application. Finally, our results suggest that the regenerative potential of pericytes depends on their tissue origin, which is an important consideration for future studies.

  5. Angiogenic evaluation of ginsenoside Rg 1 from Panax ginseng in fluorescent transgenic mice.

    Science.gov (United States)

    Lin, Kurt Ming-Chao; Hsu, Ching-Han; Rajasekaran, Subbiah

    2008-07-01

    Evaluation of angiogenesis-inducing compounds is essential in tissue engineering to develop biological substitutes for the repair or regeneration of tissue function. In this report, we evaluated the angiogenic ability of ginsenoside Rg 1 from Panax ginseng, in Matrigel implanted on fluorescent transgenic mice. The in vitro proliferation ability of each test agent was estimated by MTS assay. The Matrigel loaded with basic fibroblast growth factor (bFGF) or Rg 1 and Matrigel alone were implanted on fluorescent transgenic mice and were retrieved at 1, 4, 6 and 8 weeks after implantation to measure various conventional markers for angiogenesis including neo-vascular density and hemoglobin content. Additionally, the functional neo-vasculature in the implanted Matrigel was visualized using confocal laser scanning microscopy (CLSM). The in vitro results indicated that the stimulating effect of Rg 1 on HUVECs proliferation remained unchanged after dissolved for 30 days in culture medium at 37 degrees C when compared with the effect of bFGF. One week after implantation in transgenic mice, bFGF or Rg 1 mixed in Matrigel plug significantly enhanced angiogenesis; however, at 6 weeks a significant decrease in angiogenic effect was observed in Matrigel with bFGF, but not in Matrigel with Rg 1. The neo-vessels structure was visualized in three dimensions (3D) by CLSM and the results were in agreement with other conventional measurements for angiogenesis. These findings confirm that Rg 1 could be used in tissue tissue-engineering applications and that the fluorescent transgenic mice can be a useful experimental model for studying angiogenesis.

  6. The effect of gestational age on angiogenic gene expression in the rat placenta.

    Directory of Open Access Journals (Sweden)

    Kanchan Vaswani

    Full Text Available The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes during gestation as the fetus develops and as demands for energy substrate transfer and gas exchange increase. The molecular mechanisms that coordinate these changes have yet to be fully elucidated. The study performed a large scale screen of the transcriptome of the rat placenta throughout mid-late gestation (E14.25-E20 with emphasis on characterizing gestational age associated changes in the expression of genes involved in angiogenic pathways. Sprague Dawley dams were sacrificed at E14.25, E15.25, E17.25 and E20 (n = 6 per group and RNA was isolated from one placenta per dam. Changes in placental gene expression were identified using Illumina Rat Ref-12 Expression BeadChip Microarrays. Differentially expressed genes (>2-fold change, <1% false discovery rate, FDR were functionally categorised by gene ontology pathway analysis. A subset of differentially expressed genes identified by microarrays were confirmed using Real-Time qPCR. The expression of thirty one genes involved in the angiogenic pathway was shown to change over time, using microarray analysis (22 genes displayed increased and 9 gene decreased expression. Five genes (4 up regulated: Cd36, Mmp14, Rhob and Angpt4 and 1 down regulated: Foxm1 involved in angiogenesis and blood vessel morphogenesis were subjected to further validation. qPCR confirmed late gestational increased expression of Cd36, Mmp14, Rhob and Angpt4 and a decrease in expression of Foxm1 before labour onset (P<0.0001. The observed acute, pre-labour changes in the expression of the 31 genes during gestation warrant further investigation to elucidate their role in pregnancy.

  7. Chronic inflammation and angiogenic signaling axis impairs differentiation of dental-pulp stem cells.

    Science.gov (United States)

    Boyle, Michael; Chun, Crystal; Strojny, Chelsee; Narayanan, Raghuvaran; Bartholomew, Amelia; Sundivakkam, Premanand; Alapati, Satish

    2014-01-01

    Dental-pulp tissue is often exposed to inflammatory injury. Sequested growth factors or angiogenic signaling proteins that are released following inflammatory injury play a pivotal role in the formation of reparative dentin. While limited or moderate angiogenesis may be helpful for dental pulp maintenance, the induction of significant level of angiogenesis is probably highly detrimental. Hitherto, several studies have addressed the effects of proinflammatory stimuli on the survival and differentiation of dental-pulp stem cells (DPSC), in vitro. However, the mechanisms communal to the inflammatory and angiogenic signaling involved in DPSC survival and differentiation remain unknown. Our studies observed that short-term exposure to TNF-α (6 and 12 hours [hrs]) induced apoptosis with an upregulation of VEGF expression and NF-κB signaling. However, long-term (chronic) exposure (14 days) to TNF-α resulted in an increased proliferation with a concomitant shortening of the telomere length. Interestingly, DPSC pretreated with Nemo binding domain (NBD) peptide (a cell permeable NF-κB inhibitor) significantly ameliorated TNF-α- and/or VEGF-induced proliferation and the shortening of telomere length. NBD peptide pretreatment significantly improved TNF-α-induced downregulation of proteins essential for differentiation, such as bone morphogenic proteins (BMP)-1 & 2, BMP receptor isoforms-1&2, trasnforming growth factor (TGF), osteoactivin and osteocalcin. Additionally, inhibition of NF-κB signaling markedly increased the mineralization potential, a process abrogated by chronic exposure to TNF-α. Thus, our studies demonstrated that chronic inflammation mediates telomere shortening via NF-κB signaling in human DPSC. Resultant chromosomal instability leads to an emergence of increased proliferation of DPSC, while negatively regulating the differentiation of DPSC, in vitro.

  8. Stearic acid at physiologic concentrations induces in vitro lipotoxicity in circulating angiogenic cells.

    Science.gov (United States)

    Spigoni, Valentina; Fantuzzi, Federica; Fontana, Alessia; Cito, Monia; Derlindati, Eleonora; Zavaroni, Ivana; Cnop, Miriam; Bonadonna, Riccardo C; Dei Cas, Alessandra

    2017-10-01

    Saturated free fatty acids (SFAs) can induce lipotoxicity in different cells. No studies have investigated the effects of SFA in circulating angiogenic cells (CACs), which play a key role in endothelial repair processes. The aim of the study was to assess the effects of SFAs, specifically stearic acid (SA), on viability and function of CACs and to investigate potential underlying molecular mechanisms. CACs were isolated from healthy subjects by established methods. CACs were incubated with BSA-complexed stearate (100 μM) to assess the time course (from 8 to 24 h exposure) of the effects on viability and apoptosis (activation of caspases 3/7), angiogenic function (tube formation assay), pro-inflammatory cytokine (IL-1β, IL-6, IL-8, MCP-1 and TNFα) gene expression (qPCR) and secretion (ELISA), activation of MAPK (JNK, p38 and Erk1/2) by Western blot and endoplasmic reticulum (ER) stress marker (CHOP, BIP, ATF4, XBP-1 and sXBP-1) gene expression by qPCR. Stearic acid activates effector caspases in CACs in a dose- and time-dependent manner. SA also impairs CAC function and increases pro-inflammatory molecule (IL-1β, IL-6, IL-8, MCP-1 and TNFα) gene expression and secretion in CACs starting from 3 h of incubation. The activation of JNK by SA mediates pro-inflammatory response, but it may be not necessary for apoptosis. Moreover, SA induces the expression of ER stress markers across the three branches of the ER stress response. In humans, both function and viability of CACs are exquisitely vulnerable to physiologic concentrations of stearate; lipotoxic impairment of endothelial repair processes may be implicated in vascular damage caused by SFAs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia.

    Science.gov (United States)

    Francki, Aleksandar; Labazzo, Kristen; He, Shuyang; Baum, Ellen Z; Abbot, Stewart E; Herzberg, Uri; Hofgartner, Wolfgang; Hariri, Robert

    2016-09-01

    Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties. The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase. PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed. PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  10. Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity.

    Science.gov (United States)

    Hughes-Large, Jennifer M; Pang, Dominic K T; Robson, Debra L; Chan, Pak; Toma, Jelena; Borradaile, Nica M

    2014-12-01

    Niacin (nicotinic acid) as a monotherapy can reduce vascular disease risk, but its mechanism of action remains controversial, and may not be dependent on systemic lipid modifying effects. Niacin has recently been shown to improve endothelial function and vascular regeneration, independent of correcting dyslipidemia, in rodent models of vascular injury and metabolic disease. As a potential biosynthetic precursor for NAD(+), niacin could elicit these vascular benefits through NAD(+)-dependent, sirtuin (SIRT) mediated responses. Alternatively, niacin may act through its receptor, GPR109A, to promote endothelial function, though endothelial cells are not known to express this receptor. We hypothesized that niacin directly improves endothelial cell function during exposure to lipotoxic conditions and sought to determine the potential mechanism(s) involved. Angiogenic function in excess palmitate was assessed by tube formation following treatment of human microvascular endothelial cells (HMVEC) with either a relatively low concentration of niacin (10 μM), or nicotinamide mononucleotide (NMN) (1 μM), a direct NAD(+) precursor. Although both niacin and NMN improved HMVEC tube formation during palmitate overload, only NMN increased cellular NAD(+) and SIRT1 activity. We further observed that HMVEC express GRP109A. Activation of this receptor with either acifran or MK-1903 recapitulated niacin-induced improvements in HMVEC tube formation, while GPR109A siRNA diminished the effect of niacin. Niacin, at a low concentration, improves HMVEC angiogenic function under lipotoxic conditions, likely independent of NAD(+) biosynthesis and SIRT1 activation, but rather through niacin receptor activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Angiogenic factor AGGF1 promotes therapeutic angiogenesis in a mouse limb ischemia model.

    Directory of Open Access Journals (Sweden)

    Qiulun Lu

    Full Text Available BACKGROUND: Peripheral arterial disease (PAD is a common disease accounting for about 12% of the adult population, and causes significant morbidity and mortality. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD. METHODS AND RESULTS: We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 (AGGF1 group resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice with injection of the empty vector (control group. Color PW Doppler echocardiography showed that the blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration (n = 9/group, P = 0.049, 0.001, and 0.001, respectively. Increased blood flow in the AGGF1 group was correlated to increased density of CD31-positive vessels and decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. Ambulatory impairment was significantly reduced in the AGGF1 group compared to the control group (P = 0.004. The effect of AGGF1 was dose-dependent. At day 28 after gene transfer, AGGF1 was significantly better in increasing blood flow than FGF-2 (P = 0.034, although no difference was found for tissue necrosis and ambulatory impairment. CONCLUSIONS: These data establish AGGF1 as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.

  12. Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies.

    Science.gov (United States)

    Patrikidou, Anna; Sinapi, Isabelle; Regnault, Hélène; Fayard, Florence; Bouattour, Mohamed; Fartoux, Laetitia; Faivre, Sandrine; Malka, David; Ducreux, Michel; Boige, Valerie

    2014-10-01

    Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy. We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy. We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response. The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study.

  13. Blue-light filtering alters angiogenic signaling in human retinal pigmented epithelial cells culture model.

    Science.gov (United States)

    Vila, Natalia; Siblini, Aya; Esposito, Evangelina; Bravo-Filho, Vasco; Zoroquiain, Pablo; Aldrees, Sultan; Logan, Patrick; Arias, Lluis; Burnier, Miguel N

    2017-11-02

    Light exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD. Three experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines. A significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions. Following light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein

  14. Tamoxifen Directly Inhibits Platelet Angiogenic Potential and Platelet-Mediated Metastasis.

    Science.gov (United States)

    Johnson, Kelly E; Forward, Jodi A; Tippy, Mason D; Ceglowski, Julia R; El-Husayni, Saleh; Kulenthirarajan, Rajesh; Machlus, Kellie R; Mayer, Erica L; Italiano, Joseph E; Battinelli, Elisabeth M

    2017-04-01

    Platelets, which are mainly known for their role in hemostasis, are now known to play a crucial role in metastasis. Tamoxifen is a selective estrogen receptor modulator that is widely used for the treatment of breast cancer. Tamoxifen and its metabolites have been shown to directly impact platelet function, suggesting that this drug has additional mechanisms of action. The purpose of this study was to determine whether tamoxifen exerts antitumor effects through direct platelet inhibition. This study found that pretreatment with tamoxifen leads to a significant inhibition of platelet activation. Platelets exposed to tamoxifen released significantly lower amounts of proangiogenic regulator vascular endothelial growth factor. In vitro angiogenesis assays confirmed that tamoxifen pretreatment led to diminished capillary tube formation and decreased endothelial migration. Tamoxifen and its metabolite, 4-hydroxytamoxifen, also significantly inhibited the ability of platelets to promote metastasis in vitro. Using a membrane-based array, we identified several proteins associated with angiogenesis metastasis that were lower in activated releasate from tamoxifen-treated platelets, including angiogenin, chemokine (C-X-C motif) ligand 1, chemokine (C-C motif) ligand 5, epidermal growth factor, chemokine (C-X-C motif) ligand 5, platelet-derived growth factor dimeric isoform BB, whereas antiangiogenic angiopoietin-1 was elevated. Platelets isolated from patients on tamoxifen maintenance therapy were also found to have decreased activation responses, diminished vascular endothelial growth factor release, and lower angiogenic and metastatic potential. We demonstrate that tamoxifen and its metabolite 4-hydroxytamoxifen directly alter platelet function leading to decreased angiogenic and metastatic potential. Furthermore, this study supports the idea of utilizing targeted platelet therapies to inhibit the platelet's role in angiogenesis and malignancy. © 2017 American Heart

  15. A computational model to explore the role of angiogenic impairment on endochondral ossification during fracture healing.

    Science.gov (United States)

    OReilly, Adam; Hankenson, Kurt D; Kelly, Daniel J

    2016-10-01

    While it is well established that an adequate blood supply is critical to successful bone regeneration, it remains poorly understood how progenitor cell fate is affected by the altered conditions present in fractures with disrupted vasculature. In this study, computational models were used to explore how angiogenic impairment impacts oxygen availability within a fracture callus and hence regulates mesenchymal stem cell (MSC) differentiation and bone regeneration. Tissue differentiation was predicted using a previously developed algorithm which assumed that MSC fate is governed by oxygen tension and substrate stiffness. This model was updated based on the hypothesis that cell death, chondrocyte hypertrophy and endochondral ossification are regulated by oxygen availability. To test this, the updated model was used to simulate the time course of normal fracture healing, where it successfully predicted the observed quantity and spatial distribution of bone and cartilage at 10 and 20 days post-fracture (dpf). It also predicted the ratio of cartilage which had become hypertrophic at 10 dpf. Following this, three models of fracture healing with increasing levels of angiogenic impairment were developed. Under mild impairment, the model predicted experimentally observed reductions in hypertrophic cartilage at 10 dpf as well as the persistence of cartilage at 20 dpf. Models of more severe impairment predicted apoptosis and the development of fibrous tissue. These results provide insight into how factors specific to an ischemic callus regulate tissue regeneration and provide support for the hypothesis that chondrocyte hypertrophy and endochondral ossification during tissue regeneration are inhibited by low oxygen.

  16. Distributed Programming with Shared Data

    NARCIS (Netherlands)

    Bal, H.E.; Tanenbaum, A.S.

    1988-01-01

    Operating system primitives (e.g., problem-oriented shared memory, shared virtual memory, the Agora shared memory) and languages (e.g., Concurrent Prolog, Linda, Emerald) for programming distributed systems have been proposed that support the shared-variable paradigm without the presence of physical

  17. Risk Sharing under Incentive Constraints.

    OpenAIRE

    Wagner, W.B.

    2002-01-01

    In addressing the matter, this thesis covers issues such as the welfare gains from international risk sharing, the impact of international risk sharing on national economic policies and production efficiency, the welfare effects of international risk sharing in the presence of tax competition, and risk sharing among entrepreneurs that face financing constraints. The thesis outlines the implications of incentive constraints for the efficiency of the actual extent and pattern of risk sharing am...

  18. Sharing the dance -

    DEFF Research Database (Denmark)

    He, Jing; Ravn, Susanne

    2018-01-01

    to the highly specialized field of elite sports dance, we aim at exploring the way in which reciprocity unfolds in intensive deliberate practices of movement. In our analysis, we specifically argue that the ongoing dynamics of two separate flows of movement constitute a shared experience of dancing together....... In this sense, moving together, in sports dance, is a practical way of understanding each other. In agreement with Zahavi, our analysis emphasizes the bi-directed nature of sharing. However, at the same time, we contribute to Zahavi’s ongoing endeavour as the special case of sports dance reveals how reciprocity...... can be deliberately shaped through the mutual coordination and affective bound dynamics of movement. Our article thus both pursues the methodological point that qualitative research of expert competences can constructively enrich phenomenological analysis and indicates how movement can be fundamental...

  19. Towards A Shared Mission

    DEFF Research Database (Denmark)

    Staunstrup, Jørgen; Orth Gaarn-Larsen, Carsten

    in the context of universities. Although the economic aspects of value are important and cannot be ignored, we argue for a much richer interpretation of value that captures the many and varied results from universities. A shared mission is a prerequisite for university management and leadership. It makes......A mission shared by stakeholders, management and employees is a prerequisite for an engaging dialog about the many and substantial changes and challenges currently facing universities. Too often this essen-tial dialog reveals mistrust and misunderstandings about the role and outcome...... of the universities. The sad result is that the dialog about university development, resources, leadership, governance etc. too often ends up in rather fruitless discussions and sometimes even mutual suspicion. This paper argues for having a dialog involving both internal and external stakeholders agreeing...

  20. Shared goals and development

    DEFF Research Database (Denmark)

    Blomberg, Olle

    2015-01-01

    In 'Joint Action and Development', Stephen Butterfill argues that if several agents' actions are driven by what he calls a "shared goal" -- a certain pattern of goal-relations and expectations -- then these actions constitute a joint action. This kind of joint action is sufficiently cognitively...... a counterexample, I show that the pattern of goal-relations and expectations specified by Butterfill cannot play this role. I then provide an appropriately conceptually and cognitively undemanding amendment with which the account can be saved....

  1. Sharing data increases citations

    DEFF Research Database (Denmark)

    Drachen, Thea Marie; Ellegaard, Ole; Larsen, Asger Væring

    2016-01-01

    This paper presents some indications to the existence of a citation advantage related to sharing data using astrophysics as a case. Through bibliometric analyses we find a citation advantage for astrophysical papers in core journals. The advantage arises as indexed papers are associated with data...... by bibliographical links, and consists of papers receiving on average significantly more citations per paper per year, than do papers not associated with links to data....

  2. Shared Health Governance

    Science.gov (United States)

    Ruger, Jennifer Prah

    2014-01-01

    Health and Social Justice (Ruger 2009a) developed the “health capability paradigm,” a conception of justice and health in domestic societies. This idea undergirds an alternative framework of social cooperation called “shared health governance” (SHG). SHG puts forth a set of moral responsibilities, motivational aspirations, and institutional arrangements, and apportions roles for implementation in striving for health justice. This article develops further the SHG framework and explains its importance and implications for governing health domestically. PMID:21745082

  3. Bonobos share with strangers.

    Science.gov (United States)

    Tan, Jingzhi; Hare, Brian

    2013-01-01

    Humans are thought to possess a unique proclivity to share with others--including strangers. This puzzling phenomenon has led many to suggest that sharing with strangers originates from human-unique language, social norms, warfare and/or cooperative breeding. However, bonobos, our closest living relative, are highly tolerant and, in the wild, are capable of having affiliative interactions with strangers. In four experiments, we therefore examined whether bonobos will voluntarily donate food to strangers. We show that bonobos will forego their own food for the benefit of interacting with a stranger. Their prosociality is in part driven by unselfish motivation, because bonobos will even help strangers acquire out-of-reach food when no desirable social interaction is possible. However, this prosociality has its limitations because bonobos will not donate food in their possession when a social interaction is not possible. These results indicate that other-regarding preferences toward strangers are not uniquely human. Moreover, language, social norms, warfare and cooperative breeding are unnecessary for the evolution of xenophilic sharing. Instead, we propose that prosociality toward strangers initially evolves due to selection for social tolerance, allowing the expansion of individual social networks. Human social norms and language may subsequently extend this ape-like social preference to the most costly contexts.

  4. Sharing resources@CERN

    CERN Multimedia

    2002-01-01

    The library is launching a 'sharing resources@CERN' campaign, aiming to increase the library's utility by including the thousands of books bought by individual groups at CERN. This will improve sharing of information among CERN staff and users. Until now many people were unaware that copies of the same book (or standard, or journal) are often held not only by the library but by different divisions. (Here Eduardo Aldaz, from the PS division, and Isabel Bejar, from the ST division, read their divisional copies of the same book.) The idea behind the library's new sharing resources@CERN' initiative is not at all to collect the books in individual collections at the CERN library, but simply to register them in the Library database. Those not belonging to the library will in principle be unavailable for loan, but should be able to be consulted by anybody at CERN who is interested. "When you need a book urgently and it is not available in the library,' said PS Division engineer Eduardo Aldaz Carroll, it is a sham...

  5. Bonobos share with strangers.

    Directory of Open Access Journals (Sweden)

    Jingzhi Tan

    Full Text Available Humans are thought to possess a unique proclivity to share with others--including strangers. This puzzling phenomenon has led many to suggest that sharing with strangers originates from human-unique language, social norms, warfare and/or cooperative breeding. However, bonobos, our closest living relative, are highly tolerant and, in the wild, are capable of having affiliative interactions with strangers. In four experiments, we therefore examined whether bonobos will voluntarily donate food to strangers. We show that bonobos will forego their own food for the benefit of interacting with a stranger. Their prosociality is in part driven by unselfish motivation, because bonobos will even help strangers acquire out-of-reach food when no desirable social interaction is possible. However, this prosociality has its limitations because bonobos will not donate food in their possession when a social interaction is not possible. These results indicate that other-regarding preferences toward strangers are not uniquely human. Moreover, language, social norms, warfare and cooperative breeding are unnecessary for the evolution of xenophilic sharing. Instead, we propose that prosociality toward strangers initially evolves due to selection for social tolerance, allowing the expansion of individual social networks. Human social norms and language may subsequently extend this ape-like social preference to the most costly contexts.

  6. Attitudes of librarians toward knowledge sharing in university ...

    African Journals Online (AJOL)

    This study identified and analyzed knowledge sharing at the individual level among librarians. It explored how personality and situational characteristics influenced librarians knowledge-sharing. The personal traits that were considered include: self-esteem and self-efficacy, while cognitive appraisal was the situation ...

  7. Intención de colecho en el puerperio según características sociodemográficas de las madres: ¿Qué podemos recomendar los profesionales de enfermería? Intention of bed sharing during the postpartum period according to sociodemographic characteristics of the mother: What should professional nurses recommend?

    Directory of Open Access Journals (Sweden)

    Mª Teresa Roldán-Chicano

    2009-03-01

    Full Text Available Justificación: El colecho es una práctica muy extendida en algunos entornos culturales, sin embargo diferentes investigaciones presentan resultados muy contradictorios respecto a los beneficios y riesgos de compartir el lecho con el lactante. Objetivo: determinar la prevalencia en la intención de practicar colecho entre madres que están en la planta de maternidad (puerperio inmediato e intermedio, y relacionarla con sus características sociodemográficas. Diseño-metodología: Estudio transversal de prevalencia realizado en una muestra de 384 madres: españolas, marroquíes y ecuatorianas. Para determinar el grado de asociación entre variables categóricas se utilizó el test de la Chi-cuadrado. El tratamiento de los datos se realizó con el programa SPSS v.13. Resultados y conclusiones: Un 12% de las madres encuestadas tienen intención de practicar colecho esporádico o permanente. Las madres inmigrantes y las que tienen más hijos fueron las que más optaron por compartir el lecho con el lactante en el ámbito doméstico. Comparando nuestros resultados con los de otras investigaciones, podemos afirmar que algunas madres, aunque no tengan intención de practicar colecho, finalmente lo llevan a la práctica sin haber recibido por parte del profesional sanitario ningún consejo para que se lleve a cabo con unas condiciones de seguridad aceptables.Justification: Bed sharing is widely practised within different cultural environments, however different researches show contradicting results on the benefits and risks of parent-infant bed sharing. Objective: To determine the prevalence of the intention of bed sharing practice among mothers admitted to the maternity ward (immediate and intermediate postpartum period, and to relate this prevalence to their sociodemographic characteristics. Design-Methodology: Cross-sectional prevalence study conducted with a sample of 384 mothers: Spaniards, Moroccans and Ecuadorians. Chi-square test was used to

  8. Privacy in the Sharing Economy

    DEFF Research Database (Denmark)

    Ranzini, Giulia; Etter, Michael; Lutz, Christoph

    ’s digital services through providing recommendations to Europe’s institutions. The initial stage of this research project involves a set of three literature reviews of the state of research on three core topics in relation to the sharing economy: participation (1), privacy (2), and power (3). This piece......Report from the EU H2020 Research Project Ps2Share:Participation, Privacy, and Power in the Sharing Economy. This paper gives an in-depth overview of the topic of power in the sharing economy. It forms one part of a European Union Horizon 2020 Research Project on the sharing economy: "Ps2Share...... Participation, Privacy, and Power in the Sharing Economy". We aim to foster better awareness of the consequences which the sharing economy has on the way people behave, think, interact, and socialize across Europe. Our overarching objective is to identify key challenges of the sharing economy and improve Europe...

  9. Peer-to-Peer Service Sharing Platforms

    DEFF Research Database (Denmark)

    Andersson, Magnus; Hjalmarsson, Anders; Avital, Michel

    2013-01-01

    cost. Whereas early peer-to-peer platforms were designed to enable file sharing and goods trading, we recently witness the emergence of a new breed of peer-to-peer platforms that are designed for ordinary service sharing. Ordinary services entail intangible provisions and are defined as an economic...... activity that generates immaterial benefits and does not result in ownership of material goods. Based on a structured analysis of 41 internet-based rideshare platforms, we explore and layout the unique characteristics of peer-to-peer service sharing platforms based on three distinct temporal patterns...... that entail specific consequences for platform use as well as provide insights about their overall design imperative....

  10. Fixed Access Network Sharing

    Science.gov (United States)

    Cornaglia, Bruno; Young, Gavin; Marchetta, Antonio

    2015-12-01

    Fixed broadband network deployments are moving inexorably to the use of Next Generation Access (NGA) technologies and architectures. These NGA deployments involve building fiber infrastructure increasingly closer to the customer in order to increase the proportion of fiber on the customer's access connection (Fibre-To-The-Home/Building/Door/Cabinet… i.e. FTTx). This increases the speed of services that can be sold and will be increasingly required to meet the demands of new generations of video services as we evolve from HDTV to "Ultra-HD TV" with 4k and 8k lines of video resolution. However, building fiber access networks is a costly endeavor. It requires significant capital in order to cover any significant geographic coverage. Hence many companies are forming partnerships and joint-ventures in order to share the NGA network construction costs. One form of such a partnership involves two companies agreeing to each build to cover a certain geographic area and then "cross-selling" NGA products to each other in order to access customers within their partner's footprint (NGA coverage area). This is tantamount to a bi-lateral wholesale partnership. The concept of Fixed Access Network Sharing (FANS) is to address the possibility of sharing infrastructure with a high degree of flexibility for all network operators involved. By providing greater configuration control over the NGA network infrastructure, the service provider has a greater ability to define the network and hence to define their product capabilities at the active layer. This gives the service provider partners greater product development autonomy plus the ability to differentiate from each other at the active network layer.

  11. Risk Sharing and Layoff Risk in Profit Sharing

    OpenAIRE

    Fabella, Raul V.

    1995-01-01

    We show that if the employer is risk averse, however slightly, there is always a profit sharing contract that will Pareto-dominate the spot wage contract in the sense of pure risk sharing. The smaller is the employer risk aversion, the narrower is the room for profit sharing. The higher the workers value employment stability (less layoff risk), the more Pareto attractive is profit sharing regardless of employer risk aversion.

  12. Shared care and boundaries:

    DEFF Research Database (Denmark)

    Winthereik, Brit Ross

    2008-01-01

    between home and clinic, which the project identifies as problematic and seeks to transgress. Research limitations/implications – The pilot project, which is used as a case, is terminated prematurely. However, this does not affect the fact that more attention should be paid to the specific redistribution......Purpose – The paper seeks to examine how an online maternity record involving pregnant women worked as a means to create shared maternity care. Design/methodology/approach – Ethnographic techniques have been used. The paper adopts a theoretical/methodological framework based on science...

  13. Can power be shared?

    Science.gov (United States)

    Ten Pas, William S

    2013-01-01

    Dental insurance began with a partnership between dental service organizations and state dental associations with a view toward expanding the number of Americans receiving oral health care and as a means for permitting firms and other organizations to offer employee benefits. The goals have been achieved, but the alliance between dentistry and insurance has become strained. A lack of dialogue has fostered mutual misconceptions, some of which are reviewed in this paper. It is possible that the public, the profession, and the dental insurance industry can all be strengthened, but only through power-sharing around the original common objective.

  14. Shared Oral Care

    DEFF Research Database (Denmark)

    Hede, Børge; Elmelund Poulsen,, Johan; Christophersen, Rasmus

    2014-01-01

    Shared Oral Care - Forebyggelse af orale sygdomme på plejecentre Introduktion og formål: Mangelfuld mundhygiejne hos plejekrævende ældre er et alment og veldokumenteret sundhedsproblem, der kan føre til massiv udvikling af tandsygdomme, og som yderligere kan være medvirkende årsag til alvorlige...... ressourceanvendelse er muligt at skabe en betydeligt forbedret mundhygiejne hos plejekrævende ældre Key words: Geriatric dentistry, nursing home, community health services, prevention, situated learning...

  15. Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

    Science.gov (United States)

    Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O

    2015-01-01

    Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

  16. Everyday executive functions in Down syndrome from early childhood to young adulthood: Evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY

    Directory of Open Access Journals (Sweden)

    Nancy Raitano Lee

    2015-10-01

    Full Text Available Executive functions (EF are thought to be impaired in Down syndrome (DS and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X. However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a compared everyday EF difficulties in youth with DS, +1X, and typical development (TD; and (b examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF in DS (n=30, +1X (n=30, and a TD group (n=30, ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2’s findings for DS by examining age-EF relations in a large independent sample of youth with DS (n=85 and TD (n=43, ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

  17. Shared consultant physician posts.

    LENUS (Irish Health Repository)

    Cooke, J

    2012-01-31

    Our aim was to assess the acceptability and cost-efficiency of shared consultancy posts. Two consultant physicians worked alternate fortnights for a period of twelve months. Questionnaires were distributed to general practitioners, nurses, consultants and junior doctors affected by the arrangement. Patients or their next of kin were contacted by telephone. 1\\/17 of consultants described the experience as negative. 14\\/19 junior doctors reported a positive experience. 11 felt that training had been improved while 2 felt that it had been adversely affected. 17\\/17 GPs were satisfied with the arrangement. 1\\/86 nurses surveyed reported a negative experience. 1\\/48 patients were unhappy with the arrangement. An extra 2.2 (p<0.001) patients were seen per clinic. Length of stay was shortened by 2.49 days (p<0.001). A saving of 69,212 was made due to decreased locum requirements. We present data suggesting structured shared consultancy posts can be broadly acceptable and cost efficient in Ireland.

  18. Reconceptualising Shared Services

    Directory of Open Access Journals (Sweden)

    Peter McKinlay

    2011-12-01

    Full Text Available Endeavours to improve the efficiency and effectiveness of local government have been a persistent theme both of politicians in higher tiers of government and of interest groups, especially business. The two contenders for improvement which receive most coverage both in the research literature and in popular discussion are amalgamation and shared services. Arguments from the literature have generally favoured shared services over amalgamation. Bish (2001 in a comprehensive review of North American research dismisses the argument for amalgamation as a product of flawed nineteenth-century thinking and a bureaucratic urge for centralized control. He does so making the very reasonable point that the presumed economies of scale which will result from amalgamation are a function not of the size and scale of individual local authorities, but of the services for which those local authorities are responsible, and the point at which economies of scale will be optimised will be very different for different services. The case against amalgamation is also reinforced by the absence of any significant post-facto evidence that amalgamation achieves either the promised savings or the anticipated efficiency gains (McKinlay 2006.

  19. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Exploring the role of anti-angiogenic therapies in prostate cancer: results from the phase 3 trial of sunitinib

    Directory of Open Access Journals (Sweden)

    Himisha Beltran

    2014-08-01

    Full Text Available Prostate cancer is a leading cause of cancer death in men. Despite recent advances in our understanding and treatment of advanced disease, no systemic therapy is curative and new therapies are needed. Targeting angiogenesis is an attractive therapeutic strategy, as angiogenic pathways are upregulated in prostate tumors similar to other malignancies due to imbalance of pro- and anti-angiogenic factors secreted by tumor, endothelial and stromal cells and increased neovasculature. [1] Vascular endothelial growth factor (VEGF is the most well-characterized pro-angiogenenic factor, with several small molecule inhibitors (sunitinib, sorafenib, pazopanib, axitinib, others, antibodies (bevacizumab and other drugs that target the VEGF pathway approved and/or in development for the treatment of a wide range of tumor types.

  1. Capillary growth in human skeletal muscle: physiological factors and the balance between pro-angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Hoier, Birgitte

    2014-01-01

    In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either by me...... addresses physiological signals and angiogenic factors in skeletal muscle with a focus on human data.......In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either...... angiogenesis. A number of such regulatory proteins have been described in skeletal muscle in animal and cell models but also in human skeletal muscle. Important pro-angiogenic factors in skeletal muscle are vascular endothelial growth factor, endothelial nitric oxide synthase and angiopoietin 2, whereas...

  2. Knowledge sharing in horizontal networks

    National Research Council Canada - National Science Library

    Juliano Nunes Alves; Breno Augusto Diniz Pereira; Augusto Diniz

    2012-01-01

      The present study aimed to identify the process of sharing knowledge between the partners involved in the network, as well as the dimensions on sharing of knowledge between enterprises belonging...

  3. The acute angiogenic signalling response to low-load resistance exercise with blood flow restriction.

    Science.gov (United States)

    Ferguson, Richard A; Hunt, Julie E A; Lewis, Mark P; Martin, Neil R W; Player, Darren J; Stangier, Carolin; Taylor, Conor W; Turner, Mark C

    2018-01-17

    This study investigated protein kinase activation and gene expression of angiogenic factors in response to low-load resistance exercise with or without blood flow restriction (BFR). In a repeated measures cross-over design, six males performed four sets of bilateral knee extension exercise at 20% 1RM (reps per set = 30:15:15:continued to fatigue) with BFR (110 mmHg) and without (CON). Muscle biopsies were obtained from the vastus lateralis before, 2 and 4 h post-exercise. mRNA expression was determined using real-time RT-PCR. Protein phosphorylation/expression was determined using Western blot. p38MAPK phosphorylation was greater (p = 0.05) at 2 h following BFR (1.3 ± 0.8) compared to CON (0.4 ± 0.3). AMPK phosphorylation remained unchanged. PGC-1α mRNA expression increased at 2 h (5.9 ± 1.3 vs. 2.1 ± 0.8; p = 0.03) and 4 h (3.2 ± 0.8 vs. 1.5 ± 0.4; p = 0.03) following BFR exercise with no change in CON. PGC-1α protein expression did not change following either exercise. BFR exercise enhanced mRNA expression of vascular endothelial growth factor (VEGF) at 2 h (5.2 ± 2.8 vs 1.7 ± 1.1; p = .02) and 4 h (6.8 ± 4.9 vs. 2.5 ± 2.7; p = .01) compared to CON. mRNA expression of VEGF-R2 and hypoxia-inducible factor 1α increased following BFR exercise but only eNOS were enhanced relative to CON. Matrix metalloproteinase-9 mRNA expression was not altered in response to either exercise. Acute low-load resistance exercise with BFR provides a targeted angiogenic response potentially mediated through enhanced ischaemic and shear stress stimuli.

  4. Platelet-rich plasma modulates the secretion of inflammatory/angiogenic proteins by inflamed tenocytes.

    Science.gov (United States)

    Andia, Isabel; Rubio-Azpeitia, Eva; Maffulli, Nicola

    2015-05-01

    Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes. Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasma-induced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample. In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005-0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27-0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007-0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3-0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5-0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2-0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7-2.3; p plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells. Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.

  5. Irradiation-induced angiosarcoma and anti-angiogenic therapy: A therapeutic hope?

    Energy Technology Data Exchange (ETDEWEB)

    Azzariti, Amalia, E-mail: a.azzariti@oncologico.bari.it [Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Porcelli, Letizia [Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Mangia, Anita; Saponaro, Concetta [Functional Biomorphology Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Quatrale, Anna E. [Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Popescu, Ondina S. [Department of Pathology, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Strippoli, Sabino [Medical Oncology Unit, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Simone, Gianni [Department of Pathology, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Paradiso, Angelo [Experimental Medical Oncology, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy); Guida, Michele [Medical Oncology Unit, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari (Italy)

    2014-02-15

    Angiosarcomas are rare soft-tissue sarcomas of endothelial cell origin. They can be sporadic or caused by therapeutic radiation, hence secondary breast angiosarcomas are an important subgroup of patients. Assessing the molecular biology of angiosarcomas and identify specific targets for treatment is challenging. There is currently great interest in the role of angiogenesis and of angiogenic factors associated with tumor pathogenesis and as targets for treatment of angiosarcomas. A primary cell line derived from a skin fragment of a irradiation-induced angiosarcoma patient was obtained and utilized to evaluate cell biomarkers CD31, CD34, HIF-1alpha and VEGFRs expression by immunocytochemistry and immunofluorescence, drugs cytotoxicity by cell counting and VEGF release by ELISA immunoassay. In addition to previous biomarkers, FVIII and VEGF were also evaluated on tumor specimens by immunohistochemistry to further confirm the diagnosis. We targeted the VEGF–VEGFR-2 axis of tumor angiogenesis with two different class of vascular targeted drugs; caprelsa, the VEGFR-2/EGFR/RET inhibitor and bevacizumab the anti-VEGF monoclonal antibody. We found the same biomarkers expression either in tumor specimens and in the cell line derived from tumor. In vitro experiments demonstrated that angiogenesis plays a pivotal role in the progression of this tumor as cells displayed high level of VEGFR-2, HIF-1 alpha strongly accumulated into the nucleus and the pro-angiogenic factor VEGF was released by cells in culture medium. The evaluation of caprelsa and bevacizumab cytotoxicity demonstrated that both drugs were effective in inhibiting tumor proliferation. Due to these results, we started to treat the patient with pazopanib, which was the unique tyrosine kinase inhibitor available in Italy through a compassionate supply program, obtaining a long lasting partial response. Our data suggest that the study of the primary cell line could help physicians in choosing a therapeutic approach

  6. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.

    Directory of Open Access Journals (Sweden)

    Zhong Hua

    Full Text Available MicroRNAs (miRNAs are a class of 20-24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle. We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false

  7. Irradiation-induced angiosarcoma and anti-angiogenic therapy: a therapeutic hope?

    Science.gov (United States)

    Azzariti, Amalia; Porcelli, Letizia; Mangia, Anita; Saponaro, Concetta; Quatrale, Anna E; Popescu, Ondina S; Strippoli, Sabino; Simone, Gianni; Paradiso, Angelo; Guida, Michele

    2014-02-15

    Angiosarcomas are rare soft-tissue sarcomas of endothelial cell origin. They can be sporadic or caused by therapeutic radiation, hence secondary breast angiosarcomas are an important subgroup of patients. Assessing the molecular biology of angiosarcomas and identify specific targets for treatment is challenging. There is currently great interest in the role of angiogenesis and of angiogenic factors associated with tumor pathogenesis and as targets for treatment of angiosarcomas. A primary cell line derived from a skin fragment of a irradiation-induced angiosarcoma patient was obtained and utilized to evaluate cell biomarkers CD31, CD34, HIF-1 alpha and VEGFRs expression by immunocytochemistry and immunofluorescence, drugs cytotoxicity by cell counting and VEGF release by ELISA immunoassay. In addition to previous biomarkers, FVIII and VEGF were also evaluated on tumor specimens by immunohistochemistry to further confirm the diagnosis. We targeted the VEGF-VEGFR-2 axis of tumor angiogenesis with two different class of vascular targeted drugs; caprelsa, the VEGFR-2/EGFR/RET inhibitor and bevacizumab the anti-VEGF monoclonal antibody. We found the same biomarkers expression either in tumor specimens and in the cell line derived from tumor. In vitro experiments demonstrated that angiogenesis plays a pivotal role in the progression of this tumor as cells displayed high level of VEGFR-2, HIF-1 alpha strongly accumulated into the nucleus and the pro-angiogenic factor VEGF was released by cells in culture medium. The evaluation of caprelsa and bevacizumab cytotoxicity demonstrated that both drugs were effective in inhibiting tumor proliferation. Due to these results, we started to treat the patient with pazopanib, which was the unique tyrosine kinase inhibitor available in Italy through a compassionate supply program, obtaining a long lasting partial response. Our data suggest that the study of the primary cell line could help physicians in choosing a therapeutic approach

  8. The angiogenic effects of ischemic conditioning in experimental critical limb ischemia.

    Science.gov (United States)

    Karakoyun, R; Koksoy, C; Yilmaz, T U; Altun, H; Banli, O; Albayrak, A; Alper, M; Sener, Z

    2014-02-01

    Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury. Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups. The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups. IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis. Copyright © 2013 European Society for Vascular Surgery

  9. Shared Services Management: Critical Factors

    OpenAIRE

    Shouhong Wang; Hai Wang

    2015-01-01

    The cloud computing technology has accelerated shared services in the government and private sectors. This paper proposes a research framework of critical success factors of shared services in the aspects of strategy identification, collaborative partnership networking, optimal shared services process re-designing, and new policies and regulations. A survey has been employed to test the hypotheses. The test results indicate that clear vision of strategies of shared services, long term busines...

  10. The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.

    Directory of Open Access Journals (Sweden)

    Sofia-Paraskevi Trachana

    Full Text Available Advanced ovarian cancer (AOC is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001 and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001. This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies.

  11. Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type

    DEFF Research Database (Denmark)

    van der Plas, Mariena J A; van Dissel, Jaap T; Nibbering, Peter H

    2009-01-01

    BACKGROUND: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of mono......-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected. CONCLUSIONS: Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type....

  12. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential.

    Science.gov (United States)

    Lopatina, Tatiana; Bruno, Stefania; Tetta, Ciro; Kalinina, Natalia; Porta, Massimo; Camussi, Giovanni

    2014-04-11

    Several studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis. The angiogenic mechanism has been ascribed to paracrine factors since these cells secrete a plenty of signal molecules and growth factors. Recently it has been suggested that besides soluble factors, extracellular vesicles (EVs) that include exosomes and microvesicles may play a major role in cell-to-cell communication. It has been shown that EVs are implicated in the angiogenic process. Herein we studied whether EVs released by ASCs may mediate the angiogenic activity of these cells. Our results demonstrated that ASC-derived EVs induced in vitro vessel-like structure formation by human microvascular endothelial cells (HMEC). EV-stimulated HMEC when injected subcutaneously within Matrigel in SCID mice formed vessels. Treatment of ASCs with platelet-derived growth factor (PDGF) stimulated the secretion of EVs, changed their protein composition and enhanced the angiogenic potential. At variance of EVs released in basal conditions, PDGF-EVs carried c-kit and SCF that played a role in angiogenesis as specific blocking antibodies inhibited in vitro vessel-like structure formation. The enhanced content of matrix metalloproteinases in PDGF-EVs may also account for their angiogenic activity. Our findings indicate that EVs released by ASCs may contribute to the ASC-induced angiogenesis and suggest that PDGF may trigger the release of EVs with an enhanced angiogenic potential.

  13. Changes in uterine artery Doppler velocimetry and circulating angiogenic factors in the first half of pregnancies delivering a small-for-gestational-age neonate.

    Science.gov (United States)

    Triunfo, S; Crovetto, F; Rodriguez-Sureda, V; Scazzocchio, E; Crispi, F; Dominguez, C; Gratacos, E; Figueras, F

    2017-03-01

    To assess the relationship between longitudinal changes in placental Doppler indices and maternal circulating angiogenic factors in the first half of pregnancy and delivery of a small-for-gestational-age (SGA) neonate, and ascertain whether longitudinal evaluation of these variables improves the prediction achieved by second-trimester cross-sectional evaluation. From a prospective cohort of unselected singleton pregnancies undergoing first-trimester screening for aneuploidy, 138 were included in this study. Of these, 46 were complicated by SGA (delivering after 34 weeks' gestation with a birth weight Doppler indices and maternal circulating levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were analyzed. Compared with the AGA group, SGA pregnancies had significantly higher UtA impedance in the first (Z-score: 0.46 vs -0.57; P Doppler indices for SGA was significantly lower than that of second-trimester cross-sectional values (area under receiver-operating characteristics curve (AUC), 60.8% vs 84.3%; P = 0.0035). The detection rate of SGA, at a 10% false-positive rate (FPR), was 17.7% by longitudinal changes in UtA Doppler and 56.2% by second-trimester cross-sectional UtA Doppler values. Similarly, the predictive performance of the longitudinal changes in PlGF was significantly lower than that of early second-trimester cross-sectional values (AUC, 71.4% vs 76.5%; P = 0.008). The detection rate of SGA at a 10% FPR was 40.6% when screening by longitudinal changes in PlGF and 52.1% when screening by early second-trimester cross-sectional values. First- and second-trimester UtA Doppler velocimetry and maternal circulating angiogenic markers have clinical utility as a cross-sectional assessment for the identification of pregnancies at high risk of delivering a SGA neonate, however, they do not improve prediction when their longitudinal changes are used. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016

  14. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.

    Science.gov (United States)

    Myers, J E; Kenny, L C; McCowan, L M E; Chan, E H Y; Dekker, G A; Poston, L; Simpson, N A B; North, R A

    2013-09-01

    To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Predictive test accuracy study. Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation). Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  15. Model Sharing and Collaboration using HydroShare

    Science.gov (United States)

    Goodall, J. L.; Morsy, M. M.; Castronova, A. M.; Miles, B.; Merwade, V.; Tarboton, D. G.

    2015-12-01

    HydroShare is a web-based system funded by the National Science Foundation (NSF) for sharing hydrologic data and models as resources. Resources in HydroShare can either be assigned a generic type, meaning the resource only has Dublin Core metadata properties, or one of a growing number of specific resource types with enhanced metadata profiles defined by the HydroShare development team. Examples of specific resource types in the current release of HydroShare (http://www.hydroshare.org) include time series, geographic raster, Multidimensional (NetCDF), model program, and model instance. Here we describe research and development efforts in HydroShare project for model-related resources types. This work has included efforts to define metadata profiles for common modeling resources, execute models directly through the HydroShare user interface using Docker containers, and interoperate with the 3rd party application SWATShare for model execution and visualization. These examples demonstrate the benefit of HydroShare to support model sharing and address collaborative problems involving modeling. The presentation will conclude with plans for future modeling-related development in HydroShare including supporting the publication of workflow resources, enhanced metadata for additional hydrologic models, and linking model resources with other resources in HydroShare to capture model provenance.

  16. Fractions: How to Fair Share

    Science.gov (United States)

    Wilson, P. Holt; Edgington, Cynthia P.; Nguyen, Kenny H.; Pescosolido, Ryan S.; Confrey, Jere

    2011-01-01

    Children learn from a very early age what it means to get their "fair share." Whether it is candy or birthday cake, many children successfully create equal-size groups or parts of a collection or whole but later struggle to create fair shares of multiple wholes, such as fairly sharing four pies among a family of seven. Recent research suggests…

  17. Risk sharing and public transfers

    OpenAIRE

    Dercon, Stefan; Krishnan, Pramila

    2002-01-01

    We use public transfers in the form of food aid to test for the presence of risk sharing arrangements at the village level in rural Ethiopia. We reject perfect risk-sharing, but find evidence of partial risk-sharing via transfers. There is also evidence consistent with crowding out of informal insurance linked to food aid programmes. – risk ; public transfers ; informal insurance

  18. miR-10 Regulates the Angiogenic Behavior of Zebrafish and Human Endothelial Cells by Promoting VEGF Signaling

    Science.gov (United States)

    Hassel, David; Cheng, Paul; White, Mark P.; Ivey, Kathryn N.; Kroll, Jens; Augustin, Hellmut G.; Katus, Hugo A.; Stainier, Didier Y.R.; Srivastava, Deepak

    2012-01-01

    Rationale Formation and remodeling of the vasculature during development and disease involves a highly conserved and precisely regulated network of attractants and repellants. Various signaling pathways control the behavior of endothelial cells, but their post-transcriptional dose-titration by miRNAs is poorly understood. Objective To identify miRNAs that regulate angiogenesis. Methods and Results We show that the highly conserved microRNA family encoding miR-10 regulates the behavior of endothelial cells during angiogenesis by positively titrating pro-angiogenic signaling. Knockdown of miR-10 led to premature truncation of intersegmental vessel growth (ISV) in the trunk of zebrafish larvae, while overexpression of miR-10 promoted angiogenic behavior in zebrafish and cultured human umbilical venous endothelial cells (HUVECs). We found that miR-10 functions, in part, by directly regulating the level of fms-related tyrosine kinase 1 (FLT1), a cell-surface protein that sequesters VEGF, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1 protein levels upon miR-10 knockdown in zebrafish and in HUVECs inhibited the angiogenic behavior of endothelial cells largely by antagonizing VEGF receptor-2 signaling. Conclusion Our study provides insights into how FLT1 and VEGF receptor-2 signaling is titrated in a miRNA-mediated manner and establishes miR-10 as a potential new target for the selective modulation of angiogenesis. PMID:22955733

  19. PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

    Directory of Open Access Journals (Sweden)

    Hiroto Iwasaki

    Full Text Available Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM cells, recent clinical trials have revealed less benefit from these therapies than expected.We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+/Lin(- (SL BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  20. Angiogenic Rg1 /Sr-Doped TiO2 Nanowire/Poly(Propylene Fumarate) Bone Cement Composites.

    Science.gov (United States)

    Salarian, Mehrnaz; Xu, William Z; Bohay, Richard; Lui, Edmund M K; Charpentier, Paul A

    2017-02-01

    A new approach is provided for preparing radiopaque and angiogenic poly(propylene fumarate) (PPF) bone cements by integrating Sr-doped n-TiO2 nanowires and ginsenoside Rg1 suitable for treating osteonecrosis. High aspect ratio radiopaque TiO2 -nanowires are synthesized by strontium doping in supercritical CO2 for the first time, showing a new phase, SrTiO3 . PPF is synthesized using a transesterification method by reacting diethyl fumarate and propylene glycol, then functionalized using maleic anhydride to produce terminal carboxyl groups, which are subsequently linked to the nanowires. The strong interfacial adhesion between functionalized PPF and nanowires is examined by scanning electron microscopy, Fourier transform infrared, X-ray photoelectron spectroscopy, thermal analysis, and mechanical testing. An angiogenic modulator, ginsenoside Rg1 , is integrated into the bone cement formulation with the mechanical properties, radiopacity, drug release, and angiogenesis behavior of the formed composites explored. The results show superior radiopacity and excellent release of ginsenoside Rg1 in vitro, as well as a dose-dependent increase in the branching point numbers. The present study suggests this new methodology provides sufficient mechanical properties, radiopacity, and angiogenic activity to be suitable for cementation of necrotic bone. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Yuning Zhou

    Full Text Available Bone marrow-derived mesenchymal stem cells (BMSCs are widely used in regenerative medicine in light of their ability to differentiate along the chondrogenic and osteogenic lineages. As a type of traditional Chinese medicine, quercetin has been preliminarily reported to promote osteogenic differentiation in osteoblasts. In the present study, the effects of quercetin on the proliferation, viability, cellular morphology, osteogenic differentiation and angiogenic factor secretion of rat BMSCs (rBMSCs were examined by MTT assay, fluorescence activated cell sorter (FACS analysis, real-time quantitative PCR (RT-PCR analysis, alkaline phosphatase (ALP activity and calcium deposition assays, and Enzyme-linked immunosorbent assay (ELISA. Moreover, whether mitogen-activated protein kinase (MAPK signaling pathways were involved in these processes was also explored. The results showed that quercetin significantly enhanced the cell proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in a dose-dependent manner, with a concentration of 2 μM achieving the greatest stimulatory effect. Moreover, the activation of the extracellular signal-regulated protein kinases (ERK and p38 pathways was observed in quercetin-treated rBMSCs. Furthermore, these induction effects could be repressed by either the ERK inhibitor PD98059 or the p38 inhibitor SB202190, respectively. These data indicated that quercetin could promote the proliferation, osteogenic differentiation and angiogenic factor secretion of rBMSCs in vitro, partially through the ERK and p38 signaling pathways.

  2. Fibrin gels engineered with pro-angiogenic growth factors promote engraftment of pancreatic islets in extrahepatic sites in mice.

    Science.gov (United States)

    Najjar, Mejdi; Manzoli, Vita; Abreu, Maria; Villa, Chiara; Martino, Mikaël M; Molano, R Damaris; Torrente, Yvan; Pileggi, Antonello; Inverardi, Luca; Ricordi, Camillo; Hubbell, Jeffrey A; Tomei, Alice A

    2015-09-01

    With a view toward reduction of graft loss, we explored pancreatic islet transplantation within fibrin matrices rendered pro-angiogenic by incorporation of minimal doses of vascular endothelial growth factor-A165 and platelet-derived growth factor-BB presented complexed to a fibrin-bound integrin-binding fibronectin domain. Engineered matrices allowed for extended release of pro-angiogenic factors and for their synergistic signaling with extracellular matrix-binding domains in the post-transplant period. Aprotinin addition delayed matrix degradation and prolonged pro-angiogenic factor availability within the graft. Both subcutaneous (SC) and epididymal fat pad (EFP) sites were evaluated. We show that in the SC site, diabetes reversal in mice transplanted with 1,000 IEQ of syngeneic islets was not observed for islets transplanted alone, while engineered matrices resulted in a diabetes median reversal time (MDRT) of 38 days. In the EFP site, the MDRT with 250 IEQ of syngeneic islets within the engineered matrices was 24 days versus 86 days for islets transplanted alone. Improved function of engineered grafts was associated with enhanced and earlier (by day 7) angiogenesis. Our findings show that by engineering the transplant site to promote prompt re-vascularization, engraftment and long-term function of islet grafts can be improved in relevant extrahepatic sites. © 2015 Wiley Periodicals, Inc.

  3. Shared consultant physician posts.

    Science.gov (United States)

    Cooke, J; Molefe, C; Carew, S; Finucane, P; Clinch, D

    2009-01-01

    Our aim was to assess the acceptability and cost-efficiency of shared consultancy posts. Two consultant physicians worked alternate fortnights for a period of twelve months. Questionnaires were distributed to general practitioners, nurses, consultants and junior doctors affected by the arrangement. Patients or their next of kin were contacted by telephone. 1/17 of consultants described the experience as negative. 14/19 junior doctors reported a positive experience. 11 felt that training had been improved while 2 felt that it had been adversely affected. 17/17 GPs were satisfied with the arrangement. 1/86 nurses surveyed reported a negative experience. 1/48 patients were unhappy with the arrangement. An extra 2.2 (pposts can be broadly acceptable and cost efficient in Ireland.

  4. SHARED TECHNOLOGY TRANSFER PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    GRIFFIN, JOHN M. HAUT, RICHARD C.

    2008-03-07

    The program established a collaborative process with domestic industries for the purpose of sharing Navy-developed technology. Private sector businesses were educated so as to increase their awareness of the vast amount of technologies that are available, with an initial focus on technology applications that are related to the Hydrogen, Fuel Cells and Infrastructure Technologies (Hydrogen) Program of the U.S. Department of Energy. Specifically, the project worked to increase industry awareness of the vast technology resources available to them that have been developed with taxpayer funding. NAVSEA-Carderock and the Houston Advanced Research Center teamed with Nicholls State University to catalog NAVSEA-Carderock unclassified technologies, rated the level of readiness of the technologies and established a web based catalog of the technologies. In particular, the catalog contains technology descriptions, including testing summaries and overviews of related presentations.

  5. Borrowing brainpower - sharing insecurities

    DEFF Research Database (Denmark)

    Wegener, Charlotte; Meier, Ninna; Ingerslev, Karen

    2016-01-01

    Academic writing is a vital, yet complex skill that must be developed within a doctoral training process. In addition, becoming an academic researcher is a journey of changing sense of self and identity. Through analysis of a group session, we show how the feedback of peers addresses questions...... of structure and writing style along with wider issues of researcher identity. Thus, peer learning is demonstrated as a process of simultaneously building a text and an identity as scholarly researcher. The paper advocates ‘borrowing brainpower’ from peers in order to write better texts and, at the same time......, ‘share insecurities’ during the development of the researcher identity. Based on a distributed notion of peer learning and identity, we point to the need for further research into the everyday activities of doctoral writing groups in order to understand the dynamic relationship between production of text...

  6. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine

    Directory of Open Access Journals (Sweden)

    Sai-Wang Seto

    2016-06-01

    Full Text Available Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA. tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis.

  7. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine.

    Science.gov (United States)

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-06-06

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis.

  8. Direct isolation, culture and transplant of mouse skeletal muscle derived endothelial cells with angiogenic potential.

    Directory of Open Access Journals (Sweden)

    Nicholas Ieronimakis

    2008-03-01

    Full Text Available Although diseases associated with microvascular endothelial dysfunction are among the most prevalent illnesses to date, currently no method exists to isolate pure endothelial cells (EC from skeletal muscle for in vivo or in vitro study.By utilizing multicolor fluorescent-activated cell sorting (FACS, we have isolated a distinct population of Sca-1(+, CD31(+, CD34(dim and CD45(- cells from skeletal muscles of C57BL6 mice. Characterization of this population revealed these cells are functional EC that can be expanded several times in culture without losing their phenotype or capabilities to uptake acetylated low-density lipoprotein (ac-LDL, produce nitric oxide (NO and form vascular tubes. When transplanted subcutaneously or intramuscularly into the tibialis anterior muscle, EC formed microvessels and integrated with existing vasculature.This method, which is highly reproducible, can be used to study the biology and role of EC in diseases such as peripheral vascular disease. In addition this method allows us to isolate large quantities of skeletal muscle derived EC with potential for therapeutic angiogenic applications.

  9. Bone metabolism markers and angiogenic cytokines as regulators of human hematopoietic stem cell mobilization.

    Science.gov (United States)

    Tsirkinidis, Pantelis; Terpos, Evangelos; Boutsikas, Georgios; Papatheodorou, Athanasios; Anargyrou, Konstantinos; Lalou, Eleni; Dimitrakopoulou, Aglaia; Kalpadakis, Christina; Konstantopoulos, Konstantinos; Siakantaris, Marina; Panayiotidis, Panayiotis; Pangalis, Gerassimos; Kyrtsonis, Marie-Christine; Vassilakopoulos, Theodoros; Angelopoulou, Maria K

    2017-06-28

    Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization. Poor mobilizers had significantly higher carboxy-terminal telopeptide of collagen type I (CTX) and lower ANGP-1 at pre-mobilization samples, compared to good ones. CTX, amino-terminal telopeptide of collagen type I (NTX) and ANGP-1 pre-mobilization levels correlated significantly with circulating CD34 + peak cell counts. Our results indicate that bone formation and vessel destabilization are the two major events during human HSC mobilization. Osteoblasts seem to be the orchestrating cells, while osteoclasts are stimulated but not fully active. Moreover, ANGP-1, CTX and NTX may serve as predictors of poor mobilization.

  10. Response to Plasmapheresis Measured by Angiogenic Factors in a Woman with Antiphospholipid Syndrome in Pregnancy

    Directory of Open Access Journals (Sweden)

    Karoline Mayer-Pickel

    2015-01-01

    Full Text Available An imbalance of angiogenic and antiangiogenic placental factors such as endoglin and soluble fms-like tyrosine kinase 1 has been implicated in the pathophysiology of preeclampsia. Extraction of these substances by plasmapheresis might be a therapeutical approach in cases of severe early-onset preeclampsia. Case Report. A 21-year-old primigravida with antiphospholipid syndrome developed early-onset preeclampsia at 18 weeks’ gestation. She was treated successfully with plasmapheresis in order to prolong pregnancy. Endoglin and sflt-1-levels were measured by ELISA before and after treatment. Endoglin levels decreased significantly after treatment (p < 0.05 and showed a significant decrease throughout pregnancy. A rerise of endoglin and sflt-1 preceded placental abruption 4 weeks before onset of incident. Conclusion. Due to the limited long-term therapeutical possibilities for pregnancies complicated by PE, plasmapheresis seems to be a therapeutical option. This consideration refers especially to pregnancies with early-onset preeclampsia, in which, after first conventional treatment of PE, prolongation of pregnancy should be above all.

  11. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

    Directory of Open Access Journals (Sweden)

    Allan Lançon

    2016-03-01

    Full Text Available Resveratrol (3,4′,5 trihydroxy-trans-stilbene is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  12. The Anti-Inflammatory Cytokine Interleukin-19 Is Expressed in and Angiogenic for Human Endothelial Cells

    Science.gov (United States)

    Jain, Surbhi; Gabunia, Khatuna; Kelemen, Sheri E.; Panetti, Tracee S.; Autieri, Michael V.

    2010-01-01

    OBJECTIVE The expression and effects of anti-inflammatory interleukins on endothelial cell (EC) activation and development of angiogenesis is uncharacterized. The purpose of this study is to characterize the expression and function of Interleukin-19 (IL-19), a recently described Th2 anti-inflammatory interleukin on EC pathophysiology. METHODS and RESULTS We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal human coronary endothelium, and can be induced in cultured human EC by serum and bFGF. IL-19 is mitogenic, chemotactic, and promotes cell EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cord-like structure formation of cultured EC and also enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in matrigel plugs in vivo. CONCLUSIONS These data are the first to report expression of the anti-inflammatory interleukin IL-19 in EC, and the first to indicate that IL-19 is mitogenic and chemotactic for EC, and can induce the angiogenic potential of EC. PMID:20966397

  13. Three-dimensional rapid visualization of matrix deformations around angiogenic sprouts (Conference Presentation)

    Science.gov (United States)

    Steuwe, Christian; Vayens, Marie-Mo; Jorge Peñas, Alvaro; Krajnik, Bartosz; Van Oosterwyck, Hans; Roeffaers, Maarten B. J.

    2017-02-01

    At the cell - extracellular matrix interface, physiologically important traction forces exerted by angiogenic sprouts can be investigated indirectly by mapping the consecutive matrix deformations. In this paper we present an approach to study these forces in three dimensions and with high time resolution. The technique employs lightsheet microscopy, in which a sheet of light is used to illuminate the sample - resulting in z-sectioning capability, superior image recording speed and reduced phototoxicity. For this study, human umbilical vein endothelial cells (HUVEC) are transduced with a LifeAct adenoviral vector to visualize the actin cytoskeleton during live sprouting into a collagen type I hydrogel. The calculation of the matrix deformations is formulated as a B-spline-based 3D non-rigid image registration process that warps the image of beads inside the stressed gel to match the image after stress relaxation. Using this approach we study the role of fast moving actin filaments for filopodia- and tip-cell dynamics in 3D under chemically defined culture conditions such as inhibited acto-myosin force generation. With a time resolution in the range of ten seconds, we find that our technique is at least 20 times faster than conventional traction force microscopy based on confocal imaging. Ultimately, this approach will shed light on rapid mechano-chemical feedback mechanisms important for sprouting angiogenesis.

  14. Desmin expression in colorectal cancer stroma correlates with advanced stage disease and marks angiogenic microvessels

    Directory of Open Access Journals (Sweden)

    Arentz Georgia

    2011-12-01

    Full Text Available Abstract Introduction Biomarkers that improve stratification of colorectal cancer patients for adjuvant therapy versus resection alone, or that are predictive of response to therapeutic agents, have the potential to greatly improve patient selection for such therapies. The aim was to determine proteins differentially expressed within the malignant epithelial glands and closely associated stromal elements compared to matched normal mucosa, and to characterise the over-expression of one such protein as a potential biomarker. Methods Protein from laser microdissected tumor and normal mucosa was analysed by two dimensional difference gel electrophoresis (2D DIGE and mass spectrometry to determine differentially over expressed tumor proteins. Tumor over-expression of one such protein, desmin, was quantified using immunofluorescence staining in a larger cohort. Dual staining for desmin and vimentin, or desmin and von Willebrand factor, was performed to determine the cell type of interest. Results Desmin expression was significantly increased between stage I and III tumors, (P P Conclusion Pericyte coverage of vasculature is a marker of vessel maturation, hence desmin expression may have use as a marker for microvessel maturation. Clinical trials will be needed to determine its use in identifying tumors that will be less responsive to anti-angiogenic therapy.

  15. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity

    Directory of Open Access Journals (Sweden)

    Zhang Jianing

    2010-03-01

    Full Text Available Abstract Background fatty acids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigat the effect of fatty acid extracts from dried Lucilia sericata larvae on murine cutaneuous wound healing as well as angiogenesis. Results On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fatty acid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fatty acid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fatty acid extracts group were higher than that of vaseline group. Component analysis of the fatty acid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fatty acids in total and the ratio of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid (PUFA was: 20.57%:60.32%:19.11%. Conclusions Fatty acid extracts from dried Lucilia sericata larvae, four fifths of which are unsaturated fatty acids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts.

  16. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity.

    Science.gov (United States)

    Zhang, Zhen; Wang, Shouyu; Diao, Yunpeng; Zhang, Jianing; Lv, Decheng

    2010-03-08

    fatty acids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigate the effect of fatty acid extracts from dried Lucilia sericata larvae on murine cutaneous wound healing as well as angiogenesis. On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fatty acid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fatty acid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fatty acid extracts group were higher than that of vaseline group. Component analysis of the fatty acid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fatty acids in total and the ratio of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid (PUFA) was: 20.57%:60.32%:19.11%. Fatty acid extracts from dried Lucilia sericata larvae, four fifths of which are unsaturated fatty acids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts.

  17. Hyperoxia impairs pro-angiogenic RNA production in preterm endothelial colony-forming cells

    Directory of Open Access Journals (Sweden)

    Megan A. Ahern

    2017-04-01

    Full Text Available Disruptions in the response of endothelial progenitor cells to changes in oxygen environment may present a possible mechanism behind multiple pediatric pulmonary disease models, such as bronchopulmonary dysplasia. Using high-throughput fixed single-cell protein and RNA imaging, we have created “stop-motion” movies of Thymosin β4 (Tβ4 and Hypoxia Inducible Factor 1α (HIF-1α protein expression and vascular endothelial growth factor (vegf and endothelial nitric oxide synthase (eNOS mRNA in human umbilical cord-derived endothelial colony-forming cells (ECFC. ECFC were grown in vitro under both room air and hyperoxia (50% O2. We find elevated basal Tβ4 protein expression in ECFC derived from prematurely born infants versus full term infants. Tβ4 is a potent growth hormone that additionally acts as an actin sequestration protein and regulates the stability of HIF-1α. This basal level increase of Tβ4 is associated with lower HIF-1α nuclear localization in preterm versus term ECFC upon exposure to hyperoxia. We find altered expression in the pro-angiogenic genes vegf and eNOS, two genes that HIF-1α acts as a transcription factor for. This provides a potential link between a developmentally regulated protein and previously observed impaired function of preterm ECFC in response to hyperoxia.

  18. Osteonecrosis of the mandible due to anti-angiogenic agent, bevacizumab.

    Science.gov (United States)

    Pakosch, Daria; Papadimas, Dimitrios; Munding, Johanna; Kawa, Darafsch; Kriwalsky, Marcus Stephan

    2013-12-01

    Osteonecrosis of the jaw (ONJ) is defined by areas of tissue breakdown and exposure of bone in the maxillofacial region that fail to heal within 8 weeks after identification by a health provider in a patient who has not received radiation of the jaws. The disease affects the quality of life and produces significant morbidity in afflicted patients. ONJ is correlated with such risk factors as treatment with bisphosphonates, dental extraction-related trauma, chemotherapy, corticosteroids, renal osteodystrophy and infections. Although the use of bisphosphonates is associated with osteonecrosis of the jaw, the pathophysiology of bisphosphonate-associated ONJ is still unknown. It has been assumed that bisphosphonates lead to the inhibition of capillary angiogenesis and disturbances in the activities of both osteoblasts and osteoclasts, thereby impairing bone remodelling. Currently, inhibitors of angiogenesis used in the treatment of cancer patients are implicated in isolated cases of ONJ. This manuscript reports a case of ONJ in a female patient who received bevacizumab (Avastin®, Roche), a humanised monoclonal antibody that recognises and blocks vascular endothelial growth factor (VEGF)-A. The anti-angiogenic agent, bevacizumab, may increase the risk of osteonecrosis of the jaw. This agent inhibits VEGF and, therefore, also presumably represses the vascularisation of the jaw, which leads to healing complications. Due to increasing use of bevacizumab, patients receiving this agent should be closely monitored for possible side effects.

  19. Neuropeptide Substance P Improves Osteoblastic and Angiogenic Differentiation Capacity of Bone Marrow Stem Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Su Fu

    2014-01-01

    Full Text Available Our previous work showed that implanting a sensory nerve or vascular bundle when constructing vascularized and neurotized bone could promote bone osteogenesis in tissue engineering. This phenomenon could be explained by the regulatory function of neuropeptides. Neuropeptide substance P (SP has been demonstrated to contribute to bone growth by stimulating the proliferation and differentiation of bone marrow stem cells (BMSCs. However, there have been no prior studies on the association between Wnt signaling and the mechanism of SP in the context of BMSC differentiation. Our results have shown that SP could enhance the differentiation of BMSCs by activating gene and protein expression via the Wnt pathway and by translocating β-catenin, which can be inhibited by Wnt signaling blocker treatment or by the NK-1 antagonist. SP could also increase the growth factor level of bone morphogenetic protein-2 (BMP-2. Additionally, SP could enhance the migration ability of BMSCs, and the promotion of vascular endothelial growth factor (VEGF expression by SP has been studied. In conclusion, SP could induce osteoblastic differentiation via the Wnt pathway and promote the angiogenic ability of BMSCs. These results indicate that a vascularized and neurotized tissue-engineered construct could be feasible for use in bone tissue engineering strategies.

  20. [THE ROLE OF ANGIOGENIC FACTORS IN THE DIAGNOSTICS OF PREGNANCY COMPLICATED WITH PREECLAMPSIA].

    Science.gov (United States)

    Tagiyeva, I; Aliyeva, S; Bagirova, S; Shamsadinskaya, N; Agaeva, K

    2017-01-01

    The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of vascular growth factor (VEGF) and placental growth factor (PIGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1. Our research demonstrate that increased circulating sFlt1 in III trimester in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PIGF, resulting in endothelial dysfunction, comparing with control group. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia. 45 pregnant women with preeclampsia of different severity degrees were under observation. Control group included 20 healthy pregnant. Pregnant women with preeclampsia were subdivided into 2 groups. There were 11 (24,4%) pregnant with severe degree of preeclamsia (I group), the II group included 34 pregnant with mild degree of preeclampsia. Increased expression of soluble tyrosine kinase-1 (sFlt-1), together with decreased PIGF and VEGF signaling, were first abnormalities described. Thus, determination of levels angiogenic factors: PIGF, VEGF and sFlt-1 is very important for prediction severity of preeclampsia.

  1. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

    2013-04-15

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  2. On Cheating Immune Secret Sharing

    Directory of Open Access Journals (Sweden)

    Josef Pieprzyk

    2004-12-01

    Full Text Available The paper addresses the cheating prevention in secret sharing. We consider secret sharing with binary shares. The secret also is binary. This model allows us to use results and constructions from the well developed theory of cryptographically strong boolean functions. In particular, we prove that for given secret sharing, the average cheating probability over all cheating vectors and all original vectors, i.e., 1/n 2 n ∑ c=1...n ∑ α∈V n ρ c,α, denoted by ρ, satisfies ρ ≥ ½, and the equality holds if and only if ρ c,α satisfies ρ c,α = ½ for every cheating vector δ c and every original vector α. In this case the secret sharing is said to be cheating immune. We further establish a relationship between cheating-immune secret sharing and cryptographic criteria of boolean functions.This enables us to construct cheating-immune secret sharing.

  3. Social identities and shared realities.

    Science.gov (United States)

    Hogg, Michael A; Rinella, Mark J

    2017-11-04

    People are fundamentally motivated to establish a shared reality with others to validate their identity and experiences. Guided by social identity theory, we examine how social identity processes, such as self-categorization and depersonalization, create a shared identity and a sense of shared reality. Research demonstrates that internal states such as attitudes, feelings, and emotions are often shared among members of a group. Furthermore, research has shown that self-uncertainty motivates people to establish shared realities through group identification, often with highly entitative groups that are associated with a self-saturating reality that is shared absolutely. Finally, we review research on how group-defining norms that serve as the bases of these identity-related shared realities are constructed and communicated through group-membership based influence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Epidermal Growth Factor and Estrogen Act by Independent Pathways to Additively Promote the Release of the Angiogenic Chemokine CXCL8 by Breast Tumor Cells

    Directory of Open Access Journals (Sweden)

    Karin Haim

    2011-03-01

    Full Text Available The tumor microenvironment contains multiple cancer-supporting factors, whose joint activities promote malignancy. Here, we show that epidermal growth factor (EGF and estrogen upregulate in an additive manner the transcription and the secretion of the angiogenic chemokine CXCL8 (interleukin 8 [IL-8] in breast tumor cells. In view of published findings on cross-regulatory interactions between EGF receptors and estrogen receptors in breast tumor cells, we asked whether the additive effects of EGF and estrogen were due to their ability to (1 induce intracellular cross talk and amplify shared regulatory pathways or (2 act in independent mechanisms, which complement each other. We found that stimulation by EGF alone induced the release of CXCL8 through signaling pathways involving ErbB2, ErbB1, Erk, and phosphoinositide 3-kinase (PI3K. ErbB2 and Erk were also involved in estrogen activities on CXCL8 but to a lower extent than with EGF. However, in the joint stimulatory setup, the addition of estrogen to EGF has led to partial (ErbB2, ErbB1, Erk or complete (PI3K shutoff of the involvement of these activation pathways in CXCL8 up-regulation. Furthermore, when costimulation by EGF + estrogen was applied, the effects of estrogen were channeled to regulation of CXCL8 at the transcription level, acting through the transcription factor estrogen receptor α (ERα. In parallel, in the joint stimulation, EGF acted independently at the transcription level through AP-1, to upregulate CXCL8 expression. The independent activities of EGF and estrogen on CXCL8 transcription reinforce the need to introduce simultaneous targeting of ErbBs and ERα to achieve effective therapy in breast cancer.

  5. Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of ¹⁸F-FDG PET Imaging in Ischemic Stroke Treatment.

    Science.gov (United States)

    Hwang, Hyosook; Jeong, Hwan-Seok; Oh, Phil-Sun; Na, Kyung-Suk; Kwon, JeongIl; Kim, Jeonghun; Lim, SeokTae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2015-07-01

    Strategies to promote angiogenesis can benefit cerebral ischemia. We determined whether liposomal delivery of angiogenic peptides with a known biologic activity of vascular endothelial growth factor benefitted cerebral ischemia. Also, the study examined the potential of (18)F-FDG PET imaging in ischemic stroke treatment. Male Sprague-Dawley rats (n = 40) underwent 40 min of middle cerebral artery occlusion. After 15 min of reperfusion, the rats (n = 10) received angiogenic peptides incorporated into liposomes. Animals receiving phosphate-buffered solution or liposomes without peptides served as controls. One week later, (18)F-FDG PET imaging was performed to examine regional changes in glucose utilization in response to the angiogenic therapy. The following day, (99m)Tc-hexamethylpropyleneamine oxime autoradiography was performed to determine changes in cerebral perfusion after angiogenic therapy. Corresponding changes in angiogenic markers, including von Willebrand factor and angiopoietin-1 and -2, were determined by immunostaining and polymerase chain reaction analysis, respectively. A 40-min period of middle cerebral artery occlusion decreased blood perfusion in the ipsilateral ischemic cortex of the brain, compared with that in the contralateral cortex, as measured by (99m)Tc-hexamethylpropyleneamine oxime autoradiography. Liposomal delivery of angiogenic peptides to the ischemic hemisphere of the brain attenuated the cerebral perfusion defect compared with controls. Similarly, vascular density evidenced by von Willebrand factor-positive staining was increased in response to angiogenic therapy, compared with that of controls. This increase was accompanied by an early increase in angiopoietin-2 expression, a gene participating in angiogenesis. (18)F-FDG PET imaging measured at 7 d after treatment revealed that liposomal delivery of angiogenic peptides facilitated glucose utilization in the ipsilateral ischemic cortex of the brain, compared with that in the

  6. The science of sharing and the sharing of science.

    Science.gov (United States)

    Milkman, Katherine L; Berger, Jonah

    2014-09-16

    Why do members of the public share some scientific findings and not others? What can scientists do to increase the chances that their findings will be shared widely among nonscientists? To address these questions, we integrate past research on the psychological drivers of interpersonal communication with a study examining the sharing of hundreds of recent scientific discoveries. Our findings offer insights into (i) how attributes of a discovery and the way it is described impact sharing, (ii) who generates discoveries that are likely to be shared, and (iii) which types of people are most likely to share scientific discoveries. The results described here, combined with a review of recent research on interpersonal communication, suggest how scientists can frame their work to increase its dissemination. They also provide insights about which audiences may be the best targets for the diffusion of scientific content.

  7. Data sharing in neuroimaging research

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste ePoline

    2012-04-01

    Full Text Available Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging.

  8. Sharing Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Mohler, Bryan L.

    2004-09-01

    Workplace safety is inextricably tied to the culture – the leadership, management and organization – of the entire company. Nor is a safety lesson fundamentally different from any other business lesson. With these points in mind, Pacific Northwest National Laboratory recast its lessons learned program in 2000. The laboratory retained elements of a traditional lessons learned program, such as tracking and trending safety metrics, and added a best practices element to increase staff involvement in creating a safer, healthier work environment. Today, the Lessons Learned/Best Practices program offers the latest business thinking summarized from current external publications and shares better ways PNNL staff have discovered for doing things. According to PNNL strategic planning director Marilyn Quadrel, the goal is to sharpen the business acumen, project management ability and leadership skills of all staff and to capture the benefits of practices that emerge from lessons learned. A key tool in the PNNL effort to accelerate learning from past mistakes is one that can be easily implemented by other firms and tailored to their specific needs. It is the weekly placement of Lessons Learned/Best Practices articles in the lab’s internal electronic newsletter. The program is equally applicable in highly regulated environments, such as the national laboratories, and in enterprises that may have fewer external requirements imposed on their operations. And it is cost effective, using less than the equivalent of one fulltime person to administer.

  9. Angiogenic capacity of M1- and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9

    Science.gov (United States)

    Zajac, Ewa; Schweighofer, Bernhard; Kupriyanova, Tatyana A.; Juncker-Jensen, Anna; Minder, Petra

    2013-01-01

    A proangiogenic function of tissue-infiltrating monocytes/macrophages has long been attributed to their matrix metalloproteinase-9 zymogen (proMMP-9). Herein, we evaluated the capacity of human monocytes, mature M0 macrophages, and M1- and M2-polarized macrophages to induce proMMP-9-mediated angiogenesis. Only M2 macrophages induced angiogenesis at levels comparable with highly angiogenic neutrophils previously shown to release their proMMP-9 in a unique form, free of tissue inhibitor of metalloproteinases-1 (TIMP-1). Macrophage differentiation was accompanied by induction of low-angiogenic, TIMP-1–encumbered proMMP-9. However, polarization toward the M2, but not the M1 phenotype, caused a substantial downregulation of TIMP-1 expression, resulting in production of angiogenic, TIMP-deficient proMMP-9. Correspondingly, the angiogenic potency of M2 proMMP-9 was lost after its complexing with TIMP-1, whereas TIMP-1 silencing in M0/M1 macrophages rendered them both angiogenic. Similar to human cells, murine bone marrow–derived M2 macrophages also shut down their TIMP-1 expression and produced proMMP-9 unencumbered by TIMP-1. Providing proof that angiogenic capacity of murine M2 macrophages depended on their TIMP-free proMMP-9, Mmp9-null M2 macrophages were nonangiogenic, although their TIMP-1 was severely downregulated. Our study provides a unifying molecular mechanism for high angiogenic capacity of TIMP-free proMMP-9 that would be uniquely produced in a pathophysiological microenvironment by influxing neutrophils and/or M2 polarized macrophages. PMID:24174628

  10. 2013 Information Sharing Environment Performance Data

    Data.gov (United States)

    Information Sharing Environment — This is a survey of federal departments and agencies who share terrorism information and are therefore considered part of the Information Sharing Environment. The...

  11. 2012 Information Sharing Environment Performance Data

    Data.gov (United States)

    Information Sharing Environment — This is a survey of federal departments and agencies who share terrorism information and are therefore considered part of the Information Sharing Environment. The...

  12. SharePoint User's Guide

    CERN Document Server

    Corporation, Infusion Development

    2009-01-01

    This straightforward guide shows SharePoint users how to create and use web sites for sharing and collaboration. Learn to use the document and picture libraries for adding and editing content, add discussion boards and surveys, receive alerts when documents and information have been added or changed, and enhance security. Designed to help you find answers quickly, the book shows how to make the most of SharePoint for productivity and collaboration.

  13. Modeling Shared Variables in VHDL

    DEFF Research Database (Denmark)

    Madsen, Jan; Brage, Jens P.

    1994-01-01

    A set of concurrent processes communicating through shared variables is an often used model for hardware systems. This paper presents three modeling techniques for representing such shared variables in VHDL, depending on the acceptable constraints on accesses to the variables. Also a set...... of guidelines for handling atomic updates of multiple shared variables is given. 1 Introduction It is often desirable to partition a computational system into discrete functional units which cooperates to....

  14. Emergent Resource Sharing & Interlibrary Loan

    OpenAIRE

    Oberlander, Cyril

    2006-01-01

    Resource sharing and Interlibrary Loan face exciting opportunities to develop new connections between information and library resources and services. Emergent consumer technology is radically changing the nature of Library service; however, we can shape the transformation of resource sharing and interlibrary loan. Framing the evolution of request management systems and resource sharing workflow are communities of adaptations to the changed information and technology landscape. The redefini...

  15. Instant Social Ride-Sharing

    OpenAIRE

    Gidofalvi, Gyözö; Herenyi, Gergely; Bach Pedersen, Torben

    2008-01-01

    This paper explores the use of ride–sharing as a resource-efficient mode of personal transportation. While the perceived benefits of ride–sharing include reduced travel times, transportation costs, congestion, and carbon emissions, its wide–spread adoption is hindered by a number of barriers. These include the scheduling and coordination of routes, safety risks, social discomfort in sharing private spaces, and an imbalance of costs and benefits among parties. To address these barriers, the au...

  16. Taurolidine--a new drug with anti-tumor and anti-angiogenic effects.

    Science.gov (United States)

    Jacobi, Christoph A; Menenakos, Charalambos; Braumann, Chris

    2005-10-01

    Taurolidine [bis(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)-methane (TRD)], a product derived from the aminosulfoacid taurin, was first described as an anti-bacterial substance. It was mainly used in the treatment of patients with peritonis as well as antiendoxic agent in patients with systematic inflammatory response syndrome. Meanwhile, quite interesting new experimental findings elucidated several new mechanisms concerning not only antibiotic but also anti-tumor effects. TRD significantly reduces the pathogenicity of prokaryotes, leading to a degeneration of the bacterial wall, and binds free lipoplysaccharides (LPSs) and exotoxins. Furthermore syntheses of tumor necrosis factor-a and interleukin-1b are reduced in LPS-stimulated human macrophages in a dose dependent manner. Tumor angiogenesis is promoted by enhanced expression of all these endogenous angiogenic factors, indicating an anti-angiogenetic effect of TRD. Tumor angiogenesis has a key role in tumor growth. TRD additionally inhibits tumor cell growth by a mitochondrial cytochrome c-dependent apoptotic mechanism, has a direct and elective effect on glial and neuronal brain tumor cells via Fas-ligand-mediated cell death, and inhibits protein synthesis at an early phase of translation, which might explain its various apoptotic effects. Subsequent to these experimental observations, TRD has shown encouraging clinical results after intravenous administration in patients with gastrointestinal malignancies and tumors of the central nerve system. A remarkable experimental observation that comes to complete the above-mentioned findings is the low toxicity on leukopoiesis and erythropoiesis as well as on kidney and liver function in animal models. Several other data confirm low toxicity of the agent after its clinical administration in humans. Prospective clinical studies are currently investigating the efficacy of TRD on local and metastatic tumor growth in different malignancies.

  17. Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer.

    Science.gov (United States)

    Gröne, Jörn; Doebler, Oliver; Loddenkemper, Christoph; Hotz, Birgit; Buhr, Heinz-Johannes; Bhargava, Sarah

    2006-06-01

    The family of roundabout (Robo) proteins is related to the transmembrane receptors and plays a major role in the process of axonal guidance in neurogenesis. It has recently been shown that Robo proteins are also associated with tumor angiogenesis with Slit2 acting as the corresponding ligand. The aim of this study was to validate the differential expression by means of microarray analysis and real-time PCR and to analyze the in situ expression of Robo1 and Robo4 in colorectal cancer. Quantitative analyses of Robo1, Robo4 and Slit2 mRNA expression measured by large scale gene expression studies (Affymetrix U133A) showed a significant up-regulation of Robo1 in tumor vs. normal tissue, whereas Robo4 and Slit2 showed no significant deregulation. For subsequent real-time PCR experiments, paired colorectal tissue samples from cancerous and corresponding non-cancerous tissues were obtained from 50 colorectal cancer patients who underwent surgical resection. Robo1 mRNA overexpression in cancerous tissue compared with normal counterparts was observed in 80% of the patients with a 4-fold expression in 45% and a 12-fold expression in 15%. For Robo4, an up-regulation was detected in >70% (36/50). For Slit2, no differential expression was observed. The overexpression of Robo1 and Robo4 in tumor vs. normal tissue was verified using real-time PCR. The histological analysis revealed an expression of Robo1 mainly in tumor cells, whereas Robo4 is located primarily in endothelial cells of tumor vessels. Therefore, the Robo proteins provide potential target structures for the anti-tumorigenic and anti-angiogenic therapy of colorectal carcinoma.

  18. Impaired Endothelial Regeneration Through Human Parvovirus B19-Infected Circulating Angiogenic Cells in Patients With Cardiomyopathy.

    Science.gov (United States)

    Schmidt-Lucke, Caroline; Zobel, Thomas; Schrepfer, Sonja; Kuhl, Uwe; Wang, Dong; Klingel, Karin; Becher, Peter Moritz; Fechner, Henry; Pozzuto, Tanja; Van Linthout, Sophie; Lassner, Dirk; Spillmann, Frank; Escher, Felicitas; Holinski, Sebastian; Volk, Hans-Dieter; Schultheiss, Heinz-Peter; Tschope, Carsten

    2015-10-01

    Human parvovirus B19 (B19V) is a common pathogen in microvascular disease and cardiomyopathy, owing to infection of endothelial cells. B19V replication, however, is almost restricted to erythroid progenitor cells (ErPCs). Endothelial regeneration attributable to bone marrow-derived circulating angiogenic cells (CACs) is a prerequisite for organ function. Because of many similarities of ErPCs and CACs, we hypothesized that B19V is a perpetrator of impaired endogenous endothelial regeneration. B19V DNA and messenger RNA from endomyocardial biopsy specimens, bone marrow specimens, and circulating progenitor cells were quantified by polymerase chain reaction analysis. The highest B19V DNA concentrations were found in CD34(+)KDR(+) cells from 17 patients with chronic B19V-associated cardiomyopathy. B19V replication intermediates could be detected in nearly half of the patients. Furthermore, chronic B19V infection was associated with impaired endothelial regenerative capacity. B19V infection of CACs in vitro resulted in expression of transcripts encoding B19V proteins. The capsid protein VP1 was identified as a novel inducer of apoptosis, as were nonstructural proteins. Inhibition studies identified so-called death receptor signaling with activation of caspase-8 and caspase-10 to be responsible for apoptosis induction. B19V causally impaired endothelial regeneration with spreading of B19V in CACs in an animal model in vivo. We thus conclude that B19V infection and damage to CACs result in dysfunctional endogenous vascular repair, supporting the emergence of primary bone marrow disease with secondary end-organ damage. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Steroid hormones, prostanoids, and angiogenic systems during rescue of the corpus luteum in pigs.

    Science.gov (United States)

    Przygrodzka, E; Kaczmarek, M M; Kaczynski, P; Ziecik, A J

    2016-02-01

    In order to characterize the transition of the corpora lutea (CL) from acquisition of luteolytic sensitivity to rescue of luteal function: i) the expression of 38 factors associated with steroids, prostanoids, and angiogenic systems and ii) concentrations of the main hormones responsible for maintenance of CL function in cyclic and pregnant pigs were examined. Additionally, the effect of prostaglandin (PG) E2 and F2 α on luteal function during the estrous cycle and pregnancy was evaluated in vitro. Significantly up-regulated gene expression was revealed in CL collected on day 14 of the estrous cycle (CYP19A1, ESR2, PTGS2, HIF1A, and EDN1) and on days 12-14 of pregnancy (SCARB1, PGRMC1, STAR, HSD3B1, NR5A1, PTGFR, PTGER4, and VEGFA). Elevated concentrations of estradiol-17β and PGE2 occurred in CL on days 12 and 14 of pregnancy respectively, while an increased intraluteal PGF2 α content was noted on day 14 of the estrous cycle. Both PGs increased the synthesis of progesterone by cultured luteal slices obtained on day 14 of pregnancy, in contrast to the action of PGF2 α on the corresponding day of the estrous cycle. PGE2 stimulated cAMP production via PTGER2 and PTGER4, while PGF2 α elevated the content of CREB in cultured luteal slices from CL of pregnant pigs. In silico analysis showed that infiltration of lymphocytes and apoptosis of microvascular endothelium were activated in CL on day 12 of the estrous cycle vs pregnancy. Summarizing, an abundance of E2 and PGE2 during pregnancy regulates specific pathways responsible for steroidogenesis, the prostanoid signaling system and angiogenesis during rescue from luteolysis in porcine CL. © 2016 Society for Reproduction and Fertility.

  20. SERUM CONCENTRATIONS OF SOME ANGIOGENEIC FACTORS IN MULTIPLE MYELOMA: VEGF, bFGF IN MMP-9

    Directory of Open Access Journals (Sweden)

    Mojca Modic

    2004-12-01

    Full Text Available Background. Angiogenesis is a crucial process in progression of multiple myeloma. Vascular endothelial growth factor (VEGF, and basic fibroblast growth factor (bFGF are multifunctional cytokines that stimulate angiogenesis and myeloma growth. Matrix metalloproteinase 9 (MMP-9 plays a critical role in osteolytic bone destruction, angiogenesis and invasive growth of myeloma cells. We evaluated serum concentrations of these factors in patients with multiple myeloma.Methods. Levels of active and pro-matrix metalloproteinase 9 (total MMP-9, basic fibroblast growth factor (bFGF and vascular endothelial growth factor (VEGF were determined with a commercial quantitative enzyme immunoassay Quantikine  (R&D Systems, USA. All of these factors were measured in the serum obtained from pheripheral blood of 36 patients affected by multiple myeloma.This series included 12 patients with disease in plateau phase and without treatment, 14 patients on Thalidomide therapy and 10 patients at the beginning of chemotherapy because of active disease.Results. VEGF showed a strong correlation with MMP-9 while VEGF and bFGF did not correlate with each other. Blood platelets correlated with VEGF and MMP-9.The concentration of MMP-9 and VEGF were the highest in group of patients with active disease where the chemotherapy started. The level of bFGF was the lowest in the group devoid of treatment (plateau phase of disease.Conclusions. Production of the angiogenic factors such as VEGF, bFGF and MMP-9 are increased in multiple myeloma patients. The levels of these factors correlate with the activity of disease.

  1. The induction of an angiogenic response in corneal myofibroblasts by platelet-activating factor (PAF).

    Science.gov (United States)

    He, Jiucheng; Eastlack, Jason P; Bazan, Haydee E P

    2010-12-01

    Although the exact mechanisms underlying corneal neovascularization remain unclear, cytokines and growth factors play an important role in their development. We have shown previously that the inflammatory mediator platelet-activating factor (PAF) is a potent inducer of corneal neovascularization in vivo. In this study, we investigate the role of stromal myofibroblasts in neovascularization and the effect of PAF on this process. Myofibroblasts were obtained from rabbit corneal keratocytes and identified with anti-α-SMA antibody. Cells were treated with PAF (100 nM) for 24 hr. In some experiments, cells were pre-treated with the PAF antagonist LAU-0901 (150 nM). Expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) was examined by immunofluorescence and immunoblotting. To study the effect of myofibroblasts on vessel formation in vitro, Vybrant(®) CM-DiI labeled human umbilical vein endothelial cells (HUVECs) were cultured on myofibroblasts in a thin layer of collagen gel. CD31 was used as the cell marker of HUVEC. VEGF and TSP-1 were not detectable in keratocytes, but they were positively stained in myofibroblasts. PAF induced a significant increase in VEGF expression and a decrease in TSP-1 expression. These changes were inhibited in the presence of LAU-0901. HUVECs co-cultured with corneal myofibroblasts formed a typical structure of vessel-like tubes within 1 week. The addition of PAF to the medium increased HUVEC-induced vessel-like tube formation, which was abolished by LAU-0901. Addition of anti-VEGF antibody to the medium completely prevented the formation of vessel-like tubes. We provide evidence for the role of stromal myofibroblasts in the corneal neovascularization process. By enhancing VEGF production and decreasing TSP-1 production in myofibroblasts, PAF augments the angiogenic response. The PAF antagonist LAU-0901 could represent a new therapeutic venue for inhibiting corneal neovascularization.

  2. Effects of Ellagic Acid on Angiogenic Factors in Prostate Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Vanella, Luca; Di Giacomo, Claudia; Acquaviva, Rosaria; Barbagallo, Ignazio; Li Volti, Giovanni [Department of Drug Science, Section of Biochemistry, University of Catania, I-95125 Catania (Italy); Cardile, Venera [Department of Bio-Medical Sciences, Section of Physiology, University of Catania, I-95125, Catania (Italy); Abraham, Nader G. [Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701 (United States); Sorrenti, Valeria, E-mail: sorrenti@unict.it [Department of Drug Science, Section of Biochemistry, University of Catania, I-95125 Catania (Italy)

    2013-06-19

    Background: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor (VEGF) and heme oxygenase system (HO) have emerged as important modulators of tumor growth and metastasis. Methods: The anti-angiogenic effects of EA were investigated in the human prostatic cancer cell line LnCap. HO-1, HO-2, CYP2J2 and soluble epoxyde hydrolase (sEH) expressions were evaluated by western blotting. Levels of VEGF and osteoprotegerin (OPG) were determined in the culture supernatant using an ELISA assay, while CYP mRNAs were determined by qRT-PCR. Results: EA treatment induced a significant decrease (p < 0.05) in HO-1, HO-2 and CYP2J2 expression, and in VEGF and OPG levels. Similarly CYP2J2, CYP4F2 and CYPA22 mRNAs were significantly (p < 0.05) down-regulated by EA treatment. The decrease in CYP2J2 mRNA was associated with an increase in sEH expression. Conclusions: Results reported in the present study highlighted the ability of EA to modulate a new pathway, in addition to anti-proliferative and pro-differentiation properties, via a mechanism that involves a decrease in eicosanoid synthesis and a down-regulation of the HO system in prostate cancer.

  3. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Esposito, I; Menicagli, M; Funel, N; Bergmann, F; Boggi, U; Mosca, F; Bevilacqua, G; Campani, D

    2004-06-01

    Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness. To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance. Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker. There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages. Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.

  4. Adenoviral Transduction of Human Acid Sphingomyelinase into Neo-Angiogenic Endothelium Radiosensitizes Tumor Cure

    Science.gov (United States)

    Fuller, John D.; Rotolo, Jimmy A.; García-Barros, Mónica; Feldman, Regina; Rao, Shyam; Weichselbaum, Ralph R.; Harats, Dror; Haimovitz-Friedman, Adriana; Fuks, Zvi; Sadelain, Michel; Kolesnick, Richard

    2013-01-01

    These studies define a new mechanism-based approach to radiosensitize tumor cure by single dose radiotherapy (SDRT). Published evidence indicates that SDRT induces acute microvascular endothelial apoptosis initiated via acid sphingomyelinase (ASMase) translocation to the external plasma membrane. Ensuing microvascular damage regulates radiation lethality of tumor stem cell clonogens to effect tumor cure. Based on this biology, we engineered an ASMase-producing vector consisting of a modified pre-proendothelin-1 promoter, PPE1(3x), and a hypoxia-inducible dual-binding HIF-2α-Ets-1 enhancer element upstream of the asmase gene, inserted into a replication-deficient adenovirus yielding the vector Ad5H2E-PPE1(3x)-ASMase. This vector confers ASMase over-expression in cycling angiogenic endothelium in vitro and within tumors in vivo, with no detectable enhancement in endothelium of normal tissues that exhibit a minute fraction of cycling cells or in non-endothelial tumor or normal tissue cells. Intravenous pretreatment with Ad5H2E-PPE1(3x)-ASMase markedly increases SDRT cure of inherently radiosensitive MCA/129 fibrosarcomas, and converts radiation-incurable B16 melanomas into biopsy-proven tumor cures. In contrast, Ad5H2E-PPE1(3x)-ASMase treatment did not impact radiation damage to small intestinal crypts as non-dividing small intestinal microvessels did not overexpress ASMase and were not radiosensitized. We posit that combination of genetic up-regulation of tumor microvascular ASMase and SDRT provides therapeutic options for currently radiation-incurable human tumors. PMID:23936314

  5. Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

    2017-05-01

    The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

  6. Adenoviral transduction of human acid sphingomyelinase into neo-angiogenic endothelium radiosensitizes tumor cure.

    Directory of Open Access Journals (Sweden)

    Branka Stancevic

    Full Text Available These studies define a new mechanism-based approach to radiosensitize tumor cure by single dose radiotherapy (SDRT. Published evidence indicates that SDRT induces acute microvascular endothelial apoptosis initiated via acid sphingomyelinase (ASMase translocation to the external plasma membrane. Ensuing microvascular damage regulates radiation lethality of tumor stem cell clonogens to effect tumor cure. Based on this biology, we engineered an ASMase-producing vector consisting of a modified pre-proendothelin-1 promoter, PPE1(3x, and a hypoxia-inducible dual-binding HIF-2α-Ets-1 enhancer element upstream of the asmase gene, inserted into a replication-deficient adenovirus yielding the vector Ad5H2E-PPE1(3x-ASMase. This vector confers ASMase over-expression in cycling angiogenic endothelium in vitro and within tumors in vivo, with no detectable enhancement in endothelium of normal tissues that exhibit a minute fraction of cycling cells or in non-endothelial tumor or normal tissue cells. Intravenous pretreatment with Ad5H2E-PPE1(3x-ASMase markedly increases SDRT cure of inherently radiosensitive MCA/129 fibrosarcomas, and converts radiation-incurable B16 melanomas into biopsy-proven tumor cures. In contrast, Ad5H2E-PPE1(3x-ASMase treatment did not impact radiation damage to small intestinal crypts as non-dividing small intestinal microvessels did not overexpress ASMase and were not radiosensitized. We posit that combination of genetic up-regulation of tumor microvascular ASMase and SDRT provides therapeutic options for currently radiation-incurable human tumors.

  7. Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Ingrid C Weel

    Full Text Available Preeclampsia (PE is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE. We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1, tumor necrosis factor-alpha (TNF-α, placental growth factor (PlGF, vascular endothelial growth factor (VEGF, fms-like tyrosine-kinase-1 (Flt-1 and endoglin (Eng levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

  8. Challenges in sharing information effectively

    DEFF Research Database (Denmark)

    Sonnenwald, Diane H.

    2006-01-01

    Introduction. The goal of information sharing is to change a person's image of the world and to develop a shared working understanding. It is an essential component of collaboration. This paper examines barriers to sharing information effectively in dynamic group work situations. Method. Three...... to other high stress, unique and complex situations, such as natural disasters. Recommendations for more effective information behaviour techniques in dynamic group work situations are presented....... types of battlefield training simulations were observed and open-ended interviews with military personnel were conducted. Analysis. Observation notes and interview transcripts were analysed to identify incidents when group members erroneously believed they had shared information effectively and were...

  9. Governing Individual Knowledge Sharing Behavior

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Pedersen, Torben

    2010-01-01

    The emerging Knowledge Governance Approach asserts the need to build microfoundations grounded in individual action. Toward this goal, using the Theory of Planned Behavior, we aim to explain individual knowledge sharing behavior as being determined by the intention to share knowledge and its...... antecedents: attitude toward knowledge sharing, subjective norms, and perceived behavioral control. In addition, we consider managerial interventions (governance mechanisms) that managers can employ to influence the identified antecedents and thereby govern individual knowledge sharing behavior. We test...... a positive effect on subjective norms and perceived behavioral control, respectively....

  10. Technology Mediated Information Sharing (Monitor Sharing) in Primary Care Encounters

    Science.gov (United States)

    Asan, Onur

    2013-01-01

    The aim of this dissertation study was to identify and describe the use of electronic health records (EHRs) for information sharing between patients and clinicians in primary-care encounters and to understand work system factors influencing information sharing. Ultimately, this will promote better design of EHR technologies and effective training…

  11. Sharing models as social objects through HydroShare

    Science.gov (United States)

    Goodall, J. L.; Morsy, M. M.; Castronova, A. M.; Dash, P. K.; Merwade, V.; Sadler, J.; Horsburgh, J. S.; Tarboton, D. G.

    2016-12-01

    Many hydrologists devote a significant amount of time to applying computational models. Sharing the results of these efforts broadly would benefit the community because scientists could, when appropriate, verify, extend, and refine existing models created by others rather than creating new models from scratch. While recent attention has been devoted to sharing hydrologic data including model outputs, approaches for sharing model instances, that is the input data required to execute a model, have received less attention. To address this need, we present functionality within HydroShare that allows scientists to share both model instances and the model programs used to execute the instances. HydroShare is an NSF-funded online system with the goal of making it simple to share data and models. The approach we designed is general and applicable to any hydrology model. It includes an extensible metadata framework capable of capturing detailed metadata for specific hydrology models, while also providing general metadata applicable to any hydrology model. Another advantage of this work is that defining a structured resource type with formal metadata fosters interoperability between cyberinfrastructure systems. This is illustrated through software providing interoperability between HydroShare and a third-party application called SWATShare that is focused on providing online visualization, execution, and management of SWAT models.

  12. Shared governance and shared leadership: meeting the challenges of implementation.

    Science.gov (United States)

    Scott, Linda; Caress, Ann-Louise

    2005-01-01

    New forms of leadership are required if staff are to be effectively engaged and involved in decision-making and promoting clinical effectiveness. One such mechanism is shared governance and shared leadership to ensure practice is both practitioner owned and organizationally supported. Empowering staff is a great challenge requiring effective planning, preparation and commitment. Establishing the process of shared governance requires effective leadership, implementation of a suitable framework, multidisciplinary working and examination of the organization's structure and culture. This paper discusses the challenges of implementation, preparation of staff, and alignment with the organizational agenda. It emphasizes that shared governance is an ongoing and fluid process, requiring continual assessment and re-evaluation in order to be flexible and responsive to an ever-changing environment. The Christie model provides a sustainable framework for moving practice forward and successful implementation has led to greater coordination of practice development and sharing of best practice.

  13. Technology Sharing in Manufacturing Business Groups

    DEFF Research Database (Denmark)

    Sköld, Martin; Karlsson, Christer

    2012-01-01

    technologies. The research aim is to develop a framework to be used as an analytical tool for understanding and organizing technology sharing in manufacturing business groups. The research approach was to study technology sharing in a natural setting combining multiple in-depth sources of evidence......, consultants, partners, and others. However, the distinction between the focal firm, on the one hand, and networks, on the other, is in this paper argued to be too extensive without intermediating nuances. Less focus is given to an in-between perspective configured by business groups or concerns here defined...... as parent corporations with subsidiary companies. It is this perspective of business groups with characteristics between individual firms and open networks that is of interest in this paper. The focus is on manufacturing business groups in which the companies will typically have individual as well as common...

  14. Heterogeneity and Risk Sharing in Village Economies*

    Science.gov (United States)

    Chiappori, Pierre-André; Samphantharak, Krislert; Schulhofer-Wohl, Sam; Townsend, Robert M.

    2013-01-01

    We show how to use panel data on household consumption to directly estimate households’ risk preferences. Specifically, we measure heterogeneity in risk aversion among households in Thai villages using a full risk-sharing model, which we then test allowing for this heterogeneity. There is substantial, statistically significant heterogeneity in estimated risk preferences. Full insurance cannot be rejected. As the risk sharing, as-if-complete-markets theory might predict, estimated risk preferences are unrelated to wealth or other characteristics. The heterogeneity matters for policy: Although the average household would benefit from eliminating village-level risk, less-risk-averse households who are paid to absorb that risk would be worse off by several percent of household consumption. PMID:24932226

  15. Heterogeneity and Risk Sharing in Village Economies.

    Science.gov (United States)

    Chiappori, Pierre-André; Samphantharak, Krislert; Schulhofer-Wohl, Sam; Townsend, Robert M

    2014-03-01

    We show how to use panel data on household consumption to directly estimate households' risk preferences. Specifically, we measure heterogeneity in risk aversion among households in Thai villages using a full risk-sharing model, which we then test allowing for this heterogeneity. There is substantial, statistically significant heterogeneity in estimated risk preferences. Full insurance cannot be rejected. As the risk sharing, as-if-complete-markets theory might predict, estimated risk preferences are unrelated to wealth or other characteristics. The heterogeneity matters for policy: Although the average household would benefit from eliminating village-level risk, less-risk-averse households who are paid to absorb that risk would be worse off by several percent of household consumption.

  16. FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis.

    Science.gov (United States)

    Xu, James Xunhai; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Pazdur, Richard

    2017-03-01

    On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO, Bristol-Myers Squibb Company) for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. The approval was based on efficacy and safety data demonstrated in an open-label, randomized study of 821 patients with advanced RCC who progressed after at least one anti-angiogenic therapy. Patients were randomized to nivolumab or everolimus and followed for disease progression. The primary end point was overall survival. Subsequent therapies, including everolimus for patients who developed progressive disease on the nivolumab arm, were allowed, but no cross-over was permitted. The median overall survival was 25.0 months on the nivolumab arm and 19.6 months on everolimus arm (hazard ratio: 0.73; 95% confidence interval: 0.60-0.89). The confirmed response rates were 21.5% versus 3.9%; median durations of response were 23.0 versus 13.7 months, and median times to response were 3.0 versus 3.7 months in the nivolumab and everolimus arms, respectively. A statistically significant improvement in progression-free survival was not observed in this trial. The safety profile of nivolumab in renal cell cancer was similar to that in other disease settings. However, the incidence of immune-mediated nephritis appeared to be higher in patients with RCC. The Oncologist 2017;22:311-317 IMPLICATIONS FOR PRACTICE: The overall benefit/risk profile demonstrated in trial CA209025 supported the approval of nivolumab as an additional treatment option for patients with advanced renal cell carcinoma after anti-angiogenic therapy. The use of nivolumab in patients who had received vascular endothelial growth factor-targeted therapy resulted in a 5.4 month improvement in median overall survival compared with the everolimus arm. This difference is statistically significant and clinically meaningful. © AlphaMed Press 2017.

  17. Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

    Directory of Open Access Journals (Sweden)

    Kathleen Jee

    Full Text Available The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF, for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR, the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4 is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients. Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient and vitreous (n = 3 patients samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

  18. Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats.

    Directory of Open Access Journals (Sweden)

    Susann Minkwitz

    Full Text Available Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group to an open osteotomy (hypertrophy group led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing.

  19. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach

    Directory of Open Access Journals (Sweden)

    Chiara Bianca Maria Platania

    2015-10-01

    Full Text Available Anti-angiogenic agents are biological drugs used for treatment of retinal neovascular degenerative diseases. In this study, we aimed at in-silico analysis of interaction of vascular endothelial growth factor A (VEGFA, the main mediator of angiogenesis, with binding domains of anti-angiogenic agents used for treatment of retinal diseases, such as ranibizumab, bevacizumab and aflibercept. The analysis of anti-VEGF/VEGFA complexes was carried out by means of protein-protein docking and molecular dynamics (MD coupled to molecular mechanics-Poisson Boltzmann Surface Area (MM-PBSA calculation. Molecular dynamics simulation was further analyzed by protein contact networks. Rough energetic evaluation with protein-protein docking scores revealed that aflibercept/VEGFA complex was characterized by electrostatic stabilization, whereas ranibizumab and bevacizumab complexes were stabilized by Van der Waals (VdW energy term; these results were confirmed by MM-PBSA. Comparison of MM-PBSA predicted energy terms with experimental binding parameters reported in literature indicated that the high association rate (Kon of aflibercept to VEGFA was consistent with high stabilizing electrostatic energy. On the other hand, the relatively low experimental dissociation rate (Koff of ranibizumab may be attributed to lower conformational fluctuations of the ranibizumab/VEGFA complex, higher number of contacts and hydrogen bonds in comparison to bevacizumab and aflibercept. Thus, the anti-angiogenic agents have been found to be considerably different both in terms of molecular interactions and stabilizing energy. Characterization of such features can improve the design of novel biological drugs potentially useful in clinical practice.

  20. Cannabinoids inhibit angiogenic capacities of endothelial cells via release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells.

    Science.gov (United States)

    Ramer, Robert; Fischer, Sascha; Haustein, Maria; Manda, Katrin; Hinz, Burkhard

    2014-09-15

    Cannabinoids inhibit tumor neovascularization as part of their tumorregressive action. However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied. Cellular behavior of human umbilical vein endothelial cells (HUVEC) associated with angiogenesis was evaluated by Boyden chamber, two-dimensional tube formation and fibrin bead assay, with the latter assessing three-dimensional sprout formation. Viability was quantified by the WST-1 test. Conditioned media (CM) from A549 lung cancer cells treated with cannabidiol, Δ(9)-tetrahydrocannabinol, R(+)-methanandamide or the CB2 agonist JWH-133 elicited decreased migration as well as tube and sprout formation of HUVEC as compared to CM of vehicle-treated cancer cells. Inhibition of sprout formation was further confirmed for cannabinoid-treated A549 cells co-cultured with HUVEC. Using antagonists to cannabinoid-activated receptors the antimigratory action was shown to be mediated via cannabinoid receptors or transient receptor potential vanilloid 1. SiRNA approaches revealed a cannabinoid-induced expression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) as well as its upstream trigger, the intercellular adhesion molecule-1, to be causally linked to the observed decrease of HUVEC migration. Comparable anti-angiogenic effects were not detected following direct exposure of HUVEC to cannabinoids, but occurred after addition of recombinant TIMP-1 to HUVEC. Finally, antimigratory effects were confirmed for CM of two other cannabinoid-treated lung cancer cell lines (H460 and H358). Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 in intercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The angiogenic makeup of human hepatocellular carcinoma does not favor vascular endothelial growth factor/angiopoietin-driven sprouting neovascularization.

    Science.gov (United States)

    Zeng, Wenjiao; Gouw, Annette S H; van den Heuvel, Marius C; Zwiers, Peter J; Zondervan, Pieter E; Poppema, Sibrand; Zhang, Nong; Platteel, Inge; de Jong, Koert P; Molema, Grietje

    2008-11-01

    Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased. In hepatocellular carcinoma, tumor vascularization is not per se VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted.

  2. Attention and Visuospatial Working Memory Share the Same Processing Resources

    Directory of Open Access Journals (Sweden)

    Jing eFeng

    2012-04-01

    Full Text Available Attention and visuospatial working memory (VWM share very similar characteristics; both have the same upper bound of about four items in capacity and they recruit overlapping brain regions. We examined whether both attention and visuospatial working memory share the same processing resources using a novel dual-task-costs approach based on a load-varying dual-task technique. With sufficiently large loads on attention and VWM, considerable interference between the two processes was observed. A further load increase on either process produced reciprocal increases in interference on both processes, indicating that attention and VWM share common resources. More critically, comparison among four experiments on the reciprocal interference effects, as measured by the dual-task costs, demonstrates no significant contribution from additional processing other than the shared processes. These results support the notion that attention and VWM share the same processing resources.

  3. Questioning in Distributed Product Development Teams: Supporting Shared Understanding

    DEFF Research Database (Denmark)

    Cash, Philip; Ahmed-Kristensen, Saeema

    2015-01-01

    Distributed teams are an increasingly common feature of New Product Development (NPD). Key to the success of these teams is the development of both short and longerterm shared understanding. Lack of shared understanding has been recognized as a significant challenge, particularly in the context...... globally distributed NPD activities. Poor shared understanding can ultimately result in delays and rework. One major antecedent of shared understanding development is question asking. This work uses a quasiexperimental study to test the impact of questioning support on different types of distributed teams......, both homogeneous and heterogeneous. This extends theoretical insight into the development of shared understanding and contributes one of few empirical studies directly comparing the response characteristics of different team types. From a managerial perspective this work has implications for how...

  4. Distributed Programming with Shared Data

    NARCIS (Netherlands)

    Bal, H.E.; Tanenbaum, A.S.

    1991-01-01

    Until recently, at least one thing was clear about parallel programming: shared-memory machines were programmed in a language based on shared variables and distributed machines were programmed using message passing. Recent research on distributed systems and their languages, however, has led to new

  5. Barriers to Cyber Information Sharing

    Science.gov (United States)

    2014-12-01

    that compete for use within organizations.89 According to Kathleen Moriarty of EMC Corporation, threat information-sharing efforts must affect the...Intelligence Sharing (Hopkinton, MA: EMC , 2013). 90 Ibid. 22 release of too much information...has expressed concern that extending protections would only serve as a legal shield against liability.131 In addition, the challenges of information

  6. Benefit sharing in health research

    African Journals Online (AJOL)

    2015-08-02

    Aug 2, 2015 ... [7,9] The guideline's MTA template provides for the 'fair and equitable sharing of benefits' derived ... exposure which could assist in safeguarding the women's rights to any benefits that may accrue from ..... biological resources in developing countries: Benefit sharing without undue inducement (in press).

  7. Semaphorin 4D Enhances Angiogenic Potential and Suppresses Osteo-/Odontogenic Differentiation of Human Dental Pulp Stem Cells.

    Science.gov (United States)

    Zou, Ting; Dissanayaka, Waruna Lakmal; Jiang, Shan; Wang, Shuai; Heng, Boon Chin; Huang, Xiaojing; Zhang, Chengfei

    2017-02-01

    To investigate the roles of semaphorin 4D (Sema4D)/plexin-B1 signaling on the angiogenic potential and osteo-/odontogenic differentiation of human dental pulp stem cells (DPSCs) and to uncover the corresponding molecular mechanisms. DPSCs were treated with Sema4D (10 μg/mL) for different time durations. Osteo-/odontogenic differentiation was assessed by quantifying alkaline phosphatase activity, mineralized nodule formation, and osteo-/odontogenic gene (ALP, Col1A1, BSP, RUNX2, and DSPP) and protein (Col1A1 and DSPP) expression. Involvement of the Sema4D/plexin-B1 signaling pathway was analyzed by Western blot analysis. Additionally, angiogenic gene and protein expression was assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. In vitro endothelial tube formation assay on Matrigel (BD Biosciences, San Jose, CA) was performed to evaluate the angiogenic inductive potential of the Sema4D-treated DPSCs conditioned medium. Results were analyzed using 1-way analysis of variance and the Student t test. Sema4D significantly inhibited ALP activity and mineralized nodule formation of DPSCs. Furthermore, Sema4D-treated DPSCs displayed marked down-regulation in the expression of osteo-/odontogenic genes (ALP, Col1A1, BSP, RUNX2, and DSPP) as well as proteins (Col1A1 and DSPP). Elevated levels of plexin-B1 and downstream RhoA protein expression together with phosphorylated plexin-B1 confirmed the involvement of Sema4D/plexin-B1 signaling. Protein expression of ErbB2 was up-regulated, and Met was slightly down-regulated. Furthermore, Sema4D-treated DPSCs exhibited enhanced expression of vascular endothelial growth factor at both the messenger RNA and protein level. Accordingly, the conditioned medium of Sema4D-treated DPSCs promoted the formation of vessel-like structures as shown by the Matrigel assay. Sema4D markedly enhances the angiogenic potential but suppresses osteo-/odontogenic differentiation of DPSCs. Sema4D

  8. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment

    Science.gov (United States)

    Pasquier, Eddy; Ciccolini, Joseph; Carre, Manon; Giacometti, Sarah; Fanciullino, Raphaelle; Pouchy, Charlotte; Montero, Marie-Pierre; Serdjebi, Cindy; Kavallaris, Maria; André, Nicolas

    2011-01-01

    Recent clinical evidence revealed that the use of beta-blockers such as propranolol, prior to diagnosis or concurrently with chemotherapy, could increase relapse-free and overall survival in breast cancer patients. We therefore hypothesized that propranolol may be able to increase the efficacy of chemotherapy either through direct effects on cancer cells or via anti-angiogenic mechanisms. In vitro proliferation assay showed that propranolol (from 50-100 μM) induces dose-dependent anti-proliferative effects in a panel of 9 human cancer and “normal” cell lines. Matrigel assays revealed that propranolol displays potent anti-angiogenic properties at non-toxic concentrations (propranolol at the lowest effective concentration resulted in synergistic, additive or antagonistic effects on cell proliferation in vitro depending on the cell type and the dose of chemotherapy used. Interestingly, breast cancer and vascular endothelial cells were among the most responsive to these combinations. Furthermore, Matrigel assays indicated that low concentrations of propranolol (10 – 50 μM) potentiated the anti-angiogenic effects of 5-FU and paclitaxel. Using an orthotopic xenograft model of triple-negative breast cancer, based on injection of luciferase-expressing MDA-MB-231 cells in the mammary fat pad of nude mice, we showed that propranolol, when used alone, induced only transient anti-tumor effects, if at all, and did not increase median survival. However, the combination of propranolol with chemotherapy resulted in more profound and sustained anti-tumor effects and significantly increased the survival benefits induced by chemotherapy alone (+19% and +79% in median survival for the combination as compared with 5-FU alone and paclitaxel alone, respectively; ppropranolol can potentiate the anti-angiogenic effects and anti-tumor efficacy of chemotherapy. The current study, together with retrospective clinical data, strongly suggests that the use of propranolol concurrently

  9. Shared Contract-Obedient Endpoints

    Directory of Open Access Journals (Sweden)

    Étienne Lozes

    2012-12-01

    Full Text Available Most of the existing verification techniques for message-passing programs suppose either that channel endpoints are used in a linear fashion, where at most one thread may send or receive from an endpoint at any given time, or that endpoints may be used arbitrarily by any number of threads. The former approach usually forbids the sharing of channels while the latter limits what is provable about programs. In this paper we propose a midpoint between these techniques by extending a proof system based on separation logic to allow sharing of endpoints. We identify two independent mechanisms for supporting sharing: an extension of fractional shares to endpoints, and a new technique based on what we call reflexive ownership transfer. We demonstrate on a number of examples that a linear treatment of sharing is possible.

  10. Water demand characteristics of shared water and sanitation ...

    African Journals Online (AJOL)

    The design of the ABRs and septic tanks was based on previous in-house guidelines; however, there are no national water demand guidelines for CABs. CABs do not fit any of the scenarios presented in the SANS 10400 guidelines, as CABs include communal showers, basins, laundry facilities, toilets and urinals.

  11. Water demand characteristics of shared water and sanitation facilities

    African Journals Online (AJOL)

    The provision of communal water and sanitation facilities has been mandated by the South African Government as an interim measure for informal settlement upgrading. These services form the first step in the upgrading process and are essential in meeting the basic needs of the community. The eThekwini municipality is ...

  12. SHARING SCIENCE: CHARACTERISTICS OF EFFECTIVE SCIENTIST-TEACHER INTERACTIONS

    National Research Council Canada - National Science Library

    Nancy J. Pelaez; Barbara L. Gonzalez

    2002-01-01

    .... Conducted under the auspices of the American Association for the Advancement of Science, a symposium examined several programs where professional scientists interact with classroom teachers to improve science education...

  13. Water demand characteristics of shared water and sanitation facilities

    African Journals Online (AJOL)

    demand can be used for future hydraulic modelling of these, and other, communal ablution facilities. Keywords: informal settlements; communal sanitation; hydraulic modelling. INTRODUCTION. Sanitation is a basic need and the lack of improved facilities has significant effects on environmental and public health,.

  14. Effects of TiO₂ and Co₃O₄ nanoparticles on circulating angiogenic cells.

    Directory of Open Access Journals (Sweden)

    Valentina Spigoni

    Full Text Available Sparse evidence suggests a possible link between exposure to airborne nanoparticles (NPs and cardiovascular (CV risk, perhaps through mechanisms involving oxidative stress and inflammation. We assessed the effects of TiO2 and Co3O4 NPs in human circulating angiogenic cells (CACs, which take part in vascular endothelium repair/replacement.CACs were isolated from healthy donors' buffy coats after culturing lymphomonocytes on fibronectin-coated dishes in endothelial medium for 7 days. CACs were pre-incubated with increasing concentration of TiO2 and Co3O4 (from 1 to 100 μg/ml to test the effects of NP – characterized by Transmission Electron Microscopy – on CAC viability, apoptosis (caspase 3/7 activation, function (fibronectin adhesion assay, oxidative stress and inflammatory cytokine gene expression.Neither oxidative stress nor cell death were associated with exposure to TiO2 NP (except at the highest concentration tested, which, however, induced a higher pro-inflammatory effect compared to Co3O4 NPs (p<0.01. Exposure to Co3O4 NPs significantly reduced cell viability (p<0.01 and increased caspase activity (p<0.01, lipid peroxidation end-products (p<0.05 and pro-inflammatory cytokine gene expression (p<0.05 or lower. Notably, CAC functional activity was impaired after exposure to both TiO2 (p<0.05 or lower and Co3O4 (p<0.01 NPs.In vitro exposure to TiO2 and Co3O4 NPs exerts detrimental effects on CAC viability and function, possibly mediated by accelerated apoptosis, increased oxidant stress (Co3O4 NPs only and enhancement of inflammatory pathways (both TiO2 and Co3O4 NPs. Such adverse effects may be relevant for a potential role of exposure to TiO2 and Co3O4 NPs in enhancing CV risk in humans.

  15. VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.

    Science.gov (United States)

    Saponaro, Concetta; Malfettone, Andrea; Ranieri, Girolamo; Danza, Katia; Simone, Giovanni; Paradiso, Angelo; Mangia, Anita

    2013-01-01

    Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.

  16. Effects of TiO2 and Co3O4 Nanoparticles on Circulating Angiogenic Cells

    Science.gov (United States)

    Spigoni, Valentina; Cito, Monia; Alinovi, Rossella; Pinelli, Silvana; Passeri, Giovanni; Zavaroni, Ivana; Goldoni, Matteo; Campanini, Marco; Aliatis, Irene; Mutti, Antonio

    2015-01-01

    Background and Aim Sparse evidence suggests a possible link between exposure to airborne nanoparticles (NPs) and cardiovascular (CV) risk, perhaps through mechanisms involving oxidative stress and inflammation. We assessed the effects of TiO2 and Co3O4 NPs in human circulating angiogenic cells (CACs), which take part in vascular endothelium repair/replacement. Methods CACs were isolated from healthy donors’ buffy coats after culturing lymphomonocytes on fibronectin-coated dishes in endothelial medium for 7 days. CACs were pre-incubated with increasing concentration of TiO2 and Co3O4 (from 1 to 100 μg/ml) to test the effects of NP – characterized by Transmission Electron Microscopy – on CAC viability, apoptosis (caspase 3/7 activation), function (fibronectin adhesion assay), oxidative stress and inflammatory cytokine gene expression. Results Neither oxidative stress nor cell death were associated with exposure to TiO2 NP (except at the highest concentration tested), which, however, induced a higher pro-inflammatory effect compared to Co3O4 NPs (p<0.01). Exposure to Co3O4 NPs significantly reduced cell viability (p<0.01) and increased caspase activity (p<0.01), lipid peroxidation end-products (p<0.05) and pro-inflammatory cytokine gene expression (p<0.05 or lower). Notably, CAC functional activity was impaired after exposure to both TiO2 (p<0.05 or lower) and Co3O4 (p<0.01) NPs. Conclusions In vitro exposure to TiO2 and Co3O4 NPs exerts detrimental effects on CAC viability and function, possibly mediated by accelerated apoptosis, increased oxidant stress (Co3O4 NPs only) and enhancement of inflammatory pathways (both TiO2 and Co3O4 NPs). Such adverse effects may be relevant for a potential role of exposure to TiO2 and Co3O4 NPs in enhancing CV risk in humans. PMID:25803285

  17. Angiogenic and Osteogenic Coupling Effects of Deferoxamine-Loaded Poly(lactide-co-glycolide-Poly(ethylene glycol-Poly(lactide-co-glycolide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Manle Qiu

    2016-10-01

    Full Text Available Angiogenesis and osteogenesis coupling processes are essential for bone regeneration, and human bone marrow stromal cells (hBMSCs along with endothelial cells (ECs are crucial participants. Deferoxamine (DFO, a hypoxia-mimetic agent, could activate the hypoxia-inducible factor (HIF-1α signaling pathway and trigger angiogenic and osteogenic effects in these cells. However, the lifetime of DFO is very short, thus a suitable delivery system is urgently needed. In this study, we encapsulated DFO in Poly(lactide-co-glycolide-Poly(ethylene glycol-Poly(lactide-co-glycolide (PLGA-PEG-PLGA nanoparticles (DFO-loaded NPs to realize its long-term angiogenic and osteogenic bioactivities. Surface morphology, size, size distribution of DFO-loaded NPs as well as DFO loading content (LC, encapsulation efficiency (EE and release profile were systematically evaluated. When hBMSCs were exposed to the vehicle with DFO concentration of 100 μM, cells showed good viability, increased HIF-1α expression and enhanced vascular endothelial growth factor (VEGF secretion. The transcriptional levels of the angiogenic and osteogenic genes were also upregulated. Moreover, promoted alkaline phosphatase (ALP activity further confirmed better osteogenic differentiation. Similarly, angiogenic activity of human umbilical vein endothelial cells (HUVECs were enhanced after the addition of DFO-loaded NPs, evidenced by increased angiogenic genes expressions and tube formation. Taken together, DFO-loaded NPs could provide a sustained supply of DFO, with its angiogenic and osteogenic coupling effects preserved, which extends the potential of this system for bone defect repair.

  18. One Share-One Vote

    DEFF Research Database (Denmark)

    Poulsen, Thomas; Eklund, Johan E.

    Shares with more voting rights than cash flow rights provide their owners with a disproportional influence that is often found to destroy the value of outside equity. This is taken as evidence of discretionary use of power. However, concentration of power does not necessarily result from control...... enhancing mechanisms; it could also be that some shareholders retain a large block in a one share-one vote structure. In this paper, we develop a methodology to disentangle disproportionality, which allows us to test the effect of deviations from one share-one vote more precisely. Our empirical findings add...

  19. i-Review: Sharing Code

    Directory of Open Access Journals (Sweden)

    Jonas Kubilius

    2014-02-01

    Full Text Available Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF. GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  20. Pro-apoptotic and anti-angiogenic properties of the α /β-thujone fraction from Thuja occidentalis on glioblastoma cells.

    Science.gov (United States)

    Torres, Angelo; Vargas, Yosselyn; Uribe, Daniel; Carrasco, Cristian; Torres, Cristian; Rocha, René; Oyarzún, Carlos; San Martín, Rody; Quezada, Claudia

    2016-05-01

    The most aggressive type of brain tumor is glioblastoma multiforme, which to date remains incurable. Thuja occidentalis is used in homeopathy for the treatment of cancer, however, its mechanism of action remains unknown. We set out to study the effects of thujone fractions of Thuja on glioblastoma using in vitro and in vivo models. We found that the α/ β-thujone fraction decrease the cell viability and exhibit a potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro. In vivo assays showed that α /β-thujone promotes the regression of neoplasia and inhibits the angiogenic markers VEGF, Ang-4 and CD31 into the tumor.

  1. Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

    Directory of Open Access Journals (Sweden)

    Mingliang Sun

    2017-01-01

    Full Text Available Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF, and monocyte chemotactic protein-1 (MCP-1 in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.

  2. Methyl tert butyl ether (MTBE) is anti- angiogenic in both in vitro and in vivo mammalian model systems

    Science.gov (United States)

    Kozlosky, John; Bonventre, Josephine; Cooper, Keith

    2015-01-01

    Methyl-tertiary butyl ether (MTBE), a well known gasoline oxygenate, and FDA approved gallstone treatment, has been previously shown to specifically target teleost embryonic angiogenesis. The studies reported here were to determine if similar vascular disrupting effects occurred in higher vertebrate models. Rat brain endothelial cells were isolated and allowed to form microcapillary-like tubes on Matrigel. MTBE (0.34–34.0 mM) exposure resulted in a dose-dependent reduction of tube formation, with the LOAEL at 0.34 mM, while MTBE’s primary metabolite, tertiary butyl alcohol had no effect on tube formation. HUVECs, a primary cell line representing macrovascular cells, were able to form tubes on Matrigel in the presence of MTBE (1.25 – 80 mM), but the tubes were narrower than those formed in the absence of MTBE. In a mouse Matrigel plug implantation assay, 34.0 mM MTBE completely inhibited vessel invasion into plugs containing Endothelial Cell Growth Supplement (ECGS) compared to control plugs with ECGS alone. When timed-pregnant Fisher 344 rats were gavaged with MTBE (500–1500 mg/kg) from day 6 of organogenesis through 10 days post parturition, no organ toxicity or histological changes in pup vasculature were observed. Therefore, MTBE is anti-angiogenic at mM concentrations and therefore a potential use as an anti-angiogenic treatment for solid tumors with minimal toxicity. PMID:22407988

  3. Loading of a novel angiogenic agent, ginsenoside Rg1 in an acellular biological tissue for tissue regeneration.

    Science.gov (United States)

    Liang, Huang-Chien; Chen, Chiung-Tong; Chang, Yen; Huang, Ya-Chun; Chen, Sung-Ching; Sung, Hsing-Wen

    2005-01-01

    In this study, the effects of ginsenoside Rg1, a natural compound isolated from Panax ginseng, on human umbilical vein endothelial cell (HUVEC) behavior in vitro, and on angiogenesis and tissue regeneration in genipin-fixed acellular tissue (extracellular matrix, ECM) in vivo, were investigated. Basic fibroblast growth factor (bFGF) was used as a control. The in vitro results indicated that in the presence of bFGF or Rg1, HUVEC proliferation was significantly increased. Both bFGF and Rg1 promoted HUVEC migration in a Transwell plate assay. In addition, bFGF or Rg1 significantly increased the formation of capillary-like network by HUVECs on Matrigel. Thus, both bFGF and Rg1 enhanced multiple components of angiogenic activity in vitro. The in vivo results obtained 1 week postoperatively showed that the extent of angiogenesis in ECMs was significantly enhanced by bFGF or Rg1. At 1 month postoperatively, vascularized neoconnective tissues were found to fill the pores within ECMs loaded with bFGF or Rg1. There was a significant increase in neocapillary density from 1 week to 1 month for ECMs loaded with Rg1, whereas that observed in ECMs loaded with bFGF stayed approximately the same because of the limitations of protein stability. These results suggested that Rg1 may be a new class of angiogenic agent and may be loaded in ECMs to accelerate tissue regeneration.

  4. Amniotic mesenchymal stem cells enhance wound healing in diabetic NOD/SCID mice through high angiogenic and engraftment capabilities.

    Science.gov (United States)

    Kim, Sung-Whan; Zhang, Hong-Zhe; Guo, Longzhe; Kim, Jong-Min; Kim, Moo Hyun

    2012-01-01

    Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

  5. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin

    Science.gov (United States)

    Cheng, Wenming; Zohra Dahmani, Fatima; Zhang, Juan; Xiong, Hui; Wu, Yuanyuan; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-02-01

    Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH. The resulting LMWH-UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200-250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH-UA. Meanwhile, the in vivo antitumor effect of LMWH-UA was also evaluated using a B16F10 mouse melanoma model. LMWH-UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH-UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH-UA as a new therapeutic remedy for cancer therapy.

  6. Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Lee, Jun Hee; Han, Yong-Seok; Lee, Sang Hun

    2016-05-01

    Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

  7. Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages.

    Science.gov (United States)

    Abdel-Sayed, Philippe; Kaeppeli, Ariane; Kaeppli, Ariane; Siriwardena, Thissa; Darbre, Tamis; Perron, Karl; Jafari, Paris; Reymond, Jean-Louis; Pioletti, Dominique P; Applegate, Lee Ann

    2016-02-25

    Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis.

  8. Allergen-Induced Eotaxin-rich Pro-angiogenic Bone Marrow Progenitors: A Blood Borne Cellular Envoy for Lung Eosinophilia

    Science.gov (United States)

    Asosingh, Kewal; Hanson, Jodi D.; Cheng, Georgiana; Aronica, Mark A.; Erzurum, Serpil C.

    2010-01-01

    Background Eosinophilic inflammation is closely related to angiogenesis in asthmatic airway remodeling. In ovalbumin-sensitized mice, bone marrow-derived pro-angiogenic endothelial progenitor cells (EPCs) are rapidly recruited into the lungs after ovalbumin aerosol challenge, and promptly followed by mobilization and recruitment of eosinophils. Objective We hypothesized that bone marrow-derived EPCs initiate the recruitment of eosinophils through expression of eosinophil chemoattractant eotaxin-1. Methods EPCs were isolated from ovalbumin murine model of allergic airway inflammation and from asthma patients. Endothelial and smooth muscle cells were isolated from mice. Eotaxin-1 expression was analyzed by immunofluorescence, real-time PCR or by ELISA. In vivo recruitment of eosinophils by EPCs was analyzed in mice. Results Circulating EPCs of asthmatic individuals had higher levels of eotaxin-1 as compared to controls. In the murine model, ovalbumin allergen exposure augmented eotaxin-1 mRNA and protein levels in EPCs. The EPCs from ovalbumin-sensitized and challenged mice released high levels of eotaxin-1 upon contact with lung endothelial cells from sensitized and challenged mice, but not from control animals, and not upon contact with cardiac or hepatic endothelial cells from sensitized and challenged mice. Intranasal administration of the eotaxin-rich media overlying cultures of EPCs caused recruitment into lungs, confirming functional chemoattractant activity. Conclusions Bone marrow-derived EPCs are early responders to environmental allergen exposures, and initiate a parallel switch to a pro-angiogenic and pro-eosinophilic environment in the asthmatic lungs. PMID:20227754

  9. Cationic peptides from peptic hydrolysates of rice endosperm protein exhibit antimicrobial, LPS-neutralizing, and angiogenic activities.

    Science.gov (United States)

    Taniguchi, Masayuki; Kawabe, Junya; Toyoda, Ryu; Namae, Toshiki; Ochiai, Akihito; Saitoh, Eiichi; Tanaka, Takaaki

    2017-11-01

    In this study, we hydrolyzed rice endosperm protein (REP) with pepsin and generated 20 fractions containing multifunctional cationic peptides with varying isoelectric point (pI) values using ampholyte-free isoelectric focusing (autofocusing). Subsequently, we determined antimicrobial activities of each fraction against the pathogens Prophyromonas gingivalis, Propionibacterium acnes, Streptocossus mutans, and Candida albicans. Fractions 18, 19, and 20 had pI values greater than 12 and exhibited antimicrobial activity against P. gingivalis, P. acnes, and C. albicans, but not against S. mutans. In further experiments, we purified and identified cationic peptides from fractions 18, 19, and 20 using reversed-phase high-performance liquid chromatography and matrix-assisted laser/desorption ionization-time-of-flight mass spectroscopy. We also chemically synthesized five identified peptides (RSVSKSR, RRVIEPR, ERFQPMFRRPG, RVRQNIDNPNRADTYNPRAG, and VVRRVIEPRGLL) with pI values greater than 10.5 and evaluated antimicrobial, lipopolysaccharide (LPS)-neutralizing, and angiogenic activities. Among these synthetic peptides, only VVRRVIEPRGLL exhibited antimicrobial activity against P. gingivalis, with an IC 50 value of 87μM. However, all five cationic peptides exhibited LPS-neutralizing and angiogenic activities with little or no hemolytic activity against mammalian red blood cells at functional concentrations. These present data show dual or multiple functions of the five identified cationic peptides with little or no hemolytic activity. Therefore, fractions containing cationic peptides from REP hydrolysates have the potential to be used as dietary supplements and functional ingredients in food products. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Seasonal Changes in Testes Vascularisation in the Domestic Cat (Felis domesticus: Evaluation of Microvasculature, Angiogenic Activity, and Endothelial Cell Expression

    Directory of Open Access Journals (Sweden)

    Graça Alexandre-Pires

    2012-01-01

    Full Text Available Some male seasonal breeders undergo testicular growth and regression throughout the year. The objective of this study was to understand the effect of seasonality on: (i microvasculature of cat testes; (ii angiogenic activity in testicular tissue in vitro; and (iii testicular endothelial cells expression throughout the year. Testicular vascular areas increased in March and April, June and July, being the highest in November and December. Testes tissue differently stimulated in vitro angiogenic activity, according to seasonality, being more evident in February, and November and December. Even though CD143 expression was higher in December, smaller peaks were present in April and July. As changes in angiogenesis may play a role on testes vascular growth and regression during the breeding and non-breeding seasons, data suggest that testicular vascularisation in cats is increased in three photoperiod windows of time, November/December, March/April and June/July. This increase in testicular vascularisation might be related to higher seasonal sexual activity in cats, which is in agreement with the fact that most queens give birth at the beginning of the year, between May and July, and in September.

  11. Effect of silica nanoparticles with variable size and surface functionalization on human endothelial cell viability and angiogenic activity

    Science.gov (United States)

    Guarnieri, Daniela; Malvindi, Maria Ada; Belli, Valentina; Pompa, Pier Paolo; Netti, Paolo

    2014-02-01

    Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior effects of silica nanoparticles on primary endothelial cells. Here we investigated uptake, cytotoxicity and angiogenic properties of silica nanoparticle with positive and negative surface charge and sizes ranging from 25 to 115 nm in primary human umbilical vein endothelial cells. Dynamic light scattering measurements and nanoparticle tracking analysis were used to estimate the dispersion status of nanoparticles in cell culture media, which was a key aspect to understand the results of the in vitro cellular uptake experiments. Nanoparticles were taken up by primary endothelial cells in a size-dependent manner according to their degree of agglomeration occurring after transfer in cell culture media. Functionalization of the particle surface with positively charged groups enhanced the in vitro cellular uptake, compared to negatively charged nanoparticles. However, this effect was contrasted by the tendency of particles to form agglomerates, leading to lower internalization efficiency. Silica nanoparticle uptake did not affect cell viability and cell membrane integrity. More interestingly, positively and negatively charged 25 nm nanoparticles did not influence capillary-like tube formation and angiogenic sprouting, compared to controls. Considering the increasing interest in nanomaterials for several biomedical applications, a careful study of nanoparticle-endothelial cells interactions is of high relevance to assess possible risks associated to silica nanoparticle exposure and their possible applications in nanomedicine as safe and effective nanocarriers for vascular transport of therapeutic agents.

  12. Diminished oligomerization in the synthesis of new anti-angiogenic cyclic peptide using solution instead of solid-phase cyclization.

    Science.gov (United States)

    Rubio, Sandra; Clarhaut, Jonathan; Péraudeau, Elodie; Vincenzi, Marian; Soum, Claire; Rossi, Filomena; Guillon, Jean; Papot, Sébastien; Ronga, Luisa

    2016-05-01

    The design and synthesis of novel peptides that inhibit angiogenesis is an important area for anti-angiogenic drug development. Cyclic and small peptides present several advantages for therapeutic application, including stability, solubility, increased bio-availability and lack of immune response in the host cell. We describe here the synthesis and biological evaluations of a new cyclic peptide analog of CBO-P11: cyclo(RIKPHE), designated herein as CBO-P23M, a hexamer peptide encompassing residues 82 to 86 of VEGF which are involved in the interaction with VEGF receptor-2. CBO-P23M was prepared using in solution cyclization, therefore reducing the peptide cyclodimerization occurred during solid-phase cyclization. The cyclic dimer of CBO-P23M, which was obtained as the main side product during synthesis of the corresponding monomer, was also isolated and investigated. Both peptides markedly reduce VEGF-A-induced phosphorylation of VEGFR-2 and Erk1/2. Moreover, they exhibit anti-angiogenic activity in an in vitro morphogenesis study. Therefore CBO-P23M and CBO-P23M dimer appear as attractive candidates for the development of novel angiogenesis inhibitors for the treatment of cancer and other angiogenesis-related diseases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 368-375, 2016. © 2016 Wiley Periodicals, Inc.

  13. Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles.

    Science.gov (United States)

    Treps, Lucas; Perret, Raul; Edmond, Sébastien; Ricard, Damien; Gavard, Julie

    2017-01-01

    Glioblastoma multiforme (GBM) are mortifying brain tumours that contain a subpopulation of tumour cells with stem-like properties, termed glioblastoma stem-like cells (GSCs). GSCs largely contribute to tumour initiation, propagation and resistance to current anti-cancer therapies. GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells, thereby involved in bidirectional molecular and cellular interactions. Moreover, extracellular vesicles are suspected to carry essential information that can adapt the microenvironment to the tumour's needs, including tumour-induced angiogenesis. In GBM, extracellular vesicles produced by differentiated tumour cells and GSCs were demonstrated to disseminate locally and at distance. Here, we report that the pro-angiogenic pro-permeability factor VEGF-A is carried in extracellular vesicles secreted from ex vivo cultured patient-derived GSCs. Of note, extracellular vesicle-derived VEGF-A contributes to the in vitro elevation of permeability and angiogenic potential in human brain endothelial cells. Indeed, VEGF-A silencing in GSCs compromised in vitro extracellular vesicle-mediated increase in permeability and angiogenesis. From a clinical standpoint, extracellular vesicles isolated from circulating blood of GBM patients present higher levels of VEGF-A, as compared to healthy donors. Overall, our results suggest that extracellular vesicle-harboured VEGF-A targets brain endothelial cells and might impact their ability to form new vessels. Thus, tumour-released EV cargo might emerge as an instrumental part of the tumour-induced angiogenesis and vascular permeability modus operandi in GBM.

  14. Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses.

    Science.gov (United States)

    Azad, Neelam; Iyer, Anand Krishnan V; Wang, Liying; Liu, Yuxin; Lu, Yongju; Rojanasakul, Yon

    2013-03-01

    Single-walled carbon nanotubes (SWCNTs) are fibrous nanoparticles that are being used widely for various applications including drug delivery. SWCNTs are currently under special attention for possible cytotoxicity. Recent reports suggest that exposure to nanoparticles leads to pulmonary fibrosis. We report that SWCNT-mediated interplay of fibrogenic and angiogenic regulators leads to increased angiogenesis, which is a novel finding that furthers the understanding of SWCNT-induced cytotoxicity. SWCNTs induce fibrogenesis through reactive oxygen species-regulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Activation of p38 MAPK by SWCNTs led to the induction of transforming growth factor (TGF)-β1 as well as vascular endothelial growth factor (VEGF). Both TGF-β1 and VEGF contributed significantly to the fibroproliferative and collagen-inducing effects of SWCNTs. Interestingly, a positive feedback loop was observed between TGF-β1 and VEGF. This interplay of fibrogenic and angiogenic mediators led to increased angiogenesis in response to SWCNTs. Overall this study reveals key signalling molecules involved in SWCNT-induced fibrogenesis and angiogenesis.

  15. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images

    Science.gov (United States)

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R.; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-01-01

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots. PMID:26061817

  16. Anti-carcinogenic and anti-angiogenic properties of the extracts of Acorus calamus on gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Samaneh Rahamoz Haghighi

    2017-02-01

    Full Text Available Objective: Acorus calamus (A. calamus has been used as a medicinal plant in Asia for its effects on digestive system for the last 2000 years. To investigate the anti-cancer activity of rhizome of A. calamus, the ethanolic and methanolic extracts and essential oil of the rhizome were prepared and their effects were assessed on human gastric cancer cell line (AGS. Materials and Methods: The viability of cells which were treated with the extracts and the essential oil was assessed by MTT assay. To evaluate the anti-angiogenic property of the extracts, in vitro tube formation assay was done. Cell cycle distribution and the expression of Oct4 and Nucleostemin, after treatments, were checked by flowcytometry and quantitative RT-PCR, respectively. Furthermore, analysis of essential oil from A.calamus was done by GC-MS. Results: Our results showed that the growth of AGS cells was inhibited by the extracts and essential oil and the extracts inhibited the angiogenesis in HUVEC cells. Our data revealed that the extracts and essential oil of A. calamus caused G1 arrest in AGS cells and downregulation of Oct4 and NS after treatment. By GC-MS analysis, we found new compoundssuch as epiprezizaene, valencene and isocyclocitral in essential oil of A. Conclusions: All together, our results showed that the extracts of A. calamus have anti-proliferative and anti-angiogenic effects on cancer cells.

  17. COAST Map Sharing Plugin Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the development of a capability which will allow ecosystem managers to share a map view in terms of location, magnification level, and data layers (to...

  18. Knowledge Sharing and National Culture

    DEFF Research Database (Denmark)

    Michailova, Snejina; Hutchings, Kate

    2004-01-01

    the complexity of differencesbetween transition economies. The paper is written as a set of theoretical arguments andpropositions that is designed to elucidate more nuanced ways of thinking about knowledgesharing in China and Russia. We argue that in the case of China and Russia, verticalindividualism...... to the knowledge-sharing literature by specificallydiscussing the interplay between knowledge-sharing and national cultural factors in the context oftransition countries. The paper engages in a comparative examination of two major transitionsocieties, China and Russia, and contributes to understanding...... and particularist social relations facilitate knowledge sharing. We also maintainthat there are important differences between China and Russia in terms of motivation forknowledge sharing and propose that the differences between the two countries in terms of originsof collectivism and degree of collectivism impact...

  19. Positive train control shared network.

    Science.gov (United States)

    2015-05-01

    The Interoperable Train Control (ITC) Positive : Train Control (PTC) Shared Network (IPSN) : project investigated anticipated industry benefits : and the level of support for the development of : a hosted technological platform for PTC : messaging ac...

  20. Developing SharePoint applications

    OpenAIRE

    Rupnik, Gašper

    2011-01-01

    The thesis includes a research on SharePoint 2010 programming capabilities and a display of products created by this knowledge. The introduction part includes background information on how the topic was chosen and how the thesis was developed. The second chapter presents the SharePoint platform, which includes a description of its structure, function and usability. The third chapter focuses solely on the programming of the platform. First, some of the most useful software tools for i...

  1. Information Sharing and Environmental Policies

    Directory of Open Access Journals (Sweden)

    Nikos Tsakiris

    2010-10-01

    Full Text Available Based on the assumption that in a standard eco-dumping model governments are uncertain about future product demand and allowing governments to obtain information from firms, we examine governments’ and firms’ incentives to share information. We show that when governments regulate polluting firms through emission standards, then governments and firms will reach an agreement concerning information sharing. The opposite holds when governments regulate pollution through emission taxes.

  2. Cost-Sharing and Productivity

    OpenAIRE

    Gibson, Teresa B.; A. Mark Fendrick; Chernew, Michael E.

    2012-01-01

    A growing body of literature examines the cross price elasticities between different health care services. For example, increasing the patient out of pocket price for some health care services increases the utilization of other health care services. Yet, the literature has generally ignored the connection between cost sharing for health care services and labor market outcomes. This paper examines the direction and magnitude of the reduced form relationship between patient cost-sharing and wor...

  3. Shared Year Exchange in Nursing

    DEFF Research Database (Denmark)

    Vedsegaard, Helle Wendner; Wederkinck, Elisabeth

    2010-01-01

    Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien.......Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien....

  4. The value of shared services.

    Science.gov (United States)

    Wallace, Beverly B

    2011-07-01

    A multisite shared services organization, combined with a robust business continuity plan, provides infrastructure and redundancies that mitigate risk for hospital CFOs. These structures can position providers to do the following: move essential operations out of a disaster impact zone, if necessary. Allow resources to focus on immediate patient care needs. Take advantage of economies of scale in temporary staffing. Leverage technology. Share in investments in disaster preparedness and business continuity solutions

  5. Forecasting the State of Health of Electric Vehicle Batteries to Evaluate the Viability of Car Sharing Practices

    OpenAIRE

    Ivana Semanjski; Sidharta Gautama

    2016-01-01

    Car sharing practices are introducing electric vehicles into their fleet. However, literature suggests that at this point shared electric vehicle systems are failing to reach satisfactory commercial viability. Potential reason for this is the effect of higher vehicle usage which is characteristic for car sharing, and the implication on the battery state of health. In this paper, we forecast state of health for two identical electric vehicles shared by two different car sharing practices. For ...

  6. Institutional shared resources and translational cancer research

    Directory of Open Access Journals (Sweden)

    De Paoli Paolo

    2009-06-01

    Full Text Available Abstract The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology. In fact, the physical build-up of SRs per se is not sufficient for the successful translation of biomedical research. Appropriate policies to improve the academic culture in collaboration, the availability of educational programs for translational investigators, the existence of administrative facilitations for translational research and an efficient organization

  7. Institutional shared resources and translational cancer research.

    Science.gov (United States)

    De Paoli, Paolo

    2009-06-29

    The development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. The success or failure of a shared resource program also depends on the choice of appropriate institutional policies and requires an effective institutional governance regarding decisions on staffing, existence and composition of advisory committees, policies and of defined mechanisms of reporting, budgeting and financial support of each resource. Shared Resources represent a widely diffused model to sustain cancer research; in fact, web sites from an impressive number of research Institutes and Universities in the U.S. contain pages dedicated to the SR that have been established in each Center, making a complete view of the situation impossible. However, a nation-wide overview of how Cancer Centers develop SR programs is available on the web site for NCI-designated Cancer Centers in the U.S., while in Europe, information is available for individual Cancer centers. This article will briefly summarize the institutional policies, the organizational needs, the characteristics, scientific aims, and future developments of SRs necessary to develop effective translational research programs in oncology.In fact, the physical build-up of SRs per se is not sufficient for the successful translation of biomedical research. Appropriate policies to improve the academic culture in collaboration, the availability of educational programs for translational investigators, the existence of administrative facilitations for translational research and an efficient organization supporting clinical trial recruitment

  8. Differential expression of anti-angiogenic factors and guidance genes in the developing macula.

    Science.gov (United States)

    Kozulin, Peter; Natoli, Riccardo; O'Brien, Keely M Bumsted; Madigan, Michele C; Provis, Jan M

    2009-01-01

    The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color vision. The spatial resolution provided by the neural retina at the macula is optimized by stereotyped retinal blood vessel and ganglion cell axon patterning, which radiate away from the macula and reduce shadowing of macular photoreceptors. However, the genes that mediate these specializations, and the reasons for the vulnerability of the macula to degenerative disease, remain obscure. The aim of this study was to identify novel genes that may influence retinal vascular patterning and definition of the foveal avascular area. We used RNA from human fetal retinas at 19-20 weeks of gestation (WG; n=4) to measure differential gene expression in the macula, a region nasal to disc (nasal) and in the surrounding retina (surround) by hybridization to 12 GeneChip microarrays (HG-U133 Plus 2.0). The raw data was subjected to quality control assessment and preprocessing, using GC-RMA. We then used ANOVA analysis (Partek) Genomic Suite 6.3) and clustering (DAVID website) to identify the most highly represented genes clustered according to "biological process." The neural retina is fully differentiated at the macula at 19-20 WG, while neuronal progenitor cells are present throughout the rest of the retina. We therefore excluded genes associated with the cell cycle, and markers of differentiated neurons, from further analyses. Significantly regulated genes (pmacula versus surround" and "macula versus nasal." KEGG pathway clustering of the filtered gene lists identified 25 axon guidance-related genes that are differentially regulated in the macula. Furthermore, we found significant upregulation of three anti-angiogenic factors in the macula: pigment epithelium derived factor (PEDF), natriuretic peptide precurusor B (NPPB), and collagen type IValpha2. Differential expression of several members of the ephrin and semaphorin axon guidance gene families, PEDF, and NPPB was verified by

  9. Display Sharing: An Alternative Paradigm

    Science.gov (United States)

    Brown, Michael A.

    2010-01-01

    The current Johnson Space Center (JSC) Mission Control Center (MCC) Video Transport System (VTS) provides flight controllers and management the ability to meld raw video from various sources with telemetry to improve situational awareness. However, maintaining a separate infrastructure for video delivery and integration of video content with data adds significant complexity and cost to the system. When considering alternative architectures for a VTS, the current system's ability to share specific computer displays in their entirety to other locations, such as large projector systems, flight control rooms, and back supporting rooms throughout the facilities and centers must be incorporated into any new architecture. Internet Protocol (IP)-based systems also support video delivery and integration. IP-based systems generally have an advantage in terms of cost and maintainability. Although IP-based systems are versatile, the task of sharing a computer display from one workstation to another can be time consuming for an end-user and inconvenient to administer at a system level. The objective of this paper is to present a prototype display sharing enterprise solution. Display sharing is a system which delivers image sharing across the LAN while simultaneously managing bandwidth, supporting encryption, enabling recovery and resynchronization following a loss of signal, and, minimizing latency. Additional critical elements will include image scaling support, multi -sharing, ease of initial integration and configuration, integration with desktop window managers, collaboration tools, host and recipient controls. This goal of this paper is to summarize the various elements of an IP-based display sharing system that can be used in today's control center environment.

  10. Synergistic effect of anti-angiogenic herbal composition (Meta-X) in combination with radiotherapy on the inhibition of tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Han, Young Soo; Song, Jie Young; Yoon, Yeon Sook [Korea Institute of Radilolgical and Medical Science, Seoul (Korea, Republic of); Kim, Joon Sik; Park, Byung Young; Lee, Hee Suk; Kim, Min Yung [AngioLab, Seoul (Korea, Republic of)

    2004-07-01

    Anti-angiogenic composition called Meta-X was made from herbal medicines that are currently used oral drugs for other indications. We examined biochemical properties of Meta-X, and synergistic effect of Meta-X combined with irradiation on the inhibition of tumor growth.

  11. The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea.

    Science.gov (United States)

    Gage, Philip J; Kuang, Chen; Zacharias, Amanda L

    2014-11-01

    Correct specification of cell lineages and establishing angiogenic privilege within the developing cornea are essential for normal vision but the mechanisms controlling these processes are poorly understood. We show that the homeodomain transcription factor PItX2 is expressed in mesenchymal cells of the developing and mature cornea and use a temporal gene knockout approach to demonstrate that PITX2 is required for corneal morphogenesis and the specification of cell fates within the surface ectoderm and mesenchymal primordia. PITX2 is also required to establish angiogenic privilege in the developing cornea. Further, the expression of Dkk2 and suppression of canonical Wnt signaling activity levels are key mechanisms by which PITX2 specifies ocular surface ectoderm as cornea. In contrast, specifying the underlying mesenchyme to corneal fates and establishing angiogenic privilege in the cornea are less sensitive to DKK2 activity. Finally, the cellular expression patterns of FOXC2, PITX1, and BARX2 in Pitx2 and Dkk2 mutants suggest that these transcription factors may be involved in specifying cell fate and establishing angiogenic privilege within the corneal mesenchyme. However, they are unlikely to play a role in specifying cell fate within the corneal ectoderm. Together, these data provide important insights into the mechanisms regulating cornea development. Copyright © 2014 Wiley Periodicals, Inc.

  12. Angiogenic growth factors and their receptors in first-trimester human decidua of pregnancies further complicated by preeclampsia or fetal growth restriction

    NARCIS (Netherlands)

    Plaisier, M.; Streefland, E.; Koolwijk, P.; van Hinsbergh, V. W. M.; Helmerhorst, F. M.; Erwich, J. J. H. M.

    Disturbances in decidual and placental vascular development may play a role in the pathogenesis of pregnancy complications. This study focused on the role of angiogenic factors in the first trimester in the pathogenesis of preeeclampsia (PF) and/or fetal growth restriction (FGR). First-trimester

  13. Expression of angiogenic switch, cachexia and inflammation factors at the crossroad in undifferentiated thyroid carcinoma with BRAF(V600E).

    Science.gov (United States)

    Husain, Amjad; Hu, Nina; Sadow, Peter M; Nucera, Carmelo

    2016-10-01

    Cachexia is the result of complex metabolic alterations which cause morbidity and mortality in patients with advanced cancers including undifferentiated (anaplastic) thyroid carcinoma (ATC). ATC is a lethal disease with limited therapeutic options and unclear etiology for cachexia. We hypothesize that the BRAF(V600E) oncoprotein triggers microvascular endothelial cell tubule formation (in vitro angiogenesis) by means of factors which play a crucial role in angiogenic switch, inflammation/immune response and cachexia. We use human ATC cells and applied multiplex ELISA assay to screen for and measure angiogenic/cachectic and pro-inflammatory factors in the ATC-derived secretome. We find that vemurafenib anti-BRAF(V600E) therapy significantly reduces secreted VEGFA, VEGFC and IL6 protein levels compared to vehicle-treated ATC cells. As a result, the secretome from vemurafenib-treated ATC cells inhibits microvascular endothelial cell-related in vitro angiogenesis. Furthermore, ATC clinical samples express VEGFA, VEGFC and IL6 proteins. Our results suggest that angiogenic/cachectic and pro-inflammatory/immune response factors could play a crucial role in BRAF(V600E)-positive human ATC aggressiveness. Understanding the extent to which microenvironment-associated angiogenic factors participate in cachexia and cancer metabolism in advanced thyroid cancers will reveal new biomarkers and foster novel therapeutic approaches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Increased serum levels of anti-angiogenic factors soluble fms-like tyrosine kinase and soluble endoglin in sickle cell disease

    NARCIS (Netherlands)

    Landburg, P.P.; Elsenga, H.; Schnog, J.B.; Duits, A.J.

    2008-01-01

    The anti-angiogenic factors soluble fms-like tyrosine kinase (sFlt)-1 and soluble endoglin (sEng) have been shown to be of importance in angiogenesis by sequestering and inhibiting vascular endothelial growth factor, placenta-like growth factor and transforming growth factor-beta(1) signaling. Given

  15. Priming of mononuclear cells with a combination of growth factors enhances wound healing via high angiogenic and engraftment capabilities.

    Science.gov (United States)

    Jin, Enze; Kim, Jong-Min; Kim, Sung-Whan

    2013-12-01

    Recently, we demonstrated that a specific combination of growth factors enhances the survival, adhesion and angiogenic potential of mononuclear cells (MNCs). In this study, we sought to investigate the changes of the angiogenic potential of MNCs after short-time priming with a specific combination of growth factors. MNCs were isolated using density gradient centrifugation and incubated with a priming cocktail containing epidermal growth factor (EGF), insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, FMS-like tyrosine kinase (Flt)-3L , Angiopoietin (Ang)-1, granulocyte chemotactic protein (GCP)-2 and thrombopoietin (TPO) (all 400 ng/ml) for 15, 30 and 60 min. Wounds in nonobese diabetic-severe combined immune deficiency (NOD-SCID) mice were created by skin excision followed by cell transplantation. We performed a qRT-PCR analysis on the growth factor-primed cells. The angiogenic factors vascular endothelial growth factor (VEGF)-A, FGF-2, hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and interleukin (IL)-8 and the anti-apoptotic factors IGF-1 and transforming growth factor-β1 were significantly elevated in the MNCs primed for 30 min. (T30) compared with the non-primed MNCs (T0). The scratch wound assay revealed that T30- conditioned media (CM) significantly increased the rate of fibroblast-mediated wound closure compared with the rates from T0-CM and human umbilical vein endothelial cells (HUVEC)-CM at 20 hrs. In vivo wound healing results revealed that the T30-treated wounds demonstrated accelerated wound healing at days 7 and 14 compared with those treated with T0. The histological analyses demonstrated that the number of engrafted cells and transdifferentiated keratinocytes in the wounds were significantly higher in the T30-transplanted group than in the T0-transplanted group. In conclusion, this study suggests that short-term priming of MNCs with growth factors might be alternative therapeutic option for cell

  16. Angiogenic, hyperpermeability and vasodilator network in utero-placental units along pregnancy in the guinea-pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Chacón Cecilia

    2008-03-01

    Full Text Available Abstract Background The angiogenic and invasive properties of the cytotrophoblast are crucial to provide an adequate area for feto-maternal exchange. The present study aimed at identifying the localization of interrelated angiogenic, hyperpermeability and vasodilator factors in the feto-maternal interface in pregnant guinea-pigs. Methods Utero-placental units were collected from early to term pregnancy. VEGF, Flt-1, KDR, B2R and eNOS were analyzed by immunohistochemistry, and the intensity of the signals in placenta and syncytial streamers was digitally analysed. Flt1 and eNOS content of placental homogenates was determined by western blotting. Statistical analysis used one-way analysis of variance and Tukey's Multiple Comparison post-hoc test. Results In the subplacenta, placental interlobium and labyrinth VEGF, Flt-1, KDR, B2R and eNOS were expressed in all stages of pregnancy. Syncytial streamers in all stages of gestation, and cytotrophoblasts surrounding myometrial arteries in early and mid pregnancy – and replacing the smooth muscle at term – displayed immunoreactivity for VEGF, Flt-1, KDR, eNOS and B2R. In partly disrupted mesometrial arteries in late pregnancy cytotrophoblasts and endothelial cells expressed VEGF, Flt-1, KDR, B2R and eNOS. Sections incubated in absence of the first antibody, or in presence of rabbit IgG fraction and mouse IgG serum, yielded no staining. According to the digital analysis, Flt-1 increased in the placental interlobium in days 40 and 60 as compared to day 20 (P = 0.016, and in the labyrinth in day 60 as compared to days 20 and 40 (P = 0.026, while the signals for VEGF, KDR, B2R, and eNOS showed no variations along pregnancy. In syncytial streamers the intensity of VEGF immunoreactivity was increased in day 40 in comparison to day 20 (P = 0.027, while that of B2R decreased in days 40 and 60 as compared to day 20 (P = 0.011; VEGF, Flt-1, KDR, B2R and eNOS expression showed no variations. Western blots for

  17. Photonic spin-controlled multifunctional shared-aperture antenna array.

    Science.gov (United States)

    Maguid, Elhanan; Yulevich, Igor; Veksler, Dekel; Kleiner, Vladimir; Brongersma, Mark L; Hasman, Erez

    2016-06-03

    The shared-aperture phased antenna array developed in the field of radar applications is a promising approach for increased functionality in photonics. The alliance between the shared-aperture concepts and the geometric phase phenomenon arising from spin-orbit interaction provides a route to implement photonic spin-control multifunctional metasurfaces. We adopted a thinning technique within the shared-aperture synthesis and investigated interleaved sparse nanoantenna matrices and the spin-enabled asymmetric harmonic response to achieve helicity-controlled multiple structured wavefronts such as vortex beams carrying orbital angular momentum. We used multiplexed geometric phase profiles to simultaneously measure spectrum characteristics and the polarization state of light, enabling integrated on-chip spectropolarimetric analysis. The shared-aperture metasurface platform opens a pathway to novel types of nanophotonic functionality. Copyright © 2016, American Association for the Advancement of Science.

  18. Food Sharing among Hadza Hunter-Gatherer Children.

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    Alyssa N Crittenden

    Full Text Available Human prosociality is one of the defining characteristics of our species, yet the ontogeny of altruistic behavior remains poorly understood. The evolution of widespread food sharing in humans helped shape cooperation, family formation, life history, language, and the development of economies of scale. While the behavioral and ecological correlates of food sharing among adults are widely studied, very little is known about food sharing among children. Here, in the first study to analyze the food sharing patterns of hunter-gatherer children, we show that while sharing may be biased towards kin, reciprocity characterizes the majority of all sharing dyads, both related and unrelated. These data lend support to the recent claim that discrimination among kin might be linked with reciprocal altruism theory. Furthermore, we show that age positively correlates with an increase in sharing, both in frequency and amount, supporting recent suggestions that prosocial behaviors and egalitarianism develop strongly in middle childhood when children acquire the normative rules of their society.

  19. Expression of angiogenic basic fibroblast growth factor, platelet derived growth factor, thrombospondin-1 and their receptors at the porcine maternal-fetal interface

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    LaMarre Jonathan

    2011-01-01

    Full Text Available Abstract Background Commercial swine breeds in North America undergo two waves of spontaneous fetal loss; one during peri-attachment and another during mid-gestation. Although an exact mechanism for this loss is not known, deficits in vasculature at the attachment sites appear to be a major cause. We hypothesized that a balance between pro-angiogenic and anti-angiogenic factors is needed at the maternal-fetal interface for successful conceptus development. Six selected members of the pro-angiogenic fibroblast growth factor (FGF and platelet derived growth factor (PDGF families and anti-angiogenic factor thrombospondin-1 (TSP-1 and its receptor CD36 were quantified and localized at the porcine maternal-fetal interface at early and midgestation time points. Methods Mesometrial endometrium was collected from non-pregnant gilts (n = 8. Endometrial and chorioallantoic membrane samples were collected from healthy and arresting conceptus attachment sites at gestation day (gd 20 (n = 8 and gd 50 (n = 8. At gd20 arresting conceptus attachment sites were distinguished by decreased vasculature of the placental membranes and decreased conceptus size. At gd50 arresting conceptuses attachment sites were identified by smaller conceptus length and weight measurements. Quantitative real time PCR was used to determine relative transcript levels of genes of interest, and cellular localization was determined by immunohistochemistry in paraffin embedded endometrial sections. Results At gd20, endometrial samples from arresting conceptuses had elevated transcripts for bFGF, and PDGF-bb than healthy sites (p Conclusions We provide comprehensive analysis of pro and anti-angiogenic factors at the porcine maternal fetal interface during early and mid-pregnancy. At mRNA levels, the majority of pro-angiogenic factors investigated were elevated at the sites of fetal arrest. These observations contrast with our previous findings of decreased Vascular Endothelial Growth Factor

  20. A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial.

    Science.gov (United States)

    Falk, Roni T; Staff, Annetine Cathrine; Bradwin, Gary; Karumanchi, S Ananth; Troisi, Rebecca

    2016-08-01

    Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed. We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR. Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33-2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors. There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1.

  1. Netrin-1 acts as a non-canonical angiogenic factor produced by human Wharton's jelly mesenchymal stem cells (WJ-MSC).

    Science.gov (United States)

    Prieto, Catalina P; Ortiz, María Carolina; Villanueva, Andrea; Villarroel, Cynthia; Edwards, Sandra S; Elliott, Matías; Lattus, José; Aedo, Sócrates; Meza, Daniel; Lois, Pablo; Palma, Verónica

    2017-02-28

    Angiogenesis, the process in which new blood vessels are formed from preexisting ones, is highly dependent on the presence of classical angiogenic factors. Recent evidence suggests that axonal guidance proteins and their receptors can also act as angiogenic regulators. Netrin, a family of laminin-like proteins, specifically Netrin-1 and 4, act via DCC/Neogenin-1 and UNC5 class of receptors to promote or inhibit angiogenesis, depending on the physiological context. Mesenchymal stem cells secrete a broad set of classical angiogenic factors. However, little is known about the expression of non-canonical angiogenic factors such as Netrin-1. The aim was to characterize the possible secretion of Netrin ligands by Wharton's jelly-derived mesenchymal stem cells (WJ-MSC). We evaluated if Netrin-1 presence in the conditioned media from these cells was capable of inducing angiogenesis both in vitro and in vivo, using human umbilical vein endothelial cells (HUVEC) and chicken chorioallantoic membrane (CAM), respectively. In addition, we investigated if the RhoA/ROCK pathway is responsible for the integration of Netrin signaling to control vessel formation. The paracrine angiogenic effect of the WJ-MSC-conditioned media is mediated at least in part by Netrin-1 given that pharmacological blockage of Netrin-1 in WJ-MSC resulted in diminished angiogenesis on HUVEC. When HUVEC were stimulated with exogenous Netrin-1 assayed at physiological concentrations (10-200 ng/mL), endothelial vascular migration occurred in a concentration-dependent manner. In line with our determination of Netrin-1 present in WJ-MSC-conditioned media we were able to obtain endothelial tubule formation even in the pg/mL range. Through CAM assays we validated that WJ-MSC-secreted Netrin-1 promotes an increased angiogenesis in vivo. Netrin-1, secreted by WJ-MSC, might mediate its angiogenic effect through specific cell surface receptors on the endothelium, such as UNC5b and/or integrin α6β1, expressed in

  2. Vibrio chromosomes share common history

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    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  3. Knowledge Sharing is Knowledge Creation

    DEFF Research Database (Denmark)

    Greve, Linda

    2015-01-01

    Knowledge sharing and knowledge transfer are important to knowledge communication. However when groups of knowledge workers engage in knowledge communication activities, it easily turns into mere mechanical information processing despite other ambitions. This article relates literature of knowledge...... communication and knowledge creation to an intervention study in a large Danish food production company. For some time a specific group of employees uttered a wish for knowledge sharing, but it never really happened. The group was observed and submitted to metaphor analysis as well as analysis of co......-creation strategies. Confronted with the results, the group completely altered their approach to knowledge sharing and let it become knowledge co-creation. The conclusions are, that knowledge is and can only be a diverse and differentiated concept, and that groups are able to embrace this complexity. Thus rather than...

  4. Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics.

    Science.gov (United States)

    Papagiannaki, Chrysanthi; Clarençon, Frédéric; Ponsonnard, Sébastien; Couquet, Claude; Maizeroi-Eugène, Franck; Bresson, Damien; Yardin, Catherine; Mounayer, Charbel

    2017-02-01

    Angiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs. To develop an animal model sharing the same pathological characteristics as human brain AVMs. Ten pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of the retia was calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and the retia were harvested for pathological and immunohistochemistry examinations. At 3 months, a significantly higher rete volume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6. Unilateral endovascular occlusion of the CCA-ECA results in angiogenesis triggering of the rete mirabile with both significant augmentation of the rete volume and histological evidence of pro-angiogenic stimulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Data sharing for pharmacokinetic studies.

    Science.gov (United States)

    Anderson, Brian J; Merry, Alan F

    2009-10-01

    Pooling data from different pediatric studies can provide a single robust pharmacokinetic analysis that allows covariate analysis and hypothesis testing. Data sharing should be driven by the altruistic purpose of improving drug understanding to the clinical benefit of children. Electronic communications have rendered the sharing of data relatively easy, and data sharing within the wider scientific community has become commonplace. Data sharing allows verification of results, save costs and time, allows new interpretation of old data, and can fulfill teaching benefits. It may stimulate cooperative competition between researchers and allow individual researchers to concentrate on unique aspects of the scientific puzzle. However, there is occasionally a reluctance to share, in part because of fear of others stealing the hard work of a research group, which may not be recognized in subsequent publications that reuse data. Providing data may require additional effort for presentation in a suitable format. Data may be abused or used for purposes other than those for which they were collected. Propriety claims may limit access to industry-sponsored drug research. The question of who has ownership of data is contentious. Investigators often consider data they have collected to be their own property. Reputations and grants may be hinge on ownership of a data set. However, other team members, institutions, funding agencies, and the public also have a stake. The difficulties identified in the general scientific community also apply to data sharing for pediatric pharmacokinetic studies. There are few clearly established rules at present, and consideration of the issues hinges on ethical and philosophical arguments. The development of databases will depend on collaboration and cooperation and greater clarity and consensus over appropriate processes and procedures.

  6. N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors.

    Science.gov (United States)

    Nawaz, Imtiaz M; Chiodelli, Paola; Rezzola, Sara; Paganini, Giuseppe; Corsini, Michela; Lodola, Alessio; Di Ianni, Alessio; Mor, Marco; Presta, Marco

    2018-02-01

    The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A 165 with no effect on the activity of the non-heparin-binding VEGF-A 121 isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, and computer modeling indicate that BOC2 may interact with the heparin-binding domain of VEGF-A 165 , thus competing for heparin interaction and preventing the binding of VEGF-A 165 to tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In addition, BOC2 inhibits the interaction of a variety of heparin-binding angiogenic growth factors with heparin, including fibroblast growth factor 2 (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2 suppresses the angiogenic potential of human tumor cell lines that co-express VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding growth factor antagonist. These findings caution about the interpretation of FPR-focusing experimental data obtained with this compound and set the basis for the design of novel BOC2-derived, FPR independent multi-target angiogenesis inhibitors.

  7. 3D endothelial cell spheroid/human vitreous humor assay for the characterization of anti-angiogenic inhibitors for the treatment of proliferative diabetic retinopathy.

    Science.gov (United States)

    Rezzola, Sara; Nawaz, Imtiaz M; Cancarini, Anna; Ravelli, Cosetta; Calza, Stefano; Semeraro, Francesco; Presta, Marco

    2017-11-01

    Proliferative diabetic retinopathy (PDR) represents a main cause of acquired blindness. Despite the recognition of the key role exerted by vascular endothelial growth factor (VEGF) in the pathogenesis of PDR, limitations to anti-VEGF therapies do exist. Thus, rapid and cost-effective angiogenesis assays are crucial for the screening of anti-angiogenic drug candidates for PDR therapy. In this context, evaluation of the angiogenic potential of PDR vitreous fluid may represent a valuable tool for preclinical assessment of angiostatic molecules. Here, vitreous fluid obtained from PDR patients after pars plana vitrectomy was used as a pro-angiogenic stimulus in a 3D endothelial cell spheroid/human vitreous assay. The results show that PDR vitreous is able to stimulate the sprouting of fibrin-embedded HUVEC spheroids in a time- and dose-dependent manner. A remarkable variability was observed among 40 individual vitreous fluid samples in terms of sprouting-inducing activity that was related, at least in part, to defined clinical features of the PDR patient. This activity was hampered by various extracellular and intracellular signaling pathway inhibitors, including the VEGF antagonist ranibizumab. When tested on 20 individual vitreous fluid samples, the inhibitory activity of ranibizumab ranged between 0 and 100% of the activity measured in the absence of the drug, reflecting a variable contribution of angiogenic mediators distinct from VEGF. In conclusion, the 3D endothelial cell spheroid/human vitreous assay represents a rapid and cost-effective experimental procedure suitable for the evaluation of the anti-angiogenic activity of novel extracellular and intracellular drug candidates, with possible implications for the therapy of PDR.

  8. Rhodamine-RCA in vivo labeling guided laser capture microdissection of cancer functional angiogenic vessels in a murine squamous cell carcinoma mouse model

    Directory of Open Access Journals (Sweden)

    Bur Monica

    2006-02-01

    Full Text Available Abstract Background Cancer growth, invasion and metastasis are highly related to tumor-associated neovasculature. The presence and progression of endothelial cells in cancer is chaotic, unorganized, and angiogenic vessels are less functional. Therefore, not all markers appearing on the chaotic endothelial cells are accessible if a drug is given through the vascular route. Identifying endothelial cell markers from functional cancer angiogenic vessels will indicate the accessibility and potential efficacy of vascular targeted therapies. Results In order to quickly and effectively identify endothelial cell markers on the functional and accessible tumor vessels, we developed a novel technique by which tumor angiogenic vessels are labeled in vivo followed by Laser Capture Microdissection of microscopically isolated endothelial cells for genomic screening. Female C3H mice (N = 5 with established SCCVII tumors were treated with Rhodamine-RCA lectin by tail vein injection, and after fluorescence microscopy showed a successful vasculature staining, LCM was then performed on frozen section tissue using the PixCell II instrument with CapSure HS caps under the Rhodamine filter. By this approach, the fluorescent angiogenic endothelial cells were successfully picked up. As a result, the total RNA concentration increased from an average of 33.4 ng/ul +/- 24.3 (mean +/- S.D. to 1913.4 ng/ul +/- 164. Relatively pure RNA was retrieved from both endothelial and epithelial cells as indicated by the 260/280 ratios (range 2.22–2.47. RT-PCR and gene electrophoresis successfully detected CD31 and Beta-Actin molecules with minimal Keratin 19 expression, which served as the negative control. Conclusion Our present study demonstrates that in vivo Rhodamine RCA angiogenic vessel labeling provided a practical approach to effectively guide functional endothelial cell isolation by laser capture microdissection with fluorescent microscopy, resulting in high quality RNA and

  9. Expression and production of cardiac angiogenic mediators depend on the Trypanosoma cruzi-genetic population in experimental C57BL/6 mice infection.

    Science.gov (United States)

    Shrestha, Deena; Bajracharya, Bijay; Paula-Costa, Guilherme; Salles, Beatriz C; Leite, Ana Luísa J; Menezes, Ana Paula J; Souza, Débora Ms; Oliveira, Laser Am; Talvani, André

    2017-03-01

    Mammalian cardiac cells are important targets to the protozoan Trypanosoma cruzi. The inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. Local hypoxia is well-defined stimulus to the production of angiogenesis mediators. Assuming that different genetic T. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is a parasite strain-dependent condition. C57BL/6 mice were infected with the Y and Colombian strains of T. cruzi and euthanized at the 12th and 32nd days, respectively. The blood and heart tissue were processed in immune assays and/or qPCR (TNF, IL-17, IL-10, CCL2, CCL3, CCL5, CCR2, CCR5 and angiogenic factors VEGF, Ang-1, Ang-2) and in histological assays. The T. cruzi increased the inflammatory and angiogenic mediators in the infected mice when they were compared to non-infected animals. However, the Colombian strain has led to higher (i) leukocyte infiltration, (ii) cardiac TNF and CCL5 production/expression, (iii) cardiac tissue parasitism, and to higher (iv) ratio between heart/body weights. On the other hand, the Colombian strain has caused lower production and expression VEGF, Ang-1 and Ang-2, when it was compared to the Y strain of the parasite. The present study highlights that the T. cruzi-genetic population defines the pattern of angiogenic/inflammatory mediators in the heart tissue, and that it may contribute to the magnitude of the cardiac pathogenesis. Besides, such assumption opens windows to the understanding of the angiogenic mediator's role in association with the experimental T. cruzi infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Sharing best practice in partnerships

    DEFF Research Database (Denmark)

    Mosgaard, Mette; Remmen, Arne; Pedersen, Claus Stig

    upstream in the supply chain, and “business development” of sustainable products and product service systems. Sharing best practice in partnerships is an example of the latter, but Supply Chain Management goes beyond product chains and into partnerships where the focus is not on one main company......In this paper, the promotion of sustainable products through the sharing of best practices in product chains is examined. The general understanding is that the interactions in the supply chain are changing from a traditional focus on the supply of goods “just in time” towards a focus on value...

  11. Extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications.

    Science.gov (United States)

    Tokarz, Aleksandra; Szuścik, Iwona; Kuśnierz-Cabala, Beata; Kapusta, Maria; Konkolewska, Magdalena; Żurakowski, Aleksander; Georgescu, Adriana; Stępień, Ewa

    2015-01-01

    Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- croparticles (MPs) and exosomes, derived from cells or platelets are present in the peripheral blood and are important elements involved in the activation of the coagulation system, transport of macromolecules and intercellular communication. In patients with vascular complications (including diabetes), the number of EVs is significantly increased during the acute phase of the disease. However, less is known about EVs release in the chronic state of diabetes. To analyse the profile of inflammatory cytokines and angiogenic factors in EVs in diabetic patients with ocular and vascular complications. The study included patients with diabetes and varying degrees of ocular complications including retinopathy (n = 48) and the control group (n = 13). EV-enriched and EV-depleted fractions were obtained from platelet-poor plasma by means of the centrifugation method (16 000 g, for 90 min). In screening, the profile of cytokines with pro-angiogenic effects was preliminary assessed using the protein microarray technology for controlled diabetic patients - CD, uncontrolled diabetic patients - UD and for the control group. In all patients, concentrations of cytokines: RANTES (Regulated on Activation, Normal T-cell Expressed and secreted) and Ang-2 (angiopoietin-2) were assayed using the ELISA method. Common blood and biochemical tests were performed. In patients with diabetes, analysis of supernatant revealed significantly increased concentrations of basic fibroblast growth factor (bFGF) and soluble receptor for vascular endothelial growth factor 2 (V-EGFR2) when compared to the control group: 49 (10.5-122) vs. 24 (2-72.5) SD (p = 0.03) and 260 (195.5-351) vs. 360 (256-461.5) SD (p = 0.01). In UD patients, concentrations of RANTES, angiostatin, tumor necrosis factor-α (TNF), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2) were relatively higher in the EV-enriched fraction when

  12. Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis.

    Science.gov (United States)

    Canosa, S; Moggio, A; Brossa, A; Pittatore, G; Marchino, G L; Leoncini, S; Benedetto, C; Revelli, A; Bussolati, B

    2017-03-01

    Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis. This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9). E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline. A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment. This study was supported by the 'Research Fund ex-60%', University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential

  13. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Andreas Matthäus Bader

    Full Text Available Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis-regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, "post-ischemic" cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic

  14. Evaluation of vitreous levels of advanced glycation end products and angiogenic factors as biomarkers for severity of diabetic retinopathy.

    Science.gov (United States)

    Katagiri, Makiko; Shoji, Jun; Inada, Noriko; Kato, Satoshi; Kitano, Shigehiko; Uchigata, Yasuko

    2017-03-15

    Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups. In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods. Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10-6) and leptin (r = 0.60, p = 5.0 × 10-3) were significantly correlated with levels of PlGF. The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.

  15. Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression.

    Science.gov (United States)

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; D'Amore, Simona; Gnoni, Antonio; Pellegrino, Mariangela; Storelli, Carlo; De Caterina, Raffaele; Palasciano, Giuseppe; Carluccio, Maria Annunziata

    2016-02-01

    Previous studies have shown the antiinflammatory, antioxidant and antiangiogenic properties by pure olive oil polyphenols; however, the effects of olive oil phenolic fraction on the inflammatory angiogenesis are unknown. In this study, we investigated the effects of the phenolic fraction (olive oil polyphenolic extract, OOPE) from extra virgin olive oil and related circulating metabolites on the VEGF-induced angiogenic responses and NADPH oxidase activity and expression in human cultured endothelial cells. We found that OOPE (1-10 μg/ml), at concentrations achievable nutritionally, significantly reduced, in a concentration-dependent manner, the VEGF-induced cell migration, invasiveness and tube-like structure formation through the inhibition of MMP-2 and MMP-9. OOPE significantly (Poxidase activity, p47phox membrane translocation and the expression of Nox2 and Nox4. Moreover, the treatment of endothelial cells with serum obtained 4 h after acute intake of extra virgin olive oil, with high polyphenol content, decreased VEGF-induced NADPH oxidase activity and Nox4 expression, as well as, MMP-9 expression, as compared with fasting control serum. Overall, native polyphenols and serum metabolites of extra virgin olive oil rich in polyphenols are able to lower the VEGF-induced angiogenic responses by preventing endothelial NADPH oxidase activity and decreasing the expression of selective NADPH oxidase subunits. Our results provide an alternative mechanism by which the consumption of olive oil rich in polyphenols may account for a reduction of oxidative stress inflammatory-related sequelae associated with chronic degenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. CPU-12, a novel synthesized oxazolo[5,4-d]pyrimidine derivative, showed superior anti-angiogenic activity.

    Science.gov (United States)

    Liu, Jiping; Deng, Ya-Hui; Yang, Ling; Chen, Yijuan; Lawali, Manzo; Sun, Li-Ping; Liu, Yu

    2015-09-01

    Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  17. C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria.

    Directory of Open Access Journals (Sweden)

    Andrea Conroy

    Full Text Available Placental malaria (PM is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI enhanced C5a receptor expression (CD88 on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10, chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function.

  18. (--EPICATECHIN COMBINED WITH 8 WEEKS OF TREADMILL EXERCISE IS ASSOCIATED WITH INCREASED ANGIOGENIC AND MITOCHONDRIAL SIGNALING IN MICE

    Directory of Open Access Journals (Sweden)

    Icksoo eLee

    2015-03-01

    Full Text Available The purpose of this study was to conduct an 8 week endurance training program with and without (--epicatechin treatment and to determine whether there is a possible cumulative effect on protein markers of angiogenesis and mitochondrial biogenesis. Thirty-four 14 month old male mice (C57BL/6N were randomized into four groups: control (C; (--epicatechin only ((--Epi; control with endurance training (CE; and (--epicatechin with endurance training ((--Epi Ex. Mice in the training groups performed treadmill exercise for 8 weeks (5x/week for 60 min/session, whereas mice in the (--epicatechin group received 1.0 mg/kg of body mass twice daily during the training period. At 8 weeks, distance ran on the treadmill increased by 46%, 69%, and 84% in the (--Epi, CE, and (--Epi Ex groups, respectively compared to the control group (p < 0.001 for all comparisons. Furthermore, the ( Epi Ex group had significantly higher exercise capacity than the (--Epi and CE group. For angiogenic regulators, the (--Epi Ex group had significantly higher VEGF-R2 protein expression with a concomitant reduction in TSP-1 protein expression than the exercise group. Interestingly, FoxO1 protein expression was significantly reduced for all three experimental groups compared to the control group. Protein markers such as PGC-1beta and TFAM were significantly higher in the (--Epi Ex group compared to the three other groups. These findings suggest that (--epicatechin treatment combined with 8 weeks of endurance training provide a cumulative effect on a number of angiogenic and mitochondrial signaling which functionally translates to enhanced exercise tolerance.

  19. Targeting angiogenic pathway for chemoprevention of experimental colon cancer using C-phycocyanin as cyclooxygenase-2 inhibitor.

    Science.gov (United States)

    Saini, Manpreet Kaur; Sanyal, Sankar Nath

    2014-06-01

    An angiogenic pathway was studied that involved stromal tissue degradation with matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A), and hypoxia inducible factor-1α (HIF-1α) mediated growth regulation in a complex interaction with chemokines, such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β). Gene and protein expression was studied with real-time PCR, Western immunoblot, and immunofluorescence. Morphological and histopathological analysis of tumor was done, as also the activity of MMPs and HIF-1α by gelatin zymography and ELISA. Binding interactions of proteins were studied by molecular docking. Piroxicam, a traditional NSAID and C-phycocyanin, a biliprotein from Spirulina platensis, were utilized in the chemoprevention of DMH-induced rat colon cancer. A significant number of tumors was evident in DMH treated animals, while with piroxicam and C-phycocyanin, the number and size of tumors/lesions were reduced. Colonic tissues showed severe dysplasia, tubular adenoma, and adenocarcinoma from DMH, with invasive features along with signet ring cell carcinoma. No occurrence of carcinoma was detected in either of the drug treatments or in a combination regimen. An elevated VEGF-A, MMP-2, and MMP-9 level was observed, which is required for metastasis and invasion into surrounding tissues. Drugs induced chemoprevention by down-regulating these proteins. Piroxicam docked in VEGF-A binding site of VEGF-A receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin (a chromophore of C-phycocyanin) docked with VEGFR1 alone. HIF-1α is up-regulated which is associated with increased oxygen demand and angiogenesis. MCP-1 and MIP-1β expression was also found altered in DMH and regulated by the drugs. Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated.

  20. Early response assessment in patients with multiple myeloma during anti-angiogenic therapy using arterial spin labelling: first clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Fenchel, Michael [Eberhard-Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Eberhard-Karls University, Department of Diagnostic and Interventional Neuroradiology, Tuebingen (Germany); Konaktchieva, Marina [Eberhard-Karls University, Department of Internal Medicine, Gastroenterology, Tuebingen (Germany); Weisel, Katja; Kraus, Sabina [Eberhard-Karls University, Department of Internal Medicine, Hematology, Tuebingen (Germany); Brodoefel, Harald; Claussen, Claus D.; Horger, Marius [Eberhard-Karls University, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

    2010-12-15

    To determine if arterial-spin-labelling (ASL) MRI can reliably detect early response to anti-angiogenic therapy in patients with multiple myeloma by comparison with clinical/haematological response. Nineteen consecutive patients (10 men; mean age 63.5 {+-} 9.1 years) were included in the present study. Inclusion criteria were diagnosis of stage III multiple myeloma and clinical indication for therapeutical administration of bortezomib or lenalidomide. We performed MRI on 3.0T MR in the baseline setting, 3 weeks after onset of therapy and after 8 weeks. Clinical responses were determined on the basis of international uniform response criteria in correlation with haematological parameters and medium-term patient outcome. MRI studies were performed after approval by the local institutional review board. Fifteen patients responded to anti-myeloma therapy; 4/19 patients were non-responders to therapy. Mean tumour perfusion assessed by ASL-MRI in a reference lesion was 220.7 {+-} 132.5 ml min{sup -1} 100 g{sup -1} at baseline, and decreased to 125.7 {+-} 86.3 (134.5 {+-} 150.9) ml min{sup -1} 100 g{sup -1} 3 (8) weeks after onset of therapy (P < 0.02). The mean decrease in paraproteinaemia at week 3 (8) was 52.3 {+-} 47.7% (58.2 {+-} 58.7%), whereas {beta}2-microglobulinaemia decreased by 20.3 {+-} 53.1% (23.3 {+-} 57.0%). Correlation of ASL perfusion with outcome was significant (P = 0.0037). ASL tumour perfusion measurements are a valuable surrogate parameter for early assessment of response to novel anti-angiogenic therapy. (orig.)