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Sample records for suppression growth retardation

  1. Growth hormone suppression test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  2. Intrauterine growth retardation - small events, big consequences

    Directory of Open Access Journals (Sweden)

    Ali Syed R

    2011-09-01

    Full Text Available Abstract Intrauterine growth retardation refers to a rate of growth of a fetus that is less than normal for the growth potential of a fetus (for that particular gestational age. As one of the leading causes of perinatal mortality and morbidity, intrauterine growth retardation has immense implications for the short term and long term growth of children. It is an important public health concern in the developing countries. Health statistics encompassing parameters for maternal and child health in the Indian subcontinent have shown improvement in the past few years but they are still far from perfect. Maternal health, education and empowerment bears a strong influence on perinatal outcomes including intrauterine growth retardation and should be the primary focus of any stratagem targeted at reducing the incidence of intrauterine growth retardation. A concerted liaison of various medical and social disciplines is imperative in this regard.

  3. Unveiling causes for growth retardation in piglets

    NARCIS (Netherlands)

    Paredes Escobar, S.

    2014-01-01

    The evolution of hyper‐prolific sow breeds has led to a higher number of piglets born per sow per year. This increase in litter size has enlarged the number of light weight (or growth retarded) piglets, increased pre‐weaning mortality and heterogeneity at the end of the nursery phase (ten weeks of

  4. Obstetric interventions and perinatal asphyxia in growth retarded term infants

    DEFF Research Database (Denmark)

    Langhoff-Roos, J; Lindmark, G

    1997-01-01

    -fold (6-8%) for growth retarded infants both in SGA infants in general and infants with asymmetric body proportions. The immediate perinatal outcome, however, was favorable with Apgar below 8 at 5 min in only 2% irrespective of the type of growth retardation, in spite of the fact that less than 25...

  5. Fatigue crack growth retardation in spot heated mild steel sheet

    Indian Academy of Sciences (India)

    Spot heating; overloading; fatigue crack growth retardation; residual stress; delay cycles. ... It is observed that the extent of crack growth retardation increases with increasing level of overload as well as with increasing spot temperature. It is also ... Manuscript received: 29 November 2001; Manuscript revised: 24 June 2002 ...

  6. Fatigue crack growth retardation in spot heated mild steel sheet

    Indian Academy of Sciences (India)

    A fatigue crack can be effectively retarded by heating a spot near the crack tip under nil remote stress condition. The subcritical spot heating at a proper position modifies the crack growth behaviour in a way, more or less, similar to specimen subjected to overload spike. It is observed that the extent of crack growth retardation ...

  7. Smoke suppression properties of ferrite yellow on flame retardant thermoplastic polyurethane based on ammonium polyphosphate

    International Nuclear Information System (INIS)

    Chen, Xilei; Jiang, Yufeng; Jiao, Chuanmei

    2014-01-01

    Highlights: • Smoke suppression of FeOOH on flame retardant TPU composites has been investigated. • FeOOH has excellent smoke suppression abilities for flame retardant TPU composites. • FeOOH has good ability of char formation, hence improved smoke suppression property. -- Abstract: This article mainly studies smoke suppression properties and synergistic flame retardant effect of ferrite yellow (FeOOH) on flame retardant thermoplastic polyurethane (TPU) composites using ammonium polyphosphate (APP) as a flame retardant agent. Smoke suppression properties and synergistic flame retardant effect of FeOOH on flame retardant TPU composites were intensively investigated by smoke density test (SDT), cone calorimeter test (CCT), scanning electron microscopy (SEM), and thermal-gravimetric analysis (TGA). Remarkably, the SDT results show that FeOOH can effectively decrease the amount of smoke production with or without flame. On the other hand, the CCT data reveal that the addition of FeOOH can apparently reduce heat release rate (HRR), total heat release (THR), and total smoke release (TSR), etc. Here, FeOOH is considered to be an effective smoke suppression agent and a good synergism with APP in flame retardant TPU composites, which can greatly improve the structure of char residue realized by TGA and SEM results

  8. Intrauterine growth retardation (IUGR): epidemiology and etiology.

    Science.gov (United States)

    Romo, Agustín; Carceller, Raquel; Tobajas, Javier

    2009-02-01

    Intrauterine growth retardation (IUGR) is mainly due to a pathologic slow-down in the fetal growth pace, resulting in a fetus that is unable to reach its growth potential. IUGR frequency will vary depending on the discrimination criteria adopted. It is extremely important to use local or national fetal growth graphs in order to avoid some confounding factors. IUGR incidence in newborns would be between 3% and 7% of the total population. In our experience it is 5.13% a figure similar to the one obtained by other authors but with a progressively higher incidence during the last decade. There are multiple maternal factors that can generally be grouped into constitutional and general factors given that they affect age, weight, race, maternal cardiac volume, etc, socioeconomic factors with key incidence in the mother's nutrition level, where a poor maternal nutrition level would be the key factor in this group. We have evaluated multiple factors as possible contributors to the IUGR risk: race, parents' age, mother's height (cm), mother's birth weight and before pregnancy (kg), ponderal gain and blood pressure during pregnancy, and previous SGA newborns. Socioeconomic factors like social class, parents' profession, habitual residence, salary, immigration, and diet were also evaluated. We also included variables such as total daily working time and time mothers spent standing up, daily sleeping time (hrs), stress self-perception test at work and primiparity age. Toxic factors during pregnancy: tobacco (active and passive), alcohol, drugs and coffee consumption. Fetal or utero-placental factors were considered. In our study, the most significant etiologic factors were: Active and passive tobacco consuming, mother's stress level, increase of total months worked during pregnancy, total daily working hours and time mothers spent standing up and finally, the parent's height. Our data support the main objective of reducing the incidence of SGA newborns after IUGR by fighting

  9. Distal joint contractures, mental retardation, characteristic face and growth retardation: Chitayat syndrome revisited.

    NARCIS (Netherlands)

    Wortmann, S.B.; Rodenburg, R.J.T.; Schwahn, B.; Smeitink, J.A.M.; Morava, E.

    2007-01-01

    We report on a patient with congenital distal limb contractures, characteristic face, prominent metopic sutures, narrow forehead, severe psychomotor and growth retardation, white matter lesions and failure to thrive. The child has many overlapping features with those reported previously by Chitayat.

  10. Risk Factors to Growth Retardation in Major Thalassemia

    Directory of Open Access Journals (Sweden)

    Riva Uda

    2011-03-01

    Full Text Available The increasing in the life span of patients with major thalassemia should be followed by increased quality of life. There are factors which can affect growth retardation in these patients. The aim of this study was to find out the risk factors for growth retardation in patients with major thalassemia. An analytical study with cross-sectional design was conducted at Pediatric Thalassemia Clinics of Dr.Hasan Sadikin Hospital, Bandung, in June to July 2006. The subjects of this study were patients with major thalassemia. Inclusion criteria’s were age under 14 years old, had no chronic diseases like tuberculosis, cerebral palsy with complete medical records. Risk factors were the timing of diagnosis, initial and dose of deferoxamine, volume of transfused blood, mean pretransfusion hemoglobin level, family income, and age. Antropometric measurement indices were used to assess the growth which expressed in Z score. Growth evaluated based on height/age (H/A and growth retardation if H/A <-2 SD. Risk factors for growth retardation were analyzed separately using chi-square test and odds ratio (OR with 95% confidence interval (CI. Then they were analyzed simultaneously with logistic regression method. Subjects consisted of 152 patients with major thalassemia. Seventy three thalassemia patients were stunted. Analysis showed that age (OR: 5.42, 95% CI:2.32–12.65, p <0.001, dosage of deferoxamine (OR: 4.0, 95% CI: 1.29–12.41, p: 0.016, and family income (OR: 2.32, 95% CI: 1.06–5.06, p: 0.036 were risks factors for growth retardation. Conclusion, risk factors for growth retardation in major thalassemia are age, dosage of deferoxamine, and family income.

  11. Fatigue crack growth retardation in spot heated mild steel sheet

    Indian Academy of Sciences (India)

    Unknown

    Spot heating; overloading; fatigue crack growth retardation; residual stress; delay cycles. 1. Introduction. Despite the advances in the understanding of fatigue failure and the consequent improvement in the design of structures and components, fatigue is still the most common cause of service failure. During the growth of a.

  12. Growth retardation in children with chronic renal disease

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira

    2014-01-01

    Full Text Available Despite recent advances in the management of children with chronic renal disease (CRD, growth retardation remains its most visible comorbid condition. Growth retardation has adverse impact on morbidity and mortality rates, quality of life and education, and in adult patients on job family life, and independent leaving accomodation. Pathophysiology of impaired growth in CRD is complex and still not fully understood. The following complications are: anorexia, malnutrition, inflammation, decreased residual renal function, dialysis frequency and adequacy, renal anemia, metabolic acidosis, fluid/electrolyte imbalance, renal osteodistrophy, growth hormone (GH and insulin-like growth factor -1 (IGF-1 resistance. Malnutrition is most frequent and most important factor contributing to the degree of growth retardation in infancy. The degree of renal dysfunction is the major determinant of variability in growth from third year of age until puberty onset, while in puberty hypergonadotropic hypogonadism has negative effect. The main factors that influence growth after renal transplantation are the age of the recipient and glucocorticoid drugs dosage with negative effect and allograft function with positive effect. In order to improve growth in children with CRD it is necessary to include: diet with optimal caloric intake, correction of fluid/ electrolyte imbalance, correction of acidosis, renal osteodistrophy and anemia. If growth velocity is insufficient to normalize growth, it is necessary to start recombinant human GH (rhGH therapy at 0.05 mg/kg per day (0.35 mg/kg per week or 28 IU/m2 per week administered by subcutaneous injection.

  13. [Growth retardation in children with chronic renal disease].

    Science.gov (United States)

    2014-01-01

    Despite recent advances in the management of children with chronic renal disease (CRD), growth retardation remains its most visible comorbid condition. Growth retardation has adverse impact on morbidity and mortality rates, quality of life and education, and in adult patients on job family life, and independent leaving accomodation. Pathophysiology of impaired growth in CRD is complex and still not fully understood. The following complications are: anorexia, malnutrition, inflammation, decreased residual renal function, dialysis frequency and adequacy, renal anemia, metabolic acidosis, fluid/electrolyte imbalance, renal osteodistrophy, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) resistance. Malnutrition is most frequent and most important factor contributing to the degree of growth retardation in infancy. The degree of renal dysfunction is the major determinant of variability in growth from third year of age until puberty onset, while in puberty hypergonadotropic hypogonadism has negative effect. The main factors that influence growth after renal transplantation are the age of the recipient and glucocorticoid drugs dosage with negative effect and allograft function with positive effect. In order to improve growth in children with CRD it is necessary to include: diet with optimal caloric intake, correction of fluid/ electrolyte imbalance, correction of acidosis, renal osteodistrophy and anemia. If growth velocity is insufficient to normalize growth, it is necessary to start recombinant human GH (rhGH) therapy at 0.05 mg/kg per day (0.35 mg/kg per week or 28 IU/m2 per week) administered by subcutaneous injection.

  14. Gitelman′s syndrome: Rare presentation with growth retardation

    Directory of Open Access Journals (Sweden)

    A Gaur

    2014-01-01

    Full Text Available Gitelman′s syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypokalemia, hypomagnesaemia, hypocalciuria, hyperreninemia and without hypertension. Gitelman′s syndrome is caused by mutations of the SLC12A3 gene, which encodes the Na/Cl co-transporter (NCCT in the distal convoluted tubule. Majority of cases manifest during adolescence or adulthood and growth retardation is not the common feature. We report a rare presentation of Gitelman′s syndrome in a four-year-old boy with growth retardation.

  15. Growth Retardation in Children with Kidney Disease

    Directory of Open Access Journals (Sweden)

    Paulina Salas

    2013-01-01

    Full Text Available Growth failure is almost inextricably linked with chronic kidney disease (CKD and end-stage renal disease (ESRD. Growth failure in CKD has been associated with both increased morbidity and mortality. Growth failure in the setting of kidney disease is multifactorial and is related to poor nutritional status as well as comorbidities, such as anemia, bone and mineral disorders, and alterations in hormonal responses, as well as to aspects of treatment such as steroid exposure. This review covers updated management of growth failure in these children including adequate nutrition, treatment of metabolic alterations, and early administration of recombinant human growth hormone (GH.

  16. Psychomotor retardation in a girl with complete growth hormone deficiency.

    Science.gov (United States)

    Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

    2013-01-01

    Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

  17. Growth Retardation in Children with Kidney Disease

    OpenAIRE

    Salas, Paulina; Pinto, Viola; Rodriguez, Josefina; Zambrano, Maria Jose; Mericq, Veronica

    2013-01-01

    Growth failure is almost inextricably linked with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Growth failure in CKD has been associated with both increased morbidity and mortality. Growth failure in the setting of kidney disease is multifactorial and is related to poor nutritional status as well as comorbidities, such as anemia, bone and mineral disorders, and alterations in hormonal responses, as well as to aspects of treatment such as steroid exposure. This review c...

  18. Demonstration of scattering suppression in retardation-based plasmonic nanoantennas

    DEFF Research Database (Denmark)

    Nielsen, M.G.; Pors, A.; Nielsen, Rasmus Bundgaard

    2010-01-01

    of counter-propagating short-range surface plasmon polaritons (SR-SPP) and that the transformation of nanorods into split-rings by bending significantly influences the scattering strength. Importantly, strong suppression of scattering for the fundamental SR-SPP resonance is observed when the bend radius...

  19. GROWTH RETARDANTS: Effects on Gibberellin Biosynthesis and Other Metabolic Pathways.

    Science.gov (United States)

    Rademacher, Wilhelm

    2000-06-01

    Plant growth retardants are applied in agronomic and horticultural crops to reduce unwanted longitudinal shoot growth without lowering plant productivity. Most growth retardants act by inhibiting gibberellin (GA) biosynthesis. To date, four different types of such inhibitors are known: (a) Onium compounds, such as chlormequat chloride, mepiquat chloride, chlorphonium, and AMO-1618, which block the cyclases copalyl-diphosphate synthase and ent-kaurene synthase involved in the early steps of GA metabolism. (b) Compounds with an N-containing heterocycle, e.g. ancymidol, flurprimidol, tetcyclacis, paclobutrazol, uniconazole-P, and inabenfide. These retardants block cytochrome P450-dependent monooxygenases, thereby inhibiting oxidation of ent-kaurene into ent-kaurenoic acid. (c) Structural mimics of 2-oxoglutaric acid, which is the co-substrate of dioxygenases that catalyze late steps of GA formation. Acylcyclohexanediones, e.g. prohexadione-Ca and trinexapac-ethyl and daminozide, block particularly 3ss-hydroxylation, thereby inhibiting the formation of highly active GAs from inactive precursors, and (d) 16,17-Dihydro-GA5 and related structures act most likely by mimicking the GA precursor substrate of the same dioxygenases. Enzymes, similar to the ones involved in GA biosynthesis, are also of importance in the formation of abscisic acid, ethylene, sterols, flavonoids, and other plant constituents. Changes in the levels of these compounds found after treatment with growth retardants can mostly be explained by side activities on such enzymes.

  20. Fatigue crack growth retardation in spot heated mild steel sheet

    Indian Academy of Sciences (India)

    Unknown

    Abstract. A fatigue crack can be effectively retarded by heating a spot near the crack tip under nil remote stress condition. The subcritical spot heating at a proper position modifies the crack growth behaviour in a way, more or less, similar to specimen subjected to overload spike. It is observed that the extent of crack.

  1. Retardation of muscle growth in castrated male mice: further ...

    African Journals Online (AJOL)

    Retardation of muscle growth in castrated male mice was studied as an evidence for the influence of hormones on the development of muscle mass. Male albino mice were castrated at 28days of age by open castration method. The weights and the muscle mass indices (mg muscle weight per gram body weight) of the ...

  2. Growth patterns in children with intrauterine growth retardation and their correlation to neurocognitive development.

    Science.gov (United States)

    Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Leitner, Yael; Geva, Ronny; Eshel, Rina; Harel, Shaul

    2009-07-01

    The relationship between somatic growth and neurocognitive outcome was studied in a cohort of 136 children with intrauterine growth retardation. The children were followed up from birth to 9 to 10 years of age by annual measurements of growth parameters, neurodevelopmental evaluations, and IQ. The rate of catch-up for height between 1 and 2 years of age was significantly higher than the catch-up for weight (P importance for prediction of subsequent neurodevelopmental outcome in children with intrauterine growth retardation.

  3. Final height and intrauterine growth retardation.

    Science.gov (United States)

    Tauber, Maïthé

    2017-06-01

    Approximately 10% of small for gestational age (SGA) children maintain a small body size throughout childhood and often into adult life with a decreased pubertal spurt. Growth hormone (GH) therapy increases short-term growth in a dose-dependent manner and adult height had now been well documented. Shorter children might benefit from a higher dose at start (50μg/kg/day). The response to GH treatment was similar for both preterm and term short SGA groups and the effect of GH treatment on adult height showed a wide variation in growth response. As a whole, mean adult height is higher than -2 SDS in 60% of patients and 70% reached an adult height in their target height with better results with higher doses and combined GnRH analog therapy in those who were short at onset of puberty. Copyright © 2017. Published by Elsevier Masson SAS.

  4. A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation

    NARCIS (Netherlands)

    G.A. Kamp; D. Mul (Dick); J.J.J. Waelkens (Johan); M. Jansen (Maarten); H.A. Delemarre-van de Waal (Henriette); L. Verhoeven-Wind; M. Frölich (Marijke); W. Oostdijk (Wilma); J.M. Wit (Jan)

    2001-01-01

    textabstractWe assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and

  5. Obstetric interventions and perinatal asphyxia in growth retarded term infants

    DEFF Research Database (Denmark)

    Langhoff-Roos, J; Lindmark, G

    1997-01-01

    neonatal outcome at term have been studied in relation to different types of fetal growth retardation, including sub-groups with low ponderal index or low amount of subcutaneous fat. RESULTS: The need for obstetric intervention indicated by suspected fetal asphyxia before or during labor was increased 3......BACKGROUND: The monitoring of fetal growth during pregnancy is usually justified because of the increased perinatal risk of these babies. METHODS: In 1552 infants from the Scandinavian Small for Gestational Age Study the need for obstetric interventions, risk of fetal asphyxia and immediate...

  6. Prognosis and risk factors for intrauterine growth retardation

    DEFF Research Database (Denmark)

    Sehested, Line Thousig; Pedersen, Pernille

    2014-01-01

    INTRODUCTION: Intrauterine growth retardation (IUGR) is the term describing a foetus that has not reached its genetic growth potential. There is no international consensus on the definition of IUGR. The aim of this study was to describe a cohort of weight-restricted neonates and their mothers...... factors and neonatal growth and outcome at six weeks, five months and 12 months of age were collected. RESULTS: A total of 73 neonates and their mothers were included. Caesarean delivery was given in 78% of the cases. Maternal risk factors included gestational hypertension (33%), smoking (24......%) and placental infarction (17%). Hypoglycaemic episodes developed in 31% of the neonates. At 12 months, 90% had caught up growth and 7% had a neurologically poor outcome. No infants died. CONCLUSION: Maternal smoking and gestational hypertension are important risk factors for the development of IUGR. Special...

  7. Growth hormone treatment in growth-retarded adolescents after renal transplant

    NARCIS (Netherlands)

    Hokken-Koelega, A. C.; Stijnen, T.; de Ridder, M. A.; de Muinck Keizer-Schrama, S. M.; Wolff, E. D.; de Jong, M. C.; Donckerwolcke, R. A.; Groothoff, J. W.; Blum, W. F.; Drop, S. L.

    1994-01-01

    Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15.6, range 11.3-19.5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone,

  8. A novel reutilization method for waste printed circuit boards as flame retardant and smoke suppressant for poly (vinyl chloride)

    Energy Technology Data Exchange (ETDEWEB)

    Xiu, Fu-Rong, E-mail: xiu_chem@hotmail.com [College of Ecological Environment and Urban Construction, Fujian University of Technology, Fuzhou 350108 (China); Weng, Huiwei; Qi, Yingying; Yu, Gending; Zhang, Zhigang [College of Ecological Environment and Urban Construction, Fujian University of Technology, Fuzhou 350108 (China); Zhang, Fu-Shen [Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

    2016-09-05

    Highlights: • We report a novel electronic waste-based flame retardant for PVC. • The SCWO-treated PCBs significantly improves the flame retardancy of PVC. • The flame retardant mechanism of SCWO-treated PCBs was studied. • Appropriate amount flame retardant does not degrade the mechanical property of PVC. - Abstract: In this study, a novel reutilization method for waste printed circuit boards (PCBs) as flame retardant and smoke suppressant for poly (vinyl chloride) (PVC) was successfully testified. A supercritical water oxidation (SCWO) process was applied to treat waste PCBs before they could be used as flame retardants of PVC. The results indicated that SCWO conditions had a significant effect on the flame retarding and smoke suppressing properties of waste PCBs for PVC. Cu{sub 2}O, CuO, and SnO{sub 2} were the main active ingredients in waste PCBs-derived flame retardants. A conversion of Cu elements (Cu{sup 0} → Cu{sup +} → Cu{sup 2+}) during SCWO process with the increase of reaction temperature was found to be the key influence factor for the flame retarding properties of SCWO-treated PCBs. The experiment results also showed that there was a synergistic effect of flame retardancy between Cu{sup +} and Cu{sup 2+}. After the optimized SCWO treatment, SCWO-treated PCBs significantly improved the flame retardancy and smoke suppression of PVC. Limiting oxygen index (LOI) and char yield (CY) increased with increasing SCWO-treated PCBs content in PVC, while smoke density rating (SDR) and maximum smoke density (MSD) decreased markedly. The mechanical properties of PVC samples were influenced in different degree by adding different content SCWO-treated PCBs.

  9. Growth hormone treatment in children with rheumatic disease, corticosteroid induced growth retardation, and osteopenia

    NARCIS (Netherlands)

    F.K. Grote (Floor); L.W.A. van Suijlekom-Smit (Lisette); D. Mul (Dick); W.C.J. Hop (Wim); R. ten Cate (Rebecca); W. Oostdijk (Wilma); W.H.J. van Luijk (Wilma); C.J.A. Jansen-Van Wijngaarden (C. J A); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    2006-01-01

    textabstractBackground: In children with severe rheumatic disease (RD), treatment with corticosteroids (CS) is frequently needed and growth retardation and osteopenia may develop. A beneficial effect of human growth hormone (hGH) has been reported but mostly in trials without a control group. Aims:

  10. Growth hormone treatment in children with rheumatic disease, corticosteroid induced growth retardation, and osteopenia

    NARCIS (Netherlands)

    Grote, FK; van Suijlekom-Smit, LWA; Mul, D; Hop, WCJ; ten Cate, R; Oostdijk, W; Van Luijk, W; Jansen-van Wijngaarden, CJA; Keizer-Schrama, SMPFD

    Background: In children with severe rheumatic disease (RD), treatment with corticosteroids (CS) is frequently needed and growth retardation and osteopenia may develop. A beneficial effect of human growth hormone (hGH) has been reported but mostly in trials without a control group. Aims: To study the

  11. Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

    OpenAIRE

    Farthing, M J; Campbell, C A; Walker-Smith, J; Edwards, C R; Rees, L H; Dawson, A M

    1981-01-01

    Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five p...

  12. Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation.

    Science.gov (United States)

    Troib, Ariel; Landau, Daniel; Kachko, Leonid; Rabkin, Ralph; Segev, Yael

    2013-11-01

    Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

  13. Effect of the growth retardant Cycocel® in controlling the growth of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-07-19

    Jul 19, 2010 ... Hydroponic culture of Gladiolus tristis: Application of paclobutrazol for flowering and height control. Afr. J. Biotechnol. 7(3): 239-243. Ninnemann H, Zeevaart JAD, Kende H, Lang A (1964). The plant growth retardant CCC as an inhibitor of gibberellin biosynthesis in. Fusarium moniliforme. Planta (Bert.) ...

  14. School performance and behaviour in extremely preterm growth-retarded infants

    NARCIS (Netherlands)

    Schaap, A. H.; Wolf, H.; Bruinse, H. W.; Smolders-de Haas, H.; van Ertbruggen, I.; Treffers, P. E.

    1999-01-01

    OBJECTIVE: To describe school performance and behaviour of extremely preterm, growth-retarded infants. DESIGN: Cohort study at two tertiary care centres. Included were all surviving, singleton infants (N= 127) with fetal growth retardation due to placental insufficiency. All were delivered by

  15. Flame-retardant-wrapped polyphosphazene nanotubes: A novel strategy for enhancing the flame retardancy and smoke toxicity suppression of epoxy resins.

    Science.gov (United States)

    Qiu, Shuilai; Wang, Xin; Yu, Bin; Feng, Xiaming; Mu, Xiaowei; Yuen, Richard K K; Hu, Yuan

    2017-03-05

    The structure of polyphosphazene nanotubes (PZS) is similar to that of carbon nanotubes (CNTs) before modification. For applications of CNTs in polymer composites, surface wrapping is an economically attractive route to achieve functionalized nanotubes. Based on this idea, functionalized polyphosphazene nanotubes (FR@PZS) wrapped with a cross-linked DOPO-based flame retardant (FR) were synthesized via one-step strategy and well characterized. Then, the obtained FR@PZS was introduced into epoxy resin (EP) to investigate flame retardancy and smoke toxicity suppression performance. Thermogravimetric analysis indicated that FR@PZS significantly enhanced the thermal stability of EP composites. Cone calorimeter results revealed that incorporation of FR@PZS obviously improved flame retardant performance of EP, for example, 46.0% decrease in peak heat release rate and 27.1% reduction in total heat release were observed in the case of epoxy composite with 3wt% FR@PZS. The evolution of toxic CO and other volatile products from the EP decomposition was significantly suppressed after the introduction of FR@PZS, Therefore, the smoke toxicity associates with burning EP was reduced. The presence of both PZS and a DOPO-based flame retardant was probably responsible for this substantial diminishment of fire hazard. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Abnormal Grain Growth Suppression in Aluminum Alloys

    Science.gov (United States)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  17. Renal artery pulsatility index and renal volume: Normal fetuses versus growth-retarded fetuses

    International Nuclear Information System (INIS)

    Lee, Kyung Soon; Woo, Bock Hi

    2001-01-01

    To evaluate the blood flow velocity waveform of the renal artery and renal volume of growth-retarded fetuses and to compare them with those of normal fetuses. Pulsatility index of the renal artery and renal volume measured by three-dimensional ultrasonography were obtained from seventy eight normal fetuses at the gestational age from twenty five to thirty nine weeks and eighteen intrauterine growth retarded fetuses whose weight was below ten percentile at birth. We studied changes of the pulsatility index of the renal artery and renal volume according to the gestational age and compared with those of growth-retarded fetuses. Pulsatility index (PI) of the fetal renal artery decreased throughout the gestational period (r=0.703, p<0.0001). In growth-retarded fetuses, despite of abnormal doppler velocity waveform of the middle cerebral artery, which was showing fetal hypoxia, the renal PI was not increased significantly. The fetal renal volume increased throughout the gestational period (r=0.834, p<0.0001) whereas in growth-retarded fetuses, all renal volume was below fifth percentile of normal fetuses. In growth-retarded fetuses, fetal renal volume was decreased significantly without change of the renal vascular flow. Therefore, the fetal renal volume measured by three-dimensional ultrasonography may be a helpful parameter in the diagnosis of growth-retarded fetuses.

  18. Influence of Plant Growth Retardants on Quality of Codonopsis Radix

    Directory of Open Access Journals (Sweden)

    Yinyin Liao

    2017-10-01

    Full Text Available Plant growth retardant (PGR refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous Chinese traditional herb. However, it is still unclear whether PGR affects the medicinal quality of C. Radix. In the present study, amino acid analyses, targeted and non-targeted analyses by ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS and gas chromatography-MS were used to analyze and compare the composition of untreated C. Radix and C. Radix treated with PGR. The contents of two key bioactive compounds, lobetyolin and atractylenolide III, were not affected by PGR treatment. The amounts of polysaccharides and some internal volatiles were significantly decreased by PGR treatment; while the free amino acids content was generally increased. Fifteen metabolites whose abundance were affected by PGR treatment were identified by UPLC-TOF-MS. Five of the up-regulated compounds have been reported to show immune activity, which might contribute to the healing efficacy (“buqi” of C. Radix. The results of this study showed that treatment of C. Radix with PGR during cultivation has economic benefits and affected some main bioactive compounds in C. Radix.

  19. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  20. Neonatal cardiovascular system adaptation in babies with intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    I. N. Petrova

    2016-01-01

    Full Text Available Objective: to reveal the adaptive features of the cardiovascular system in newborn infants with intrauterine growth retardation (IUGR on the basis of a clinical instrumental study.Subjects and methods. A study group included 100 newborn infants with IUGR; a control group consisted of 40 babies with normal anthropometric measurements at birth. Medical history and clinical data and electrocardiographic and echocardiographic findings were analyzed.Results. All the examinees with IUGR had manifestations of cardiovascular system dysadaptation. There was a high rate of electrocardiographic changes, such as cardiac arrhythmias; low voltage; systolic overload of the right heart and left ventricle; signs of ventricular hypertrophy; and transient myocardial ischemia. The specific features of cardiac hemodynamics were decreased sizes of the left ventricle, lower parameters of its systolic function, and longer functioning of fetal communications.Conclusion. IUGR is associated with the development of cardiovascular system dysadaptation syndrome, which is due to prior perinatal hypoxia. The findings necessitate a follow-up of children by involving a cardiologist.

  1. Severe linear growth retardation in rural Zambian children: the influence of biological variables.

    NARCIS (Netherlands)

    Hautvast, J.L.A.; Tolboom, J.J.M.; Kaftwembe, E.M.; Musonda, R.M.; Mwanakasale, V.; Staveren, W.A. van; Hof, M.A. van 't; Sauerwein, R.W.; Willems, J.L.; Monnens, L.A.H.

    2000-01-01

    BACKGROUND: The prevalence of stunting in preschool children in Zambia is high; stunting has detrimental effects on concurrent psychomotor development and later working capacity. OBJECTIVE: Our objective was to investigate biological variables that may contribute to linear growth retardation in

  2. Global transcriptome profiles of Italian Mediterranean buffalo embryos with normal and retarded growth.

    Directory of Open Access Journals (Sweden)

    Maria Strazzullo

    Full Text Available The transcriptome profiles were compared for buffalo embryos with normal growth and embryos with retarded growth on Day 25 after mating. Embryos with retarded growth on Day 25 after mating have a reduced likelihood of undergoing attachment to the uterine endometrium and establishing a pregnancy. Italian Mediterranean buffaloes were mated by AI and on Day 25 underwent trans-rectal ultrasonography to ascertain embryo development. Embryos with an embryonic width (EW>2.7 mm were classed as normal embryos and embryos with an EW<2.7 mm were classed as retarded embryos. Three buffaloes with embryos of the largest EW (3.7, 3.7 and 3.9 mm and three buffaloes with embryos of the smallest EW (1.5, 1.6 and 1.9 mm were slaughtered on Day 27 to recover embryos for transcriptome analysis using a bovine custom designed oligo array. A total of 1,047 transcripts were differentially expressed between embryos with normal growth and embryos with retarded growth. Retarded embryos showed 773/1,047 (74% transcripts that were down-regulated and 274/1,047 (26% transcripts that were up-regulated relative to normal embryos; in silico analyses focused on 680/1,047 (65% of the differentially expressed transcripts. The most altered transcripts observed in retarded embryos were associated with membrane structure and function and with metabolic and homeostasis maintenance functions. Other notable functions altered in retarded embryos were developmental processes and in particular nervous system differentiation and function. Specific biochemical pathways such as the complement cascade and coagulation were also altered in retarded embryos. It was concluded from the findings that buffalo embryos with retarded growth on Day 25 after mating show altered gene expression compared with normal embryos, and some de-regulated functions are associated with attachment to the uterine endometrium.

  3. Void growth suppression by dislocation impurity atmospheres

    International Nuclear Information System (INIS)

    Weertman, J.; Green, W.V.

    1976-01-01

    A detailed calculation is given of the effect of an impurity atmosphere on void growth under irradiation damage conditions. Norris has proposed that such an atmosphere can suppress void growth. The hydrostatic stress field of a dislocation that is surrounded by an impurity atmosphere was found and used to calculate the change in the effective radius of a dislocation line as a sink for interstitials and vacancies. The calculation of the impurity concentration in a Cottrell cloud takes into account the change in hydrostatic pressure produced by the presence of the cloud itself. It is found that void growth is eliminated whenever dislocations are surrounded by a condensed atmosphere of either oversized substitutional impurity atoms or interstitial impurity atoms. A condensed atmosphere will form whenever the average impurity concentration is larger than a critical concentration

  4. Amplitude of pubertal growth in short stature children with intrauterine growth retardation.

    Science.gov (United States)

    Lienhardt, Anne; Carel, Jean-Claude; Preux, Pierre-Marie; Coutant, Régis; Chaussain, Jean-Louis

    2002-01-01

    Pubertal growth contributes to 15-18% of adult height. A blunted pubertal peak could contribute to short adult height in short children born with intrauterine growth retardation (IUGR). Pubertal growth, from onset of puberty to final height, was investigated in 75 short IUGR children: 47 were treated with recombinant human growth hormone (GH) (tx) before pubertal onset (mean dose: 0.4 IU/kg/week); 28 were not treated (no-tx). They were compared with 98 normal children. Puberty occurred later in IUGR children than in controls (boys 14.2 +/- 1 years vs. 12.1 +/- 0.8 years; girls 12 +/- 1 years vs. 11.2 +/- 0.8 years; p pubertal spurt, a finding that should be further evaluated in clinical trials. Copyright 2002 S. Karger AG, Basel

  5. Plant-made trastuzumab (herceptin inhibits HER2/Neu+ cell proliferation and retards tumor growth.

    Directory of Open Access Journals (Sweden)

    Tatiana V Komarova

    Full Text Available BACKGROUND: Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb, trastuzumab (Herceptin. A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells. METHODOLOGY/PRINCIPAL FINDINGS: We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells. CONCLUSIONS/SIGNIFICANCE: We conclude that PMT is active in suppression of cell proliferation and tumor growth.

  6. Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.

    Science.gov (United States)

    Kliegman, R M

    1989-03-01

    Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.

  7. Comparison between Urinary Oestrogen Assay and Serial Ultrasonic Cephalometry in Assessment of Fetal Growth Retardation

    Science.gov (United States)

    Campbell, Stuart; Kurjak, Asim

    1972-01-01

    Urinary oestrogen assay and serial ultrasonic cephalometry were performed on 284 patients who were considered on clinical grounds to be at risk of having a growth-retarded fetus. It was found that ultrasonic cephalometry was significantly better than oestrogens in diagnosing the small-for-dates baby, but that there was no significant difference between the two methods in predicting perinatal asphyxia. Of the 14 stillbirths, three were in the normal ultrasonic growth rate group and five had normal oestrogen excretion. Both methods were found to be of value in the diagnosis of fetal growth-retardation, although cephalometry would seem to have some advantages, especially in distinguishing between fetal growth-retardation and mistaken maturity. PMID:4673993

  8. Language development in preschool children born after asymmetrical intrauterine growth retardation.

    Science.gov (United States)

    Simić Klarić, Andrea; Kolundžić, Zdravko; Galić, Slavka; Mejaški Bošnjak, Vlatka

    2012-03-01

    After intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions. The assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation. Examinees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed. There were statistically significant differences (p language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference - head circumference at birth)/(Body weight - birth weight)] and language outcome. Children with neonatal complications had lower results (p language comprehension and total expressive language. Intrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. The influence of growth retardants and cytokinins on flowering of ornamental plants

    Directory of Open Access Journals (Sweden)

    Anna Pobudkiewicz

    2012-12-01

    Full Text Available Growth retardants are applied in order to obtain short and well compact plants. They usually inhibit stem elongation, but also can influence the flowering of plants. The aim of cytokinin application is to obtain well branched plants without removing the apical meristem. Cytokinins usually increase the number of axillary shoots but also can influence flowering. Growth retardants and cytokinins can affect flower size, pedicel length, number of flowers, flower longevity, abortion of flower buds and number of days from potting plants to the first open flower. Flowering of growth retardant and cytokinin treated plants might depend on the method of growth regulator used (foliar spray or soil drench, plant species or even a plant cultivar, but in the highest degree it depends on the growth regulator rate used. These growth regulators, when are applied at rates appropriate for height and habit control, very seldom influence flowering of ornamental plants, but applied at high rates can delay flowering, diminish flower diameter or flower pedicel length and also can decrease the number of flowers per plant. In cultivation of bulb plants, growth retardants, used at very high rates, also cause abortion of flower buds.

  10. Growth retardation and functional disability in patients with juvenile idiopathic arthritis

    International Nuclear Information System (INIS)

    Saeed, S.; Zammurrad, S.; Rasheed, U.

    2017-01-01

    To determine the frequency of growth retardation and functional disability in patients with juvenile idiopathic arthritis (JIA). Methods: This descriptive cross sectional study was carried out at the Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad from March 2016 to December 2016. 92 patients with JIA were included in the study. Height and weight of each patient was recorded and BMI calculated. Functional Disability was determined by calculating the CHAQ Score, while disease activity was estimated through JADAS 27 score. Growth Retardation was defined as height, weight and/or BMI below the 3rd centile according to the CDC growth charts. A cut off of ?1 for CHAQ Score was used to define severe functional disability. Results: Out of 92 patients, there were 47 male (51.1%) and 45 (48.9%) females. Height, weight and BMI below 3rd centile was observed in 30(32.6%), 49(53.3%) and 41(44.6%) patients, respectively. The overall frequency of growth retardation was 64.1% (n=59) and severe functional disability (CHAQ Score ?1) was seen in 32.6% (n=30) of patients. Conclusions: Growth retardation was seen in more than half of patients with JIA and a significant proportion had severe functional disability. Severe functional disability was seen only in patients with active disease. (author)

  11. An autosomal recessive disorder with retardation of growth, mental deficiency, ptosis, pectus excavatum and camptodactyly

    International Nuclear Information System (INIS)

    Khaldi, F.; Bennaceur, B.; Hammou, A.; Hamza, M.; Gharbi, H.A.

    1988-01-01

    Two strikingly similar brothers issued from consanguineous parents in the second degree present the following patterns of anomalies: Retardation of growth, mental deficiency, ocular abnormalities, pectus excavatum and camptodactyly. The ocular abnormalities include ptosis, microphthalmia and hypertelorism. No endocrine or metabolic aberrations are found. The authors conclude that the disorder has probably an autosomal recessive mode of transmission. (orig.)

  12. CONTINUOUS MATERNAL HYPEROXYGENATION IN THE TREATMENT OF EARLY FETAL GROWTH-RETARDATION

    NARCIS (Netherlands)

    RIBBERT, LSM; VANLINGEN, RA; VISSER, GHA

    Continuous maternal hyperoxygenation treatment (2.5 l/min by means of a nasopharyngeal cannula) was given in four patients presenting with intrauterine growth-retarded (IUGR) fetuses and decelerative fetal heart rate (FHR) patterns at 27-28 weeks of gestation. The effect of maternal hyperoxia was

  13. Cardiac and extra-cardiac flow velocity waveforms in the growth-retarded human fetus

    NARCIS (Netherlands)

    I.A.L. Groenenberg (Irene)

    1991-01-01

    textabstractThe central theme in this thesis is the documentation of Doppler flow velocity waveforms in a number of cardiac and extra-cardiac arterial vessels with emphasis on changes in the flow velocity waveforms relative to intrauterine growth retardation and fetal and neonatal condition. The

  14. Superior flame retardancy and smoke suppression of epoxy-based composites with phosphorus/nitrogen co-doped graphene.

    Science.gov (United States)

    Feng, Yuezhan; He, Chengen; Wen, Yingfeng; Ye, Yunsheng; Zhou, Xingping; Xie, Xiaolin; Mai, Yiu-Wing

    2018-03-15

    Phosphorus and/or nitrogen doping is an effective method of improving the physical and chemical properties of reduced graphene oxide (rGO). In this work, phosphorus and nitrogen co-doped rGO (PN-rGO), synthesized using a scalable hydrothermal and microwave process, was used as an additive to improve the flame retardancy of epoxy resin (EP) for the first time. Chemical structure and morphology characterization confirmed that the nitrogen and phosphorus atoms were doped into the graphite lattice adopting pyrrolic-N, pyridinic-N, quaternary-N and pyrophosphate and metaphosphate forms. Doping increased the oxidization resistance of rGO and the thermal-oxidative stability of its composites' char, while also improving the catalytic charring ability of polymer. Both effects resulted in the formation of a stable char protective layer during burning and to a significant improvement in flame retardation and smoke suppression in the final composites. The peak heat release rate (PHRR), total heat release (THR) and total smoke production (TSP) for the EP-based composite (containing 5 wt% PN-rGO) decreased by 30.9%, 29.3% and 51.3%, respectively, compared to neat EP. Our work has produced a promising graphene-based flame retardant additive for the mass production of high-performance composites, also expended the application of heteroatom-doped graphene. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. [Definitions: small for gestational age and intrauterine growth retardation].

    Science.gov (United States)

    Ego, A

    2013-12-01

    Screening for intrauterine growth restriction (IUGR) is a major component of antenatal care, but the debate about the choice of birthweight standards is longstanding. The objective of this first chapter is to provide guidelines about optimal definition of IUGR. Literature review about available birthweight curves to define IUGR, including the analysis of their diagnosis accuracy and their relevance to identify babies at risk of poor perinatal outcomes. Intrauterine growth curves are more suitable for "normal" growth modeling than birth weight curves, and fetal growth is influenced by individual characteristics, fetal gender being the most important among them (EL2). Infants with a low birth weight are either constitutionally small babies or babies with pathological fetal growth failure. Use of "SGA" for all Small for Gestational Age infants is now recommended, "IUGR" being appropriate only for infants with pathological growth restriction (Professional consensus). Depending on reference curves, identified SGA babies and pregnancy outcomes may be different. Customized birth weight standards are based on an intrauterine growth modeling adjusted for fetal gender, maternal height, weight and parity, and appear to be the most accurate to identify SGA births at risk (EL3). However, their benefit on perinatal morbidity and mortality has not been demonstrated by prospective studies. Benefits and drawbacks of customized birth weight curves seem in favor of their use. Their application in ante and postnatal investigations is a real opportunity to standardize clinical practice and make information provided to parents more consistent. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Umbilical vessel wall fatty acids after normal and retarded fetal growth.

    OpenAIRE

    Felton, C V; Chang, T C; Crook, D; Marsh, M; Robson, S C; Spencer, J A

    1994-01-01

    In a prospective observational study, the fatty acid content of human umbilical artery and vein wall phospholipids was determined in fetuses classified according to their change in abdominal circumference during the third trimester. Three groups were identified: appropriate for gestational age (AGA; 24 infants) and small for gestational age (SGA; 38 infants) with normal antenatal growth rate, and SGA with fetal growth retardation (22 infants). The venous linoleic acid (18:2 omega 6) content (...

  17. by recycled subirrigational supply of plant growth retardants

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-16

    May 16, 2008 ... seeds were sawed in 288-cell plug tray and subirrigated with nutrient solution mixed by six different concentrations of paclo- butrazol or uniconazole. After five ... of recirculation and used to culture the radish plants. After five days, the length of hypocotyle was measured and compared to the standard growth ...

  18. Prognosis and risk factors for intrauterine growth retardation

    DEFF Research Database (Denmark)

    Sehested, Line Thousig; Pedersen, Pernille

    2014-01-01

    focusing on risk factors, catch up and neonatal outcome. MATERIAL AND METHODS: This was a retrospective descriptive study of IUGR neonates with a birth weight below 70% of the expected whose mothers were admitted to the Neonatal Ward at Hvidovre Hospital during 2007-2009. Obstetrical and maternal risk...... factors and neonatal growth and outcome at six weeks, five months and 12 months of age were collected. RESULTS: A total of 73 neonates and their mothers were included. Caesarean delivery was given in 78% of the cases. Maternal risk factors included gestational hypertension (33%), smoking (24......%) and placental infarction (17%). Hypoglycaemic episodes developed in 31% of the neonates. At 12 months, 90% had caught up growth and 7% had a neurologically poor outcome. No infants died. CONCLUSION: Maternal smoking and gestational hypertension are important risk factors for the development of IUGR. Special...

  19. Changes in GH/IGF-1 axis in intrauterine growth retardation: consequences of fetal programming?

    Science.gov (United States)

    Setia, S; Sridhar, M G

    2009-11-01

    Fetal growth is a complex process that depends on the genotype and epigenotype of the fetus, maternal nutrition, the availability of nutrients and oxygen to the fetus, intrauterine insults, and a variety of growth factors and proteins of maternal and fetal/placental origin. In the fetus, growth hormone (GH) plays little or no role in regulating fetal growth, and insulin-like growth factors (IGFs) control growth directly independent of fetal GH secretion. Placental growth hormone (PGH) is the prime regulator of maternal serum IGF-1 during pregnancy. Total as well as free PGH and IGFs are significantly lower in pregnancies with intrauterine growth retardation (IUGR). The GH/IGF axis is significantly affected by intrauterine growth retardation and some of these alterations may lead to permanent pathological programming of the IGF axis. Alterations in the IGF axis may play a role in the future occurrence of insulin resistance and hypertension. In this review we focus on the regulation of fetal growth and the role of fetal programming in the late consequences of a poor fetal environment reflected in IUGR.

  20. Growth retardation in artistic compared with rhythmic elite female gymnasts.

    Science.gov (United States)

    Georgopoulos, Neoklis A; Markou, Kostas B; Theodoropoulou, Anastasia; Benardot, Dan; Leglise, Michel; Vagenakis, Apostolos G

    2002-07-01

    We studied 129 female rhythmic gymnasts (RG) and 142 female artistic gymnasts (AG) who participated in the 1999 Gymnastics World Championship for RG in Osaka, Japan, and the 1999 and 2001 Gymnastics World Championships for AG in Tianjin, China (n = 48), and Ghent, Belgium (n = 94), respectively. RG were taller than average, with a mean height SD score above the 50th percentile, whereas AG were relatively short, with a mean height SD score below the 50th percentile. Both RG and AG followed their respective reported target height SD score, which was above the 50th percentile for the RG and below the 50th percentile for the AG. The RG followed a growth pattern that was higher than their reported target height, whereas AG exhibited a negative growth pattern. RG and AG weighed less than the population mean, with the mean weight for age below the 50th percentile for both groups. RG were taller than AG (t = 17.15; P < 0.001), with a higher reported target height SD score (t = 6.44; P < 0.001), a greater Delta height-reported target height (t = 2.74; P < 0.001), and a lower mean body fat (t = -11.83; P < 0.001) and body mass index (t = -10.73; P < 0.001) than AG. AG started their training at an earlier age than RG (t = 4.13; P < 0.001). Using multiple regression analysis, actual height SD score was independently influenced positively by weight SD score for both RG (b = 0.421; t = 4.317; P < 0.001) and AG (b = 1.404; t = 16.514; P = <0.001), and by reported target height only for RG (b = 0.299; t = 3.139; P = 0.002), and negatively by body mass index only for AG (b = -0.80; t = -9.88; P < 0.001). In conclusion, in elite female AG, a deterioration of growth potential was observed, whereas in RG the genetic predisposition to growth was preserved.

  1. A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

    Science.gov (United States)

    Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

    2015-04-01

    Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

  2. Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep.

    Science.gov (United States)

    Manikkam, Mohan; Crespi, Erica J; Doop, Douglas D; Herkimer, Carol; Lee, James S; Yu, Sunkyung; Brown, Morton B; Foster, Douglas L; Padmanabhan, Vasantha

    2004-02-01

    Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

  3. Alterations of growth, blood biochemical components and hormone profiles by intensified nutrition in growth retarded Japanese Black cattle.

    Science.gov (United States)

    Watanabe, Daisaku; Ikeda, Hiroki; Kazamatsuri, Hiroyuki; Ando, Takaaki; Ohtsuka, Hiromichi; Kobayashi, Shigeki; Oikawa, Masaaki; Sugimoto, Yoshikazu

    2010-09-01

    In order to determine the clinical conditions of Japanese Black (JB) cattle with growth retardation, we determined the changes of body growth, blood profiles of metabolism and hormones caused by intensified nutrition (sufficient total digestible nutrients and digestible crude protein for a target daily gain set at 1.2-1.3 kg/day) in three cattle. The daily gain (DG) was increased during the intensified period (Intense) compared with the preparation period (Pre), but the DG in the Intense period was 36-66% of the target DG. Serum albumin, total cholesterol, insulin and IGF-1 increased during the Intense period compared with the Pre period. Serum GH showed high levels in the Pre period, whereas it showed lower levels in the Intense period. These results suggested that the present growth retarded cattle had abnormalities in their metabolic systems and lacked nutrient absorption.

  4. THE COURSE OF THE EARLY NEONATAL PERIOD OF LIFE IN NEWBORNS WITH INTRAUTERINE GROWTH RETARDATION

    Directory of Open Access Journals (Sweden)

    L. V. Kozlova

    2017-01-01

    Full Text Available Based on the complex clinical and anamnestic, laboratory, instrumental examination, a number of aspects of the health status of children born in the outcome of physiologically occurring and complicated pregnancies in practically healthy mothers (including delayed development of the fetus and without it, as well as in mothers with aggravated somatic and gynecological anamnesis. The intrauterine growth retardation was associated with cerebral ischaemia of I-II degrees of severity, toxic erythema, polycythemia, hypoglycaemia, prolapse of the anterior mitral valve leaf, limited and less sympathetic activity, tension of depleted compensatory resources, acceleration of atrio-ventricular conduction, lower frequency of contractile and impaired relaxation functions of the myocardium. As a result of the work, the criteria for early diagnosis of health disorders in term infants with intrauterine growth retardation were determined. The features of the course of the early neonatal period of life, adaptation, and the state of the vegetative nervous and cardiovascular systems are proved.  

  5. Plant growth retardation and conserved miRNAs are correlated to Hibiscus chlorotic ringspot virus infection.

    Science.gov (United States)

    Gao, Ruimin; Wan, Zi Yi; Wong, Sek-Man

    2013-01-01

    Virus infection may cause a multiplicity of symptoms in their host including discoloration, distortion and growth retardation. Hibiscus chlorotic ringspot virus (HCRSV) infection was studied using kenaf (Hibiscus cannabinus L.), a non-wood fiber-producing crop in this study. Infection by HCRSV reduced the fiber yield and concomitant economic value of kenaf. We investigated kenaf growth retardation and fluctuations of four selected miRNAs after HCRSV infection. Vegetative growth (including plant height, leaf size and root development) was severely retarded. From the transverse and radial sections of the mock and HCRSV-infected kenaf stem, the vascular bundles of HCRSV-infected plants were severely disrupted. In addition, four conserved plant developmental and defence related microRNAs (miRNAs) (miR165, miR167, miR168 and miR171) and their respective target genes phabulosa (PHB), auxin response factor 8 (ARF8), argonaute 1 (AGO1) and scarecrow-like protein 1 (SCL1) displayed variation in expression levels after HCRSV infection. Compared with the mock inoculated kenaf plants, miR171 and miR168 and their targets SCL1 and AGO1 showed greater fluctuations after HCRSV infection. As HCRSV upregulates plant SO transcript in kenaf and upregulated AGO1 in HCRSV-infected plants, the expression level of AGO1 transcript was further investigated under sulfite oxidase (SO) overexpression or silencing condition. Interestingly, the four selected miRNAs were also up- or down-regulated upon overexpression or silencing of SO. Plant growth retardation and fluctuation of four conserved miRNAs are correlated to HCRSV infection.

  6. A Comparative Pathophysiological Study of Normal and Growth Retarded Human Placental Tissue

    Directory of Open Access Journals (Sweden)

    Adam Moyosore Afodun

    2014-01-01

    Full Text Available This study compares the pathophysiology of normal and growth retarded human placental tissues. Female patients were recruited from the Antenatal Clinic of Dolu Specialist Hospital, Mafoluku, Oshodi, Lagos, between 2008 and 2012. A total of 48 normal term placentas and 15 placentas of known IUGR cases were used for this study. IUGR cases were confirmed on the basis of ultrasound follow-up and diagnosis. Normal term placentas were collected at the point of delivery by a consultant gynaecologist, the cords were clamped, and membranes were then carefully trimmed after which each placenta was weighed. About 1 cm thickness of both normal and growth retarded placenta tissues was cut, processed for hematoxylin and eosin stain, while tissues for enzyme (ALP assay were homogenized in cold 0.5 M sucrose solution. Comparative analysis of the data was done using ANOVA; P<0.05 was taken as significant. The photomicrographs were observed/studied under light microscope, using the X150 and X600 magnifications. It was revealed therein that placental tissues are homogenous (regionally, compromised of maternal spiral arterioles and deregulated villous vasculogenesis, and that there is a significant difference in the level of alkaline phosphatase enzyme. We therefore concluded that there is a distinct difference between the normal and growth retarded human placenta tissue.

  7. Preparation and Flame Retardant and Smoke Suppression Properties of Bamboo-Wood Hybrid Scrimber Filled with Calcium and Magnesium Nanoparticles

    Directory of Open Access Journals (Sweden)

    Bin Fu

    2014-01-01

    Full Text Available The physical and mechanical properties of bamboo-wood hybrid scrimber filled with different loadings of nanoparticles were studied. The effects of nanoparticles on flame retardant and smoke suppression properties of bamboo-wood hybrid scrimber were studied by means of thermogravimetric analysis (TGA, cone calorimeter (CONE, and scanning electron microscope (SEM. The results showed that the physical and mechanical properties of bamboo-wood hybrid scrimber were improved by adding a moderate loading of nanoparticles; the optimal loading of nanoparticles was 10%. The heat transfer in bamboo-wood hybrid scrimber was prevented and the escaping channel of combustible gas was blocked by the uniformly filling effect of nanoparticles. The gas concentration was diluted by the noncombustible gas produced by pyrolysis of nanoparticles; the combustion chain reaction was suppressed by highly reactive free radicals produced by pyrolysis of nanoparticles. The residual mass of bamboo-wood hybrid scrimber filled with nanoparticles in thermogravimetric (TG curve at 900 s and burned by method of cone calorimeter (CONE at 600 s was increased compared to that of untreated one, which showed that inorganic mineral powder has the effect of catalytic charring.

  8. Endocrine dysfunction and growth retardation assessment in children with beta -thalassemia major

    International Nuclear Information System (INIS)

    Noureldin, A.M.; Ahmed, A.M.

    2002-01-01

    Children suffering from beta-thalassemia major are reported to have endocrine abnormalities and growth retardation. This study was carried out to study the cause of their growth retardation and determine the extent and rate of endocrine complications. Twenty beta-thalassemic major pubertal children, with mean baemoglobin and ferritin concentration of 8.8±0.6 and 3.597± 1.931, respectively, and twenty pubertal control children were used in the study. The anthropometric measurements that carried out revealed significant low growth rate in patient groups in comparison with control. Patients divided into two groups; I) D-thal with delayed growth and II) S-thal with stunted growth. Basal serum thyoid hormones (T 3 and T 4 ) and thyroid stimulating hormone (TSH) were measured in patient groups and control group. T 3 showed highly significant decrease (P 4 showed non-significant change and TSH showed highly significant increase (P<0.001). Serum growth hormone showed significant lower concentrations in patient groups with values of 2.163±0.9 ng/ml, (P<0.01) and 1.832±1.9ng/ml, (P<0.01) for delayed growth thalassemic group (D-thal) and stunted growth thalassemic group (S-thal), respectively. Serum concentration of insulin growth factor-1 (IGF-1) hormone was studied. D-thal and S-thal had significant lower basal IGF-1 concentrationsof-58.44% (P<0.001) for D-thal and -64.37%, (P<0.001) for S-thal

  9. Rates of nitrogen and growth retardant trinexapac-ethyl on wheat.

    OpenAIRE

    ESPINDULA, M. C.; ROCHA, V. S.; SOUZA, L. T. de.; SOUZA, M. A. de.; CAMPANHARO, M.; GROSSI, J. A. S.

    2011-01-01

    The objective in this study was to evaluate the effects of nitrogen rates in association with rates of the growth retardant trinexapac-ethyl on wheat. The experiment was conducted in Viçosa, MG and arranged in a 5×4 factorial, randomized block design, with four repetitions. A combination of five nitrogen rates (30, 60, 90, 120 and 150kg ha-1) with four rates of trinexapac-ethyl (0, 62.5, 125 and 187.5g ha-1) were tested. Trinexapac-ethyl promotes reduction of soot dry mass and grain yie...

  10. The maternal periodontal disease as a risk factor of intrauterine growth retardation

    OpenAIRE

    Carranza Samanez, Maynor; García Linares, Sixto; Profesor Asociado del D.A. Médico Quirúrgico; Dulanto Vargas, Julissa

    2014-01-01

    This study evaluates the relationship between the intrauterine growth retardation (IUGR) and the maternal periodontal disease (MPD). This case-control study of 120 mothers, 38 cases (mothers of babies with IUGR) and 82 controls (mothers of babies without IUGR) at the “Madre Niño San Bartolomé” Teaching Hospital. The mothers were interrogated and their medical histories were reviewed. Data was recorded, such as: the education level, marital status, smoking, alcohol and drug habits. All the mot...

  11. Horseshoe kidney with growth retardation: Don't forget Turner syndrome.

    Science.gov (United States)

    Arslansoyu-Çamlar, Seçil; Soylu, Alper; Abacı, Ayhan; Türkmen, Mehmet Atilla; Ülgenalp, Ayfer; Kavukçu, Salih

    2016-01-01

    Horseshoe kidney is the most frequent renal fusion anomaly that is usually asymptomatic and isolated malformation. However it can be seen with various syndromes and chromosomal anomalies. It was reported that 15-35% of Turner syndrome cases (TS) also display horseshoe kidney condition. TS is a chromosomal anomaly that had been characterized by delayed puberty, short body height and gonadal dysgenesis. In this report a five-year-old girl with horseshoe kidney, which has growth retardation during follow-up as only symptom of Turner syndrome.

  12. Prediction of fatigue crack growth and experimental result on overload retardation

    International Nuclear Information System (INIS)

    Shibata, K.; Kawamura, T.; Hashimoto, M.

    1980-01-01

    The phenomena of crack growth retardation are frequently observed under variable amplitude or irregular loading fatigue tests. This paper describes a prediction method on crack growth retardation caused by an overload during fatigue loads. The prediction reported in this paper is performed by the following procedure using the yield strength and da/dN vs. ΔK relationship of the material. 1) Determination of the residual stress distribution caused by cyclic load and overload based on the Dugdale model. 2) Determination of the effective residual stress intensity factor and effective stress intensity range (ΔKsub(eff.)). 3) Prediction of the crack growth rate using ΔKsub(eff) and da/dN vs. ΔK relationship of the material. From the viewpoint to apply the prediction to a structural component, experiments have been carried out on steel pipes with an axial through thickness crack, which are subject to an overpressure during cyclic pressure. In the paper, the experimental results are compared with the prediction. (orig.)

  13. EFFECT OF SOME PLANT GROWTH REGULATORS WITH RETARDING ACTIVITY ON SPRING PEA FOR GRAIN

    Directory of Open Access Journals (Sweden)

    Tsenka ZHELYAZKOVA

    2012-12-01

    Full Text Available A field experiment was conducted at Trakia University - Stara Zagora to establish the effect of some growth retardants on morphological and productive parameters in spring pea for grain variety Bogatir. Three combined preparations: Trisalvit (phenylphthalamic acid + chlorocholine chloride + chlorophenoxyacetic acid +salicylic acid at doses of 300 and 400 сmз*ha-1; SM-21 (phenylphthalamic acid + chlorocholine chloride at doses of 300 and 400 сmз*ha-1 and PNSA-44 (phenylphthalamic acid + naphthaleneacetic acid + chlorophenoxyacetic acid at doses of 200 and 300 сmз*ha-1 were applied in the early growth phase of the plant up to a height of 15-20 cm. The study showed that the greatest reduction in the stem height (by 12.8% compared to untreated plants was achieved by applying SM-21 (400 сmз*ha-1. The application of growth regulators Trisalvit and SM-21 had no appreciable effect on the production of spring pea grain. Maximum values of yield structure components (number of pods and grain per plant, grain mass per plant and mass of 1000 grain and the yield were obtained after application of PNSA-44 (300 сmз*ha-1 - up to 5.6% (117.2 kg*ha-1 more grain than the control. The investigation of the influence of tested factors (retardant, dose and year demonstrated that the conditions of the year as a factor had the strongest effect on plant height and grain yield.

  14. [Linear growth retardation in children under five years of age: a baseline study].

    Science.gov (United States)

    Rissin, Anete; Figueiroa, José Natal; Benício, Maria Helena D'Aquino; Batista Filho, Malaquias

    2011-10-01

    The scope of this study was to describe the prevalence of, and analyze factors associated with, linear growth retardation in children. The baseline study analyzed 2040 children under the age of five, establishing a possible association between growth delay (height/age index sanitary, maternal, biological and healthcare access. Multivariate analysis was performed using Poisson regression with the robust standard error option, obtaining adjusted prevalence ratios with a CI of 95% and the respective significant probability values. Among non-binary variables, there was a positive association with roof type and number of inhabitants per room and a negative association with income per capita, mother's schooling and birth weight. The adjusted analysis also indicated water supply, visit from the community health agent, birth delivery location, internment for diarrhea, or for pneumonia and birth weight as significant variables. Several risk factors were identified for linear growth retardation pointing to the multi-causal aspects of the problem and highlighting the need for control measures by the various hierarchical government agents.

  15. Formation of layer-by-layer assembled titanate nanotubes filled coating on flexible polyurethane foam with improved flame retardant and smoke suppression properties.

    Science.gov (United States)

    Pan, Haifeng; Wang, Wei; Pan, Ying; Song, Lei; Hu, Yuan; Liew, Kim Meow

    2015-01-14

    A fire blocking coating made from chitosan, titanate nanotubes and alginate was deposited on a flexible polyurethane (FPU) foam surface by a layer-by-layer assembly technique in an effort to reduce its flammability. First, titanate nanotubes were prepared by a hydrothermal method. And then the coating growth was carried out by alternately submerging FPU foams into chitosan solution, titanate nanotubes suspension and alginate solution. The mass gain of coating on the surface of FPU foams showed dependency on the concentration of titanate nanotubes suspension and the trilayers's number. Scanning electron microscopy indicated that titanate nanotubes were distributed well on the entire surface of FPU foam and showed a randomly oriented and entangled network structure. The cone calorimeter result indicated that the coated FPU foams showed reduction in the peak heat release rate (peak HRR), peak smoke production rate (peak SPR), total smoke release (TSR) and peak carbon monoxide (CO) production compared with those of the control FPU foam. Especially for the FPU foam with only 5.65 wt % mass gain, great reduction in peak HRR (70.2%), peak SPR (62.8%), TSR (40.9%) and peak CO production (63.5%) could be observed. Such a significant improvement in flame retardancy and the smoke suppression property for FPU foam could be attributed to the protective effect of titanate nanotubes network structure formed, including insulating barrier effect and adsorption effect.

  16. Classically induced suppression of energy growth in a chaotic ...

    Indian Academy of Sciences (India)

    ically kicked particles evolve from a confined region of the potential, (2) to show that the energy growth of these evolving particles, under certain circumstances, is suppressed. This system does not obey the Kolmogorov–Arnold–Moser (KAM) theorem [6]. In addition, the momentum-dependent boundary conditions due to ...

  17. Classically induced suppression of energy growth in a chaotic ...

    Indian Academy of Sciences (India)

    Classically induced suppression of energy growth in a chaotic quantum system. HARINDER PAL1 and M S SANTHANAM2,∗. 1Physical Research Laboratory, Navrangpura, Ahmedabad 380 009, India. 2Indian Institute of Science Education and Research, Pashan Road, Pune 411 008, India. ∗. Corresponding author.

  18. Growth retardation of paramecium and mouse cells by shielding them from background radiation

    International Nuclear Information System (INIS)

    Kawanishi, Masanobu; Okuyama, Katsuyuki; Shiraishi, Kazunori; Matsuda, Yatsuka; Taniguchi, Ryoichi; Shiomi, Nobuyuki; Yonezawa, Morio; Yagi, Takashi

    2012-01-01

    In the 1970s and 1980s, Planel et al. reported that the growth of paramecia was decreased by shielding them from background radiation. In the 1990s, Takizawa et al. found that mouse cells displayed a decreased growth rate under shielded conditions. The purpose of the present study was to confirm that growth is impaired in organisms that have been shielded from background radiation. Radioprotection was produced with a shielding chamber surrounded by a 15 cm thick iron wall and a 10 cm thick paraffin wall that reduced the γ ray and neutron levels in the chamber to 2% and 25% of the background levels, respectively. Although the growth of Paramecium tetraurelia was not impaired by short-term radioprotection (around 10 days), which disagreed with the findings of Planel et al., decreased growth was observed after long-term (40-50 days) radiation shielding. When mouse lymphoma L5178Y cells were incubated inside or outside of the shielding chamber for 7 days, the number of cells present on the 6th and 7th days under the shielding conditions was significantly lower than that present under the non-shielding conditions. These inhibitory effects on cell growth were abrogated by the addition of a 137 Cs γ-ray source disk to the chamber. Furthermore, no growth retardation was observed in XRCC4-deficient mouse M10 cells, which display impaired DNA double strand break repair. (author)

  19. Thyroid stimulating hormone and leptin levels and severe growth retardation among beta- thalassaemic patients

    International Nuclear Information System (INIS)

    Dayer, D.; Salahcheh, M.; Jazayeri, S.M.H.; Kaydani, G.A.; Kadkhodaei Elyaderani, M.K.; Shaneh, S.

    2012-01-01

    Objective: It has been proposed that thyroid stimulating hormone (TSH) influences leptin secretion from adipocytes. We evaluated the association between TSH and leptin levels in thalassaemic patients with growth retardation. Methodology: Blood samples were collected from 30 major thalassaemic patients and 24 normal subjects (range: 12 - 20 y). Both Leptin and TSH were measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. The anthropomorphic data were collected based on standard methods. Independent sample t-test and Pearson's correlation were used to analyze data. Results: Patients had severe growth retardation. Mean concentration of leptin in thalassaemic mean value of serum TSH concentration of lepton in thalassaemic patients was significantly lower than normal subjects (2.26 +- 2,61 vs 13.14 +- 15.95 ng/ml). The mean value os serum TSH concentration in beta- thalassaemic patients was higher than normal subjects. But the difference was not statistically significant (P = 0.146). There was no marked relationship between TSH and leptin concentration in thalassaemic patients (r= -0.022, P =0.909) and in control group (r =0.289, P=0.214). Conclusion: In beta - thalassaemic patients and normal group leptin secretion is a not affected by TSH concentration. (author)

  20. Efficient Flame-Retardant and Smoke-Suppression Properties of Mg-Al-Layered Double-Hydroxide Nanostructures on Wood Substrate.

    Science.gov (United States)

    Guo, Bingtuo; Liu, Yongzhuang; Zhang, Qi; Wang, Fengqiang; Wang, Qingwen; Liu, Yixing; Li, Jian; Yu, Haipeng

    2017-07-12

    Improving the flame retardancy of wood is an imperative yet highly challenging step in the application of wood in densely populated spaces. In this study, Mg-Al-layered double-hydroxide (LDH) coating was successfully fabricated on a wood substrate to confer flame-retardant and smoke-suppression properties. The chemical compositions and bonding states characterized by energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy confirmed the coating constituents of Mg-Al LDH. The coating evenly covered the sample wood surfaces and provided both mechanical enhancement and flame-retardancy effects. The limiting oxygen index of the Mg-Al LDH-coated wood increased to 39.1% from 18.9% in the untreated wood. CONE calorimetry testing revealed a 58% reduction in total smoke production and a 41% reduction in maximum smoke production ratio in the Mg-Al LDH-coated wood compared to the untreated wood; the peak heat release rate and total heat release were also reduced by 49% and 40%, respectively. The Mg-Al LDH coating is essentially hydrophilic, but simple surface modification by fluoroalkyl silane could make it superhydrophobic, with a water contact angle of 152° and a sliding angle of 8.6°. The results of this study altogether suggest that Mg-Al LDH coating is a feasible and highly effective approach to nanoconstructing wood materials with favorable flame-retardant and smoke-suppression properties.

  1. Numerical simulation of fatigue crack growth rate and crack retardation due to an overload using a cohesive zone model

    NARCIS (Netherlands)

    Silitonga, S.; Maljaars, J.; Soetens, F.; Snijder, H.H.

    2014-01-01

    In this work, a numerical method is pursued based on a cohesive zone model (CZM). The method is aimed at simulating fatigue crack growth as well as crack growth retardation due to an overload. In this cohesive zone model, the degradation of the material strength is represented by a variation of the

  2. Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice.

    Science.gov (United States)

    Murakami, Tomohiko; Hino, Shin-Ichiro; Nishimura, Riko; Yoneda, Toshiyuki; Wanaka, Akio; Imaizumi, Kazunori

    2011-03-01

    Old astrocyte specifically induced substance (OASIS), which is a new type of endoplasmic reticulum (ER) stress transducer, is a basic leucine zipper transcription factor of the CREB/ATF family that contains a transmembrane domain and is processed by regulated intramembrane proteolysis in response to ER stress. OASIS is selectively expressed in certain types of cells such as astrocytes and osteoblasts. We have previously demonstrated that OASIS activates transcription of the type I collagen gene Col1a1 and contributes to the secretion of bone matrix proteins in osteoblasts, and that OASIS-/- mice exhibit osteopenia and growth retardation. In the present study, we examined whether osteopenia in OASIS-/- mice is rescued by OASIS introduction into osteoblasts. We generated OASIS-/- mice that specifically expressed OASIS in osteoblasts using a 2.3-kb osteoblast-specific type I collagen promoter (OASIS-/-;Tg mice). Histological analysis of OASIS-/-;Tg mice revealed that osteopenia in OASIS-/- mice was rescued by osteoblast-specific expression of the OASIS transgene. The decreased expression levels of type I collagen mRNAs in the bone tissues of OASIS-/- mice were recovered by the OASIS transgene accompanied by the rescue of an abnormal expansion of the rough ER in OASIS-/- osteoblasts. In contrast, growth retardation in OASIS-/- mice did not improve in OASIS-/-;Tg mice. Interestingly, the serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-1 were downregulated in OASIS-/- mice compared with those in wild-type mice. These decreased GH and IGF-1 levels in OASIS-/- mice did not change when OASIS was introduced into osteoblasts. Taken together, these results indicate that OASIS regulates skeletal development by osteoblast-dependent and -independent mechanisms. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. ROLE OF DOPPLER STUDY IN THE EVALUATION OF INTRAUTERINE GROWTH RETARDATION

    Directory of Open Access Journals (Sweden)

    Prasad

    2015-10-01

    Full Text Available BACKGROUND AND OBJECTIVE : Intrauterine growth retardation (IUGR is a fetal growth disorder defined on the basis of a fetal weight below 10 th percentile for the corresponding gestational age. Our study was an effort at establishing the role of Umbilical artery (UA and Middle cere bral artery (MCA Doppler indices in predicting the adverse perinatal out come in clinically suspected IUGR pregnancies, and to determine the role of Doppler velocimetry in clinical management of such pregnancies. Elevation of the umbilical artery systolic /diastolic ratio or of the pulsatility index (PI; absent or reversed end - diastolic flow in the umbilical artery and decreased systolic/diastolic ratio or pulsatility index in the fetal internal carotid and middle cerebral arteries are the predictors of ab normal perinatal outcome. Our study was to evaluate the role of ratio of pulsatility index (PI which is called as Cerebroplacental Ratio i.e. MCAPI/UAPI Doppler ratio as the most accurate predictor of adverse perinatal outcome among women with clinical sus picion of IUGR attending our (SVRR Govt. hospital. METHODOLOGY : 50 Antenatal women attending the antenatal O.P.D who were clinically suspected as having growth retardation based on clinical history of previous child with growth retardation , signs of pallor ( anaemia and high documented Blood pressures – s/o PIH, reduced abdominal height for gestational age , were evaluated using screening ultrasound. Doppler velocity wave forms were obtained from umbilical artery and fetal middle cerebral artery fro m all the 50 cases. 16 cases were followed up with repeat Doppler. Pulsatility index ratio of middle cerebral artery and umbilical artery, also called as Cerebroplacental ratio was evaluated in each case. Abnormal ratio is defined as Cerebroplacental ratio < 1.08 was considered as a cut off value. Ratio was calculated and correlated clinically with the perinatal outcomes – in the form of IUD’s, low APGAR

  4. Infant growth patterns in the slums of Dhaka in relation to birth weight, intrauterine growth retardation, and prematurity.

    Science.gov (United States)

    Arifeen, S E; Black, R E; Caulfield, L E; Antelman, G; Baqui, A H; Nahar, Q; Alamgir, S; Mahmud, H

    2000-10-01

    Relations between size and maturity at birth and infant growth have been studied inadequately in Bangladesh, where the incidence of low birth weight is high and most infants are breast-fed. This study was conducted to describe infant growth patterns and their relations to birth weight, intrauterine growth retardation, and prematurity. A total of 1654 infants born in selected low-socioeconomic areas of Dhaka, Bangladesh, were enrolled at birth. Weight and length were measured at birth and at 1, 3, 6, 9, and 12 mo of age. The infants' mean birth weight was 2516 g, with 46.4% weighing birth weight, SGA, or preterm categories were retained throughout infancy. Mean z scores based on the pooled breast-fed sample were -2.38, -1. 72, and -2.34 at birth, 3 mo, and 12 mo. Correlation analysis showed greater plasticity of growth in the first 3 mo of life than later in the first year. Infant growth rates were similar to those observed among breast-fed infants in developed countries. Most study infants experienced chronic intrauterine undernourishment. Catch-up growth was limited and weight at 12 mo was largely a function of weight at birth. Improvement of birth weight is likely to lead to significant gains in infant nutritional status in this population, although interventions in the first 3 mo are also likely to be beneficial.

  5. Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

    Science.gov (United States)

    Troib, Ariel; Guterman, Mayan; Rabkin, Ralph; Landau, Daniel; Segev, Yael

    2016-08-01

    Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  6. [Etiology, prevalence of chronic renal failure and growth retardation in Lithuanian children].

    Science.gov (United States)

    Pundziene, Birute; Masalskiene, Jūrate; Jankauskiene, Augustina; Cerkauskiene, Rimante; Aleksyniene, Vilte; Dobiliene, Diana; Rudaitis, Sarūnas

    2007-01-01

    The aim of the study was to evaluate the causes, prevalence, and grades of chronic renal failure in Lithuanian children and to assess its influence on children's growth. The study was performed in Vilnius University Children's Hospital and Clinic of Children's Diseases, Kaunas University of Medicine. By March 31, 2006, 65 children with chronic renal failure had been registered. The prevalence was 88.3 cases per million children. The mean age was 10.8+/-4.9 years. The leading causes of chronic renal failure were congenital diseases (37%) and obstruction with interstitial nephritis (33.8%). At presentation, 23 (35.40%) children had mild, 17 (26.15%) had moderate, 9 (23.85%) had severe renal failure, and 16 (24.6%) had end-stage renal disease. Fourteen (21.54%) children were below the third percentile in height for their age. Growth failure was observed in one (4.35%) child with Grade 1 renal failure. The deterioration of renal function had a significant influence on growth impairment, and 13 (30.95%) children with glomerular filtration rate of less than 60 mL/min/1.73 m2 and 7 (43.75%) with end-stage renal disease had a height below the third percentile. Growth retardation as one of the symptoms of impairment of children's physical development depends on the severity of renal function.

  7. Effects of triazole derivatives on strigolactone levels and growth retardation in rice.

    Directory of Open Access Journals (Sweden)

    Shinsaku Ito

    Full Text Available We previously discovered a lead compound for strigolactone (SL biosynthesis inhibitors, TIS13 (2,2-dimethyl-7-phenoxy-4-(1H-1,2,4-triazol-1-ylheptan-3-ol. Here, we carried out a structure-activity relationship study of TIS13 to discover more potent and specific SL biosynthesis inhibitor because TIS13 has a severe side effect at high concentrations, including retardation of the growth of rice seedlings. TIS108, a new TIS13 derivative, was found to be a more specific SL biosynthesis inhibitor than TIS13. Treatment of rice seedlings with TIS108 reduced SL levels in both roots and root exudates in a concentration-dependent manner and did not reduce plant height. In addition, root exudates of TIS108-treated rice seedlings stimulated Striga germination less than those of control plants. These results suggest that TIS108 has a potential to be applied in the control of root parasitic weeds germination.

  8. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation

    Science.gov (United States)

    Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

    2016-01-01

    The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38–83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway. PMID:26894743

  9. Growth Retardation of Chick Embryo Exposed to a Low Dose of Electromagnetic Waves

    International Nuclear Information System (INIS)

    Siddiqi, N.; Norrish, M.; Heming, T.

    2016-01-01

    Background: The objectives of this study were to explore the effects of low dose of the non-ionizing (REW) emitted by a mobile phone on the development of chick embryo. Methods: one hundred and twenty chick fertilized eggs were equally divided into a control and an exposed group. Sixty fertilized eggs were placed in an egg incubator with a mobile phone (SAR US: 1.10W/kg (head) 0.47 W/kg body) in silent mode having vibration disable mode. Mobile was called for a total of 20 minutes in 24 hours. Twenty embryos each were sacrificed at day 5, 10 and 15, mortality, wet body weight, head to rump length, eye diameter and morphological changes were noted. The control group, 60 eggs were incubated in the same conditions, having removed the phone. Results: No mortality was noted. The experimental group exposed to REW showed subcutaneous haemorrhagic areas and significant growth retardation at day 10 as evidence by smaller eye diameter, wet weight and CR length than the control group. There were no significant growth differences at either day 5 or at day 15. Conclusion: Electromagnetic waves emitted from mobile phones even though for a very short duration of 20 minutes per day have affected the growth of the chick embryo at day 10 of incubation, Hence exposure of these waves are not 100 percent safe. (author)

  10. Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Alibegovic, Amra C; Sonne, Mette P

    2011-01-01

    Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involved...

  11. The effects of 3g eicosapentaenoic acid daily on recurrence of intrauterine growth-retardation and pregnancy-induced hypertension

    NARCIS (Netherlands)

    Bulstra-Ramakers, M. T. E. W.; Huisjes, H. J.; Visser, G. H. A.

    Objective To study the effects of addition of 3 g eicosapentaenoic acid daily to the diet, on recurrence rate of intrauterine growth retardation and pregnancy induced hypertension in a high risk population. Design Prospective, double blind, randomised multicentre study, Eicosapentaenoic acid or

  12. Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

    Science.gov (United States)

    Noguchi, Y; Saito, A; Miyagi, Y; Yamanaka, S; Marat, D; Doi, C; Yoshikawa, T; Tsuburaya, A; Ito, T; Satoh, S

    2000-06-30

    We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

  13. Heterogeneous growth and mental development of intrauterine growth-retarded infants during the first 3 years of life.

    Science.gov (United States)

    Villar, J; Smeriglio, V; Martorell, R; Brown, C H; Klein, R E

    1984-11-01

    Postnatal growth and development were studied in two groups of term infants with intrauterine growth retardation (IUGR) and one group of infants with normal birth weight up to 3 years of age (total sample, 205 infants). Infants with IUGR were classified as having low ponderal index (IUGR-LPI) or adequate ponderal index (IUGR-API). At birth, the two groups of infants with IUGR had similar birth weight, but length and head circumference measurements were significantly different. Overall, the IUGR-API infants remained lighter and shorter and had smaller head circumferences up to 30 months of age. The IUGR-LPI infants experienced catch-up growth in weight during the first months, because of greater fat deposition. At 24 months of age, the IUGR-API infants scored below the others on mental items. At 3 years of age the IUGR-API infants had the lowest values on seven of eight developmental measures and on the composite score; at these two time periods, the group with normal birth weight scored the highest, and the IUGR-LPI infants obtained intermediate values. It is concluded that infants with IUGR tend to follow postnatal growth and developmental patterns that are associated with their physical characteristics at birth.

  14. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

    Science.gov (United States)

    Endo, Toyoshi; Kobayashi, Tetsuro

    2013-09-01

    Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

  15. Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks

    NARCIS (Netherlands)

    Bijlenga, D.; Boers, K.E.; Birnie, E.; Mol, B.W.J.; Vijgen, S.C.M.; van der Post, J.A.M.; de Groot, C.J.; Rijnders, R.J.P.; Pernet, P.J.; Roumen, F.J.; Stigter, R.H.; Delemarre, F.M.C.; Bremer, H.A.; Porath, M.; Scherjon, S.A.; Bonsel, G.J.

    2011-01-01

    Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial

  16. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Birgitte Holst

    Full Text Available Secretory vesicles in endocrine cells store hormones such as growth hormone (GH and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs domain protein PICK1 (protein interacting with C kinase 1 as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of

  17. Solution-mediated growth of NBA-ZSM-5 crystals retarded by gel entrapment

    Science.gov (United States)

    Aguilar-Mamani, Wilson; Akhtar, Farid; Hedlund, Jonas; Mouzon, Johanne

    2018-04-01

    The synthesis of flat tablet-shaped ZSM-5 crystals from a gel using metakaolin as aluminosilicate source and n-butyl amine as structure directing agent was investigated. The evolution inside the solid phase was characterized by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, thermogravimetry and mass spectrometry. A kinetic study indicated that the nucleation of the majority crystals occurred concurrently with the formation of the gel upon heating the starting liquid suspension. Microstructural evidences undeniably showed that the gel precipitated on ZSM-5 crystals and mineral impurities originating from kaolin. As a result, crystal growth was retarded by gel entrapment, as indicated by the configuration and morphology of the embedded crystals. The results presented herein are harmonized with a solution-mediated nucleation and growth mechanism. Our observations differ from the autocatalytic model that suggests that the nuclei rest inside the gel until released when the gel is consumed. Our results show instead that it is crystals that formed in an early stage before entrapment inside the gel that rest inside the gel until exposed at the gel surface. These results illustrate the limitation of the classical method used in the field to determine nucleation profiles when the crystals become trapped inside the gel.

  18. Two tank-mix adjuvants effect on yield and quality attributes of wheat treated with growth retardants

    Directory of Open Access Journals (Sweden)

    Wojciech Miziniak

    2016-09-01

    Full Text Available ABSTRACT: The objective of this study was to evaluate the quality of seeds and yield of winter wheat under different retardants application. The two years field trials on winter wheat were carried out in the Institute of Plant Protection - National Research Institute in Poznan (Poland. Treatments consisted of trinexapac-ethyl, chlormequat and prohexadione calcium applied in mixtures with paraffin oil adjuvant or organosilicone surfactant in BBCH 31 growth stage of winter wheat. No lodging occurred in any experimental year. The retardants had varying effect on the quality parameters of wheat grain. The highest fluctuations in the content of protein, gluten and the Zeleny value were observed after the application of chlormequat chloride. Starch content in wheat grain, regardless of the retardant application method, was negatively correlated with others grain quality parameters evaluated in the experiment. Depending on the year of study and weather conditions, increased or decreased wheat quality.

  19. Yogurt protects against growth retardation in weanling rats fed diets high in phytic acid

    Science.gov (United States)

    Gaetke, Lisa M.; McClain, Craig J.; Toleman, C. Jean; Stuart, Mary A.

    2010-01-01

    The purpose of this study was to determine the affects of adding yogurt to animal diets which were high in phytic acid (PA) and adequate in zinc (38 μg Zn/g). The PA:Zn molar ratio was 60:1. Zinc status was determined by documenting growth and measuring the zinc concentration in bone (tibia) and plasma. For 25 days, 6 groups (n=6) of Sprague-Dawley weanling rats were fed one of the following AIN-76 diets. Half of the diets contained PA. Four of the diets contained yogurt with either active or heat-treated (inactive) cultures added at 25% of the diet. Diets: (without PA) 1) AIN, 2) AIN with active yogurt, 3) AIN and inactive yogurt; and (with PA) 4) AIN with PA, 5) AIN with PA plus active yogurt, and 6) AIN with PA plus inactive yogurt. Body weight, weight gain, and zinc concentration in bone and plasma were measured, and feed efficiency ratio (FER) was calculated. Rats fed diets with PA and yogurt had normal growth compared to the control group. Growth retardation was evident in the group fed the diet with PA and no yogurt. This group had significantly lower body weight compared to all other groups (p<0.05). Rats fed diets with PA, with or without yogurt, had significantly lower zinc concentration in bone and plasma (p<0.05). Adding yogurt to diets high in PA resulted in normal growth in weanling rats, however, zinc concentration in bone and plasma was still sub-optimal. PMID:19269152

  20. Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.

    Directory of Open Access Journals (Sweden)

    Tomohiro Nishimura

    Full Text Available Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez(-/- were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis-time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine and taurine were not affected. Lack of hypotaurine in Ez(-/- mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.

  1. Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

    Science.gov (United States)

    Vaiman, Daniel; Mondon, Françoise; Garcès-Duran, Alexandra; Mignot, Thérèse-Marie; Robert, Brigitte; Rebourcet, Régis; Jammes, Hélène; Chelbi, Sonia T; Quetin, Frédérique; Marceau, Geoffrey; Sapin, Vincent; Piumi, François; Danan, Jean-Louis; Rigourd, Virginie; Carbonne, Bruno; Ferré, Françoise

    2005-01-01

    Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR). Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the

  2. Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation

    Directory of Open Access Journals (Sweden)

    Danan Jean-Louis

    2005-08-01

    Full Text Available Abstract Background As a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH were applied to early (11 weeks human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas were hybridized to the membranes. Results Three hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR. Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals. Conclusion We could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5, which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically

  3. Potential Utility of Melatonin in Preeclampsia, Intrauterine Fetal Growth Retardation, and Perinatal Asphyxia.

    Science.gov (United States)

    Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Reiter, Russel J; Gitto, Eloisa

    2016-08-01

    Reactive oxygen species play an important role in the pathogenesis of several diseases during gestation and the perinatal period. During pregnancy, increased oxygen demand augments the rate of production of free radicals. Oxidative stress is involved in pregnancy disorders including preeclampsia and intrauterine fetal growth retardation (IUGR). Moreover, increased levels of oxidative stress and reduced antioxidative capacities may contribute to the pathogenesis of perinatal asphyxia. Melatonin, an efficient antioxidant agent, diffuses through biological membranes easily and exerts pleiotropic actions on every cell and appears to be essential for successful gestation. This narrative review summarizes current knowledge concerning the role of melatonin in reducing complications during human pregnancy and in the perinatal period. Melatonin levels are altered in women with abnormally functioning placentae during preeclampsia and IUGR. Short-term melatonin therapy is highly effective and safe in reducing complications during pregnancy and in the perinatal period. Because melatonin has been shown to be safe for both mother and fetus, it could be an attractive therapy in pregnancy and is considered a promising neuroprotective agent in perinatal asphyxia. We believe that the use of melatonin treatment during the late fetal and early neonatal period might result in a wide range of health benefits, improved quality of life, and may help limit complications during the critical periods prior to, and shortly after, delivery. © The Author(s) 2015.

  4. Color Doppler myocardial imaging demonstrates reduced diastolic tissue velocity in growth retarded fetuses with flow redistribution.

    Science.gov (United States)

    Larsen, Lene U; Petersen, Olav B; Sloth, Erik; Uldbjerg, Niels

    2011-04-01

    In fetuses suffering from intrauterine growth retardation with cerebroplacental redistribution (IUGR CPR), the diastolic heart function may be particularly susceptible to hypoxemia as described in postnatal pathological conditions. Using the newly introduced ultrasound technique, color Doppler myocardial imaging (CDMI), we investigated the correlation between diastolic tissue velocities and diastolic blood flow velocities and compared diastolic myocardial tissue velocities in fetuses with IUGR CPR and normal fetuses. Peak early and active atrial tissue velocities (E' and A') were acquired from both ventricular free walls in 18 fetuses with IUGR CPR and 42 normal fetuses. In 35 normal fetuses, blood flow across the atrio-ventricular valves was also recorded. Umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) flows were obtained in all fetuses. Nonparametric tests were used for statistical analysis. There was a tendency towards increased E' and A' with fetal age in normal pregnancies. No correlation between tissue velocity and blood flow velocity was established. IUGR CPR fetuses had significantly lower E' and A', but when indexing to heart length, only A' remained significantly lower. E'/A' ratio was increased in the left ventricle but unchanged in the right. CDMI is easily applicable during standard fetal echocardiography and provides new information on the diastolic properties of the fetal myocardium. In fetuses with IUGR CPR, diastolic tissue velocities are abnormal and especially A' may be a marker of diastolic dysfunction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

    Directory of Open Access Journals (Sweden)

    Xu Xue-Feng

    2013-02-01

    Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

  6. Mental and growth retardation after medulloblastoma radiation therapy. MRI assessment of radiation injuries

    International Nuclear Information System (INIS)

    Miyagi, Koichi; Mukawa, Jiro; Mekaru, Susumu; Harakuni, Tsuyoshi; Yamaguchi, Keiichiro; Tominaga, Daisuke; Nakasone, Susumu.

    1996-01-01

    We report on 3 cases of a medulloblastoma and discuss the usefulness of calculating the T2 value from long-term follow-up MRIs of 1.5 T in order to analyze the cause of mental retardation. Of 13 medulloblastoma patients who were treated at our hospital from 1970 through 1984, 4 patients survived. Excluding 1 of these patients, a 2-year-old child, the remaining 3 cases are discussed. The 3 patients underwent surgery and received postoperative craniospinal irradiation and chemotherapy. The radiation dose (tumoral dose) was 40 to 85 Gy to the posterior fossa, 0 to 30.4 Gy to the spinal cord, and 25.6 to 35.2 Gy to the whole brain. The long-term effects were evaluated by calculating the T2 value and conducting a psychometric analysis from 2 to 11 years after radiation therapy. Their respective Tanaka-Vineland IQ test results were 32, 46, and 102 and their respective growth heights were -3.6 SD, -6.4 SD, and +0.18 SD. Growth hormone deficiencies were identified in all 3 patients. The decline in ability and failure to grow became more pronounced with time. The calculated T2 values showed alterations in the hippocampus, the occipital white matter, and the hypothalamus of all 3 patients. The hippocampal alteration contributed to a decline in intellectual ability and resulted in learning difficulties at school. It should be noted that in addition to whole-brain radiation that was pursued, the focal radiation provided delivers the same radiation dose to the hippocampus as to the tumor. Such a high radiation dose thus might be responsible for the decline in intellectual ability. Therefore, to avoid radiation injury to these areas, stereotactic radiosurgery must be planned for focal radiation therapy. (K.H.)

  7. Growth retardation due to idiopathic growth hormone deficiencies: MR findings in 24 patients

    International Nuclear Information System (INIS)

    Ochi, M.; Morikawa, M.; Yoshimoto, M.; Kinoshita, E.; Hayashi, K.

    1992-01-01

    In this study we evaluated the pituitary-hypothalamic abnormalities of ''idiopathic growth hormone (GH) deficiency'' as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with ''idiopathic GH deficiency'' had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life. (orig./GD)

  8. Intrauterine Growth Retarded Progeny of Pregnant Sows Fed High Protein:Low Carbohydrate Diet Is Related to Metabolic Energy Deficit

    OpenAIRE

    Metges, Cornelia C.; Lang, Iris S.; Hennig, Ulf; Br?ssow, Klaus-Peter; Kanitz, Ellen; Tuchscherer, Margret; Schneider, Falk; Weitzel, Joachim M.; Steinhoff-Ooster, Anika; Sauerwein, Helga; Bellmann, Olaf; N?rnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2012-01-01

    High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 10...

  9. INTRAUTERINE GROWTH RETARDATION AND ITS IMPACT ON CHILDREN'S HEALTH IN LATER LIFE. THE POSSIBILITY OF NUTRITIONAL SUPPORT

    Directory of Open Access Journals (Sweden)

    T. V. Belousova

    2015-01-01

    Full Text Available The sources of development, homeostasis and metabolism habits, long-term effects on the health of infants delivered with intrauterine growth retardation are considered. Principals and aspects of nutrition choice for these particular infants as well as some controversial aspects on this topic are discussed. Research data represents nutrition of newborns and up to 3 months infants, including those with the IGR and moderate postnatal inanition, fed with goat milk based formula, containing pre- and probiotics. 

  10. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  11. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

    Science.gov (United States)

    Li, Jun; Sung, Cecilia Ying Ju; Lee, Nikki; Ni, Yueqiong; Pihlajamäki, Jussi; Panagiotou, Gianni; El-Nezami, Hani

    2016-01-01

    The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment. PMID:26884164

  12. Tumor-penetrating nanosystem strongly suppresses breast tumor growth

    Science.gov (United States)

    Sharma, Shweta; Kotamraju, Venkata Ramana; Mölder, Tarmo; Tobi, Allan; Teesalu, Tambet; Ruoslahti, Erkki

    2018-01-01

    Antiangiogenic and vascular disrupting compounds have shown promise in cancer therapy, but tend to be only partially effective. We previously reported a potent theranostic nanosystem that was highly effective in glioblastoma and breast cancer mouse models, retarding tumor growth and producing some cures [Agemy et al. 2011,2013]. The nanosystem consists of iron oxide NPs (“nanoworms”) coated with a composite peptide with tumor-homing and pro-apoptotic domains. The homing component targets tumor vessels by binding to p32/gC1qR at the surface or tumor endothelial cells. We sought to further improve the efficacy nanosystem by searching for an optimally effective homing peptide that would also incorporate a tumor-penetrating function. To this effect, we tested a panel of candidate p32 binding peptides with a sequence motif that conveys tumor-penetrating activity (CendR motif). We identified a peptide designated as Linear TT1 (Lin TT1) (sequence: AKRGARSTA) as most effective in causing tumor homing and penetration of the nanosystem. This peptide had the lowest affinity for p32 among the peptides tested. The low affinity may have moderated the avidity effect from the multivalent presentation on nanoparticles (NPs), such that the NPs avoid getting trapped by the so called “binding-site barrier”, which can hinder tissue penetration of compounds with a high affinity for their receptors. Treatment of breast cancer mice with the LinTT1 nanosystem showed greatly improved efficacy compared to the original system. These results identify a promising treatment modality and underscore the value of tumor penetration effect in improving the efficacy tumor treatment. PMID:28178415

  13. Nitrogen, potassium and plant growth retardant effects on oil content and quality of cotton seed

    Directory of Open Access Journals (Sweden)

    Alkassas, A. R.

    2007-09-01

    Full Text Available The aim of this field experiment was to investigate the effect of nitrogen, potassium and a plant growth retardant (PGR on seed yield and protein and oil content of an Egyptian cotton cultivar (Gossypium barbadense Giza 86. Treatments consisted of: soil application of N (95 and 143 kg N ha-1 in the form ammonium nitrate, foliar application of potassium (0, 319, 638 or 957 g K ha-1 as potassium sulfate and foliar application of mepiquat chloride (MC (0 and 48 + 24 g active ingredient ha-1 on seed, protein and oil yields and oil properties of Egyptian cotton cultivar “Giza 86” (Gossypium barbadense. After applying the higher N-rate, foliar application of potassium and plant growth retardant MC significantly increased seed yield and the content of seed protein and oil, seed oil refractive index, unsaponifiable matter and total unsaturated fatty acids (oleic and linoleic. In contrast, oil acid and saponification value as well as total saturated fatty acids were decreased by foliar application of potassium and MC. The seed oil content was decreased with soil application of N.El objetivo de los experimentos de campo fue investigar el efecto del nitrogeno, potasio y retardantes del crecimiento de plantas sobre el contenido en proteínas y aceite de una semilla de algodón cultivada en Egipto (Gossypium barbadense Giza 86. Los tratamientos consistieron en la aplicación en suelo de N (95 and 143 kg N ha-1 en forma de nitrato amónico, aplicación foliar de K (0, 319, 638 or 957 g K ha-1 como sulfato potásico y aplicación foliar de cloruro de m mepiquat (MC (0 and 48 + 24 g de ingrediente activo ha-1 sobre un cultivar de algodón «Giza 86» (Gossypium barbadense. La aplicación de la cantidad más elevada de N, unida a la aplicación de potasio y del retardador MC, aumentó significativamente el rendimiento en semilla, así como el contenido en proteinas y en aceite. Respecto al aceite, aumentó el índice de refracción, la fracci

  14. Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies

    Science.gov (United States)

    Munger, R.; Isacson, P.; Hu, S.; Burns, T.; Hanson, J.; Lynch, C.F.; Cherryholmes, K.; Van Dorpe, P.; Hausler, W.J.

    1997-01-01

    In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987 the Rathbun rural water system was found to contain elevated levels of triazine herbicides. Rates of low birth weight, prematurity, and intrauterine growth retardation (IUGR) in live singleton births during the period 1984-1990 by women living in 13 communities served by the Rathbun water system were compared to other communities of similar size in the same Iowa counties. The Rathbun communities had a greater risk of IUGR than southern Iowa communities with other surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7). Multiple linear regression analyses revealed that levels of the herbicides atrazine, metolachlor, and cyanazine were each significant predictors of community IUGR rates in southern Iowa after controlling for several potentially confounding factors including maternal smoking and socioeconomic variables. The association with IUGR was strongest for atrazine, but all three herbicides were intercorrelated and the independent contributions of each to IUGR risk could not be determined. We conclude that communities in southern Iowa with drinking water supplies contaminated with herbicides have elevated rates of IUGR compared to neighboring communities with different water supplies. Because of the limitations of the ecologic design of this study, including aggregate rather than individual measures of exposure and limited ability to control for confounding factors related to source of drinking water and risk of IUGR, a strong causal relationship between any specific water contaminant and risk of IUGR cannot yet be inferred. The association between the water supplied to the Rathbun communities and the increased risk of IUGR should be considered a preliminary finding that needs to be verified by more detailed epidemiologic studies.

  15. Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, and metaphyseal dysplasia (Shwachman syndrome). : Report of a case with extensive skin lesions (clinical, histological, and ultrastructural findings)

    NARCIS (Netherlands)

    M. Goeteyn (M.); A.P. Oranje (Arnold); V.D. Vuzevski (Vojislav); R. de Groot (Ronald); L.W.A. van Suijlekom-Smit (Lisette)

    1991-01-01

    textabstractThe Shwachman syndrome comprises exocrine pancreatic insufficiency, growth retardation, and bone marrow hypoplasia resulting in neutropenia. Clinical, morphological, and ultrastructural studies, as well as hair analysis, were performed in a patient with Shwachman's syndrome and severe

  16. Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation.

    Directory of Open Access Journals (Sweden)

    Boris V Skryabin

    2007-12-01

    Full Text Available Prader-Willi syndrome (PWS [MIM 176270] is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr(m-/p+ are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr(m+/p- consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.

  17. No effect of plant growth retarding compounds and growth stimulators on indolo-3-acetic acid oxidase activity in greening cucumber cotyledons

    Directory of Open Access Journals (Sweden)

    J. S. Knypl

    2015-01-01

    Full Text Available Cotyledons dissected from 5-day-old etiolated cucumber seedlings were incubated in solutions on AMO-1618, B-Nine, CCC and Phosfon D for 48 h in light. In some tests the retardants were applied in mixed solutions with GA3 or BAP. IAA oxidase was extracted and purified by means of molecular sieving through a bed of Sephadex G-25. The retardants inhibited chlorophyll synthesis by 50 % or more, and had essentially no effect on IAA oxidase activity per cotyledon basis. GA3 and BAP also had no effect on enzyme activity in spite of a fact that the compounds stimulated growth of the cotyledons. The crude enzyme extract from B-Nine treated cotyledons showed lower IAA oxidase activity in comparison with the water treated control, the effect being due to a longer lag-phase preceding the initiation of IAA oxidation. KNO3 strikingly stimulated expansional growth of the cotyledons, the effect being correlated with the accelerated chlorophyll accumulation. KNO3 had no effect on IAA oxidase activity per cotyledon and decreased it per gram fr wt. It is concluded that [1] the growth rate of cucumber cotyledons is not correlated with IAA oxidase activity, and ;[2] the growth retarding compounds do not affect IAA oxidase system is this tissue.

  18. The impact of disease and antirheumatic therapy factors on growth retardation in children suffering from juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    T.M. Bzarova

    2006-01-01

    Full Text Available THE STUDY EVALUATED THE IMPACT OF REFRACTORY JUVENILE IDIOPATHIC ARTHRITIS (JIA AND INTERFERENCE OF ANTIRHEUMATIC THERAPY ON PHYSICAL STATURE AND GROWTH AND PHYSICAL DEVELOPMENT IN CHILDREN. WE OBSERVED 133 PATIENTS WITH JIA WITH AGE FROM 4.6 TO 18 YEARS. WE ASSESSED PATIENTS' PHYSICAL STATURE (DOCUMENTING HEIGHT AND WEIGHT AND FURTHER GROWTH AND DEVELOPMENT STARING FROM BIRTH, BEFORE THE ONSET OF JIA, AT THE FIRST YEAR FROM THE ONSET OF THE DISB EASE AND LATER ON. PHYSICAL RETARDATION WAS MARKED IN ALL CHILDREN IN THE FIRST YEAR FROM THE ONSET OF JIA. SYSTEMIC JIA, WHICH IS KNOWN FOR HIGH ACTIVITY AND POLYARTICULAR OR GENERALIZED JOINT LESION, WAS LINKED TO SIGNIFICANT PHYSICAL RETARDATION IN ALL CHILDREN WITH SYSBTEMIC JIA. LONGBTERM GLUCOCORTICOID ADMINISTRATION, EVEN AT LOW DOSES, ACCENTUATED THE NEGATIVE IMPACT OF JIA ON GROWTH RESULTING IN MARKED GROWTH DELAY OR ITS' TOTAL ARREST. WE HAVE ELABORATED RISK FACTORS FOR SHORT STATURE IN CHILDREN WITH JIA, WHICH SUGGEST THERAPY GUIDELINES, PRESENTED IN THIS ARTICLE.KEY WORDS: JUVENILE IDIOPATHIC ARTHRITIS, СHILDREN.

  19. P2X7R suppression promotes glioma growth through epidermal growth factor receptor signal pathway.

    Science.gov (United States)

    Fang, Jingqin; Chen, Xiao; Zhang, Letian; Chen, Jinhua; Liang, Yi; Li, Xue; Xiang, Jianbo; Wang, Lili; Guo, Guangkuo; Zhang, Bo; Zhang, Weiguo

    2013-06-01

    P2X7 receptor (P2X7R) has been shown to mediate an anticancer effect via apoptosis in different types of cancer. However, whether P2X7R exerts a promoting or suppressive effect on brain glioma is still a controversial issue and its underlying mechanism remains unknown. We showed here that P2X7R suppression exerted a pro-growth effect on glioma through directly promoting cells proliferation and pro-angiogenesis, which was associated with epidermal growth factor receptor (EGFR) signaling. The P2X7R was markedly downregulated by cells exposure to the P2X7R antagonist, brilliant blue G (BBG), moreover, the cells proliferation was enhanced in a dose-dependent manner and the expression of EGFR or p-EGFR protein was significantly upregulated. By constructing C6 cells with reduced expression of P2X7R using shRNA, we also demonstrated strong upregulation in cells proliferation and EGFR/p-EGFR expression. However, this effect of BBG was reversed in the presence of gefitinib or suramin. Magnetic resonance imaging and computed tomography perfusion showed that the BBG or P2X7R shRNA promoted the tumor growth by about 40% and 50%, respectively, and significantly increased angiogenesis. Nissl and Ki-67 staining also confirmed that BBG or P2X7R shRNA notably increased the tumor growth. More importantly, either BBG or P2X7R shRNA could markedly upregulated the expression of EGFR, p-EGFR, HIF-1α and VEGF in glioma cells. In conclusion, P2X7R suppression exerts a promoting effect on glioma growth, which is likely to be related to upregulated EGFR, HIF-1α and VEGF expression. These findings provide important clues to the molecular basis of anticancer effect of targeting purinergic receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Behavioral Suppression of Seriously Disruptive Behavior in Psychotic and Retarded Patients: A Review of Punishment and Its Alternatives.

    Science.gov (United States)

    Harris, Sandra L.; Ersner-Hershfield, Robin

    1978-01-01

    Reviews research on the effectiveness of such procedures as differential reinforcement of behaviors incompatible with disruptive behavior (DRO), a contingent removal of reinforcement (time-out), overcorrection, and punishment to suppress seriously disruptive and self-injurious behaviors. Research on the generalization, maintenance, and side…

  1. The effect of antenatal administration of solcoseryl on hepatic glycogen synthesis in rat fetuses with intrauterine growth retardation.

    Science.gov (United States)

    Takahashi, H; Cheng, K M; Araki, T

    1993-06-01

    The effect of antenatal solcoseryl administration on hepatic glycogen synthesis and storage was studied in normal developing and intrauterine growth-retarded (IUGR) rat fetuses using biochemical analyses. The maximal effect of solcoseryl occurred 2 hours after administration. The glycogen content of the liver showed a significant increase in normal and IUGR fetuses with antenatal solcoseryl administration compared to their non-solcoseryl counterparts (p solcoseryl administration. Active synthase also increased in normal fetuses with antenatal solcoseryl administration (p solcoseryl administration stimulates hepatic glycogen synthesis and storage in IUGR rat fetuses, and thus might favorably influence the development of neonatal hypoglycemia.

  2. Graphitic carbon nitride/phosphorus-rich aluminum phosphinates hybrids as smoke suppressants and flame retardants for polystyrene.

    Science.gov (United States)

    Shi, Yongqian; Yu, Bin; Duan, Lijin; Gui, Zhou; Wang, Bibo; Hu, Yuan; Yuen, Richard K K

    2017-06-15

    Graphitic carbon nitride/organic aluminum hypophosphites (g-C 3 N 4 /OAHPi) hybrids, i.e., CPDCPAHPi and CBPODAHPi, were synthesized by esterification and salification reactions, and then incorporated into polystyrene (PS) to prepare composites through a melt blending method. Structure and morphology characterizations demonstrated the successful synthesis of PDCPAHPi, BPODAHPi and their hybrids. The g-C 3 N 4 protected OAHPi from external heat and thus improved the thermal stability of OAHPi. Combining g-C 3 N 4 with OAHPi contributed to reduction in peak of heat release rate, total heat release and smoke production rate of PS matrix. Reduced smoke released has also been demonstrated by smoke density chamber testing. Additionally, introduction of the hybrids led to decreased release of flammable aromatic compounds. These properties improvement could be attributed to gas phase action and physical barrier effect in condensed phase: phosphorus-containing low-energy radicals generated from OAHPi effectively captured high-energy free-radicals evolved from PS; g-C 3 N 4 nanosheets retarded the permeation of heat and the escape of volatile degradation products. Therefore, g-C 3 N 4 /OAHPi hybrids will provide a potential strategy to reduce the fire hazards of PS. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Morpholine or methylpiperazine and salicylaldimine based heteroleptic square planner platinum (II) complexes: In vitro anticancer study and growth retardation effect on E. coli.

    Science.gov (United States)

    Rahman, Faiz-Ur; Ali, Amjad; Khan, Inam Ullah; Duong, Hong-Quan; Yu, Shang-Bo; Lin, Yue-Jian; Wang, Hui; Li, Zhan-Ting; Zhang, Dan-Wei

    2017-05-05

    Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II) 2 (bis-salicylaldimine)(morpholine) 2 Cl 2 C4a and Pt(II) 2 (bis-salicylaldimine)(methylpiperazine) 2 Cl 2 C4b were prepared. These complexes were characterized by 1 H, 13 C, 19 F, 2D NOESY NMR, HR ESI-MS and elemental analyses, while structures of C2a, C3a and C4b were determined by single crystal X-ray analysis. All these complexes were studied for their in vitro cytotoxic effect on breast (MCF-7), liver (HepG2) and lung (A549) cancer cell lines. All these complexes showed considerable cytotoxic effect on these tested cancer cell lines comparable to cisplatin. Moreover three complexes C1a, C4a and C1b were studied in details. Time- and dose-dependent study was performed for C1a, C4a and C1b. These complexes induced the expression of p53 that suppresses cancer cell growth. Induction of PUMA gene and repression of MYC oncogene suggested that these complexes targeted different genes to suppress cancer progression. TUNEL assay showed induction of apoptosis and invasion analysis showed reduction in invasion ability of breast cancer cells treated with C1a, C4a or C1b. Importantly, these novel complexes suppressed the expression of EMT and metastasis promoter genes. Similarly these complexes induced autophagy by enhancing the expression of autophagy related genes such as beclin, atg-5 and atg-7. The E. coli growth retardation study showed stronger growth inhibitory effects and subsequently resulted in filamentous morphology of bacterial cells. Gel electrophoresis study proved the interaction of these complexes with DNA. All these analysis revealed anticancer

  4. Use of growth retardants in wheat Utilização de redutores de crescimento em trigo

    Directory of Open Access Journals (Sweden)

    M.C. Espindula

    2009-06-01

    Full Text Available In general, lodging has been controlled by restricting nitrogen fertilizer application and/or using short cultivars. Growth retardants can also be used to solve this problem.The objective of this study was to evaluate the effect of rates and application times of three growth retardants on Pioneiro wheat cultivar. The trial was carried out in Viçosa-MG, from May to September 2005, in a factorial and hierarchical scheme, in a randomized block design with four replications and a control treatment. The treatments consisted of 500, 1,000 and 1,500 g ha-1 of chlormequat; 62.5, 125 and 187.5 g ha-1 of trinexapac-ethyl and 40, 80 and 120 g ha-1 of paclobutrazol applied at growth stages 6 or 8, growth stage used on the scale of Feeks and Large, and a control treatment without growth retardant application. Only trinexapac-ethyl and chlormequat were efficient in reducing plant height; the effect of chlormequat and paclobutrazol on plant height was independent of the application time, but the trinexapac-ethyl at growth stage 8 produced shorter plant height than at stage 6. Increasing growth retardant rates produced shorter plant heights; chlormequat and paclobutrazol did not affect grain yield. However, the highest trinexapac-ethyl rates reduced wheat yield.De modo geral, o acamamento tem sido controlado mediante restrição da aplicação de fertilizantes nitrogenados e/ou o uso de cultivares de porte baixo. No entanto, esse problema também pode ser solucionado pela utilização de redutores de crescimento. Objetivou-se com este trabalho avaliar o efeito de doses e épocas de aplicação de três redutores de crescimento sobre plantas de trigo do cultivar Pioneiro. O experimento, conduzido em Viçosa-MG de maio a setembro de 2005, foi instalado com os tratamentos dispostos em esquema fatorial e hierárquico com uma testemunha, no delineamento de blocos casualizados com quatro repetições. Os tratamentos foram: 500, 1.000 e 1.500 g ha-1 de clormequat; 62

  5. Etiology and treatment of growth retardation in children with chronic kidney disease and end-stage renal disease: a historical perspective.

    Science.gov (United States)

    Fine, Richard N

    2010-04-01

    Dramatic changes have occurred in our understanding of the etiology of the growth retardation associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD) during the past 50 years. Significant interest has been focused on preventing and/or correcting the growth retardation because of the emergence of the dual therapeutic modalities of dialysis and renal transplantation to prolong the lives of infants, children, and adolescents afflicted with CKD and ESRD. These efforts have resulted in a significant improvement in the height Z-score over the past two decades of children with CKD and ESRD. This has had a salutary impact on the final adult height of such children which should hopefully lead to an enhanced quality of life in the future. This report addresses the progress that has been made in the management of growth retardation in the pediatric population with CKD and ESRD.

  6. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...... postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease....

  7. Silencing of E2F3 suppresses tumor growth of Her2+ breast cancer cells by restricting mitosis.

    Science.gov (United States)

    Lee, Miyoung; Oprea-Ilies, Gabriela; Saavedra, Harold I

    2015-11-10

    The E2F transcriptional activators E2F1, E2F2 and E2F3a regulate many important cellular processes, including DNA replication, apoptosis and centrosome duplication. Previously, we demonstrated that silencing E2F1 or E2F3 suppresses centrosome amplification (CA) and chromosome instability (CIN) in Her2+ breast cancer cells without markedly altering proliferation. However, it is unknown whether and how silencing a single E2F activator, E2F3, affects malignancy of human breast cancer cells. Thus, we injected HCC1954 Her2+ breast cancer cells silenced for E2F3 into mammary fat pads of immunodeficient mice and demonstrated that loss of E2F3 retards tumor growth. Surprisingly, silencing of E2F3 led to significant reductions in mitotic indices relative to vector controls, while the percentage of cells undergoing S phase were not affected. Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA. In this report, we found that Nek2 overexpression rescued back the CA caused by silencing of shE2F3. However, the effects of Nek2 overexpression in affecting tumor growth rates of shE2F3 and shE2F3; GFP cells were inconclusive. Taken together, our results indicate that E2F3 silencing decreases mammary tumor growth by reducing percentage of cells undergoing mitosis.

  8. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12...... postnatal growth, insulin resistance and consequently the risk of cardiovascular disease. Thus IGF-I may serve as a link between fetal growth and adult-onset disease.......Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...

  9. AN EFFECT OF SHOT PEENING ON GROWTH AND RETARDATION OF PHYSICALLY SHORT FATIGUE CRACKS IN AN AIRCRAFT Al-ALLOY

    Directory of Open Access Journals (Sweden)

    Ivo Černý

    2009-11-01

    Full Text Available Results of an investigation of effect of shot peening on development of physically short fatigue crack in an aircraft V-95 Al-alloy, which is of a similar type as 7075 alloy, are described and discussed in the paper. The first part deals with adaptation and verification of direct current potential drop method for detection and measurement of short crack initiation and growth. The specific material and quite large dimensions of flat specimens with side necking of a low stress concentration factor had to be considered when position of electrodes was specified and the measurement method verified. The specimen type and dimensions were proposed taking account of the investigation of shot peening effects. Physically short fatigue cracks of the length from 0.2 mm to more than 3 mm, most of them between 0.8 – 1.5 mm, were prepared under high cycle fatigue loading of a constant nominal stress amplitude plus/minus 160 MPa. Specimens with existing short fatigue cracks were shot peened using two different groups of parameters. Development of crack growth after shot peening was measured and compared with crack growth in specimens without shot peening. Retardation of crack growth was significant particularly with cracks shorter than 2 mm. For the specific stress amplitude, evaluated results enable to estimate threshold length of defects, which after the application of shot peening will be reliably arrested.

  10. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    Science.gov (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  11. Influence of gamma-irradiation, growth retardants and coatings on the shelf life of winter guava fruits (Psidium guajava L.)

    International Nuclear Information System (INIS)

    Pandey, S.K.; Joshua, Jean E.; Bisen; Abhav

    2010-01-01

    Experiment was conducted to study the effect of gamma irradiation, growth retardants and coatings (coconut oil, mustard oil and liquid paraffin) on shelf life of winter guava fruits during storage. The results revealed that the superiority of coconut oil coating over other post harvest treatments. Physiological loss in weight (7.1%), marketable fruits retained over control (86.7%), total soluble solid (16.1%), ascorbic acid (195 mg/100 g pulp) and total sugar (10%) of fruit were positively influenced by coconut oil coating up to 12 days of storage. The treatment was found significantly effective in increasing the post harvest life of fruits for 12 days over control without adversely affecting the fruit quality. Coconut oil coating gave highest consumer acceptability while, maintaining sufficient level of total soluble solids and sugar content in fruits. (author)

  12. Suppressive Effect of Some Forage Plants on the Growth of Ambrosia artemisiifolia and Iva xanthiifolia

    Directory of Open Access Journals (Sweden)

    Senka Milanova

    2010-01-01

    Full Text Available A pot trial in greenhouse conditions has been carried out to investigate the role ofsome plant species in suppression of Ambrosia artemisiifolia and Iva xanthiifolia growth.Screening of several plant species (Medicago sativa L., Lolium perenne L., Dactylis glomerataL. and Elymus repens (L. Gould – all from both turf and seeds was conducted. Theresults of the experiment showed that some perennial plants, especially L. perenne, D.glomerata and M. sativa, can be a reliable means of suppression of the growth and seedproduction of A. artemisiifolia and I. xanthiifolia. Moreover, simple greenhouse screeningturned to be a reliable method for predicting this potential suppressive role under certainconditions.

  13. [Age-dependent alteration of insulin and ghrelin expression in pancreatic islets of intrauterine growth-retarded rats].

    Science.gov (United States)

    Wang, Xiu-Min; Liang, Li; Du, Li-Zhong

    2008-05-01

    To evaluate the age-dependent alteration of insulin and ghrelin expression in the pancreatic islets of intrauterine growth-retarded (IUGR) rats during development and to identify the role of ghrelin in insulin resistance induced by IUGR. Neonatal SD rats were divided into normal birth weight group (N group) and intrauterine growth-retarded group (I group). Plasma glucose, ghrelin and serum insulin were analyzed at day 1, 3, 7 and 10 and at week 2, 3, 4,8 and 12 after birth.Entire pancreas samples were collected for determination of ghrelin and insulin mRNA. Immunohistochemical double-staining and confocal microscopy was performed on rat pancreas. Plasma insulin levels of I group were lower than those of N group at day 1, 3 and 7 (P insulin resistance index (HOMA-IR) of I group was higher than that of N group at day 1, 3 and 7 (Pinsulin, HOMA-IR and ghrelin concentrations decreased in an age-dependent manner (F = 4.12 to approximately 125.97, P insulin (+) cells and ghrelin (+) cells in both groups decreased in an age-dependent manner (F = -49.29 to approximately 427.28, PInsulin secretion was negatively correlated with ghrelin contents in both groups (r=-0.895, P=0.000; r=-0.458, P=0.002). Percentage of insulin(+) cells was negatively correlated with the percentage of ghrelin (+) cells in pancreatic islets in both groups (r=-0.810,P=0.000; r=-0.714, P=0.000). The distributions of ghrelin (+) cells in pancreatic islets of I group were different from those of N group. The effects of IUGR on weight, plasma ghrelin levels and insulin secretion of pups rats persist after birth and ghrelin may be involved in the process of insulin resistance in IUGR rats.

  14. Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay.

    Science.gov (United States)

    Daoud, Hussein; Zhang, Dong; McMurray, Fiona; Yu, Andrea; Luco, Stephanie M; Vanstone, Jason; Jarinova, Olga; Carson, Nancy; Wickens, James; Shishodia, Shifali; Choi, Hwanho; McDonough, Michael A; Schofield, Christopher J; Harper, Mary-Ellen; Dyment, David A; Armour, Christine M

    2016-03-01

    A homozygous loss-of-function mutation p.(Arg316Gln) in the fat mass and obesity-associated (FTO) gene, which encodes for an iron and 2-oxoglutarate-dependent oxygenase, was previously identified in a large family in which nine affected individuals present with a lethal syndrome characterised by growth retardation and multiple malformations. To date, no other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. We investigated a 21-month-old girl who presented distinctive facial features, failure to thrive, global developmental delay, left ventricular cardiac hypertrophy, reduced vision and bilateral hearing loss. We performed targeted next-generation sequencing of 4813 clinically relevant genes in the patient and her parents. We identified a novel FTO homozygous missense mutation (c.956C>T; p.(Ser319Phe)) in the affected individual. This mutation affects a highly conserved residue located in the same functional domain as the previously characterised mutation p.(Arg316Gln). Biochemical studies reveal that p.(Ser319Phe) FTO has reduced 2-oxoglutarate turnover and N-methyl-nucleoside demethylase activity. Our findings are consistent with previous reports that homozygous mutations in FTO can lead to rare growth retardation and developmental delay syndrome, and further support the proposal that FTO plays an important role in early development of human central nervous and cardiovascular systems. 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/

  15. Ethylene Antagonizes Salt-Induced Growth Retardation and Cell Death Process via Transcriptional Controlling of Ethylene-, BAG- and Senescence-Associated Genes in Arabidopsis.

    Science.gov (United States)

    Pan, Ya-Jie; Liu, Ling; Lin, Ying-Chao; Zu, Yuan-Gang; Li, Lei-Peng; Tang, Zhong-Hua

    2016-01-01

    The existing question whether ethylene is involved in the modulation of salt-induced cell death to mediate plant salt tolerance is important for understanding the salt tolerance mechanisms. Here, we employed Arabidopsis plants to study the possible role of ethylene in salt-induced growth inhibition and programmed cell death (PCD) profiles. The root length, DNA ladder and cell death indicated by Evan's blue detection were measured by compared to the control or salt-stressed seedlings. Secondly, the protoplasts isolated from plant leaves and dyed with Annexin V-FITC were subjected to flow cytometric (FCM) assay. Our results showed that ethylene works effectively in seedling protoplasts, antagonizing salt-included root retardation and restraining cell death both in seedlings or protoplasts. Due to salinity, the entire or partial insensitivity of ethylene signaling resulted in an elevated levels of cell death in ein2-5 and ein3-1 plants and the event were amended in ctr1-1 plants after salt treatment. The subsequent experiment with exogenous ACC further corroborated that ethylene could modulate salt-induced PCD process actively. Plant Bcl-2-associated athanogene (BAG) family genes are recently identified to play an extensive role in plant PCD processes ranging from growth, development to stress responses and even cell death. Our result showed that salinity alone significantly suppressed the transcripts of BAG6, BAG7 and addition of ACC in the saline solution could obviously re-activate BAG6 and BAG7 expressions, which might play a key role to inhibit the salt-induced cell death. In summary, our research implies that ethylene and salinity antagonistically control BAG family-, ethylene-, and senescence-related genes to alleviate the salt-induced cell death.

  16. Withaferin A Suppresses Liver Tumor Growth in a Nude Mouse ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of withaferin A on tumor growth and metastasis in liver in a nude mouse model. Methods: Withaferin A was injected through a portal vein to the orthotopic liver tumor in a nude mice model. Xenogen in vivo imaging system was used to monitor tumor growth and metastasis. The effect of ...

  17. Deletions and rearrangements of the H19/IGF2 enhancer region in patients with Silver-Russell syndrome and growth retardation

    DEFF Research Database (Denmark)

    Grønskov, Karen; Poole, Rebecca L; Hahnemann, Johanne M D

    2011-01-01

    Silver-Russell syndrome (SRS) is characterised by prenatal and postnatal growth retardation, dysmorphic facial features, and body asymmetry. In 35-60% of SRS cases the paternally methylated imprinting control region (ICR) upstream of the H19 gene (H19-ICR) is hypomethylated, leading to downregula...

  18. The relationship between the quantity and quality of prenatal movements in pregnancies complicated by intra-uterine growth retardation and premature rupture of the membranes

    NARCIS (Netherlands)

    Sival, D A; Visser, G H; Prechtl, H F

    1992-01-01

    In 17 fetuses with intrauterine growth retardation (IUGR), we studied the quantity of general movements and fetal breathing movements both cross-sectionally and longitudinally. In IUGR fetuses, cross-sectional comparisons were made between the quantity of fetal movements and (1) the fetal clinical

  19. THE RELATIONSHIP BETWEEN THE QUANTITY AND QUALITY OF PRENATAL MOVEMENTS IN PREGNANCIES COMPLICATED BY INTRAUTERINE GROWTH-RETARDATION AND PREMATURE RUPTURE OF THE MEMBRANES

    NARCIS (Netherlands)

    Sival, DA; VISSER, GHA; PRECHTL, HFR

    1992-01-01

    In 17 fetuses with intrauterine growth retardation (IUGR), we studied the quantity of general movements and fetal breathing movements both cross-sectionally and longitudinally. In IUGR fetuses, cross-sectional comparisons were made between the quantity of fetal movements and (1) the fetal clinical

  20. Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine

    NARCIS (Netherlands)

    Lambert, JS; Watts, DH; Mofenson, L; Stiehm, ER; Harris, DR; Bethel, J; Whitehouse, J; Jimenez, E; Gandia, J; Scott, G; O'Sullivan, MJ; Kovacs, A; Stek, A; Shearer, WT; Hammill, H; van Dyke, R; Maupin, R; Silio, M; Fowler, MG

    2000-01-01

    Objective: To evaluate independent contributions of maternal factors to adverse pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy (ART). Design: Risk factors for preterm birth (<37 weeks gestation), low birth weight (LBW) (<2500 g), and intrauterine growth retardation

  1. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy

    DEFF Research Database (Denmark)

    Mickiewicz, M; Zabielski, R; Grenier, B

    2012-01-01

    Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in pigle...

  2. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy

    DEFF Research Database (Denmark)

    Mickiewicz, M; Zabielski, R; Grenier, B

    2012-01-01

    Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets...

  3. Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks

    NARCIS (Netherlands)

    D. Bijlenga (Denise); K.E. Boers (Kim); E. Birnie (Erwin); B.W.J. Mol (Ben); S.C.M. Vijgen (Sylvia); J.A.M. van der Post (Joris); C.J.M. de Groot (Christianne); R.J.P. Rijnders (Robbert); P.J. Pernet (Paula); F.J.M.E. Roumen (Frans); R.H. Stigter (Rob); F.M.C. Delemarre (Friso); H.A. Bremer (Henk); M. Porath (Martina); S.A. Scherjon (Sico); G.J. Bonsel (Gouke)

    2011-01-01

    textabstractObjective: Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine

  4. Growth retardants and nutrition characteristics of the Thompson seedless and Italia grape cultivars

    Directory of Open Access Journals (Sweden)

    Albuquerque Teresinha Costa Silveira de

    2000-01-01

    Full Text Available Two experiments were carried out in a greenhouse to evaluate the variability in macronutrient contents in relation to growth regulator sprays on ?Thompson Seedless? and ?Italia? grapevines. The treatments were: chlormequat - 1,500mg L-1; daminozide - 3,000mg L-1; uniconazole - 30mg L-1; mepiquat chloride - 300mg .L-1 and control. The cuttings were grafted on the ?Tropical? rootstock and were rooted in sand. After 105 days of growth they were transplanted to 35L pots with a mixture of 1:1:1 volume of sand, soil and organic matter. Grapevines were pruned each 150 days, leaving two canes with six buds each for the ?Italia? cultivar and with fifteen buds for the ?Thompson Seedless? cultivar. Water was supplied through drip irrigation (1L/plant/day. Grapevines were fertilized with 1L of manure and micronutrient solution at each pruning. Macronutrients (MAP-1.45g, Ca2NO3-3.42g, urea-1.61g de , KCl-3.53g and MgSO4-1.94g were suplied each 15 days during the plant growth. The petioles and the shoots were sampled each growth season (150 days and dry matter was evaluated for yield and macronutrient contents (N, P, K, Ca and Mg. Results show that the spray of growth regulators induced alteration in the macronutrient patterns due to the decrease of shoot rate growth and increase in fruitfull shoots.

  5. Growth of high-density ZnO nanorods on wood with enhanced photostability, flame retardancy and water repellency

    Science.gov (United States)

    Kong, Lizhuo; Tu, Kunkun; Guan, Hao; Wang, Xiaoqing

    2017-06-01

    Zinc oxide (ZnO) nanorod arrays were successfully assembled on the wood surface in situ via a two-step process consisting of formation of ZnO seeds and subsequent crystal growth under hydrothermal conditions at a low temperature. The morphology and crystalline structure of the formed ZnO nanorods were studied by field-emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD). Highly dense and uniform arrays of ZnO nanorods with well-defined hexagonal facets were generated on the wood surface by tuning the concentration of the ZnO growth solution during the hydrothermal treatment. Accelerated weathering tests indicated that the assembled ZnO nanorod arrays were highly protective against UV radiation and greatly enhanced the photostability of the coated wood. Meanwhile, the ZnO nanorod-coated wood can withstand continuous exposure to flame with only minor smoldering in contrast with the pristine wood catching fire easily and burning rapidly. Moreover, when further modified with low-surface-energy stearic acid, the ZnO nanorod decorated wood surface can be transformed into a superhydrophobic surface, with a water contact angle (CA) of ∼154°. Such ZnO nanorod-modified woods with enhanced photostability, flame retardancy and water repellency offer an interesting alternative to conventional wood preservation strategies, highlighting their potential applications in some novel wood products.

  6. Psychomotor and intellectual development of children born with intrauterine growth retardation (IUGR).

    Science.gov (United States)

    Puga, B; Ferrández Longás, A; García Romero, R; Mayayo, E; Labarta, J I

    2004-03-01

    The possible impact of IUGR on the intellectual outcome of children born with IUGR gives special relevance to this condition. In order to determine the psychomotor and intellectual development of such children, we analyzed the evolution of 60 children through appropriate tests, along the years, and the possible influence of two factors, the socio-economic status of the family, and whether or not there was catch-up growth. Our results show a negative impact of IUGR on the intellectual outcome of these children, independent of catch-up growth, although those with catch-up growth showed better evolution. The socio-economic status plays a limited role only at older age. Those children followed longitudinally for 1 year did not show any amelioration of their IQ.

  7. Anemia and growth retardation associated with Schistosoma haematobium infection in Mali

    DEFF Research Database (Denmark)

    Stecher, Chalotte W; Sacko, Moussa; Madsen, Henry

    2017-01-01

    BackgroundThe aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. MethodsUrine, feces a....... Lower height for age z-scores were also associated with anemia. ConclusionsS. haematobium infection is likely to impact on child growth and possibly also anemia in all age groups and advocates for inclusion of whole populations into future control programes.......BackgroundThe aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. MethodsUrine, feces...

  8. Withaferin A Suppresses Liver Tumor Growth in a Nude Mouse ...

    African Journals Online (AJOL)

    The effect of withaferin A on tumor volume, invasive growth pattern, expression of Pyk2, upregulation of BAX/P53, apoptotic signaling and ... the direct effect of withaferin A on liver cancer cells and endothelial cells was further investigated. Results: A significant ... tumor cell invasiveness in colon cancer [7] and is related to ...

  9. Classically induced suppression of energy growth in a chaotic ...

    Indian Academy of Sciences (India)

    Recent experiments with Bose–Einstein condensates (BEC) in traps and speckle potentials have explored the dynamical regime in which the evolving BEC clouds localize due to the influence of classical dynamics. The growth of their mean energy is effectively arrested. This is in contrast with the well-known localization ...

  10. Bergenin suppresses the growth of colorectal cancer cells by ...

    African Journals Online (AJOL)

    It also led to marked accumulation of intracellular reactive oxygen species (ROS), a breaker of DNA strand in HCT116 cells. ..... regulating cell proliferation described in the literature have been related to malignant transformation [12]. Thus, we assumed that bergenin-induced cell growth inhibition was due to cell cycle arrest.

  11. Growth retardants and nutrition characteristics of the Thompson seedless and Italia grape cultivars

    OpenAIRE

    Albuquerque Teresinha Costa Silveira de; Dechen Antonio Roque; Castro Paulo Roberto de Camargo e

    2000-01-01

    Two experiments were carried out in a greenhouse to evaluate the variability in macronutrient contents in relation to growth regulator sprays on ‘Thompson Seedless’ and ‘Italia’ grapevines. The treatments were: chlormequat - 1,500mg L-1; daminozide - 3,000mg L-1; uniconazole - 30mg L-1; mepiquat chloride - 300mg .L-1 and control. The cuttings were grafted on the ‘Tropical’ rootstock and were rooted in sand. After 105 days of growth they were transplanted to 35L pots with a mixture of 1:1:1 vo...

  12. Pyridine 2,4-Dicarboxylic Acid Suppresses Tomato Seedling Growth.

    Science.gov (United States)

    Fragkostefanakis, Sotirios; Kaloudas, Dimitrios; Kalaitzis, Panagiotis

    2018-01-01

    Pyridine 2,4-dicarboxylic acid is a structural analog of 2-oxoglutarate and is known to inhibit 2-oxoglutare-dependent dioxygenases. The effect of this inhibitor in tomato seedlings grown in MS media supplied with various concentrations of PDCA was investigated, resulting in shorter roots and hypocotyls in a dose-dependent manner. The partial inhibition of growth in roots was more drastic compared to hypocotyls and was attributed to a decrease in the elongation of root and hypocotyl cells. Concentrations of 100 and 250 μM of PDCA decreased hydroxyproline content in roots while only the 250 μM treatment reduced the hydroxyproline content in shoots. Seedlings treated with 100 μM PDCA exhibited enhanced growth of hypocotyl and cotyledon cells and higher hydroxyproline content resulting in cotyledons with greater surface area. However, no alterations in hypocotyl length were observed. Prolyl 4 hydroxylases (P4Hs) are involved in the O-glycosylation of AGPs and were also highly expressed during seedling growth. Moreover PDCA induced a decrease in the accumulation of HRGPs and particularly in AGPs-bound epitopes in a dose dependent-manner while more drastic reduction were observed in roots compared to shoots. In addition, bulged root epidermal cells were observed at the high concentration of 250 μM which is characteristic of root tissues with glycosylation defects. These results indicate that PDCA induced pleiotropic effects during seedling growth while further studies are required to better investigate the physiological significance of this 2-oxoglutarate analog. This pharmacological approach might be used as a tool to better understand the physiological significance of HRGPs and probably P4Hs in various growth and developmental programs in plants.

  13. Pyridine 2,4-Dicarboxylic Acid Suppresses Tomato Seedling Growth

    Directory of Open Access Journals (Sweden)

    Sotirios Fragkostefanakis

    2018-01-01

    Full Text Available Pyridine 2,4-dicarboxylic acid is a structural analog of 2-oxoglutarate and is known to inhibit 2-oxoglutare-dependent dioxygenases. The effect of this inhibitor in tomato seedlings grown in MS media supplied with various concentrations of PDCA was investigated, resulting in shorter roots and hypocotyls in a dose-dependent manner. The partial inhibition of growth in roots was more drastic compared to hypocotyls and was attributed to a decrease in the elongation of root and hypocotyl cells. Concentrations of 100 and 250 μM of PDCA decreased hydroxyproline content in roots while only the 250 μM treatment reduced the hydroxyproline content in shoots. Seedlings treated with 100 μM PDCA exhibited enhanced growth of hypocotyl and cotyledon cells and higher hydroxyproline content resulting in cotyledons with greater surface area. However, no alterations in hypocotyl length were observed. Prolyl 4 hydroxylases (P4Hs are involved in the O-glycosylation of AGPs and were also highly expressed during seedling growth. Moreover PDCA induced a decrease in the accumulation of HRGPs and particularly in AGPs-bound epitopes in a dose dependent-manner while more drastic reduction were observed in roots compared to shoots. In addition, bulged root epidermal cells were observed at the high concentration of 250 μM which is characteristic of root tissues with glycosylation defects. These results indicate that PDCA induced pleiotropic effects during seedling growth while further studies are required to better investigate the physiological significance of this 2-oxoglutarate analog. This pharmacological approach might be used as a tool to better understand the physiological significance of HRGPs and probably P4Hs in various growth and developmental programs in plants.

  14. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...... to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene...... in healthy adults, and this decline could hypothetically be responsible for the increased risk of IHD with ageing. A recent nested case-control study found that adults without IHD, but with low circulating IGF-I levels and high IGF binding protein-3 levels, had a significantly increased risk of developing...

  15. Chlorpyrifos reduces nickel-induced growth retardation of the soil dwelling Collembolan Folsomia candida.

    NARCIS (Netherlands)

    Broerse, M.; van Gestel, C.A.M.

    2010-01-01

    For 7 weeks, we studied the effects on body size and growth rate of Folsomia candida exposed to nickel and chlorpyrifos and their mixtures in a natural Lufa 2.2 soil. Nickel significantly reduced the development of body size of the springtails, although no complete dose-response curve was obtained.

  16. Intrauterine growth retardation and consequences for endocrine and cardiovascular diseases in adult life

    DEFF Research Database (Denmark)

    Jensen, Rikke Bodin Beck; Chellakooty, Marla; Vielwerth, Signe

    2003-01-01

    to 40 weeks of gestation, but IGF-I levels are four to five times lower than those in the maternal circulation. Thus IGF-I levels in fetal as well as in maternal circulation are thought to regulate fetal growth. Circulating levels of IGF-I are thought to be genetically controlled and several IGF-I gene......Low birth weight has been associated with an increased incidence of ischaemic heart disease (IHD) and type 2 diabetes. Endocrine regulation of fetal growth by growth hormone (GH) and insulin-like growth factor (IGF)-I is complex. Placental GH is detectable in maternal serum from the 8th to the 12th...... gestational week, and rises gradually during pregnancy where it replaces pituitary GH in the maternal circulation. The rise in placental GH may explain the pregnancy-induced rise in maternal serum IGF-I levels. In the fetal compartment, IGF-I levels increase significantly in normally growing fetuses from 18...

  17. Triparanol suppresses human tumor growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Bi, Xinyu; Han, Xingpeng; Zhang, Fang; He, Miao; Zhang, Yi; Zhi, Xiu-Yi; Zhao, Hong

    2012-01-01

    Highlights: ► Demonstrate Triparanol can block proliferation in multiple cancer cells. ► Demonstrate Triparanol can induce apoptosis in multiple cancer cells. ► Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. ► Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  18. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    International Nuclear Information System (INIS)

    Deng, Yu; Cao, Hong; Cu, Fenglong; Xu, Dan; Lei, Youying; Tan, Yang; Magdalou, Jacques; Wang, Hui; Chen, Liaobin

    2013-01-01

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes

  19. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Yu; Cao, Hong; Cu, Fenglong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Lei, Youying [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Tan, Yang [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  20. Fagopyrum esculentum Alters Its Root Exudation after Amaranthus retroflexus Recognition and Suppresses Weed Growth.

    Science.gov (United States)

    Gfeller, Aurélie; Glauser, Gaétan; Etter, Clément; Signarbieux, Constant; Wirth, Judith

    2018-01-01

    Weed control by crops through growth suppressive root exudates is a promising alternative to herbicides. Buckwheat ( Fagopyrum esculentum ) is known for its weed suppression and redroot pigweed ( Amaranthus retroflexus ) control is probably partly due to allelopathic root exudates. This work studies whether other weeds are also suppressed by buckwheat and if the presence of weeds is necessary to induce growth repression. Buckwheat and different weeds were co-cultivated in soil, separating roots by a mesh allowing to study effects due to diffusion. Buckwheat suppressed growth of pigweed, goosefoot and barnyard grass by 53, 42, and 77% respectively without physical root interactions, probably through allelopathic compounds. Root exudates were obtained from sand cultures of buckwheat (BK), pigweed (P), and a buckwheat/pigweed mixed culture (BK-P). BK-P root exudates inhibited pigweed root growth by 49%. Characterization of root exudates by UHPLC-HRMS and principal component analysis revealed that BK and BK-P had a different metabolic profile suggesting that buckwheat changes its root exudation in the presence of pigweed indicating heterospecific recognition. Among the 15 different markers, which were more abundant in BK-P, tryptophan was identified and four others were tentatively identified. Our findings might contribute to the selection of crops with weed suppressive effects.

  1. Report of a consultants meeting on causes and consequences of intrauterine growth retardation (IUGR) in populations from developing countries

    International Nuclear Information System (INIS)

    2003-01-01

    The International Atomic Energy Agency (IAEA) at its Headquarters in Vienna convened a consultants meeting from 9-13 December, 2002, to provide the Agency current insights into the application of nuclear and isotopic techniques as tool to support studies aimed at assessing the causes of Intrauterine Growth Retardation (IUGR). The consultants were: Dr. B. Caballero, Dr. D. Labadarios, Dr. G. Carroli, Dr. L.S. Bakketeig and Dr. P.T.V Nair. Representatives from the World Health Organization (WHO), Dr. G. Glugston and Dr. S. Khanum, were present as observers during the initial part of the meeting. Given the Consultants' areas of expertise and the topics covered in the discussions, the scope of the Meeting was modified to 'The application of isotopic and nuclear techniques to address the problem of intrauterine growth retardation (IUGR) in populations from developing countries'. The objectives of the meeting were to: (i) Evaluate the overall scope of a new co-ordinated research project (CRP) and suggest options for specific areas of research within that scope; (ii) Examine the applicability of nuclear and isotope based techniques in researches related to practical approaches for monitoring maternal weight and weight gain during pregnancy (e.g. body composition and energy balance assessment); (iii) Establish harmonised methods and criteria for appropriate weight gain and foetal growth charts for pregnant women in developing countries; (iv) Suggest approaches to assess the effectiveness of nutrition interventions aimed at reducing IUGR and its consequences. This meeting benefited from the broad areas of experience of scientists from both developed and developing countries. Their expertise in the use of isotopes and nuclear techniques, and in studies on human nutrition, epidemiology, IUGR, Low birth weight and undernutrition provided the advocacy and approaches to fellow in the application of nuclear and isotopic techniques as part of maternal malnutrition and IUGR studies

  2. Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.

    Science.gov (United States)

    Chitambar, Christopher R; Al-Gizawiy, Mona M; Alhajala, Hisham S; Pechman, Kimberly R; Wereley, Janine P; Wujek, Robert; Clark, Paul A; Kuo, John S; Antholine, William E; Schmainda, Kathleen M

    2018-03-28

    Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMECs) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSCs) lines express TfRs and that their growth is inhibited by gallium maltolate (GaM) in vitro. After 24-h of incubation with GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose-dependent decrease in oxygen consumption and a decrease in the activity of the iron-dependent M2 subunit of ribonucleotide reductase (RRM2). Immunohistochemical staining of rat and human tumor-bearing brains showed that glioblastoma, but not normal glial cells, expressed TfR1 and RRM2 and that glioblastoma expressed greater levels of H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma xenograft rat model, GaM retarded the growth of brain tumors relative to untreated control (p=0.0159) and reduced tumor mitotic figures (p=0.045). Tumors in GaM-treated animals displayed an upregulation of TfR1 expression relative to control animals thus indicating that gallium produced tumor iron deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U-87 MG and D54 cells in vitro. We conclude that GaM enters the brain via TfR1 on BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor growth. Further development of novel gallium compounds for brain tumor treatment is warranted. Copyright ©2018, American Association for Cancer Research.

  3. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

    DEFF Research Database (Denmark)

    Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M

    2013-01-01

    Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here...... for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis....

  4. Color Doppler monitoring of changes of utero-placental-fetal circulation in normal pregnancy and intrauterine growth retardation.

    Science.gov (United States)

    Xu, J; Wen, L; Ma, T; Zhang, Y; Zhang, Q; Gao, S; Zhao, M; Wu, H; Hu, J

    1997-01-01

    The utero-placental-fetal circulation (UPFC) of 150 subjects during second and third trimester was examined by using color Doppler. Of them 89 were normal woman and 58 were patients with intrauterine growth retardation IUGR). Our results showed that UPFC was increased gradually during normal pregnant period. In IUGR patients it was revealed that TAV and Q of UmA, UmV and UtA decreased at 20th week of gestation, especially after 30th week. PI, RI and S/D ratio of UmA were increased, but TAV, Q of UmA and UmV were markly reduced, so was UtA. PI were increased, but the changes of RI, S/D ratio in UtA were not significant. Hemodynamical findings of UmA, UmV and UtA were abnormal in 92.53% of IUGR patients. Only 81.03% present abnormal S/D ratio of UmA (P UtA. Our results suggested that using color doppler ultrasound for examination of hemodynamical changes of UmA, UmV and UtA could revealed UPFC function directly. It is one of the best methods for monitoring IUGR and might be used for early diagnosis of IUGR. The main pathophysiological changes of IUGR were UPFC obstruction and placental disfunction.

  5. Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate.

    Science.gov (United States)

    Lindgren, Amelia M; Hoyos, Tatiana; Talkowski, Michael E; Hanscom, Carrie; Blumenthal, Ian; Chiang, Colby; Ernst, Carl; Pereira, Shahrin; Ordulu, Zehra; Clericuzio, Carol; Drautz, Joanne M; Rosenfeld, Jill A; Shaffer, Lisa G; Velsher, Lea; Pynn, Tania; Vermeesch, Joris; Harris, David J; Gusella, James F; Liao, Eric C; Morton, Cynthia C

    2013-05-01

    We describe a female subject (DGAP100) with a 46,X,t(X;5)(p11.3;q35.3)inv(5)(q35.3q35.1)dn, severe psychomotor retardation with hypotonia, global postnatal growth restriction, microcephaly, globally reduced cerebral volume, seizures, facial dysmorphia and cleft palate. Fluorescence in situ hybridization and whole-genome sequencing demonstrated that the X chromosome breakpoint disrupts KDM6A in the second intron. No genes were directly disrupted on chromosome 5. KDM6A is a histone 3 lysine 27 demethylase and a histone 3 lysine 4 methyltransferase. Expression of KDM6A is significantly reduced in DGAP100 lymphoblastoid cells compared to control samples. We identified nine additional cases with neurodevelopmental delay and various other features consistent with the DGAP100 phenotype with copy number variation encompassing KDM6A from microarray databases. We evaluated haploinsufficiency of kdm6a in a zebrafish model. kdm6a is expressed in the pharyngeal arches and ethmoid plate of the developing zebrafish, while a kdm6a morpholino knockdown exhibited craniofacial defects. We conclude KDM6A dosage regulation is associated with severe and diverse structural defects and developmental abnormalities.

  6. Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice

    Directory of Open Access Journals (Sweden)

    Philip E. Lapinski

    2013-11-01

    In mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2 tyrosine phosphatase, results in severe skeletal abnormalities. To understand the extent to which skeletal abnormalities can be attributed to perturbation of SHP-2 function in bone-forming osteoblasts and chondrocytes, we generated mice in which disruption of Ptpn11 is restricted to mesenchymal stem cells (MSCs and their progeny, which include both cell types. MSC-lineage-specific SHP-2 knockout (MSC SHP-2 KO mice exhibited postnatal growth retardation, limb and chest deformity, and calvarial defects. These skeletal abnormalities were associated with an absence of mature osteoblasts and massive chondrodysplasia with a vast increase in the number of terminally differentiated hypertrophic chondrocytes in affected bones. Activation of mitogen activated protein kinases (MAPKs and protein kinase B (PKB; also known as AKT was impaired in bone-forming cells of MSC SHP-2 KO mice, which provides an explanation for the skeletal defects that developed. These findings reveal a cell-autonomous role for SHP-2 in bone-forming cells in mice in the regulation of skeletal development. The results add to our understanding of the pathophysiology of skeletal abnormalities observed in humans with germline mutations in the PTPN11 gene (e.g. Noonan syndrome and LEOPARD syndrome.

  7. Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism.

    Science.gov (United States)

    Alsemari, Abdulaziz; Al-Younes, Banan; Goljan, Ewa; Jaroudi, Dyala; BinHumaid, Faisal; Meyer, Brian F; Arold, Stefan T; Monies, Dorota

    2017-11-14

    Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We expand aaRSs-related phenotypes through characterization of the clinical and molecular basis of a novel autosomal-recessive syndrome manifesting severe mental retardation, ataxia, speech impairment, epilepsy, short stature, microcephaly, hypogonadism, and growth hormone deficiency. A G>A variant in exon 29 of VARS2 (c.3650G>A) (NM_006295) was identified in the index case. This homozygous variant was confirmed by Sanger sequencing and segregated with disease in the family studied. The c.3650G>A change results in alteration of arginine to histidine at residue 1217 (R1217H) of the mature protein and is predicted to be pathogenic. These findings contribute to a growing list of aaRSs disorders, broadens the spectrum of phenotypes attributable to VARS2 mutations, and provides new insight into genotype-phenotype correlations among the mitochondrial synthetase genes.

  8. Genetic markers for inherited thrombophilia are associated with fetal growth retardation in the population of Central Russia.

    Science.gov (United States)

    Reshetnikov, Evgeny; Zarudskaya, Oksana; Polonikov, Alexey; Bushueva, Olga; Orlova, Valentina; Krikun, Evgeny; Dvornyk, Volodymyr; Churnosov, Mikhail

    2017-07-01

    The aim of this study was to examine the role of hereditary thrombophilia in the development of fetal growth retardation (FGR) in the population of Central Russia. The case-control study sample included 497 women in the third trimester of pregnancy recruited during 2009-2013. The participants were enrolled into two groups: patients with FGR (n = 250) and controls without FGR (n = 247). The participants were genotyped for four genetic markers of hereditary thrombophilia: factor V Leiden (G > A FV, rs6025), prothrombin (G > A FII, rs1799963), factor VII (G > A FVII, rs6046), and fibrinogen (G > A FI, rs1800790). The genetic factors for an increased risk of FGR were allele G of rs6046 (odds ratio [OR] = 2.34) and genotype GG of rs6046 (OR = 2.64), whereas genotype GA of rs6046 had the protective value (OR = 0.42). A combination of alleles G of rs1799963, A of rs6046, and G of rs1800790 (OR = 0.31) reduces the risk of FGR. Polymorphism rs6046 of the FVII gene is associated with the development of FGR. © 2017 Japan Society of Obstetrics and Gynecology.

  9. Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

    KAUST Repository

    Alsemari, Abdulaziz

    2017-11-14

    Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We expand aaRSs-related phenotypes through characterization of the clinical and molecular basis of a novel autosomal-recessive syndrome manifesting severe mental retardation, ataxia, speech impairment, epilepsy, short stature, microcephaly, hypogonadism, and growth hormone deficiency.A G>A variant in exon 29 of VARS2 (c.3650G>A) (NM_006295) was identified in the index case. This homozygous variant was confirmed by Sanger sequencing and segregated with disease in the family studied. The c.3650G>A change results in alteration of arginine to histidine at residue 1217 (R1217H) of the mature protein and is predicted to be pathogenic.These findings contribute to a growing list of aaRSs disorders, broadens the spectrum of phenotypes attributable to VARS2 mutations, and provides new insight into genotype-phenotype correlations among the mitochondrial synthetase genes.

  10. Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

    Directory of Open Access Journals (Sweden)

    Angela Wang

    2016-12-01

    Full Text Available Procyanidins are a family of plant metabolites that have been suggested to mitigate osteoarthritis pathogenesis in mice. However, the underlying mechanism is largely unknown. This study aimed to determine whether procyanidins mitigate traumatic injury-induced osteoarthritis (OA disease progression, and whether procyanidins exert a chondroprotective effect by, at least in part, suppressing vascular endothelial growth factor signaling. Procyanidins (extracts from pine bark, orally administered to mice subjected to surgery for destabilization of the medial meniscus, significantly slowed OA disease progression. Real-time polymerase chain reaction revealed that procyanidin treatment reduced expression of vascular endothelial growth factor and effectors in OA pathogenesis that are regulated by vascular endothelial growth factor. Procyanidin-suppressed vascular endothelial growth factor expression was correlated with reduced phosphorylation of vascular endothelial growth factor receptor 2 in human OA primary chondrocytes. Moreover, components of procyanidins, procyanidin B2 and procyanidin B3 exerted effects similar to those of total procyanidins in mitigating the OA-related gene expression profile in the primary culture of human OA chondrocytes in the presence of vascular endothelial growth factor. Together, these findings suggest procyanidins mitigate OA pathogenesis, which is mediated, at least in part, by suppressing vascular endothelial growth factor signaling.

  11. Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit.

    Science.gov (United States)

    Metges, Cornelia C; Lang, Iris S; Hennig, Ulf; Brüssow, Klaus-Peter; Kanitz, Ellen; Tuchscherer, Margret; Schneider, Falk; Weitzel, Joachim M; Steinhoff-Ooster, Anika; Sauerwein, Helga; Bellmann, Olaf; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2012-01-01

    High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.

  12. Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit.

    Directory of Open Access Journals (Sweden)

    Cornelia C Metges

    Full Text Available High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR. To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP, adequate (12.1%, AP, and high (30%, HP protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC, %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.

  13. Growth of high-density ZnO nanorods on wood with enhanced photostability, flame retardancy and water repellency

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Lizhuo; Tu, Kunkun; Guan, Hao [Research Institute of Wood Industry, Chinese Academy of Forestry, Beijing 100091 (China); Wang, Xiaoqing, E-mail: wangxq@caf.ac.cn [Research Institute of Forestry New Technology, Chinese Academy of Forestry, Beijing 100091 (China); Research Institute of Wood Industry, Chinese Academy of Forestry, Beijing 100091 (China)

    2017-06-15

    Highlights: • ZnO nanorod arrays were deposited on the wood surface via a hydrothermal process. • The assembled ZnO nanorod arrays greatly enhanced the photostability of wood. • The treated wood can sustain direct exposure to flame with only minor smoldering. • The ZnO-coated wood modified with stearic acid showed a superhydrophobic surface. - Abstract: Zinc oxide (ZnO) nanorod arrays were successfully assembled on the wood surface in situ via a two-step process consisting of formation of ZnO seeds and subsequent crystal growth under hydrothermal conditions at a low temperature. The morphology and crystalline structure of the formed ZnO nanorods were studied by field-emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD). Highly dense and uniform arrays of ZnO nanorods with well-defined hexagonal facets were generated on the wood surface by tuning the concentration of the ZnO growth solution during the hydrothermal treatment. Accelerated weathering tests indicated that the assembled ZnO nanorod arrays were highly protective against UV radiation and greatly enhanced the photostability of the coated wood. Meanwhile, the ZnO nanorod-coated wood can withstand continuous exposure to flame with only minor smoldering in contrast with the pristine wood catching fire easily and burning rapidly. Moreover, when further modified with low-surface-energy stearic acid, the ZnO nanorod decorated wood surface can be transformed into a superhydrophobic surface, with a water contact angle (CA) of ∼154°. Such ZnO nanorod-modified woods with enhanced photostability, flame retardancy and water repellency offer an interesting alternative to conventional wood preservation strategies, highlighting their potential applications in some novel wood products.

  14. Crustose coralline algae can suppress macroalgal growth and recruitment on Hawaiian coral reefs

    NARCIS (Netherlands)

    Vermeij, M.J.A.; Dailer, M.L.; Smith, C.M.

    2011-01-01

    Crustose coralline algae are important components of tropical reef communities because they promote successful settlement by corals and contribute to solidification of the reef framework. We show experimentally that crustose coralline algae are also capable of suppressing the growth and recruitment

  15. Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Lerche, Christian J; Christophersen, Lars J

    2018-01-01

    Biofilm-infected wounds are clinically challenging. Vascular endothelial growth factor and host defence S100A8/A9 are crucial for wound healing but may be suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm infection was compared in central and peripheral zones of burn-wo...

  16.  Distal Renal Tubular Acidosis, Hypokalemic Paralysis, Nephrocalcinosis, Primary Hypothyroidism, Growth Retardation, Osteomalacia and Osteoporosis Leading to Pathological Fracture: A Case Report

    Directory of Open Access Journals (Sweden)

    Mayada Mohammad Swar

    2011-07-01

    Full Text Available  Renal tubular acidosis (RTA is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA, hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA have been reported.

  17. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    Energy Technology Data Exchange (ETDEWEB)

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan); Ogawa, Atsushi [Department of Biological Production, Akita Prefectural University, Shimosinjyou-nakano 241-438, Akita 010-0195 (Japan); Suzuki, Shunji, E-mail: suzukis@yamanashi.ac.jp [Laboratory of Fruit Genetic Engineering, The Institute of Enology and Viticulture, University of Yamanashi, Kofu, Yamanashi 400-0005 (Japan)

    2011-02-18

    Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.

  18. ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

    International Nuclear Information System (INIS)

    Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki; Ogawa, Atsushi; Suzuki, Shunji

    2011-01-01

    Highlights: → VIGG is an ER stress-induced protein in plant. → We examine the characteristics of VIGG-overexpressing Arabidopsis plants. → VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. → VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.

  19. miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao; Zhang, Haiping [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China); Zhu, Wei, E-mail: zhuwei_2020@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2016-07-01

    As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3′ untranslated region (3′UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation and colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. -- Highlights: •First reported overexpression of AURKA in melanoma. •Targeting AURKA inhibits melanoma growth in vitro and in vivo. •Further found miR-137 suppressed cell growth by binding to AURKA 3′UTR. •Re-expression of AURKA rescued miR-137-mediated suppression. •miR-137-AURKA axis may be potential therapeutic targets of melanoma.

  20. Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids.

    Science.gov (United States)

    Perry, R J; Findlay, C A; Donaldson, M D C

    2002-07-01

    We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.

  1. Comparison of blood lead levels of mothers and cord blood in intrauterine growth retarded neonates and normal term neonates

    International Nuclear Information System (INIS)

    Iranpour, R.; Besharati, Amir A.; Nasseri, F.; Hashemipour, M.; Kelishadi, R.; Balali-Mood, M.

    2007-01-01

    Objective was to compare the blood lead levels of mothers and cord blood in intrauterine growth retarded (IUGR) neonates and normal term neonates. From April 2005, we carried out a cross-sectional, prospective study in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were measured in the umbilical cord and maternal venous blood samples in the 32 mother-infant pairs with IUGR full term neonates and 34 mother-infant pairs with normal full term neonates. Blood-lead levels were analyzed by atomic absorption spectrometry. The mean lead concentration in neonates of IUGR and normal groups was not significantly different (107.47+- 16.75 versus 113.08+-19.08 ug/L, p=0.2). The mean lead concentration in mothers of IUGR group was lower than normal groups, but this difference was not significant (124.56+-19.71 versus 135.26+-26.91 ug/L, p=0.07). Maternal lead levels were strongly related with related with cord blood in both IUGR and normal groups (r=0.8, p 100ug/L by the centers for disease control; however, this was not statistically different between the groups. Our results indicate that the mean lead level was not higher in IUGR neonates, and the whole blood lead was not related to the birth weight. In addition, maternal and cord blood lead levels were strongly correlated, and there were remarkable lead burdens on both the mothers and their neonates in this industrial area. (author)

  2. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects.

    Directory of Open Access Journals (Sweden)

    Kerri M Luzzo

    Full Text Available Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment.We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage.Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes.

  3. Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.

    Science.gov (United States)

    Wang, Ying; Rishi, Arun K; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I; Wali, Anil

    2011-11-01

    Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.

  4. Dual inhibition of Wnt and Yes-associated protein signaling retards the growth of triple-negative breast cancer in both mesenchymal and epithelial states.

    Science.gov (United States)

    Sulaiman, Andrew; McGarry, Sarah; Li, Li; Jia, Deyong; Ooi, Sarah; Addison, Christina; Dimitroulakos, Jim; Arnaout, Angel; Nessim, Carolyn; Yao, Zemin; Ji, Guang; Song, Haiyan; Gadde, Suresh; Li, Xuguang; Wang, Lisheng

    2018-04-01

    Triple-negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer-related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesenchymal-like and epithelial-like states have been revealed in breast CSCs. Thus, strategies capable of simultaneously inhibiting bulk and CSC populations in both mesenchymal and epithelial states have yet to be developed. Wnt/β-catenin and Hippo/YAP pathways are crucial in tumorigenesis, but importantly also possess tumor suppressor functions in certain contexts. One possibility is that TNBC cells in epithelial or mesenchymal state may differently affect Wnt/β-catenin and Hippo/YAP signaling and CSC phenotypes. In this report, we found that YAP signaling and CD44 high /CD24 -/low CSCs were upregulated while Wnt/β-catenin signaling and ALDH+ CSCs were downregulated in mesenchymal-like TNBC cells, and vice versa in their epithelial-like counterparts. Dual knockdown of YAP and Wnt/β-catenin, but neither alone, was required for effective suppression of both CD44 high /CD24 -/low and ALDH+ CSC populations in mesenchymal and epithelial TNBC cells. These observations were confirmed with cultured tumor fragments prepared from patients with TNBC after treatment with Wnt inhibitor ICG-001 and YAP inhibitor simvastatin. In addition, a clinical database showed that decreased gene expression of Wnt and YAP was positively correlated with decreased ALDH and CD44 expression in patients' samples while increased patient survival. Furthermore, tumor growth of TNBC cells in either epithelial or mesenchymal state was retarded, and both CD44 high /CD24 -/low and ALDH+ CSC subpopulations were diminished in a human xenograft model after dual administration of ICG-001 and simvastatin. Tumorigenicity was also hampered after secondary transplantation. These data suggest a new

  5. MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yanxin [Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191 (China); Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036 (China); Yue, Xupeng [Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036 (China); Cui, Yuanyuan [Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191 (China); Zhang, Jufeng, E-mail: jfzhang111@163.com [Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036 (China); Wang, KeWei, E-mail: wangkw@bjmu.edu.cn [Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191 (China); Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036 (China); Department of Molecular and Cellular Pharmacology, State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191 (China)

    2013-11-29

    Highlights: •miR-124 is down-regulated in hepatocellular carcinoma HepG2 cells. •Over-expression of miR-124 suppresses proliferation and induces apoptosis in HepG2 cells. •miR-124 inhibits xenograft tumor growth in nude mice implanted with HepG2 cells by reducing STAT3 expression. •STATs function as a novel target of miR-124 in HCC HepG2 cells. -- Abstract: The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3′-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC.

  6. Virus-like particles suppress growth of the red-tide-forming marine dinoflagellate Gymnodinium mikimotoi.

    Science.gov (United States)

    Onji, Masashi; Nakano, Shin-ichi; Suzuki, Satoru

    2003-01-01

    We isolated 2 virus-like agents that suppressed growth of Gymnodinium mikimotoi from coastal waters of the Uwa Sea, Japan. The agents found in the flagellate cells, named GM6 and GM7, were filterable in a 0.22-microm-pore filter with approximately 100-nm shapes. Electron microscopic observation showed the presence of virus-like particles in severely damaged G. mikimotoi cells infected by GM6. The growth-suppression activity of the agents (GM6 or GM7) was lost by heating at 50 degrees C, with treatments of DNase and protease, and filtration through a 0.05-microm filter. Our results suggest that the agents are DNA viruses infectious to and virulent for G. mikimotoi. This is the first report of a virus-like agent specific to G. mikimotoi.

  7. Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

    International Nuclear Information System (INIS)

    Hara, H.; Seon, B.K.

    1987-01-01

    In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment

  8. Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade.

    Directory of Open Access Journals (Sweden)

    Jiaoyuan Jia

    Full Text Available Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC cell lines and the molecular mechanisms involved. For this purpose, we performed cell proliferation assay by colony-forming ability in seven human HCC cells subjected to XAV-939 and G007-LK Tankyrase inhibitors. Noticeably, the two Tankyrase inhibitors suppressed the HCC cell growth in a dose-dependent manner. Furthermore, we found that Tankyrase inhibitors synergized with MEK and AKT inhibitors to suppress HCC cell proliferation. At the molecular level, Tankyrase inhibitors significantly decreased YAP protein levels, reduced the expression of YAP target genes, and inhibited YAP/TEAD luciferase reporter activity. In addition, Tankyrase inhibitors administration was accompanied by upregulation of Angiomotin-like 1 (AMOTL1 and Angiomotin-like 2 (AMOTL2 proteins, two major negative regulators of YAP. Altogether, the present data indicate that XAV-939 and G007-LK Tankyrase inhibitors could suppress proliferation of hepatocellular carcinoma cells and downregulate YAP/TAZ by stabilizing AMOTL1 and AMOTL2 proteins, thus representing new potential anticancer drugs against hepatocellular carcinoma.

  9. Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

    Science.gov (United States)

    Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

    2015-12-01

    The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

  10. The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor α chain (CD25) in murine splenocytes

    International Nuclear Information System (INIS)

    Pullen, Sabine; Boecker, Ronald; Tiegs, Gisa

    2003-01-01

    Polybrominated flame retardants (PBF) are frequently used additives in electronical equipment. They are ubiquitous environmental contaminants which bioaccumulate with several health effects for humans and the environment. This study investigated immunotoxic effects of the PBF tetrabromobisphenol A (TBBP A), tetrabromobisphenol A-bisallylether (TBBP A-AE), tetrabromobisphenol A-bis-(2,3-dibromopropyl-ether) (TBBP A-PE), decabromodiphenylether (DBDE), and 2,4,6-tribromophenol (TBP) in vitro. The structurally related polychlorinated aromatic hydrocarbon 3,4,3',4'-tetrachlorobiphenyl (PCB77) and dioxins mediate their immunotoxicity via the Ah-receptor gene complex. A highly relevant function of the Ah receptor, the induction of CYP 1A1 in hepatocytes of C57BL/6 mice by the established inducers 3-methylcholanthrene (MC) and PCB77 was compared to the effect of PBF by measurement of ethoxyresorufin-o-deethylase (EROD) activity. The PBF did not show any induction of CYP 1A1, while EROD activity of hepatocytes exposed to MC and PCB77 was induced 10.8- and 8.7-fold, respectively. To investigate immunotoxic effects of the flame retardants, splenocytes of C57BL/6 mice were incubated with subtoxic doses of the flame retardants and PCB77 and activated by concanavalin A (Con A). The flame retardants TBBP A and TBBP A-AE significantly inhibited the expression of interleukin-2 receptor α chain (CD25) in contrast to TBBP A-PE, DBDE, TBP, and PCB77 as shown by immunohistochemistry and quantitative analysis by laser scanning cytometry. None of the substances had any effect on the Con A-induced production of cytokines. Hence, TBBP A and TBBP A-AE may act as immunotoxic compounds by specifically inhibiting the expression of CD25

  11. Effects of medium-chain triglycerides on intestinal morphology and energy metabolism of intrauterine growth retarded weanling piglets.

    Science.gov (United States)

    Zhang, Li-Li; Zhang, Hao; Li, Yue; Wang, Tian

    2017-06-01

    It has been shown that there is a relationship between intrauterine growth retardation (IUGR) and postnatal intestinal damage involved in energy deficits. Therefore, the present study was conducted to investigate the effect of medium-chain triglycerides (MCT) on the intestinal morphology, intestinal function and energy metabolism of piglets with IUGR. At weaning (21 ± 1.1 d of age), 24 IUGR piglets and 24 normal birth weight (NBW) piglets were selected according to their birth weights (BW) (IUGR: 0.95 ± 0.04 kg BW; NBW: 1.58 ± 0.04 kg BW) and their weights at the time of weaning (IUGR: 5.26 ± 0.15 kg BW; NBW: 6.98 ± 0.19 kg BW). The piglets were fed a diet of either long-chain triglycerides (LCT) (containing 5% LCT) or MCT (containing 1% LCT and 4% MCT) for 28 d. Then, the piglets' intestinal morphology, biochemical parameters and mRNA abundance related to intestinal damage and energy metabolism were determined. IUGR was found to impair intestinal morphology, with evidence of decreased villus height and increased crypt depth; however, these negative effects of IUGR were ameliorated by MCT treatment. IUGR piglets showed compromised intestinal digestion and absorption functions when compared with NBW piglets. However, feeding MCT increased the maltase activity in the jejunum and alleviated IUGR-induced reductions in plasma d-xylose concentrations and jejunal sucrase activity. IUGR decreased the efficiency of the piglets' intestinal energy metabolism; however, piglets fed an MCT diet exhibited increased adenosine triphosphate (ATP) concentrations and ATP synthase F1 complex beta polypeptide expression, as well as decreased adenosine monophosphate-activated kinase alpha 1 expression in the jejunum of piglets. In addition, up-regulation of the piglets' citrate synthase and succinate dehydrogenase levels was found to occur following MCT treatment at both the activity and the transcriptional levels of the jejunum. Therefore, it can be postulated that

  12. Chemical interference with iron transport systems to suppress bacterial growth of Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Yang

    Full Text Available Iron is an essential nutrient for the growth of most bacteria. To obtain iron, bacteria have developed specific iron-transport systems located on the membrane surface to uptake iron and iron complexes such as ferrichrome. Interference with the iron-acquisition systems should be therefore an efficient strategy to suppress bacterial growth and infection. Based on the chemical similarity of iron and ruthenium, we used a Ru(II complex R-825 to compete with ferrichrome for the ferrichrome-transport pathway in Streptococcus pneumoniae. R-825 inhibited the bacterial growth of S. pneumoniae and stimulated the expression of PiuA, the iron-binding protein in the ferrichrome-uptake system on the cell surface. R-825 treatment decreased the cellular content of iron, accompanying with the increase of Ru(II level in the bacterium. When the piuA gene (SPD_0915 was deleted in the bacterium, the mutant strain became resistant to R-825 treatment, with decreased content of Ru(II. Addition of ferrichrome can rescue the bacterial growth that was suppressed by R-825. Fluorescence spectral quenching showed that R-825 can bind with PiuA in a similar pattern to the ferrichrome-PiuA interaction in vitro. These observations demonstrated that Ru(II complex R-825 can compete with ferrichrome for the ferrichrome-transport system to enter S. pneumoniae, reduce the cellular iron supply, and thus suppress the bacterial growth. This finding suggests a novel antimicrobial approach by interfering with iron-uptake pathways, which is different from the mechanisms used by current antibiotics.

  13. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

    International Nuclear Information System (INIS)

    Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

    2008-01-01

    Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

  14. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

    2016-01-15

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

  15. Bisphenol A in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout.

    Directory of Open Access Journals (Sweden)

    Neelakanteswar Aluru

    Full Text Available BACKGROUND: Bisphenol A (BPA, used in the manufacture of plastics, is ubiquitously distributed in the aquatic environment. However, the effect of maternal transfer of these xenobiotics on embryonic development and growth is poorly understood in fish. We tested the hypothesis that BPA in eggs, mimicking maternal transfer, impact development, growth and stress performance in juveniles of rainbow trout (Oncorhynchus mykiss. METHODOLOGY/PRINCIPAL FINDINGS: Trout oocytes were exposed to 0, 30 and 100 microg.mL(-1 BPA for 3 h in ovarian fluid, followed by fertilization. The embryos were maintained in clean water and sampled temporally over 156-days post-fertilization (dpf, and juveniles were sampled at 400-dpf. The egg BPA levels declined steadily after exposure and were undetectable after 21- dpf. Oocyte exposure to BPA led to a delay in hatching and yolk absorption and a consistently lower body mass over 152-dpf. The growth impairment, especially in the high BPA group, correlated with higher growth hormone (GH content and lower GH receptors gene expression. Also, mRNA abundances of insulin-like growth factors (IGF-1 and IGF-2 and their receptors were suppressed in the BPA treated groups. The juvenile fish grown from the BPA-enriched eggs had lower body mass and showed perturbations in plasma cortisol and glucose response to an acute stressor. CONCLUSION: BPA accumulation in eggs, prior to fertilization, leads to hatching delays, growth suppression and altered stress response in juvenile trout. The somatotropic axis appears to be a key target for BPA impact during early embryogenesis, leading to long term growth and stress performance defects in fish.

  16. Heterologous expression of a ketohexokinase in potato plants leads to inhibited rates of photosynthesis, severe growth retardation and abnormal leaf development

    DEFF Research Database (Denmark)

    Geigenberger, P.; Regierer, B.; Lytovchenko, A.

    2004-01-01

    of ketohexokinase but did not accumulate fructose 1-phosphate. They were, however, characterised by a severe growth retardation and abnormal leaf development. Studies of (14)CO(2) assimilation and metabolism, and of the levels of photosynthetic pigments, revealed that these lines exhibited restricted photosynthesis......-phosphoglycerate, and these lines were also characterised by an accumulation of glyceraldehyde. The transformants neither displayed consistent changes in the activities of Calvin cycle enzymes nor in enzymes of sucrose synthesis but displayed a metabolic profile partially reminiscent of that brought about by end...

  17. Fire and smoke retardants

    Science.gov (United States)

    Drews, M. J.

    Despite a reduction in Federal regulatory activity, research concerned with flame retardancy and smoke suppression in the private sector appears to be increasing. This trend seem related to the increased utilization of plastics for end uses which traditionally have employed metal or wood products. As a result, new markets have appeared for thermally stable and fire resistance thermoplastic materials, and this in turn has spurred research and development activity. In addition, public awareness of the dangers associated with fire has increased as a result of several highly publicized hotel and restaurant fires within the past two years. The consumers recognition of flammability characteristics as important materials property considerations has increased. The current status of fire and smoke retardant chemistry and research are summarized.

  18. Retardo estatural em menores de cinco anos: um estudo "baseline" Linear growth retardation in children under five years of age: a baseline study

    Directory of Open Access Journals (Sweden)

    Anete Rissin

    2011-10-01

    Full Text Available OBJETIVO: Descrever a prevalência e analisar fatores associados ao retardo estatural em menores de cinco anos. MÉTODOS: Estudo "baseline", que analisou 2.040 crianças, verificando possíveis associações entre o retardo estatural (índice altura/idade The scope of this study was to describe the prevalence of, and analyze factors associated with, linear growth retardation in children. The baseline study analyzed 2040 children under the age of five, establishing a possible association between growth delay (height/age index < 2 scores Z and variables in six hierarchical blocks: socio-economic, residence, sanitary, maternal, biological and healthcare access. Multivariate analysis was performed using Poisson regression with the robust standard error option, obtaining adjusted prevalence ratios with a CI of 95% and the respective significant probability values. Among non-binary variables, there was a positive association with roof type and number of inhabitants per room and a negative association with income per capita, mother's schooling and birth weight. The adjusted analysis also indicated water supply, visit from the community health agent, birth delivery location, internment for diarrhea, or for pneumonia and birth weight as significant variables. Several risk factors were identified for linear growth retardation pointing to the multi-causal aspects of the problem and highlighting the need for control measures by the various hierarchical government agents.

  19. Syntaxin 1B suppresses macropinocytosis and semaphorin 3A-induced growth cone collapse.

    Science.gov (United States)

    Kabayama, Hiroyuki; Takeuchi, Makoto; Taniguchi, Masahiko; Tokushige, Naoko; Kozaki, Shunji; Mizutani, Akihiro; Nakamura, Takeshi; Mikoshiba, Katsuhiko

    2011-05-18

    Growth cone collapse is a crucial process for repulsive axon guidance and is accompanied by a reduction in growth cone surface area. This process of reduction may be regulated by endocytosis; however, its molecular mechanism is unclear. Macropinocytosis is a clathrin-independent form of endocytosis in which large areas of plasma membrane can be engulfed. We have reported previously that macropinocytosis is induced in growth cones of chick dorsal root ganglion neurons by semaphorin 3A (Sema3A), a repulsive axon guidance cue, and that Sema3A-induced reduction in growth cone surface area and macropinocytic vacuole area were correlated, suggesting a positive role for macropinocytosis in Sema3A-induced growth cone collapse. In the present study, we found that syntaxin 1B (Syx1B), a membrane trafficking protein, is a negative regulator of macropinocytosis, and its expression is downregulated by Sema3A signaling. Macropinocytosis inhibitor ethylisopropylamiloride or Syx1B overexpression suppressed Sema3A-induced macropinocytosis and growth cone collapse. These results indicate that Syx1B couples macropinocytosis-mediated massive internalization of the plasma membrane to Sema3A-induced growth cone collapse.

  20. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  1. Height suppression of tomato plug seedlings by an environment ...

    African Journals Online (AJOL)

    Height suppression of tomato plug seedlings by an environment friendly seed treatment of plant growth retardants. ... Then seeds were washed in tap water and were dried in a 5°C chamber for 1 day. Finally, dried seeds were used in both a germination test in a chamber and a growing test in a greenhouse. Differences ...

  2. Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma.

    Science.gov (United States)

    Kittipongdaja, Wasakorn; Wu, Xuesong; Garner, Justine; Liu, Xiping; Komas, Steven M; Hwang, Sam T; Schieke, Stefan M

    2015-09-01

    The mTOR pathway is a master regulator of cellular growth and metabolism. The biosynthetic and energetic demand of rapidly proliferating cells such as cancer cells is met by metabolic adaptations such as an increased glycolytic rate known as the Warburg effect. Herein, we characterize the anti-tumor effect of rapamycin in a mouse model of T-cell lymphoma and examine the metabolic effects in vitro. The murine T-cell lymphoma line, MBL2, and human cutaneous T-cell lymphoma (CTCL) lines, HH and Hut78, were used in syngeneic or standard NSG mouse models to demonstrate a marked suppression of tumor growth by rapamycin accompanied by inhibition of mTORC1/2. Analysis of the metabolic phenotype showed a substantial reduction in the glycolytic rate and glucose utilization in rapamycin-treated lymphoma cells. This was associated with reduced expression of glucose transporters and glycolytic enzymes in cultured cells and xenograft tumors. As a result of the decrease in glycolytic state, rapamycin-treated cells displayed reduced sensitivity to low-glucose conditions but continued to rely on mitochondrial oxidative phosphorylation (OXPHOS) with sensitivity to inhibition of OXPHOS. Taken together, we demonstrate that rapamycin suppresses growth of T-cell lymphoma tumors and leads to a reduction in aerobic glycolysis counteracting the Warburg effect of cancer cells.

  3. Noise suppress or express exponential growth for hybrid Hopfield neural networks

    International Nuclear Information System (INIS)

    Zhu Song; Shen Yi; Chen Guici

    2010-01-01

    In this Letter, we will show that noise can make the given hybrid Hopfield neural networks whose solution may grows exponentially become the new stochastic hybrid Hopfield neural networks whose solution will grows at most polynomially. On the other hand, we will also show that noise can make the given hybrid Hopfield neural networks whose solution grows at most polynomially become the new stochastic hybrid Hopfield neural networks whose solution will grows at exponentially. In other words, we will reveal that the noise can suppress or express exponential growth for hybrid Hopfield neural networks.

  4. Nematode suppression and growth stimulation in corn plants (Zea mays L.) irrigated with domestic effluent.

    Science.gov (United States)

    Barros, Kenia Kelly; do Nascimento, Clístenes Williams Araújo; Florencio, Lourdinha

    2012-01-01

    Treated wastewater has great potential for agricultural use due to its concentrations of nutrients and organic matter, which are capable of improving soil characteristics. Additionally, effluents can induce suppression of plant diseases caused by soil pathogens. This study evaluates the effect of irrigation with effluent in a UASB reactor on maize (Zea mays L.) development and on suppression of the diseases caused by nematodes of the genus Meloidogyne. Twelve lysimeters of 1 m(3) each were arranged in a completely randomized design, with four treatments and three replicates. The following treatments were used: T1 (W+I), irrigation with water and infestation with nematodes; T2 (W+I+NPK), irrigation with water, infestation with nematodes and fertilization with nitrogen (N), phosphorus (P) and potassium (K); T3 (E+I), irrigation with effluent and infestation with nematodes; and T4 (E+I+P), irrigation with effluent, infestation with nematodes and fertilization with phosphorus. The plants irrigated with the effluent plus the phosphorus fertilizer had better growth and productivity and were more resistant to the disease symptoms caused by the nematodes. The suppression levels may have been due to the higher levels of Zn and NO(3)(-) found in the leaf tissue of the plants irrigated with the effluent and phosphorus fertilizer.

  5. SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth.

    Science.gov (United States)

    Sun, Ye; Ju, Meihua; Lin, Zhiqiang; Fredrick, Thomas W; Evans, Lucy P; Tian, Katherine T; Saba, Nicholas J; Morss, Peyton C; Pu, William T; Chen, Jing; Stahl, Andreas; Joyal, Jean-Sébastien; Smith, Lois E H

    2015-09-22

    Neurons and glial cells in the retina contribute to neovascularization, or the formation of abnormal new blood vessels, in proliferative retinopathy, a condition that can lead to vision loss or blindness. We identified a mechanism by which suppressor of cytokine signaling 3 (SOCS3) in neurons and glial cells prevents neovascularization. We found that Socs3 expression was increased in the retinal ganglion cell and inner nuclear layers after oxygen-induced retinopathy. Mice with Socs3 deficiency in neuronal and glial cells had substantially reduced vaso-obliterated retinal areas and increased pathological retinal neovascularization in response to oxygen-induced retinopathy, suggesting that loss of neuronal/glial SOCS3 increased both retinal vascular regrowth and pathological neovascularization. Furthermore, retinal expression of Vegfa (which encodes vascular endothelial growth factor A) was higher in these mice than in Socs3 flox/flox controls, indicating that neuronal and glial SOCS3 suppressed Vegfa expression during pathological conditions. Lack of neuronal and glial SOCS3 resulted in greater phosphorylation and activation of STAT3, which led to increased expression of its gene target Vegfa, and increased endothelial cell proliferation. In summary, SOCS3 in neurons and glial cells inhibited the STAT3-mediated secretion of VEGF from these cells, which suppresses endothelial cell activation, resulting in decreased endothelial cell proliferation and angiogenesis. These results suggest that neuronal and glial cell SOCS3 limits pathological retinal angiogenesis by suppressing VEGF signaling. Copyright © 2015, American Association for the Advancement of Science.

  6. Suppression of Growth by Multiplicative White Noise in a Parametric Resonant System

    Science.gov (United States)

    Ishihara, Masamichi

    2015-02-01

    The growth of the amplitude in a Mathieu-like equation with multiplicative white noise is studied. To obtain an approximate analytical expression for the exponent at the extremum on parametric resonance regions, a time-interval width is introduced. To determine the exponents numerically, the stochastic differential equations are solved by a symplectic numerical method. The Mathieu-like equation contains a parameter α determined by the intensity of noise and the strength of the coupling between the variable and noise; without loss of generality, only non-negative α can be considered. The exponent is shown to decrease with α, reach a minimum and increase after that. The minimum exponent is obtained analytically and numerically. As a function of α, the minimum at α≠0, occurs on the parametric resonance regions of α=0. This minimum indicates suppression of growth by multiplicative white noise.

  7. Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.

    Directory of Open Access Journals (Sweden)

    Vino T Cheriyan

    Full Text Available Dithiocarbamate compound Disulfiram (DSF that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM suppressive effects of DSF-Cu and the molecular mechanisms involved. DSF-Cu inhibited growth of the murine as well as human MPM cells in part by increasing levels of ubiquitinated proteins. DSF-Cu exposure stimulated apoptosis in MPM cells that involved activation of stress-activated protein kinases (SAPKs p38 and JNK1/2, caspase-3, and cleavage of poly-(ADP-ribose-polymerase, as well as increased expression of sulfatase 1 and apoptosis transducing CARP-1/CCAR1 protein. Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes including matrix metallopeptidase 3 and 10. DSF inhibited MPM cell growth and survival by upregulating cell cycle inhibitor p27Kip1, IGFBP7, and inhibitors of NF-κB such as ABIN 1 and 2 and Inhibitory κB (IκBα and β proteins. DSF-Cu promoted cleavage of vimentin, as well as serine-phosphorylation and lysine-63 linked ubiquitination of podoplanin. Administration of 50 mg/kg DSF-Cu by daily i.p injections inhibited growth of murine MPM cell-derived tumors in vivo. Although podoplanin expression often correlates with metastatic disease and poor prognosis, phosphorylation of serines in cytoplasmic domain of podoplanin has recently been shown to interfere with cellular motility and migration signaling. Post-translational modification of podoplanin and cleavage of vimentin by DSF-Cu underscore a metastasis inhibitory property of this agent and together with our in vivo studies underscore its potential as an anti-MPM agent.

  8. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    Science.gov (United States)

    Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

    2014-07-01

    Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38α phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

  9. Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer.

    Science.gov (United States)

    Li, Yining; Xu, Shuxiong; Wang, Xiangwei; Shi, Hua; Sun, Zhaolin; Yang, Zhao

    2013-02-01

    To explore the exact mechanism of Pokemon in prostate cancer. Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry. The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth. Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Growth suppression of Leydig TM3 cells mediated by aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Iseki, Minoru; Ikuta, Togo; Kobayashi, Tetsuya; Kawajiri, Kaname

    2005-01-01

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces developmental toxicity in reproductive organs. To elucidate the function of AhR, we generated stable transformants of TM3 cells overexpressing wild-type aryl hydrocarbon receptor (AhR) or its mutants which carried mutations in nuclear localization signal or nuclear export signal. In the presence of 3-methylcholanthrene (MC), proliferation of the cells transfected with wild-type AhR was completely suppressed, whereas cells expressing AhR mutants proliferated in a manner equivalent to control TM3 cells, suggesting AhR-dependent growth inhibition. The suppression was associated with up-regulation of cyclin-dependent kinase inhibitor p21 Cip1 , which was abolished by pretreatment with actinomycin D. A p38 MAPK specific inhibitor, SB203580, blocked the increase of p21 Cip1 mRNA in response to MC. Treatment with indigo, another AhR ligand, failed to increase of p21 Cip1 mRNA, although up-regulation of mRNA for CYP1A1 was observed. These data suggest AhR in Leydig cells mediates growth inhibition by inducing p21 Cip1

  11. MiR-214 inhibits cell growth in hepatocellular carcinoma through suppression of {beta}-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun [Liver Diseases Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Chen, Ji [Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China); Li, Feng [Department of Pathology, Fujian Provincial Hospital, Fuzhou (China); Lin, Yanting [Liver Diseases Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zhang, Xiaoping; Lv, Zhongwei [Department of Interventional Therapy, Shanghai 10th People' s Hospital, School of Medicine, Tongji University, Shanghai (China); Jiang, Jiaji, E-mail: jiang_jjcn@yahoo.com.cn [Liver Diseases Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer miR-214 is frequently downregulated in human HCC cell lines and tissues. Black-Right-Pointing-Pointer miR-214 overexpression inhibits HCC cell growth in vitro and in vivo. Black-Right-Pointing-Pointer miR-214 directly targets {beta}-catenin 3 Prime -UTR in HCC cells. Black-Right-Pointing-Pointer miR-214 regulates {beta}-catenin downstream signaling molecules. -- Abstract: Mounting evidence has shown that microRNAs (miRNAs) are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. Recent profile studies of miRNA expression have documented a deregulation of miRNA (miR-214) in hepatocellular carcinoma (HCC). However, its potential functions and underlying mechanisms in hepatocarcinogenesis remain largely unknown. Here, we confirmed that miR-214 is significantly downregulated in HCC cells and specimens. Ectopic overexpression of miR-214 inhibited proliferation of HCC cells in vitro and tumorigenicity in vivo. Further studies revealed that miR-214 could directly target the 3 Prime -untranslated region (3 Prime -UTR) of {beta}-catenin mRNA and suppress its protein expression. Similar to the restoring miR-214 expression, {beta}-catenin downregulation inhibited cell growth, whereas restoring the {beta}-catenin expression abolished the function of miR-214. Moreover, miR-214-mediated reduction of {beta}-catenin resulted in suppression of several downstream genes including c-Myc, cyclinD1, TCF-1, and LEF-1. These findings indicate that miR-214 serves as tumor suppressor and plays substantial roles in inhibiting the tumorigenesis of HCC through suppression of {beta}-catenin. Given these, miR-214 may serve as a useful prognostic or therapeutic target for treatment of HCC.

  12. Delayed Growth Suppression and Radioresistance Induced by Long-Term Continuous Gamma Irradiation.

    Science.gov (United States)

    Nakajima, Hiroo; Furukawa, Chiharu; Chang, Young-Chae; Ogata, Hiromitsu; Magae, Junji

    2017-08-01

    Biological response to ionizing radiation depends not only on the type of radiation and dose, but also on the duration and dose rate of treatment. For a given radiation dose, the biological response may differ based on duration and dose rate. We studied the properties of two human cell lines, M059K glioma and U2OS osteosarcoma, continuously exposed to γ rays for long time periods of more than five months. Growth inhibition in both cell lines was dependent on total dose when exposed to acute radiation over several minutes, whereas prolonged growth inhibition was dependent on dose rate after continuous irradiation over several months. The minimum dose rate for growth inhibition was 53.6 mGy/h. Cell cycle analysis showed G 1 phase accumulation in cell populations continuously exposed to γ rays, and G 2 phase accumulation in cells acutely exposed to high-dose-rate γ rays. Cells continuously exposed to γ rays continued to exhibit delayed growth suppression even after one month in an environment of background radiation, and maintained a high-level expression of c-Jun and its phosphorylation forms, as well as resistance to apoptosis induced by staurosporine and chemotherapeutic agents. These delayed effects were not observed in cells acutely exposed to 5 Gy of radiation. These results suggest that optimization of the irradiation schedule is crucial for risk estimation, protection and therapeutic utilization of ionizing radiation.

  13. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy.

    Science.gov (United States)

    Mickiewicz, M; Zabielski, R; Grenier, B; Le Normand, L; Savary, G; Holst, J J; Oswald, I P; Metges, C C; Guilloteau, P

    2012-06-01

    Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ≤1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes.

  14. Some observations of wood density and anatomical properties in a Douglas-fir sample with suppressed growth

    Science.gov (United States)

    J.Y. Zhu; David W. Vahey; C. Tim Scott

    2008-01-01

    This study used ring width correlations to examine the effects of tree-growth suppression on within-tree local wood density and tracheid anatomical properties. A wood core sample was taken from a 70-yr-old Douglas-fir that grew under various degrees of suppression in a natural forest setting. SilviScan and an imaging technique were used to obtain wood density and...

  15. Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets.

    Science.gov (United States)

    Su, Weipeng; Xu, Wen; Zhang, Hao; Ying, Zhixiong; Zhou, Le; Zhang, Lili; Wang, Tian

    2017-04-01

    The study was conducted to evaluate the effects of dietary leucine supplementation on mitochondrial biogenesis and energy metabolism in the liver of normal birth weight (NBW) and intrauterine growth-retarded (IUGR) weanling piglets. A total of sixteen pairs of NBW and IUGR piglets from sixteen sows were selected according to their birth weight. At postnatal day 14, all piglets were weaned and fed either a control diet or a leucine-supplemented diet for 21 d. Thereafter, a 2 × 2 factorial experimental design was used. Each treatment consisted of eight replications with one piglet per replication. Compared with NBW piglets, IUGR piglets had a decreased ( P supplementation increased ( P supplemented diet exhibited increases ( P supplementation may exert beneficial effects on mitochondrial biogenesis and energy metabolism in NBW and IUGR weanling piglets.

  16. miR-203 Suppresses Tumor Growth and Angiogenesis by Targeting VEGFA in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Xiangyu Zhu

    2013-07-01

    Full Text Available Background/Aims: MicroRNA (miRNA plays important roles in the development of different cancers. In this study, we investigated the roles and mechanisms of miR-203 in human cervical cancer. Methods: miR-203 expression was detected in cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the promoter region of miR-203 was examined by methylation-specific PCR. The functional effect of miR-203 was determined by both in vitro and in vivo assays. Results: miR-203 was frequently down-regulated in cervical cancer tumors and cell lines. This down-regulation of miR-203 was associated with methylation of the miR-203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth factor alpha (VEGFA expression by directly targeting its 3'-untranslated region. Functional assays revealed that miR-203 suppressed cervical cancer cell proliferation, tumor growth, and angiogenesis in nude mice, whereas forced expression of VEGFA rescued this inhibitory effect. Conclusion: Our collective findings indicate that miR-203 functions as a tumor suppressor by targeting VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR-203 may be a potential therapeutic target and prognostic marker in cervical cancer.

  17. Human chorionic gonadotropin suppresses human breast cancer cell growth directly via p53-mediated mitochondrial apoptotic pathway and indirectly via ovarian steroid secretion.

    Science.gov (United States)

    Yuri, Takashi; Kinoshita, Yuichi; Emoto, Yuko; Yoshizawa, Katsuhiko; Tsubura, Airo

    2014-03-01

    The tumor-suppressive effects of human chorionic gonadotropin (hCG) against human breast cancer cells were examined. In cell viability assays, hCG inhibited the growth of three human breast cancer cell lines (estrogen receptor (ER)-positive KPL-1 and MCF-7, and ER-negative MKL-F cells), and the growth inhibition activity of hCG was most pronounced against KPL-1 cells (luteinizing hormone/chorionic gonadotropin receptor (LHCGR)-positive and luminal-A subtype). In hCG-treated KPL-1 cells, immunoblotting analysis revealed the expression of tumor suppressor protein p53 peaking at 12 h following treatment, followed by cleavage of caspase-9 and caspase-3 at 24 h and 48 h, respectively. KPL-1-transplanted athymic mice were divided into 3 groups: a sham-treated group that received an inoculation of KPL-1 cells at 6 weeks of age followed by daily intraperitoneal (i.p.) injection of saline; an in vitro hCG-treated KPL-1 group that received an inoculation of KPL-1 cells pre-treated with 100 IU/ml hCG in vitro for 48 h at 6 weeks of age, followed by daily i.p. injection of saline; and an in vivo hCG-treated group that received an KPL-1 cell inoculation at 6 weeks of age, followed by daily i.p. injection of 100 IU hCG. The daily injections of saline or hCG continued until the end of the experiment when mice reached 11 weeks of age. KPL-1 tumor growth was retarded in in vitro and in vivo hCG-treated mice compared to sham-treated controls, and the final tumor volume and tumor weight tended to be suppressed in the in vitro hCG-treated group and were significantly suppressed in the in vivo hCG-treated group. In vivo 100-IU hCG injections for 5 weeks elevated serum estradiol levels (35.7 vs. 23.5 pg/ml); thus, the mechanisms of hCG action may be directly coordinated via the p53-mediated mitochondrial apoptotic pathway and indirectly through ovarian steroid secretion that elevates estrogen levels. It is thus concluded that hCG may be an attractive agent for treating human breast

  18. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk

    Science.gov (United States)

    Cornford, Andrea S.; Barkan, Ariel L.; Hinko, Alexander

    2012-01-01

    Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass−1·day−1; 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P overeating also blunted the increase in systemic proteolysis (P overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating. PMID:23011065

  19. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk.

    Science.gov (United States)

    Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander; Horowitz, Jeffrey F

    2012-11-15

    Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass(-1)·day(-1); 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P overeating also blunted the increase in systemic proteolysis (P overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating.

  20. Study of the evolution of the placenta and fetal pancreas in the pathophysiology of growth retardation intrauterine due to restricted maternal diet

    Directory of Open Access Journals (Sweden)

    Marilza Vieira Cunha Rudge

    1999-03-01

    Full Text Available CONTEXT: Intrauterine growth retard (IUGR continues to be a significant perinatology problem at the end of this century. The nature of the etiologic agent, the time when the attack occurred during pregnancy and its duration affect the type of IUGR. OBJECTIVE: To study the evolution of fetal pancreas and placenta between the 18th and 21st day of pregnancy in rats submitted to maternal protein-calorie restriction. DESIGN: Randomized controlled trial on laboratory animal. SAMPLE: Forty-one normoglycemic pregnant Wistar rats. INTERVENTION: Rats were divided into six experimental groups according to their access to food and date of cesarean section (18th or 21st day: control with free access to food; diet restricted to 25% introduced on 1st day of pregnancy; and diet restricted to 25% after the 3rd day of pregnancy. MAIN MEASUREMENTS: Newborn weight, placenta weight, histopathological study (morphological histochemistry RESULTS: Maternal protein-calorie malnutrition caused intrauterine growth retard (IUGR after the 18th day of pregnancy. Dietary restriction did not interfere with the morphology of the fetal pancreas and the immunohistochemical study of the placenta showed that glycogen stores were decreased between the 18th and 21st day in the control group and in a diet restricted to 25% from the first day of pregnancy. Dietary restriction after the 3rd day of pregnancy led to low placental glycogen concentrations on the 18th day and disappearance on the 21st day. CONCLUSION: The pathophysiology of IUGR due to maternal protein-calorie restriction in rats is related to lower placental weight and low placental glycogen stores.

  1. Suppression of tumor growth in vivo by local and systemic 90K level increase

    DEFF Research Database (Denmark)

    Jallal, B; Powell, J; Zachwieja, J

    1995-01-01

    Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by dire...... signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression....... action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm...

  2. Growth suppressive effect of pegylated arginase in malignant pleural mesothelioma xenografts.

    Science.gov (United States)

    Lam, Sze-Kwan; Li, Yuan-Yuan; Xu, Shi; Leung, Leanne Lee; U, Kin-Pong; Zheng, Yan-Fang; Cheng, Paul Ning-Man; Ho, James Chung-Man

    2017-05-02

    Malignant pleural mesothelioma (MPM) is a difficult-to-treat global disease. Pegylated arginase (BCT-100) has recently shown anti-tumor effects in hepatocellular carcinoma, acute myeloid leukemia and melanoma. This study aims to investigate the effects of PEG-BCT-100 in MPM. A panel of 5 mesothelioma cell lines (H28, 211H, H226, H2052 and H2452) was used to study the in vitro effects of BCT-100 by crystal violet staining. The in vivo effects of BCT-100 were studied using 211H and H226 nude mice xenografts. Protein expression (argininosuccinate synthetase, ornithine transcarbamylase, cleaved PARP, cleaved caspase 3, cyclins (A2, D3, E1 and H), CDK4 and Ki67) and arginine concentration were evaluated by Western blot and ELISA respectively. Cellular localization of BCT-100 was detected by immunohistochemistry and immunoflorescence. TUNEL assay was used to identify cellular apoptotic events. Argininosuccinate synthetase was expressed in H28, H226, and H2452 cells as well as 211H and H266 xenografts. Ornithine transcarbamylase was undetectable in all cell lines and xenograft models. BCT-100 reduced in vitro cell viability (IC 50 values at 13-24 mU/ml, 72 h) across different cell lines and suppressed tumor growth in both 211H and H226 xenograft models. BCT-100 (60 mg/kg) significantly suppressed tumor growth (p mesothelioma xenograft models. The findings provide scientific evidence to support further clinical development of BCT-100 in treatment of MPM.

  3. Targeted p53 activation by saRNA suppresses human bladder cancer cells growth and metastasis.

    Science.gov (United States)

    Wang, Chenghe; Ge, Qiangqiang; Zhang, Qingsong; Chen, Zhong; Hu, Jia; Li, Fan; Ye, Zhangqun

    2016-03-25

    Previous study showed that dsP53-285 has the capacity to induce tumor suppressor gene p53 expression by targeting promoter in non-human primates' cells. And it is well known that TP53 gene is frequently mutant or inactivated in human bladder cancer. Hereby, whether this small RNA can activate the expression of wild-type p53 and inhibit human bladder cancer cells remains to be elucidated. Oligonucleotide and lentivirus were used to overexpress dsP53-285 and dsControl. Real-time PCR and western blot were used to detect genes' mRNA and protein expression, respectively. Cell proliferation assay, colony formation, flow cytometry, transwell assay and wound healing assay were performed to determine the effects on bladder cancer cells proliferation and migration/invasion in vitro. Animal models were carried out to analyze the effects on cells growth and metastasis in vivo. Transfection of dsP53-285 into human bladder cancer cell lines T24 and EJ readily activate wild-type p53 expression by targeting promoter. Moreover, dsP53-285 exhibited robust capacity to inhibit cells proliferation and colony formation, induce cells G0/G1 arrest, suppress migration and invasion. Besides, the Cyclin-CDK genes (Cyclin D1 and CDK4/6) were down-regulated and the EMT-associated genes (E-cadherin, β-catenin, ZEB1 and Vimentin) were also expressed inversely after dsP53-285 treatment. In addition, dsP53-285 could also significantly suppress the growth of bladder cancer xenografts and metastasis in nude mice. Most importantly, the anti-tumor effects mediated by dsP53-285 were mainly achieved by manipulating wild-type p53 expression. Our findings indicate that the dsP53-285 can upregulate wild-type p53 expression in human bladder cancer cells through RNA activation, and suppresses cells proliferation and metastasis in vitro and in vivo.

  4. Mandibulofacial syndrome with growth and mental retardation, microcephaly, ear anomalies with skin tags, and cleft palate in a mother and her son: autosomal dominant or X-linked syndrome?

    Science.gov (United States)

    Guion-Almeida, Maria Leine; Vendramini-Pittoli, Siulan; Passos-Bueno, Maria Rita Santos; Zechi-Ceide, Roseli Maria

    2009-12-01

    We report on a Brazilian mother and her son affected with mandibulofacial dysostosis, growth and mental retardation, microcephaly, first branchial arch anomalies, and cleft palate. To date only three males and one female, all sporadic cases, with a similar condition have been reported. This article describes the first familial case with this rare condition indicating autosomal dominant or X-linked inheritance.

  5. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    Science.gov (United States)

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer. © 2014 Wiley Periodicals, Inc.

  6. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  7. Mechanisms of plant growth promotion and disease suppression by Pseudomonas aeruginosa strain 2apa.

    Science.gov (United States)

    Hariprasad, P; Chandrashekar, S; Singh, S Brijesh; Niranjana, S R

    2014-08-01

    A new Pseudomonas strain, designated as 2apa was isolated from tomato rhizosphere and identified as a member of species Pseudomonas aeruginosa based on its morphology, conventional, biochemical, cell wall fatty acid methyl ester analysis, and 16S rRNA gene sequence analysis. The strain 2apa was positive for root colonization, indole acetic acid (IAA), salicylic acid and siderophore production and inhibited the growth of wide range of microorganisms. Antimicrobial substances produced by this strain with further purification and structure elucidation proved to be phenazine. Under laboratory and greenhouse conditions the strain promoted plant growth and suppressed a wide range of foliar and root pathogens in tomato. The protection offered by strain 2apa to foliar pathogens is considered as induced systemic resistance and was further confirmed by enhanced accumulation of phenolics, elicitation of lipoxygenas activity, and jasmonic acid levels. The broad-spectrum antimicrobial and induced systemic resistance exhibiting strain P. aeruginosa 2apa can be used as an effective biological control candidate against devastating fungal and bacterial pathogens, which attack both root and foliar portions of tomato plant. Production of other functional traits such as IAA and siderophore may enhance its potential as biofertilizer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Identification of derlin-1 as a novel growth factor-responsive endothelial antigen by suppression subtractive hybridization

    International Nuclear Information System (INIS)

    Ran Yuliang; Jiang Yangfu; Zhong Xing; Zhou Zhuan; Liu Haiyan; Hu Hai; Lou Jinning; Yang Zhihua

    2006-01-01

    Endothelial cells play an important regulatory role in embryonic development, reproductive functions, tumor growth and progression. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify differentially expressed genes between non-stimulated endothelial cells and activated endothelial cells. Following mRNA isolation of non-stimulated and hepatocellular carcinoma homogenate-stimulated cells, cDNAs of both populations were prepared and subtracted by suppressive PCR. Sequencing of the enriched cDNAs identified a couple of genes differentially expressed, including derlin-1. Derlin-1 was significantly up-regulated by tumor homogenates, VEGF, and endothelial growth supplements in a dose-dependent manner. Knock-down of derlin-1 triggered endothelial cell apoptosis, inhibited endothelial cell proliferation, and blocked the formation of a network of tubular-like structures. Our data reveal that derlin-1 is a novel growth factor-responsive endothelial antigen that promotes endothelial cell survival and growth

  9. SH003 suppresses breast cancer growth by accumulating p62 in autolysosomes.

    Science.gov (United States)

    Choi, Youn Kyung; Cho, Sung-Gook; Choi, Yu-Jeong; Yun, Yee Jin; Lee, Kang Min; Lee, Kangwook; Yoo, Hye-Hyun; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-10-24

    Drug markets revisits herbal medicines, as historical usages address their therapeutic efficacies with less adverse effects. Moreover, herbal medicines save both cost and time in development. SH003, a modified version of traditional herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been revealed to inhibit tumor growth and metastasis on highly metastatic breast cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is imperative for maintenance cellular homeostasis, thereby playing critical roles in cancer progression. Inhibition of autophagy by pharmacological agents induces apoptotic cell death in cancer cells, resulting in cancer treatment. In this study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive oxygen species (ROS) generation and attenuates tumor growth. SH003 induced autophagosome and autolysosome formation by inhibiting activation of STAT3- and mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins, resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of p62/SQSTM1 caused the increase of ROS, which resulted in the induction of apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could function as an important mediator for ROS generation-dependent cell death suggesting that SH003 may be useful for treating breast cancer.

  10. Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Petru Edgar

    2010-03-01

    Full Text Available Abstract Background Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat on MES-SA uterine sarcoma cells in vitro and in vivo. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21WAF1 and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma in vivo. Results Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3 as well as class II (HDAC7 were preferentially affected by this treatment. Vorinostat significantly increased p21WAF1 expression and apoptosis. Nude mice injected with 5 × 106 MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice. Conclusions Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.

  11. MELATONIN-INDUCED SUPPRESSION OF PC12 CELL GROWTH IS MEDIATED BY ITS GI COUPLED TRANSMEMBRANE RECEPTORS. (R826248)

    Science.gov (United States)

    The effects of pertussis toxin, an uncoupler of Gi protein from adenylate cyclase, and luzindole, a competitive inhibitor of melatonin receptor binding, were examined for their ability to inhibit melatonin-induced suppression of PC12 cell growth. Both agents inhibited the mela...

  12. Developmental exposure to a brominated flame retardant: An assessment of effects on physiology, growth, and reproduction in a songbird, the zebra finch

    International Nuclear Information System (INIS)

    Eng, Margaret L.; Williams, Tony D.; Elliott, John E.

    2013-01-01

    Mixtures of polybrominated diphenyl ethers (PBDEs) have been widely used as additive flame retardants, and BDE-99 is one of the most predominant congeners found in the environment. BDE-99 has been reported in avian samples worldwide, yet knowledge of its toxicity to birds is minimal. We assessed the short- and long-term effects of nestling exposure to environmentally relevant levels of BDE-99 in a model passerine, the zebra finch. Early exposure to BDE-99 did not affect hematocrit, oxidative stress, or thyroid hormones in either the juvenile or adult stages, and there were no effects on chick growth or survival. BDE-99 exposure caused a dose-dependent delay in timing of reproduction, but there were no other effects on reproductive success. In zebra finches, endpoints related to reproductive behavior appear to be the most sensitive to BDE-99. However, passerines overall appear to be less sensitive than birds of prey or mammals to PBDE exposure. -- Highlights: •We exposed zebra finches nestlings to BDE-99 and raised them to sexual maturity. •Found no effects on physiology, chick growth, survival, or reproductive success. •As BDE-99 dose increased, laying interval increased. •Passerine birds possibly less sensitive to BDE-99 than mammals or other bird species. -- Nestling exposure to BDE-99 affects timing of breeding in zebra finches, but overall passerines appear to be less sensitive to PBDEs than mammals or other bird species

  13. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    Science.gov (United States)

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  14. Ocular disorder in children with mental retardation.

    Science.gov (United States)

    Joshi, Rajesh Subhash; Somani, Abhishek Arun Kumar

    2013-04-01

    Ocular problems are common in mentally retarded children. Due to population growth these problems are increasing. Prevalence rate is variable from region to region. Data on ocular problems in mentally retarded school children is lacking in this region. The aim of the present study was to identify the ocular disorders in children with mental retardation attending special schools in a district and to study their relationship with the degree of retardation. A total of 241 mentally retarded school children in the age group of 6-16 years attending special schools for the mentally retarded children in a district in central India were examined by a team of ophthalmologist, psychiatrist, and a resident in ophthalmology department of a medical college. Complete ocular examination was done. Ocular problems were identified and categorized according to the intelligent quotient. One hundred and twenty four children (51.45%) had ocular problems. Strabismus (10.37%) and refractive error (20.75%) were the common ocular problems seen in this study. An association was found between the severity of mental retardation and ocular problems (P<0.005). However, no association was seen between the severity of mental retardation and strabismus and refractive error. A high prevalence of ocular problems was seen in mentally retarded school children. Children with mental retardation should undergo annual ophthalmological check up. Early detection and correction of ocular problems will prevent visual impairment in future.

  15. Newborn length predicts early infant linear growth retardation and disproportionately high weight gain in a low-income population.

    Science.gov (United States)

    Berngard, Samuel Clark; Berngard, Jennifer Bishop; Krebs, Nancy F; Garcés, Ana; Miller, Leland V; Westcott, Jamie; Wright, Linda L; Kindem, Mark; Hambidge, K Michael

    2013-12-01

    Stunting is prevalent by the age of 6 months in the indigenous population of the Western Highlands of Guatemala. The objective of this study was to determine the time course and predictors of linear growth failure and weight-for-age in early infancy. One hundred and forty eight term newborns had measurements of length and weight in their homes, repeated at 3 and 6 months. Maternal measurements were also obtained. Mean ± SD length-for-age Z-score (LAZ) declined from newborn -1.0 ± 1.01 to -2.20 ± 1.05 and -2.26 ± 1.01 at 3 and 6 months respectively. Stunting rates for newborn, 3 and 6 months were 47%, 53% and 56% respectively. A multiple regression model (R(2) = 0.64) demonstrated that the major predictor of LAZ at 3 months was newborn LAZ with the other predictors being newborn weight-for-age Z-score (WAZ), gender and maternal education∗maternal age interaction. Because WAZ remained essentially constant and LAZ declined during the same period, weight-for-length Z-score (WLZ) increased from -0.44 to +1.28 from birth to 3 months. The more severe the linear growth failure, the greater WAZ was in proportion to the LAZ. The primary conclusion is that impaired fetal linear growth is the major predictor of early infant linear growth failure indicating that prevention needs to start with maternal interventions. © 2013.

  16. Retardation of Listeria monocytogenes growth in mozzarella cheese using antimicrobial sachets containing rosemary oil and thyme oil.

    Science.gov (United States)

    Han, Jung H; Patel, Dhaval; Kim, Jung Eun; Min, Sea C

    2014-11-01

    An antimicrobial sachet containing microcellular foam starch (MFS) with embedded rosemary oil and thyme oil was developed to reduce bacterial growth in shredded mozzarella cheese. The efficacy of the volatiles of oils at various concentrations in reducing Listeria monocytogenes as well as the release of the oils from the MFS have been also determined in this study. The cheese, inoculated with a cocktail of 5 strains of L. monocytogenes (approximately 3 log CFU/g), was packaged in a Nylon/EVOH/PE bag. A paper sachet containing MFS embedded with rosemary oil and thyme oil, separately or together, was inserted into the bag. Rosemary and thyme oil volatiles released from the sachet restricted the growth of L. monocytogenes, resulting in a 2.5 log CFU/g reduction on day 9 at 10 °C. The volatile oils also showed inhibitory effects on the growth of lactic acid bacteria (LAB) and total aerobic bacteria (TAB). After 15 d at 10 °C, the numbers of LAB and TAB in the samples containing the sachet with both oils experienced a 1.2 and 1.4 log CFU/g reduction, respectively, compared to untreated samples. Nonetheless, the sachet treatment produced a distinct odor, unfavorably received by the panelists. The results suggest the potential for application of the sachet system for the reduction of growth of L. monocytogenes, LAB, and TAB in food products. © 2014 Institute of Food Technologists®

  17. Growth suppression by transforming growth factor beta 1 of human small-cell lung cancer cell lines is associated with expression of the type II receptor

    DEFF Research Database (Denmark)

    Nørgaard, P; Damstrup, L; Rygaard, K

    1994-01-01

    the growth-suppressive effect of TGF-beta 1, the expression of functional pRb, as characterised by nuclear localisation, was examined by immunocytochemistry. Nuclear association of pRb was only seen in two of the five TGF-beta 1-responsive cell lines. These results indicate that in SCLC pRb is not required...

  18. Inhibition of TMEM16A expression suppresses growth and invasion in human colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Yujie Sui

    Full Text Available Metastasis leads to poor prognosis in colorectal cancer patients, and there is a growing need for new therapeutic targets. TMEM16A (ANO1, DOG1 or TAOS2 has recently been identified as a calcium-activated chloride channel (CaCC and is reported to be overexpressed in several malignancies; however, its expression and function in colorectal cancer (CRC remains unclear. In this study, we found expression of TMEM16A mRNA and protein in high-metastatic-potential SW620, HCT116 and LS174T cells, but not in primary HCT8 and SW480 cells, using RT-PCR, western blotting and immunofluorescence labeling. Patch-clamp recordings detected CaCC currents regulated by intracellular Ca(2+ and voltage in SW620 cells. Knockdown of TMEM16A by short hairpin RNAs (shRNA resulted in the suppression of growth, migration and invasion of SW620 cells as detected by MTT, wound-healing and transwell assays. Mechanistically, TMEM16A depletion was accompanied by the dysregulation of phospho-MEK, phospho-ERK1/2 and cyclin D1 expression. Flow cytometry analysis showed that SW620 cells were inhibited from the G1 to S phase of the cell cycle in the TMEM16A shRNA group compared with the control group. In conclusion, our results indicate that TMEM16A CaCC is involved in growth, migration and invasion of metastatic CRC cells and provide evidence for TMEM16A as a potential drug target for treating metastatic colorectal carcinoma.

  19. Mycoepoxydiene suppresses HeLa cell growth by inhibiting glycolysis and the pentose phosphate pathway.

    Science.gov (United States)

    Jin, Kehua; Li, Li; Sun, Xihuan; Xu, Qingyan; Song, Siyang; Shen, Yuemao; Deng, Xianming

    2017-05-01

    Upregulation of glycolysis and the pentose phosphate pathway (PPP) is a major characteristic of the metabolic reprogramming of cancer and provides cancer cells with energy and vital metabolites to support their rapid proliferation. Targeting glycolysis and the PPP has emerged as a promising antitumor therapeutic strategy. Marine natural products are attractive sources for anticancer therapeutics, as evidenced by the antitumor drug Yondelis. Mycoepoxydiene (MED) is a natural product isolated from a marine fungus that has shown promising inhibitory efficacy against HeLa cells in vitro. We used a proteomic approach with two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry to explore the cellular targets of MED and to unravel the molecular mechanisms underlying the antitumor activity of MED in HeLa cells. Our proteomic data showed that triosephosphate isomerase (TPI) and 6-phosphogluconolactonase (PGLS), which participate in glycolysis and the PPP, respectively, were significantly downregulated by MED treatment. Functional studies revealed that the expression levels of several other enzymes involved in glycolysis and the PPP, including hexokinase 2 (HK2), phosphofructokinase 1 (PFKM), aldolase A (ALDOA), enolase 1 (ENO1), lactate dehydrogenase A (LDHA), and glucose-6-phosphate dehydrogenase (G6PD), were also reduced in a dose-dependent manner. Moreover, the LDHA and G6PD enzymatic activities in HeLa cells were inhibited by MED, and overexpression of these downregulated enzymes rescued HeLa cells from the growth inhibition induced by MED. Our data suggest that MED suppresses HeLa cell growth by inhibiting glycolysis and the PPP, which provides a mechanistic basis for the development of new therapeutics against cervical cancer.

  20. Cardamonin Regulates miR-21 Expression and Suppresses Angiogenesis Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Fu-Sheng Jiang

    2015-01-01

    Full Text Available Cardamonin has promising potential in cancer prevention and therapy by interacting with proteins and modifying the expressions and activities, including factors of cell survival, proliferation, and angiogenesis. In our precious study, we have demonstrated that cardamonin suppressed vascular endothelial growth factor- (VEGF- induced angiogenesis as evaluated in the mouse aortic ring assay. It is also known that microRNAs (miRNAs play important roles in angiogenesis. Herein, we hypothesized whether antiangiogenesis effect of cardamonin in human umbilical vein endothelial cells (HUVECs triggered by VEGF was associated with miRNAs. We found that cardamonin reduced the miR-21 expression induced by VEGF in HUVECs. Treatment with miR-21 mimics abolished the effects of cardamonin on VEGF-induced cell proliferation, migration, and angiogenesis in HUVECs. However, treatment with miR-21 inhibitors presented the opposite effects, indicating the vital role of miR-21 in this process. Our study provides a new insight of the preliminary mechanism of anti-VEGF-induced angiogenesis by cardamonin in HUVECs.

  1. Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.

    Science.gov (United States)

    Lyu, Junfang; Yang, Eun Ju; Head, Sarah A; Ai, Nana; Zhang, Baoyuan; Wu, Changjie; Li, Ruo-Jing; Liu, Yifan; Yang, Chen; Dang, Yongjun; Kwon, Ho Jeong; Ge, Wei; Liu, Jun O; Shim, Joong Sup

    2017-11-28

    Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to enhance the growth of hepatoma cells.

    Science.gov (United States)

    Shi, Hui; Fang, Runping; Li, Yinghui; Li, Leilei; Zhang, Weiying; Wang, Huawei; Chen, Fuquan; Zhang, Shuqin; Zhang, Xiaodong; Ye, Lihong

    2016-11-28

    Hepatitis B X-interacting protein (HBXIP) as an oncoprotein plays crucial roles in the development of cancer, involving glucose metabolism reprogramming. In this study, we are interested in whether the oncoprotein HBXIP is involved in the modulation of gluconeogenesis in liver cancer. Here, we showed that the expression level of phosphoenolpyruvate carboxykinase (PCK1), a key enzyme of gluconeogenesis, was lower in clinical hepatocellular carcinoma (HCC) tissues than that in normal tissues. Mechanistically, HBXIP inhibited the expression of PCK1 through down-regulating transcription factor FOXO1 in hepatoma cells, and up-regulated miR-135a targeting the 3'UTR of FOXO1 mRNA in the cells. In addition, HBXIP increased the phosphorylation levels of FOXO1 protein by activating PI3K/Akt pathway, leading to the export of FOXO1 from nucleus to cytoplasm. Strikingly, over-expression of PCK1 could abolish the HBXIP-promoted growth of hepatoma cells in vitro and in vivo. Thus, we conclude that the oncoprotein HBXIP is able to depress the gluconeogenesis through suppressing PCK1 to promote hepatocarcinogenesis, involving miR-135a/FOXO1 axis and PI3K/Akt/p-FOXO1 pathway. Our finding provides new insights into the mechanism by which oncoprotein HBXIP modulates glucose metabolism reprogramming in HCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Factors Associated with Growth Retardation in Children Suffering from Sickle Cell Anemia: First Report from Central Africa

    Directory of Open Access Journals (Sweden)

    Aimé Lukusa Kazadi

    2017-01-01

    Full Text Available Background. The aim of this study was to investigate and determine the risk factors associated with poor growth among SCA children. Methods. A cross-sectional study was conducted in Kinshasa, the capital’s country. The nutritional status was assessed using the Z scores of the anthropometric indices. Results. We gathered data on the 256 patients, 138 females (53.9%, who entered the study. The mean age at presentation was 8.4 ± 4.9 years of age. Underweight, stunting, and wasting were found, respectively, in 47.7%, 10.5%, and 50.3% of SCA children. A history of hand-foot syndrome, more than 3 blood transfusions, being less than 12 months of age when receiving the first transfusion, more than two severe sickle crises per year, a medical history of severe infections, and the presence of hepatomegaly were associated with poor growth. When comparing sickle cell patients under 12 years of age (n=159 to a group of 296 age-matched children with normal Hb-AA, a significantly higher proportion of subjects with stunting and underweight were found among SCA. Conclusion. Nutritional status encountered in Congolese sickle cell children has been described for the first time in this study. A high prevalence of poor growth in SCA children was found in our study.

  4. Biocontrol traits of plant growth suppressive arbuscular mycorrhizal fungi against root rot in tomato caused by Pythium aphanidermatum

    DEFF Research Database (Denmark)

    Larsen, John; Graham, James H.; Cubero, Jaime

    2012-01-01

    Arbuscular mycorrhizal (AM) fungi known to cause plant growth depressions in tomato were examined for their biocontrol effects against root rot caused by Pythium aphanidermatum. The main hypothesis was that plant growth suppressive AM fungi would elicit a defence response in the host plant reducing...... after AM fungi inoculation, roots were challenged with P. aphanidermatum. Variables evaluated at each harvest were root colonization levels of the interacting fungi, plant growth responses, and expression of a plant pathogenesis related protein gene (PR-1). All of the tested AM fungi caused marked...

  5. Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice

    Directory of Open Access Journals (Sweden)

    He Wu

    2018-01-01

    Full Text Available Whole body vibration (WBV has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS. To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE−/− AS mice, which were trained by WBV (15 Hz, 30 min for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1, insulin-like growth factor 1 receptor (IGF-1R, interleukin 6 (IL-6, and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL and oxidized low-density lipoprotein (ox-LDL in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

  6. Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice.

    Science.gov (United States)

    Wu, He; Zhang, Yibo; Yang, Xuan; Li, Xian; Shao, Zhenya; Zhou, Zipeng; Li, Yuanlong; Pan, Shuwen; Liu, Chang

    2018-01-01

    Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE -/- ) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (ox-LDL) in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

  7. Uterine Doppler wave form and the prediction of the recurrence of pre-eclampsia and intra-uterine growth retardation in patients treated with low-dose aspirin.

    Science.gov (United States)

    Haddad, B; Uzan, M; Bréart, G; Uzan, S

    1995-10-01

    To examine if early uterine Doppler remains a predictor of vascular complications in pregnant women treated with low-dose aspirin for a poor previous obstetrical history. A study of the uterine diastolic index and the uterine notch with a continuous wave Doppler ultrasound. The maternity Hospital Port-Royal Baudelocque Paris, France. All pregnant women between 1991-1992 (n = 48) early treated with 100 mg daily of aspirin (15.9 (S.D. = 1) weeks) for a poor previous obstetrical history. The 48 patients underwent a uterine Doppler examination at 23.8 (S.D. = 2.6) weeks. A diastolic index was calculated and the presence of diastolic notch was noted. Vascular complications (pre-eclampsia, intra-uterine growth retardation), birth weight. Twenty six patients (54.2%) had an abnormal early uterine Doppler. Nine patients (18.7%) had a vascular complication, which occurred more frequently in pregnant patients with an abnormal uterine Doppler (8/26 vs. 1/22; P < 0.05). The mean birth weight was lower in patients with a pathological uterine Doppler (2419 (S.D. = 679) vs. 2841 (S.D. = 482) g; P < 0.05). In pregnant, early treated with low-dose aspirin for poor previous pregnancies, early uterine Doppler predicted patients with a high-risk of recurrence of vascular complications.

  8. Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage.

    Science.gov (United States)

    Yokoi, Ryohei; Hayashi, Morimichi; Tamura, Toru; Kobayashi, Kazuo; Kuroda, Junji; Kusama, Hiroshi; Kagami, Hiroshi; Ono, Tamao

    2008-12-01

    Embryonic mortality and intrauterine growth retardation (IUGR) are induced by exposure of rodents to xenobiotic agents during the pregastrulation period of development. We examined the time course of the effects of methyl methanesulfonate (MMS), an alkylating agent, on conceptus development in order to clarify the relative roles of the embryo and the placenta in their induction. Pregnant rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation day (GD) 6 (peri-implantation stage). Embryonic mortality was increased on GD12 and thereafter by MMS treatment, with newly dead embryos showing placental hypoplasia at GD12. Embryo or fetal weight was also smaller for MMS-treated dams than for control dams from GD14 to GD20. The labyrinth zone and junctional zone (JZ) of the placenta were thinner in MMS-treated rats from GD12 to GD17 and from GD12 to GD20 (except for GD17), respectively. Furthermore, MMS-treated dams showed a smaller number of glycogen cells in the JZ on GD14. In contrast, the placental glycogen concentration was higher and the expression of glucose transporter 1 in the JZ remained at GD20. These results indicate that exposure of pregnant rats to MMS at the peri-implantation stage of embryogenesis affects placental development and growth. The placental impairment induced by MMS was likely responsible for the embryonic death observed 6 days after exposure of dams to this agent as well as for the IUGR of surviving embryos or fetuses throughout the gestation period.

  9. Bioactive Compound Rich Indian Spices Suppresses the Growth of β-lactamase Produced Multidrug Resistant Bacteria

    Directory of Open Access Journals (Sweden)

    Eadlapalli Siddhartha

    2017-01-01

    Full Text Available Background: Multidrug Resistance (MDR among bacteria become a global concern due to failure of antibiotics, is drawn attention for best antimicrobials from the spices which have been using ancient days in Indian culinary and traditional medicine. Aim and Objectives: The present study was undertaken to evaluate the bioactive compounds and their antibacterial activity in routinely used culinary Indian spices against β-lactamase produced MDR bacteria. Material and Methods: Ethanolic extracts prepared from twenty spices and were evaluated for total phenolics, flavonoids, alkaloids, terpenoids, antioxidant properties, and also assayed their antibacterial activities against β-lactamase producing MDR bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. β-Lactamase and cell viability assays were performed in MDR bacteria. Results: Among twenty spices, cinnamon and clove exhibited highest levels of phenolics and terpenoids with elevated antioxidant potential and also showing greater reducing potential at lower concentrations of extract (2.3 and 4.06 µg GAE/gm, respectively. Further, the spices extracts were assessed for antimicrobial activity against β-lactamase produced tested MDR bacteria and observed higher antimicrobial activity with cinnamon, garlic, tamarind and clove at lowest concentrations of MIC and MBC at 16 - 32 µg GAE/ml, as compared to standard drug, amoxiclav (16/8 µg/ml. Spices significantly inhibited the β-lactamase activity (80–94% and also cell viability in tested MDR bacteria. Conclusion: Indian spices consist of rich bioactive profile and antioxidant activity inhibited the bacterial growth effectively by suppressing β-lactamase production in MDR bacteria. Results indicating the spices as functional foods and could be used in prevention of antibiotic resistance.

  10. [Risk factors associated to growth retardation in children 12 to 120 months of age in Arandas, Jalisco, México].

    Science.gov (United States)

    Vásquez Garibay, Edgar M; Ortiz Ortega, Miguel Angel; Romero Velarde, Enrique; Nápoles Rodríguez, Francisco

    2008-12-01

    The purpose was to identify risk factors associated to deficit on linear growth in children from a semi-rural population in Arandas, Jalisco, Mexico. In a cross sectional study 432 children, 12 to 120 months old were included. Social, demographic, economical, dietetic and pathological characteristics and deficit in the height/age index ( 3 children in the family [OR 1.71 (1.01, 2.87)], soft drinks consumption > 4 times a week [OR 2.36 (1.19-4.73)], family's monthly income salary (100 USA dollars a month) [OR 1.81 (1.06, 3.09)]; age < 24 months [OR 2.02 (1.09, 3.75)], adding sweeteners to the bottle [OR 8.56 (1.84, 54.9)], diet modification during diarrhea [OR 2.40 (1.02, 5.77)], milk intake < 4 times a week [OR 2.71 (1.55, 4.73)] and nearly significant, bean consumption [1.75 (0.98, 3.13). Protection factors: nuclear family [OR 0.28 (0.09, 0.85)] and an adequate infant formula dilution [OR 0.71 (0.60, 0.85)]. In multivariate models associated factors to deficit of height were higher consumption of soft drinks, beans and the addition of sweeteners to the bottle. In addition to socioeconomic variables, lower consumption of high quality food and proteins and higher intake of legumes were important risk factors for mild and moderate deficit height/age.

  11. Suppression of polymorphonuclear (PMN) and monocyte-mediated inhibition of Candida albicans growth by delta-9-tetrahydrocannabinol

    Energy Technology Data Exchange (ETDEWEB)

    Djeu, J.Y.; Parapanios, A.; Halkias, D.; Friedman, H.

    1986-03-05

    This study was an in vitro attempt to identify the effector cells responsible for growth inhibition of the opportunistic fungus, candida albicans, and to determine if THC or another marijuana derivatives, 11-hydroxyTHC, would adversely affect their function. Using a 24h radiolabel assay, the authors found that growth inhibition of C. albicans was primarily mediated by PMN and monocytes that could be isolated normal human peripheral blood. Both effector cell types caused almost complete inhibition of Candida growth at effector/target ratio of 300/1 and inhibition was often still seen at 30/1-. Incubation of PMN, PBL, or monocytes for 1 hr at 37C with THC or 11-hydroxyTHC caused a marked suppression of function in all 3 cell populations. Maximal suppression was obtained with 7.5-10..mu..g/ml of the drugs in medium containing 10% fetal bovine serum (FBS) or with 2-4..mu..g/ml in 1% FBS. These drug concentrations did not affect lymphoid cell viability or candida growth in the absence of lymphoid effector cells. Marijuana derivatives, therefore, are doubly dangerous in that opportunistic fungi such as C. albicans can grow in their presence while the effector cells that control fungal growth are readily inactivated.

  12. Suppression of polymorphonuclear (PMN) and monocyte-mediated inhibition of Candida albicans growth by delta-9-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    Djeu, J.Y.; Parapanios, A.; Halkias, D.; Friedman, H.

    1986-01-01

    This study was an in vitro attempt to identify the effector cells responsible for growth inhibition of the opportunistic fungus, candida albicans, and to determine if THC or another marijuana derivatives, 11-hydroxyTHC, would adversely affect their function. Using a 24h radiolabel assay, the authors found that growth inhibition of C. albicans was primarily mediated by PMN and monocytes that could be isolated normal human peripheral blood. Both effector cell types caused almost complete inhibition of Candida growth at effector/target ratio of 300/1 and inhibition was often still seen at 30/1-. Incubation of PMN, PBL, or monocytes for 1 hr at 37C with THC or 11-hydroxyTHC caused a marked suppression of function in all 3 cell populations. Maximal suppression was obtained with 7.5-10μg/ml of the drugs in medium containing 10% fetal bovine serum (FBS) or with 2-4μg/ml in 1% FBS. These drug concentrations did not affect lymphoid cell viability or candida growth in the absence of lymphoid effector cells. Marijuana derivatives, therefore, are doubly dangerous in that opportunistic fungi such as C. albicans can grow in their presence while the effector cells that control fungal growth are readily inactivated

  13. Introduction to Mental Retardation

    Science.gov (United States)

    Arc of the United States, 2004

    2004-01-01

    The purpose of this document is to define mental retardation and answer questions related to this topic. According to the American Association on Mental Retardation (AAMR), mental retardation is a disability that occurs before age 18. It is characterized by significant limitations in intellectual functioning and adaptive behaviors as expressed in…

  14. Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth.

    Science.gov (United States)

    Evagelidou, Eleni N; Giapros, Vasileios I; Challa, Anna S; Kiortsis, Dimitrios N; Tsatsoulis, Agathocles A; Andronikou, Styliani K

    2007-02-01

    Insulin resistance has been linked to intrauterine growth retardation (IUGR); adiponectin is a protein with insulin-sensitizing properties. This study was designed to test whether being born small for gestational age (SGA) has an effect on blood levels of adiponectin and leptin, insulin resistance parameters, and lipid profile in pre-puberty, taking into consideration the severity of IUGR. Serum levels of adiponectin, leptin, total cholesterol (t-CHOL), high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, apolipoproteins A-1 (Apo A-1), Apo B and Apo E, lipoprotein(a) (Lp(a)), fasting glucose, and insulin (Ins), the homeostasis model assessment insulin resistance index (HOMA-IR) and anthropometric indices were evaluated in 70 children aged 6-8 years, born appropriate for gestational age (AGA; n = 35) and SGA (n = 35), matched for age, gender, height, and BMI. SGA children were divided into two subgroups according to the severity of IUGR: SGA<3rd percentile (n = 20), and SGA 3rd-10th percentile (n = 15). They were also subdivided in two subgroups, those with (n = 25) and those without (n = 10) catch-up growth, considering their actual height corrected for mid-parental height. SGA children had higher Ins and HOMA-IR than AGA children (Ins, 42 +/- 23 vs 32 +/- 11 pmol/l; HOMA-IR, 1.30 +/- 0.8 vs 0.92 +/- 0.3; P<0.05). No significant difference in serum leptin was found between the SGA and the AGA groups but adiponectin showed a trend to be higher in SGA children (13.6 +/- 5.7 vs 10.8 +/- 5.9 microg/ml respectively). SGA children without catch-up growth had higher adiponectin (15.6 +/- 8.5 microg/ml, P<0.05) than AGA children. Among the SGA children, the subgroup <3rd percentile had higher Lp(a) than the subgroup 3rd-10th percentile (P<0.05). An independent positive correlation between adiponectin and Lp(a) was observed in SGA children (R = 0.59, P<0.01). SGA children, although more insulin resistant, had similar or

  15. The isoflavone metabolite 6-methoxyequol inhibits angiogenesis and suppresses tumor growth

    Directory of Open Access Journals (Sweden)

    Bellou Sofia

    2012-05-01

    Full Text Available Abstract Background Increased consumption of plant-based diets has been linked to the presence of certain phytochemicals, including polyphenols such as flavonoids. Several of these compounds exert their protective effect via inhibition of tumor angiogenesis. Identification of additional phytochemicals with potential antiangiogenic activity is important not only for understanding the mechanism of the preventive effect, but also for developing novel therapeutic interventions. Results In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have screened a set of hitherto untested phytoestrogen metabolites concerning their anti-angiogenic effect, using endothelial cell proliferation as an end point. Here, we show that a novel phytoestrogen, 6-methoxyequol (6-ME, inhibited VEGF-induced proliferation of human umbilical vein endothelial cells (HUVE cells, whereas VEGF-induced migration and survival of HUVE cells remained unaffected. In addition, 6-ME inhibited FGF-2-induced proliferation of bovine brain capillary endothelial (BBCE cells. In line with its role in cell proliferation, 6-ME inhibited VEGF-induced phosphorylation of ERK1/2 MAPK, the key cascade responsible for VEGF-induced proliferation of endothelial cells. In this context, 6-ME inhibited in a dose dependent manner the phosphorylation of MEK1/2, the only known upstream activator of ERK1/2. 6-ME did not alter VEGF-induced phosphorylation of p38 MAPK or AKT, compatible with the lack of effect on VEGF-induced migration and survival of endothelial cells. Peri-tumor injection of 6-ME in A-431 xenograft tumors resulted in reduced tumor growth with suppressed neovasularization compared to vehicle controls (P  Conclusions 6-ME inhibits VEGF- and FGF2-induced proliferation of ECs by targeting the phosphorylation of MEK1/2 and it downstream substrate ERK1/2, both key components of the mitogenic MAPK

  16. Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Chalmers Laura J

    2011-05-01

    Full Text Available Abstract Background Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences. Methods In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks, birth weight (kg, birth length (cm and parental heights (cm were obtained. Mid-parental height was considered in the analyses. Results Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (P > 0.05. The expected sex difference in favor of heavier males was not seen (P > 0.05. Of the 105 subjects, 44 (27%; 34 females, 10 males had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile, which differed from the expected standard population median of 50th percentile (P = 0.0082. The expected sex difference in favor of longer males was also not seen (P > 0.05. Conclusion The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who

  17. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    International Nuclear Information System (INIS)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-01-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by 1 H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome

  18. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    Energy Technology Data Exchange (ETDEWEB)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Zhang, Yuanzhen [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China)

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal

  19. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

    Science.gov (United States)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Measles virus C protein suppresses gamma-activated factor formation and virus-induced cell growth arrest

    International Nuclear Information System (INIS)

    Yokota, Shin-ichi; Okabayashi, Tamaki; Fujii, Nobuhiro

    2011-01-01

    Measles virus (MeV) produces two accessory proteins, V and C, from the P gene. These accessory proteins have been reported to contribute to efficient virus proliferation through the modulation of host cell events. Our previous paper described that Vero cell-adapted strains of MeV led host cells to growth arrest through the upregulation of interferon regulatory factor 1 (IRF-1), and wild strains did not. In the present study, we found that C protein expression levels varied among MeV strains in infected SiHa cells. C protein levels were inversely correlated with IRF-1 expression levels and with cell growth arrest. Forced expression of C protein released cells from growth arrest. C-deficient recombinant virus efficiently upregulated IRF-1 and caused growth arrest more efficiently than the wild-type virus. C protein preferentially bound to phosphorylated STAT1 and suppressed STAT1 dimer formation. We conclude that MeV C protein suppresses IFN-γ signaling pathway via inhibition of phosphorylated STAT1 dimerization.

  1. Suppression of Tumor Growth in Mice by Rationally Designed Pseudopeptide Inhibitors of Fibroblast Activation Protein and Prolyl Oligopeptidase

    Directory of Open Access Journals (Sweden)

    Kenneth W. Jackson

    2015-01-01

    Full Text Available Tumor microenvironments (TMEs are composed of cancer cells, fibroblasts, extracellular matrix, microvessels, and endothelial cells. Two prolyl endopeptidases, fibroblast activation protein (FAP and prolyl oligopeptidase (POP, are commonly overexpressed by epithelial-derived malignancies, with the specificity of FAP expression by cancer stromal fibroblasts suggesting FAP as a possible therapeutic target. Despite overexpression in most cancers and having a role in angiogenesis, inhibition of POP activity has received little attention as an approach to quench tumor growth. We developed two specific and highly effective pseudopeptide inhibitors, M83, which inhibits FAP and POP proteinase activities, and J94, which inhibits only POP. Both suppressed human colon cancer xenograft growth >90% in mice. By immunohistochemical stains, M83- and J94-treated tumors had fewer microvessels, and apoptotic areas were apparent in both. In response to M83, but not J94, disordered collagen accumulations were observed. Neither M83- nor J94-treated mice manifested changes in behavior, weight, or gastrointestinal function. Tumor growth suppression was more extensive than noted with recently reported efforts by others to inhibit FAP proteinase function or reduce FAP expression. Diminished angiogenesis and the accompanying profound reduction in tumor growth suggest that inhibition of either FAP or POP may offer new therapeutic approaches that directly target TMEs.

  2. Efecto del retardo prenatal de crecimiento y la subnutrición postnatal en el crecimiento craneofacial / Craneofacial effect of prenatal growth retardation and postnatal undernutrition in craniofacial growth

    Directory of Open Access Journals (Sweden)

    María Eugenia Luna

    2016-03-01

    Full Text Available El objetivo fue analizar en animales con retardo prenatal de crecimiento (RPC el efecto de la subnutrición proteico-calórica lactacional y postlactacional sobre la morfología craneofacial, particularizando en el crecimiento de los componentes funcionales neural y facial. Ratas Wistar fueron divididas en los grupos: Control, RPC (inducido por ligamiento parcial de ambas arterias uterinas el día 15 de gestación y Sham-operado (con igual técnica quirúrgica que RPC aunque sin ligamiento de las arterias. A su vez, el grupo RPC se dividió en: (a crías lactantes de madres con nutrición normal y a partir del destete alimentadas ad-libitum y (b crías lactantes de madres con restricción alimentaria del 25% y a partir del destete alimentadas con el 50% de lo consumido por un animal control. Se tomaron radiografías a las edades 1, 21, 42, 63 y 84 y se midieron longitud, ancho y altura de los componentes neural y facial. Se calcularon los índices volumétricos neural y facial y morfométrico neurofacial. Se aplicaron ANOVA y pruebas post-hoc y se calcularon diferencias porcentuales entre medias. Los resultados permitieron concluir que el estrés primario ocurrido durante la vida intrauterina resulta crítico en lo inmediato y en la vida postnatal, ya que aun mediando normonutrición postnatal el retardo de crecimiento perdura. Además, cuando al estrés prenatal le continúa restricción nutricional postnatal los efectos adversos son aditivos provocando retardo del crecimiento aún mayor. Finalmente, mientras que el componente neural es más resistente a las deficiencias nutricionales, el facial presenta mayor plasticidad, hecho que se evidencia en cambios de forma. Palabras clave: crecimiento craneofacial; desnutrición pre y postnatal; craneometría funcional    The aim of the study was to analyze the effect of protein-calorie malnutrition during lactation and post-lactation on craniofacial morphology in intrauterine growth-retarded (IUGR

  3. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1{beta} secretion

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Lixia Z.; Liu, Weimin; Luo, Yuchun; Okamoto, Miyako; Qu, Dovina; Dunn, Jeffrey H. [Department of Dermatology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Fujita, Mayumi, E-mail: mayumi.fujita@ucdenver.edu [Department of Dermatology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Denver Veterans Affairs Medical Center, Denver, CO 80220 (United States)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer EGCG inhibits melanoma cell growth at physiological doses (0.1-1 {mu}M). Black-Right-Pointing-Pointer EGCG inhibits melanoma cell growth via inflammasomes and IL-1{beta} suppression. Black-Right-Pointing-Pointer Inflammasomes and IL-1{beta} could be potential targets for future melanoma therapeutics. -- Abstract: Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1-1 {mu}M). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-{kappa}B was inhibited, and that reduced NF-{kappa}B activity was associated with decreased IL-1{beta} secretion from melanoma cells. Since inflammasomes are involved in IL-1{beta} secretion, we investigated whether IL-1{beta} suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation {yields} decreased IL-1{beta} secretion {yields} decreased NF-{kappa}B activities {yields} decreased cell growth. In addition, it suggests inflammasomes and IL-1{beta} could be potential targets for future melanoma therapeutics.

  4. Comparative proteomic analysis reveals the suppressive effects of dietary high glucose on the midgut growth of silkworm.

    Science.gov (United States)

    Feng, Fan; Chen, Liang; Lian, Chaoqun; Xia, Hengchuan; Zhou, Yang; Yao, Qin; Chen, Keping

    2014-08-28

    The silkworm, Bombyx mori, is an important model of lepidoptera insect, and it has been used for several models of human diseases. In human being, long-term high-sugar diet can induce the occurrence of diabetes and other related diseases. Interestingly, our experiments revealed the high glucose diet also has a suppressive effect on the development of silkworms. To investigate the molecular mechanism by which high-glucose diet inhibited the midgut growth in silkworms, we employed comparative proteomic analysis to globally identify proteins differentially expressed in normal and high-glucose diet group silkworms. In all, 28 differently proteins were suppressed and 5 proteins induced in high-glucose diet group. Gene ontology analysis showed that most of these differently proteins are mainly involved in metabolic process, catalytic and cellular process. A development related protein, imaginal disk growth factor (IDGF), was further confirmed by western blot exclusively expressing in the normal diet group silkworms. Taken together, our data suggests that IDGF plays a critical role in impairing the development of silkworms by a high-glucose diet. Glucose has been thought to play essential roles in growth and development of silkworm. In this paper, we certified firstly that high-glucose diet can suppress the growth of silkworm, and comparative proteomic was employed to reveal the inhibition mechanism. Moreover, an important regulation related protein (IDGF) was found to involve in this inhibition process. These results will help us get a deeper understanding of the relationship between diet and healthy. Furthermore, IDGF may be the critical protein for reducing the blood sugar in silkworm, and it may be used for screening human hypoglycemic drug. The work has not been submitted elsewhere for publication, in whole or in part, and all the authors have approved the manuscript. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

    DEFF Research Database (Denmark)

    Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike

    2016-01-01

    LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size...

  6. Oral Supplementation with a Special Additive of Retinyl Palmitate and Alpha Tocopherol Reduces Growth Retardation in Young Pancreatic Duct Ligated Pigs Used as a Model for Children Suffering from Exocrine Pancreatic Insufficiency

    Directory of Open Access Journals (Sweden)

    Anne Mößeler

    2016-09-01

    Full Text Available Pancreatic exocrine insufficiency (PEI is a disease of diverse aetiology—e.g., majority of patients suffering from cystic fibrosis (CF show PEI congenitally. Malnutrition and malabsorption of nutrients impair growth and nutritional status. As reduced fat digestion leads to a deficiency of fat-soluble vitamins the supplementation is standard, but absorption is a critical point in PEI-patients. The pancreatic duct ligated (PL pig is an established model for PEI in humans and has been proven to be a suitable model to compare different vitamin additives for supplementation. In a former study, PEI caused distinct growth retardation in young piglets, but did not affect growth in older ones. Our study hypothesised that this age-dependent effect is caused by exhausted body reserves of fat-soluble vitamins and, therefore, extra supply reduces growth retardation. PEI was induced by PL at the age of seven (PL-7 or 16 weeks (PL-16. Controls (C underwent a sham surgery. Some PL-7 pigs (PL-7 + Vit were fed a special vitamin additive. PEI reduced the mean final body weight (kg at 26 weeks of age significantly with lower effect in PL-16-pigs (C:117; PL-7:49.5; PL-7 + Vit:77.1; PL-16:96.4. Extra vitamin supply resulted in an increased growth and normalised serum concentration of alpha-tocopherol, underlining the importance of special supplementation in PEI-patients.

  7. Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α.

    Science.gov (United States)

    Liang, Hua; Yang, Cheng Xiang; Zhang, Bin; Wang, Han Bing; Liu, Hong Zhen; Lai, Xiao Hong; Liao, Mei Juan; Zhang, Tao

    2015-12-01

    Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated. A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting. Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia. Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

  8. U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

    Directory of Open Access Journals (Sweden)

    Rafal Goraczniak

    2013-01-01

    Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

  9. A comprehensive siRNA screen for kinases that suppress macroautophagy in optimal growth conditions

    DEFF Research Database (Denmark)

    Szyniarowski, Piotr; Corcelle-Termeau, Elisabeth; Farkas, Thomas

    2011-01-01

    , whereas CSNK1A1, BUB1, PKLR and NEK4 suppressed autophagosome formation downstream or independent of mTORC1. Importantly, all identified kinases except for BUB1 regulated macroautophagy also in immortalized MCF-10A breast epithelial cells. The kinases identified here shed light to the complex regulation...

  10. Isolation and Identification of Plant Growth Promoting Rhizobacteria from Cucumber Rhizosphere and Their Effect on Plant Growth Promotion and Disease Suppression.

    Science.gov (United States)

    Islam, Shaikhul; Akanda, Abdul M; Prova, Ananya; Islam, Md T; Hossain, Md M

    2015-01-01

    Plant growth promoting rhizobacteria (PGPR) are the rhizosphere bacteria that may be utilized to augment plant growth and suppress plant diseases. The objectives of this study were to identify and characterize PGPR indigenous to cucumber rhizosphere in Bangladesh, and to evaluate their ability to suppress Phytophthora crown rot in cucumber. A total of 66 isolates were isolated, out of which 10 (PPB1, PPB2, PPB3, PPB4, PPB5, PPB8, PPB9, PPB10, PPB11, and PPB12) were selected based on their in vitro plant growth promoting attributes and antagonism of phytopathogens. Phylogenetic analysis of 16S rRNA sequences identified these isolates as new strains of Pseudomonas stutzeri, Bacillus subtilis, Stenotrophomonas maltophilia, and Bacillus amyloliquefaciens. The selected isolates produced high levels (26.78-51.28 μg mL(-1)) of indole-3-acetic acid, while significant acetylene reduction activities (1.79-4.9 μmole C2H4 mg(-1) protein h(-1)) were observed in eight isolates. Cucumber plants grown from seeds that were treated with these PGPR strains displayed significantly higher levels of germination, seedling vigour, growth, and N content in root and shoot tissue compared to non-treated control plants. All selected isolates were able to successfully colonize the cucumber roots. Moreover, treating cucumber seeds with these isolates significantly suppressed Phytophthora crown rot caused by Phytophthora capsici, and characteristic morphological alterations in P. capsici hyphae that grew toward PGPR colonies were observed. Since these PGPR inoculants exhibited multiple traits beneficial to the host plants, they may be applied in the development of new, safe, and effective seed treatments as an alternative to chemical fungicides.

  11. Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells.

    Science.gov (United States)

    Kato, Taigo; Inoue, Hiroyuki; Imoto, Seiya; Tamada, Yoshinori; Miyamoto, Takashi; Matsuo, Yo; Nakamura, Yusuke; Park, Jae-Hyun

    2016-04-05

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.

  12. Untreated growth hormone deficiency with extremely short stature, bone dysplasia, cleft lip--palate and severe mental retardation in a 26-year-old man with a de novo unbalanced translocation t(1;12)(q24;q24).

    Science.gov (United States)

    Callier, P; Faivre, L; Marle, N; Thauvin-Robinet, C; Mosca, A L; Masurel-Paulet, A; Borgnon, J; Falcon-Eicher, S; Danino, A; Malka, G; Le Merrer, M; Huet, F; Mugneret, F

    2007-01-01

    We report on a 26-year-old patient presenting with extremely short stature (height 72cm, weight 6.5kg, OFC 42.5cm), facial dysmorphism, cleft lip--palate, severe mental retardation and de novo 1q24.2--q25.2 and 12q24.31 interstitial deletion. He was the only child of non-consanguineous parents and his birth length was 43cm. He had severe feeding difficulties and required enteral nutrition until the age of 3 years. Standard cytogenetic analysis showed an apparently balanced de novo translocation t(1;12)(q24;q24). Endocrine studies at 11 years of age for severe growth retardation revealed multiple pituitary hormone deficiency with severe growth hormone deficiency, but the child was untreated because of associated mental retardation. At 26 years of age, he could not walk or speak and had no signs of puberty. Investigations revealed spondylo-epi-metaphyseal dysplasia with severe osteoporosis, enlarged aorta when compared to the patient's size and apparently normal pituitary development. High resolution karyotype showed a 1q24-q25 deletion, and comparative genomic hybridization studies confirmed the 1q interstitial deletion. FISH studies of both breakpoints using PACs and BACs enabled us to further characterize the 1q interstitial deletion (1q24.2-1q25.2) and also revealed a 12q24.31 interstitial microdeletion. This case is compared with previously reported patients with similar deletions, but the untreated pituitary deficiency could also be responsible in part for the severity of the growth deficiency. This observation is of interest for two reasons. First, these deletions could be a clue in the search for a gene responsible for growth hormone deficiency/midline defects. Second, it shows the importance of molecular cytogenetics in the study of de novo apparently balanced translocation with abnormal phenotype.

  13. Rates of nitrogen and growth retardant trinexapac-ethyl on wheat Doses de nitrogênio e do redutor de crescimento trinexapac-etil na cultura do trigo

    Directory of Open Access Journals (Sweden)

    Marcelo Curitiba Espindula

    2011-12-01

    Full Text Available The objective in this study was to evaluate the effects of nitrogen rates in association with rates of the growth retardant trinexapac-ethyl on wheat. The experiment was conducted in Viçosa, MG and arranged in a 5×4 factorial, randomized block design, with four repetitions. A combination of five nitrogen rates (30, 60, 90, 120 and 150kg ha-1 with four rates of trinexapac-ethyl (0, 62.5, 125 and 187.5g ha-1 were tested. Trinexapac-ethyl promotes reduction of soot dry mass and grain yield at the lowest N rates, but at the highest N rates there is increase in these characteristics. The combination between N and trinexapac-ethyl rates that promotes higher shoot dry mass is 150kg ha-1 and 187g ha-1 but that promotes higher grain yield is 100kg ha-1 and 120g ha-1, respectively.O objetivo neste estudo foi avaliar os efeitos de doses de nitrogênio associadas às doses do redutor de crescimento trinexapac-etil na cultura do trigo. O experimento, conduzido em Viçosa-MG, seguiu um esquema fatorial 5×4, no delineamento experimental de blocos casualizados, com quatro repetições. Os tratamentos foram 30, 60, 90, 120 e 150kg ha-1 de N, combinados com 0, 62,5, 125 e 187,5g ha-1 de trinexapac-etil. Trinexapac-etil promove redução da massa seca da parte aérea e do rendimento de grãos nas menores doses de N, mas sob doses elevadas de N o trinexapac-etil promove aumento dessas características. A combinação entre doses de N e trinexapac-etil que promove maior massa seca da parte aérea é de 150kg ha-1 e 187g ha-1, mas a que promove maior produção de grãos é de 100kg ha-1 e 120g ha-1, respectivamente.

  14. Complete biallelic insulation at the H19/Igf2 imprinting control region position results in fetal growth retardation and perinatal lethality.

    Directory of Open Access Journals (Sweden)

    Dong-Hoon Lee

    2010-09-01

    Full Text Available The H19/Igf2 imprinting control region (ICR functions as an insulator exclusively in the unmethylated maternal allele, where enhancer-blocking by CTCF protein prevents the interaction between the Igf2 promoter and the distant enhancers. DNA methylation inhibits CTCF binding in the paternal ICR allele. Two copies of the chicken β-globin insulator (ChβGI(2 are capable of substituting for the enhancer blocking function of the ICR. Insulation, however, now also occurs upon paternal inheritance, because unlike the H19 ICR, the (ChβGI(2 does not become methylated in fetal male germ cells. The (ChβGI(2 is a composite insulator, exhibiting enhancer blocking by CTCF and chromatin barrier functions by USF1 and VEZF1. We asked the question whether these barrier proteins protected the (ChβGI(2 sequences from methylation in the male germ line.We genetically dissected the ChβGI in the mouse by deleting the binding sites USF1 and VEZF1. The methylation of the mutant versus normal (ChβGI(2 significantly increased from 11% to 32% in perinatal male germ cells, suggesting that the barrier proteins did have a role in protecting the (ChβGI(2 from methylation in the male germ line. Contrary to the H19 ICR, however, the mutant (mChβGI(2 lacked the potential to attain full de novo methylation in the germ line and to maintain methylation in the paternal allele in the soma, where it consequently functioned as a biallelic insulator. Unexpectedly, a stricter enhancer blocking was achieved by CTCF alone than by a combination of the CTCF, USF1 and VEZF1 sites, illustrated by undetectable Igf2 expression upon paternal transmission.In this in vivo model, hypomethylation at the ICR position together with fetal growth retardation mimicked the human Silver-Russell syndrome. Importantly, late fetal/perinatal death occurred arguing that strict biallelic insulation at the H19/Igf2 ICR position is not tolerated in development.

  15. A chemical pollen suppressant inhibits auxin-induced growth in maize coleoptile sections

    International Nuclear Information System (INIS)

    Vesper, M.J.; Cross, J.W.

    1990-01-01

    Chemical inhibitors of pollen development having a phenylcinnoline carboxylate structure were found to inhibit IAA- and 1-NAA-induced growth in maize coleoptile sections. The inhibitor (100 μM) used in these experiments caused approx. 35% reduction in auxin-induced growth over the auxin concentration range of 0.3 to 100 μM. Growth inhibition was noted as a lengthening of the latent period and a decrease in the rate of an auxin-induced growth response. An acid growth response to pH 5 buffer in abraded sections was not impaired. The velocity of basipetal transport of [ 3 H]IAA through the coleoptile sections also was not inhibited by the compound, nor was uptake of [ 3 H]IAA. Similarly, the inhibitor does not appear to alter auxin-induced H + secretion. We suggest that the agent targets some other process necessary for auxin-dependent growth

  16. ABA Suppresses Root Hair Growth via the OBP4 Transcriptional Regulator1[OPEN

    Science.gov (United States)

    Kawamura, Ayako; Schäfer, Sabine; Breuer, Christian; Shibata, Michitaro; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Matsui, Minami

    2017-01-01

    Plants modify organ growth and tune morphogenesis in response to various endogenous and environmental cues. At the cellular level, organ growth is often adjusted by alterations in cell growth, but the molecular mechanisms underlying this control remain poorly understood. In this study, we identify the DNA BINDING WITH ONE FINGER (DOF)-type transcription regulator OBF BINDING PROTEIN4 (OBP4) as a repressor of cell growth. Ectopic expression of OBP4 in Arabidopsis (Arabidopsis thaliana) inhibits cell growth, resulting in severe dwarfism and the repression of genes involved in the regulation of water transport, root hair development, and stress responses. Among the basic helix-loop-helix transcription factors known to control root hair growth, OBP4 binds the ROOT HAIR DEFECTIVE6-LIKE2 (RSL2) promoter to repress its expression. The accumulation of OBP4 proteins is detected in expanding root epidermal cells, and its expression level is increased by the application of abscisic acid (ABA) at concentrations sufficient to inhibit root hair growth. ABA-dependent induction of OBP4 is associated with the reduced expression of RSL2. Furthermore, ectopic expression of OBP4 or loss of RSL2 function results in ABA-insensitive root hair growth. Taken together, our results suggest that OBP4-mediated transcriptional repression of RSL2 contributes to the ABA-dependent inhibition of root hair growth in Arabidopsis. PMID:28167701

  17. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

    International Nuclear Information System (INIS)

    Gao, Yong; Luo, Ling-hui; Li, Shuai; Yang, Cao

    2014-01-01

    Highlights: • miR-17 was increased in OS tissues and cell lines. • Inhibition of miR-17 suppressed OS cell proliferation. • Inhibition of miR-17 suppressed OS cell migration and invasion. • PTEN was a target of miR-17. • miR-17 was negatively correlated with PTEN in OS tissues. - Abstract: MicroRNAs (miRNAs) play essential roles in cancer development and progression. Here, we investigated the role of miR-17 in the progression and metastasis of osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines. Inhibition of miR-17 in OS cell lines substantially suppressed cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN by direct binding to its 3′-untranslated region (3′-UTR). Expression of miR-17 was negatively correlated with PTEN in OS tissues. Together, these findings indicate that miR-17 acts as an oncogenic miRNA and may contribute to the progression and metastasis of OS, suggesting miR-17 as a potential novel diagnostic and therapeutic target of OS

  18. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yong, E-mail: gaoyongunion@163.com [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Luo, Ling-hui [Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Li, Shuai; Yang, Cao [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2014-02-07

    Highlights: • miR-17 was increased in OS tissues and cell lines. • Inhibition of miR-17 suppressed OS cell proliferation. • Inhibition of miR-17 suppressed OS cell migration and invasion. • PTEN was a target of miR-17. • miR-17 was negatively correlated with PTEN in OS tissues. - Abstract: MicroRNAs (miRNAs) play essential roles in cancer development and progression. Here, we investigated the role of miR-17 in the progression and metastasis of osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines. Inhibition of miR-17 in OS cell lines substantially suppressed cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN by direct binding to its 3′-untranslated region (3′-UTR). Expression of miR-17 was negatively correlated with PTEN in OS tissues. Together, these findings indicate that miR-17 acts as an oncogenic miRNA and may contribute to the progression and metastasis of OS, suggesting miR-17 as a potential novel diagnostic and therapeutic target of OS.

  19. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.

    Directory of Open Access Journals (Sweden)

    Ron Firestein

    2008-04-01

    Full Text Available Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR, a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies.

  20. The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth

    Science.gov (United States)

    Oberdoerffer, Philipp; Ogino, Shuji; Campbell, Jennifer; Bhimavarapu, Anupama; Luikenhuis, Sandra; de Cabo, Rafael; Fuchs, Charles; Hahn, William C.; Guarente, Leonard P.; Sinclair, David A.

    2008-01-01

    Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a β-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates β-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of β-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of β−catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in β−catenin-driven malignancies. PMID:18414679

  1. Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific immune response.

    Directory of Open Access Journals (Sweden)

    Zhizhong Zhou

    Full Text Available Dendritic cells (DCs play a key role in the initiation stage of an antigen-specific immune response. A variety of tumor-derived factors (TDFs can suppress DC maturation and function, resulting in defects in the tumor-specific immune response. To identify unknown TDFs that may suppress DCs maturation and function, we established a high-throughput screening technology based on a human liver tumor T7 phage cDNA library and screened all of the proteins derived from hepatoma cells that potentially interact with immature DCs. Growth/differentiation factor-15 (GDF-15 was detected and chosen for further study. By incubation of DCs cultures with GDF-15, we demonstrate that GDF-15 can inhibit surface protrusion formation during DC maturation; suppress the membrane expression of CD83, CD86 and HLA-DR on DCs; enhance phagocytosis by DCs; reduce IL-12 and elevate TGF-β1 secretion by DCs; inhibit T cell stimulation and cytotoxic T lymphocyte (CTL activation by DCs. By building tumor-bearing mouse models, we demonstrate that GDF-15 can inhibit the ability of DCs to stimulate a tumor-specific immune response in vivo. These results indicate that GDF-15 may be one of the critical molecules that inhibit DC maturation and function and are involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor immunotherapy.

  2. Antrodia camphorata Grown on Germinated Brown Rice Suppresses Melanoma Cell Proliferation by Inducing Apoptosis and Cell Differentiation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Minjung Song

    2013-01-01

    Full Text Available Antrodia camphorata grown on germinated brown rice (CBR was prepared to suppress melanoma development. CBR extracts were divided into hexane, EtOAc, BuOH, and water fractions. Among all the fractions, EtOAc fraction showed the best suppressive effect on B16F10 melanoma cell proliferation by CCK-8 assay. It also showed the increased cell death and the changed cellular morphology after CBR treatment. Annexin V-FITC/PI, flow cytometry, and western blotting were performed to elucidate anticancer activity of CBR. The results showed that CBR induced p53-mediated apoptotic cell death of B16F10. CBR EtOAc treatment increased melanin content and melanogenesis-related proteins of MITF and TRP-1 expressions, which supports its anticancer activity. Its potential as an anticancer agent was further investigated in tumor-xenografted mouse model. In melanoma-xenografted mouse model, melanoma tumor growth was significantly suppressed under CBR EtOAc fraction treatment. HPLC analysis of CBR extract showed peak of adenosine. In conclusion, CBR extracts notably inhibited B16F10 melanoma cell proliferation through the p53-mediated apoptosis induction and increased melanogenesis. These findings suggest that CBR EtOAc fraction can act as an effective anticancer agent to treat melanoma.

  3. Growth retardants in wheat and its effect in physiological quality of seeds Redutores de crescimento em plantas de trigo e seus efeitos na qualidade fisiológica de sementes

    Directory of Open Access Journals (Sweden)

    Leandro Torres de Souza

    2010-06-01

    Full Text Available Plant lodging in wheat has been controlled through growth retardants. However, there is lack of information on the effect of these products on the physiological quality of seeds. The objective of this study was to evaluate the physiological quality of wheat seeds obtained under different rates and application times of three growth retardants. The trial was carried out in Viçosa-MG, from May to September 2005, in a factorial and hierarchical scheme, in randomized block design with four replications and a control treatment. The treatments consisted of 500, 1000 and 1500g ha-1 of chlormequat; 40, 80 and 120g ha-1 of paclobutrazol and 62.5, 125 and 187.5g ha-1 of trinexapac-ethyl applied at the 6 or 8 growth stage based on the scale of Feeks and Large, and a control treatment without growth retardant application. Leaf application of growth retardants as chlormequat, paclobutrazol and trinexapac-ethyl did not affect the germination and vigor of wheat seeds.O acamamento de plantas na cultura do trigo tem sido controlado com o uso de redutores de crescimento. No entanto, há carência de informações sobre o efeito desses produtos na qualidade fisiológica de sementes. O objetivo deste estudo foi avaliar a qualidade fisiológica das sementes de trigo obtidas sob efeito de doses e épocas de aplicação de três redutores de crescimento. O experimento, conduzido em Viçosa, Minas Gerais, entre maio e setembro de 2005, foi instalado com tratamentos em esquema fatorial e hierárquico com uma testemunha, no delineamento em blocos casualizados, com quatro repetições. Os tratamentos foram 500, 1000 e 1500g ha-1 de clormequat; 40, 80 e 120g ha-1 de paclobutrazol e 62,5, 125 e 187,5g ha-1 de trinexapac-etil aplicados no estádio 6 ou 8 da escala Feeks e Large, mais uma testemunha sem aplicação de redutor. A aplicação foliar dos redutores de crescimento clormequat, paclobutrazol e trinexapac-etil não afeta a germinação e o vigor das sementes de trigo.

  4. Breviscapine suppresses the growth of non-small cell lung cancer ...

    Indian Academy of Sciences (India)

    Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells.However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimedto study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 and A549 cells ...

  5. Breviscapine suppresses the growth of non-small cell lung cancer ...

    Indian Academy of Sciences (India)

    2017-02-10

    Feb 10, 2017 ... Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells. However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimed to study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 ...

  6. Procedure for growing Bi4Ge3O12 bismuth germanate single crystals with suppressed growth defects

    International Nuclear Information System (INIS)

    Zikmund, J.; Blazek, K.; Jarolimek, O.; Horak, J.

    1991-01-01

    The method developed allows high-quality scintillator material to be grown reproducibly by the Czochralski method. The crystals attain diameters up to 80 mm and lengths up to 200 mm. The growth is performed on instruments equipped with devices for continuous measurement of weight increments of the growing crystals with a precision better than 10 mg. The growth parameters are controlled with a computer and based on actual data. The crystals are grown using an axial temperature gradient within the range of 25 to 35 degC/cm and a constant drawing rate within the range of 0.5 to 1.2 mm/h. An interface shape suitable for the suppression of defect development is achieved through a combination of the weight increment and rotation of the crystal. (M.D.)

  7. Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

    Science.gov (United States)

    Kuroyanagi, Gen; Otsuka, Takanobu; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Nakakami, Akira; Mizutani, Jun; Kozawa, Osamu; Tokuda, Haruhiko

    2014-01-01

    It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation. PMID:25290095

  8. Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Young-Chae Kim

    Full Text Available The androgen receptor (AR mediates the developmental, physiologic, and pathologic effects of androgens including 5α-dihydrotestosterone (DHT. However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti-AR, and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S-phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation.

  9. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

    Directory of Open Access Journals (Sweden)

    Mingzhu Zhuang

    Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

  10. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy.

  11. MiR-203 Determines Poor Outcome and Suppresses Tumor Growth by Targeting TBK1 in Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Shiping Liu

    2015-11-01

    Full Text Available Background/Aims: Increasing evidence has shown that miR-203 plays important role in human cancer progression. However, little is known about the function of miR-203 in osteosarcoma (OS. Methods: The expression of miR-203 in OS tissues and cell lines were examined by qRT-PCR. The biological role of miR-20 in OS cell proliferation was examined in vitro and in vivo. The targets of miR-203 were identified by a luciferase reporter gene assay. Results: miR-203 was down regulated in OS tissues and cell lines; decreased miR-203 was associated with a poor overall survival in OS patients. Restoration of miR-203 expression reduced cell growth in vitro and suppressed tumorigenicity in vivo. In contrast, inhibition of miR-203 stimulated OS cell growth both in vitro and in vivo. In addition, TANK binding kinase 1 (TBK1 was identified as a direct target of miR-203; overexpression of TBK1 partly reversed the suppressive effects of miR-203. Furthermore, TBK1 was found up-regulated and inversely correlated with miR-203 in OS tissues. Conclusion: Taken together, these findings suggest that miR-203 acts as a tumor suppressor via regulation of TBK1 expression in OS progression, and miR-203 may be a promising therapeutic target for OS.

  12. Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.

    Science.gov (United States)

    Jiang, Jiahua; Slivova, Veronika; Harvey, Kevin; Valachovicova, Tatiana; Sliva, Daniel

    2004-01-01

    Ganoderma lucidum (Reishi, Lingzhi) is a popular Asian mushroom that has been used for more than 2 millennia for the general promotion of health and was therefore called the "Mushroom of Immortality." Ganoderma lucidum was also used in traditional Chinese medicine to prevent or treat a variety of diseases, including cancer. We previously demonstrated that Ganoderma lucidum suppresses the invasive behavior of breast cancer cells by inhibiting the transcription factor NF-kappaB. However, the molecular mechanisms responsible for the inhibitory effects of Ganoderma lucidum on the growth of highly invasive and metastatic breast cancer cells has not been fully elucidated. Here, we show that Ganoderma lucidum inhibits proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB signaling. Ganoderma lucidum suppresses phosphorylation of Akt on Ser473 and downregulates the expression of Akt, which results in the inhibition of NF-kappaB activity in MDA-MB-231 cells. The biological effect of Ganoderma lucidum was demonstrated by cell cycle arrest at G0/G1, which was the result of the downregulation of expression of NF-kappaB-regulated cyclin D1, followed by the inhibition of cdk4. Our results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic use for the treatment of breast cancer.

  13. Blockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Li, Hui-Min; Yang, Jie-Gang; Liu, Zhuo-Jue; Wang, Wei-Ming; Yu, Zi-Li; Ren, Jian-Gang; Chen, Gang; Zhang, Wei; Jia, Jun

    2017-01-07

    Many cancers including head and neck squamous cell carcinoma (HNSCC) are characterized by a metabolic rewiring with increased glucose uptake and lactate production, termed as aerobic glycolysis. Targeting aerobic glycolysis presents a promising strategy for cancer therapy. This study investigates the therapeutic potential of glycolysis blockage by targeting phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) in HNSCC. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was determined by measuring glucose uptake, lactate production and ATP yield. PFKFB3 expression was examined using HNSCC tissue arrays. Cell proliferation, apoptosis and motility were analysed. HNSCC xenograft mouse model and metastasis mouse model were established to examine the therapeutic efficacy of PFK15 in vivo. HNSCC showed an increased PFKFB3 expression compared with adjacent mucosal tissues (P < 0.01). Targeting PFKFB3 via PFK15 significantly reduced the glucose uptake, lactate production and ATP generation in HNSCC cell lines. PFK15 suppressed cell proliferation, halted cell cycle progression and induced cell apoptosis. The invadopodia of HNSCC cells was markedly reduced after PFK15 treatment, thereby impairing cell motility and extracellular matrix degradation ability. The in vivo data from the xenograft mice models proved that PFK15 administration suppressed the tumor growth. And the results from the metastatic mice models showed administration of PFK15 alleviated the lung metastasis of HNSCC and extended the life expectancy of mice. The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.

  14. Parental Attitude Towards Mental Retardation

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    LEOKADIA WIATROWSKA

    2017-10-01

    Full Text Available https://doaj.org/puChild's developmental retardation is an undoubted condition for the absence of educational attainment and its unpleasant mental state. Due to the nature of multidimensional state of that, parental attitudes become relevant, as they affect the acceleration or retardation of development. Positive parental attitudes are the strong weapon for the child and his struggles on the way to an equal start and equal development opportunities. For this reason you should emphasize those factors that build the structures supporting developmental progression.An ecosystem approach to human development emphasizes each factor as relevant component for growth and expansion, without denying its own human activity and his self-determination rightblisher/metadata

  15. Rapid suppression of growth hormone concentration by overeating: potential mediation by hyperinsulinemia.

    Science.gov (United States)

    Cornford, Andrea S; Barkan, Ariel L; Horowitz, Jeffrey F

    2011-03-01

    The very low GH concentration in obesity is commonly attributed to high body fat mass; however, the influence of overeating on GH secretion is not clear. The aim of the study was to examine the effects of 2 wk of overeating on changes in GH secretion. Subjects were admitted to the hospital and stayed within the Michigan Clinical Research Unit throughout the entire 2-wk overeating period. We studied seven healthy, nonobese men (body mass index, 24 ± 1 kg/m(2); age, 25 ± 1 yr). Subjects ate standardized meals containing 70 kcal/kg fat free mass/d (∼4000 kcal/d) for 2 wk. Twenty-four-hour plasma concentrations of GH (every 20 min) and insulin (every 2 h) were measured before overeating (baseline), on d 3, and after 2 wk of overeating. Compared with baseline, average 24-h plasma GH concentration declined nearly 80% by d 3 of overeating (1.30 ± 0.18 vs. 0.36 ± 0.09 ng/ml; P = 0.01). This marked suppression of GH secretion occurred in the absence of an increase in body weight (77.0 ± 2.2 vs. 76.4 ± 2.4 kg). At the same time, average 24-h insulin concentration doubled (16.6 ± 2.1 vs. 31.7 ± 5.8 μU/ml; P = 0.009). After 2 wk, body weight significantly increased (79.0 ± 2.1 kg; P overeating markedly suppressed GH secretion before any measurable weight gain and was accompanied by chronic hyperinsulinemia. Increased body weight and body fat by 2 wk of overeating did not further suppress GH secretion.

  16. Deletion of 4.4 Mb at 2q33.2q33.3 May Cause Growth Deficiency in a Patient with Mental Retardation, Facial Dysmorphic Features and Speech Delay.

    Science.gov (United States)

    Papoulidis, Ioannis; Paspaliaris, Vassilis; Papageorgiou, Elena; Siomou, Elissavet; Dagklis, Themistoklis; Sotiriou, Sotirios; Thomaidis, Loretta; Manolakos, Emmanouil

    2015-01-01

    A patient with a rare interstitial deletion of chromosomal band 2q33.2q33.3 is described. The clinical features resembled the 2q33.1 microdeletion syndrome (Glass syndrome), including mental retardation, facial dysmorphism, high-arched narrow palate, growth deficiency, and speech delay. The chromosomal aberration was characterized by whole genome BAC aCGH. A comparison of the current patient and Glass syndrome features revealed that this case displayed a relatively mild phenotype. Overall, it is suggested that the deleted region of 2q33 causative for Glass syndrome may be larger than initially suggested. © 2015 S. Karger AG, Basel.

  17. Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy.

    Science.gov (United States)

    Feng, Qian; Lin, Sien; Zhang, Kunyu; Dong, Chaoqun; Wu, Tianyi; Huang, Heqin; Yan, Xiaohui; Zhang, Li; Li, Gang; Bian, Liming

    2017-04-15

    Recently, hyaluronic acid (HA) hydrogels have been extensively researched for delivering cells and drugs to repair damaged tissues, particularly articular cartilage. However, the in vivo degradation of HA is fast, thus limiting the clinical translation of HA hydrogels. Furthermore, HA cannot bind proteins with high affinity because of the lack of negatively charged sulfate groups. In this study, we conjugated tunable amount of sulfate groups to HA. The sulfated HA exhibits significantly slower degradation by hyaluronidase compared to the wild type HA. We hypothesize that the sulfation reduces the available HA octasaccharide substrate needed for the effective catalytic action of hyaluronidase. Moreover, the sulfated HA hydrogels significantly improve the protein sequestration, thereby effectively extending the availability of the proteinaceous drugs in the hydrogels. In the following in vitro study, we demonstrate that the HA hydrogel sulfation exerts no negative effect on the viability of encapsulated human mesenchymal stem cells (hMSCs). Furthermore, the sulfated HA hydrogels promote the chondrogenesis and suppresses the hypertrophy of encapsulated hMSCs both in vitro and in vivo. Moreover, intra-articular injections of the sulfated HA hydrogels avert the cartilage abrasion and hypertrophy in the animal osteoarthritic joints. Collectively, our findings demonstrate that the sulfated HA is a promising biomaterial for the delivery of therapeutic agents to aid the regeneration of injured or diseased tissues and organs. In this paper, we conjugated sulfate groups to hyaluronic acid (HA) and demonstrated the slow degradation and growth factor delivery of sulfated HA. Furthermore, the in vitro and in vivo culture of hMSCs laden HA hydrogels proved that the sulfation of HA hydrogels not only promotes the chondrogenesis of hMSCs but also suppresses hypertrophic differentiation of the chondrogenically induced hMSCs. The animal OA model study showed that the injected

  18. Mental Retardation in Perspective.

    Science.gov (United States)

    Horvath, Michael; And Others

    This monograph presents a general introduction to the history, classification, and characteristics of mental retardation. It begins with a discussion of the history of mental retardation from ancient Greece and Rome to the present. The beginnings of special education are traced to the early 19th century in Europe. Major influences in treatment of…

  19. Growth theory after Keynes, part I: the unfortunate suppression of the Harrod-Domar model

    Directory of Open Access Journals (Sweden)

    Hendrik Van den Berg

    2013-11-01

    Full Text Available After Harrod and Domar independently developed a dynamic Keynesian circular flow model to illustrate the instability of a growing economy, mainstream economists quickly reduced their model to a supply side-only growth model, which they subsequently rejected as too simplistic and replaced with Solow’s neoclassical growth model. The rejection process of first diminishing the model and then replaced it with a neoclassical alternative was similar to how the full Keynesian macroeconomic paradigm was diminished into IS-LM analysis and then replaced by a simplistic neoclassical framework that largely ignored the demand side of the economy. Furthermore, subsequent work by mainstream economists has resulted in a logically inconsistent framework for analyzing economic growth; the popular endogenous growth models, which use Schumpeter’s concept of profit-driven creative destruction to explain the technological change that Solow left as exogenous, are not logically compatible with the Solow model.

  20. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells.

    Science.gov (United States)

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells. Our

  1. Suppression of glucan, water dikinase in the endosperm alters wheat grain properties, germination and coleoptile growth.

    Science.gov (United States)

    Bowerman, Andrew F; Newberry, Marcus; Dielen, Anne-Sophie; Whan, Alex; Larroque, Oscar; Pritchard, Jenifer; Gubler, Frank; Howitt, Crispin A; Pogson, Barry J; Morell, Matthew K; Ral, Jean-Philippe

    2016-01-01

    Starch phosphate ester content is known to alter the physicochemical properties of starch, including its susceptibility to degradation. Previous work producing wheat (Triticum aestivum) with down-regulated glucan, water dikinase, the primary gene responsible for addition of phosphate groups to starch, in a grain-specific manner found unexpected phenotypic alteration in grain and growth. Here, we report on further characterization of these lines focussing on mature grain and early growth. We find that coleoptile length has been increased in these transgenic lines independently of grain size increases. No changes in starch degradation rates during germination could be identified, or any major alteration in soluble sugar levels that may explain the coleoptile growth modification. We identify some alteration in hormones in the tissues in question. Mature grain size is examined, as is Hardness Index and starch conformation. We find no evidence that the increased growth of coleoptiles in these lines is connected to starch conformation or degradation or soluble sugar content and suggest these findings provide a novel means of increasing coleoptile growth and early seedling establishment in cereal crop species. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Consumo calórico, estado nutricional materno, y retraso del crecimiento intrauterino Energy intake, maternal nutritional status and intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Eliana Bender Martins

    2003-02-01

    Full Text Available Para conocer la asociación entre el consumo de energía en el embarazo y el retraso del crecimiento intrauterino (RCIU, se llevó a cabo un estudio de caso-cohorte en tres hospitales de maternidad de la ciudad de México, entre enero y agosto de 1995. De un total de 4.000 partos que ocurrieron en este período, nos referimos en este estudio a los resultados de un análisis de 264 casos de RCIU y 892 controles. Se procedió a un análisis de regresión logística no condicionada, en el que también se ajustaron los factores maternos potencialmente proclives a la confusión. Para el total de los casos no se observó un efecto directo del consumo de energía en el RCIU (RM: 0,99; IC 95%: 0,99-1,00. Sin embargo, entre las mujeres que comenzaron el embarazo con un peso de 50 kilos o menos, el consumo de energía en relación a RCIU mostró una razón de momios de 2,31 (RM: 2,31; IC 95%: 1,59-3,36; para las mujeres primigestas de 1,72 (RM: 1,72; IC 95%: 1,18-2,51; en aquellas con antecedente de bajo peso al nacer de 3,54 (RM: 3,54; IC 95%: 1,93-6,46 y para aquellas que presentaron tensión arterial alta en el embarazo de 1,61 (RM: 1,61; IC 95%: 1,00-2,59.To explore the association between low caloric intake during pregnancy and intrauterine growth retardation (IUGR, a case-control study with 264 cases and 892 controls was conducted in three maternity hospitals in Mexico City from January to August 1995. Nutritional information on pregnancy was recorded using a previously validated food frequency questionnaire. After adjusting for other known maternal risk factors in the non-conditional logistic regression analysis, for the total sample, caloric intake did not present a direct effect on IUGR (OR: 0.99; CI 95%: 0.99-1.00. However the odds ratios were as follows for women: with low pre-gestational weight (OR: 2.31; CI 95%: 1.59-3.36, in first gestation (OR: 1.72; CI 95%: 1.18-2.51, with low birth weight infants (OR: 3.54; CI 95%: 1.93-6.46, and

  3. Transforming growth factor-β suppresses metastasis in a subset of human colon carcinoma cells

    International Nuclear Information System (INIS)

    Simms, Neka A K; Rajput, Ashwani; Sharratt, Elizabeth A; Ongchin, Melanie; Teggart, Carol A; Wang, Jing; Brattain, Michael G

    2012-01-01

    TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling. To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. Abrogation of TGFβ signaling through introduction of a dominant negative TGFβ receptor II (TGFβRII) in non-metastatic FETα human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFβ signaling in FETα-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFβ signaling is a metastasis suppressor, we rescued TGFβ signaling in CBS metastatic colon cancer cells that had lost TGFβ receptor expression due to epigenetic repression. Restoration of TGFβ signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFβ signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. The observations presented here indicate a metastasis suppressor role for TGF

  4. Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.

    Directory of Open Access Journals (Sweden)

    Long Cheng

    Full Text Available Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.

  5. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    Science.gov (United States)

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  6. THE RED-TIDE DINOFLAGELLATE, ALEXANDRIUM MONILATUM, SUPPRESSES GROWTH OF MIXED NATURAL PHYTOPLANKTON

    Science.gov (United States)

    Alexandrium monilatum is a large, chain-forming, autotrophic dinoflagellate associated with red-tides and fish kills along the US Gulf of Mexico coast. When cultured inocula of A. monilatum were added to nutrient-amended seawater samples, growth rates and biomass yields of the na...

  7. Weed Suppressing Potential and Isolation of Potent Plant Growth Inhibitors from Castanea crenata Sieb. et Zucc

    Directory of Open Access Journals (Sweden)

    Phung Thi Tuyen

    2018-02-01

    Full Text Available This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc, a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass, Lactuca sativa (lettuce, and Raphanus sativus (radish. Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p-hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves. By column chromatography and spectral data (1H- and 13C-NMR, IR, and LC-MS analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid (1 was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves. This constituent showed potent inhibition on growth of E. crus-galli, a problematic weed in agricultural practice. The inhibition of the compound 1 (IC50 = 2.62 and 0.41 mM was >5 fold greater than that of p-hydroxybenzoic acid (IC50 = 15.33 and 2.11 mM on shoot and root growth of E. crus-galli, respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli. This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential.

  8. Weed Suppressing Potential and Isolation of Potent Plant Growth Inhibitors from Castanea crenata Sieb. et Zucc.

    Science.gov (United States)

    Tuyen, Phung Thi; Xuan, Tran Dang; Tu Anh, Truong Thi; Mai Van, Truong; Ahmad, Ateeque; Elzaawely, Abdelnaser Abdelghany; Khanh, Tran Dang

    2018-02-07

    This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut ( Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass), Lactuca sativa (lettuce), and Raphanus sativus (radish). Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p -hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves). By column chromatography and spectral data (¹H- and 13 C-NMR, IR, and LC-MS) analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid ( 1 ) was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves). This constituent showed potent inhibition on growth of E. crus-galli , a problematic weed in agricultural practice. The inhibition of the compound 1 (IC 50 = 2.62 and 0.41 mM) was >5 fold greater than that of p -hydroxybenzoic acid (IC 50 = 15.33 and 2.11 mM) on shoot and root growth of E. crus-galli , respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli . This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential.

  9. Insulin-like growth factor-1 suppresses the Myostatin signaling pathway during myogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Retamales, A.; Zuloaga, R.; Valenzuela, C.A. [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Gallardo-Escarate, C. [Laboratory of Biotechnology and Aquatic Genomics, Universidad de Concepción, Concepción (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile); Molina, A. [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile); Valdés, J.A., E-mail: jvaldes@unab.cl [Laboratorio de Biotecnología Molecular, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago (Chile); Interdisciplinary Center for Aquaculture Research (INCAR), P.O. Box 160-C, Concepción (Chile)

    2015-08-21

    Myogenic differentiation is a complex and well-coordinated process for generating mature skeletal muscle fibers. This event is autocrine/paracrine regulated by growth factors, principally Myostatin (MSTN) and Insulin-like Growth Factor-1 (IGF-1). Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of skeletal muscle growth in vertebrates that exerts its inhibitory function by activating Smad transcription factors. In contrast, IGF-1 promotes the differentiation of skeletal myoblasts by activating the PI3K/Akt signaling pathway. This study reports on a novel functional crosstalk between the IGF-1 and MSTN signaling pathways, as mediated through interaction between PI3K/Akt and Smad3. Stimulation of skeletal myoblasts with MSTN resulted in a transient increase in the pSmad3:Smad3 ratio and Smad-dependent transcription. Moreover, MSTN inhibited myod gene expression and myoblast fusion in an Activin receptor-like kinase/Smad3-dependent manner. Preincubation of skeletal myoblasts with IGF-1 blocked MSTN-induced Smad3 activation, promoting myod expression and myoblast differentiation. This inhibitory effect of IGF-1 on the MSTN signaling pathway was dependent on IGF-1 receptor, PI3K, and Akt activities. Finally, immunoprecipitation assay analysis determined that IGF-1 pretreatment increased Akt and Smad3 interaction. These results demonstrate that the IGF-1/PI3K/Akt pathway may inhibit MSTN signaling during myoblast differentiation, providing new insight to existing knowledge on the complex crosstalk between both growth factors. - Highlights: • IGF-1 inhibits Myostatin canonical signaling pathway through IGF-1R/PI3K/Akt pathway. • IGF-1 promotes myoblast differentiation through a direct blocking of Myostatin signaling pathway. • IGF-1 induces the interaction of Akt with Smad3 in skeletal myoblast.

  10. Bacteria on housefly eggs, Musca domestica, suppress fungal growth in chicken manure through nutrient depletion or antifungal metabolites

    Science.gov (United States)

    Lam, Kevin; Thu, Kelsie; Tsang, Michelle; Moore, Margo; Gries, Gerhard

    2009-09-01

    Female houseflies, Musca domestica (Diptera: Muscidae), lay their eggs in ephemeral resources such as animal manure. Hatching larvae compete for essential nutrients with fungi that also colonize such resources. Both the well-known antagonistic relationship between bacteria and fungi and the consistent presence of the bacterium Klebsiella oxytoca on housefly eggs led us to hypothesize (1) that K. oxytoca, and possibly other bacteria on housefly eggs, help curtail the growth of fungal resource competitors and (2) that such fungi indeed adversely affect the development of housefly larvae. Bacteria washed from housefly eggs significantly reduced the growth of fungi in chicken manure. Nineteen bacterial strains and ten fungal strains were isolated from housefly eggs or chicken manure, respectively. Co-culturing each of all the possible bacterium-fungus pairs revealed that the bacteria as a group, but no single bacterium, significantly suppressed the growth of all fungal strains tested. The bacteria's adverse effect on fungi is due to resource nutrient depletion and/or the release of antifungal chemicals. Well-established fungi in resources significantly reduced the number of larval offspring that completed development to adult flies.

  11. 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway.

    Science.gov (United States)

    Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

    2015-03-01

    The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway

    Science.gov (United States)

    Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

    2015-01-01

    The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. PMID:25712415

  13. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

    Directory of Open Access Journals (Sweden)

    Zhen-Wei Zou

    2018-06-01

    Full Text Available Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer. Keywords: Melatonin, Thyroid cancer, Radioresistance, p65, Reactive oxygen species

  14. Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

    Science.gov (United States)

    Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

    2012-10-01

    For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.

  15. MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma.

    Science.gov (United States)

    Wu, Manya; Huang, Chaoyuan; Huang, Xinping; Liang, Rong; Feng, Yan; Luo, Xiaoling

    2017-10-01

    In our previous studies, the Illumine Soledad massively parallel signature sequencing of miRNomes in non‑tumor and hepatocellular carcinoma (HCC) tissues revealed that microRNA (miR)-144-3p was significantly downregulated in HCC, but its role in HCC development, especially angiogenesis, remains unclear. In this investigation, we found recovering miR‑144‑3p expression can significantly suppress the growth, migration and induced angiogenic capacity of HCC cells through both in vivo and in vitro experiments. Moreover, clinical correlation analysis showed that low expression of miR‑144‑3p was positively correlated to poor disease-free survival (DFS) of HCC patients. Mechanistically, serum and glucocorticoid kinase 3 (SGK3), the putative targets of miR‑144‑3p, was predicted by Target Scan database and identified to be suppressed by miR‑144‑3p so that inhibiting the activation of mTOR-VEGF downstream signals was activated by the phosphoinositide 3-kinase (PI3K)-independent pathway. Hence, we concluded that miR‑144‑3p, which is frequently downregulated in HCC, can inhibit proliferation, migration and repress angiogenesis by regulating SGK3 activation with PI3K independent signal pathway, and acts as a prognostic factor for HCC patients.

  16. Brief Communication: Copper suppression of vascular endothelial growth factor receptor-2 is involved in the regression of cardiomyocyte hypertrophy.

    Science.gov (United States)

    Wang, Tao; Li, Rui; Lin, Chen; Sun, Miao; Kang, Y James

    2014-08-01

    Previous studies revealed that copper (Cu)-induced regression of cardiomyocyte hypertrophy is associated with enhanced activity in the vascular endothelial growth factor receptor-1 (VEGFR-1) signaling pathway. The mechanism by which Cu enhances the activity of VEGFR-1 pathway remains to be defined. The present study was undertaken to test the hypothesis that Cu enhances the VEGFR-1 signaling pathway via suppression of the VEGFR-2 signaling pathway. Primary cultures of neonatal rat cardiomyocytes were exposed to phenylephrine (PE) at a final concentration of 100 µM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cardiomyocytes were exposed to copper sulfate at a final concentration of 5 µM Cu in cultures for 24 h. Western blot analysis showed that PE increased the protein levels of both VEGFR-1 and VEGFR-2. Cu supplementation significantly reduced the increase in VEGFR-2, but had no effect on the elevation of VEGFR-1. Real-time polymerase chain reaction analysis found no difference in the mRNA levels between the VEGFR-1 and VEGFR-2 under the conditions defined above. This study thus demonstrated that Cu selectively suppressed PE-elevated VEGFR-2 levels likely via post-translational regulation, leading to the VEGFR-1 signaling pathway becoming dominant and thereby regressing cardiomyocyte hypertrophy. © 2014 by the Society for Experimental Biology and Medicine.

  17. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  18. Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

    Science.gov (United States)

    McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

    2016-07-01

    Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Tumour suppression associated with expression of human insulin-like growth factor II.

    OpenAIRE

    Schofield, P. N.; Lee, A.; Hill, D. J.; Cheetham, J. E.; James, D.; Stewart, C.

    1991-01-01

    Recent circumstantial evidence has implicated Insulin-like growth factor II in the genesis of several tumour types, notably developmental tumours (Scott et al., 1985; Schofield & Tate, 1987; Wilkins et al., 1989). This type of tumour, thought to originate during the defective differentiation of organ precursors (Miereau et al., 1987), often expresses greatly elevated levels of mRNA for IGF-II, a known mitogen for these cells and abundantly expressed in their presumed normal counterparts (Scot...

  20. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Dietmar Abraham

    2013-09-01

    Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

  1. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jun-Hai; Zhao, Chun-Liu [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China); Ding, Lan-Bao [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Zhou, Xi, E-mail: modelmap@139.com [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China)

    2015-10-09

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  2. Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells.

    Science.gov (United States)

    Yu, Qingxiang; Wang, Xiaoyu; Wang, Li; Zheng, Jia; Wang, Jiang; Wang, Bangmao

    2016-10-01

    Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated. In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay. Dose response curve analysis was performed in AGS and MKN-45 cells with stable ASNS knockdown to assess sensitivity to cisplatin. Xenograft experiment was performed to examine in vivo synergistic effects of ASNS depletion and cisplatin on tumor growth. Expression level of ASNS was evaluated in human patient samples using quantitative PCR. Kaplan-Meier curve analysis was performed to evaluate association between ASNS expression and patient survival. Transient knockdown of ASNS inhibited cell proliferation and colony formation in AGS and MKN-45 cells. Stable knockdown of ASNS conferred sensitivity to cisplatin in these cells. Depletion of ASNS and cisplatin treatment exerted synergistic effects on tumor growth in AGS xenografts. Moreover, ASNS was found to be up-regulated in human gastric cancer tissues compared with matched normal colon tissues. Low expression of ASNS was significantly associated with better survival in gastric cancer patients. ASNS may contribute to gastric cancer tumorigenesis and may represent a novel therapeutic target for prevention or intervention of gastric cancer.

  3. Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed

    Science.gov (United States)

    Rasher, Douglas B.; Hay, Mark E.

    2014-01-01

    Many seaweeds and terrestrial plants induce chemical defences in response to herbivory, but whether they induce chemical defences against competitors (allelopathy) remains poorly understood. We evaluated whether two tropical seaweeds induce allelopathy in response to competition with a reef-building coral. We also assessed the effects of competition on seaweed growth and seaweed chemical defence against herbivores. Following 8 days of competition with the coral Porites cylindrica, the chemically rich seaweed Galaxaura filamentosa induced increased allelochemicals and became nearly twice as damaging to the coral. However, it also experienced significantly reduced growth and increased palatability to herbivores (because of reduced chemical defences). Under the same conditions, the seaweed Sargassum polycystum did not induce allelopathy and did not experience a change in growth or palatability. This is the first demonstration of induced allelopathy in a seaweed, or of competitors reducing seaweed chemical defences against herbivores. Our results suggest that the chemical ecology of coral–seaweed–herbivore interactions can be complex and nuanced, highlighting the need to incorporate greater ecological complexity into the study of chemical defence. PMID:24403332

  4. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yan, Jun-Hai; Zhao, Chun-Liu; Ding, Lan-Bao; Zhou, Xi

    2015-01-01

    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

  5. Cystatin A suppresses tumor cell growth through inhibiting epithelial to mesenchymal transition in human lung cancer.

    Science.gov (United States)

    Ma, Yunxia; Chen, Yuan; Li, Yong; Grün, Katja; Berndt, Alexander; Zhou, Zhongwei; Petersen, Iver

    2018-03-06

    Cystatin A ( CSTA ), belonging to type 1 cystatin super-family, is expressed primarily in epithelial and lymphoid tissues for protecting cells from proteolysis of cytoplasmic and cytoskeletal proteins by cathepsins B, H and L. CSTA acts as a tumor suppressor in esophageal cancer, however, its role in lung cancer has not yet been elucidated. Here we found that CSTA was down-regulated in all lung cancer cell lines compared to normal lung epithelial cells. CSTA was restored in most lung cancer cell lines after treatment with demethylation agent 5-aza-2-deoxycytidine and deacetylation agent Trichostatin. Bisulfite sequencing revealed that CSTA was partially methylated in the promoter and exon 1. In primary lung tumors, squamous cell carcinoma (SCC) significantly expressed more CSTA compared to adenocarcinoma (pgrade (ptransition (MET) and prevented the TGF-β1-induced epithelial to mesenchymal transition (EMT) through inhibiting the ERK/MAPK pathway. In conclusion, our date indicate 1) epigenetic regulation is associated with CSTA gene silencing; 2) CSTA exerts tumor suppressive function through inhibiting MAPK and AKT pathways; 3) Overexpression of CSTA leads to MET and prevents TGF-β1-induced EMT by modulating the MAPK pathway; 4) CSTA may be a potential biomarker for lung SCC and tumor differentiation.

  6. Integrating transcriptomics and proteomics to show that tanshinone IIA suppresses cell growth by blocking glucose metabolism in gastric cancer cells.

    Science.gov (United States)

    Lin, Li-Ling; Hsia, Chieh-Ren; Hsu, Chia-Lang; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-02-05

    Tanshinone IIA (TIIA) is a diterpene quinone extracted from the plant Danshen (Salvia miltiorrhiza) used in traditional Chinese herbal medicine. It has been reported to have anti-tumor potential against several kinds of cancer, including gastric cancer. In most solid tumors, a metabolic switch to glucose is a hallmark of cancer cells, which do this to provide nutrients for cell proliferation. However, the mechanism associated with glucose metabolism by which TIIA acts on gastric cancer cells remains to be elucidated. We found that TIIA treatment is able to significantly inhibit cell growth and the proliferation of gastric cancer in a dose-dependent manner. Using next-generation sequencing-based RNA-seq transcriptomics and quantitative proteomics-isobaric tags for relative and absolute quantification (iTRAQ), we characterized the mechanism of TIIA regulation in gastric cancer cell line AGS. In total, 16,603 unique transcripts and 102 proteins were identified. After enrichment analysis, we found that TIIA regulated genes are involved in carbohydrate metabolism, the cell cycle, apoptosis, DNA damage and cytoskeleton reorganization. Our proteomics data revealed the downregulation of intracellular ATP levels, glucose-6-phosphate isomerase and L-lactate dehydrogenase B chains by TIIA, which might work with disorders of glucose metabolism and extracellular lactate levels to suppress cell proliferation. The up-regulation of p53 and down-regulation of AKT was shown in TIIA- treated cells, which indicates the transformation of oncogenes. Severe DNA damage, cell cycle arrest at the G2/M transition and apoptosis with cytoskeleton reorganization were detected in TIIA-treated gastric cancer cells. Combining transcriptomics and proteomics results, we propose that TIIA treatment could lead cell stresses, including nutrient deficiency and DNA damage, by inhibiting the glucose metabolism of cancer cells. This study provides an insight into how the TIIA regulatory metabolism in

  7. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    2012-04-01

    Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

  8. Triplets with growth failure, microcephaly, mental retardation, nail hypoplasia and corpus callosum agenesis: is it a variant of Coffin-Siris or a new syndrome?

    Science.gov (United States)

    Kirel, B; Kural, N; Yakut, A; Adapinar, B

    2000-01-01

    We report eight-year-old triplet girls whose clinical features included microcephaly, severe mental retardation, hypoplasia of distal phalanges of both fifth and second fingers and nail hypoplasia on second fingers, dysmorphic facial features, and partial corpus callosum agenesis. During infancy, a Pavlik harness was used for congenital hip dislocation, and they had difficulty in feeding. One had been operated for patent ductus arteriosus. To our knowledge, this rare combination has not been previously reported in triplets whose clinical features closely resemble those of Coffin-Siris syndrome. The other diagnostic possibilities are also reviewed.

  9. Fire retardant formulations

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to compositions where a substrate is liable to catch fire such as bituminous products, paints, carpets or the like. The invention relates to a composition comprising 40-95 weight % of a substrate to be rendered fire resistant such as bituminous material or paint......, carpets which substrate is mixed with 5-60 weight % of a fire retardant component. The invention relates to a fire retardant component comprising or being constituted of attapulgite, and a salt being a source of a blowing or expanding agent, where the attapulgite and the salt are electrostatically...... connected by mixing and subjecting the mixture of the two components to agitation. Also, the invention relates to compositions comprising 40-95 weight % of a substrate to be rendered fire resistant mixed with 5-60 weight % of a fire retardant according to claim 1 or 2, which fire retardant component...

  10. Suppression of lymphangiogenesis by soluble vascular endothelial growth factor receptor-2 in a mouse lung cancer model.

    Science.gov (United States)

    Maehana, Shotaro; Nakamura, Masaki; Ogawa, Fumihiro; Imai, Rimika; Murakami, Rei; Kojima, Fumiaki; Majima, Masataka; Kitasato, Hidero

    2016-12-01

    The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2 into lung cancer cells and evaluated the influence on tumor progression and on genes regulating lymphatic formation and metastasis in vivo. A retroviral vector was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC), which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture supernatant by these cells were detected by western blotting using specific antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC-sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14days after injection, immunohistochemistry was performed using an antibody directed against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were directly inoculated into the left lung in C57BL/6 mice and the number of micro-metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant. There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2 into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2 group compared with the control group. Furthermore, there were fewer micro-metastases in the

  11. Radiation and mental retardation

    International Nuclear Information System (INIS)

    Pochin, E.E.

    1988-01-01

    A brief article discusses mental retardation in children who had been exposed to ionizing radiation in utero. The time of greatest sensitivity is between the 8th and 15th week after conception and the time of lesser sensitivity between the 16th and 25th weeks. An examination of the thresholds for exposure indicate that severe mental retardation would not result from any present environmental exposures of the public. (U.K.)

  12. Akt- or MEK-mediated mTOR inhibition suppresses Nf1 optic glioma growth.

    Science.gov (United States)

    Kaul, Aparna; Toonen, Joseph A; Cimino, Patrick J; Gianino, Scott M; Gutmann, David H

    2015-06-01

    Children with neurofibromatosis type 1 (NF1) develop optic pathway gliomas, which result from impaired NF1 protein regulation of Ras activity. One obstacle to the implementation of biologically targeted therapies is an incomplete understanding of the individual contributions of the downstream Ras effectors (mitogen-activated protein kinase kinase [MEK], Akt) to optic glioma maintenance. This study was designed to address the importance of MEK and Akt signaling to Nf1 optic glioma growth. Primary neonatal mouse astrocyte cultures were employed to determine the consequence of phosphatidylinositol-3 kinase (PI3K)/Akt and MEK inhibition on Nf1-deficient astrocyte growth. Nf1 optic glioma-bearing mice were used to assess the effect of Akt and MEK inhibition on tumor volume, proliferation, and retinal ganglion cell dysfunction. Both MEK and Akt were hyperactivated in Nf1-deficient astrocytes in vitro and in Nf1 murine optic gliomas in vivo. Pharmacologic PI3K or Akt inhibition reduced Nf1-deficient astrocyte proliferation to wild-type levels, while PI3K inhibition decreased Nf1 optic glioma volume and proliferation. Akt inhibition of Nf1-deficient astrocyte and optic glioma growth reflected Akt-dependent activation of mammalian target of rapamycin (mTOR). Sustained MEK pharmacologic blockade also attenuated Nf1-deficient astrocytes as well as Nf1 optic glioma volume and proliferation. Importantly, these MEK inhibitory effects resulted from p90RSK-mediated, Akt-independent mTOR activation. Finally, both PI3K and MEK inhibition reduced optic glioma-associated retinal ganglion cell loss and nerve fiber layer thinning. These findings establish that the convergence of 2 distinct Ras effector pathways on mTOR signaling maintains Nf1 mouse optic glioma growth, supporting the evaluation of pharmacologic inhibitors that target mTOR function in future human NF1-optic pathway glioma clinical trials. © The Author(s) 2014. Published by Oxford University Press on behalf of the

  13. Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes.

    Directory of Open Access Journals (Sweden)

    Naomi Ohta

    Full Text Available Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP and follistatin (FST, that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.

  14. Wwox suppresses breast cancer cell growth through modulation of the hedgehog–GLI1 signaling pathway

    International Nuclear Information System (INIS)

    Xiong, Anwen; Wei, Li; Ying, Mingzhen; Wu, Hongmei; Hua, Jin; Wang, Yajie

    2014-01-01

    Highlights: • We investigated Gli1 as a novel partner of Wwox. • We observed a physical association between Wwox and the Gli1. • Wwox–Gli1 interaction affects Gli1 intracellular localization. • Gli1 Blocks Wwox-induced growth inhibition and apoptosis in T47D cells. - Abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog–GLI1 signaling pathway in tumorigenesis

  15. Wwox suppresses breast cancer cell growth through modulation of the hedgehog–GLI1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Anwen [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wei, Li [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Department of Oncology, NO. 401 hospital of PLA, Qingdao, Shandong (China); Ying, Mingzhen; Wu, Hongmei; Hua, Jin [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wang, Yajie, E-mail: yajiewang@live.com [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-01-24

    Highlights: • We investigated Gli1 as a novel partner of Wwox. • We observed a physical association between Wwox and the Gli1. • Wwox–Gli1 interaction affects Gli1 intracellular localization. • Gli1 Blocks Wwox-induced growth inhibition and apoptosis in T47D cells. - Abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog–GLI1 signaling pathway in tumorigenesis.

  16. Lemur Tyrosine Kinase-3 Suppresses Growth of Prostate Cancer Via the AKT and MAPK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Pengcheng Sun

    2017-08-01

    Full Text Available Background/Aims: Lemur tyrosine kinase (LMTK-3 is a member of the receptor tyrosine kinase (RTK family. Abnormal expression of LMTK-3 exists in various types of cancers, especially in endocrine-resistant breast cancers; however, the precise level of expression and the biological function in prostate cancer are poorly understood. Methods: In the present study, we determined the expression of LMTK-3 in prostate cancer using immunohistochemistry and Western blotting. We infected PC3 and LNCaP cells with lentivirus-LMTK-3 and observed the biologic characteristics of the PC3 and LNCaP cells in vitro with TUNEL, and migration and invasion assays, respectively. We also established a transplant tumor model of human prostate cancer with infected cells in 15 BALB/c-nu/nu nude mice. Results: LMTK-3 was expressed in prostate epithelial cells. There was a significant decline in the level of LMTK-3 expression in prostate cancers compared to normal tissues. LMTK-3 inhibited PC3 and LNCaP cell growth, migration, and invasion, and induced cell apoptosis in vitro. We also observed that LMTK-3 induced PC3 cell apoptosis in vivo. Further study showed that LMTK-3 inhibited phosphorylation of AKT and ERK, and promoted phosphorylation and activation of p38 kinase and Jun kinase (JNK. Conclusion: Recombinant lentivirus with enhanced expression of LMTK-3 inhibited prostate cancer cell growth and induced apoptosis in vitro and in vivo. AKT and MAPK signaling pathways may contribute to the process.

  17. Crack retardation by load reduction during fatigue crack propagation

    International Nuclear Information System (INIS)

    Kim, Hyun Soo; Nam, Ki Woo; Ahn, Seok Hwan; Do, Jae Yoon

    2003-01-01

    Fracture life and crack retardation behavior were examined experimentally using CT specimens of aluminum alloy 5083. Crack retardation life and fracture life were a wide difference between 0.8 and 0.6 in proportion to ratio of load reduction. The wheeler model retardation parameter was used successfully to predict crack growth behavior. By using a crack propagation rule, prediction of fracture life can be evaluated quantitatively. A statistical approach based on Weibull distribution was applied to the test data to evaluate the dispersion in the retardation life and fracture life by the change of load reduction

  18. FOXO/TXNIP pathway is involved in the suppression of hepatocellular carcinoma growth by glutamate antagonist MK-801

    International Nuclear Information System (INIS)

    Yamaguchi, Fuminori; Hirata, Yuko; Akram, Hossain; Kamitori, Kazuyo; Dong, Youyi; Sui, Li; Tokuda, Masaaki

    2013-01-01

    Accumulating evidence has suggested the importance of glutamate signaling in cancer growth, yet the signaling pathway has not been fully elucidated. N-methyl-D-aspartic acid (NMDA) receptor activates intracellular signaling pathways such as the extracellular-signal-regulated kinase (ERK) and forkhead box, class O (FOXO). Suppression of lung carcinoma growth by NMDA receptor antagonists via the ERK pathway has been reported. However, series of evidences suggested the importance of FOXO pathways for the regulation of normal and cancer cell growth. In the liver, FOXO1 play important roles for the cell proliferation such as hepatic stellate cells as well as liver metabolism. Our aim was to investigate the involvement of the FOXO pathway and the target genes in the growth inhibitory effects of NMDA receptor antagonist MK-801 in human hepatocellular carcinoma. Expression of NMDAR1 in cancer cell lines from different tissues was examined by Western blot. NMDA receptor subunits in HepG2, HuH-7, and HLF were examined by reverse transcriptase polymerase chain reaction (RT-PCR), and growth inhibition by MK-801 and NBQX was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of MK-801 on the cell cycle were examined by flow cytometry and Western blot analysis. Expression of thioredoxin-interacting protein (TXNIP) and p27 was determined by real-time PCR and Western blotting. Activation of the FOXO pathway and TXNIP induction were examined by Western blotting, fluorescence microscopy, Chromatin immunoprecipitation (ChIP) assay, and reporter gene assay. The effects of TXNIP on growth inhibition were examined using the gene silencing technique. NMDA receptor subunits were expressed in all cell lines examined, and MK-801, but not NBQX, inhibited cell growth of hepatocellular carcinomas. Cell cycle analysis showed that MK-801 induced G1 cell cycle arrest by down-regulating cyclin D1 and up-regulating p27. MK-801 dephosphorylated

  19. miR-216b promotes cell growth and enhances chemosensitivity of colorectal cancer by suppressing PDZ-binding kinase.

    Science.gov (United States)

    Zou, Jun; Kuang, Weihua; Hu, Jilong; Rao, Huamin

    2017-06-24

    PDZ-binding kinase (PBK/TOPK) acts as oncogene in various cancers and correlates with drug response. However, few studies have examined the expression and roles of PBK in colonrectal cancer (CRC). In this study, we found a significant increase in the expression of PBK in CRC tissues and cell lines. While overexpression of PBK promoted cell growth and decreased the toxicity effect of oxaliplation (OXA), targeting PBK with short hairpin RNA (shRNA) or novel PBK inhibitor HI-TOPK-032 effectively suppressed tumor growth and potentiated chemosensitivity in vitro and in vivo. Furthermore, there was a significant inverse correlation between the expressions of miR-216b and PBK. Further found that miR-216b could down-regulate PBK levels by binding to the 3' untranslated region (3'UTR) of PBK. Notably, while miR-216b decreased cell proliferation and enhanced sensitivity of CRC cells to oxaliplation, re-expression of PBK dramatically reversed these events. Collectively, our data indicated that miR-216b may function as a tumor suppressor though regulating PBK expression, which provided promising targets and possible therapeutic strategies for CRC treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

    Science.gov (United States)

    Li, Hui; Zhou, Fusheng; Du, Wenhui; Dou, Jinfa; Xu, Yu; Gao, Wanwan; Chen, Gang; Zuo, Xianbo; Sun, Liangdan; Zhang, Xuejun; Yang, Sen

    2016-05-01

    Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  1. Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model.

    Science.gov (United States)

    Yang, Gui; Geng, Xiao-Rui; Song, Jiang-Ping; Wu, Yingying; Yan, Hao; Zhan, Zhengke; Yang, Litao; He, Weiyi; Liu, Zhi-Qiang; Qiu, Shuqi; Liu, Zhigang; Yang, Ping-Chang

    2014-06-01

    The functions of regulatory T (Treg) cells are important in immunity, and the regulatory mechanisms of Treg cell activities are not fully understood yet. We sought to investigate the role of insulin-like growth factor (IGF) 2 in the upregulation of Treg cell function. The expression of insulin-like growth factor 2 receptor (IGF2R) on T cells was assessed by using flow cytometry. Treg cell functions were evaluated by assessing the suppressor effect on proliferation of other effector T (Teff) cells. The effect of IGF2 on regulating Treg cell functions were evaluated with a cell-culture model and a food allergy mouse model. Expression of IGF2R was observed in more than 90% of murine and human Treg cells but in less than 10% of effector CD4(+) T cells. Activation of IGF2R and T-cell receptor induced marked Treg cell proliferation and release of TGF-β from Treg cells, which enhanced Treg cell immune suppressor effects on other Teff cell activities and allergic inflammation in the intestine. Activation of IGF2R enhances Treg cell functions in suppressing other Teff cell activities and inhibiting allergic inflammation in the intestine. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Anti-hyphal formation property of allicin in suppression of Aspergillus fumigatus growth

    Directory of Open Access Journals (Sweden)

    Sajali, N.

    2013-01-01

    Full Text Available Aims: The aim of this study was to examine whether allicin, a compound derived from fresh garlic, leads to growth inhibition and changes in the ultrastructure of the cell surface on medically important filamentous fungi, particularly Aspergillus fumigatus.Methodology and results: The minimum inhibitory concentration (MIC of allicin in A. fumigatus ATCC 36607 was determined by broth microdilution method according to the CLSI M38-A2 documents whereby the minimal fungicidal concentration (MFC was determined by plating suspensions from visibly clear wells onto Sabouraud dextrose agar (SDA. Morphological changes on cell surface were observed through scanning electron microscopy (SEM after 48 h incubation with allicin. In addition, time kill assay was conducted by incubating A. fumigatus at selected time points within 24 h period. Our finding indicated that the MIC and MFC for allicin were both 3.2 µg/mL. Quantitative data for optical density obtained through microplate reader indicated that p<0.05 at MIC value in comparison with untreated control. Observation of allicin-treated cells through SEM demonstrated complete abrogation of hyphae formation at 3.2 µg/mL and reduced mycelial growth at 1.6 µg/mL of allicin. This finding revealed anti-hyphal activity of allicin at 3.2 µg/mL. When A. fumigatus was incubated with 3.2 µg/mL allicin in the time course assay, the inhibitory effect of allicin was evident after 12 h incubation. Conclusion, significance and impact of study: Our finding strongly implied that allicin exerts its antifungal activity against A. fumigatus via inhibiting the fungal cell proliferation as well as hindering transformation of the conidia into hyphae. Thus, this study depicted potential antifungal property of allicin to be used as alternative therapy to alleviate invasive fungal infection caused by A. fumigatus.

  3. miR-29a suppresses MCF-7 cell growth by downregulating tumor necrosis factor receptor 1.

    Science.gov (United States)

    Zhao, Yiling; Yang, Fenghua; Li, Wenyuan; Xu, Chunyan; Li, Li; Chen, Lifei; Liu, Yancui; Sun, Ping

    2017-02-01

    Tumor necrosis factor receptor 1 is the main receptor mediating many tumor necrosis factor-alpha-induced cellular events. Some studies have shown that tumor necrosis factor receptor 1 promotes tumorigenesis by activating nuclear factor-kappa B signaling pathway, while other studies have confirmed that tumor necrosis factor receptor 1 plays an inhibitory role in tumors growth by inducing apoptosis in breast cancer. Therefore, the function of tumor necrosis factor receptor 1 in breast cancer requires clarification. In this study, we first found that tumor necrosis factor receptor 1 was significantly increased in human breast cancer tissues and cell lines, and knockdown of tumor necrosis factor receptor 1 by small interfering RNA inhibited cell proliferation by arresting the cell cycle and inducing apoptosis. In addition, miR-29a was predicted as a regulator of tumor necrosis factor receptor 1 by TargetScan and was shown to be inversely correlated with tumor necrosis factor receptor 1 expression in human breast cancer tissues and cell lines. Luciferase reporter assay further confirmed that miR-29a negatively regulated tumor necrosis factor receptor 1 expression by binding to the 3' untranslated region. In our functional study, miR-29a overexpression remarkably suppressed cell proliferation and colony formation, arrested the cell cycle, and induced apoptosis in MCF-7 cell. Furthermore, in combination with tumor necrosis factor receptor 1 transfection, miR-29a significantly reversed the oncogenic role caused by tumor necrosis factor receptor 1 in MCF-7 cell. In addition, we demonstrated that miR-29a suppressed MCF-7 cell growth by inactivating the nuclear factor-kappa B signaling pathway and by decreasing cyclinD1 and Bcl-2/Bax protein levels. Taken together, our results suggest that miR-29a is an important regulator of tumor necrosis factor receptor 1 expression in breast cancer and functions as a tumor suppressor by targeting tumor necrosis factor receptor 1 to

  4. Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Hage-Sleiman, Rouba; Herveau, Stéphanie; Matera, Eva-Laure; Laurier, Jean-Fabien; Dumontet, Charles

    2010-01-01

    Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both in vitro and in xenografts. These

  5. EFEMP1 Suppresses Growth and Invasion of Lung Cancer Cells 
by Downregulating Matrix Metalloproteinase-7 Expression

    Directory of Open Access Journals (Sweden)

    Yuanyuan LANG

    2015-02-01

    Full Text Available Background and objective EFEMP1, a member of fibulin family proteins, is a very important extracellular matrix protein which is involved in cell metabolism and its role in tumor occurrence and progression is still poorly understood. The aim of this study is to investigate the functional effect and mechanism of EFEMP1 in lung cancer cell growth and invasion. Methods EFEMP1 expression in lung cancer cells was determined by Western blot. The promoter methylation status of EFEMP1 was detected by methylation-specific PCR (MSP. After transfection of control or EFEMP1 vector in lung cancer cells, the ability of colony formation and invasion was detected by colony formation experiment and matrigel invasion method. Western blot and real-time PCR were used to detect matrix metalloproteinase-7 (MMP-7 expression. Luciferase assay was used to detect expression of MMP-7 reporter construct transfected with or without EFEMP1 in lung cancer cells. Results Western blot result showed EFEMP1 expression was downregulated in lung cancer cells. The promoter region of EFEMP1 was methylated in A549 and H1299 and after treatment with 5-aza-2’-deoxycytidine, the EFEMP1 expression was upregulated. The growth and invasion of A549 and H1299 were all significantly suppressed by transfecting with EFEMP1 and the MMP-7 expression was dowanregulated by EFEMP1 as well. Expression activity of MMP-7 reporter construct was decreased by cotransfecting with EFEMP1. Conclusion Collectively, these results suggest that EFEMP1 functions as a suppressor of lung cancer growth and invasion. Epigenetic silencing of EFEMP1 promotes lung cancer invasion and metastasis by activating MMP-7 expression.

  6. microRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation.

    Science.gov (United States)

    Jin, Xiu-Li; Sun, Qin-Sheng; Liu, Feng; Yang, Hong-Wei; Liu, Min; Liu, Hong-Xia; Xu, Wei; Jiang, Yu-Yang

    2013-07-01

    Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network. Copyright © 2013 Wiley Periodicals, Inc.

  7. A morel improved growth and suppressed Fusarium infection in sweet corn.

    Science.gov (United States)

    Yu, Dan; Bu, Fangfang; Hou, Jiaojiao; Kang, Yongxiang; Yu, Zhongdong

    2016-12-01

    A post-fire morel collected from Populus simonii stands in Mt. Qingling was identified as Morchella crassipes Mes-20 by using nuclear ribosomal DNA internal transcribed spacer phylogeny. It was inoculated into sweet corn to observe colonized roots in purified culture and in greenhouse experiments. The elongation and maturation zones of sweet corn were remarkably colonized at the cortex intercellular and intracellular cells, vessel cells, and around the Casparian strip, forming ectendomycorrhiza-like structures. Colonization was also observed in the zone of cell division proximal to the root cap. Greenhouse assays with sweet corn showed that this morel stimulated the development of the root system and significantly increased the dry root biomass. M. crassipes also significantly reduced the incidence of Fusarium verticillioides in the kernels of mature ears when inoculated into young ears before Fusarium inoculation and prevented Fusarium infection in corn ears compared with that of the control in the greenhouse. When grown under axenic conditions, M. crassipes produced the phytohormones abscisic acid, indole-3-acetic acid, and salicylic acid. The benefits to plants elicited by M. crassipes may result from these phytohormones which may improve the drought resistance, biomass growth and resistance to Fusarium.

  8. Andrographolide Suppress Tumor Growth by Inhibiting TLR4/NF-κB Signaling Activation in Insulinoma

    Science.gov (United States)

    Zhang, Qian-Qian; Ding, Yi; Lei, Yan; Qi, Cui-Ling; He, Xiao-Dong; Lan, Tian; Li, Jiang-Chao; Gong, Ping; Yang, Xuesong; Geng, Jian-Guo; Wang, Li-Jing

    2014-01-01

    Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma. PMID:24719558

  9. Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer.

    Science.gov (United States)

    Yi, Fuming; Amarasinghe, Baru; Dang, Thao P

    2013-01-01

    Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch's response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.

  10. Andrographolide suppress tumor growth by inhibiting TLR4/NF-κB signaling activation in insulinoma.

    Science.gov (United States)

    Zhang, Qian-Qian; Ding, Yi; Lei, Yan; Qi, Cui-Ling; He, Xiao-Dong; Lan, Tian; Li, Jiang-Chao; Gong, Ping; Yang, Xuesong; Geng, Jian-Guo; Wang, Li-Jing

    2014-01-01

    Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma.

  11. Suppression of vascular endothelial growth factor expression by cannabinoids in a canine osteosarcoma cell line

    Directory of Open Access Journals (Sweden)

    Figueiredo AS

    2013-07-01

    Full Text Available Andreza S Figueiredo,1 Hiram J García-Crescioni,1 Sandra C Bulla,1 Matthew K Ross,2 Chelsea McIntosh,1 Kari Lunsford,3 Camilo Bulla11Department of Pathobiology and Population Medicine, 2Department of Basic Sciences, 3Department of Clinical Sciences and Animal Health Center, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USAAbstract: Vascular endothelial growth factor (VEGF is a key regulator in both physiologic and pathologic angiogenesis, and cannabinoids decrease VEGF release in human and murine cancer cells. The aim of this study was to assess the in vitro effects of a synthetic cannabinoid, WIN-55,212-2, on the expression of the proangiogenic factor VEGF-A in the canine osteosarcoma cell line 8. After analysis of gene expression by quantitative real-time polymerase chain reaction, the compound decreased VEGF-A expression by 35% ± 10% (P < 0.0001 as compared with the control. This synthetic cannabinoid shows promise as a potential inhibitor of angiogenesis, and further studies are warranted to investigate its in vivo effects and to explore the potential of this and related compounds as adjuvant cancer therapy in the dog.Keywords: dog, cancer, angiogenesis, cannabinoids

  12. Growth suppression of MCF-7 cancer cell-derived xenografts in nude mice by caveolin-1

    International Nuclear Information System (INIS)

    Wu Ping; Wang Xiaohui; Li Fei; Qi Baoju; Zhu Hua; Liu Shuang; Cui Yeqing; Chen Jianwen

    2008-01-01

    Caveolin-1 is an essential structural constituent of caveolae membrane domains that has been implicated in mitogenic signaling and oncogenesis. However, the exact functional role of caveolin-1 still remains controversial. In this report, utilizing MCF-7 human breast adenocarcinoma cells stably transfected with caveolin-1 (MCF-7/cav-1 cells), we demonstrate that caveolin-1 expression dramatically inhibits invasion and migration of these cells. Importantly, in vivo experiments employing xenograft tumor models demonstrated that expression of caveolin-1 results in significant growth inhibition of breast tumors. Moreover, a dramatic delay in tumor progression was observed in MCF-7/cav-1 cells as compared with MCF-7 cells. Histological analysis of tumor sections demonstrated a marked decrease in the percentage of proliferating tumor cells (Ki-67 assay) along with an increase in apoptotic tumor cells (TUNEL assay) in MCF-7/cav-1-treated animals. Our current findings provide for the first time in vivo evidence that caveolin-1 can indeed function as a tumor suppressor in human breast adenocarcinoma derived from MCF-7 cells rather than as a tumor promoter

  13. Ruxolitinib combined with vorinostat suppresses tumor growth and alters metabolic phenotype in hematological diseases.

    Science.gov (United States)

    Civallero, Monica; Cosenza, Maria; Pozzi, Samantha; Sacchi, Stefano

    2017-11-28

    JAK-2 dysregulation plays an important role as an oncogenic driver, and is thus a promising therapeutic target in hematological malignancies. Ruxolitinib is a pyrrolo[2.3-d]pyrimidine derivative with inhibitory activity against JAK1 and JAK2, moderate activity against TYK2, and minor activity against JAK3. Vorinostat is an HDAC inhibitor that reduces JAK-2 expression, thus affecting JAK-2 mRNA expression and increasing JAK-2 proteasomal deterioration. Here we hypothesized that the combination of ruxolitinib and vorinostat could have synergistic effects against hematological disease. We tested combinations of low doses of ruxolitinib and vorinostat in 12 cell lines, and observed highly synergistic cytotoxic action in six cell lines, which was maintained for up to 120 h in the presence of stromal cells. The sensitivity of the six cell lines may be explained by the broad effects of the drug combination, which can affect various targets. Treatment with the combination of ruxolitinib and vorinostat appeared to induce a possible reversal of the Warburg effect, with associated ROS production, apoptotic events, and growth inhibition. Decreased glucose metabolism may have markedly sensitized the six more susceptible cell lines to combined treatment. Therapeutic inhibition of the JAK/STAT pathway seems to offer substantial anti-tumor benefit, and combined therapy with ruxolitinib and vorinostat may represent a promising novel therapeutic modality for hematological neoplasms.

  14. Iced photochemical reduction to synthesize atomically dispersed metals by suppressing nanocrystal growth.

    Science.gov (United States)

    Wei, Hehe; Huang, Kai; Wang, Da; Zhang, Ruoyu; Ge, Binghui; Ma, Jingyuan; Wen, Bo; Zhang, Shuai; Li, Qunyang; Lei, Ming; Zhang, Cheng; Irawan, Joshua; Liu, Li-Min; Wu, Hui

    2017-11-14

    Photochemical solution-phase reactions have been widely applied for the syntheses of nanocrystals. In particular, tuning of the nucleation and growth of solids has been a major area of focus. Here we demonstrate a facile approach to generate atomically dispersed platinum via photochemical reduction of frozen chloroplatinic acid solution using ultraviolet light. Using this iced-photochemical reduction, the aggregation of atoms is prevented, and single atoms are successfully stabilized. The platinum atoms are deposited on various substrates, including mesoporous carbon, graphene, carbon nanotubes, titanium dioxide nanoparticles, and zinc oxide nanowires. The atomically dispersed platinum on mesoporous carbon exhibits efficient catalytic activity for the electrochemical hydrogen evolution reaction, with an overpotential of only 65 mV at a current density of 100 mA cm -2 and long-time durability (>10 h), superior to state-of-the-art platinum/carbon. This iced-photochemical reduction may be extended to other single atoms, for example gold and silver, as demonstrated in this study.

  15. Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

    International Nuclear Information System (INIS)

    Cho, O Yeon; Hwang, Hye Sook; Lee, Bok Soon; Oh, Young Taek; Kim, Chul Ho; Chun, Mi Son

    2015-01-01

    Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy

  16. Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Cho, O Yeon; Hwang, Hye Sook; Lee, Bok Soon; Oh, Young Taek; Kim, Chul Ho; Chun, Mi Son [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2015-12-15

    Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

  17. SOD mimetics: A Novel Class of Androgen Receptor Inhibitors that Suppresses Castration-Resistant Growth of Prostate Cancer

    Science.gov (United States)

    Thomas, Rusha; Sharifi, Nima

    2011-01-01

    Advanced prostate cancer (PCa) is the second-leading cause of cancer-related deaths among American men. The androgen receptor (AR) is vital for PCa progression, even in the face of castrate levels of serum testosterone following androgen ablation therapy, a mainstay therapy for advanced PCa. Downregulation of superoxide dismutase 2 (SOD2), a major intracellular antioxidant enzyme, occurs progressively during PCa progression to advanced states, and is known to promote AR activity in PCa. Therefore, this study investigated the effects of SOD mimetics on AR expression and function in AR-dependent LNCaP, CWR22Rv1, and LAPC-4AD PCa cells. Treatment with Tempol, a SOD mimetic, not only lowered cellular superoxide levels, but also concomitantly attenuated AR transcriptional activity and AR target gene expression in a dose- and time-dependent manner, in the presence and absence of dihydrotestosterone, the major endogenous AR agonist. Tempol's inhibition of AR was mediated, in large part, by its ability to decrease AR protein via increased degradation, in the absence of any inhibitory effects on other nuclear receptors. Tempol's inhibitory effects on AR were also reproducible with other SOD mimetics, MnTBAP and MnTMPyP. Importantly, Tempol's effects on AR function were accompanied by significant in vitro and in vivo reduction in castration-resistant PCa survival and growth. Collectively, this study has demonstrated for the first time that SOD mimetics, by virtue of their ability to suppress AR function, may be beneficial in treating the currently incurable castration-resistant PCa in which SOD2 expression is highly suppressed. PMID:22172488

  18. A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

    Directory of Open Access Journals (Sweden)

    Noritoshi Fukushima

    Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

  19. Sirt2 suppresses glioma cell growth through targeting NF-κB–miR-21 axis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ya’nan; Dai, Dongwei [Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Lu, Qiong; Fei, Mingyu [Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai (China); Li, Mengmeng [Department of Rheumatology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Wu, Xi, E-mail: xiwuchh@sina.com [Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2013-11-22

    Highlights: •Sirt2 expression is down-regulated in human glioma tissues and cell lines. •Sirt2 regresses glioma cell growth and colony formation via inducing apoptosis. •miR-21 is essential for the functions of Sirt2 in glioma cells. •Sirt2 deacetylates p65 to decrease miR-21 expression. -- Abstract: Sirtuins are NAD{sup +}-dependent deacetylases that regulate numerous cellular processes including aging, DNA repair, cell cycle, metabolism, and survival under stress conditions. The roles of sirtuin family members are widely studied in carcinogenesis. However, their roles in glioma remain unclear. Here we report that Sir2 was under expressed in human glioma tissues and cell lines. We found that Sirt2 overexpression decreased cell proliferation and colony formation capacity. In addition, Sirt2 overexpression induced cellular apoptosis via up-regulating cleaved caspase 3 and Bax, and down-regulating anti-apoptotic protein Bcl-2. Sirt2 knockdown obtained opposing results. We showed that Sirt2 overexpression inhibited miR-21 expression, and Sirt2 was not sufficient to reduce cell proliferation and colony formation as well as to induce apoptosis when miR-21 was knocked down in glioma cells. Mechanically, we demonstrated that Sirt2 deacetylated p65 at K310 and blocked p65 binding to the promoter region of miR-21, thus regressing the transcription of miR-21. In summary, Sirt2 is critical in human glioma via NF-κB–miR-21 pathway and Sirt2 activator may serve as candidate drug for glioma therapy.

  20. Flood Plain Aggradation Rates Based on Tree-Ring Growth-Suppression Dates

    Science.gov (United States)

    Friedman, J. M.

    2003-12-01

    When woody riparian plants are partially buried subsequent tree rings of the buried stems resemble those of roots. Annual rings in a buried stem are narrower and have larger vessels then those in unburied sections of the same stem. We have used this phenomenon to date flood plain sediments exposed in trenches, along two ephemeral streams in New Mexico (Rio Puerco and Chaco Wash) where the sediments are predominantly silt and very fine sand and the plants are predominantly tamarisk and willow. Cross dating down the stem allows dating of the first growth-season following burial by thick beds, and constrains the age of all stratigraphic units deposited since germination of the tree. We observed that the anatomical reaction to burial increases with bed thickness and cumulative deposition. Beds that are thicker than 30 cm can be dated to the year of the deposition event. Beds 10 to 30 cm thick can usually be dated to within several years. The period of deposition of multiple very thin beds can be constrained to the decade. Results can be improved by analyzing multiple stems from one tree and multiple trees linked together by the stratigraphy. Along our study streams, sites far from the channel tend to have moderate and relatively steady point-aggradation rates. Levees next to the channel tend to have the thickest deposits per flood and variable long-term rates, which can differ from the whole flood plain aggradation rates by several fold. Cross-sectionally averaged flood plain aggradation has been as large as a meter per decade along our study streams.

  1. Chitosan nanoparticle-based delivery of fused NKG2D–IL-21 gene suppresses colon cancer growth in mice

    Directory of Open Access Journals (Sweden)

    Tan L

    2017-04-01

    Full Text Available Lunmei Tan,1 Sen Han,2 Shizhen Ding,2 Weiming Xiao,3,4 Yanbing Ding,3 Li Qian,2,4 Chenming Wang,1,5 Weijuan Gong1–5 1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 2Department of Immunology, School of Medicine, 3Department of Gastroenterology, The Second Clinical Medical College, 4Department of Integrated Chinese and Western Medicine, School of Medicine, 5Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, People’s Republic of China Abstract: Nanoparticles can be loaded with exogenous DNA for the potential expression of cytokines with immune-stimulatory function. NKG2D identifies major histocompatibility complex class I chain-related protein in human and retinoic acid early induced transcript-1 in mouse, which acts as tumor-associated antigens. Biologic agents based on interleukin 21 (IL-21 have displayed antitumor activities through lymphocyte activation. The NKG2D–IL-21 fusion protein theoretically identifies tumor cells through NKG2D moiety and activates T cells through IL-21 moiety. In this study, double-gene fragments that encode the extracellular domains of NKG2D and IL-21 genes were connected and then inserted into the pcDNA3.1(– plasmid. PcDNA3.1–dsNKG2D–IL-21 plasmid nanoparticles based on chitosan were generated. Tumor cells pretransfected with dsNKG2D–IL-21 gene nanoparticles can activate natural killer (NK and CD8+ T cells in vitro. Serum IL-21 levels were enhanced in mice intramuscularly injected with the gene nanoparticles. DsNKG2D–IL-21 gene nanoparticles accumulated in tumor tissues after being intravenously injected for ~4–24 h. Treatment of dsNKG2D–IL-21 gene nanoparticles also retarded tumor growth and elongated the life span of tumor-bearing mice by activating NK and T cells in vivo. Thus, the dsNKG2D–IL-21 gene nanoparticles exerted efficient antitumor activities and would be potentially used for tumor therapy. Keywords: NKG2

  2. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

    2013-01-01

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

  3. Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

    2016-01-01

    AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

  4. Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

    Science.gov (United States)

    Wang, Lu-Lu; Guo, Hui-Hui; Zhan, Yun; Feng, Chen-Lin; Huang, Shuai; Han, Yan-Xing; Zheng, Wen-Sheng; Jiang, Jian-Dong

    2017-01-01

    The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53–/−) and HT-29 were transfected with the p21-saRNA-322. The expression of P21 protein and p21 mRNA were measured using the Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA-322 on cancer cells was evaluated in vitro; and furthermore, a xenograft colorectal tumor mode in mice was established to estimate the tumor suppressing ability of p21-saRNA-322 in vivo. The results showed that in all three colorectal cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused apoptosis and cell cycle arrest at the G0/G1. Furthermore, anti-proliferation effect, reduction of colonies formation and cell senescence were observed in p21-saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment significantly inhibited the HT-29 tumor growth and facilitated p21 activation in vivo. These results indicated that, p21-saRNA-322-induceded up-regulation of p21 might be a promising therapeutic option for the treatment of colorectal cancer. PMID:28445988

  5. Disrupting glucose-6-phosphate isomerase fully suppresses the "Warburg effect" and activates OXPHOS with minimal impact on tumor growth except in hypoxia.

    Science.gov (United States)

    de Padua, Monique Cunha; Delodi, Giulia; Vučetić, Milica; Durivault, Jérôme; Vial, Valérie; Bayer, Pascale; Noleto, Guilhermina Rodrigues; Mazure, Nathalie M; Ždralević, Maša; Pouysségur, Jacques

    2017-10-20

    As Otto Warburg first observed, cancer cells largely favor fermentative glycolysis for growth even under aerobic conditions. This energy paradox also extends to rapidly growing normal cells indicating that glycolysis is optimal for fast growth and biomass production. Here we further explored this concept by genetic ablation of fermentative glycolysis in two fast growing cancer cell lines: human colon adenocarcinoma LS174T and B16 mouse melanoma. We disrupted the upstream glycolytic enzyme, glucose-6-phosphate isomerase ( GPI ), to allow cells to re-route glucose-6-phosphate flux into the pentose-phosphate branch. Indeed, GPI -KO severely reduced glucose consumption and suppressed lactic acid secretion, which reprogrammed these cells to rely on oxidative phosphorylation and mitochondrial ATP production to maintain viability. In contrast to previous pharmacological inhibition of glycolysis that suppressed tumor growth, GPI -KO surprisingly demonstrated only a moderate impact on normoxic cell growth. However, hypoxic (1% O 2 ) cell growth was severely restricted. Despite in vitro growth restriction under hypoxia, tumor growth rates in vivo were reduced less than 2-fold for both GPI -KO cancer cell lines. Combined our results indicate that exclusive use of oxidative metabolism has the capacity to provide metabolic precursors for biomass synthesis and fast growth. This work and others clearly indicate that metabolic cancer cell plasticity poses a strong limitation to anticancer strategies.

  6. Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth

    Directory of Open Access Journals (Sweden)

    Li J

    2015-02-01

    Full Text Available Jie Li,1 Chao Zhang,1 Hongchuan Jiang,1 Jiao Cheng21Department of General Surgery, 2Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Beijing, People’s Republic of ChinaAbstract: Hypoxia-inducible factor-1 (HIF-1 is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10-7 mol/L, by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.Keywords: Andrographolide (Andro, HIF-1α, inhibit, breast cancer, hypoxia, PI3k/AKT/mTOR pathway

  7. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Science.gov (United States)

    Zhao, Tiejun; Sun, Qiang; del Rincon, Sonia V; Lovato, Amanda; Marques, Maud; Witcher, Michael

    2014-01-01

    Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn) has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1) as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP) injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  8. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  9. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma.

    Science.gov (United States)

    Thiyagarajan, Varadharajan; Tsai, May-Jywan; Weng, Ching-Feng

    2015-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT) proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK.

  10. Antroquinonol Targets FAK-Signaling Pathway Suppressed Cell Migration, Invasion, and Tumor Growth of C6 Glioma.

    Directory of Open Access Journals (Sweden)

    Varadharajan Thiyagarajan

    Full Text Available Focal adhesion kinase (FAK is a non-receptor protein tyrosine that is overexpressed in many types of tumors and plays a pivotal role in multiple cell signaling pathways involved in cell survival, migration, and proliferation. This study attempts to determine the effect of synthesized antroquinonol on the modulation of FAK signaling pathways and explore their underlying mechanisms. Antroquinonol significantly inhibits cell viability with an MTT assay in both N18 neuroblastoma and C6 glioma cell lines, which exhibits sub G1 phase cell cycle, and further induction of apoptosis is confirmed by a TUNEL assay. Antroquinonol decreases anti-apoptotic proteins, whereas it increases p53 and pro-apoptotic proteins. Alterations of cell morphology are observed after treatment by atomic force microscopy. Molecular docking results reveal that antroquinonol has an H-bond with the Arg 86 residue of FAK. The protein levels of Src, pSrc, FAK, pFAK, Rac1, and cdc42 are decreased after antroquinonol treatment. Additionally, antroquinonol also regulates the expression of epithelial to mesenchymal transition (EMT proteins. Furthermore, antroquinonol suppresses the C6 glioma growth in xenograft studies. Together, these results suggest that antroquinonol is a potential anti-tumorigenesis and anti-metastasis inhibitor of FAK.

  11. siRNA-mediated Erc gene silencing suppresses tumor growth in Tsc2 mutant renal carcinoma model.

    Science.gov (United States)

    Imamura, Osamu; Okada, Hiroaki; Takashima, Yuuki; Zhang, Danqing; Kobayashi, Toshiyuki; Hino, Okio

    2008-09-18

    Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery of siRNAs for stable treatment except short hairpin RNAs (shRNAs). On the other hand, there are many reports of systemic delivery of siRNAs for transient treatment using liposome carriers and others. With regard to shRNAs, a report showed fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Therefore, we decided to use original siRNA microspheres instead of shRNA for stable treatment of disease. In this study, we designed rat-specific siRNA sequences for Erc/mesothelin, which is a tumor-specific gene expressed in the Eker (Tsc2 mutant) rat model of hereditary renal cancer and confirmed the efficacy of gene silencing in vitro. Then, by using siRNA microspheres, we found that the suppression of Erc/mesothelin caused growth inhibition of Tsc2 mutant renal carcinoma cells in tumor implantation experiments in mice.

  12. A Functional Role of Fibroblast Growth Factor Receptor 1 (FGFR1 in the Suppression of Influenza A Virus Replication.

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    Xin Liu

    Full Text Available Influenza A virus causes annual epidemics and occasional pandemics in humans. Here, we investigated four members of the fibroblast growth factor receptor (FGFR family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection. We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8 and A/Anhui/01/2005 (H5N1 virus replication. Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects. Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication. Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry. These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.

  13. Suppression subtractive hybridization profiles of radial growth phase and metastatic melanoma cell lines reveal novel potential targets

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    Espreafico Enilza M

    2008-01-01

    Full Text Available Abstract Background Melanoma progression occurs through three major stages: radial growth phase (RGP, confined to the epidermis; vertical growth phase (VGP, when the tumor has invaded into the dermis; and metastasis. In this work, we used suppression subtractive hybridization (SSH to investigate the molecular signature of melanoma progression, by comparing a group of metastatic cell lines with an RGP-like cell line showing characteristics of early neoplastic lesions including expression of the metastasis suppressor KISS1, lack of αvβ3-integrin and low levels of RHOC. Methods Two subtracted cDNA collections were obtained, one (RGP library by subtracting the RGP cell line (WM1552C cDNA from a cDNA pool from four metastatic cell lines (WM9, WM852, 1205Lu and WM1617, and the other (Met library by the reverse subtraction. Clones were sequenced and annotated, and expression validation was done by Northern blot and RT-PCR. Gene Ontology annotation and searches in large-scale melanoma expression studies were done for the genes identified. Results We identified 367 clones from the RGP library and 386 from the Met library, of which 351 and 368, respectively, match human mRNA sequences, representing 288 and 217 annotated genes. We confirmed the differential expression of all genes selected for validation. In the Met library, we found an enrichment of genes in the growth factors/receptor, adhesion and motility categories whereas in the RGP library, enriched categories were nucleotide biosynthesis, DNA packing/repair, and macromolecular/vesicular trafficking. Interestingly, 19% of the genes from the RGP library map to chromosome 1 against 4% of the ones from Met library. Conclusion This study identifies two populations of genes differentially expressed between melanoma cell lines from two tumor stages and suggests that these sets of genes represent profiles of less aggressive versus metastatic melanomas. A search for expression profiles of melanoma in

  14. Suppression subtractive hybridization profiles of radial growth phase and metastatic melanoma cell lines reveal novel potential targets

    International Nuclear Information System (INIS)

    Sousa, Josane F; Espreafico, Enilza M

    2008-01-01

    Melanoma progression occurs through three major stages: radial growth phase (RGP), confined to the epidermis; vertical growth phase (VGP), when the tumor has invaded into the dermis; and metastasis. In this work, we used suppression subtractive hybridization (SSH) to investigate the molecular signature of melanoma progression, by comparing a group of metastatic cell lines with an RGP-like cell line showing characteristics of early neoplastic lesions including expression of the metastasis suppressor KISS1, lack of αvβ3-integrin and low levels of RHOC. Two subtracted cDNA collections were obtained, one (RGP library) by subtracting the RGP cell line (WM1552C) cDNA from a cDNA pool from four metastatic cell lines (WM9, WM852, 1205Lu and WM1617), and the other (Met library) by the reverse subtraction. Clones were sequenced and annotated, and expression validation was done by Northern blot and RT-PCR. Gene Ontology annotation and searches in large-scale melanoma expression studies were done for the genes identified. We identified 367 clones from the RGP library and 386 from the Met library, of which 351 and 368, respectively, match human mRNA sequences, representing 288 and 217 annotated genes. We confirmed the differential expression of all genes selected for validation. In the Met library, we found an enrichment of genes in the growth factors/receptor, adhesion and motility categories whereas in the RGP library, enriched categories were nucleotide biosynthesis, DNA packing/repair, and macromolecular/vesicular trafficking. Interestingly, 19% of the genes from the RGP library map to chromosome 1 against 4% of the ones from Met library. This study identifies two populations of genes differentially expressed between melanoma cell lines from two tumor stages and suggests that these sets of genes represent profiles of less aggressive versus metastatic melanomas. A search for expression profiles of melanoma in available expression study databases allowed us to point to a

  15. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB‑231 partly through suppression of the Akt pathway.

    Science.gov (United States)

    Jin, Hana; Lee, Won Sup; Eun, So Young; Jung, Ji Hyun; Park, Hyeon-Soo; Kim, Gonsup; Choi, Yung Hyun; Ryu, Chung Ho; Jung, Jin Myung; Hong, Soon Chan; Shin, Sung Chul; Kim, Hye Jung

    2014-10-01

    Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

  16. Radionuclide therapy using ¹³¹I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression.

    Science.gov (United States)

    Li, Wei; Liu, Zhongyun; Li, Chengxia; Li, Ning; Fang, Lei; Chang, Jin; Tan, Jian

    2016-03-01

    compared with those of the control BSA-PCL. The EGFR-targeted radioactive nanoparticle (131)I-EGFR-BSA-PCL exhibited favorable intracellular retention of (131)I. Radionuclide therapy using (131)I-EGFR-BSA-PCL, which showed excellent targeted cell killing, suppressed cancer cell growth caused by EGFR overexpression.

  17. Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo.

    Directory of Open Access Journals (Sweden)

    Masami Suzuki

    Full Text Available The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to "wake up" these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX enhances the effect of docetaxel (Doc by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs. The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs.

  18. CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunjung; Son, Joe Eun; Byun, Sanguine; Lee, Seung Joon; Kim, Yeong A [WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921 (Korea, Republic of); Liu, Kangdong [The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States); Kim, Jiyoung [WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921 (Korea, Republic of); Lim, Soon Sung; Park, Jung Han Yoon [Department of Food Science and Nutrition, College of Natural Science, Hallym University, Chuncheon, 200-702 (Korea, Republic of); Dong, Zigang [The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States); Lee, Ki Won, E-mail: kiwon@snu.ac.kr [WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921 (Korea, Republic of); Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270 (Korea, Republic of); Lee, Hyong Joo, E-mail: leehyjo@snu.ac.kr [WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921 (Korea, Republic of); Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270 (Korea, Republic of)

    2013-10-01

    Licorice extract which is used as a natural sweetener has been shown to possess inhibitory effects against prostate cancer, but the mechanisms responsible are poorly understood. Here, we report a compound, isoangustone A (IAA) in licorice that potently suppresses the growth of aggressive prostate cancer and sought to clarify its mechanism of action. We analyzed its inhibitory effects on the growth of PTEN-deleted human prostate cancer cells, in vitro and in vivo. Administration of IAA significantly attenuated the growth of prostate cancer cell cultures and xenograft tumors. These effects were found to be attributable to inhibition of the G1/S phase cell cycle transition and the accumulation of p27{sup kip1}. The elevated p27{sup kip1} expression levels were concurrent with the decrease of its phosphorylation at threonine 187 through suppression of CDK2 kinase activity and the reduced phosphorylation of Akt at Serine 473 by diminishing the kinase activity of the mammalian target of rapamycin (mTOR). Further analysis using recombinant proteins and immunoprecipitated cell lysates determined that IAA exerts suppressive effects against CDK2 and mTOR kinase activity by direct binding with both proteins. These findings suggested that the licorice compound IAA is a potent molecular inhibitor of CDK2 and mTOR, with strong implications for the treatment of prostate cancer. Thus, licorice-derived extracts with high IAA content warrant further clinical investigation for nutritional sources for prostate cancer patients. - Highlights: • Isoangustone A suppresses growth of PC3 and LNCaP prostate cancer cells. • Administration of isoangustone A inhibits tumor growth in mice. • Treatment of isoangustone A induces cell cycle arrest and accumulation of p27{sup kip1}. • Isoangustone A inhibits CDK2 and mTOR activity. • Isoangustone A directly binds with CDK2 and mTOR complex in prostate cancer cells.

  19. ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors

    Directory of Open Access Journals (Sweden)

    Shinichi Yamashita

    2012-01-01

    Full Text Available Early studies suggested androgen receptor (AR splice variants might contribute to the progression of prostate cancer (PCa into castration resistance. However, the therapeutic strategy to target these AR splice variants still remains unresolved. Through tissue survey of tumors from the same patients before and after castration resistance, we found that the expression of AR3, a major AR splice variant that lacks the AR ligand-binding domain, was substantially increased after castration resistance development. The currently used antiandrogen, Casodex, showed little growth suppression in CWR22Rv1 cells. Importantly, we found that AR degradation enhancer ASC-J9 could degrade both full-length (fAR and AR3 in CWR22Rv1 cells as well as in C4-2 and C81 cells with addition of AR3. The consequences of such degradation of both fAR and AR3 might then result in the inhibition of AR transcriptional activity and cell growth in vitro. More importantly, suppression of AR3 specifically by short-hairpin AR3 or degradation of AR3 by ASC-J9 resulted in suppression of AR transcriptional activity and cell growth in CWR22Rv1-fARKD (fAR knockdown cells in which DHT failed to induce, suggesting the importance of targeting AR3. Finally, we demonstrated the in vivo therapeutic effects of ASC-J9 by showing the inhibition of PCa growth using the xenografted model of CWR22Rv1 cells orthotopically implanted into castrated nude mice with undetectable serum testosterone. These results suggested that targeting both fAR- and AR3-mediated PCa growth by ASC-J9 may represent the novel therapeutic approach to suppress castration-resistant PCa. Successful clinical trials targeting both fAR and AR3 may help us to battle castration-resistant PCa in the future.

  20. Development of low-smoke, flame-retarding cables

    International Nuclear Information System (INIS)

    Kato, H.; Kanemitsuya, K.; Furukawa, K.; Mio, K.

    1983-01-01

    A great deal of attention has been given to the potential fire hazard of combustion gases from organic materials. Although cable industries have developed flame-retarding organic materials for the insulation and jacketing of wires and cables, there was insufficient prevention of toxic gas formation during combustion. To cope with these problems associated with conventional PVC cables, the authors have directed to develop low-smoke, flame-retarding plasticized PVC formulations retaining the original mechanical, electrical and aging properties. A series of basic investigations on smoke suppression followed by an evaluation on practical cables could indicate some effective means to end these problems. This paper describes the results and discussion on smoke suppressing study of plasticized PVC as well as behavior and characteristics of the low-smoke, flame-retarding PVC wires and cables using these materials. (author)

  1. Gli1 activation and protection against hepatic encephalopathy is suppressed by circulating transforming growth factor β1 in mice.

    Science.gov (United States)

    McMillin, Matthew; Galindo, Cheryl; Pae, Hae Yong; Frampton, Gabriel; Di Patre, Pier Luigi; Quinn, Matthew; Whittington, Eric; DeMorrow, Sharon

    2014-12-01

    Hepatic encephalopathy (HE) is a neurologic disorder that develops during liver failure. Few studies exist investigating systemic-central signalling during HE outside of inflammatory signalling. The transcription factor Gli1, which can be modulated by hedgehog signalling or transforming growth factor β1 (TGFβ1) signalling, has been shown to be protective in various neuropathies. We measured Gli1 expression in brain tissues from mice and evaluated how circulating TGFβ1 and canonical hedgehog signalling regulate its activation. Mice were injected with azoxymethane (AOM) to induce liver failure and HE in the presence of Gli1 vivo-morpholinos, the hedgehog inhibitor cyclopamine, Smoothened vivo-morpholinos, a Smoothened agonist, or TGFβ-neutralizing antibodies. Molecular analyses were used to assess Gli1, hedgehog signalling, and TGFβ1 signalling in the liver and brain of AOM mice and HE patients. Gli1 expression was increased in brains of AOM mice and in HE patients. Intra-cortical infusion of Gli1 vivo-morpholinos exacerbated the neurologic deficits of AOM mice. Measures to modulate hedgehog signalling had no effect on HE neurological decline. Levels of TGFβ1 increased in the liver and serum of mice following AOM administration. TGFβ neutralizing antibodies slowed neurologic decline following AOM administration without significantly affecting liver damage. TGFβ1 inhibited Gli1 expression via a SMAD3-dependent mechanism. Conversely, inhibiting TGFβ1 increased Gli1 expression. Cortical activation of Gli1 protects mice from induction of HE. TGFβ1 suppresses Gli1 in neurons via SMAD3 and promotes the neurologic decline. Strategies to activate Gli1 or inhibit TGFβ1 signalling might be developed to treat patients with HE. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. LyP-1-conjugated Fe3O4nanoparticles suppress tumor growth by magnetic induction hyperthermia.

    Science.gov (United States)

    Teo, Peishan; Wang, Xiaowen; Zhang, Jieying; Zhang, Han; Yang, Xin; Huang, Yun; Tang, Jintian

    2018-02-01

    To find a promising drug carrier to suppress tumor using magnetic induction hyperthermia (MIH) and targeted therapy, two superparamagnetic iron oxide nanoparticles (SPIONs) coated with polyethylene glycol (PEG) and LyP-1, respectively, were prepared and compared. The particle size ranges of PEG-SPIONs and LyP-1-SPIONs were 10-15 nm, and 15-20 nm, respectively. In FTIR spectra, PEG-SPIONs and LyP-1-SPIONs had strong peaks between 575 and 1630 cm -1 . Specifically, the PEG-SPIONs mainly has peaks in 581 and 1630 cm -1 . The LyP-1-SPIONs mainly had peaks in 575, 1050 and 1625 cm -1 . The contents of Fe 3 O 4 in the PEG-SPIONs and LyP-1-SPIONs were about 94.24 and 89.26%, respectively. The iron contents in the MCF-7 and CT-26 cells were 33.1 ± 1.8 and 27.9 ± 0.95 pg, respectively, after co-incubation with LyP-1-SPIONs for 8 h. The LyP-1-SPIONs accumulated in the nucleus of MCF-7 cells while PEG-SPIONs in cytoplasma. In vitro, after 30 days we can found the tumor almost stopped to grow in Group LyP-1-SPIONs. LyP-1-SPIONs are promising in treating cancer as they accumulated in the nucleus of MCF-7 cells which expressed p32 and almost stopped tumor growth by combined MIH and targeted therapy.

  3. Polo-like kinase 1 (PLK1 inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

    Directory of Open Access Journals (Sweden)

    Harris Peter S

    2012-03-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1 is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. Methods We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Results Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y-box 2 (SOX2 mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Conclusions Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of

  4. Accelerated development in Johnsongrass seedlings (Sorghum halepense suppresses the growth of native grasses through size-asymmetric competition.

    Directory of Open Access Journals (Sweden)

    Susanne Schwinning

    Full Text Available Invasive plant species often dominate native species in competition, augmenting other potential advantages such as release from natural enemies. Resource pre-emption may be a particularly important mechanism for establishing dominance over competitors of the same functional type. We hypothesized that competitive success of an exotic grass against native grasses is mediated by establishing an early size advantage. We tested this prediction among four perennial C4 warm-season grasses: the exotic weed Johnsongrass (Sorghum halepense, big bluestem (Andropogon gerardii, little bluestem (Schizachyrium scoparius and switchgrass (Panicum virgatum. We predicted that a the competitive effect of Johnsongrass on target species would be proportional to their initial biomass difference, b competitive effect and response would be negatively correlated and c soil fertility would have little effect on competitive relationships. In a greenhouse, plants of the four species were grown from seed either alone or with one Johnsongrass neighbor at two fertilizer levels and periodically harvested. The first two hypotheses were supported: The seedling biomass of single plants at first harvest (50 days after seeding ranked the same way as the competitive effect of Johnsongrass on target species: Johnsongrass < big bluestem < little bluestem/switchgrass, while Johnsongrass responded more strongly to competition from Johnsongrass than from native species. At final harvest, native plants growing with Johnsongrass attained between 2-5% of their single-plant non-root biomass, while Johnsongrass growing with native species attained 89% of single-plant non-root biomass. Fertilization enhanced Johnsongrass' competitive effects on native species, but added little to the already severe competitive suppression. Accelerated early growth of Johnsongrass seedlings relative to native seedlings appeared to enable subsequent resource pre-emption. Size-asymmetric competition and resource

  5. Abrogation of Gli3 expression suppresses the growth of colon cancer cells via activation of p53

    International Nuclear Information System (INIS)

    Kang, Han Na; Oh, Sang Cheul; Kim, Jun Suk; Yoo, Young A.

    2012-01-01

    p53, the major human tumor suppressor, appears to be related to sonic hedgehog (Shh)–Gli-mediated tumorigenesis. However, the role of p53 in tumor progression by the Shh–Gli signaling pathway is poorly understood. Herein we investigated the critical regulation of Gli3–p53 in tumorigenesis of colon cancer cells and the molecular mechanisms underlying these effects. RT-PCR analysis indicated that the mRNA level of Shh and Gli3 in colon tumor tissues was significantly higher than corresponding normal tissues (P < 0.001). The inhibition of Gli3 by treatment with Gli3 siRNA resulted in a clear decrease in cell proliferation and enhanced the level of expression of p53 proteins compared to treatment with control siRNA. The half-life of p53 was dramatically increased by treatment with Gli3 siRNA. In addition, treatment with MG132 blocked MDM2-mediated p53 ubiquitination and degradation, and led to accumulation of p53 in Gli3 siRNA-overexpressing cells. Importantly, ectopic expression of p53 siRNA reduced the ability of Gli3 siRNA to suppress proliferation of those cells compared with the cells treated with Gli3 siRNA alone. Moreover, Gli3 siRNA sensitized colon cancer cells to treatment with anti-cancer agents (5-FU and bevacizumab). Taken together, our studies demonstrate that loss of Gli3 signaling leads to disruption of the MDM2–p53 interaction and strongly potentiate p53-dependent cell growth inhibition in colon cancer cells, indicating a basis for the rational use of Gli3 antagonists as a novel treatment option for colon cancer.

  6. Panaxanthone isolated from pericarp of Garcinia mangostana L. suppresses tumor growth and metastasis of a mouse model of mammary cancer.

    Science.gov (United States)

    Doi, Hitoshi; Shibata, Masa-Aki; Shibata, Eiko; Morimoto, Junji; Akao, Yukihiro; Iinuma, Munekazu; Tanigawa, Nobuhiko; Otsuki, Yoshinori

    2009-07-01

    The antitumor growth and antimetastatic activity of panaxanthone (approximately 80% alpha-mangostin and 20% gamma-mangostin) were studied in a mouse metastatic mammary cancer model that produces a metastatic spectrum similar to that seen in human breast cancer. Mammary tumors, induced by inoculation of syngeneic BALB/c mice with BJMC3879 cells, were subsequently treated with panaxanthone at 0, 2,500, or 5,000 ppm in their diet. In vitro studies were also conducted to evaluate the effects of alpha-mangostin, the main component of panaxanthone, on BJMC3879 cells. In the in vivo study, tumor volumes were significantly suppressed in mice treated with 2,500 and 5,000 ppm panaxanthone in their diet. The multiplicity of lung metastasis was significantly lower in the 5,000 ppm group. Lymph node metastasis also tended to decrease in the 5,000 ppm group but not significantly. The antitumor effects of panaxanthone were associated with elevation of apoptotic cell death, antiproliferation (inhibition of PCNA) and antiangiogenesis (inhibition of microvessel density). The in vitro study demonstrated that alpha-mangostin induced apoptosis, as evidenced by increased numbers of TUNEL-positive cells, elevated activities of caspases and a decrease in mitochondrial membrane potential, cell cycle arrest in the G(1)-phase and decreases in the cell population in the S- and G(2)/M-phases. These results suggest that the observed antimetastatic activity of panaxanthone may be of clinical significance as adjuvant therapy in metastatic human breast cancer, and may also be useful as a chemopreventative of breast cancer development.

  7. Abrogation of Gli3 expression suppresses the growth of colon cancer cells via activation of p53

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Han Na [Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Oh, Sang Cheul; Kim, Jun Suk [Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Yoo, Young A., E-mail: ydanbi@korea.ac.kr [Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of)

    2012-03-10

    p53, the major human tumor suppressor, appears to be related to sonic hedgehog (Shh)-Gli-mediated tumorigenesis. However, the role of p53 in tumor progression by the Shh-Gli signaling pathway is poorly understood. Herein we investigated the critical regulation of Gli3-p53 in tumorigenesis of colon cancer cells and the molecular mechanisms underlying these effects. RT-PCR analysis indicated that the mRNA level of Shh and Gli3 in colon tumor tissues was significantly higher than corresponding normal tissues (P < 0.001). The inhibition of Gli3 by treatment with Gli3 siRNA resulted in a clear decrease in cell proliferation and enhanced the level of expression of p53 proteins compared to treatment with control siRNA. The half-life of p53 was dramatically increased by treatment with Gli3 siRNA. In addition, treatment with MG132 blocked MDM2-mediated p53 ubiquitination and degradation, and led to accumulation of p53 in Gli3 siRNA-overexpressing cells. Importantly, ectopic expression of p53 siRNA reduced the ability of Gli3 siRNA to suppress proliferation of those cells compared with the cells treated with Gli3 siRNA alone. Moreover, Gli3 siRNA sensitized colon cancer cells to treatment with anti-cancer agents (5-FU and bevacizumab). Taken together, our studies demonstrate that loss of Gli3 signaling leads to disruption of the MDM2-p53 interaction and strongly potentiate p53-dependent cell growth inhibition in colon cancer cells, indicating a basis for the rational use of Gli3 antagonists as a novel treatment option for colon cancer.

  8. Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

    International Nuclear Information System (INIS)

    Harris, Peter S; Foreman, Nicholas K; Vibhakar, Rajeev; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Donson, Andrew M; Knipstein, Jeffrey; Dubuc, Adrian; Taylor, Michael D; Handler, Michael H

    2012-01-01

    Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. Analysis of gene expression in two independent cohorts revealed that PLK1 mRNA is overexpressed in some, but not all, medulloblastoma patient samples when compared to normal cerebellum. Inhibition of PLK1 by RNAi significantly decreased medulloblastoma cell proliferation and clonogenic potential and increased cell apoptosis. Similarly, a low nanomolar concentration of BI 2536, a small molecule inhibitor of PLK1, potently inhibited cell growth, strongly suppressed the colony-forming ability, and increased cellular apoptosis of medulloblastoma cells. Furthermore, BI 2536 pretreatment sensitized medulloblastoma cells to ionizing radiation. Inhibition of PLK1 impaired tumor sphere formation of medulloblastoma cells and decreased the expression of SRY (sex determining region Y)-box 2 (SOX2) mRNA in tumor spheres indicating a possible role in targeting tumor inititiating cells. Our data suggest that targeting PLK1 with small molecule inhibitors, in combination with radiation therapy, is a novel strategy in the treatment of medulloblastoma that warrants further investigation

  9. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

    Directory of Open Access Journals (Sweden)

    Mohamed A Alfaleh

    Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

  10. Trehalose Liposomes Suppress the Growth of Tumors on Human Lung Carcinoma-bearing Mice by Induction of Apoptosis In Vivo.

    Science.gov (United States)

    Ichihara, Hideaki; Kuwabara, Keiji; Matsumoto, Yoko

    2017-11-01

    Previous evidence demonstrates that trehalose liposomes (DMTreC14) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and α-D-glycopyranosyl-α-D-glucopyranoside monomyristate (TreC14) inhibit proliferation and invasion on lung carcinoma (A549 cells) in vitro. Here, we aimed to investigate suppressive effects of DMTreC14 on the growth of tumor on human lung carcinoma bearing mice. DMTreC14 composed of 30 mol% DMPC and 70 mol% TreC14 were prepared by the sonication method. Anti-tumor activities of DMTreC14 using the subcutaneous and orthotopic graft-bearing mice of A549 cells were investigated in vivo. The remarkable reduction of volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were obtained. Apoptotic-positive cells in the subcutaneous tumor slice of subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were observed using TUNEL staining. Lung weights on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 were markedly decreased compared to those of the control group. Remarkable decrease in dimensions of tumor area of lung on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 was obtained in histological analysis using the hematoxylin and eosin staining. Remarkably high anti-tumor activities of DMTreC14 for the subcutaneous and orthotopic graft-bearing mice of lung carcinoma accompanied with apoptosis were revealed for the first time in vivo. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Suppression of Tumor Growth and Muscle Wasting in a Transgenic Mouse Model of Pancreatic Cancer by the Novel Histone Deacetylase Inhibitor AR-42.

    Science.gov (United States)

    Henderson, Sally E; Ding, Li-Yun; Mo, Xiaokui; Bekaii-Saab, Tanios; Kulp, Samuel K; Chen, Ching-Shih; Huang, Po-Hsien

    2016-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. This study was aimed at evaluating the efficacy of AR-42 (formerly OSU-HDAC42), a novel histone deacetylase (HDAC) inhibitor currently in clinical trials, in suppressing tumor growth and/or cancer-induced muscle wasting in murine models of PDAC. The in vitro antiproliferative activity of AR-42 was evaluated in six human pancreatic cancer cell lines (AsPC-1, COLO-357, PANC-1, MiaPaCa-2, BxPC-3, SW1990). AsPC-1 subcutaneous xenograft and transgenic KP fl/fl C (LSL-Kras G12D ;Trp53 flox/flox ;Pdx-1-Cre) mouse models of pancreatic cancer were used to evaluate the in vivo efficacy of AR-42 in suppressing tumor growth and/or muscle wasting. Growth suppression in AR-42-treated cells was observed in all six human pancreatic cancer cell lines with dose-dependent modulation of proliferation and apoptotic markers, which was associated with the hallmark features of HDAC inhibition, including p21 upregulation and histone H3 hyperacetylation. Oral administration of AR-42 at 50 mg/kg every other day resulted in suppression of tumor burden in the AsPC-1 xenograft and KP fl/fl C models by 78% and 55%, respectively, at the end of treatment. Tumor suppression was associated with HDAC inhibition, increased apoptosis, and inhibition of proliferation. Additionally, AR-42 as a single agent preserved muscle size and increased grip strength in KP fl/fl C mice. Finally, the combination of AR-42 and gemcitabine in transgenic mice demonstrated a significant increase in survival than either agent alone. These results suggest that AR-42 represents a therapeutically promising strategy for the treatment of pancreatic cancer. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling

    Directory of Open Access Journals (Sweden)

    Kodela R

    2015-08-01

    Full Text Available Ravinder Kodela,1 Niharika Nath,2 Mitali Chattopadhyay,1 Diandra E Nesbitt,1 Carlos A Velázquez-Martínez,3 Khosrow Kashfi11Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, 2Department of Life Sciences, New York Institute of Technology, New York, NY, USA; 3Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada Abstract: Colorectal cancer (CRC is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives of NSAIDs. In this study, we examined the growth inhibitory effect of a novel H2S-releasing naproxen (HS-NAP, which has a repertoire as a cardiovascular-safe NSAID, for its effects on cell proliferation, cell cycle phase transitions, and apoptosis using HT-29 human colon cancer cells. We also investigated its effect as a chemopreventive agent in a xenograft mouse model. HS-NAP suppressed the growth of HT-29 cells by induction of G0/G1 arrest and apoptosis and downregulated NF-κB. Tumor xenografts in mice were significantly reduced in volume. The decrease in tumor mass was associated with a reduction of cell proliferation, induction of apoptosis, and decreases in NF-κB levels in vivo. Therefore, HS-NAP demonstrates strong anticancer potential in CRC. Keywords: nonsteroidal anti-inflammatory drugs, cell cycle, apoptosis, xenograft, NF

  13. Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor

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    Guang-ju Zhao

    2017-01-01

    Full Text Available Background. Growth arrest-specific (Gas 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk, and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.

  14. Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the Host Antiviral and Immune Responses.

    Science.gov (United States)

    Hayashi, Tsuyoshi; MacDonald, Leslie A; Takimoto, Toru

    2015-06-01

    Influenza virus infection causes global inhibition of host protein synthesis in infected cells. This host shutoff is thought to allow viruses to escape from the host antiviral response, which restricts virus replication and spread. Although the mechanism of host shutoff is unclear, a novel viral protein expressed by ribosomal frameshifting, PA-X, was found to play a major role in influenza virus-induced host shutoff. However, little is known about the impact of PA-X expression on currently circulating influenza A virus pathogenicity and the host antiviral response. In this study, we rescued a recombinant influenza A virus, A/California/04/09 (H1N1, Cal), containing mutations at the frameshift motif in the polymerase PA gene (Cal PA-XFS). Cal PA-XFS expressed significantly less PA-X than Cal wild type (WT). Cal WT, but not Cal PA-XFS, induced degradation of host β-actin mRNA and suppressed host protein synthesis, supporting the idea that PA-X induces host shutoff via mRNA decay. Moreover, Cal WT inhibited beta interferon (IFN-β) expression and replicated more rapidly than Cal PA-XFS in human respiratory cells. Mice infected with Cal PA-XFS had significantly lower levels of viral growth and greater expression of IFN-β mRNA in their lungs than mice infected with Cal WT. Importantly, more antihemagglutinin and neutralizing antibodies were produced in Cal PA-XFS-infected mice than in Cal WT-infected mice, despite the lower level of virus replication in the lungs. Our data indicate that PA-X of the pandemic H1N1 virus has a strong impact on viral growth and the host innate and acquired immune responses to influenza virus. Virus-induced host protein shutoff is considered to be a major factor allowing viruses to evade innate and acquired immune recognition. We provide evidence that the 2009 H1N1 influenza A virus protein PA-X plays a role in virus replication and inhibition of host antiviral response by means of its host protein synthesis shutoff activity both in vitro

  15. G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells

    International Nuclear Information System (INIS)

    Wu, Chang-Chieh; Tsai, Fu-Ming; Shyu, Rong-Yaun; Tsai, Ya-Ming; Wang, Chun-Hua; Jiang, Shun-Yuan

    2011-01-01

    Tazarotene-induced gene 1 (TIG1) is a retinoid-inducible type II tumour suppressor gene. The B isoform of TIG1 (TIG1B) inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform are yet to be reported. Therefore, this study investigated the effects of the TIG1A and TIG1B isoforms on cell growth and gene expression profiles using colon cancer cells. TIG1A and TIG1B stable clones derived from HCT116 and SW620 colon cancer cells were established using the GeneSwitch system; TIG1 isoform expression was induced by mifepristone treatment. Cell growth was assessed using the WST-1 cell proliferation and colony formation assays. RNA interference was used to examine the TIG1 mediating changes in cell growth. Gene expression profiles were determined using microarray and validated using real-time polymerase chain reaction, and Western blot analyses. Both TIG1 isoforms were expressed at high levels in normal prostate and colon tissues and were downregulated in colon cancer cell lines. Both TIG1 isoforms significantly inhibited the growth of transiently transfected HCT116 cells and stably expressing TIG1A and TIG1B HCT116 and SW620 cells. Expression of 129 and 55 genes was altered upon induction of TIG1A and TIG1B expression, respectively, in stably expressing HCT116 cells. Of the genes analysed, 23 and 6 genes were upregulated and downregulated, respectively, in both TIG1A and TIG1B expressing cells. Upregulation of the G-protein-coupled receptor kinase 5 (GRK5) was confirmed using real-time polymerase chain reaction and Western blot analyses in both TIG1 stable cell lines. Silencing of TIG1A or GRK5 expression significantly decreased TIG1A-mediated cell growth suppression. Expression of both TIG1 isoforms was observed in normal prostate and colon tissues and was downregulated in colon cancer cell lines. Both TIG1 isoforms suppressed cell growth and

  16. Flame Retardant Epoxy Resins

    Science.gov (United States)

    Thompson, C. M.; Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.; Lyon, R. E.

    2004-01-01

    As part of a program to develop fire resistant exterior composite structures for future subsonic commercial aircraft, flame retardant epoxy resins are under investigation. Epoxies and their curing agents (aromatic diamines) containing phosphorus were synthesized and used to prepare epoxy formulations. Phosphorus was incorporated within the backbone of the epoxy resin and not used as an additive. The resulting cured epoxies were characterized by thermogravimetric analysis, propane torch test, elemental analysis and microscale combustion calorimetry. Several formulations showed excellent flame retardation with phosphorous contents as low as 1.5% by weight. The fracture toughness of plaques of several cured formulations was determined on single-edge notched bend specimens. The chemistry and properties of these new epoxy formulations are discussed.

  17. A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

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    Stroh Thorsten

    2011-05-01

    Full Text Available Abstract Background In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC cell lines and the signaling pathways involved. Methods Four human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined. Results L.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase. Conclusions The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary treatment option for HCC.

  18. Retardadores de crescimento na produção de plantas floridas envasadas de açafrão-da-cochinchina Growth retardants on production of flowering potted thai tulip

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    Ana Christina Rossini Pinto

    2006-01-01

    Full Text Available A introdução de novos produtos na floricultura brasileira é importante para o crescimento do setor. O açafrão-da-cochinchina (Curcuma alismatifolia possui inflorescência e folhagem altamente decorativas e grande potencial para produção como florífera envasada, com o auxílio de retardadores de crescimento, usados na produção de plantas compactas e atrativas. Avaliou-se o efeito de retardadores de crescimento na produção de açafrão-da-cochinchina `Pink', de 3/12/2004 a 28/4/2005, sob ambiente protegido, em Holambra (SP. Instalou-se experimento em blocos casualizados com três repetições e onze tratamentos: controle, paclobutrazol (20; 25; 30 e 35 mg i.a./vaso, via substrato, duas, três e cinco pulverizações de daminozide na concentração de 2,125 g L-1 e duas, três e cinco pulverizações de solução de daminozide (1,275 g L-1 mais chlormequat (0,2 g L-1. O propágulo foi plantado em vaso plástico (1,0 L com substrato comercial e fertirrigado diariamente. Paclobutrazol (35 mg i.a./vaso reduziu significativamente a altura da parte aérea e da folhagem e o comprimento da haste floral, sem alterar o comprimento da inflorescência e atrasar o ciclo de produção. Entretanto, as plantas não ficaram suficientemente compactas para atender às exigências de qualidade do mercado. Os demais retardadores estudados não afetaram significativamente a altura da folhagem e o comprimento da haste floral comparado ao controle.The introduction of new products is important for the growth of Brazilian floriculture industry. The thai tulip (Curcuma alismatifolia has a highly attractive inflorescence and foliage, and great prospect as a flowering potted plant with the aid of growth retardants, which are used to produce compact plants. The effect of growth retardants on `Pink' thai tulip production was evaluated under controlled growing conditions at Holambra, SP. The experimental design was randomized blocks, with three replications and

  19. Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

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    Linghan Jia

    Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

  20. Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

    Science.gov (United States)

    Jia, Linghan; Liu, Wen; Guan, Lizhao; Lu, Min; Wang, KeWei

    2015-01-01

    Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs) that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

  1. Imatinib mesylate inhibits cell growth of malignant peripheral nerve sheath tumors in vitro and in vivo through suppression of PDGFR-β.

    Science.gov (United States)

    Ohishi, Jun; Aoki, Mikiko; Nabeshima, Kazuki; Suzumiya, Junji; Takeuchi, Tamotsu; Ogose, Akira; Hakozaki, Michiyuki; Yamashita, Yuichi; Iwasaki, Hiroshi

    2013-05-04

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 - 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.

  2. Flame retardancy and ultraviolet resistance of silk fabric coated by graphene oxide

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    Ji Yi-Min

    2017-01-01

    Full Text Available Silk fabrics were coated by graphene oxide hydrosol in order to improve its flame retardancy and ultraviolet resistance. In addition, montmorillonoid was doped into the graphene oxide hydrosol to further improve the flame retardancy of silk fabrics. The flame retardancy and ultraviolet resistance were mainly characterized by limiting oxygen index, vertical flame test, smoke density test, and ultraviolet protection factor. The synergistic effect of graphene oxide and montmorillonoid on the thermal stabilization property of the treated silk fabrics was also investigated. The results show that the treated silk fabrics have excellent flame retardancy, thermal stability, smoke suppression, and ultraviolet resistance simultaneously.

  3. Retardo mental Mental retardation

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    Marcio M. Vasconcelos

    2004-04-01

    Full Text Available OBJETIVO: Esta revisão aborda as recentes descobertas da neurobiologia do retardo mental, enfatizando os novos recursos da citogenética, das técnicas moleculares e da neurorradiologia para esclarecer o diagnóstico. FONTES DE DADOS: O autor pesquisou o banco de dados MEDLINE da National Library of Medicine utilizando as palavras-chave "mental retardation", "developmental disability", "child" e "adolescent" em diferentes combinações, abrangendo o período de janeiro de 2000 a outubro de 2003. Também foram utilizados os bancos de dados das revistas científicas Pediatrics e New England Journal of Medicine através da palavra-chave "mental retardation". No total, o autor consultou cerca de 1.500 títulos de artigos e 500 resumos, e teve acesso direto a 150 artigos completos pertinentes. Quando oportuno, algumas referências dos artigos consultados também foram consideradas. O site Online Mendelian Inheritance in Man foi utilizado como fonte de informações em genética clínica. SÍNTESE DOS DADOS: Em outubro de 2003, o total de síndromes genéticas associadas a retardo mental chegou a 1.149. Considerando-se o conjunto das causas genéticas ou ambientais e congênitas ou adquiridas de retardo mental, a avaliação diagnóstica atual é capaz de esclarecer a etiologia em 50 a 70% dos casos. CONCLUSÕES: O autor sugere uma avaliação diagnóstica do retardo mental em etapas lógicas, visando ao uso racional dos dispendiosos recursos da citogenética, biologia molecular e neuroimagem.OBJECTIVE: This paper describes recent advances in the neurobiology of mental retardation, emphasizing new diagnostic resources provided by cytogenetics, molecular testing, and neuroimaging. SOURCES OF DATA: MEDLINE (January 2000 through October 2003, using the following key words: mental retardation, developmental disability, child, and adolescent. Search of the Pediatrics and New England Journal of Medicine websites using the key word mental retardation. The

  4. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori

    2007-01-01

    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

  5. Retroviral expression of a kinase-defective IGF-I receptor suppresses growth and causes apoptosis of CHO and U87 cells in-vivo

    International Nuclear Information System (INIS)

    Seely, B Lynn; Samimi, Goli; Webster, Nicholas JG

    2002-01-01

    Phosphatidylinositol-3,4,5-triphosphate (PtdInsP3) signaling is elevated in many tumors due to loss of the tumor suppressor PTEN, and leads to constitutive activation of Akt, a kinase involved in cell survival. Reintroduction of PTEN in cells suppresses transformation and tumorigenicity. While this approach works in-vitro, it may prove difficult to achieve in-vivo. In this study, we investigated whether inhibition of growth factor signaling would have the same effect as re-expression of PTEN. Dominant negative IGF-I receptors were expressed in CHO and U87 cells by retroviral infection. Cell proliferation, transformation and tumor formation in athymic nude mice were assessed. Inhibition of IGF-IR signaling in a CHO cell model system by expression of a kinase-defective IGF-IR impairs proliferation, transformation and tumor growth. Reduction in tumor growth is associated with an increase in apoptosis in-vivo. The dominant-negative IGF-IRs also prevented growth of U87 PTEN-negative glioblastoma cells when injected into nude mice. Injection of an IGF-IR blocking antibody αIR3 into mice harboring parental U87 tumors inhibits tumor growth and increases apoptosis. Inhibition of an upstream growth factor signal prevents tumor growth of the U87 PTEN-deficient glioma to the same extent as re-introduction of PTEN. This result suggests that growth factor receptor inhibition may be an effective alternative therapy for PTEN-deficient tumors

  6. Transforming growth factor-β1 suppresses hepatitis B virus replication by the reduction of hepatocyte nuclear factor-4α expression.

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    Ming-Hsiang Hong

    Full Text Available Several studies have demonstrated that cytokine-mediated noncytopathic suppression of hepatitis B virus (HBV replication may provide an alternative therapeutic strategy for the treatment of chronic hepatitis B infection. In our previous study, we showed that transforming growth factor-beta1 (TGF-β1 could effectively suppress HBV replication at physiological concentrations. Here, we provide more evidence that TGF-β1 specifically diminishes HBV core promoter activity, which subsequently results in a reduction in the level of viral pregenomic RNA (pgRNA, core protein (HBc, nucleocapsid, and consequently suppresses HBV replication. The hepatocyte nuclear factor 4alpha (HNF-4α binding element(s within the HBV core promoter region was characterized to be responsive for the inhibitory effect of TGF-β1 on HBV regulation. Furthermore, we found that TGF-β1 treatment significantly repressed HNF-4α expression at both mRNA and protein levels. We demonstrated that RNAi-mediated depletion of HNF-4α was sufficient to reduce HBc synthesis as TGF-β1 did. Prevention of HNF-4α degradation by treating with proteasome inhibitor MG132 also prevented the inhibitory effect of TGF-β1. Finally, we confirmed that HBV replication could be rescued by ectopic expression of HNF-4α in TGF-β1-treated cells. Our data clarify the mechanism by which TGF-β1 suppresses HBV replication, primarily through modulating the expression of HNF-4α gene.

  7. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth.

    Science.gov (United States)

    Cramer, Shira L; Saha, Achinto; Liu, Jinyun; Tadi, Surendar; Tiziani, Stefano; Yan, Wupeng; Triplett, Kendra; Lamb, Candice; Alters, Susan E; Rowlinson, Scott; Zhang, Yan Jessie; Keating, Michael J; Huang, Peng; DiGiovanni, John; Georgiou, George; Stone, Everett

    2017-01-01

    Cancer cells experience higher oxidative stress from reactive oxygen species (ROS) than do non-malignant cells because of genetic alterations and abnormal growth; as a result, maintenance of the antioxidant glutathione (GSH) is essential for their survival and proliferation. Under conditions of elevated ROS, endogenous L-cysteine (L-Cys) production is insufficient for GSH synthesis. This necessitates uptake of L-Cys that is predominantly in its disulfide form, L-cystine (CSSC), via the xCT(-) transporter. We show that administration of an engineered and pharmacologically optimized human cyst(e)inase enzyme mediates sustained depletion of the extracellular L-Cys and CSSC pool in mice and non-human primates. Treatment with this enzyme selectively causes cell cycle arrest and death in cancer cells due to depletion of intracellular GSH and ensuing elevated ROS; yet this treatment results in no apparent toxicities in mice even after months of continuous treatment. Cyst(e)inase suppressed the growth of prostate carcinoma allografts, reduced tumor growth in both prostate and breast cancer xenografts and doubled the median survival time of TCL1-Tg:p53 -/- mice, which develop disease resembling human chronic lymphocytic leukemia. It was observed that enzyme-mediated depletion of the serum L-Cys and CSSC pool suppresses the growth of multiple tumors, yet is very well tolerated for prolonged periods, suggesting that cyst(e)inase represents a safe and effective therapeutic modality for inactivating antioxidant cellular responses in a wide range of malignancies.

  8. Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins.

    Science.gov (United States)

    Parraguez, Victor H; Mamani, Sandra; Cofré, Eileen; Castellaro, Giorgio; Urquieta, Bessie; De Los Reyes, Mónica; Astiz, Susana; Gonzalez-Bulnes, Antonio

    2015-01-01

    Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well-characterized sheep-model, we aimed to determine whether long- and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long- and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage.

  9. Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins

    Science.gov (United States)

    Parraguez, Victor H.; Mamani, Sandra; Cofré, Eileen; Castellaro, Giorgio; Urquieta, Bessie; De los Reyes, Mónica; Astiz, Susana; Gonzalez-Bulnes, Antonio

    2015-01-01

    Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well-characterized sheep-model, we aimed to determine whether long- and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long- and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage. PMID:26560325

  10. The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

    Science.gov (United States)

    Lai, Yi-Hua; Yu, Sung-Liang; Chen, Hsuan-Yu; Wang, Chi-Chung; Chen, Huei-Wen; Chen, Jeremy J W

    2013-05-01

    HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

  11. Overexpression of a natural chloroplast-encoded antisense RNA in tobacco destabilizes 5S rRNA and retards plant growth

    Directory of Open Access Journals (Sweden)

    Stern David B

    2010-09-01

    Full Text Available Abstract Background The roles of non-coding RNAs in regulating gene expression have been extensively studied in both prokaryotes and eukaryotes, however few reports exist as to their roles in organellar gene regulation. Evidence for accumulation of natural antisense RNAs (asRNAs in chloroplasts comes from the expressed sequence tag database and cDNA libraries, while functional data have been largely obtained from artificial asRNAs. In this study, we used Nicotiana tabacum to investigate the effect on sense strand transcripts of overexpressing a natural chloroplast asRNA, AS5, which is complementary to the region which encodes the 5S rRNA and tRNAArg. Results AS5-overexpressing (AS5ox plants obtained by chloroplast transformation exhibited slower growth and slightly pale green leaves. Analysis of AS5 transcripts revealed four distinct species in wild-type (WT and AS5ox plants, and additional AS5ox-specific products. Of the corresponding sense strand transcripts, tRNAArg overaccumulated several-fold in transgenic plants whereas 5S rRNA was unaffected. However, run-on transcription showed that the 5S-trnR region was transcribed four-fold more in the AS5ox plants compared to WT, indicating that overexpression of AS5 was associated with decreased stability of 5S rRNA. In addition, polysome analysis of the transformants showed less 5S rRNA and rbcL mRNA associated with ribosomes. Conclusions Our results suggest that AS5 can modulate 5S rRNA levels, giving it the potential to affect Chloroplast translation and plant growth. More globally, overexpression of asRNAs via chloroplast transformation may be a useful strategy for defining their functions.

  12. MicroRNA-124 suppresses growth and aggressiveness of osteosarcoma and inhibits TGF-β-mediated AKT/GSK-3β/SNAIL-1 signaling.

    Science.gov (United States)

    Bo, Yu; Kaibiao, Jiang; Jidong, Zhang

    2018-02-27

    Osteosarcoma is one of the most common malignant tumors in adolescent populations and the prognosis remains incompletely understand. Previous reports have demonstrated that microRNA‑124 (miR‑124) has inhibitory effects on various human malignancies and is associated with tumor progression. However, the clinical significance and potential mechanisms of miR‑124 in the progression of osteosarcoma is not clearly understood. In this study, the potential molecular mechanism of miR‑124 in osteosarcoma tumorigenesis, growth and aggressiveness was investigated. The growth, proliferation, apoptosis, migration and invasion of osteosarcoma cells were investigated following miR‑124 transfection were determined by colony formation assay, western blotting, immunofluorescence, migration/invasion assays and reverse transcription‑quantitative polymerase chain reaction. In vivo anti‑cancer effects of miR‑124 were analyzed by a tumor growth assay, immunohistochemistry and survival rate observations. The results demonstrated that miR‑124 transfection significantly decreased integrin expression in osteosarcoma cells, and further inhibited growth, proliferation, migration and invasion of osteosarcoma cells. Flow cytometry assays indicated that miR‑124 transfection attenuated apoptosis resistance of osteosarcoma to tunicamycin, potentially via the downregulation of P53 and Bcl‑2 apoptosis regulator expression. Mechanistic assays demonstrated that miR‑124 transfection suppressed TGF‑β expression in osteosarcoma. An animal study revealed that tumor growth was reduced in tumor cells transfected with miR‑124 compared with control cells, and the survival rate was prolonged in mice with miR‑124 transfected xenografts compared with control tumors. In conclusion, these results indicate that miR‑124 transection inhibits the growth and aggressive of osteosarcoma, potentially via suppression of TGF‑β‑mediated AKT/GSK‑3β/snail family transcriptional repressor

  13. Transfer of hexabromocyclododecane flame retardant isomers from captive American kestrel eggs to feathers and their association with thyroid hormones and growth.

    Science.gov (United States)

    Marteinson, Sarah C; Eulaers, Igor; Jaspers, Veerle L B; Covaci, Adrian; Eens, Marcel; Letcher, Robert J; Fernie, Kim J

    2017-01-01

    Feathers are useful for monitoring contaminants in wild birds and are increasingly used to determine persistent organic pollutants. However, few studies have been conducted on birds with known exposure levels. We aimed to determine how well nestling feather concentrations reflect in ovo exposure to hexabromocyclododecane (α-, β- and γ-HBCDD), and to determine if feather concentrations are related to physiological biomarkers. Captive kestrels (n = 11) were exposed in ovo to maternally transferred HBCDD-isomers at concentrations of 127, 12 and 2 ng/g wet weight of α-, β- and γ-HBCDD (measured in sibling eggs), respectively, and compared to controls (n = 6). Nestling growth was monitored at 5 d intervals and circulating thyroid hormone concentrations assessed at d 20. Tail feathers were collected prior to the first molt and analyzed for HBCDD isomers. The mean ΣHBCDD concentration in feathers was 2405 pg/g dry weight (in exposed birds) and α-, β- and γ-HBCDD made up 32%, 13%, and 55%, respectively of the ΣHBCDD concentrations. This isomer distribution deviated from the typical dominance of α-HBCDD reported in vertebrate samples. Exposed chicks had significantly higher feather concentrations of β- and γ-HBCDD compared with controls (p = 0.007 and p = 0.001 respectively), while α-HBCDD concentrations did not differ between the two groups. Feather concentrations of α-HBCDD were best explained by egg concentrations of β- or γ-HBCDD concentrations (w i  = 0.50, 0.30 respectively), while feather concentrations of β- and γ-HBCDD were influenced by growth parameters (rectrix length: w i  = 0.61; tibiotarsus length: w i  = 0.28). These results suggest that feather α-HBCDD concentrations may reflect internal body burdens, whereas β- and γ-HBCDD may be subject to selective uptake. The α-HBCDD concentrations in the feathers were negatively associated with the ratio of plasma free triiodothyronine to free thyroxine (T 3 :T 4 ; p = 0

  14. Characterization of community structure of culturable endophytic fungi in sweet cherry composite trees and their growth-retarding effect against pathogens.

    Science.gov (United States)

    Haddadderafshi, Neda; Pósa, Tímea Borbála; Péter, Gábor; Gáspár, László; Ladányi, Márta; Hrotkó, Károly; Lukács, Noémi; Halász, Krisztián

    2016-09-01

    Endophytic fungi have the potential to protect their host plants in stress situations. Characterizing the ecology and complex interaction between these endophytes and their host plants is therefore of great practical importance, particularly in horticultural plants. Among horticultural plants, fruit trees form a special category because of their longevity and because they are composites of rootstock and scion, which often belong to different plant species. Here we present the first characterization of culturable endophytic fungal community of sweet cherry. Samples from the Hungarian cultivar 'Petrus' grafted on 11 different rootstocks were collected in autumn and in spring in a bearing orchard and the dependence of colonization rate and endophyte diversity on rootstock, organ and season was analysed. On the basis of their ITS sequences 26 fungal operational taxonomic units were identified at least down to the genus level. The dominant genus, comprising more than 50% of all isolates, was Alternaria, followed by different Fusarium and Epicoccum species. We observed some organ-specificity amongst endophytes, and organs showed more sizeable differences in colonization rates and endophyte diversity than rootstocks. Most dynamic endophyte populations, strongly influenced by environmental conditions and crop management, were observed in leaves. The potential of selected endophytes to confer protection against Monilinia laxa was also analysed and 7 isolates were found to inhibit the growth of this pathogen in vitro.

  15. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhai, Jian; Qu, Shuping; Li, Xiaowei; Zhong, Jiaming; Chen, Xiaoxia; Qu, Zengqiang; Wu, Dong

    2015-01-01

    Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3’-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC. - Highlights: • Decreased of miR-129 is found in HCC and associated with advanced stage and metastasis. • miR-129 suppresses proliferation and invasion of HCC cells. • miR-129 directly targets the 3′ UTR of PAK5 and diminishes PAK5 expression. • PAK5 is involved in miR-129 mediated suppression functions

  16. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Jian [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Shuping [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Li, Xiaowei; Zhong, Jiaming; Chen, Xiaoxia [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Zengqiang, E-mail: drquzengqiang@163.com [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Wu, Dong, E-mail: wudongstc@126.com [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China)

    2015-08-14

    Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3’-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC. - Highlights: • Decreased of miR-129 is found in HCC and associated with advanced stage and metastasis. • miR-129 suppresses proliferation and invasion of HCC cells. • miR-129 directly targets the 3′ UTR of PAK5 and diminishes PAK5 expression. • PAK5 is involved in miR-129 mediated suppression functions.

  17. Peroxisome Proliferator-Activated Receptor-γ Inhibits Transformed Growth of Non-Small Cell Lung Cancer Cells through Selective Suppression of Snail

    Directory of Open Access Journals (Sweden)

    Rashmi Choudhary

    2010-03-01

    Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.

  18. X-linked mental retardation.

    NARCIS (Netherlands)

    Ropers, H.H.; Hamel, B.C.J.

    2005-01-01

    Genetic factors have an important role in the aetiology of mental retardation. However, their contribution is often underestimated because in developed countries, severely affected patients are mainly sporadic cases and familial cases are rare. X-chromosomal mental retardation is the exception to

  19. Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response.

    Directory of Open Access Journals (Sweden)

    Nicole Bedke

    Full Text Available Rhinovirus (RV infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-β, influences interferon (IFN production by primary bronchial epithelial cells (PBECs following RV infection. Exogenous TGF-β(2 increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA. Conversely, neutralizing TGF-β antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-β(2 levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-β on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-β and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-β contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3.

  20. Production of human growth hormone in transgenic rice seeds: co-introduction of RNA interference cassette for suppressing the gene expression of endogenous storage proteins.

    Science.gov (United States)

    Shigemitsu, Takanari; Ozaki, Shinji; Saito, Yuhi; Kuroda, Masaharu; Morita, Shigeto; Satoh, Shigeru; Masumura, Takehiro

    2012-03-01

    Rice seeds are potentially useful hosts for the production of pharmaceutical proteins. However, low yields of recombinant proteins have been observed in many cases because recombinant proteins compete with endogenous storage proteins. Therefore, we attempt to suppress endogenous seed storage proteins by RNA interference (RNAi) to develop rice seeds as a more efficient protein expression system. In this study, human growth hormone (hGH) was expressed in transgenic rice seeds using an endosperm-specific promoter from a 10 kDa rice prolamin gene. In addition, an RNAi cassette for reduction of endogenous storage protein expressions was inserted into the hGH expression construct. Using this system, the expression levels of 13 kDa prolamin and glutelin were effectively suppressed and hGH polypeptides accumulated to 470 μg/g dry weight at the maximum level in transgenic rice seeds. These results suggest that the suppression of endogenous protein gene expression by RNAi could be of great utility for increasing transgene products.

  1. Retardo do crescimento e condições sociais em escolares de Osasco, São Paulo, Brasil Linear growth retardation and social factors among schoolchildren from the city of Osasco, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Doris Lucia Martini Lei

    1997-04-01

    Full Text Available Este trabalho teve por objetivo identificar a associação existente entre classe social e retardo do crescimento físico, ocorrido nos primeiros anos de vida. Com base em um censo de estatura, envolvendo alunos ingressantes em todas as escolas (públicas e particulares do Município de Osasco, região metropolitana de São Paulo, Brasil, realizado no início do ano letivo de 1989, foram selecionados casos e controles para a investigação retrospectiva dos determinantes sociais do retardo do crescimento. Os casos, totalizando 125 ingressantes de sete a oito anos de idade, foram caracterizados pelo índice altura/idade inferior a -2 escores Z da população de referência do NHCS/OMS. Os controles, totalizando 139 ingressantes da mesma idade, foram caracterizados pelo índice altura/idade superior a -1 escore Z. Escolaridade do chefe da casa e da mãe, renda familiar per capita, condições de habitação e saneamento, ou seja, variáveis que devem mediar a relação entre classe social e déficit de estatura, foram fatores que se associaram significativamente com o risco de retardo do cresimento. Quanto à inserção da família no processo social de produção, avaliada através da classe social do chefe, as crianças do subproletariado apresentaram uma chance sete vezes maior de retardo do crescimento quando comparadas com as dos grupos da pequena burguesia, refletindo os efeitos biológicos da recessão econômica dos anos 80.Cases and controls were selected for this retrospective investigation of the social determinants of growth retardation, from a Height Census carried out in the 1989 school year,involving children attending the first grade of all public and private schools in Osasco (in the Greater Metropolitan Area of São Paulo, Brazil. The cases, totalling 125 children entering school aged 7-8 years old, were characterized by a height-for-age index below -2 z score of the NCHS/WHO reference. The controls, totalling 139 children

  2. Acetylbritannilactone suppresses growth via upregulation of krüppel-like transcription factor 4 expression in HT-29 colorectal cancer cells.

    Science.gov (United States)

    Fang, Xin-Mei; Liu, Bin; Liu, Ya-Bin; Wang, Jun-Jie; Wen, Jin-Kun; Li, Bing-Hui; Han, Mei

    2011-11-01

    Acetylbritannilactone (ABL) is a new active compound isolated from Inula Britannica L, a traditional Chinese medicinal herb. It has been reported that ABL can inhibit the proliferation of vascular smooth muscle cells (VSMCs) and neointima formation after balloon injury in rats. ABL also shows chemopreventive properties by inducing cell apoptosis in breast and ovarian cancers, but the antitumor activity and the molecular targets of ABL in colon cancer cells have not been determined. In this study, we showed that ABL inhibits the growth in dose- and time-dependent manners by inducing cell cycle arrest in G0/G1 phase of HT-29 human colon cancer cells. This suppression was accompanied by a strong decrease of cyclin E and CDK4 protein levels, and an increase in p21 protein expression in HT-29 cells. We also show that ABL-induced growth inhibition is associated with the upregulation of KLF4 expression. The overexpression of KLF4 by infection with pAd-KLF4 resulted in growth inhibition, with decrease in the protein levels of cyclin E and CDK4, and increase in the expression of p21, similarly to the effects of ABL. Conversely, knockdown of KLF4 using a specific siRNA impaired the ABL-induced growth inhibition in HT-29 cells. These results suggest that KLF4 as an important cellular target of ABL mediates the growth inhibition of HT-29 cells induced by ABL via upregulation of p21 expression.

  3. Identification of growth phenotype-related genes in Aspergillus oryzae by heterologous macroarray and suppression subtractive hybridization

    NARCIS (Netherlands)

    Biesebeke, R. te; Levin, A.; Sagt, C.; Bartels, J.; Goosen, T.; Ram, A.; Hondel, C. van den; Punt, P.

    2005-01-01

    Aspergillus oryzae requires polarized growth for colonization of solid substrates, and this growth phenotype differs from that seen in liquid medium. Various experimental approaches were used to identify genes that are differentially expressed when A. oryzae is grown on wheat kernels and in a

  4. Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

    DEFF Research Database (Denmark)

    Schepeler, T; Holm, A; Halvey, P

    2012-01-01

    Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Although detailed knowledge exists regarding Wnt-regulated protein-coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array...... as inferred from expression microarray and ChIP-chip data. A module of miRNAs induced by abrogated Wnt signaling in vitro was downregulated in two independent series of human primary CRCs (n=76) relative to normal adjacent mucosa (n=34). Several of these miRNAs (miR-145, miR-126, miR-30e-3p and miR-139-5p......RNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth with concomitant suppression of several growth-stimulatory cancer-related genes....

  5. Astragaloside IV suppresses transforming growth factor-β1 induced fibrosis of cultured mouse renal fibroblasts via inhibition of the MAPK and NF-κB signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Che, Xiajing; Wang, Qin; Xie, Yuanyuan; Xu, Weijia; Shao, Xinghua; Mou, Shan, E-mail: shan_mou@126.com; Ni, Zhaohui, E-mail: doctor_nzh@126.com

    2015-09-04

    Renal fibrosis, a progressive process characterized by the accumulation of extracellular matrix (ECM) leading to organ dysfunction, is a characteristic of chronic kidney diseases. Among fibrogenic factors known to regulate the renal fibrotic process, transforming growth factor-β (TGF-β) plays a central role. In the present study, we examined the effect of Astragaloside IV (AS-IV), a component of the traditional Chinese medicinal plant Astragalus membranaceus, on the processes associated with renal fibrosis in cultured mouse renal fibroblasts treated with TGF-β1. RT-PCR, western blotting, immunofluorescence staining and collagen assays showed that AS-IV suppressed TGF-β1 induced fibroblast proliferation, transdifferentiation, and ECM production in a dose-dependent manner. Examination of the underlying mechanisms showed that the effect of AS-IV on the inhibition of fibroblast differentiation and ECM formation were mediated by its modulation of the activity of the MAPK and NF-κB signaling pathways. Taken together, our results indicate that AS-IV alleviates renal interstitial fibrosis via a mechanism involving the MAPK and NF-κB signaling pathways and demonstrate the therapeutic potential of AS-IV for the treatment of chronic kidney diseases. - Highlights: • AS-IV suppressed TGF-β1 induced renal fibroblast proliferation. • AS-IV suppressed TGF-β1 induced renal fibroblast transdifferentiation. • AS-IV suppressed TGF-β1 induced ECM production. • AS-IV alleviates renal fibrosis via the MAPK and NF-κB signaling pathways.

  6. Local Equilibrium and Retardation Revisited.

    Science.gov (United States)

    Hansen, Scott K; Vesselinov, Velimir V

    2018-01-01

    In modeling solute transport with mobile-immobile mass transfer (MIMT), it is common to use an advection-dispersion equation (ADE) with a retardation factor, or retarded ADE. This is commonly referred to as making the local equilibrium assumption (LEA). Assuming local equilibrium, Eulerian textbook treatments derive the retarded ADE, ostensibly exactly. However, other authors have presented rigorous mathematical derivations of the dispersive effect of MIMT, applicable even in the case of arbitrarily fast mass transfer. We resolve the apparent contradiction between these seemingly exact derivations by adopting a Lagrangian point of view. We show that local equilibrium constrains the expected time immobile, whereas the retarded ADE actually embeds a stronger, nonphysical, constraint: that all particles spend the same amount of every time increment immobile. Eulerian derivations of the retarded ADE thus silently commit the gambler's fallacy, leading them to ignore dispersion due to mass transfer that is correctly modeled by other approaches. We then present a particle tracking simulation illustrating how poor an approximation the retarded ADE may be, even when mobile and immobile plumes are continually near local equilibrium. We note that classic "LEA" (actually, retarded ADE validity) criteria test for insignificance of MIMT-driven dispersion relative to hydrodynamic dispersion, rather than for local equilibrium. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  7. Candidate tumour suppressor CCDC19 regulates miR-184 direct targeting of C-Myc thereby suppressing cell growth in non-small cell lung cancers.

    Science.gov (United States)

    Liu, Zhen; Mai, Chunping; Yang, Huiling; Zhen, Yan; Yu, Xiaoli; Hua, Shengni; Wu, Qiangyun; Jiang, Qinping; Zhang, Yajie; Song, Xin; Fang, Weiyi

    2014-08-01

    We previously reported and revised the nasopharyngeal epithelium specific protein CCDC19 and identified it as a potential tumour suppressor in nasopharyngeal carcinoma. The purpose of this study was to investigate the involvement of CCDC19 in the pathogenesis of human non-small cell lung cancers (NSCLC). Down-regulated CCDC19 expression was observed in NSCLC tissues and cells compared to normal tissues. However, reduced protein expression did not correlate with the status of NSCLC progression. Instead, we observed that patients with lower CCDC19 expression had a shorter overall survival than did patients with higher CCDC19 expression. Lentiviral-mediated CCDC19 overexpression significantly suppressed cell proliferation and cell cycle transition from G1 to S and G2 phases in NSCLC cells. Knocking down CCDC19 expression significantly restored the ability of cell growth in CCDC19 overexpressing NSCLC cells. Mechanistically CCDC19 functions as a potential tumour suppressor by stimulating miR-184 suppression of C-Myc thus blocking cell growth mediated by the PI3K/AKT/C-Jun pathway. Our studies are the first to demonstrate that reduced expression of CCDC19 is an unfavourable factor in NSCLC. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  8. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  9. Point mutation in the NF2 gene of HEI-193 human schwannoma cells results in the expression of a merlin isoform with attenuated growth suppressive activity

    Energy Technology Data Exchange (ETDEWEB)

    Lepont, Pierig; Stickney, John T.; Foster, Lauren A.; Meng, Jin-Jun; Hennigan, Robert F. [Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Ip, Wallace [Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States)], E-mail: wallace.ip@uc.edu

    2008-01-01

    Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by the formation of bilateral schwannomas of the eighth cranial nerve. Although the protein product of the NF2 gene (merlin) is a classical tumor suppressor, the mechanism by which merlin suppresses cell proliferation is not fully understood. The availability of isolated tumor cells would facilitate a better understanding of the molecular function of merlin, but primary schwannoma cells obtained from patients grow slowly and do not yield adequate numbers for biochemical analysis. In this study, we have examined the NF2 mutation in HEI-193 cells, an immortalized cell line derived from the schwannoma of an NF2 patient. Previous work showed that the NF2 mutation in HEI-193 cells causes a splicing defect in the NF2 transcript. We have confirmed this result and further identified the resultant protein product as an isoform of merlin previously designated as isoform 3. The level of isoform 3 proteins in HEI-193 cells is comparable to the levels of merlin isoforms 1 and 2 in normal human Schwann cells and several other immortalized cell lines. In contrast to many mutant forms of merlin, isoform 3 is as resistant to proteasomal degradation as isoforms 1 and 2 and can interact with each of these isoforms in vivo. Cell proliferation assays showed that, in NF2{sup -/-} mouse embryonic fibroblasts, exogenously expressed merlin isoform 3 does exhibit growth suppressive activity although it is significantly lower than that of identically expressed merlin isoform 1. These results indicate that, although HEI-193 cells have undetectable levels of merlin isoforms 1 and 2, they are, in fact, not a merlin-null model because they express the moderately active growth suppressive merlin isoform 3.

  10. High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

    Science.gov (United States)

    Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

    2017-05-05

    N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

  11. Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.

    Science.gov (United States)

    Arum, Oge; Boparai, Ravneet K; Saleh, Jamal K; Wang, Feiya; Dirks, Angela L; Turner, Jeremy G; Kopchick, John J; Liu, Jun-Li; Khardori, Romesh K; Bartke, Andrzej

    2014-12-01

    In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1). The RIP::IGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-β-cell cell types. Multiple (nonsurvivorship) longevity-associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR-KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

    Science.gov (United States)

    Kumar, Gaurav; Moussa, Marwan; Wang, Yuanguo; Rozenblum, Nir; Galun, Eithan; Goldberg, S. Nahum

    2016-01-01

    Purpose To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Materials and Methods Rats were used in this institutional animal care and use committee–approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met–negative R3230 tumors for comparison with the native c-Met–positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. Results After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor

  13. Inhibition of IL-17A suppresses enhanced-tumor growth in low dose pre-irradiated tumor beds.

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    Eun-Jung Lee

    Full Text Available Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1 in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds.

  14. Neutrophils with protumor potential could efficiently suppress tumor growth after cytokine priming and in presence of normal NK cells.

    Science.gov (United States)

    Sun, Rui; Luo, Jing; Li, Dong; Shu, Yu; Luo, Chao; Wang, Shan-Shan; Qin, Jian; Zhang, Gui-Mei; Feng, Zuo-Hua

    2014-12-30

    In tumor-bearing state, the function of neutrophils is converted from tumor-suppressing to tumor-promoting. Here we report that priming with IFN-γ and TNF-α could convert the potential of neutrophils from tumor-promoting to tumor-suppressing. The neutrophils with protumor potential have not lost their responsiveness to IFN-γ and TNF-α. After priming with IFN-γ and TNF-α, the potential of the neutrophils to express Bv8 and Mmp9 genes was reduced. Conversely, the tumor-promotional neutrophils recovered the expression of Rab27a and Trail, resumed the activation levels of PI3K and p38 MAPK pathways in response to stimuli, and expressed higher levels of IL-18 and NK-activating ligands such as RAE-1, MULT-1, and H60. Therefore, the anti-tumor function of the neutrophils was augmented, including the cytotoxicity to tumor cells, the capability of degranulation, and the capacity to activate NK cells. Since the function of NK cells is impaired in tumor-bearing state, the administration of normal NK cells could significantly augment the efficiency of tumor therapy based on neutrophil priming. These findings highlight the reversibility of neutrophil function in tumor-bearing state, and suggest that neutrophil priming by IFN-γ/TNF-α might be a potential approach to eliminate residual tumor cells in comprehensive strategy for tumor therapy.

  15. Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties.

    Energy Technology Data Exchange (ETDEWEB)

    Huang, E. Y.; Madireddi, M. T.; Gopalkrishnan, R. V.; Leszczyniecka, M.; Su, Z. Z.; Lebedeva, I. V.; Kang, D. C.; Jian, H.; Lin, J. J.; Alexandre, D.; Chen, Y.; Vozhilla, N.; Mei, M. X.; Christiansen, K. A.; Sivo, F.; Goldstein, N. I.; Chada, S.; Huberman, E.; Pestka, S.; Fisher, P. B.; Biochip Technology Center; Columbia Univ.; Introgen Therapeutics Inc.; UMDNJ-Robert Wood Johnson Medical School

    2001-10-25

    Abnormalities in cellular differentiation are frequent occurrences in human cancers. Treatment of human melanoma cells with recombinant fibroblast interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ) results in an irreversible loss in growth potential, suppression of tumorigenic properties and induction of terminal cell differentiation. Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7), as a gene induced during these physiological changes in human melanoma cells. Ectopic expression of mda-7 by means of a replication defective adenovirus results in growth suppression and induction of apoptosis in a broad spectrum of additional cancers, including melanoma, glioblastoma multiforme, osteosarcoma and carcinomas of the breast, cervix, colon, lung, nasopharynx and prostate. In contrast, no apparent harmful effects occur when mda-7 is expressed in normal epithelial or fibroblast cells. Human clones of mda-7 were isolated and its organization resolved in terms of intron/exon structure and chromosomal localization. Hu-mda-7 encompasses seven exons and six introns and encodes a protein with a predicted size of 23.8 kDa, consisting of 206 amino acids. Hu-mda-7 mRNA is stably expressed in the thymus, spleen and peripheral blood leukocytes. De novo mda-7 mRNA expression is also detected in human melanocytes and expression is inducible in cells of melanocyte/melanoma lineage and in certain normal and cancer cell types following treatment with a combination of IFN-beta plus MEZ. Mda-7 expression is also induced during megakaryocyte differentiation induced in human hematopoietic cells by treatment with TPA (12-O-tetradecanoyl phorbol-13-acetate). In contrast, de novo expression of mda-7 is not detected nor is it inducible by IFN-beta+MEZ in a spectrum of additional normal and cancer cells. No correlation was observed between induction of mda-7 mRNA expression and growth suppression following treatment with IFN-beta+MEZ and

  16. PKA activity is essential for relieving the suppression of hyphal growth and appressorium formation by MoSfl1 in Magnaporthe oryzae.

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    Yang Li

    2017-08-01

    Full Text Available In the rice blast fungus Magnaporthe oryzae, the cAMP-PKA pathway regulates surface recognition, appressorium turgor generation, and invasive growth. However, deletion of CPKA failed to block appressorium formation and responses to exogenous cAMP. In this study, we generated and characterized the cpk2 and cpkA cpk2 mutants and spontaneous suppressors of cpkA cpk2 in M. oryzae. Our results demonstrate that CPKA and CPK2 have specific and overlapping functions, and PKA activity is essential for appressorium formation and plant infection. Unlike the single mutants, the cpkA cpk2 mutant was significantly reduced in growth and rarely produced conidia. It failed to form appressoria although the intracellular cAMP level and phosphorylation of Pmk1 MAP kinase were increased. The double mutant also was defective in plant penetration and Mps1 activation. Interestingly, it often produced fast-growing spontaneous suppressors that formed appressoria but were still non-pathogenic. Two suppressor strains of cpkA cpk2 had deletion and insertion mutations in the MoSFL1 transcription factor gene. Deletion of MoSFL1 or its C-terminal 93-aa (MoSFL1ΔCT was confirmed to suppress the defects of cpkA cpk2 in hyphal growth but not appressorium formation or pathogenesis. We also isolated 30 spontaneous suppressors of the cpkA cpk2 mutant in Fusarium graminearum and identified mutations in 29 of them in FgSFL1. Affinity purification and co-IP assays showed that this C-terminal region of MoSfl1 was essential for its interaction with the conserved Cyc8-Tup1 transcriptional co-repressor, which was reduced by cAMP treatment. Furthermore, the S211D mutation at the conserved PKA-phosphorylation site in MoSFL1 partially suppressed the defects of cpkA cpk2. Overall, our results indicate that PKA activity is essential for appressorium formation and proper activation of Pmk1 or Mps1 in M. oryzae, and phosphorylation of MoSfl1 by PKA relieves its interaction with the Cyc8-Tup1 co

  17. Superior mesenteric artery syndrome causing growth retardation

    Directory of Open Access Journals (Sweden)

    Halil İbrahim Taşcı

    2013-03-01

    Full Text Available Superior mesenteric artery syndrome is a rare and lifethreateningclinical condition caused by the compressionof the third portion of the duodenum between the aortaand the superior mesenteric artery’s proximal part. Thiscompression may lead to chronic intermittent, acute totalor partial obstruction. Sudden weight-loss and the relateddecrease in the fat tissue are considered to be the etiologicalreason of acute stenosis. Weight-loss accompaniedby nausea, vomiting, anorexia, epigastric pain, andbloating are the leading complaints. Barium radiographs,computerized tomography, conventional angiography,tomographic and magnetic resonance angiography areused in the diagnosis. There are medical and surgical approachesto treatment. We hereby present the case ofa patient with superior mesenteric artery syndrome withdelayed diagnosis.Key words: superior mesenteric artery syndrome, nausea-vomiting, anorexia

  18. Aspirin suppresses growth in PI3K-mutant breast cancer by activating AMPK and inhibiting mTORC1 signaling

    Science.gov (United States)

    Henry, Whitney S.; Laszewski, Tyler; Tsang, Tiffany; Beca, Francisco; Beck, Andrew H.; McAllister, Sandra S.; Toker, Alex

    2016-01-01

    Despite the high incidence of oncogenic mutations in PIK3CA, the gene encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), PI3K inhibitors have yielded little clinical benefit for breast cancer patients. Recent epidemiological studies have suggested a therapeutic benefit from aspirin intake in cancers harboring oncogenic PIK3CA. Here we show that mutant PIK3CA-expressing breast cancer cells have greater sensitivity to aspirin-mediated growth suppression than their wild-type counterparts. Aspirin decreased viability and anchorage-independent growth of mutant PIK3CA breast cancer cells independently of its effects on cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB). We ascribed the effects of aspirin to AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin complex 1 (mTORC1) inhibition, and autophagy induction. In vivo, oncogenic PIK3CA-driven mouse mammary tumors treated daily with aspirin resulted in decreased tumor growth kinetics, while combination therapy of aspirin and a PI3K inhibitor further attenuated tumor growth. Our study supports evaluation of aspirin and PI3K pathway inhibitors as combination therapy for targeting breast cancer. PMID:27940576

  19. Dietary supplementation with β-hydroxy-β-methylbutyrate calcium during the early postnatal period accelerates skeletal muscle fibre growth and maturity in intra-uterine growth-retarded and normal-birth-weight piglets.

    Science.gov (United States)

    Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De

    2016-04-01

    Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (Psupplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (Psupplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.

  20. A genetic and metabolic analysis revealed that cotton fiber cell development was retarded by flavonoid naringenin.

    Science.gov (United States)

    Tan, Jiafu; Tu, Lili; Deng, Fenglin; Hu, Haiyan; Nie, Yichun; Zhang, Xianlong

    2013-05-01

    The cotton (Gossypium spp.) fiber is a unique elongated cell that is useful for investigating cell differentiation. Previous studies have demonstrated the importance of factors such as sugar metabolism, the cytoskeleton, and hormones, which are commonly known to be involved in plant cell development, while the secondary metabolites have been less regarded. By mining public data and comparing analyses of fiber from two cotton species (Gossypium hirsutum and Gossypium barbadense), we found that the flavonoid metabolism is active in early fiber cell development. Different flavonoids exhibited distinct effects on fiber development during ovule culture; among them, naringenin (NAR) could significantly retard fiber development. NAR is a substrate of flavanone 3-hydroxylase (F3H), and silencing the F3H gene significantly increased the NAR content of fiber cells. Fiber development was suppressed following F3H silencing, but the overexpression of F3H caused no obvious effects. Significant retardation of fiber growth was observed after the introduction of the F3H-RNA interference segment into the high-flavonoid brown fiber G. hirsutum T586 line by cross. A greater accumulation of NAR as well as much shorter fibers were also observed in the BC1 generation plants. These results suggest that NAR is negatively associated with fiber development and that the metabolism mediated by F3H is important in fiber development, thus highlighting that flavonoid metabolism represents a novel pathway with the potential for cotton fiber improvement.

  1. Neurotoxicity of brominated flame retardants

    Science.gov (United States)

    Polybrominated diphenyl ethers (PBDEs) have been commonly used as commercial flame retardants in a variety of products including plastics and textiles. Despite their decreasing usage worldwide, congeners continue to accumulate in the environment, including soil, dust, food, anima...

  2. Can earthworms survive fire retardants?

    Science.gov (United States)

    Beyer, W.N.; Olson, A.

    1996-01-01

    Most common fire retardants are foams or are similar to common agricultural fertilizers, such as ammonium sulfate and ammonium phosphate. Although fire retardants are widely applied to soils, we lack basic information about their toxicities to soil organisms. We measured the toxicity of five fire retardants (Firetrol LCG-R, Firetrol GTS-R, Silv-Ex Foam Concentrate, Phos-chek D-75, and Phos-chek WD-881) to earthworms using the pesticide toxicity test developed for earthworms by the European Economic Community. None was lethal at 1,000 ppm in the soil, which was suggested as a relatively high exposure under normal applications. We concluded that the fire retardants tested are relatively nontoxic to soil organisms compared with other environmental chemicals and that they probably do not reduce earthworm populations when applied under usual firefighting conditions.

  3. Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Martey O

    2017-10-01

    Full Text Available Orleans Martey,1 Mhairi Nimick,1 Sebastien Taurin,1 Vignesh Sundararajan,1 Khaled Greish,2 Rhonda J Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene-1-methylpiperidine-4-one (RL71, that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles. Keywords: curcumin derivatives, nanomedicine, EGFR, biodistribution

  4. Inverse agonist of estrogen-related receptor α suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways.

    Science.gov (United States)

    Wu, Ying-Min; Chen, Zhuo-Jia; Jiang, Guan-Min; Zhang, Kun-Shui; Liu, Qiao; Liang, Shu-Wei; Zhou, Yan; Huang, Hong-Bin; Du, Jun; Wang, Hong-Sheng

    2016-03-15

    There is an urgent clinical need for targeted therapy approaches for triple-negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRα) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRα by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IκBα, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-κB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-κB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRα-based therapies for TNBC patients.

  5. Effect of gonadotropin releasing factor suppression with an immunological on growth performance, estrus activity, carcass characteristics, and meat quality of market gilts.

    Science.gov (United States)

    Bohrer, B M; Flowers, W L; Kyle, J M; Johnson, S S; King, V L; Spruill, J L; Thompson, D P; Schroeder, A L; Boler, D D

    2014-10-01

    Objectives were to evaluate the administration of an anti-gonadotropin releasing factor (GnRF) analog on suppression of estrus, consistency of feed intake, and growth performance in market gilts and to investigate the impact the physiological changes would have on carcass characteristics and fresh meat quality. Gonadotropin releasing factor stimulates the anterior pituitary to release luteinizing hormone that acts on the ovary to induce follicle development and indirectly initiates ovulation. Improvest (Zoetis, Kalamazoo, MI) contains an incomplete version of naturally occurring GnRF and causes the production of anti-GnRF antibodies that bind to the GnRF receptor and thus render GnRF inactive. This in turn suppresses estrus in female pigs. Gilts were initially separated into 10 blocks based on age and then within each block allotted to a pen (n = 114; 5 pigs/pen) based on BW. Gilts received the first dose at 12 wk of age and the second dose at 16 wk of age, were exposed to a boar daily from 20 to 26 wk of age, and were slaughtered at 26 wk of age (10 wk after second dose). Meat quality was analyzed on the 2 gilts closest to pen average ending live weight in 5 of the 10 blocks. Pen served as the experimental unit for all data analysis. During the 15-wk finishing period, ADG was 0.03 kg greater (P gilts administered GnRF suppression (treated) compared with untreated gilts (control). The majority of improvements in growth performance were observed from 16 to 20 wk of age (4 wk after second dose), as ADG was 0.07 kg greater (P gilts compared with control gilts. Ovarian weights were reduced (P gilts exhibiting puberty were reduced by 87.80% (P gilts compared with control gilts. Back fat depth was 3.78 mm greater (P gilts compared with control gilts. With the exception of subjective color, there were no differences (P ≥ 0.12) in meat quality parameters between treated and control gilts. Subjective color was darker (P = 0.03) in treated gilts compared with control gilts

  6. Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

    Science.gov (United States)

    Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

    2017-06-01

    Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

  7. Catalase gene disruptant of the human pathogenic yeast Candida albicans is defective in hyphal growth, and a catalase-specific inhibitor can suppress hyphal growth of wild-type cells.

    Science.gov (United States)

    Nakagawa, Yoshiyuki

    2008-01-01

    Although the catalase gene (CAT1) disruptant of the human pathogenic yeast Candida albicans was viable under ordinary growth conditions, we previously found that it could not grow on YPD (yeast extract/peptone/dextrose) containing SDS or at higher growth temperatures. To investigate the pleiotrophic nature of the disruptant, we examined the effect of the catalase inhibitor 3-AT on the growth of wild-type strains. Surprisingly, the addition of 3-AT and SDS caused the wild-type cells to be non-viable on YPD plates. We found an additional phenotype of the catalase gene disruptant: it did not produce normal hyphae on Spider medium. Hyphal growth was observed in a CAP1 (Candida AP-1-like protein gene) disruptant, a HOG1 (high-osmolarity glycerol signaling pathway gene) disruptant, and the double CAP1/HOG1 disruptant, suggesting that the defect in hyphal formation by the catalase disruptant was independent of these genes. Addition of 3-AT and SDS to hyphae-inducing media suppressed growth of normal hyphae in the wild-type strain. The potential necessity for catalase action upon exposure to hyphae-inducing conditions was confirmed by the immediate elevation of the catalase gene message. In spite of the requirement for catalase during hyphal growth, the catalase gene disruptant was capable of forming germ tubes in medium containing serum.

  8. MES buffer affects Arabidopsis root apex zonation and root growth by suppressing superoxide generation in root apex

    Directory of Open Access Journals (Sweden)

    Tomoko eKagenishi

    2016-02-01

    Full Text Available In plants, growth of roots and root hairs is regulated by the fine cellular control of pH and reactive oxygen species. MES, 2-(N-morpholinoethanesulfonic acid as one of the Good’s buffers has broadly been used for buffering medium, and it is thought to suit for plant growth with the concentration at 0.1% (w/v because the buffer capacity of MES ranging pH 5.5-7.0 (for Arabidopsis, pH 5.8. However, many reports have shown that, in nature, roots require different pH values on the surface of specific root apex zones, namely meristem, transition zone and elongation zone. Despite the fact that roots always grow on a media containing buffer molecule, little is known about impact of MES on root growth. Here, we have checked the effects of different concentrations of MES buffer using growing roots of Arabidopsis thaliana. Our results show that 1% of MES significantly inhibited root growth, the number of root hairs and length of meristem, whereas 0.1% promoted root growth and root apex area (region spanning from the root tip up to the transition zone. Furthermore, superoxide generation in root apex disappeared at 1% of MES. These results suggest that MES disturbs normal root morphogenesis by changing the reactive oxygen species (ROS homeostasis in root apex.

  9. MES Buffer Affects Arabidopsis Root Apex Zonation and Root Growth by Suppressing Superoxide Generation in Root Apex.

    Science.gov (United States)

    Kagenishi, Tomoko; Yokawa, Ken; Baluška, František

    2016-01-01

    In plants, growth of roots and root hairs is regulated by the fine cellular control of pH and reactive oxygen species (ROS). MES, 2-(N-morpholino)ethanesulfonic acid as one of the Good's buffers has broadly been used for buffering medium, and it is thought to suit for plant growth with the concentration at 0.1% (w/v) because the buffer capacity of MES ranging pH 5.5-7.0 (for Arabidopsis, pH 5.8). However, many reports have shown that, in nature, roots require different pH values on the surface of specific root apex zones, namely meristem, transition zone, and elongation zone. Despite the fact that roots always grow on a media containing buffer molecule, little is known about impact of MES on root growth. Here, we have checked the effects of different concentrations of MES buffer using growing roots of Arabidopsis thaliana. Our results show that 1% of MES significantly inhibited root growth, the number of root hairs and length of meristem, whereas 0.1% promoted root growth and root apex area (region spanning from the root tip up to the transition zone). Furthermore, superoxide generation in root apex disappeared at 1% of MES. These results suggest that MES disturbs normal root morphogenesis by changing the ROS homeostasis in root apex.

  10. Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.

    Directory of Open Access Journals (Sweden)

    Jasmine George

    Full Text Available Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01. This combination also significantly regressed tumor volume and number (p<0.01. Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15 in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.

  11. Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation

    NARCIS (Netherlands)

    Hennekam, R. C.; Geerdink, R. A.; Hamel, B. C.; Hennekam, F. A.; Kraus, P.; Rammeloo, J. A.; Tillemans, A. A.

    1989-01-01

    We report on two male and two female relatives with intestinal lymphangiectasia; severe lymphedema of limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation. Main facial anomalies are a flat face, flat nasal bridge, hypertelorism, small

  12. Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGFβ signaling.

    Science.gov (United States)

    Xia, L; Xiao, X; Liu, W L; Song, Y; Liu, T J J; Li, Y J; Zacksenhaus, E; Hao, X J; Ben-David, Y

    2018-01-18

    Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects. First, CLP/Cotl1 re-expression in FE1.2 and in human MCF7 breast cancer cells induced expression of the growth-suppressor gene interleukin-24 (IL-24), which independently of p53 upregulates the tumor-suppressor genes p53 apoptosis effector related to PMP-22 (PERP) and p21 cip1 . Second, overexpression of CLP/Cotl1 potentiated the growth-suppressive effect of transforming growth factor-β1 (TGFβ1), leading to downregulation of TGFβ-responsive genes vascular growth factor A/B (VEGFA/VEGFB), hypoxia inducing factor 1α (HIF-1α) and trombospondin 1 (TSP1), which mediate various hallmarks of cancer progression including angiogenesis, invasion and metastasis. CLP/Cotl1 inhibited TGFβ signaling via a non-canonical signaling involving IL-24-instigated inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphorylation and subsequent post-transcriptional downregulation of SMAD2 and SMAD4. We also showed that CLP/COTL1 expression sensitizes breast cancer cells to chemotherapeutic drugs, and this was further enhanced by addition of exogenous TGFβ1. CLP/Cotl1 expression is lost in many human malignancies including prostate, uterine and breast cancers. Thus, our results uncover a novel tumor-suppressor role for CLP/Cotl1 and identify the downstream effectors interleukin 24 (IL-24)/PERP and IL-24/MAPK/ERK/TGFβ as potential targets for precision therapy.

  13. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

    International Nuclear Information System (INIS)

    Klenke, Frank Michael; Gebhard, Martha-Maria; Ewerbeck, Volker; Abdollahi, Amir; Huber, Peter E; Sckell, Axel

    2006-01-01

    The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases

  14. An assessment of sex chromosome copy number in a phenotypic female patient with hypergonadtropic hypogonadism, primary amenorrhea and growth retardation by GTG-banding and FISH in peripheral blood and skin tissues

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, I.M.D.; DeMoranville, B.; Grollino, M.G. [Brown Univ. School of Medicine, Providence, RI (United States)] [and others

    1994-09-01

    The present report describes studies performed on an 18-year-old phenotypic female referred because of primary amenorrhea, hypergonadotropic hypoganadism and growth retardation. The clinical features raised the possibility of a gonadal dysgenesis. The ovaries were not identified on either side. Her testosterone was significantly elevated, with serum level at 48 ng/dl, and her free testosterone at 7 pg/ml. A GTG-banding analysis of 33 peripheral blood leukocytes revealed the modal number of chromosomes to be 46 per cell with a male sex constitution and normal appearing banding patterns (46,XY). In view of the clinical findings, additional cells were scored to rule out low percentage mosaicism. Out of 35 additional GTG-banded cells scored for the sex chromosomes, 4 cells (11.5%) were found to contain only one copy of the X chromosome. Fluorescent in situ hybridization (FISH) using dual color biotinylated X and Y probes (Imagenetics) was subsequently performed. Out of approximately 500 cells scored, 87% were found to be XY and 9% were found to be positive for the X signal only, versus 7% and 3% X signal only for 2 XY controls, aged 61 and 46, respectively. As loss of the Y chromosome has been reported in elderly males as well as certain males with leukemia, the age of the controls was important to note. To unequivocally establish the presence of mosaicism, a skin biopsy was obtained for fibroblast culture. Out of 388 total cells scored, 286 (74%) were found to be XY and 46 (12%) were found to be X, versus 99% XY and <1% X in controls. GTG-banding analysis of the same fibroblast culture is currently in progress. Preliminary data on this specimen thus far corroborate results of the FISH study. The presence of XY cells, along with an increased testosterone level, raises the distinct possibility of a gonadoblastoma. In view of this increased risk, arrangements are being made for the patient to have a laparoscopy and surgical removal of her presumptive streak gonads.

  15. [The laboratory evaluation of pathogenic factors under retarded consolidation of fractures of bones of lower extremities].

    Science.gov (United States)

    Stogov, V M; Kireeva, E A; Karasev, A G

    2014-12-01

    The study was carried out to comparatively analyze metabolic profile and content of growth factors in blood serum of patients with retarded consolidation of fractures of bones of lower extremities. The evaluation was applied to concentration of metabolites, growth factors and enzyme activity of blood serum in 13 patients with retarded consolidation of fractures of thigh and shank bones (main group). The comparative group included 14 patients with solid fractures of thigh and shank bones. The analysis established that as compared to patients with solid fractures of bones, in patients with retarded consolidation of fractures blood serum contained reliably higher concentration of triglycerides, products of glycolysis, epidermal growth factor and transforming growth factors TGF-α and TGF-β2. The content of vitamin E and insullin-like growth factor (IGF-1) was decreased The given markers can be labeled as potential markers of diagnostic and prognosis of development of retarded consolidation of fractures.

  16. Vanillin Analogues o-Vanillin and 2,4,6-Trihydroxybenzaldehyde Inhibit NFĸB Activation and Suppress Growth of A375 Human Melanoma.

    Science.gov (United States)

    Marton, Annamária; Kúsz, Erzsébet; Kolozsi, Csongor; Tubak, Vilmos; Zagotto, Giuseppe; Buzás, Krisztina; Quintieri, Luigi; Vizler, Csaba

    2016-11-01

    Constitutive activation of nuclear factor kappa-B (NFĸB) is a hallmark of various cancer types, including melanoma. Chemotherapy may further increase tumour NFĸB activity, a phenomenon that, in turn, exacerbates drug resistance. This study aimed at preliminary screening of a panel of aromatic aldehydes, including vanillin, for cytotoxicity and suppression of tumour cell NFĸB activity. The cytotoxic and NFĸB-inhibitory effects of 10 aromatic aldehydes, including vanillin, were investigated in cultured A375 human melanoma cells. Each compound was assayed alone and in combination with the model NFĸB-activating drug doxorubicin. The most promising analogues were then tested alone and in combination with 4-hydroperoxycyclophosphamide in vitro, and with cyclophosphamide in mice bearing A375 xenografts. The vanillin analogues o-vanillin and 2,4,6-trihydroxybenzaldehyde exhibited cytotoxicity against cultured A375 cells, and inhibited doxorubicin- and 4-hydroperoxycyclophosphamide-induced NFĸB activation. They also suppressed A375 cell growth in mice. o-vanillin and 2,4,6-trihydroxybenzaldehyde deserve further evaluation as potential anticancer drugs. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells.

    Science.gov (United States)

    Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

    2016-09-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus , has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

  18. Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1.

    Science.gov (United States)

    Maharjan, Sony; Park, Byoung Kwon; Lee, Su In; Lim, Yoonho; Lee, Keunwook; Kwon, Hyung-Joo

    2018-03-28

    A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.

  19. Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1

    Directory of Open Access Journals (Sweden)

    Kathrin Rupertus

    2012-01-01

    Full Text Available Background. Mobilization of c-Kit+ hematopoietic cells (HCs contributes to tumor vascularization. Whereas survival and proliferation of HCs are regulated by binding of the stem cell factor to its receptor c-Kit, migration of HCs is directed by stromal cell-derived factor (SDF-1. Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy. Methods. BALB/c mice (=16 were pretreated with an anti-c-Kit antibody followed by implantation of CT26.WT-GFP colorectal cancer cells into dorsal skinfold chambers. Animals (=8 additionally received a neutralizing anti-SDF-1 antibody. Animals (=8 treated with a control antibody served as controls. Investigations were performed using intravital fluorescence microscopy, immunohistochemistry, flow cytometry and western blot analysis. Results. Blockade of c-Kit significantly enhanced tumor cell engraftment compared to controls due to stimulation of tumor cell proliferation and invasion without markedly affecting tumor vascularization. C-Kit blockade significantly increased VEGF and CXCR4 expression within the growing tumors. Neutralization of SDF-1 completely antagonized this anti-c-Kit-associated tumor growth by suppression of tumor neovascularization, inhibition of tumor cell proliferation and reduction of muscular infiltration. Conclusion. Our study indicates that bone marrow suppression via anti-c-Kit pretreatment enhances tumor cell engraftment of colorectal metastases due to interaction with the SDF-1/CXCR4 pathway which is involved in HC-mediated tumor angiogenesis.

  20. Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

    Science.gov (United States)

    Pack, Svetlana D; Alper, Ozgül M; Stromberg, Kurt; Augustus, Meena; Ozdemirli, Metin; Miermont, Anne M; Klus, Greg; Rusin, Marek; Slack, Rebecca; Hacker, Neville F; Ried, Thomas; Szallasi, Zoltan; Alper, Ozge

    2004-02-01

    Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype.

  1. Thymidine selectively enhances growth suppressive effects of camptothecin/irinotecan in MSI+ cells and tumors containing a mutation of MRE11

    DEFF Research Database (Denmark)

    Rodriguez, Rene; Hansen, Lasse Tengbjerg; Phear, Geraldine

    2008-01-01

    PURPOSE: DNA synthesis inhibitors and damaging agents are widely used in cancer therapy; however, sensitivity of tumors to such agents is highly variable. The response of tumor cells in culture to these agents is strongly influenced by the status of DNA damage response pathways. Here, we attempt...... is not a direct result of MMR, p53, or p21 status. However MMR-deficient cell lines containing an intronic frameshift mutation of MRE11 show greatest sensitivity to these agents. Increased sensitivity to this combination is also evident in vivo as thymidine enhances irinotecan-induced growth suppression of MMR......-deficient tumors carrying the MRE11 mutation in mouse xenografts. CONCLUSION: Irinotecan-thymidine combinations may be particularly effective when targeted to MSI+ tumors containing this readily detectable MRE11 mutation....

  2. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  3. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  4. Angiopoietin-2 impairs collateral artery growth associated with the suppression of the infiltration of macrophages in mouse hindlimb ischaemia

    Directory of Open Access Journals (Sweden)

    Xiaoyong Tan

    2016-10-01

    Full Text Available Abstract Background Angiopoietin-2 (Ang-2, a ligand of the Tie-2 receptor, plays an important role in maintaining endothelial cells and in destabilizing blood vessels. Collateral artery growth (arteriogenesis is a key adaptive response to arterial occlusion. It is unknown whether the destabilization of blood vessels by Ang-2 can affect arteriogenesis and modulate mononuclear cell function. This study aimed to investigate the effects of Ang-2 on collateral artery growth. Methods Hindlimb ischaemia model was produced in C57BL/6 mice by femoral artery ligation. Blood flow perfusion was measured using a laser Doppler perfusion imager quantitative RT-PCR analysis was applied to identify the level of angiogenic factors. Results After the induction of hindlimb ischaemia, blood flow recovery was impaired in mice treated with recombinant Ang-2 protein; this was accompanied by a reduction of peri-collateral macrophage infiltration. In addition, quantitative RT-PCR analysis revealed that Ang-2 treatment decreased monocyte chemotactic protein-1 (MCP-1, platelet-derived growth factor-BB (PDGF-BB mRNA levels in ischaemic adductor muscles. Ang-2 can lead to macrophage M1/M2 polarization shift inhibition in the ischaemic muscles. Furthermore, Ang-2 reduced the in vitro inflammatory response in macrophages and vascular cells involved in arteriogenesis. Conclusions Our results demonstrate that Ang-2 is essential for efficient arteriogenesis, which controls macrophage infiltration.

  5. Suppression of skeletal growth in scleractinian corals by decreasing ambient carbonate-ion concentration: a cross-family comparison.

    Science.gov (United States)

    Marubini, Francesca; Ferrier-Pages, Christine; Cuif, Jean-Pierre

    2003-01-22

    Biogenic calcification is influenced by the concentration of available carbonate ions. The recent confirmation of this for hermatypic corals has raised concern over the future of coral reefs because [CO(3)(2-)] is a decreasing function of increasing pCO(2) in the atmosphere. As one of the overriding features of coral reefs is their diversity, understanding the degree of variability between species in their ability to cope with a change in [CO(3)(2-)] is a priority. We cultured four phylogenetically and physiologically different species of hermatypic coral (Acropora verweyi, Galaxea fascicularis, Pavona cactus and Turbinaria reniformis) under 'normal' (280 micromol kg(-1)) and 'low' (140 micromol kg(-1)) carbonate-ion concentrations. The effect on skeletogenesis was investigated quantitatively (by calcification rate) and qualitatively (by microstructural appearance of growing crystalline fibres using scanning electron microscopy (SEM)). The 'low carbonate' treatment resulted in a significant suppression of calcification rate and a tendency for weaker crystallization at the distal tips of fibres. However, while the calcification rate was affected uniformly across species (13-18% reduction), the magnitude of the microstructural response was highly species specific: crystallization was most markedly affected in A. verweyi and least in T. reniformis. These results are discussed in relation to past records and future predictions of carbonate variability in the oceans.

  6. MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1.

    Science.gov (United States)

    Huang, Xin-Ping; Hou, Jin; Shen, Xiao-Yun; Huang, Chao-Yuan; Zhang, Xue-Hui; Xie, Yu-An; Luo, Xiao-Ling

    2015-02-01

    Deregulated microRNAs and their roles in carcinogenesis and cancer progression have attracted much attention. In previous studies conducted in our laboratory, t