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Sample records for 125iepidermal growth factor

  1. New thrombopoietic growth factors

    Kuter, David J.

    2007-01-01

    Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions o...

  2. Growth factors in haemopoiesis.

    Jones, A L; Millar, J L

    1989-01-01

    Haemopoietic growth factors have for over two decades allowed experimentalists to grow haemopoietic bone marrow cells in vitro. With refinements in technique and the discovery of novel growth factors, all of the known haemopoietic lineages can now be grown in vitro. This has allowed a much greater understanding of the complex process of haemopoiesis from the haemopoietic stem cell to the mature, functioning end-cell. The in vivo action of these growth factors has been harder to investigate. Although recombinant technology has afforded us the much greater quantities necessary for in vivo work, problems remain with administration because of effects on other tissues. Interpretation of results is difficult because of the complex inter-relationships which exist between factors. Some of these have been defined in vitro and it appears likely that they also operate in vivo. Erythropoietin is a physiological regulator of erythropoiesis. It has been detected in vivo with levels responding appropriately to stress (i.e. elevated in anaemia) and, when administered in pharmacological doses, has been shown to correct anaemia. Granulocyte/macrophage colony-stimulating factor (GM-CSF) has been detected in vivo and may influence the production and function of granulocytes and macrophages, although how it is regulated is unknown. Granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor are ore lineage-specific. Interleukin 3 (IL-3), although it has not been detected in vivo, may act on a primitive marrow precursor by expanding the population and making these cells more susceptible to other growth factors, such as GM-CSF. Interleukin 1 (IL-1) has been detected in vivo, does not appear to have any isolated action on bone marrow (except possibly radioprotection) but probably acts synergistically with other growth factors, such as G-CSF. Interleukins 2, 4, 5 and 6 have not been detected in vivo. All have effects on B-cells. In addition IL-2 is an essential

  3. Growth factors in tumor microenvironment

    Zhang, Xuejing; Nie, Daotai; Chakrabarty, Subhas

    2010-01-01

    Tumor microenvironment plays a critical role in tumor initiation and progression. Components in the microenvironment can modulate the growth of tumor cells, their ability to progress and metastasize. A major venue of communication between tumor cells and their microenvironment is through polypeptide growth factors and receptors for these growth factors. This article discusses three major classes of growth-stimulatory polypeptide growth factors and receptors for these growth factors. It also d...

  4. Mammalian epidermal growth factor promotes plant growth

    Dyer, Melvin I.

    1980-01-01

    Application of mouse submaxillary gland epidermal growth factor to young sorghum seedlings at low concentrations (≈0.4-4 μM) increased shoot growth significantly over 3- and 6-day periods. The effects were dose dependent.

  5. Demographic factors of economic growth

    Fabiánová, Jana

    2013-01-01

    Development of the economic situation in recent years raises number of issues, including defining what are the factors of this development and whether it is possible to affect them. This thesis deals with the demographic factors of economic growth; those are factors associated with general population and factors which may have an impact on the country's economy. The main aim of this work is to precisely identify the demographic factor and analyze their development in the Czech Republic since ...

  6. Growth factors and new periodontology

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  7. Epidermal growth factor and growth in vivo

    Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of 3H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of 3H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated

  8. Factors Behind Industrial Profit Growth

    郑玉歆; 李玉红

    2008-01-01

    This paper analyzes Chinese enterprise industrial profit distribution and profitability rise between 1998 and 2005. Looking at it from the perspective of drivers of total growth, this paper will provide an in-depth analysis of the origins and industry-level factors involved in this growth. It reaches the conclusion that structural change in profits was the main driving force for profit increases, to which heavy industry contributed greatly. Light and machine building industry profit rates improved due to increases in productivity levels, while energy and raw material industry profits increased due to increases in product prices. In addition, average wages grew slower than GDP, and wages among industries varied widely. In general however, this paper sets out to determine which enterprises gained from increases in industrial profitability, and how this gain came about.

  9. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  10. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  11. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    Bor, M V; Sørensen, B S; Vinter-Jensen, L; Flyvbjerg, A; Pedersen, S B; Nexø, E

    2000-01-01

    I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth......BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well as the...

  12. The genome of Shope fibroma virus, a tumorigenic poxvirus, contains a growth factor gene with sequence similarity to those encoding epidermal growth factor and transforming growth factor alpha.

    Chang, W.; Upton, C; Hu, S L; Purchio, A F; McFadden, G

    1987-01-01

    Degenerate oligonucleotide probes corresponding to a highly conserved region common to epidermal growth factor, transforming growth factor alpha, and vaccinia growth factor were used to identify a novel growth factor gene in the Shope fibroma virus genome. Sequence analysis indicates that the Shope fibroma growth factor is a distinct new member of this family of growth factors.

  13. Nerve growth factor and asthma.

    Bonini, S; Lambiase, A; Lapucci, G; Properzi, F; Bresciani, M; Bracci Laudiero, M L; Mancini, M J; Procoli, A; Micera, A; Sacerdoti, G; Bonini, S; Levi-Schaffer, F; Rasi, G; Aloe, L

    2002-01-01

    An increasing body of evidence shows that nerve growth factor (NGF) exerts biological activity not only on the central and peripheral nervous system, but also on the immune system thereby influencing allergic diseases and asthma. (1) NGF circulating levels are increased in patients with allergic diseases and asthma, and are related to the severity of the inflammatory process and disease. In vernal keratoconjunctivitis, NGF plasma levels correlate with the number of mast cells infiltrating the conjunctiva, and NGF mRNA is increased in nasal mucosal scrapings of patients with allergic rhinitis who have high levels of NGF in serum and nasal fluids; NGF is further increased in nasal fluids after specific allergen challenge. (2) NGF is produced and released by several modulatory and effector cells of allergic inflammation and asthma, for example T-helper 2 lymphocytes, mast cells and eosinophils. (3) NGF receptors are expressed on the conjunctival epithelium of patients with allergic conjunctivitis and the number of NGF-receptor positive cells is increased in the conjunctiva of these patients. Indeed, local administration of NGF induces fibroblast activation and healing processes of human corneal ulcers, which suggests that NGF plays a role in tissue remodelling processes occurring in asthma. (4) NGF increases airway hyperreactivity to histamine in an animal model of asthma, while anti-NGF treatment reduces airway hyperreactivity induced by ovalbumin topical challenge in the sensitized mouse. PMID:12144547

  14. Fibroblast growth factors in neurodevelopment and psychopathology

    Terwisscha van Scheltinga, Afke F; Bakker, Steven C; Kahn, René S; Kas, Martien J H

    2013-01-01

    In psychiatric disorders, the effect of genetic and environmental factors may converge on molecular pathways and brain circuits related to growth factor functioning. In this review, we describe how disturbances in fibroblast growth factors (FGFs) and their receptors influence behavior by affecting b

  15. Growth factor involvement in tension-induced skeletal muscle growth

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  16. Risk factors for the regional economic growth

    Yevgeniy Sapiro; Tatyana Mirolyubova

    2008-01-01

    The article features principal aspects of economic growth in Permsky Krai as one of the representative regions of present Russia. It determines features of performance of economy sectors in Permsky Krai and specifies structure of the export-oriented sector. The author analyses the factors affecting economic growth in the region given the existing sources of economic growth of Permsky Krai are retained.

  17. Growth factors for the treatment of ischemic brain injury (growth factor treatment).

    Larpthaveesarp, Amara; Ferriero, Donna M; Gonzalez, Fernando F

    2015-01-01

    In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans. PMID:25942688

  18. The growth hormone axis and insulin-like growth factors

    Radosavljević Tatjana

    2005-01-01

    Full Text Available Introduction Growth is regulated by the interaction of environmental signals with endogenous neuroendocrine responses to the genetic programs that determine the body plan. The insulin-like growth factors (IGFs are integral components of multiple systems controlling both growth and metabolism. The IGF system The IGF system is thought to be more complex than other endocrine systems, as genes for six IGF-binding proteins (IGFBPs have been identified so far. The IGFs play a critical role in both cell cycle control and apoptosis, two functions involved in regulation of tumorigenesis. Insulin-like growth factor-I (IGF-I is essential for normal growth. Confirmation of the significance of IGF-I in human physiology was obtained by the discovery of a patient with intrauterine growth retardation and postnatal growth failure associated with a mutation in the IGF-1 gene. Stages of evolution of the somatomedin hypothesis The original somatomedin hypothesis postulated that somatic growth was regulated by growth hormone's (GH's stimulation of hepatic IGF-1 production, with IGF-1 acting in an endocrine fashion to promote growth. The dual effectors theory proposed an alternative view, involving direct effects by GH on peripheral tissues not mediated by IGF-1 and GH-stimulated local IGF-1 production for autocrine/paracrine action. It is now clear that G H stimulates the formation of ternary IGF binding complex, which stabilizes IGF-I in the serum.

  19. Growth factor parametrization in curved space

    Gong, Yungui; Wang, Anzhong

    2009-01-01

    The growth rate of matter perturbation and the expansion rate of the Universe can be used to distinguish modified gravity and dark energy models in explaining the cosmic acceleration. We explore here the inclusion of spatial curvature into the growth factor. We expand previous results using the approximation $\\Omega_{m}^\\gamma$ and then suggest a new form, $\\Omega_m^\\gamma+(\\gamma-4/7)\\Omega_k$, as an approximation for the growth factor when the curvature $\\Omega_k$ is not negligible, and where the growth index $\\gamma$ is usually model-dependent. The expression recovers the standard results for the curved and flat $\\Lambda$CDM and Dvali-Gabadadze-Porrati models (DGP). Fitting the growth factor to observational data, we obtain $\\gamma_{\\Lambda}(\\Omega_{k} \

  20. Factors explaining emerging economies’ growth slowdown

    K. Buysse; Vincent, E.

    2015-01-01

    Over the past decade, emerging market economies have staged a period of impressive growth, boosting their share in world GDP. In recent years, however, growth in emerging markets has slowed substantially and is projected to remain sluggish for the foreseeable future. The aim of the article is to highlight several structural factors that can explain this synchronised slowdown. The article focuses on four structural factors that have already had an impact on the economic performance of emerging...

  1. Epidermal growth factor in the rat prostate

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier;

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  2. Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate

    1993-01-01

    Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of bet...

  3. Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

    Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier;

    1993-01-01

    basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through......Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF...... receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated...

  4. Epidermal Growth Factor and Intestinal Barrier Function

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  5. Multilayered assemblies for growth factor delivery

    Kumorek, Marta Maria; Kubies, Dana; Houska, Milan; Riedel, Tomáš; Filová, E.; Rypáček, František

    Prague : Institute of Macromolecular Chemistry AS CR, 2013. L9. ISBN 978-80-85009-76-7. [Workshop "Career in Polymers" /5./. 12.07.2013-13.07.2013, Prague] Institutional support: RVO:61389013 Keywords : fibroblast growth factor * tissue engineering Subject RIV: CD - Macromolecular Chemistry

  6. Fibroblast growth factor 23--et fosfatregulerende hormon

    Beck-Nielsen, Signe Sparre; Pedersen, Susanne Møller; Kassem, Moustapha;

    2010-01-01

    Fibroblast growth factor 23 (FGF23) is a recently identified phosphatonin. Its main physiological functions are to maintain serum phosphate within its reference range and to counter regulate the effects of vitamin D. Diseases correlated to high serum values of FGF23 are hypophosphatemic rickets, ...

  7. Modulation of radiosensitivity by growth factors

    The full text of the publication follows. For the past 70 years, radiotherapy protocols were defined to target and kill cancer cells. New research developments showed that the tissue or tumor radiosensitivities might be directly modulated by its own microenvironment. Between all the micro-environmental cells, endothelial cells are playing a unique role due to the need of angio-genesis for tumor genesis and to the microvascular endothelial cell apoptosis involved in acute normal tissue and tumor radiosensitivities. Both endothelial behaviours may be controlled by specific growth factors secreted by tumor cells. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two cytokines involved in angio genesis and endothelial cell survival. Because radiation exposure develops opposite molecular and cellular responses by inhibiting proliferation and by enhancing apoptosis, inhibiting these cytokines has been proposed as a relevant strategy to improve radiotherapy efficiency. Drugs or antibody against VEGF, or other growth factors have been used with success to limit endothelial cell resistance, but also to transiently normalize of blood vessels to improve oxygen distribution into the tumor. However, better characterisation of the role of the cytokines will help to better improve the strategy of the use of their antagonists. We demonstrate that bFGF or sphingosin 1 phosphate (S1P), a lipid endothelial growth factor, protects endothelial cells from radiation stress by inhibiting the pre-mitotic apoptosis through enhancement of pro-survival molecular cascade, such as the Pi3K/AKT pathway, but not post-mitotic death. This discrepancy allowed a specific use of S1P as pharmacological drug protecting quiescent endothelial cells, present in normal tissue blood vessels, but not in proliferating angiogenic blood vessels, majority present in tumor blood vessel. In vivo studies are underway. (author)

  8. Epidermal growth factor (EGF) receptor gene transcription

    The authors have studied in vitro transcription of the human epidermal growth factor (EGF) receptor proto-oncogene using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. With the in vitro system we found that Sp1 and other trans-acting factors bound to the EGF receptor promoter regions and are required for maximal expression. Fractionation showed that a DEAE-Sepharose fraction (BA) contained a novel factor, which specifically stimulated EGF receptor transcription 5- to 10-fold. The molecular mass of the native form of the factor is about 270-kDa based on its migration on Sephacryl S-300. This factor may activate transcription of the proto-oncogene through a weak or indirect interaction with the DNA template

  9. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  10. Growth hormone, insulin-like growth factor system and carcinogenesis.

    Boguszewski, Cesar Luiz; Boguszewski, Margaret Cristina da Silva; Kopchick, John J

    2016-01-01

    The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. (Endokrynol Pol 2016; 67 (4): 414-426). PMID:27387246

  11. Growth hormone-insulinlike growth factor I and immune function.

    Gelato, M C

    1993-04-01

    Growth hormone (GH) and insulinlike growth factor I (IGF-I) may be part of a neuroendocrine immune axis that stimulates cellular proliferation of primary lymphoid organs (bone marrow, thymus) as well as stimulates activation of peripheral lymphocytes and macrophages to enhance specific immune responses. GH can also stimulate production of thymic hormones and cytokines, and in this way impact on immune function. It is not clear whether GH and IGF-I act independently or whether the action of GH is mediated by local production of IGF-I by lymphocytes. Both GH and IGF-I and their receptors are present in lymphocytes. Thus, cells of the immune system may be important targets of the GH-IGF-I axis. PMID:18407143

  12. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  13. Factor Endowment, Structural Change, and Economic Growth

    Che, Natasha Xingyuan

    2010-01-01

    This paper aims (1) to test the endowment-based structural change theory proposed by recent studies such as Acemoglu & Guerrieri (2008) and Ju, Lin & Wang (2009); and (2) to explore the linkage between structural coherence and economic growth. By structural coherence, I refer to the degree that a country’s industrial structure optimally reflects its factor endowment fundamentals. Using data from 27 industries across 15 countries, I examine whether higher capital endowment is associated w...

  14. The Fibroblast Growth Factor signaling pathway

    Ornitz, David M.; Itoh, Nobuyuki

    2015-01-01

    The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STA...

  15. Binding of epidermal growth factor and insulin-like growth factor I in human myometrium and leiomyomata

    Samples of uterine myometrium and leiomyoma from 11 women were analyzed for the presence of epidermal growth factor receptors and insulin-like growth factor I receptors. In addition, the content of soluble insulin-like growth factor binding protein (IGF-BP/PP12) was measured in the tissue cytosols. Cell membrane preparations of myoma tissue bound significantly more insulin-like growth factor I than did those of adjacent normal myometrium, whereas myoma tissue bound less epidermal growth factor than did the normal myometrium. The differences in both insulin-like growth factor I and epidermal growth factor binding were due to changes in receptor concentration rather than to alterations in receptor affinity. Neither myoma nor myometrial tissue contained detectable levels of insulin-like growth factor binding protein. The changes in epidermal growth factor and insulin-like growth factor I binding to the myometrium may play a role in the pathogenesis of uterine leiomyomata

  16. Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors.

    Rubio, Roman G; Adamis, Anthony P

    2016-01-01

    Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases. PMID:26502333

  17. Growth Hormone and Insulin-Like Growth Factor-1.

    Nicholls, Adam R; Holt, Richard I G

    2016-01-01

    Human growth hormone (GH) was first isolated from the human pituitary gland in 1945 and found to promote the growth of children with hypopituitarism. Since the formation of the World Anti-Doping Association, human GH has appeared on the list of forbidden substances. There is a significant amount of anecdotal evidence that human GH is misused by athletes to enhance performance, and there have been a number of high-profile cases of GH use in professional sport. GH secretagogues (GH-Ss), which increase GH secretion, and insulin-like growth factor (IGF-1), which mediates many of the effects of GH, are also misused, although there is less evidence for this. The effectiveness of GH, IGF-1, and GH-Ss as performance-enhancing drugs remains unclear. Evidence from studies of GH use in people with hypopituitarism show several desirable outcomes, including increased lean body mass, increased strength, and increased exercise capacity. These anabolic and metabolic properties, coupled with the difficulty in detecting them, make them attractive as agents of misuse. Studies in healthy young adults have also demonstrated a performance benefit with GH and IGF-1. PMID:27347885

  18. The multiple interactions between growth factors and microenvironment in vivo

    2006-01-01

    Cell, growth factors and extracellular matrices (ECMs) coexist in a dynamic tissue envi- ronment. A knowledge of multiple interactions among them is highly important for effectively raising the biological activities of growth factors, regulating cell life cycle, designing and preparing exogenous mat- rices to control growth factors release in tissue or organ regeneration by engineering means. This paper addresses the characteristics and functions of growth factors, interactions between growth factors and ECMs, the manners and correlative signaling of growth factors acting on cells, and briefly summarizes the biomimetic requisites for controlled release mat- rices, hoping to provide a useful reference for co- rrelative research in tissue engineering.

  19. EXPRESSION OF GROWTH-FACTORS AND GROWTH-FACTOR RECEPTORS IN NORMAL AND TUMOROUS HUMAN THYROID TISSUES

    van der Laan, B.F.A.M.; FREEMAN, JL; ASA, SL

    1995-01-01

    A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates w

  20. Radioreceptor assay for epidermal growth factor

    An established cell line of human lung fibroblasts with a high number of surface receptors for mouse epidermal growth factor (mEGF) was used to deveop a simple and highly sensitive radioreceptor assay for EGF. 125I-Labeled mEGF competed mole for mole with unlabeled mEGF for specific receptors. Optimal range for discriminating EGF concentrations in body fluids and tissue extracts by a competitive binding assay was between 5 and 100 ng/ml. Interassay correlation of variation was 8.47% and the recovery of highly purified mEGF added to serum and urine samples was greater than 95%. Human serum and amniotic fluids contained about 24 and 4 ng/ml, respectively, of mEGF equivalents. Concentrations of mEGF in mouse urine and serum were highly variable and were 2- to 10-fold greater than that previously detected by radioimmune assay. Hypophysectomy nearly abolished submaxillary mEGF content in both male and female mice, but testosterone treatment of hypophysectomized animals restored normal concentrations of mEGF to the glands. mEGF added to culture medium disappeared with time as a function of the number of cellular EGF receptors indicating cellular degradation of the growth factor. The radioreceptor assay for EGF is based on the close biologic relationship between the cell receptor site and the native hormone and should prove to be a useful complementary tool to characterize the physiological role of EGF

  1. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  2. Epidermal growth factor as a biologic switch in hair growth cycle

    Mak, KKL; Chan, SY

    2003-01-01

    The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular...

  3. Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma

    Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10(-10) M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms

  4. Growth Factors and Breast Tumors, Comparison of Selected Growth Factors with Traditional Tumor Markers

    Kučera, R.; Černá, M.; Ňaršanská, A.; Svobodová, Š.; Straková, M.; Vrzalová, J.; Fuchsová, R.; Třešková, I.; Kydlíček, T.; Třeška, V.; Pecen, Ladislav; Topolčan, O.; Padziora, P.

    2011-01-01

    Roč. 31, č. 12 (2011), s. 4653-4656. ISSN 0250-7005 Grant ostatní: GA MZd(CZ) NS9727; GA MZd(CZ) NS10238; GA MZd(CZ) NS10253 Institutional research plan: CEZ:AV0Z10300504 Keywords : growth factor * breast cancer * tumor markers * CA 15-3 * CEA * IGF1 * EGF * HGF Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

  5. Nerve growth factor-induced alteration in the response of PC12 pheochromocytoma cells to epidermal growth factor

    Huff, K; End, D; Guroff, G

    1981-01-01

    PC12 cells, which differentiate morphologically and biochemically into sympathetic neruonlike cells in response to nerve growth fact, also respond to epidermal growth factor. The response to epidermal growth factor is similar in certain respects to the response to nerve growth fact. Both peptides produce rapid increases in cellular adhesion and 2-deoxyglucose uptake and both induce ornithine decarboxylase. But nerve growth factor causes a decreased cell proliferation and a marked hypertrophy ...

  6. Human epidermal growth factor receptor residue covalently cross-linked to epidermal growth factor

    An epidermal growth factor (EGF) receptor monoclonal antibody (mAb), mAb LA22, was used to analyze the covalent coupling of human EGF receptors to mouse EGF by the amine-reactive cross-linking agent disuccinimidyl suberate. A soluble Mr 105,000 truncated form of the receptor secreted by A-431 epidermoid carcinoma cells and consisting of the ligand-binding extracellular domain was cross-linked to 125I-labeled EGF. Digestion of this complex with an endoproteinase that specifically cleaves at the COOH side of glutamyl residue released a single radiolabeled glycosylated fragment of Mr18,000 that reacted with mAb LA22. The receptor residue(s) involved in the covalent coupling of rat 125I-labeled transforming growth factor α was similarly localized to this region of the receptor. This receptor interval, which included two glycosylated asparaginyl residues at positions 328 and 337, contained but three amino acid residues that were potentially reactive with disuccinimidyl suberate: Lys-332, Lys-333, and Lys-336. These results indicated that disuccinimidyl suberate cross-linked the NH2 group of EGF residue Asn-1 to the human EGF receptor residue Lys-336. The results further suggest that EGF and transforming growth factor α, two members of the EGF family of peptide growth factors, interact with closely apposed or identical features of the receptor

  7. Fibroblast growth factor 23 and bone mineralisation

    Yu-Chen Guo; Quan Yuan

    2015-01-01

    Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts in bone. The critical role of FGF23 in mineral ion homeostasis was first identified in human genetic and acquired rachitic diseases and has been further characterised in animal models. Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease (CKD) and may play a critical role in mineral ion disorders and bone metabolism in these patients. Our recent publications have also shown that FGF23 and its cofactor, Klotho, may play an independent role in directly regulating bone mineralisation instead of producing a systematic effect. In this review, we will discuss the new role of FGF23 in bone mineralisation and the pathophysiology of CKD-related bone disorders.

  8. Aldosterone as a renal growth factor.

    Thomas, Warren

    2011-04-05

    Aldosterone regulates blood pressure through its effects on the cardiovascular system and kidney. Aldosterone can also contribute to the development of hypertension that leads to chronic pathologies such as nephropathy and renal fibrosis. Aldosterone directly modulates renal cell proliferation and differentiation as part of normal kidney development. The stimulation of rapidly activated protein kinase cascades is one facet of how aldosterone regulates renal cell growth. These cascades may also contribute to myofibroblastic transformation and cell proliferation observed in pathological conditions of the kidney. Polycystic kidney disease is a genetic disorder that is accelerated by hypertension. EGFR-dependent proliferation of the renal epithelium is a factor in cyst development and trans-activation of EGFR is a key feature in initiating aldosterone-induced signalling cascades. Delineating the components of aldosterone-induced signalling cascades may identify novel therapeutic targets for proliferative diseases of the kidney.

  9. Factor-structure of economic growth in E-commerce

    吴隽; 刘洪久; 栾天行

    2003-01-01

    In order to analyze the factors having effect on economic growth of E-commerce, the economic growthprocess of E-commerce is divided into three stages; growth stage, stabilization stage and re-growth stage. Thesethree different stages are analysed using several economic growth theories, a set of factor-structure is proposedfor each stage of the economic growth process of E-commerce.

  10. Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor

    Raaberg, Lasse; Nexø, Ebba; Jørgensen, P E;

    1995-01-01

    We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The study was focused on organs known to contain EGF or its receptor. Compared with controls, the offspring of autoimmune rats had a higher perinatal mortality and a......, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight...

  11. Economic growth factors system: theoretical and methodological aspect

    H.Ya. Hlukha

    2014-01-01

    The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine...

  12. Radioimmunoassay of human epidermal growth factor (urogastrone)

    Epidermal growth factor (EGF) is a polypeptide hormone that stimulates growth of a variety of tissues. Although it was originally discovered in male mouse submaxillary glands, EGF has recently been isolated from human urine. A heterologous radioimmunoassay for human EGF (hEGF) has been developed, using purified hEGF as reference standard and radioiodinated tracer and antibodies raised against mouse EGF. Purified hEGF specifically displaced radioiodinated hEGF from the antibodies; no other human peptide hormone tested demonstrated any cross-reaction. Twenty-four hour urinary excretion of RIA-hEGF in normal adult males and females was 97.8 +- 10.7 and 72.0 +- 4.5 (mean +- SE) μg/total volume, or 51.7 +- 4.5 and 57.0 +- 4.9 μg/g of creatinine, respectively. Urinary excretion in normal children increased with age, from less than 40 μg/24 h at 4 years of age to adult levels at about the age of puberty. The concentration of RIA-hEGF in human saliva ranged from 5.6 to 16.8 ng/ml, was about 80 ng/ml in human milk and was undetectable in human amniotic fluid (<1.4 ng/ml). It was recently been suggested that human EGF is identical with human urogastrone. However, the tissue secreting this ''new'' human hormone and the role of hEGF in health and disease have yet to be determined

  13. Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

    Therkildsen, M H; Poulsen, Steen Seier; Bretlau, P

    1993-01-01

    Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected with a...... monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-alpha and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-alpha. In sections including normal differentiated oral mucosa......, the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells...

  14. Nerve growth factor actions on the brain

    We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with [125I]NGF suggested that high affinity receptors were localized to the neuron-like population. Only low-affinity receptors were localized to the non-neuron-like cells. Moreover, employing combined immunocytochemistry and [125I]NGF autoradiography, we detected a subpopulation of CAT-containing neutrons that exhibited high-affinity binding. Unexpectedly, a gamma-aminobutyric acid (GABA)-containing cell group also expressed high affinity binding. However, only subsets of cholinergic or GABA neurons expressed high-affinity biding, suggesting that these transmitter populations are composed of differentially response subpopulations

  15. Radiotherapy and receptor of epidermal growth factor

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  16. Platelet-rich growth factor in oral and maxillofacial surgery

    Pal, Uma Shanker; Mohammad, Shadab; Singh, Rakesh K.; Das, Somdipto; Singh, Nimisha; Singh, Mayank

    2012-01-01

    Platelet-rich growth factor is an innovative regenerative therapy used to promote hard and soft tissue healing. It involves the application of autologous platelet-leukocyte-rich plasma containing growth factors and thrombin directly to the site of treatment. It is the intrinsic growth factors released by activated platelets which are concentrated in a topical gel formula. Clinically, it is an affordable treatment with potentially broad spectrum of applications in maxillofacial surgery especia...

  17. Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice

    Wei-hong Lin; Li-Jun Xiang; Hong-Xue Shi; Jian Zhang; Li-ping Jiang; Ping-tao Cai; Zhen-Lang Lin; Bei-Bei Lin; Yan Huang; Hai-Lin Zhang; Xiao-Bing Fu; Ding-Jiong Guo; Xiao-Kun Li; Xiao-Jie Wang; Jian Xiao

    2015-01-01

    Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric ana...

  18. Organisational Factors of Rapid Growth of Slovenian Dynamic Enterprises

    Pšeničny Viljem

    2013-01-01

    Full Text Available The authors provide key findings on the internal and external environmental factors of growth that affect the rapid growth of dynamic enterprises in relation to individual key organisational factors or functions. The key organisational relationships in a growing enterprise are upgraded with previous research findings and identified key factors of rapid growth through qualitative and quantitative analysis based on the analysis of 4,511 dynamic Slovenian enterprises exhibiting growth potential. More than 250 descriptive attributes of a sample of firms from 2011 were also used for further qualitative analysis and verification of key growth factors. On the basis of the sample (the study was conducted with 131 Slovenian dynamic enterprises, the authors verify whether these factors are the same as the factors that were studied in previous researches. They also provide empirical findings on rapid growth factors in relation to individual organisational functions: administration - management - implementation (entrepreneur - manager - employees. Through factor analysis they look for the correlation strength between individual variables (attributes that best describe each factor of rapid growth and that relate to the aforementioned organisational functions in dynamic enterprises. The research findings on rapid growth factors offer companies the opportunity to consider these factors during the planning and implementation phases of their business, to choose appropriate instruments for the transition from a small fast growing firm to a professionally managed growing company, to stimulate growth and to choose an appropriate growth strategy and organisational factors in order to remain, or become, dynamic enterprises that can further contribute to the preservation, growth and development of the Slovenian economy

  19. Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

    TAKAOKA, MUNENORI; Harada, Hideki; Andl, Claudia D; Oyama, Kenji; Naomoto, Yoshio; Dempsey, Kelly L.; Klein-Szanto, Andres J.; El-Deiry, Wafik S; GRIMBERG, ADDA; Nakagawa, Hiroshi

    2004-01-01

    Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most up-regulated gene. IGFBP-3 regulates cell proliferation through both insulin-like growth factor-dependent and independent mechanisms. We found that IGF...

  20. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    McLoughlin Paul

    2011-01-01

    Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

  1. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    Sands, Michelle

    2011-01-25

    Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

  2. Keratinocyte growth factor is a growth factor for mammary epithelium in vivo. The mammary epithelium of lactating rats is resistant to the proliferative action of keratinocyte growth factor.

    Ulich, T. R.; Yi, E. S.; Cardiff, R; Yin, S.; Bikhazi, N.; Biltz, R; Morris, C. F.; Pierce, G. F.

    1994-01-01

    Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family. KGF is secreted by stromal cells and affects epithelial but not mesenchymal cell proliferation. KGF injected intravenously was found to cause dramatic proliferation of mammary epithelium in the mammary glands of rats. KGF causes ductal neogenesis and intraductal epithelial hyperplasia but not lobular differentiation in nulliparous female rats. KGF causes ductal and lobular epithelial hyperplasia in male...

  3. Tumor epidermal growth factor receptor molecular imaging research

    Because of the importance of epidermal growth factor signaling pathway in oncogenesis, maintenance, and progression of different types of tumors, there are great significance that non-invasive monitoring of epidermal growth factor receptor (EGFR) in the diagnosis and the judge of therapeutic efficacy. The studys of radioactive tracers for EGFR have provided a good basis for the molecular imaging of EGFR. (authors)

  4. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor

    1986-01-01

    Epidermal regeneration depends on mitosis and migration of keratinocytes. Epidermal growth factor is known to stimulate growth of keratinocytes in vitro, thus it might be expected to promote wound healing. The results of this study show that topical application of biosynthetic human epidermal growth factor accelerates epidermal regeneration in split-thickness wounds and partial-thickness burns. The significant enhancement of epidermal regeneration suggests the potential for clinical use of ep...

  5. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

    Poulsen, Steen Seier

    1983-01-01

    The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300...... was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal...... growth factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition...

  6. Vascular Endothelial Growth Factor is a Secreted Angiogenic Mitogen

    Leung, David W.; Cachianes, George; Kuang, Wun-Jing; Goeddel, David V.; Ferrara, Napoleone

    1989-12-01

    Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.

  7. Abnormal growth factor and cytokine expression in Dupuytren's contracture.

    Baird, K S; Crossan, J F; Ralston, S H

    1993-01-01

    AIM--To analyse patterns of gene expression for peptide regulatory factors in patients with Dupuytren's contracture. METHODS--Tissue samples (palmer fascia) from 12 patients with Dupuytren's contracture and 12 controls were studied using the reverse transcription/polymerase chain reaction (RT/PCR) technique. RESULTS--Tissue from patients with Dupuytren's contracture expressed a higher percentage of peptide regulatory factors than that of controls: interleukin-1 alpha (83% v 16%; p < 0.01); interleukin-1 beta (66% v 8%; p < 0.01); transforming growth factor beta (75% v 25%; p < 0.02); and basic fibroblast growth factor (66% v 25%; p < 0.05). Platelet derived growth factors alpha and beta were also expressed more commonly (66% v 33% and 25% v 16%, respectively), but these differences were not significant. CONCLUSIONS--The increased prevalence of expression for the above mRNAs in Dupuytren's tissue is relevant as interleukin-1, basic fibroblast growth factor, and transforming growth factor beta stimulate the growth of fibroblasts and transforming growth factor beta also enhances production of collagen and other extracellular matrix proteins. Excessive local release of these peptide regulatory factors may have an important role in the pathogenesis of Dupuytren's contracture. Images PMID:8320323

  8. Growth Hormone, Insulin-Like Growth Factors, and the Skeleton

    Giustina, Andrea; Mazziotti, Gherardo; Canalis, Ernesto

    2008-01-01

    GH and IGF-I are important regulators of bone homeostasis and are central to the achievement of normal longitudinal bone growth and bone mass. Although GH may act directly on skeletal cells, most of its effects are mediated by IGF-I, which is present in the systemic circulation and is synthesized by peripheral tissues. The availability of IGF-I is regulated by IGF binding proteins. IGF-I enhances the differentiated function of the osteoblast and bone formation. Adult GH deficiency causes low ...

  9. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    TITLE:TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  10. Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

    Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.; Russell, J.D.; Trupin, J.S.

    1988-01-01

    Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloid fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.

  11. High-growth-factor implosions (HEP4)

    Landen, O.L.; Keane, C.J.; Hammel, B.A. [and others

    1996-06-01

    In inertial confinement fusion (ICF), the kinetic energy of an ablating, inward-driven, solid spherical shell is used to compressionally heat the low-density fuel inside. For a given drive, the maximum achievable compressed fuel density and temperature - and hence the maximum neutron production rate depend on the degree of shell isentropy and integrity maintained during the compression. Shell integrity will be degraded by hydrodynamic instability growth of areal density imperfections in the capsule. Surface imperfections on the shell grow as a result of the Richtmyer-Meshkov and Rayleigh-Taylor (RT) instabilities when the shell is accelerated by the ablating lower-density plasma. Perturbations at the outer capsule surface are transferred hydrodynamically to the inner surface, where deceleration of the shell by the lower-density fuel gives rise to further RT growth at the pusher-fuel interface.

  12. Epidermal growth factor receptor targeted molecularly therapies of cancers

    Epidermal growth factor receptor (EGFR) has been known to be a significant factor in the development and growth of many types of cancers. It is now accepted that the EGFR signal transduction net work plays an important role in multiple tumorigenic processes, contributing to cancer cell proliferation, angiogenesis, and metastasis, as well as protection from apoptosis. Recently, EGFR monoclonal antibodies (McAb) and epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors have been validated as new treatment approach for those EGFR-positive cancers and have shown activity aginst advanced, chemofractory cancers in clinical trials. This article focuses on three EGFR targeted molecularly therapies of cancers. (authors)

  13. Intestinal hormones and growth factors: Effects on the small intestine

    Laurie Drozdowski; Alan BR Thomson

    2009-01-01

    There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting,such as in persons with short bowel syndrome. In partⅠ, we focus first on insulin-like growth factors,epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide (GLP)-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.

  14. Vascular Endothelial Growth Factor/Placental Growth Factor Heterodimer Levels in Preterm Infants with Bronchopulmonary Dysplasia.

    Procianoy, Renato S; Hentges, Cláudia R; Silveira, Rita C

    2016-04-01

    Background Bronchopulmonary dysplasia (BPD) is associated with changes in pulmonary angiogenesis. However, the role of the vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer, an antiangiogenic factor, remains unknown in this disease. Objective To compare VEGF/PlGF levels in preterm infants with and without BPD. Methods This study was approved by the Institutional Review Board. Preterm neonates with birth weight institutions after 72 hours of life; death before blood collection; presence of major congenital malformations, inborn errors of metabolism, and early sepsis; and mothers with multiple pregnancies, TORCH infections, HIV infection, or autoimmune diseases. BPD was defined as the need for oxygen therapy for a period equal to or greater than 28 days, accompanied by radiographic changes compatible with the disease. Blood was collected from neonates in the first 72 hours of life. VEGF/PlGF levels were measured using the enzyme-linked immunosorbent assay method. The chi-square test, t-test, Mann-Whitney test, analysis of variance, and Kruskal-Wallis test were used for statistical analysis. Variables found to be significant in the univariate analysis were included in the multivariate analysis. Results Seventy-three patients were included (19 with BPD, 43 without BPD, and 11 neonates who died in the first 28 days of life), with a mean (SD) gestational age of 30.32 (2.88) weeks and birth weight of 1,288 (462) g. Median VEGF/PlGF levels were higher in the groups with BPD and death in the first 28 days of life than in the group without BPD (16.46 [IQR, 12.19-44.57] and 20.64 [IQR, 13.39-50.22], respectively, vs. 9.14 [IQR, 0.02-20.64] pg/mL], p < 0.001). Higher VEGF/P1GF levels remained associated with BPD and death in the first 28 days of life in the multivariate analysis. Conclusion Higher plasma VEGF/PlGF levels were found in preterm neonates with BPD and in those who died in the first 28 days of life, suggesting an

  15. Progress in Relevant Growth Factors Promoting the Growth of Hair Follicle

    Wang, J. M.; J. T. Zhang

    2012-01-01

    Hair is a protective appendage on the body that is considered accessory structure of the integument. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. The morphological changes of the hair cycle have been very clear that hair morphogenesis and epidermal development are orchestrated by an array of growth factors. In this review, we summarize the major growth factors involved in promoting growth of hair follicles

  16. Organizational Creativity: A Substantial Factor to Growth

    Malikeh Beheshtifar

    2013-03-01

    Full Text Available Organizations are increasingly seeking to foster creativity, because it is an important source of organizational innovation as well as competitive advantage. Creativity has been studied from different perspectives and is associated with a number of defining factors and elements. creative organization define as encompassing factors concerning the removal of barriers demonstrating managed innovation, idea evaluation procedures, motivational stimuli, communication procedures, development of idea sources, and evidence of the creative planning process; and organizational creativity is as the creation of a valuable, useful new product, service, idea, procedure, or process by individuals working together in a complex social system. The creative climate encourages people to generate new ideas and helps the organization to grow and increase its efficiency and at the same time it enables members to generate and implement creative ideas more effectively.

  17. Insulin-like growth factor 2

    Valleh, Mehdi Vafaye; Hyttel, Poul; Rasmussen, Mikkel Aabech;

    2014-01-01

    Intrinsic defects within the embryos, reflected by elevated cell death and low proliferative ability, are considered the most critical factors associated with bovine infertility. The identification of embryonic factors, which are responsible for successful embryo development, is thus critical in.......g., excellent, good, and poor) of bovine blastocysts produced by IVF. Variation in total blastocyst cell numbers as well as their allocation to inner cell mass and trophectoderm lineages were also determined by differential CDX2 staining. Results showed that transcript levels for IGF-II, BCL2-L1, and the BCL2-L...... not only greater total cell number but also greater mean inner cell mass/total cell number proportion than that of poor-quality blastocysts (P<0.01). The expression levels of IGF-II showed negative correlation with the levels of HSP70 (r=-0.70; P<0.05); however, the correlation of expression levels of...

  18. Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (IGF-I) in patients with epithelial ovarian carcinoma

    Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (EGF-I) were estimated in 58 patients with epithelial ovarian cancer and were correlated with clinically and biochemically important prognosticators. EGF-I levels were significantly low in patients as compared to controls. The relation of growth factors with clinically important prognosticators was non - significant. Moreover, the levels of EGF and IGF - I in ER+/PR+ and ER-/PR- groups and in the low and high EGFR + tumors did not differ significantly. Patients with EGF1.0 ng/ml. (author)

  19. An immunologic approach to induction of epidermal growth factor deficiency

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier;

    1995-01-01

    Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency....

  20. Factor Accumulation and Economic Growth in Pakistan: Incorporating Human Capital

    Arshad, Shahzad; Munir, Kashif

    2015-01-01

    The objective of this study is to analyze relationship between factor accumulation and economic growth in Pakistan for the time period of 1973 to 2014 using ARDL bound testing approach to cointegration. Considering human capital as a core factor of production we have constructed a series of human capital as average year of schooling and real capital stock is also generated on the basis of gross fixed capital formation. Under endogenous growth model bound testing approach to cointegration sugg...

  1. Clinical Application of Growth Factors and Cytokines in Wound Healing

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and crit...

  2. Neonatal Fibroblast Growth Factor Treatment Enhances Cocaine Sensitization

    Clinton, Sarah M; Turner, Cortney A.; Flagel, Shelly B.; Simpson, Danielle N.; Watson, Stanley J.; Akil, Huda

    2012-01-01

    Growth factors are critical in neurodevelopment and neuroplasticity, and recent studies point to their involvement in addiction. We previously reported increased levels of basic fibroblast growth factor (FGF2) in high novelty/drug-seeking rats (bred High Responders, bHR) compared to low novelty/drug-seeking rats (bred Low Responders, bLRs). The present study asked whether an early life manipulation of the FGF system (a single FGF2 injection on postnatal day 2) can impact cocaine sensitization...

  3. Cardiac Regeneration using Growth Factors: Advances and Challenges

    Juliana de Souza Rebouças; Nereide Stela Santos-Magalhães; Fabio Rocha Formiga

    2016-01-01

    Abstract Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remod...

  4. Exercise and angiogenic growth factors in human skeletal muscle

    Gustafsson, Thomas

    2005-01-01

    Long-term electrical stimulation and endurance exercise increase the amount of capillaries in skeletal muscle. VEGF-A is a well-characterized stimulatory angiogenic growth factor and has shown to play an important role in angiogenesis in pathological conditions in humans and in physiological conditions in animal models. A close relationship has recently been observed between VEGF-A and another group of endothelial specific growth factors, angiopoietins, during development an...

  5. Vascular Endothelial Growth Factor, diagnostic and therapeutic aspects

    Kusumanto, Yoka Hadiani

    2006-01-01

    This thesis focuses on the diagnostic and therapeutic potential of Vascular Endothelial Growth Factor, an angiogenic growth factor. Since the recognition of VEGF’s pivotal role in physiological and pathological angiogenesis research has evolved from cell culture and animal experiments to application in humans. The studies described in this thesis aim to contribute to the evaluation of circulating VEGF as a surrogate marker in the quantification of angiogenesis and of the therapeutic role of V...

  6. Factors that determine the evolution of high-growth businesses

    Oriol Amat

    2013-09-01

    Full Text Available Objective: The study herein discusses research aimed at elucidating the factors that contribute to a business’ ability to maintain high growth. Design/Methodology/Perspective: The database from the Iberian Balance Sheet Analysis System (SABI, from its initials in Spanish was used to identify 250 industrial Catalonian businesses with high growth during 2004-2007. These companies participated in a survey on strategies and management practices; in 2013, they were re-analyzed to investigate the factors that contributed to continued growth for certain companies. Contributions: Through diverse statistical techniques, business policies related to quality, innovation, internationalization and finance were shown to influence business growth and sustainability over time. Limitations of the Research: This study focuses on industrial businesses at least ten years old in Catalonia; thus, the conclusions may differ in other geographic locations and economic sectors, as well as for smaller businesses. Practical Implications: Because growth is a measure of business success, identifying variables that contribute to high growth and its sustainability is helpful for businesses that seek to adopt effective policies. Social Implications: Generating employment is one of the primary contributions by high-growth businesses. For years with high unemployment, authorities may be interested in corporate policies that strengthen high-growth businesses. Originality/Added Value: High-growth businesses have been studied throughout the world, but this is the first study to investigate the evolution of businesses after a high-growth phase.

  7. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis***

    Zhihong Chen; Songhe Yang; Yaqiang He; Chengjun Song; Yongping Liu

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mel itus. In this study, a rat type 2 diabetes mel itus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, fol owing which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to al eviate hippocampal damage in diabetic rats.

  8. LU分解的增长因子%ON GROWTH FACTORS OF THE LU FACTORIZATION

    魏木生; 刘巧华

    2008-01-01

    In this article, we derive upper bounds of different growth factors for the LU factorization, which are dominated by A11(k)-1A12(k),A21(k)A11(k)-1, where A11(k), A12(k), A21(k), A22(k) are sub-matrices of A. We also derive upper bounds of growth factors for the Cholesky factorization. Numerical examples are presented to verify our findings.

  9. EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMING GROWTH FACTOR-a AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS

    ZHANG; Long

    2001-01-01

    [1]LIU Xu-wen, FU Pei-yu, GAO Zhi-xian. Expression of epidermal growth factor receptors in human glioma [J]. Chin J Neurosurgery 1998; 14:71.[2]Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas [J]. Proc Natl Acad Sci USA 1992; 89:4309.[3]Webster J, Ham J, Bevan JS. Preliminary characterization of growth factors secreted by human pituitary tumors [J]. J Clin Endocrinol Metab 1991; 72:687.[4]Klibanski A. Nonsecreting pituitary tumors [J]. Endocrinol Metab Clin North Am 1987; 16:793.[5]LeRiche VK, Asa SL, Ezzat S. Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness [J]. J Clin Endocrinol Metab 1996; 81:656.

  10. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  11. Heparin-Binding Epidermal Growth Factor-like Growth Factor/Diphtheria Toxin Receptor in Normal and Neoplastic Hematopoiesis

    Fabrizio Vinante; Antonella Rigo

    2013-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) belongs to the EGF family of growth factors. It is biologically active either as a molecule anchored to the membrane or as a soluble form released by proteolytic cleavage of the extracellular domain. HB-EGF is involved in relevant physiological and pathological processes spanning from proliferation and apoptosis to morphogenesis. We outline here the main activities of HB-EGF in connection with normal or neoplastic differentiative or proliferativ...

  12. Intracellular growth factors in polycythemia vera and other myeloproliferative disorders.

    Eid, J.; Ebert, R F; Gesell, M S; Spivak, J L

    1987-01-01

    In polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis, hematopoietic cell proliferation is increased in the absence of a recognizable stimulus, suggesting the autonomous production of growth factors in these disorders. Sonicates of peripheral blood mononuclear cells (PBMNC) from patients with polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis contained soluble factors that stimulated the proliferation of quiescent-confluent 3T3 cells. PBMNC sonica...

  13. Instability restricts signaling of multiple fibroblast growth factors

    Buchtová, Marcela; Chaloupková, R.; Zakrzewska, M.; Veselá, I.; Celá, Petra; Barathová, J.; Gudernová, I.; Zajíčková, R.; Trantírek, L.; Martin, J.; Kostas, M.; Otlewski, J.; Damborský, J.; Kozubík, Alois; Wiedlocha, A.; Krejčí, P.

    2015-01-01

    Roč. 72, č. 12 (2015), s. 2445-2459. ISSN 1420-682X R&D Projects: GA ČR(CZ) GA14-31540S; GA ČR GBP302/12/G157 Institutional support: RVO:67985904 ; RVO:68081707 Keywords : fibroblast growth factor * FGF * unstable Subject RIV: EA - Cell Biology Impact factor: 5.808, year: 2014

  14. Risk Factors to Growth Retardation in Major Thalassemia

    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.

  15. Some Environmental Factors Affecting on Growth Characteristics

    N. Tuzemen

    2007-01-01

    Full Text Available Live weights, weight gains and some body measurements at different ages of Eastern Anatolian Red Cattle (EAR were determined and some environmental factors affecting on these traits were investigated. The effect of dam’s age on the birth weight was highly significant (P<0.01. Although the lowest birth weight was obtained from calves of dams at the 3 years of age, the highest birth weight was obtained from calves given birth by cows at the 5 years of age. The males had heavier live weights and weight gains at different ages than the females. The effect of the sex on the live weights except for 9 and 12 months weights was found as highly significant (P<0.01. Feeding of the calves with different amount of milk had significant (P<0.01 influence on the 3, 6 and 9 months weights as well as weight gains. The effect of the years on the daily weight gains in EAR was also highly significant (P<0.01. The results shows the importance of the environmental effects on the traits studied and revealed that there is need for them to be corrected prior to the improvement studies.

  16. Insulin-like growth factor-II: possible local growth factor in pheochromocytoma.

    Gelato, M C; Vassalotti, J

    1990-11-01

    Pheochromocytomas, neural crest tumors, express an abundance of insulin-like growth factor-II (IGF-II). To assess further the potential for IGF-II to play an autocrine role for these tumors, we measured 1) IGF-II content by RRA in 7 pheochromocytomas and peripheral blood in these patients, 2) IGF-II receptors by Western analysis, and 3) characterized the tumor binding proteins by ligand blot studies. IGF-II levels in the tumors varied from 2.8-41 micrograms/g. Chromatography revealed that 60% of the peptide eluted as a large mol wt form of IGF-II (8.7-10 kDa); the remainder coeluted with mature peptide (7.5 kDa). This was in contrast to IGF-II levels in normal adrenal tissue (0.225 +/- 0.005 micrograms/g) or another neural crest-derived tumor, medullary carcinoma of the thyroid (0.63 +/- 0.02 micrograms/g). Serum IGF-II levels in the 7 patients with pheochromocytoma (720 +/- 71 ng/mL) were similar to those in 35 normal controls (762 +/- 69 ng/mL). Radiolabeled IGF-II (9 +/- 1%) and IGF-I (20 +/- 2%) bound specifically to pheochromocytoma membranes. Western analysis of these membranes using a specific antiserum directed against the type II receptor demonstrated a band at 210 kDa. Affinity cross-linking studies with [125I]IGF-I demonstrated a specific band at 140 kDa. Ligand blot analysis was performed on the void volume pools from the Sephadex G-75 column and demonstrated bands at about 30 and 25 kDa. In conclusion, these data 1) confirm that pheochromocytomas have increased levels of IGF-II; 2) demonstrate that despite high IGF-II concentrations in the tumors, peripheral levels are not elevated, suggesting that very little tumoral IGF-II is released into the circulation, unlike catecholamines; 3) demonstrate the presence of IGF-II and IGF-I receptors; 4) describe binding protein species similar to those present in other tissues. Thus, the presence of high levels of IGF-II and both type I and type II receptors suggests that IGF II may act through both receptors to

  17. Making a tooth: growth factors, transcription factors, and stem cells

    Yah Ding ZHANG; Zhi CHEN; Yi Qiang SONG; Chao LIU; Yi Ping CHEN

    2005-01-01

    Mammalian tooth development is largely dependent on sequential and reciprocal epithelial-mesenchymal interactions.These processes involve a series of inductive and permissive interactions that result in the determination, differentiation,and organization of odontogenic tissues. Multiple signaling molecules, including BMPs, FGFs, Shh, and Wnt proteins,have been implicated in mediating these tissue interactions. Transcription factors participate in epithelial-mesenchymal interactions via linking the signaling loops between tissue layers by responding to inductive signals and regulating the expression of other signaling molecules. Adult stem cells are highly plastic and multipotent. These cells including dental pulp stem cells and bone marrow stromal cells could be reprogrammed into odontogenic fate and participated in tooth formation. Recent progress in the studies of molecular basis of tooth development, adult stem cell biology, and regeneration will provide fundamental knowledge for the realization of human tooth regeneration in the near future.

  18. Factor Function Characteristics and Origin of Economic Growth of China

    Zhiqing Dong; Linhui Wang; Jia Sun

    2011-01-01

    The paper makes an empirical study on factor contribution and its stage variation characteristics during 1952¨C2005 and 1978¨C2005 in China. GMM and OLS tests show that the robustness and significance level of the institution, the physical capital and human capital¡¯s contributions are much higher than other factors, and 70% of economic growth is boosted by the capital and the labor input. Factor contribution decomposition and TFP growth indicate trade has the most remarkable influence on eco...

  19. Factors affecting growth and pigmentation of Penicillium caseifulvum

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.; Larsen, Thomas Ostenfeld

    2002-01-01

    Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, Mg...... formation. Among the factors contributing to yellow color formation, pH and salt concentration are easy to control for the cheesemaker, while the third factor, P-concentration, is not. Naturally occurring variations in the P-concentration in milk delivered to Blue Cheese plants, could be responsible for the...... metabolites, appeared at low pH (pH 4). Mold growth was not correlated to the yellow color formation. Salt concentration was the most important factor affecting mold growth and length of lag phase. Production of secondary metabolites was strongly influenced by both pH and salt concentration. The screening...

  20. A placenta growth factor 2 variant acts as dominant negative of vascular endothelial growth factor A by heterodimerization mechanism

    Tarallo, Valeria; Tudisco, Laura; Falco, Sandro De

    2010-01-01

    Angiogenesis is one of the crucial events for cancer development and growth and vascular endothelial growth factor (VEGF) family plays an essential role in this biological phenomenon. The members of VEGF family mainly involved in angiogenesis are VEGF-A, VEGF-B and placental growth factor (PlGF), which exert their activity through the binding and activation of two VEGF receptors, VEGFR-1 and VEGFR-2. Human VEGF-A and PlGF are expressed in different isoforms and have the peculiarity to form he...

  1. Effects of Electromagnetic Field and Basic Fibroblast Growth Factor on Osteoblast's Growth

    GUOYong; ZHANGXi-zheng; WANGHao; LIBin; LIRui-xin; WUJin-hui; ZHAOYun-shan; WUJi-min

    2004-01-01

    Osteoblasts of rat cultured in vitro were stimulated with pulsed 50 Hz electromagnetic field and basic fibroblast growth factor(bFGF). The MTT method, flow cytometry and histochemistry staining were used to detect cell proliferation, cell cycle and alkaline phosphatase. The results indicated : after stimulated by 1 mT electromagnetic field, the cells are more abundant,have more S phase percentages, 2 mT electromagnetic field have no evident effect on cells' growth;compared with electromagnetic field, the cells stimulated by bFGF are more abundant and have larger S phase ratios. Electromagnetic field and bFGF have no effect on cells, alkaline phosphatase. Therefore ,we concluded that electromagnetic field can enhance osteoblasts growth like some growth factor such as basic fibroblast growth factor, and the osteoblasts', characteristics was not changed.

  2. Short-latency local actions of nerve growth factor at the growth cone.

    Seeley, P J; Greene, L A

    1983-01-01

    Cultures of neurite-bearing pheochromocytoma (PC12) cells and of sympathetic neurons have been examined by time-lapse video microscopy. In the presence of nerve growth factor (NGF), the neurites of such cultures elongated and their growth cones changed geometry, via microspike and lamellipodial motion, on a time scale of minutes. Withdrawal of NGF caused process extension to cease and a progressive reduction in growth-cone area as a result of retraction of lamellipodia and microspikes. By app...

  3. Active synthesis of epidermal growth factor in human mammary glands

    Mieczysław Walczak

    2010-06-01

    Full Text Available Background. Human milk contains considerable number of growth factors, including epidermal growth factor (EGF and insulin-like growth factor-1 (IGF-1. There are no data comparing the EGF and IGF-1 levels in the serum and milk of breast-feeding women. Therefore, the aim of our study was to assess a possible relationship between the concentrations of these growth factors. Material and methods. Thirty-nine women in child-birth were included in the study. All women provided blood and milk samples during the first six hours after delivery. EGF (by immunoenzymatic method and IGF-1 (by radioimmunossay method concentrations were measured in both media. Results. EGF breast milk concentrations ranged from 3.18 to 4.51 ng/ml and on average were significantly higher (p < 0.0001 than those found in the women’s serum (from 0.02 to 0.13 ng/ml. The opposite distribution was found for IGF-1 levels. Its milk concentrations ranged from 8.8 to 61.9 ng/ml and on average were significantly lower (p < 0.0001 than the serum concentrations (from 192.6 to 595.3 ng/ml. No correlation was found between the serum and milk concentrations of both growth factors. Conclusion. EGF seems to be synthesized locally in mammary glands, whereas IGF-1 probably permeates into the milk from the vascular bed.  

  4. Urinary transforming growth factors in neoplasia: separation of 125I-labeled transforming growth factor-alpha from epidermal growth factor in human urine

    Purified human epidermal growth factor (hEGF) from urine promotes anchorage-independent cell growth in soft agar medium. This growth is enhanced by transforming growth factor-beta (TGF-beta), and is specifically inhibited by hEGF antiserum. Transforming growth factors of the alpha type (TGF-alpha), potentially present in normal human urine or urine from tumor-bearing patients, also promote anchorage-independent cell growth and compete with EGF for membrane receptor binding. Consequently, TGF-alpha cannot be distinguished from urinary hEGF by these two functional assays. Therefore, a technique for separation of TGF-alpha and related peptides from urinary EGF based on biochemical characteristics would be useful. Radioiodination of characterized growth factors [mouse EGF (mEGF), hEGF, and rat TGF-alpha (rTGF-alpha)], which were then separately added to human urine, was used to evaluate a resolution scheme that separates TGF-alpha from the high level of background hEGF present in human urine. Methyl bonded microparticulate silica efficiently adsorbed the 125I-labeled mEGF, 125I-labeled hEGF, and 125I-labeled rTGF-alpha that were added to 24-h human urine samples. Fractional elution with acetonitrile (MeCN) of the adsorbed silica released approximately 70 to 80% of the 125I-labeled mEGF and 125I-labeled hEGF between 25 and 30% MeCN, and over 80% of the 125I-labeled rTGF-alpha between 15 and 25% MeCN, with retention after dialysis of less than 0.2 and 1.7% of the original urinary protein, respectively. A single-step enrichment of about 400-fold for mEGF and hEGF, and 50-fold for rTGF-alpha were achieved rapidly. 125I-labeled mEGF and 125I-labeled hEGF eluted later than would be predicted on the basis of their reported molecular weight of approximately 6000, whereas 125I-labeled rTGF-alpha eluted from Bio-Gel P-10 at an approximate molecular weight of 8000 to 9000

  5. Growth-promoting action and growth factor release by different platelet derivatives.

    Passaretti, F; Tia, M; D'Esposito, V; De Pascale, M; Del Corso, M; Sepulveres, R; Liguoro, D; Valentino, R; Beguinot, F; Formisano, P; Sammartino, G

    2014-01-01

    Abstract Platelet derivatives are commonly used in wound healing and tissue regeneration. Different procedures of platelet preparation may differentially affect growth factor release and cell growth. Preparation of platelet-rich fibrin (PRF) is accompanied by release of growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGFβ1), and several cytokines. When compared with the standard procedure for platelet-rich plasma (PRP), PRF released 2-fold less PDGF, but >15-fold and >2-fold VEGF and TGFβ1, respectively. Also, the release of several cytokines (IL-4, IL-6, IL-8, IL-10, IFNγ, MIP-1α, MIP-1β and TNFα) was significantly increased in PRF-conditioned medium (CM), compared to PRP-CM. Incubation of both human skin fibroblasts and human umbilical vein endothelial cells (HUVECs) with PRF-derived membrane (mPRF) or with PRF-CM enhanced cell proliferation by >2-fold (pVEGF in the PRF-CM. Thus, the procedure of PRP preparation leads to a larger release of PDGF, as a possible result of platelet degranulation, while PRF enhances the release of proangiogenic factors. PMID:23855408

  6. Factor income taxation, growth, and investment specific technological change

    Monisankar Bishnu; Chetan Ghate; Pawan Gopalakrishnan

    2013-01-01

    We construct a tractable endogenous growth model with production externalities in which the public capital stock augments investment speci?c technological change. We characterize the ?rst best ?scal policy and show that there exist several labor and capital tax-subsidy combinations that decentralize the planner?s growth rate. The optimal factor income tax mix is therefore indeterminate which gives the planner the flexibility to choose policy rules from a large set. Our model explains why many...

  7. Perinatal factors, growth and development, and osteosarcoma risk

    Troisi, R; Masters, M N; Joshipura, K; Douglass, C; Cole, B. F.; Hoover, R N

    2006-01-01

    Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients (n=158) and controls with benign orthopaedic conditions (n=141) under age 40 were recruited from US orthopaedic surgery departments. Exposures were ascertained by interview, birth, and growth records. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age- and sex-specific height percentiles were not associ...

  8. Insulin-like growth factor-1: roles in androgenetic alopecia.

    Panchaprateep, Ratchathorn; Asawanonda, Pravit

    2014-03-01

    Of all the cytokines or growth factors that have been postulated to play a role in hair follicle, insulin-like growth factor-1 (IGF-1) is known to be regulated by androgens. However, how IGF-1 is altered in the balding scalp has not yet been investigated. In this study, expressions of IGF-1 and its binding proteins by dermal papilla (DP) cells obtained from balding versus non-balding hair follicles were quantified using growth factor array. DP cells from balding scalp follicles were found to secrete significantly less IGF-1, IGFBP-2 and IGFBP-4 (P balding counterparts. Our data confirmed that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness. PMID:24499417

  9. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

    Fazio, Alessandro; Jewett, Michael Christopher; Daran-Lapujade, Pascale;

    2008-01-01

    Background: Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of Saccharomyces cerevisiae. The three...... factors we considered were specific growth rate, nutrient limitation, and oxygen availability. Results: We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which m...

  10. Nerve growth factor levels and localisation in human asthmatic bronchi.

    Olgart Höglund, C; de Blay, F; Oster, J P; Duvernelle, C; Kassel, O; Pauli, G; Frossard, N

    2002-11-01

    Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from

  11. The Effect of Insulin-Like Growth Factor System on Embryo Growth and Development

    H.B. Ciftci

    2011-10-01

    Full Text Available Insulin like growth factors (IGF-I and IGF-II are expressed in embryos and reproductive tracts of several species including cow, sheep and swine. They are mitogenic and have endocrine, paracrine and autocrine function infusing cell division, blastocyst formation, implantation and embryo growth. Increase in embryo growth will probably result with a higher implantation rates leading to consequent increases in the number of live offspring. In this review, insulin, IGFs, their receptors and their physiology and function in embryonic growth development were concerned.

  12. Small Is Beautiful: Insulin-Like Growth Factors and Their Role in Growth, Development, and Cancer

    Maki, Robert G.

    2010-01-01

    Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role in growth, development, organism survival, and in cancer, both epithelial cancers and sarcomas. Recent developments regarding phase I to II clinical trials of such agents are discussed, as well as potential studies to consider in the future, given the lack of efficacy of one such monoclonal antibody in combination with cytotoxic chemotherapy in a first-line study in metastatic non–small-cell lung adenocarcinoma. Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed. PMID:20975071

  13. Factor prices and productivity growth during the British Industrial Revolution

    Antras, Pol; Voth, Hans-Joachim

    2000-01-01

    This paper presents new estimates of total factor productivity growth in Britain for the period 1770–1860. We use the dual technique and argue that the estimates we derive from factor prices are of similar quality to quantity-based calculations. Our results provide further evidence, calculated on the basis of an independent set of sources, that productivity growth during the British Industrial Revolution was relatively slow. The Crafts–Harley view of the Industrial Revolution is thus rein...

  14. Preliminary evaluation of a radioimmunoassay for platelet derived growth factor

    Together with insulin and epidermal growth factor, platelet derived growth factor (PDGF) is one of the most important and powerful mitogens. The authors developed a radioimmunoassay (RIA) with a double incubation solid phase for human PDGF, in some biological fluids. Immunoglobulins were immobilized via protein A. using purified recombinant protein A at 1 mg/L with monoclonal antibody against human recombinant PDGF (BB) at 1000 fmol/tube, a binding capacity of approx. 17% was obtained. Non-specific binding (NSB%) was 50 ng/mL in 9 of 10 serum samples tested. (author). 18 refs, 8 figs

  15. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  16. Cytokines and growth factors which regulate bone cell function

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  17. The effects of hematopoietic growth factors on neurite outgrowth.

    Ye Su

    Full Text Available Stem cell factor (SCF and granulocyte colony-stimulating factor (G-CSF are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  18. Prognosis and risk factors for intrauterine growth retardation

    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. Cheiradone: a vascular endothelial cell growth factor receptor antagonist

    Ahmed Nessar

    2008-01-01

    Full Text Available Abstract Background Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing and pathological conditions (tumour development. Vascular endothelial growth factor (VEGF, fibroblast growth factor-2 (FGF-2 and epidermal growth factor (EGF are the major angiogenic regulators. We have identified a natural product (cheiradone isolated from a Euphorbia species which inhibited in vivo and in vitro VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation and in vivo (the chick chorioallantoic membrane models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC50 was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated. Results Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC50 values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC50 values of 2.9 and 0.61 μM respectively. Conclusion Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.

  20. TOTAL FACTOR PRODUCTIVITY - INFLUENCE FACTOR OF THE ECONOMIC GROWTH POTENTIAL. PRACTICAL APPLICATION

    Florina Popa

    2015-07-01

    Full Text Available Adequate to the new requirements of economy, the economic research has achieved progresses in addressing the issues regarding the growth and development, the economists drawing a number of theories and models, in order to find resorts that lead to sustainable growth. The paper refers to the means of assessment and forecast of the potential growth of an economy, by using a mathematical model, whose production function takes into consideration the role of three factors, being highlighted the role of the Total Factor Productivity, as an element of influence on growth with the other two factors. The study includes an application of the model use, for the analysis of the growth potential of the economy, at national level.

  1. Antivascular Endothelial Growth Factor Antibody for Treatment of Glioblastoma Multiforme

    Hanson, Joseph A.; Hsu, Frank P K; Jacob, Arun T; Bota, Daniela A.; Alexandru, Daniela

    2013-01-01

    Despite aggressive investigation, glioblastoma multiforme (GBM) remains one of the deadliest cancers, with low progression-free survival and high one-year mortality. Current first-line therapy includes surgery with adjuvant radiation therapy and cytotoxic chemotherapy, but virtually all tumors recur. Given the highly vascular nature of GBM and its high expression of vascular endothelial growth factor and other angiogenic factors, recent investigation has turned to bevacizumab, an antivascular...

  2. The role of macrophage derived growth factors in pulmonary fibrosis

    Factors released from rat alveolar macrophages exposed to high (95 μg/mL) concentrations of the fibrogenic agent, nickel subsulfide, were found to inhibit the proliferation of cultured lung epithelial cells and stimulate the growth of fibroblasts. Such factors, if present in the alveoli of rats exposed by inhalation to nickel subsulfide in vivo, may play a role in inhibiting re-epithelization of nickel-damaged lungs and in stimulating fibroblast proliferation, leading to pulmonary fibrosis. (author)

  3. Growth/differentiation factor-15: prostate cancer suppressor or promoter?

    Vaňhara, P.; Hampl, A.; Kozubík, Alois; Souček, Karel

    2012-01-01

    Roč. 15, č. 4 (2012), s. 320-328. ISSN 1365-7852 R&D Projects: GA MZd NS9600; GA MZd NS9956 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : MACROPHAGE-INHIBITORY CYTOKINE-1 * GROWTH-DIFFERENTIATION FACTOR-15 * TGF-BETA SUPERFAMILY Subject RIV: BO - Biophysics Impact factor: 2.811, year: 2012

  4. Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function

    Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix. The review will also highlight the involvement of the IGF axis in breast cancer

  5. Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1

    Dongliang Zhang

    2011-01-01

    Full Text Available Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE, water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. Results: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1 mRNA and protein level to increase HF size and hair length. Conclusions: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.

  6. Immunolocalization of transforming growth factor alpha in normal human tissues

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    immunoreactivity. TGF-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the...... anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical...

  7. Insulin-like growth factor-I and the liver

    Bonefeld, Karen; Møller, Søren

    2011-01-01

    has a strong antifibrotic effect that acts directly through the GH/IGF system and indirectly by the regulation of hepatoprotective and profibrogenic factors. It is most likely that IGF-I deficiency contributes to the diverse metabolic complications of cirrhosis. At present, liver transplantation......Insulin-like growth factors (IGFs) play an essential role in growth and development, as well as in the overall cellular regulation and metabolism in the human body. In chronic liver disease, IGF levels are decreased, and the circulating levels correlate to the extent of hepatocellular dysfunction...... consequences in cirrhosis are only partly understood. Disruption of the growth hormone (GH)-IGF-I axis seems to be closely associated with the development of liver disease, and treatment with recombinant human IGF (rhIGF)-I has been shown to halt, and even reverse, the fibrotic degeneration. IGF-I in itself...

  8. Vascular endothelial growth factor signaling in acute myeloid leukemia

    Kampen, Kim R.; ter Elst, Arja; de Bont, Eveline S. J. M.

    2013-01-01

    This review is designed to provide an overview of the current literature concerning vascular endothelial growth factor signaling (VEGF) in acute myeloid leukemia (AML). Aberrant VEGF signaling operates in the bone marrow of AML patients and is related to a poor prognosis. The altered signaling pathw

  9. Role of fibroblast growth factors in organ regeneration and repair.

    El Agha, Elie; Kosanovic, Djuro; Schermuly, Ralph T; Bellusci, Saverio

    2016-05-01

    In its broad sense, regeneration refers to the renewal of lost cells, tissues or organs as part of the normal life cycle (skin, hair, endometrium etc.) or as part of an adaptive mechanism that organisms have developed throughout evolution. For example, worms, starfish and amphibians have developed remarkable regenerative capabilities allowing them to voluntarily shed body parts, in a process called autotomy, only to replace the lost parts afterwards. The bizarre myth of the fireproof homicidal salamander that can survive fire and poison apple trees has persisted until the 20th century. Salamanders possess one of the most robust regenerative machineries in vertebrates and attempting to draw lessons from limb regeneration in these animals and extrapolate the knowledge to mammals is a never-ending endeavor. Fibroblast growth factors are potent morphogens and mitogens that are highly conserved among the animal kingdom. These growth factors play key roles in organogenesis during embryonic development as well as homeostatic balance during postnatal life. In this review, we provide a summary about the current knowledge regarding the involvement of fibroblast growth factor signaling in organ regeneration and repair. We also shed light on the use of these growth factors in previous and current clinical trials in a wide array of human diseases. PMID:26459973

  10. Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

    Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory;

    2010-01-01

    understanding of pathological processes. In our study we create and integrate data on phosphorylations that are initiated by several growth factor receptors. We present an approach for quantitative, time-resolved phosphoproteomic profiling that integrates the important contributions by phosphotyrosines. Methods...

  11. Hematopoietic growth factors for the treatment of myelodysplastic syndromes

    Hansen, P B; Penkowa, M; Johnsen, H E

    1998-01-01

    of leukemic myelopoiesis and subsequent progression into overt acute myeloid leukemia. In conclusion, combinations of hematopoietic growth factors may be of clinical benefit in some patients with MDS. However, due to the cost and unpredictable clinical outcome there is a need for extended laboratory research...... to understand the functional defects of MDS stem cells and progenitors....

  12. Human embryonic growth : Periconception parental and environmental factors

    E.M. van Uitert (Evelyne Mariët)

    2014-01-01

    markdownabstract__abstract__ Prenatal growth in the second half of pregnancy and subsequent birth weight have been studied for decades and have been shown to be associated not only with pregnancy outcome but also with health and disease in adult life. Many parental and environmental factors during

  13. Nerve Growth Factor in Cancer Cell Death and Survival

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  14. *609436 FIBROBLAST GROWTH FACTOR 21; FGF21 [OMIM

    Full Text Available FIELD NO 609436 FIELD TI 609436 FIBROBLAST GROWTH FACTOR 21; FGF21 FIELD TX CLONING Nishimura et ... f hypoglycemic effects. FGF21-transgenic mice were lean , had lower fasted glucose levels, were resistant t ... and 29 obese Chinese individuals compared with 105 lean ... controls. In 29 healthy premenopausal Chinese wome ...

  15. Mapping growth-factor-modulated Akt signaling dynamics.

    Gross, Sean M; Rotwein, Peter

    2016-05-15

    Growth factors alter cellular behavior through shared signaling cascades, raising the question of how specificity is achieved. Here, we have determined how growth factor actions are encoded into Akt signaling dynamics by real-time tracking of a fluorescent sensor. In individual cells, Akt activity was encoded in an analog pattern, with similar latencies (∼2 min) and half-maximal peak response times (range of 5-8 min). Yet, different growth factors promoted dose-dependent and heterogeneous changes in signaling dynamics. Insulin treatment caused sustained Akt activity, whereas EGF or PDGF-AA promoted transient signaling; PDGF-BB produced sustained responses at higher concentrations, but short-term effects at low doses, actions that were independent of the PDGF-α receptor. Transient responses to EGF were caused by negative feedback at the receptor level, as a second treatment yielded minimal responses, whereas parallel exposure to IGF-I caused full Akt activation. Small-molecule inhibitors reduced PDGF-BB signaling to transient responses, but only decreased the magnitude of IGF-I actions. Our observations reveal distinctions among growth factors that use shared components, and allow us to capture the consequences of receptor-specific regulatory mechanisms on Akt signaling. PMID:27044757

  16. Chemical strategies for the presentation and delivery of growth factors

    Cabanas Danés, Jordi; Huskens, Jurriaan; Jonkheijm, Pascal

    2014-01-01

    Since the first demonstration of employing growth factors (GFs) to control cell behaviour in vitro, the spatiotemporal availability of GFs in vivo has received continuous attention. In particular, the ability to physically confine the mobility of GFs has been used in various tissue engineering appli

  17. Factors affecting growth and pigmentation of Penicillium caseifulvum

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.;

    2002-01-01

    Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, M...

  18. Insulin infusion reduces hepatocyte growth factor in lean humans

    de Courten, Barbora; de Courten, Maximilian; Dougherty, Sonia;

    2013-01-01

    OBJECTIVE: Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF. MATERIALS/METHODS: Twenty-two parti...

  19. Signal transduction by growth factor receptors: signaling in an instant

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy; Andersen, Jens S

    2007-01-01

    mass spectrometry-based proteomics has allowed exciting views on the very early events in signal transduction. Activation profiles of regulated phosphorylation sites on epidermal growth factor receptor and downstream signal transducers showed different kinetics within the first ten seconds of...

  20. [Expression of tissue factor and vascular endothelial growth factor in colorectal carcinoma].

    Altomare, D F; Rotelli, M T; Memeo, V; Martinelli, E; Guglielmi, A; DeFazio, M; D'Elia, G; Pentimone, A; Colucci, M; Semeraro, N

    2003-01-01

    Tissue factor (TF) and vascular endothelial growth factor (VEGF) play an important role in tumor progression and metastasis. We analyzed their expression in the carcinoma and normal mucosa of 53 colorectal cancer patients. VEGF levels were significantly higher in the tumor and correlated with TF expression. No correlation was found with tumor stage. TF may influence tumor growth and metastasis by modulating VEGF expression and neoangiogenesis. PMID:12903530

  1. Transforming growth factor beta (TGF-β) in milk: a review

    Fernanda Lopes da Silva; Michele da Silva Pinto; Antônio Fernandes de Carvalho; Ítalo Tuler Perrone

    2016-01-01

    Bovine milk and colostrum contain growth factors such as insulin-like growth factor IGF-I, IGF-II, transforming growth factor TGF-β1, TGF-β2, epidermal growth factor EGF, basic fibroblast growth factor bFGF and platelet-derived growth factor PDGF. In recent years, intense scientific interest has been focused on the identification of factors within bovine milk that may be relevant to improving human health. Then a number of methodologies for the extraction of milk growth factors from milk, col...

  2. Insulin-like growth factor 1 and growth hormone in chronic liver disease

    Møller, Søren; Becker, Povl Ulrik

    1992-01-01

    Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of insulin-like growth factor 1 (IGF-1) is low in patients with chronic liver disease...... mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary, and...... hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver...

  3. COW PLACENTA EXTRACT PROMOTES MURINE HAIR GROWTH THROUGH ENHANCING THE INSULIN - LIKE GROWTH FACTOR-1

    Dongliang Zhang; Lijuan Gu; Jingjie Li; Zheng Li; Chunyan Wang; Zhen Wang; Lei Liu; Mira Li; Changkeun Sung

    2011-01-01

    Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE), water and minoxidil applied separately on the back of depilated B57CL/6 mice fo...

  4. In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

    Fernando M. Reis; Lhullier, Cintia; Edelweiss, Maria Isabel; Spritzer, Poli Mara

    2005-01-01

    Purpose: The present study evaluated the in vivo effect of medroxyprogesterone acetate (MPA) on the localization of immunoreactive transforming growth factor alpha (TGFα), epidermal growth factor (EGF), and their common receptor (EGF-R) in the human endometrium.

  5. Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation

    Sugiyama, Nami; Varjosalo, Markku; Meller, Pipsa; Lohi, Jouko; Hyytiäinen, Marko; Kilpinen, Sami; Kallioniemi, Olli; Ingvarsen, Signe; Engelholm, Lars H; Taipale, Jussi; Alitalo, Kari; Keski-Oja, Jorma; Lehti, Kaisa

    2010-01-01

    Aberrant expression and polymorphism of fibroblast growth factor receptor 4 (FGFR4) has been linked to tumor progression and anticancer drug resistance. We describe here a novel mechanism of tumor progression by matrix degradation involving epithelial-to-mesenchymal transition in response to memb...

  6. Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix

    Burgess, Janette K; Ge, Qi; Poniris, Maree H; Boustany, Sarah; Twigg, Stephen M; Black, Judith L; Johnson, Peter R A

    2006-01-01

    Airway remodeling describes the structural changes that occur in the asthmatic airway that include airway smooth muscle hyperplasia, increases in vascularity due to angiogenesis, and thickening of the basement membrane. Our aim in this study was to examine the effect of transforming growth factor-be

  7. Stimulation of glucose uptake by transforming growth factor β: evidence for the requirement of epidermal growth factor-receptor activation

    Transforming growth factor β (TGF-β), derived from human platelets, stimulates the uptake of 2-deoxyglucose by cultured cell monolayers 2- to 4-fold. Stimulation can be detected as early as 30 min with as little as 0.1 ng of TGF-β per ml and maximal effects can be obtained at 2 hr with 1 ng of the growth factor per ml. TGF-β-induced stimulation of sugar uptake is enhanced by the co-addition of platelet-derived growth factor (10 ng/ml) or epidermal growth factor (EGF, 1 ng/ml). The NR-6 variant of mouse 3T3 cells, which lack EGF receptors, is not stimulated by TGF-β. Antisera to EGF receptors that block 125I-labeled EGF binding also inhibit TGF-β stimulation of 2-deoxyglucose uptake, although 125I-labeled TGF-β binding remains unimpaired. In contrast, antisera to the EGF receptor, which do not block EGF binding, have no measurable effect on the TGF-β-stimulated uptake of 2-deoxyglucose. The authors confirm that the receptor for TGF-β is distinct from the receptor for EGF and the authors conclude that TGF-β stimulation of 2-deoxyglucose uptake requires the co-activation of the EGF receptor kinase system

  8. FGF19 functions as autocrine growth factor for hepatoblastoma

    Elzi, David J.; Song, Meihua; Blackman, Barron; Weintraub, Susan T.; López-Terrada, Dolores; Chen, Yidong; Tomlinson, Gail E.; Shiio, Yuzuru

    2016-01-01

    Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma. To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells. We determined that silencing FGF19 by shRNAs or neutralizing secreted FGF19 by anti-FGF19 antibody inhibits the proliferation of hepatoblastoma cells. Furthermore, blocking FGF19 signaling by an FGF receptor kinase inhibitor suppressed hepatoblastoma growth. RNA expression analysis in hepatoblastoma tumors revealed that the high expression of FGF19 signaling pathway components as well as the low expression of FGF19 signaling repression targets correlates with the aggressiveness of the tumors. These results suggest the role of FGF19 as autocrine growth factor for hepatoblastoma.

  9. Transforming growth factor (TGF)-α in human milk

    Transforming growth factor (TGF)-α and epidermal growth factor (EGF) were measured in human milk by means of homologous radioimmunoassay. As previously reported, EGF concentration in the colostrum was approximately 200 ng/ml and decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF-α was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the concentration of IR-TGF-α was fairly stable during the 7 postpartum days. There was no relationship between the concentrations of IR-TGF-α and IR-EGF, suggesting that the regulatory mechanism in the release of the two growth factors is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared in the fraction corresponding to that of authentic human EGF, while 70%-80% of the IR-TGF-α was eluted as a species with a molecular weight greater than that of authentic human TGF-α. Although the physiological role of TGF-α in milk is not known, it is possible that it is involved in the development of the mammary gland and/or the growth of newborn infants

  10. Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues.

    J.A. Takahashi; Mori, H.; Fukumoto, M; Igarashi, K; Jaye, M; Oda, Y.; Kikuchi, H; Hatanaka, M

    1990-01-01

    The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type beta were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meninglomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was signi...

  11. Steady Impact Factor Growth for MDPI Open Access Journals

    Alexander Thiesen

    2012-09-01

    Full Text Available For the past three years MDPI has announced the newly released impact factors for its Open Access journals by the means of an annual editorial [1–3]. In 2012 we are—once again—pleased to report that the growth of the impact factors of MDPI’s Open Access journals continues. This year’s edition of the Journal Citation Reports (JCR, which is published annually by Thomson Reuters, includes 10 journals published by MDPI, including three that have received their first official Impact Factors—International Journal of Environmental Research and Public Health (IJERPH, Materials and Nutrients. Table 1 reports the latest Impact Factors for 2011. Figure 1 graphically depicts the evolution of the Impact Factors for four MDPI open access journals that have received Impact Factors in the past. Table 2 reports the ranking of the MDPI journals within the subject categories of the Science Citation Index Expanded (SCIE.

  12. Therapeutic systems for Insulin-like growth factor-1

    Schultz, Isabel

    2015-01-01

    SUMMARY Insulin-like growth factor I (IGF-I) is a polypeptide with a molecular weight of 7.649 kDa and an anabolic potential. Thereby, IGF-I has a promising therapeutic value e.g. in muscle wasting diseases such as sarcopenia. IGF-I is mainly secreted by the liver in response to growth hormone (GH) stimulation and is rather ubiquitously found within all tissues. The effects of IGF-I are mediated by its respective IGF-I transmembrane tyrosine kinase receptor triggering the stimulation of pr...

  13. Growth Rate Factor Analysis of Turkey Using Grey System Theory

    Ceviz, Emre; Erden, Caner

    2015-01-01

    In this study, by using Grey System Theory (GST), factors of Gross Domestic Product (GDP) growth rate is analyzed. Macro-economic and financial data in the 2000s is used to evaluate the economic growth of Turkey. GST which can be used with little or inadequate amount of data, was preferred in the analysis. Although discovered in 1982, GST increases the amount of usage and publication especially after the 2000s. The gray system theory in the study focused on the impact on economic analysis. At...

  14. Insulin-like growth factor- I and factors affecting it in thalassemia major

    Ashraf T Soliman

    2015-01-01

    Full Text Available Despite improvement of blood transfusion regimens and iron chelation therapy growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis still occur in good number of thalassemic patients. Decreased IGF-1 secretion occurs in the majority of the thalassemic patients particularly those with growth and pubertal delay. Many factors contribute to this decreased synthesis of IGF-I including disturbed growth hormone (GH - insulin-like growth factor - I (IGF-I axis. The possible factors contributing to low IGF-I synthesis in thalassemia and the possible interaction between low IGF-I secretion and the occurrence of these complications is discussed in this mini-review. Improvement of IGF-I secretion in thalassemic patients should be intended to improve linear growth and bone mineral accretion in thalassemic patients. This can be attained through adequate correction of anemia and proper chelation, nutritional supplementation (increasing caloric intake, correction of vitamin D and zinc deficiencies, induction of puberty and correction of hypogonadism at the proper time and treating GH deficiency. This review paper provides a summary of the current state of knowledge regarding IGF-I and factors affecting it in patients with thalassaemia major (TM. Search on PubMed and reference lists of articles with the term ′IGF-I, GH, growth, thalassemia, thyroxine, anemia, vitamin D, and zinc′ was carried out. A hundred and forty-eight articles were found and used in the write up and the data analyzed was included in this report.

  15. Fatores determinantes do crescimento infantil Determinant factors of infant growth

    Sylvia de Azevedo Mello Romani

    2004-03-01

    Full Text Available Esta revisão enfoca os fatores que interferem no crescimento de crianças nos primeiros anos de vida. Foram utilizadas informações de artigos publicados em revistas científicas, teses e publicações de organizações internacionais. O crescimento infantil se constitui em um dos melhores indicadores de saúde da criança e o retardo estatural representa atualmente, a característica antropométrica mais representativa do quadro epidemiológico da desnutrição no Brasil. Ressaltando a importância do fator genético no crescimento, a revisão abrange com maior ênfase a atuação dos fatores extrínsecos, sabendo-se que o processo de crescimento resulta da interação entre a carga genética e os fatores do meio ambiente, os quais premitirão a maior ou menor expressão do potencial genético. Face a comprovada natureza multicausal do crescimento infantil, vários estudos têm sido desenvolvidos, buscando relacionar variáveis biológicas, socioeconômicas, maternas, ambientais, culturais, demográficas, nutricionais, entre outras, com a sua etiologia, seu desenvolvimento e sua manutenção. A revisão apresentada reforça o interesse em investigações sobre o crescimento na primeira infância que devem ser permanentes, devido, principalmente, às repercussões a longo prazo sobre a saúde infantil.This review focuses on factors interfering with growth during the first years of life. Information was collected from articles published in indexed scientific journals, theses, technical books and publications of international organizations. Infant growth is one of the best health indicators, and linear growth retardation is currently the most representative anthropometric characteristic of child nutrition epidemiology in Brazil. The review indicates the value of genetics in growth, focusing, however on the influence of the extrinsic factors. Growth process results from interaction between genetic and environmental factors, determining variation

  16. Does Single Intramuscular Application of Autologous Conditioned Plasma Influence Systemic Circulating Growth Factors?

    Gert Schippinger; Florian Fankhauser; Karl Oettl; Stefan Spirk; Peter Hofmann

    2012-01-01

    Platelet-rich plasma (PRP) has been employed to treat sports injuries to possibly accelerate healing and regeneration. This method offers some potential, especially for athletes. Growth factors are generally prohibited by the World Anti Doping Agency with exception to PRP which may induce adverse effects. The aim of this study was to evaluate any systemic increase of growth factors such as Insulin Like Growth Factor-1, Endothelial Growth Factors, Platelet-Derived Growth Factors, Fibroblast Gr...

  17. Effects of medium flow on axon growth with or without nerve growth factor.

    Kumamoto, Junichi; Kitahata, Hiroyuki; Goto, Makiko; Nagayama, Masaharu; Denda, Mitsuhiro

    2015-09-11

    Axon growth is a crucial process in regeneration of damaged nerves. On the other hand, elongation of nerve fibers in the epidermis has been observed in skin of atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an effective strategy to accelerate nerve regeneration and/or to reduce itching in pruritus dermatosis. We previously demonstrated that neurons and epidermal keratinocytes similarly contain multiple receptors that are activated by various environmental factors, and in particular, keratinocytes are influenced by shear stress. Thus, in the present study, we evaluated the effects of micro-flow of the medium on axon growth in the presence or absence of nerve growth factor (NGF), using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXIS™, consists of two chambers connected by a set of microgrooves, through which signaling molecules and axons, but not living cells, can pass. When DRG cells were present in chamber 1, NGF was present in chamber 2, and micro-flow was directed from chamber 1 to chamber 2, axon growth was significantly increased compared with other conditions. Acceleration of axon growth in the direction of the micro-flow was also observed in the absence of NGF. These results suggest that local micro-flow might significantly influence axon growth. PMID:26212442

  18. Growth factors in idiopathic pulmonary fibrosis: relative roles

    Allen Jeremy T

    2001-11-01

    Full Text Available Abstract Treatment of idiopathic pulmonary fibrosis patients has evolved very slowly; the fundamental approach of corticosteroids alone or in combination with other immunosuppressive agents has had little impact on long-term survival. The continued use of corticosteroids is justified because of the lack of a more effective alternative. Current research indicates that the mechanisms driving idiopathic pulmonary fibrosis reflect abnormal, dysregulated wound healing within the lung, involving increased activity and possibly exaggerated responses by a spectrum of profibrogenic growth factors. An understanding of the roles of these growth factors, and the way in which they modulate events at cellular level, could lead to more targeted therapeutic strategies, improving patients' quality of life and survival.

  19. Transforming growth factor-β and smooth muscle differentiation

    2012-01-01

    Transforming growth factor(TGF)-β family members are multifunctional cytokines regulating diverse cel- lular functions such as growth,adhesion,migration, apoptosis,and differentiation.TGF-βs elicit their effects via specific typeⅠand typeⅡserine/threonine kinase receptors and intracellular Smad transcription factors. Knockout mouse models for the different components of the TGF-β signaling pathway have revealed their critical roles in smooth muscle cell(SMC)differentia- tion.Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular disorders such as aorta aneurysm and congenital heart diseases due to SMC defects.In this review,the current understanding of TGF-β function in SMC differentiation is highlighted,and the role of TGF-βsignaling in SMC- related diseases is discussed.

  20. Soluble vascular endothelial growth factor in various blood transfusion components

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    sVEGF was determined in nonfiltered and prestorage white cell-reduced whole blood (WB), buffy coat-depleted saline-adenine-glucose-mannitol (SAGM) blood, platelet-rich plasma (PRP), and buffy coat-derived platelet (BCP) pools obtained from volunteer, healthy blood donors. As a control, total content...... of platelet-derived soluble plasminogen activator inhibitor type 1 (sPAI-1) was determined by an EIA in the same samples. Finally, the extracellular accumulation of sVEGF was determined in nonfiltered WB and SAGM blood during storage for 35 days and in BCP pools during storage for 7 days. RESULTS: In......BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. The...

  1. Ecological factors regulating growth of seaweeds in Arctic communities

    Shoshina E. V.

    2016-03-01

    Full Text Available Features of seaweeds in the Arctic communities in connection with periodic and unperiodic influences of ecological factors have been analyzed. It has been shown that the existence of benthic algae biocenosis of the northern seas is mainly controlled by the primary periodic environmental factors acting as triggers that determine the direction of vegetative and generative processes, as well as contribute to the emergence of adaptive devices to extreme environmental conditions. Therefore, periodic exposure to environmental factors cause only structural changes in plant communities due to the elastic stability of fucus algae populations acquired as a result of the long process of adaptation to the northern seas conditions. Unperiodic primary factors also violate the ratio of the number by elimination and inhibit growth of certain algae age stages. However thanks to the stability of resistant the algae community can eventually restore its structural and functional organization

  2. Adipocytokines, gut hormones and growth factors in anorexia nervosa.

    Kowalska, Irina; Karczewska-Kupczewska, Monika; Strączkowski, Marek

    2011-09-18

    Anorexia nervosa is a complex eating disorder of unknown etiology which affects adolescent girls and young women and leads to chronic malnutrition. Clinical manifestations of prolonged semistarvation include a variety of physical features and psychiatric disorders. The study of different biological factors involved in the pathophysiology of anorexia nervosa is an area of active interest. In this review we have described the role of adipocytokines, neurotrophins, peptides of the gastrointestinal system and growth factors in appetite regulation, energy balance and insulin sensitivity in anorexia nervosa patients. PMID:21699889

  3. Teamwork and technology: Success factors for creating growth

    The petroleum industry faces many challenges moving toward the next century. How effectively these challenges are addressed and managed will determine whether or not the exploration and production business grows and prospers in the future. This presentation relates to success factors for growth creation. Themes discussed here are succeeding in a global energy market, evolution of relationships between oil and gas companies and service companies, the power of technology, and effectively combining teamwork and technology

  4. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes

    Geetanjali Kharmate; Elham Hosseini-Beheshti; Josselin Caradec; Mei Yieng Chin; Tomlinson Guns, Emma S.

    2016-01-01

    Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa). However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR) as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it ...

  5. Human embryonic growth : Periconception parental and environmental factors

    Uitert, Evelyne Mariët

    2014-01-01

    markdownabstract__abstract__ Prenatal growth in the second half of pregnancy and subsequent birth weight have been studied for decades and have been shown to be associated not only with pregnancy outcome but also with health and disease in adult life. Many parental and environmental factors during pregnancy have been shown to influence birth weight. Yet although the embryonic period is perhaps the most important period of prenatal development as this is the period in which organogenesis is co...

  6. Proepithelin is an autocrine growth factor for bladder cancer

    Lovat, Francesca; Bitto, Alessandro; Xu, Shi-Qiong; Fassan, Matteo; Goldoni, Silvia; Metalli, David; Wubah, Vera; McCue, Peter; Serrero, Ginette; Gomella, Leonard G.; Baffa, Raffaele; Iozzo, Renato V.; Morrione, Andrea

    2009-01-01

    The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCO...

  7. The Fibroblast Growth Factor System is Downregulated Following Social Defeat

    Turner, Cortney A; Calvo, Nelson; Frost, Douglas O.; Akil, Huda; Watson, Stanley J.

    2007-01-01

    The fibroblast growth factor (FGF) system has previously been found to be altered in post-mortem brains of individuals with major depressive disorder (MDD). The present study tested whether the FGF system is altered following acute social defeat. Rats were exposed to four consecutive days of either a social defeat paradigm or novel cages. Animals were sacrificed after the last social defeat session and gene expression was assessed in the hippocampus by mRNA in situ hybridization. Molecular co...

  8. Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

    Hillman, Sara; Peebles, Donald M.; Williams, David J.

    2013-01-01

    OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who...

  9. Milk minor constituents, enzymes, hormones, growth factors, and organic acids

    Rodrigues, L. R.

    2013-01-01

    Milk and derived products contain essential nutrients, such as proteins, lactose, minerals, vitamins, and enzymes. Additionally, despite of their low concentrations in milk, many other minor constituents present important physiological and/or technological roles (e.g. hormones, growth factors). Dairy industries face many challenges regarding milk processing. Also, the full knowledge on these constituents’ physiological roles and effects on health is still lacking. Technological...

  10. Phylogenetic Analysis of Vascular Endothelial Growth Factor Diversity

    KASAP, Murat

    2005-01-01

    The secreted glycoprotein vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells, capable of stimulating angiogenesis during embryonic development and tumor formation. Despite intensive research, the functions of several VEGF family members remain a mystery. Insight into their evolutionary relationships could profoundly improve our understanding of why there are so many VEGFs and why we have not been able to dissect their function to our sati...

  11. Vascular Endothelial Growth Factor: Biology and Therapeutic Applications

    Ho, Quoc T.; Kuo, Calvin J.

    2007-01-01

    While the development of anti-angiogenic therapy, as it pertains to cancer treatment, may still be in its infancy relative to well-established modalities such as chemotherapy, radiation, and surgery, major strides made in the past several decades have allowed translation of basic science discoveries in this field into clinical reality. The discovery of key molecular modulators of angiogenesis, notably Vascular Endothelial Growth Factor (VEGF), has catalyzed the development of numerous neutral...

  12. EGF: new tricks for an old growth factor.

    Carpenter, G

    1993-04-01

    During the past year, the biology of epidermal growth factor (EGF) has been investigated in lower organisms (Caenorhabditis elegans, Drosophila and bacteria). These experiments have produced some surprising results: the identification of defects produced by mutation of EGF-like genes; the role of EGF receptors in bacterial invasion; and the role of EGF-like precursors as receptors for a bacteria toxin. PMID:8507498

  13. Factors of Economic Growth in Russia’s Regions

    Sergey Drobyshevsky; Oleg Lugovoy; Ekaterina Astafieva; Anna Kozlovskaya; Pavel Trunin; Lew Lederman

    2005-01-01

    The monograph deals with analysis of the factors that determine the diversity in the degree and pace of economic development of Russia's regions. In particular, basing on the data of main socio economic indicators of RF constituent regions' performance, the authors have empirically tested various convergence concepts and attempted to conduct decomposition of economic growth and assess the dynamics of labor productivity in Russia's regions. One of the sections of the monograph focuses on the C...

  14. Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

    Ye-Rang Yun; Jong Eun Won; Eunyi Jeon; Sujin Lee; Wonmo Kang; Hyejin Jo; Jun-Hyeog Jang; Ueon Sang Shin; Hae-Won Kim

    2010-01-01

    Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain opt...

  15. Transforming Growth Factor-β Induces Airway Smooth Muscle Hypertrophy

    Goldsmith, Adam M.; Bentley, J. Kelley; Zhou, Limei; Jia, Yue; Bitar, Khalil N; Fingar, Diane C.; Hershenson, Marc B.

    2005-01-01

    Although smooth muscle hypertrophy is present in asthmatic airways, little is known about the biochemical pathways regulating airway smooth muscle protein synthesis, cell size, or accumulation of contractile apparatus proteins. We sought to develop a model of airway smooth muscle hypertrophy in primary cells using a physiologically relevant stimulus. We hypothesized that transforming growth factor (TGF)-β induces hypertrophy in primary bronchial smooth muscle cells. Primary human bronchial sm...

  16. Epidermal growth factor receptor expression in canine transitional cell carcinoma

    HANAZONO, Kiwamu; Fukumoto, Shinya; KAWAMURA, Yoshio; ENDO, Yoshifumi; Kadosawa, Tsuyoshi; IWANO, Hidetomo; UCHIDE, Tsuyoshi

    2014-01-01

    Transitional cell carcinoma (TCC), a urinary bladder tumor with high mortality, is encountered commonly in dogs. Whereas overexpression of epidermal growth factor receptor (EGFR) is associated with development of human urinary bladder cancer, information on EGFR expression in canine TCC is lacking. In this study, EGFR protein and mRNA expression in canine normal bladder (n=5), polypoid cystitis (n=5) and TCC (n=25) were examined by immunohistochemistry and real-time polymerase chain reaction....

  17. The Insulin-Like Growth Factor System and Nutritional Assessment

    Callum Livingstone

    2012-01-01

    Over recent years there has been considerable interest in the role of the insulin-like growth factor (IGF) system in health and disease. It has long been known to be dysregulated in states of under- and overnutrition, serum IGF-I levels falling in malnourished patients and responding promptly to nutritional support. More recently, other proteins in this system have been observed to be dysregulated in both malnutrition and obesity. Currently no biochemical marker is sufficiently specific for u...

  18. Placental growth factor promotes atherosclerotic intimal thickening and macrophage accumulation

    Khurana, R.; Moons, L; Shafi, S.; A. Luttun; Collen, D; Martin, J. F.; Carmeliet, P.; Zachary, I. C.

    2005-01-01

    Background: Placental growth factor (PlGF) has been implicated in the pathophysiological angiogenesis and monocyte recruitment that underlie chronic inflammatory disease, but its role in atherosclerosis has not been examined. We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis...

  19. Posttraumatic Growth and Related Factors of Child Protective Service Workers

    Rhee, Young Sun; Ko, Young Bin; Han, In Young

    2013-01-01

    Objectives The aim of the study is to measure the level of vicarious trauma, posttraumatic growth (PTG), and other factors affecting PTG among child protective service workers. Methods We include posttraumatic stress, social support, stress coping, and demographic data as independent variables. Data was collected from 255 full-time social workers from 43 child protective agencies as acomplete enumeration and 204 included in the final analysis. Results The major findings of the study were as f...

  20. Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

    Lindsey, Richard C; Mohan, Subburaman

    2016-09-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis. PMID:26408965

  1. Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk

    Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formal that contained 1.2, 3.0, and 6.0 μg/ml EGF for 39 h had greater incorporation of [3H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate, in part, breast milk-enhanced neonatal intestinal growth

  2. INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS

    2000-01-01

    Objective To investigate the relationship between intrauterine growth retardation (IUGR) and en docrine parameters so as to assess the effects of the main endocrine factors on IUGR. The concentrations of growth hormone (GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum. Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants' weight were taken as control. Growth hormone and insulin were mea sured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentra tions of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH 4. 63μg/L vs 7.01μg/L, insulin 10. 68μIU/ml vs 31.44μIU/ml, T4 87. 39nmol/L vs 138. 10nmol/L. P <0. 05, 0. 05 and 0. 05, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (10. 84μmIU/L vs 5. 75μmIU/L, P <0. 01). The concentration of growth hormone in maternal serum and the concen tration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1.77μg/L vs 2.74μg/L, P <0. 01, insulin 5. 84μIU/mi vs 15. 64μIU/ml, P <0. 01). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relative scarcity of growth hormone and insulin seems to be a factor to compromise the fetus' metabolism. Be sides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

  3. Serum Levels of Growth Factors in Alcohol-dependent Patients according to Comorbid Depressive Symptoms

    Han, Changwoo; Ahn, Donghyun; Hahm, Woong; Nam, Junghyun; Park, Yongchon; Lim, Seulgi; Kim, Dai-Jin

    2016-01-01

    Objective This study aims to reveal the relationship of depression with growth factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and insulin-like growth factor-1 (IGF-1) in inpatients diagnosed with alcohol dependence, and to identify candidate growth factors as biological markers to indicate the comorbid of alcohol dependence and depression. Methods This study examined demographic factors in 45 alcohol-dependent patients. The ADS (Korean version of the Alco...

  4. ATP differentially upregulates fibroblast growth factor 2 and transforming growth factor α in neonatal and adult mice: effect on neuroproliferation.

    Jia, C; Cussen, A R; Hegg, C C

    2011-03-17

    Multiple neurotrophic factors play a role in proliferation, differentiation and survival in the olfactory epithelium (OE); however, the signaling cascade has not been fully elucidated. We tested the hypotheses that ATP induces the synthesis and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and transforming growth factor alpha (TGFα), and that these neurotrophic factors have a role in inducing proliferation. Protein levels of FGF2 and TGFα were increased 20 h post-intranasal instillation of ATP compared to vehicle control in adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor antagonist pyridoxal-phosphate-6-azophenyl-20,40-disulfonic acid (PPADS) significantly blocked this ATP-induced increase, indicating that upregulation of FGF2 and TGFα expression is mediated by purinergic receptor activation. However, in neonatal mouse, intranasal instillation of ATP significantly increased the protein levels of FGF2, but not TGFα. Likewise, ATP evoked the secretion of FGF2, but not TGFα, from neonatal mouse olfactory epithelial slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the role of FGF2 and TGFα in inducing proliferation, 5-bromo-2-deoxyuridine (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal treatment with FGF receptor inhibitor PD173074 or epidermal growth factor receptor inhibitor AG1478 following ATP instillation significantly blocked ATP-induced BrdU incorporation. Collectively, these data demonstrate that ATP induces proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFα synthesis and activation of their receptors. These data suggest that different mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFα may have different roles throughout development. PMID:21187124

  5. Mutagenesis of the crystal contact of acidic fibroblast growth factor

    Several mutations at Glu81 located on the crystal contact of human acidic fibroblast growth factor were studied in an effort to improve crystal growth. Mutation to Ser and Thr resulted in crystallization of a rather bulky form of the wild type, whereas mutation to Val prohibited crystallization. These results suggest that crystal growth may be controlled by designing a new interface by protein engineering. An attempt has been made to improve a crystal contact of human acidic fibroblast growth factor (haFGF; 140 amino acids) to control the crystal growth, because haFGF crystallizes only as a thin-plate form, yielding crystals suitable for X-ray but not neutron diffraction. X-ray crystal analysis of haFGF showed that the Glu81 side chain, located at a crystal contact between haFGF molecules, is in close proximity with an identical residue related by crystallographic symmetry, suggesting that charge repulsion may disrupt suitable crystal-packing interactions. To investigate whether the Glu residue affects the crystal-packing interactions, haFGF mutants in which Glu81 was replaced by Ala, Val, Leu, Ser and Thr were constructed. Although crystals of the Ala and Leu mutants were grown as a thin-plate form by the same precipitant (formate) as the wild type, crystals of the Ser and Thr mutants were grown with increased thickness, yielding a larger overall crystal volume. X-ray structural analysis of the Ser mutant determined at 1.35 Å resolution revealed that the hydroxy groups of Ser are linked by hydrogen bonds mediated by the formate used as a precipitant. This approach to engineering crystal contacts may contribute to the development of large protein crystals for neutron crystallography

  6. Role of growth factors in the growth of normal and transformed cells

    Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both 125I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product

  7. Vascular Endothelial Growth Factor A Regulates the Secretion of Different Angiogenic Factors in Lung Cancer Cells.

    Frezzetti, Daniela; Gallo, Marianna; Roma, Cristin; D'Alessio, Amelia; Maiello, Monica R; Bevilacqua, Simona; Normanno, Nicola; De Luca, Antonella

    2016-07-01

    Vascular endothelial growth factor A (VEGFA) is one of the main mediators of angiogenesis in non-small cell lung cancer (NSCLC). Recently, it has been described an autocrine feed-forward loop in NSCLC cells in which tumor-derived VEGFA promoted the secretion of VEGFA itself, amplifying the proangiogenic signal. In order to investigate the role of VEGFA in lung cancer progression, we assessed the effects of recombinant VEGFA on proliferation, migration, and secretion of other angiogenic factors in A549, H1975, and HCC827 NSCLC cell lines. We found that VEGFA did not affect NSCLC cell proliferation and migration. On the other hand, we demonstrated that VEGFA not only produced a strong and persistent increase of VEGFA itself but also significantly induced the secretion of a variety of angiogenic factors, including follistatin (FST), hepatocyte growth factor (HGF), angiopoietin-2 (ANGPT2), granulocyte-colony stimulating factor (G-CSF), interleukin (IL)-8, leptin (LEP), platelet/endothelial cell adhesion molecule 1 (PECAM-1), and platelet-derived growth factor bb (PDGF-BB). PI3K/AKT, RAS/ERK, and STAT3 signalling pathways were found to mediate the effects of VEGFA in NSCLC cell lines. We also observed that VEGFA regulation mainly occurred at post-transcriptional level and that NSCLC cells expressed different isoforms of VEGFA. Collectively, our data suggested that VEGFA contributes to lung cancer progression by inducing a network of angiogenic factors, which might offer potential for therapeutic intervention. PMID:26542886

  8. An expandable, inducible hemangioblast state regulated by fibroblast growth factor.

    Vereide, David T; Vickerman, Vernella; Swanson, Scott A; Chu, Li-Fang; McIntosh, Brian E; Thomson, James A

    2014-12-01

    During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that "trap" murine cells in a proliferative state and endow them with a hemangioblast potential. These "expandable" hemangioblasts (eHBs) are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines. PMID:25458896

  9. Expression of transforming growth factor alpha and epidermal growth factor receptor in rat lung neoplasms induced by plutonium-239

    Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation. 44 refs., 4 figs., 1 tab

  10. Insulin-like growth factor-I in growth and metabolism

    Backeljauw, P; Bang, P; Dunger, D B; Juul, A; Le Bouc, Y; Rosenfeld, R

    proper interpretation of data. Recombinant human IGF-I (rhIGF-I) treatment improves stature in patients with severe primary IGFD, and has also been shown to improve glycaemic control and insulin sensitivity in patients with severe insulin resistance. Ongoing studies of patients receiving rhIGF-I will......Deficiency of insulin-like growth factor-I (IGF-I) results in growth failure. A variety of molecular defects have been found to underlie severe primary IGF-I deficiency (IGFD), in which serum IGF-I concentrations are substantially decreased and fail to respond to GH therapy. Identification of more...

  11. Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

    Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

    2016-08-01

    Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival. PMID:26943480

  12. Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes

    Smith Logan B

    2012-12-01

    Full Text Available Abstract Background Fibroblast growth factor receptor 3 (FGFR3 inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone (T3 plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase (TERT and RNA component of telomerase (TR, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity (p 3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity (p 3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions The results suggest that FGFR3 inhibits chondrocyte proliferation by down-regulating TERT expression and reducing telomerase activity indicating an important role for telomerase in sustaining chondrocyte proliferative capacity during bone elongation.

  13. Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.

    Rosenthal, S M; Hulse, J A; Kaplan, S L; Grumbach, M. M.

    1986-01-01

    Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-N...

  14. Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma

    Wang, Qifeng; Zhu, Hongxia; Xiao, Zefen; Zhang, Wencheng; Liu, Xiao; Zhang, Xun; He, Jie; Kelin SUN; Wang, Lvhua; Xu, Ningzhi

    2013-01-01

    Background The overall survival of patients with esophageal squamous cell carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based on histological assessment of tumor invasion and lymph node metastasis, but a biomarker with better predictive accuracy could be more useful. Because overexpression of epidermal growth factor receptor (EGFR) has been associated with poor prognosis, this study investigated whether EGFR is an independent prognostic factor for overall survival ...

  15. The growth factor independence-1 transcription factor: New functions and new insights☆

    Kazanjian, Avedis; Gross, Eleanore A.; Grimes, H. Leighton

    2006-01-01

    The growth factor independence-1 (Gfi1) transcription factor is required for proper development of neuroendocrine cells, sensory neurons, and blood. Patients with mutations in Gfi1 exhibit severe congenital neutropenia (SCN) or non-immune chronic idiopathic neutropenia of adults. Gfi1 was initially described as an oncoprotein that mediates tumor progression in a mouse model of leukemia; however, recent data suggest that Gfi1 may act as either an oncogene or an anti-proliferative tumor suppres...

  16. The discovery of angiogenic growth factors: the contribution of Italian scientists

    Ribatti, Domenico

    2014-01-01

    Angiogenesis is regulated, under both physiological and pathological conditions, by numerous “non-classic” pro-angiogenic factors, including fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and “non-classic” pro-angiogenic factors, including granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and erythropoietin (EPO). In the context of the most important discoveries in this ...

  17. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment

  18. Epidermal growth factor receptor in primary human lung cancer

    Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g-1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g-1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

  19. Interdependent epidermal growth factor receptor signalling and trafficking.

    Jones, Sylwia; Rappoport, Joshua Z

    2014-06-01

    Epidermal growth factor (EGF) receptor (EGFR) signalling regulates diverse cellular functions, promoting cell proliferation, differentiation, migration, cell growth and survival. EGFR signalling is critical during embryogenesis, in particular in epithelial development, and disruption of the EGFR gene results in epithelial immaturity and perinatal death. EGFR signalling also functions during wound healing responses through accelerating wound re-epithelialisation, inducing cell migration, proliferation and angiogenesis. Upregulation of EGFR signalling is often observed in carcinomas and has been shown to promote uncontrolled cell proliferation and metastasis. Therefore aberrant EGFR signalling is a common target for anticancer therapies. Various reports indicate that EGFR signalling primarily occurs at the plasma membrane and EGFR degradation following endocytosis greatly attenuates signalling. Other studies argue that EGFR internalisation is essential for complete activation of downstream signalling cascades and that endosomes can serve as signalling platforms. The aim of this review is to discuss current understanding of intersection between EGFR signalling and trafficking. PMID:24681003

  20. Inhibition of placenta growth factor with TB-403

    Nielsen, Dorte Lisbet; Sengeløv, Lisa

    2012-01-01

    targeting angiogenesis. AREAS COVERED: The data are obtained by searching in the PubMed database. The search terms used included antiangiogenic therapy, TB-403 (RO5323441), placenta growth factor (PlGF) and VEGFR-1 (Flt-1). We review preclinical data concerning the function and inhibition of PlGF and...... summarize data on expression of PlGF in cancer patients. Data from early-phase clinical trials of TB-403 (RO5323441), a monoclonal antibody inhibiting PlGF, are discussed. Future development strategies, therapeutic potentials and limitations of TB-403 are further evaluated. EXPERT OPINION: There are some...... conflicting data on the function of PlGF and the importance of its role in primary tumor growth. Data from some preclinical models of PlGF inhibition and early-phase clinical trials with TB-403 are, however, promising, although the true potential of the drug is yet to be determined. Further clinical...

  1. The emerging role of hepatocyte growth factor in renal diseases.

    Mao, Song; Zhang, Jianhua

    2016-06-01

    Hepatocyte growth factor (HGF), a kringle-containing polypeptide, acts on various epithelial cells to regulate cell growth, cell motility, and morphogenesis. HGF also accelerates tissue regeneration of injured organs and is regarded as a key molecule in organ regeneration. Besides the regeneration of the liver, HGF also plays a role in the renal regeneration. In addition, an adaptive alteration of HGF status in various renal diseases occurs. However, the precise role of HGF in various renal diseases remains elusive. The signaling pathways of HGF may be associated with renal diseases. In this review, we will try to provide an in-depth understanding of the underlying role of HGF and its possible interactions with other molecules in renal diseases. PMID:26460681

  2. Epidermal growth factor in mammary glands and milk from rats

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba;

    1993-01-01

    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF......-immunoreactivity was revealed homogeneously in the cytoplasm of the secretory cells, which might suggest that EGF is present as a precursor molecule in the mammary glands. Altered glucose metabolism during lactation results in secondary hypoinsulinaemia in the lactating rat. As insulin is also known to affect...... lactation in several species, we treated normal lactating rats daily with insulin and studied the effect on the composition of milk. A significant increase in the content of total protein and milk fat was observed after a few days of insulin-treatment, as compared to a control group [total protein: 50 (36...

  3. Rapamycin promotes Schwann cell migration and nerve growth factor secretion

    Fang Liu; Haiwei Zhang; Kaiming Zhang; Xinyu Wang; Shipu Li; Yixia Yin

    2014-01-01

    Rapamycin, similar to FK506, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of rapamycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration (1.53 nmol/L) more signiifcantly promoted Schwann cell migration than the highest FK506 concentration (100μmol/L). Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not signiifcantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.

  4. Concentration Variations of Growth Factors in Colostrum and Normal Milk of Sows

    LI Yao; SHAN An-shan; FENG Zi-ke

    2004-01-01

    An experiment was conducted to determine the concentration variation of epidermal growth factors (EGF), include insulin-like growth factor - Ⅰ (IGF- I ), transforming growth factor-beta(TGF-β), and basic fibroblast growth factor (bFGF) in colostrum and normal milk of sows within 35 days after parturition. The results showed that the concentration of EGF, IGF- I , TGF-β, bFGF was significantly higher in colostrum than that in normal milk. The concentration of these growth factors in colostrum was significantly decreased with the stage lapse of lactation, and then they remained stable in normal milk. Parity had a slight effect on the concentration of these growth factors.

  5. Insulin-like growth factor binding proteins: a structural perspective

    Briony eForbes

    2012-03-01

    Full Text Available Insulin-like growth factor binding proteins (IGFBP-1 to -6 bind insulin-like growth factors-I and -II (IGF-I and IGF-II with high affinity. These binding proteins maintain IGFs in the circulation and direct them to target tissues, where they promote cell growth, proliferation, differentiation and survival via the type 1 IGF receptor (IGF-1R. IGFBPs also interact with many other molecules, which not only influence their modulation of IGF action but also mediate IGF-independent activities that influence processes such as cell migration and apoptosis by influencing gene transcription.IGFBPs-1 to -6 are structurally similar proteins consisting of three distinct domains, N-terminal, Linker and C-terminal. There have been major advances in our understanding of IGFBP structure in the last decade and a half. While there is still no structure of an intact IGFBP to date, several structures of individual N- and C-domains have been solved. The structure of a complex of N-BP-4:IGF-I:C-BP-4 has also been solved, providing a detailed picture of the structural features of the IGF binding site and the mechanism of binding. Structural studies have also identified features important for interaction with extracellular matrix components and integrins. This review summarises structural studies reported so far and highlights features important for binding not only IGF but also other partners. It also highlights future directions in which structural studies will add to our knowledge of the role played by the IGFBP family in normal growth and development, as well as in disease.

  6. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  7. Hematological and hepatic effects of vascular epidermal growth factor (VEGF) used to stimulate hair growth in an animal model

    Gnann, Laís Angelo; Castro, Rafael Ferreira; Azzalis, Ligia Ajaime; Feder, David; Perazzo, Fabio Ferreira; Pereira, Edimar Cristiano; Rosa, Paulo César Pires; Junqueira, Virginia Berlanga Campos; Rocha, Katya Cristina; Machado, Carlos D’ Aparecida; Paschoal, Francisco Camargo; de Abreu, Luiz Carlos; Valenti, Vitor Engrácia; Fonseca, Fernando Luiz Affonso

    2013-01-01

    Background Alopecia areata is the hair loss usually reversible, in sharply defined areas. The treatment of alopecia using growth factors shows interesting activity in promoting hair growth. In this concept, VEGF (vascular endothelial growth factor) is a marker of angiogenesis, stimulating hair growth by facilitating the supply of nutrients to the hair follicle, increasing follicular diameter. The aim of this study was the evaluation of a topical gel enriched with VEGF liposomes on the hair gr...

  8. Defining human insulin-like growth factor I gene regulation.

    Mukherjee, Aditi; Alzhanov, Damir; Rotwein, Peter

    2016-08-01

    Growth hormone (GH) plays an essential role in controlling somatic growth and in regulating multiple physiological processes in humans and other species. Insulin-like growth factor I (IGF-I), a conserved, secreted 70-amino acid peptide, is a critical mediator of many of the biological effects of GH. Previous studies have demonstrated that GH rapidly and potently promotes IGF-I gene expression in rodents and in some other mammals through the transcription factor STAT5b, leading to accumulation of IGF-I mRNAs and production of IGF-I. Despite this progress, very little is known about how GH or other trophic factors control human IGF1 gene expression, in large part because of the absence of any cellular model systems that robustly express IGF-I. Here, we have addressed mechanisms of regulation of human IGF-I by GH after generating cells in which the IGF1 chromosomal locus has been incorporated into a mouse cell line. Using this model, we found that physiological levels of GH rapidly stimulate human IGF1 gene transcription and identify several potential transcriptional enhancers in chromatin that bind STAT5b in a GH-regulated way. Each of the putative enhancers also activates a human IGF1 gene promoter in reconstitution experiments in the presence of the GH receptor, STAT5b, and GH. Thus we have developed a novel experimental platform that now may be used to determine how human IGF1 gene expression is controlled under different physiological and pathological conditions. PMID:27406741

  9. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia.

    Wang, Zongwei; Olumi, Aria F

    2011-01-01

    Diabetes significantly increases the risk of benign prostatic hyperplasia (BPH) and low urinary tract symptoms (LUTS). The major endocrine aberration in connection with the metabolic syndrome is hyperinsulinemia. Insulin is an independent risk factor and a promoter of BPH. Insulin resistance may change the risk of BPH through several biological pathways. Hyperinsulinemia stimulates the liver to produce more insulin-like growth factor (IGF), another mitogen and an anti-apoptotic agent which binds insulin receptor/IGF receptor and stimulates prostate growth. The levels of IGFs and IGF binding proteins (IGFBPs) in prostate tissue and in blood are associated with BPH risk, with the regulation of circulating androgen and growth hormone. Stromal-epithelial interactions play a critical role in the development and growth of the prostate gland and BPH. Previously, we have shown that the expression of c-Jun in the fibroblastic stroma can promote secretion of IGF-I, which stimulates prostate epithelial cell proliferation through activating specific target genes. Here, we will review the epidemiologic, clinical, and molecular findings which have evaluated the relation between diabetes and development of BPH. PMID:21536370

  10. The distribution and excretion of nerve growth factor in mice

    Nerve growth factor (NGF) was iodolabelled with chloramine-T method and its distribution and excretion in mice were investigated. The results showed that the highest levels were found in superior cervical ganglia, thyroid, bile, kidneys and adrenals between 20-30 min after injection, and the peak time in most tissues was also found at 20-30 min. About 72.55% of the injected dose was excreted in stool and urine, among them 65.6% was excreted in urine and only 7.0% in stool within 72 h after intramuscular injection

  11. Astrocyte Mitogen Inhibitor Related to Epidermal Growth Factor Receptor

    Nieto-Sampedro, Manuel

    1988-06-01

    Epidermal growth factor (EGF) is a well-characterized polypeptide hormone with diverse biological activities, including stimulation of astrocyte division. A soluble astrocyte mitogen inhibitor, immunologically related to the EGF receptor, is present in rat brain. Injury to the brain causes a time-dependent reduction in the levels of this inhibitor and the concomitant appearance of EGF receptor on the astrocyte surface. Intracerebral injection of antibody capable of binding the inhibitor caused the appearance of numerous reactive astrocytes. EGF receptor-related inhibitors may play a key role in the control of glial cell division in both normal and injured brain.

  12. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Santiago Vernia; Julie Cavanagh-Kyros; Tamera Barrett; Cathy Tournier; Roger J. Davis

    2016-01-01

    The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21) is a target of the hepatic JNK signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21-deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. ...

  13. Renal origin of rat urinary epidermal growth factor

    Nexø, Ebba; Poulsen, Steen Seier

    1984-01-01

    The origin of rat urinary epidermal growth factor (EGF) has been investigated. Unilateral nephrectomy decreased the concentration, total output of EGF and EGF/creatinine ratio by approximately 50%, while the output of creatinine was unchanged. Removal of the submandibular glands and duodenal......-phase HPLC. At isoelectric focusing the pI of submandibular EGF was 4.8 and 5.4 while that of urinary EGF was 5.3 and 6.4. In conclusion, this study demonstrates that urinary EGF mainly originates from the kidneys and is localized to the renal juxtaglomerular apparatus....

  14. Immunohistochemical localization of epidermal growth factor in rat and man

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands is...... well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  15. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity.

    Hartnett, M Elizabeth

    2014-12-01

    In this article, the growing problem of retinopathy of prematurity (ROP) worldwide, treatments for severe ROP including standard-of-care laser treatment, and the need for new treatments are discussed. Also discussed are the reasons to consider inhibiting the vascular endothelial growth factor (VEGF) signaling pathway in severe ROP and the concerns about broad VEGF inhibition. Finally, the potential role of VEGF in ROP based on studies in animal models of oxygen-induced retinopathy, the effects of anti-VEGF based on basic research data, and the clinical relevance of these data are covered. PMID:25459781

  16. Treatment of Skin Avulsion Injuries with Basic Fibroblast Growth Factor

    Hajime Matsumine, MD, PhD

    2015-01-01

    Summary: This report describes favorable outcomes in 9 patients with skin avulsion injuries of the extremities who underwent full-thickness skin grafting and basic fibroblast growth factor (bFGF) application. Following removal of contaminated subcutaneous fat tissue on the inside of skin, the avulsed skin was processed into a full-thickness skin graft, with as much of the skin used as possible irrespective of damage. Several drainage holes (5–10 mm in diameter) were made on the graft for drai...

  17. Preparing T Cell Growth Factor from Rat Splenocytes

    Beeton, Christine; Chandy, K. George

    2007-01-01

    Maintenance of antigen-specific T cell lines or clones in culture requires rounds of antigen-induced activation separated by phases of cell expansion 1,2. Addition of interleukin 2 to the culture media during the expansion phase is necessary to prevent cell death and sufficient to maintain short-term T cell lines but has been shown to increase Th1 polarization 3. Replacement of interleukin 2 by T cell growth factor (TCGF) which contains a mix of cytokines is more effective than interleukin 2...

  18. Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury

    Doan, Phuong L.; Himburg, Heather A.; Helms, Katherine; Russell, J. Lauren; Fixsen, Emma; Quarmyne, Mamle; Harris, Jeffrey R; Deoliviera, Divino; Sullivan, Julie M.; Chao, Nelson J.; Kirsch, David G.; Chute, John P

    2013-01-01

    The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2+ cells (Tie2Cre;Bak1−/−;Baxfl/− mice), which displayed radioprotection of the HSC pool and 100% survival following lethal dose total body irradiation (TBI). BM HSCs from wild type mice expressed functional EGFR and systemic administration of EGF p...

  19. The insulin-like growth factor system in Multiple Myeloma

    Bieghs, Liesbeth; Johnsen, Hans E; Maes, Ken;

    2016-01-01

    Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy. The MM cells reside in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, proliferation, and drug resistance. As in most cancers, the insulin-like growth factor (IGF) system has been...... preclinical evidence indicates that IGF-I is also involved in the development of drug resistance against current standard-of-care agents against MM, including proteasome inhibitors, immunomodulatory agents, and corticoids. IGF-IR targeting has been able to overcome or revert this drug resistance in animal...

  20. Fibroblast Growth Factor-21 May Mediate Growth Hormone Resistance in Anorexia Nervosa

    Fazeli, Pouneh K.; Misra, Madhusmita; Goldstein, Mark; Miller, Karen K.; Klibanski, Anne

    2009-01-01

    Context: Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. Fibroblast growth factor (FGF)-21, a hormone produced in the liver and adipocytes, is induced in the liver by fasting and peroxisome proliferator-activated receptor-α agonists. In a transgenic mouse model, FGF-21 reduces IGF-I levels by inhibiting signal transducer and activator of transcription-5, a mediator of the intracellular ...

  1. Recombinant sea urchin vascular endothelial growth factor directs single-crystal growth and branching in vitro.

    Knapp, Regina T; Wu, Ching-Hsuan; Mobilia, Kellen C; Joester, Derk

    2012-10-31

    Biomineralization in sea urchin embryos is a crystal growth process that results in oriented single-crystalline spicules with a complex branching shape and smoothly curving surfaces. Uniquely, the primary mesenchyme cells (PMCs) that construct the endoskeleton can be cultured in vitro. However, in the absence of morphogenetic cues secreted by other cells in the embryo, spicules deposited in PMC culture lack the complex branching behavior observed in the embryo. Herein we demonstrate that recombinant sea urchin vascular endothelial growth factor (rVEGF), a signaling molecule that interacts with a cell-surface receptor, induces spiculogenesis and controls the spicule shape in PMC culture. Depending on the rVEGF concentration, PMCs deposit linear, "h"- and "H"-shaped, or triradiate spicules. Remarkably, the change from linear to triradiate occurs with a switch from bidirectional crystal growth parallel to the calcite c axis to growth along the three a axes. This finding has implications for our understanding of how cells integrate morphogenesis on the multi-micrometer scale with control over lattice orientation on the atomic scale. The PMC model system is uniquely suited to investigate this mechanism and develop biotechnological approaches to single-crystal growth. PMID:23066927

  2. Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis

    Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies. (paper)

  3. Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis

    Zheng, Wenjing; Yang, Licong; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Zhou, Yunshan; Liu, Jie

    2014-06-01

    Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies.

  4. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

    2016-04-01

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

  5. Growth differentiation factor-5 stimulates the growth and anabolic metabolism of articular chondrocytes

    Xu Peng; Guo Xiong; Yao Jianfeng; Zhang Yingang; Klaus von der Mark

    2005-01-01

    Objective: To observe the effect of growth differentiation factor-5 (GDF-5) on the growth and anabolic metabolism of articular chondrocytes. Methods: The articular chondrocytes isolated from rats were treated with various concentrations of rmGDF-5, and the growth of chondrocytes measured by MTT assay, the cellular cartilage matrices formation detected sulfated glycosaminoglycan by Alcian blue staining and type Ⅱ collagen by RT-PCR,the collagen phenotypic expression of chondrocytes detected by immunofluorescence. Results: After 7 days culture,MTT assay showed that GDF-5 enhanced the growth of chondrocytes in a dose-dependent manner, RT-PCR showed that GDF-5 clearly induced the synthesis of type Ⅱ collagen because of the col2a1 mRNA band more and more strong in a dose-dependent. Chondrocytes were cultured with GDF-5 for 14 days, the intensity of Alcian blue staining was greatly enhanced, especially, at a high concentration of 1000ng/ml, and GDF-5 enhanced the accumulation of the Alcian blue-stainable material in a concentration-dependent manner and in a does-dependent manner. Chondrocytes were cultured with GDF-5 for 21 days, immunofluorescent staining of type Ⅱ collagen was clear, the type Ⅰ and X collagen were negative. Conclusion: GDF-5 enhanced the growth of mature articular chondrocytes, and stimulated the cellular cartilage matrices formation, but did not change the collagen phenotypic expression of chondrocytes in mono-layer culture.

  6. Growth Differentiation Factor-5 Stimulates the Growth and Anabolic Metabolism of Articular Chondrocytes

    Xu Peng; Yao Jianfeng; Guo Xiong; Zhang Yingang; Klaus von der Mark

    2009-01-01

    Objective: To observe the effect of growth differentiation factor-5 (GDF-5) on the growth and anabolic metabolism of articular chondrocytes. Methods: The articular chondrocytes isolated from rats were treated with various concentrations of rmGDF-5, and the growth of chondrocytes measured by MTr assay, the cellular cartilage matrices formation detected sulfated glycosaminoglycan by Alcian blue staining and type 11 collagen by RT-PCR, the collagen phenotypic expression of chondrocytes detected by immunofluorescence. Results: After 7 days culture, MTF assay showed that GDF-5 enhanced the growth of ehondrocytes in a dose-dependent manner, RT-PCR showed that GDF-5 clearly induced the synthesis of type Ⅱ collagen because of the colal mRNA band more and more strong in a dose-dependent. Chondrocytes were cultured with GDF-5 for 14 days, the intensity of Alcian blue staining was gready enhanced, especially, at a high concentration of 1000ng/ml, and GDF-5 enhanced the accumulation of the Alcian blue-stainable material in a concentration-dependent manner and in a does-dependent manner. Chondrocytes were cultured with GDF-5 for 21 days, immunofluorescent staining of type Ⅱ collagen was clear, the type Ⅰ and Ⅹ collagen were negative. Conclusion: GDF-5 enhanced the growth of mature articular chon-drocytes, and stimulated the cellular cartilage matrices formation, but did not change the collagen phenotypic ex-pression of chondrocytes in mono-layer culture.

  7. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6–95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps. (paper)

  8. Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

    Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

  9. Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds.

    Pierce, G F; Vande Berg, J.; Rudolph, R; Tarpley, J.; Mustoe, T A

    1991-01-01

    Recombinant platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) influence the rate of extracellular matrix formed in treated incisional wounds. Because incisional healing processes are difficult to quantify, a full-thickness excisional wound model in the rabbit ear was developed to permit detailed analyses of growth-factor-mediated tissue repair. In the present studies, quantitative and qualitative differences in acute inflammatory cell influx, glycosamino...

  10. Epidermal growth factor in the treatment of radiogenic proctitis

    Radiogenic proctitis is a frequent complication of therapeutic radiation at the pelvic region. The aim of this study was to determine the efficacy of the epidermal growth factor (EGF) in treating patients with proctitis as a complication of radiotherapy of gynecological tumors. A phase II, placebo-controlled, randomized, double blind clinical trial was carried out. The treatment groups were: A) a solution of human recombinant epidermal growth factor (10 μg/ml) in carboxymethyl cellulose or B) placebo (carboxymethylcellulose solution alone); the treatment was administered as a retention enema (20 mL) twice a day after bowel movement for 6 months. We included women of 18-75 years of age with proctitis as a complication of an ionizing radiation treatment of gynecological malignant tumors, confirmed by endoscopy, who gave their consent to participate. Thirty-seven patients were included. The basic demographic variables and were homogeneous among groups, which were comparable. There were more responses in group A (EGF) than in the control (placebo), but the difference was not statistically significant. Considering only those patients who completed the treatment, the difference in response was greater with EGF (86% vs60%). The symptoms disappeared more rapidly in the group treated with EGF (p=0.027 and p=0.016, for bleeding and tenesmus, respectively). The product under study was well tolerated. Although there are signs of improvement in some symptoms, the sample was too small to demonstrate the effectiveness of Hebervis in the treatment of proctitis. (Author)

  11. Insulin-like growth factors and fish reproduction.

    Reinecke, Manfred

    2010-04-01

    Knowledge of fish reproduction is of high relevance to basic fish biology and comparative evolution. Furthermore, fish are excellent biomedical models, and the impact of aquaculture on worldwide food production is steadily increasing. Consequently, research on fish reproduction and the potential modes of its manipulation has become more and more important. Reproduction in fish is regulated by the integration of endogenous neuroendocrine (gonadotropins), endocrine, and autocrine/paracrine signals with exogenous (environmental) factors. The main endocrine regulators of gonadal sex differentiation and function are steroid hormones. However, recent studies suggest that other hormones are also involved. Most prominent among these hormones are the insulin-like growth factors (Igfs), i.e., Igf1, Igf2, and, most recently, Igf3. Thus, the present review deals with the expression patterns and potential physiological functions of Igf1 and Igf2 in male and female gonads. It further considers the potential involvement of growth hormone (Gh) and balances the reasons for endocrine vs. autocrine/paracrine action of the Igfs on the gonads of fish. Finally, this review discusses the early and late development of gonadal Igf1 and Igf2 and whether they are targets of endocrine-disrupting compounds. Future topics for novel research investigation on Igfs and fish reproduction are presented. PMID:19864315

  12. Growth factors and IL-17 in hereditary angioedema.

    Salemi, M; Mandalà, V; Muggeo, V; Misiano, G; Milano, S; Colonna-Romano, G; Arcoleo, F; Cillari, E

    2016-05-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman's correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value <0.05) higher values in crisis states rather than in basal states for the three growth factors and cytokine IL-17. When comparing healthy subjects versus HAE patients at basal state, we found out significantly higher values in HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients, there is a connection between IL-17 and growth factors. The low-grade inflammation in absence of attacks is demonstrated by constant higher amount of IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that in this disease there is a level of activation that maintains the system in a "tick-over state," that can be activate by several stimuli that are able to induce a increase in inflammatory mediators during the acute attack. PMID:25773165

  13. Epidermal growth factor-stimulated protein phosphorylation in rat hepatocytes

    Epidermal growth factor (EGF) causes a 6-fold increase in the phosphorylation state of a cytosolic protein (pp36, M/sub r/ = 36,000, pI = 5.5) in hepatocytes isolated from fasted, male, Wistar rats. Stimulation of 32P incorporation is observed as early as 1 min following treatment of hepatocytes with EGF and is still present at 30 min after exposure to the growth factor. The phosphate incorporated into pp36 in response to EGF is located predominantly in serine but not tyrosine residues. Phosphorylation of pp36 does not occur in response to insulin or to agents which specifically activate the cAMP-dependent protein kinase (S/sub p/ -cAMPS), protein kinase C (PMA) or Ca2+/calmodulin-dependent protein kinases (A23187) in these cells. Prior treatment of hepatocytes with the cAMP analog, S/sub p/-cAMPS, or ADP-ribosylation of N/sub i/, the inhibitory GTP-binding protein of the adenylate cyclase complex, does not prevent EGF-stimulated phosphorylation of pp36. However, as seen in other cell types, pretreatment of hepatocytes with PMA abolishes all EGF-mediated responses including phosphorylation of pp36. These results suggest that EGP specifically activates an uncharacterized, serine protein kinase in hepatocytes that is distal to the intrinsic EGF receptor tyrosine protein kinase. The rapid activation of this kinase suggests that it may play an important role in the early response of the cell to EGF

  14. Upregulation of epidermal growth factor receptor 4 in ora leukoplakia

    Hiroshi Kobayashi; Kenichi Kumagai; Akito Gotoh; Takanori Eguchi; Hiroyuki Yamada; Yoshiki Hamada; Satsuki Suzuki; Ryuji Suzuki

    2013-01-01

    In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ ErbB 1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP), The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

  15. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF)

    He, Yonghua; Schmidt, Monica A.; Erwin, Christopher; Guo, Jun; Sun, Raphael; Pendarvis, Ken; Warner, Brad W.; Herman, Eliot M.

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. PMID:27314851

  16. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-04-17

    Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of the ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.

  17. Compound list: transforming growth factor beta 1 [Open TG-GATEs

    Full Text Available transforming growth factor beta 1 TGFB1 00182 ftp://ftp.biosciencedbc.jp/archive/op...en-tggates/LATEST/Human/in_vitro/transforming_growth_factor_beta_1.Human.in_vitro.Liver.zip ...

  18. Nerve growth factor mRNA in brain: localization by in situ hybridization

    Nerve Growth Factor is a 118 amino acid polypeptide that plays an important role in the differentiation and survival of neurons. The recent discovery that a mRNA that encodes beta Nerve Growth Factor is present in brain suggests that the Nerve Growth Factor gene may not only regulate gene expression of peripheral but also of central neurons. To identify the site(s) of Nerve Growth Factor mRNA production in the brain and to determine which cells express the Nerve Growth Factor gene, the technique of in situ hybridization was employed. A 32P-labeled RNA probe complementary to Nerve Growth Factor mRNA hybridized to cells in the stratum granulosum of the dentate gyrus and the stratum pyramidale of the hippocampus. These observations identify for the first time cellular sites of Nerve Growth Factor gene expression in the central nervous system, and suggest that Nerve Growth Factor mRNA is produced by neurons

  19. Controlled release of nerve growth factor from heparin-conjugated fibrin gel within the nerve growth factor-delivering implant

    Lee, Jin-Yong; Kim, Soung-Min; Kim, Myung-Jin; Lee, Jong-Ho

    2014-01-01

    Objectives Although nerve growth factor (NGF) could promote the functional regeneration of an injured peripheral nerve, it is very difficult for NGF to sustain the therapeutic dose in the defect due to its short half-life. In this study, we loaded the NGF-bound heparin-conjugated fibrin (HCF) gel in the NGF-delivering implants and analyzed the time-dependent release of NGF and its bioactivity to evaluate the clinical effectiveness. Materials and Methods NGF solution was made of 1.0 mg of NGF ...

  20. Valproic acid overcomes transforming growth factor-β-mediated sorafenib resistance in hepatocellular carcinoma

    Matsuda, Yasunobu; Wakai, Toshifumi; Kubota, Masayuki; Osawa, Mami; Hirose, Yuki; Sakata, Jun; Kobayashi, Takashi; Fujimaki, Shun; Takamura, Masaaki; Yamagiwa, Satoshi; Aoyagi, Yutaka

    2014-01-01

    Sorafenib is a multi-kinase inhibitor approved for hepatocellular carcinoma, but rarely causes tumor regression in patients with chronic liver diseases. To investigate whether growth factor-mediated signaling is involved in sorafenib resistance, HepG2 and PLC/PRF/5 hepatoma cells were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF) or transforming growth factor-β (TGF-β) prior to treatment with sorafenib. Furthermore, to identify an effective combination treatment wit...

  1. Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes.

    Parker, T G; Packer, S E; Schneider, M. D.

    1990-01-01

    Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide growth factors, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes. Transforming growth factor-beta 1 (TGF beta 1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes ...

  2. Insulin-like Growth Factor Binding Protein 7 Mediates Glioma Cell Growth and Migration

    Wei Jiang

    2008-12-01

    Full Text Available Insulin-like growth factor binding protein 7 (IGFBP-7 is the only member of the IGFBP superfamily that binds strongly to insulin, suggesting that IGFBP-7 may have different functions from other IGFBPs. Unlike other IGFBPs, the expression and functions of IGFBP-7 in glioma tumors have not been reported. Using cDNA microarray analysis, we found that expression of IGFBP-7 correlated with the grade of glioma tumors and the overall patient survival. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. We used RNAi to examine the role of IGFBP-7 in glioma cells, inhibiting IGFBP-7 expression by short interfering RNA transfection. Cell proliferation was suppressed after IGFBP-7 expression was inhibited for 5 days, and glioma cell growth was stimulated consistently by the addition of recombinant IGFBP-7 protein. Moreover, glioma cell migration was attenuated by IGFBP-7 depletion but enhanced by IGFBP-7 overexpression and addition. Overexpression of AKT1 in IGFBP-7-overxpressed cells attenuated the IGFBP-7-promoted migration and further enhanced inhibition of IGFBP-7 depletion on the migration. Phosphorylation of AKT and Erk1/2 was also inversely regulated by IGFBP-7 expression. These two factors together suggest that IGFBP-7 can regulate glioma cell migration through the AKT-ERK pathway, thereby playing an important role in glioma growth and migration.

  3. Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

    Marchal Joëlle

    2005-10-01

    Full Text Available Abstract Background Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. Methods Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. Results Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. Conclusion The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers.

  4. Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle

    Johnson, Peter R A; Burgess, Janette K; Ge, Qi; Poniris, Maree; Boustany, Sarah; Twigg, Stephen M; Black, Judith L

    2006-01-01

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in airway smooth muscle cells isolated from patients with ast

  5. The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease

    Williams, Aislinn J.; Umemori, Hisashi

    2014-01-01

    Growth factors play important roles in synapse formation. Mouse models of neuropsychiatric diseases suggest that defects in synaptogenic growth factors, their receptors, and signaling pathways can lead to disordered neural development and various behavioral phenotypes, including anxiety, memory problems, and social deficits. Genetic association studies in humans have found evidence for similar relationships between growth factor signaling pathways and neuropsychiatric phenotypes. Accumulating...

  6. Changes in the level of growth hormone, insulin like growth factor-1 and insulin like growth factor binding proteine-3 in young males 24 hours after submaximaltraining

    ÇOKNAZ, Hakkı

    2011-01-01

    The study was accomplished as a control study, under the question whether 6-weeks endurance training affects the growth hormone (GH), insulin like growth factor-1 (IGF-1) and the IGF bindings protein-3 (IGFBP-3) levels. Sixty male subjects participated in the study. The subjects were separated into 2 groups as control (n=30; mean age=21,13±1,16 years) and study (n=30; mean age=21,53±1,61 years) randomly, prior to the runtest. Blood samples were drawn before breakfast and analyzed in the labor...

  7. NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells: molecular targeting of angiogenic growth factor.

    Du, Wenlin; Hattori, Yutaka; Yamada, Taketo; Matsumoto, Kunio; Nakamura, Toshikazu; Sagawa, Morihiko; Otsuki, Takemi; Niikura, Takako; Nukiwa, Toshihiro; Ikeda, Yasuo

    2007-04-01

    Hepatocyte growth factor (HGF) promotes cell growth and motility and also increases neovascularization. Multiple myeloma (MM) cells produce HGF, and the plasma concentration of HGF is significantly elevated in patients with clinically active MM, suggesting that HGF might play a role in the pathogenesis of MM. NK4, an antagonist of HGF, is structurally homologous to angiostatin, and our previous report showed that NK4 inhibited the proliferation of vascular endothelial cells induced by HGF stimulation. The purposes of this study were to elucidate the contribution of HGF to the growth of MM cells as well as to investigate the possibility of the therapeutic use of NK4. In vitro study showed that NK4 protein stabilized the growth of MM cell lines and regulated the activation of c-MET, ERK1/2, STAT3, and AKT-1. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4) was injected intramuscularly into Icr/scid mice bearing tumors derived from HGF-producing MM cells. AdCMV.NK4 significantly inhibited the growth of these tumors in vivo. Histologic examination revealed that AdCMV.NK4 induced apoptosis of MM cells, accompanied by a reduction in neovascularization in the tumors. Thus, NK4 inhibited the growth of MM cells via antiangiogenic as well as direct antitumor mechanisms. The molecular targeting of HGF by NK4 could be applied as a novel therapeutic approach to MM. PMID:17179234

  8. CD44 function as a growth factor co-receptor

    Chen, L.

    2003-06-01

    CD44 splice variant proteins containing exon v6 encoded sequence have been implicated in tumour metastasis. The work presented in this thesis shows that CD44 isoforms containing exon v6 encoded sequences act as coreceptor for the c-Met receptor, a tyrosine kinase receptor that is involved in growth control and invasive growth. The c-Met receptor and its ligand hepatocyte growth factor (HGF) have also been implicated in tumour metastasis. My results show the cooperation between CD44, HGF and c-Met. A CD44 isoform containing variant exon v6 encoded sequences is strictly required for c-Met activation by HGF/SF in rat and human carcinoma cells. In a non-metastatic cell line BSp73AS cells which only expressed CD44 standard form, HGF can not activate c-Met. Upon transfection with the CD44 bearing v6 encoded sequences, the cells become HGF inducible. Antibodies against two CD44 exon v6-encoded epitopes inhibit autophosphorylation of c-Met. The CD44 isoform is required for the assembly of signalling complex containing at least HGF, c-Met and CD44 v6 bearing isoform. Furthermore, this growth factor co-receptor function could be a more general mechanism. I have investigated the involvement of CD44 isoforms in the signalling by the EGF receptor family. My results show that HB-EGF, EGF and Amphiregulin activate their receptors in a CD44 dependent manner. CD44 v6 specific antibodies can interfere with HB-EGF, EGF and Amphiregulin signalling both at Erk level and at receptor level. (orig.) [German] In der nicht metastasierenden Zelllinie Bsp73 AS, die ausschliesslich die CD44 Standardform exprimiert, fuehrt HGF nicht zur Aktivierung von c-Met. Durch Transfektion mit unterschiedlichen CD44 v6 enthaltenden Isoformen, werden die Zellen HGF-induzierbar. Antikoerper gegen zwei von CD44 Exon v6 kodierte Epitope verhindern die Autophosphorylierung von c-Met. Die CD44 Isoform wird zur Bildung eines Signalkomplexes benoetigt, der zumindest HGF, c-Met und CD44v6 tragende Isoformen

  9. Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654

    Addition of platelet-derived growth factor (PDGF) to quiescent WI-38 human fetal lung fibroblasts mimics the effect of tumor-promoting phorbol diesters to inhibit the high-affinity binding of 125I-labeled epidermal growth factor (125I-EGF). PDGF, like phorbol diesters, was found to increase the phosphorylation state of EGF receptors immunoprecipitated from intact fibroblasts that were labeled to equilibrium with [32P]phosphate. Phosphoamino acid analysis of the EGF receptors indicated that both PDGF and phorbol diesters increased the level of [32P]phosphoserine and [32P]phosphothreonine. Phosphopeptide mapping of the EGF receptor demonstrated that PDGF increased the phosphorylation of several sites and induced the phosphorylation of a site that was not observed to be phosphorylated on EGF receptors isolated from control cells. This latter phosphorylation site on the EGF receptor was identified as threonine-654. These results are consistent with the hypothesis that increases in diacylglycerol and Ca2+ levels caused by addition of PDGF to fibroblasts activate protein kinase C and that this kinase, at least in part, mediates the effect of PDGF on the phosphorylation of the EGF receptor. The data further suggest that protein kinase C may play an important role in the regulation of cellular metabolism and proliferation by PDGF

  10. An Expandable, Inducible Hemangioblast State Regulated by Fibroblast Growth Factor

    David T. Vereide

    2014-12-01

    Full Text Available During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that “trap” murine cells in a proliferative state and endow them with a hemangioblast potential. These “expandable” hemangioblasts (eHBs are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.

  11. Growth hormone and insulin-like growth factor I in a Sydney Olympic gold medallist.

    Armanini, D; Faggian, D; Scaroni, C; Plebani, M

    2002-04-01

    An Italian athlete who won a gold medal at the Sydney Olympic Games was studied. She was accused of doping after the finding of high levels of plasma growth hormone (GH) before the Games. She was studied firstly under stressed and then under unstressed conditions. In the first study, GH was measured every 20 minutes for one hour; it was above the normal range in all blood samples, whereas insulin-like growth factor I (IGF-I) was normal. In the second study, GH progressively returned to accepted normal levels; IGF-I was again normal. It was concluded that the normal range for GH in athletes must be reconsidered for doping purposes, because athletes are subject to stress and thus to wide variations in GH levels. PMID:11916901

  12. Growth factors, glucose and insulin kinetics after low dose growth hormone in HIV - lipodystrophy

    Haugaard, Steen B; Andersen, Ove; Flyvbjerg, Allan;

    2006-01-01

    temporary reduction in insulin sensitivity was caused by a reduction in non-oxidative glucose metabolism (n=5). GH-administration reduced hepatic extraction of insulin alleviating the demand for insulin secretion (n=5). No adverse effects of GH were detected. CONCLUSIONS: As judged from effects on......OBJECTIVES: Low-dose growth hormone (GH) administration has been suggested as a treatment for HIV-lipodystrophy. METHODS: Postglucose GH-secretion, kinetics of insulin-like growth factors (IGFs), insulin, and glucose metabolism were examined in six male HIV-infected lipodystrophic patients (two...... normal-weight patients with normal glucose-tolerance (NGT), two normal-weight with impaired glucose-tolerance (IGT), and two obese patients with diabetes (DM)) during a 16 weeks open-labelled pilot-study of low-dose GH, 0.7 mg/day. RESULTS: DM, compared to NGT and IGT, displayed an impaired rebound of GH...

  13. Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

    Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa;

    2012-01-01

    Placental Growth Factor (PGF) is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes) suggesting its use as a potential therapeutic agent....... However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have...... associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability....

  14. Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

    Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa; Aversano, Mario; Husemoen, Lise-Lotte; Linneberg, Allan; Bourgain, Catherine; Leutenegger, Anne-Louise; Ciullo, Marina

    2012-01-01

    . However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have...... associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability.......Placental Growth Factor (PGF) is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes) suggesting its use as a potential therapeutic agent...

  15. Enhanced effect of fibroblast growth factor-2-containing dalteparin/protamine nanoparticles on hair growth

    Takabayashi Y

    2016-05-01

    Full Text Available Yuki Takabayashi,1 Masaki Nambu,1 Masayuki Ishihara,2 Masahiro Kuwabara,1 Koichi Fukuda,2 Shingo Nakamura,2 Hidemi Hattori,2Tomoharu Kiyosawa1 1Department of Plastic and Reconstructive Surgery, 2Division of Biomedical Engineering, Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan Purpose: Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs can effectively carry growth factors (GFs such as fibroblast GF (FGF-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs on hair growth.Patients and methods: In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL and D/P NPs (56 μg/mL was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter.Results: The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience.Conclusion: The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia. Keywords: hair growth, dalteparin/protamine nanoparticles, fibroblast growth factor, transdermal application

  16. Growth hormone-insuline-like growth factor-I system in pejerrey Odontesthes bonariensis (Atheriniformes

    S.E. Arranz

    2008-07-01

    Full Text Available Using biotechnology to increase the growth rates of fish is likely to reduce production costs per unit of food. Among vertebrates, fish appear to occupy a unique position, when growth patterns are considered. With few exceptions, fish species tend to grow indeterminately, implying that size is never fixed. Both hyperplasia and hypertrophy contribute to post-larval muscle growth in fish. Growth hormone (GH - Insulin-like Growth Factor I (IGF-I is the most important growth axis in fish. Our experimental model, the pejerrey, Odontesthes bonariensis (Ateriniformes is a South American inland water fish considered to be a promising species for intensive aquaculture. However, one major drawback to achieve this goal is its slow growth in captivity. In order to understand how growth is regulated in this species, our first objective was to characterized pejerrey GH- IGF-I axis. We first cloned and characterized pejerrey (pj GH, IGF-I and the growth hormone receptors (GHRs I and II. In addition to providing valuable data for evolutionary comparison of GH, investigation of GH action in teleosts is particularly important because of its potential application in aquaculture. GH can not only promote the somatic growth in fish but also lower dietary protein requirements. A prerequisite for providing sufficient amounts of GH for basic research and aquaculture application is a large-scale production of GH. For that purpose, recombinant pjGH was expressed in a bacterial system. Protocols for solubilization and proper folding were achieved. Activity of recombinant pjGH was assessed in fish by measuring the liver IGF-I response to different doses of GH. IGF-I transcript was measured in the liver after pjGHr in vivo stimulation by means of quantitative real-time PCR assays. A dose-dependent response of IGF-I mRNA was observed after pjGHr administration, and reached a 6 fold IGF-I maximum increase over control group when 2.5 µg pjGH /g-body weight were injected

  17. Chronic administration of epidermal growth factor to pigs induces growth, especially of the urinary tract with accumulation of epithelial glycoconjugates

    Vinter-Jensen, Lars; Juhl, C O; Poulsen, Steen Seier; Djurhuus, Jens Christian; Dajani, E Z; Nexø, Ebba

    1995-01-01

    Epidermal growth factor (EGF) receptor hyperstimulation induced by systemically administered EGF or by the development of transgenic mice overexpressing transforming growth factor alpha (TGF alpha) or other EGF-related ligands is known to induce various effects, such as acceleration of developmen...... in a species with greater anatomic resemblance to humans than rodents....

  18. Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function

    Kopke, Richard D; Jackson, Ronald L; Li, Geming; Rasmussen, Mark D.; Hoffer, Michael E.; Frenz, Dorothy A.; Costello, Michael; Schultheiss, Peter; Van De Water, Thomas R.

    2001-01-01

    The vestibules of adult guinea pigs were lesioned with gentamicin and then treated with perilymphatic infusion of either of two growth factor mixtures (i.e., GF I or GF II). GF I contained transforming growth factor α (TGFα), insulin-like growth factor type one (IGF-1), and retinoic acid (RA), whereas GF II contained those three factors and brain-derived neurotrophic factor. Treatment with GF I significantly enhanced vestibular hair cell renewal in ototoxin-damaged ...

  19. СOLORECTAL CANCER AND INCULIN-LIKE GROWTH FACTORS

    A. A. Nikolayev

    2015-02-01

    Full Text Available Insulin-like growth factors (IGF 1 and 2 and IGF binding proteins (IGFBP 1 and 3 levels were measured by ELISA techniques in blood serum of 74 primary colorectal cancer (СRC patients and 30 control practically healthy persons. Significant increase of IGF-1 level and decrease of IGFBP-3 level were demonstrated in patients’ serum as compared to control group. Sensitivity of IGF-1 as a prospective diagnostic СRС marker comprised 80 % with 75 % specificity using 140 ng/ml as cut-off level. Significant negative association was found be-tween both patients and donors’ age and serum IGF-1 levels, but in CRC patients it was much weaker than in control group. No associations were found between serum IGF 1 and 2 levels and main criteria of colorectal cancer progression.

  20. Redox-dependent regulation of epidermal growth factor receptor signaling.

    Heppner, David E; van der Vliet, Albert

    2016-08-01

    Tyrosine phosphorylation-dependent cell signaling represents a unique feature of multicellular organisms, and is important in regulation of cell differentiation and specialized cell functions. Multicellular organisms also contain a diverse family of NADPH oxidases (NOXs) that have been closely linked with tyrosine kinase-based cell signaling and regulate tyrosine phosphorylation via reversible oxidation of cysteine residues that are highly conserved within many proteins involved in this signaling pathway. An example of redox-regulated tyrosine kinase signaling involves the epidermal growth factor receptor (EGFR), a widely studied receptor system with diverse functions in normal cell biology as well as pathologies associated with oxidative stress such as cancer. The purpose of this Graphical Redox Review is to highlight recently emerged concepts with respect to NOX-dependent regulation of this important signaling pathway. PMID:26722841

  1. Molecular diversity of snake venom nerve growth factors.

    Trummal, Katrin; Tõnismägi, Külli; Paalme, Viiu; Järvekülg, Lilian; Siigur, Jüri; Siigur, Ene

    2011-09-15

    Nerve growth factor (NGF) is a protein which stimulates the differentiation and maintenance of sympathetic and embryonic sensory neurons. Snake venoms are a rich source of NGF. Due to small quantities it is sometimes difficult and laborious to isolate NGF from the venoms. In this study the use of Ni-NTA-agarose for isolation of NGF is studied. Anti-Vipera lebetina NGF antibodies were used for identification of NGF during Ni-NTA-agarose fractionation as well as for cross-reaction studies with 21 snake venoms. All studied venoms contained NGF. The molecular masses of the NGFs from Echis ocellatus, Agkistrodon contortrix contortrix, A. bilineatus, A. blomhoffii, A. saxatilis, Calloselasma rhodostoma, Bothrops jararaca and B. lanceolatus were determined for the first time. Some previous results of the NGF studies are revaluated. PMID:21801740

  2. Insulin and insulin-like growth factor receptors and responses

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  3. Role of the fibroblast growth factor receptor axis in cholangiocarcinoma.

    Ang, Celina

    2015-07-01

    Advanced cholangiocarcinoma (CCA) is a highly lethal disease with limited therapeutic options beyond cytotoxic chemotherapy. Molecular profiling of CCA has provided insights into the pathogenesis of this disease and identified potential therapeutic targets. The fibroblast growth factor receptor (FGFR) axis is important for maintaining tissue homeostasis. Aberrations in FGFR activity have been implicated in the development and progression of CCA and other malignancies, which has generated significant interest in exploring FGFR's therapeutic potential. FGFR2 fusion events are present in up to 17% of intrahepatic CCAs and appear to predict sensitivity to FGFR inhibitors even after progression on chemotherapy. These observations have led to a clinical trial evaluating FGFR inhibition in patients with CCA enriched for FGFR alterations. This review summarizes current knowledge about the role of the FGFR pathway in cholangiocarcinogenesis and ongoing work in developing FGFR-directed therapies as an antineoplastic strategy for CCA. PMID:25678238

  4. Vascular endothelial growth factor: a neurovascular target in neurological diseases.

    Lange, Christian; Storkebaum, Erik; de Almodóvar, Carmen Ruiz; Dewerchin, Mieke; Carmeliet, Peter

    2016-08-01

    Brain function critically relies on blood vessels to supply oxygen and nutrients, to establish a barrier for neurotoxic substances, and to clear waste products. The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, but was later co-opted by blood vessels to regulate vascular function. Consequently, VEGF represents an attractive target to modulate brain function at the neurovascular interface. On the one hand, VEGF is neuroprotective, through direct effects on neural cells and their progenitors and indirect effects on brain perfusion. In accordance, preclinical studies show beneficial effects of VEGF administration in neurodegenerative diseases, peripheral neuropathies and epilepsy. On the other hand, pathologically elevated VEGF levels enhance vessel permeability and leakage, and disrupt blood-brain barrier integrity, as in demyelinating diseases, for which blockade of VEGF may be beneficial. Here, we summarize current knowledge on the role and therapeutic potential of VEGF in neurological diseases. PMID:27364743

  5. Epidermal growth factor in rat milk is dependent on insulin

    Thulesen, J; Poulsen, Steen Seier; Nexo, E;

    1993-01-01

    Epidermal growth factor (EGF) was measured in milk from four groups of rats: untreated diabetic, insulin-treated diabetic, insulin-treated normal and control rats. In the untreated diabetic group the volume of milk, and the concentration of EGF and the total output of EGF were significantly...... decreased when compared to the control group. In contrast, the total protein concentration in milk from the untreated diabetic rats was similar to the concentration in milk from the control rats. Insulin-treatment of diabetic rats almost completely reversed the decrease in the milk volume and in the...... concentration of EGF, and thus normalized the total output of EGF. The insulin-treated normal rats which remained euglycemic had a significantly increased concentration of EGF and of total protein without any difference in the volume of milk when compared to the controls. The results indicate that the secretion...

  6. Nerve growth factor, sphingomyelins, and sensitization in sensory neurons

    Grant D. Nicol

    2008-01-01

    @@ Because nerve growth factor (NGF) is elevated during inflammation, plays a causal role in the initiation of hyperalgesia, and is known to activate the sphingomyelin signalling pathway, we examined whether NGF and its putative second messenger, ceramide, could modulate the excitability of capsaicin-sensitive adult sensory neurons.Using the whole-cell patch-clamp recording technique,exposure of isolated sensory neurons to either 100 ng/mL NGF or 1 mmol/L N-acetyl sphingosine (C2-ceramide) produced a 3-4 fold increase in the number of action po-tentials (APs) evoked by a ramp of depolarizing current in a time-dependent manner. Intracellular perfusion with bac- terial sphingomyelinase (SMase) also increased the num- ber of APs suggesting that the release of native ceramide enhanced neuronal excitability.

  7. Vascular endothelial growth factor blocking agents in retinal vein occlusion

    Chris Canning

    2008-01-01

    Full Text Available This paper summarises the current status of the use of vascular endothelial growth factor (VEGF blocking agents in retinal vein occlusion. There have been no randomised controlled trials comparing this treatment with the current standard treatment (largely laser so the lower grade evidence of single treatment case series and anecdotal reports are discussed. VEGF blockers are good at reducing macular oedema in the short term, do improve visual acuity in many cases, and do not seem to adversely affect the long term revascularisation that is necessary to overcome the vein occlusion. VEGF blocking agents are not used in isolation in this condition - they will remain an adjunct to systemic and other local treatments. The literature was reviewed in online searches of Embase and Ovid and the papers quoted are a representative sample of a larger body of publications.

  8. Growth restriction factor in Al-Si-Mg-Cu alloys

    The Growth Restriction Factor, Q, proved to be useful to analyse and control grain refinement during solidification of alloys. It is known that in multicomponent alloys a simple summation of the Qi values of the individual constituents taken from the binary phase diagrams can lead to grossly wrong results and that the ternary or higher-level phase diagram needs to be evaluated. This work demonstrates that the actual evaluation of Q using the liquidus gradient and partition coefficients of the multicomponent phase diagram requires some precautions and may be cumbersome. More importantly, this approach entirely fails if an intermetallic phase turns out to be the primary solidifying phase even in tiny amount. A very simple and general solution of this problem is illustrated for Al-Si-Mg-Cu alloys.

  9. PLACENTAL GROWTH FACTOR AND CORONARY NEOANGIOGENESIS IN CORONARY HEART DISEASE

    M. V. Tulikov

    2013-01-01

    Full Text Available Neoangiogenesis in coronary heart disease is a protective reaction aimed to improve ischemic myocardial perfusion, by increasing the number and size of arterial collaterals. Placental growth factor (PlGF is one of the key peptides regulating angiogenic processes in atherosclerosis. In particular, a number of investigators have shown that injection of recombinant PlGF into the system or regional blood flow can stimulate neoangiogenesis. On the other hand, there is evidence confirming the involvement of PlGF in the progression of atherosclerosis and in the development of acute coronary syndrome. In this connection, the problem of investigating the efficiency and safety of possible use of PlGF preparations, as well as its place in the diagnosis of coronary heart disease and acute coronary syndrome remains urgent

  10. Insulin-like Growth Factor Binding Protein 7 Mediates Glioma Cell Growth and Migration1

    Jiang, Wei; Xiang, Cunli; Cazacu, Simona; Brodie, Chaya; Mikkelsen, Tom

    2008-01-01

    Insulin-like growth factor binding protein 7 (IGFBP-7) is the only member of the IGFBP superfamily that binds strongly to insulin, suggesting that IGFBP-7 may have different functions from other IGFBPs. Unlike other IGFBPs, the expression and functions of IGFBP-7 in glioma tumors have not been reported. Using cDNA microarray analysis, we found that expression of IGFBP-7 correlated with the grade of glioma tumors and the overall patient survival. This finding was further validated by real-time...

  11. Insulin-like Growth Factor Binding Protein 7 Mediates Glioma Cell Growth and Migration

    Wei Jiang; Cunli Xiang; Simona Cazacu; Chaya Brodie; Tom Mikkelsen

    2008-01-01

    Insulin-like growth factor binding protein 7 (IGFBP-7) is the only member of the IGFBP superfamily that binds strongly to insulin, suggesting that IGFBP-7 may have different functions from other IGFBPs. Unlike other IGFBPs, the expression and functions of IGFBP-7 in glioma tumors have not been reported. Using cDNA microarray analysis, we found that expression of IGFBP-7 correlated with the grade of glioma tumors and the overall patient survival. This finding was further validated by real-time...

  12. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) μg/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 μg/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 μg/g creatinine; P 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion

  13. Epidermal growth factor and its receptors in human pancreatic carcinoma

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

  14. Structural basis for agonism and antagonism of hepatocyte growth factor

    Tolbert, W. David; Daugherty-Holtrop, Jennifer; Gherardi, Ermanno; Vande Woude, George; Xu, H. Eric (Van Andel); (MRCLMB)

    2010-11-01

    Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration but abnormal activation of Met has been implicated in growth, invasion, and metastasis of many types of solid tumors. HGF has two natural splice variants, NK1 and NK2, which contain the N-terminal domain (N) and the first kringle (K1) or the first two kringle domains of HGF. NK1, which is a Met agonist, forms a head-to-tail dimer complex in crystal structures and mutations in the NK1 dimer interface convert NK1 to a Met antagonist. In contrast, NK2 is a Met antagonist, capable of inhibiting HGF's activity in cell proliferation without clear mechanism. Here we report the crystal structure of NK2, which forms a 'closed' monomeric conformation through interdomain interactions between the N- domain and the second kringle domain (K2). Mutations that were designed to open up the NK2 closed conformation by disrupting the N/K2 interface convert NK2 from a Met antagonist to an agonist. Remarkably, this mutated NK2 agonist can be converted back to an antagonist by a mutation that disrupts the NK1/NK1 dimer interface. These results reveal the molecular determinants that regulate the agonist/antagonist properties of HGF NK2 and provide critical insights into the dimerization mechanism that regulates the Met receptor activation by HGF.

  15. Medical tourism: a new growth factor for Indian healthcare industry

    Manoj Kumar Gupta

    2015-09-01

    Full Text Available Epidemiological transition has given the opportunity to grow the traditional system of medicine across the world. Indian healthcare system which is already famous for providing quality of medical services at affordable cost as compared to developed countries took advantage of this opportunity and created a and lsquo;basket of services' by merging traditional medicines in existing allopathic system to attract patients across the borders. Government has made efforts in the direction of promoting medical tourism in the country and this has been fuelled by the private players both nationally and internationally. Recently this medical tourism has proved a major growth factor for expansion of Indian economy. However, the growth in this sector is underscored in terms of market share and cost advantages due to various challenges. There is also a need for proper diversion of revenue by a clear cut mechanism to strengthen the nation's healthcare sector. [Int J Res Med Sci 2015; 3(9.000: 2161-2163

  16. Neonatal fibroblast growth factor treatment enhances cocaine sensitization.

    Clinton, Sarah M; Turner, Cortney A; Flagel, Shelly B; Simpson, Danielle N; Watson, Stanley J; Akil, Huda

    2012-11-01

    Growth factors are critical in neurodevelopment and neuroplasticity, and recent studies point to their involvement in addiction. We previously reported increased levels of basic fibroblast growth factor (FGF2) in high novelty/drug-seeking rats (bred high responders, bHR) compared to low novelty/drug-seeking rats(bred low responders, bLRs). The present study asked whether an early life manipulation of the FGF system(a single FGF2 injection on postnatal day 2) can impact cocaine sensitization and associated neurobiological markers in adult bHR/bLR animals. Neonatal FGF2- and vehicle-treated bHR/bLR rats were sensitized to cocaine(7 daily injections, 15 mg/kg/day, i.p.) in adulthood. Neonatal FGF2 markedly increased bLRs' typically low psychomotor sensitization to cocaine (day 7 locomotor response to cocaine), but had little effect on bHRs' cocaine sensitization. Gene expression studies examined dopaminergic molecules as well as FGF2 and the FGFR1 receptor in cocaine naïve animals, to investigate possible neurobiological alterations induced by neonatal FGF2 exposure that may influence behavioral response to cocaine. bLRs showed decreased tyrosine hydroxylase in the ventral tegmental area (VTA), decreased D1 and increased D2 receptor expression in the nucleus accumbens core, as well as decreased FGF2 in the VTA, substantia nigra, accumbens core, and caudate putamen compared to bHRs. Neonatal FGF2 selectively increased D1 receptor and FGF2 mRNA in the accumbens core of bLRs, which may contribute to their heightened cocaine sensitization. Our results suggest increased FGF2 in the mesodopaminergic circuit (as in baseline bHRs and neonatal FGF2-exposed bLRs vs. baseline bLRs) enhances an individual's susceptibility to cocaine sensitization and may increase vulnerability to drug seeking and addiction. PMID:22819969

  17. Vascular Endothelium Growth Factor, Surgical Delay, and Skin Flap Survival

    Lineaweaver, William C.; Lei, Man-Ping; Mustain, William; Oswald, Tanya M.; Cui, Dongmei; Zhang, Feng

    2004-01-01

    Objective: Cytokines may be a mechanism by which surgical delay can increase flap survival. We previously found that preoperative vascular endothelium growth factor (VEGF) administration in the rat transverse rectus abdominis myocutaneous (TRAM) flap could improve skin paddle survival. In this study, we used partial elevation of the rat TRAM flap as a surgical delay to assess endogenous cytokine expression and tissue survival comparable to undelayed TRAM flaps. Methods: In Part I, TRAM flaps underwent surgical delay procedures; 7 days later, the flaps were completely elevated and reinset. At the same time, other flaps were raised and reinset without delay. Skin paddle survival in both groups was evaluated at 7 days. In Part II, skin biopsies from TRAM zones I to IV were taken at the time of delay and at intervals of 12, 24, 48, and 72 hours. Specimens were assessed for selected cytokine gene expression by reverse transcription-polymerase chain reaction analysis (TR-PCR). Results: Surgical delay significantly (P < 0.001) increased skin paddle survival in the delayed TRAM flaps (16.14 ± 1.53 cm, 81.9%) compared with undelayed flaps (7.68 ± 3.16 cm, 40.9%). TGF-β and PDGF expressions were not changed by surgical delay, but basic fibroblast growth factor (bFGF) and VEGF expressions increased significantly (P < 0.05 and P < 0.01) after delay. Conclusions: In the rat TRAM model, surgical delay resulted in increased VEGF expression and increased skin paddle survival. These results correlate with previous studies showing the preoperative injection of VEGF increases skin paddle survival. VEGF may be an important element in the delay phenomenon and may be an agent for pharmacological delay. PMID:15166966

  18. Growth hormone releasing factor: comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy.

    Grossman, A; Lytras, N; Savage, M O; Wass, J. A.; Coy, D H; Rees, L. H.; Jones, A. E.; Besser, G M

    1984-01-01

    Human pancreatic growth hormone releasing factor (hpGHRF(1-40] stimulates the release of growth hormone in normal subjects and some patients with growth hormone deficiency. A study comparing the shorter chain amidated analogue hpGHRF(1-29) with an equivalent dose of hpGHRF(1-40) in seven normal subjects showed no significant difference in growth hormone response between the two preparations. Six patients with prolactinomas were also tested; these patients had received megavoltage radiotherapy...

  19. Epidermal growth factor and imagine diagnosis and therapy of tumour with radionuclides

    It has a direct proportion correlation between the epidermal growth factor receptor levels of tumour and tumour differentiation degree, tumour sizes, stage, mototic index or cancer recurrence. Epidermal growth factor receptor is detected in 90% of the tumours, in which, 54% of epidermal growth factor receptor of malignant tumours can link with external genous ligand. Therefore, radionuclide labelled epidermal growth factor will bring about the imaging diagnosis and therapy of malignant tumours. The research present situation and clinical significance of radionuclide labelled epidermal growth factor for receptor imaging diagnosis and therapy of tumour are emphatically elaborated

  20. Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte Rønde;

    2004-01-01

    Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV......-lipodystrophy. These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy. In LIPO, abdominal fat mass and insulin...

  1. Mecasermin (recombinant human insulin-like growth factor I).

    Rosenbloom, Arlan L

    2009-01-01

    Growth hormone (GH) exercises its growth effects by stimulating insulin-like growth factor I (IGF-I) synthesis in the liver (endocrine IGF-I) and by inducing chondrocyte differentiation/replication and local production of IGF-I (paracrine/autocrine IGF-I). Injectable recombinant human (rh)IGF-I (mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an insulin-sensitizing agent in severe insulin-resistant conditions. Although the insulin-sensitizing effect may benefit both type 1 and type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of IGF-I and include chronic liver disease, cystic fibrosis, wound healing, AIDS muscle wasting, burns, osteoporosis, Crohn's disease, anorexia nervosa, Werner syndrome, X-linked severe combined immunodeficiency, Alzheimer's disease, muscular dystrophy, amyotrophic lateral sclerosis, hearing loss prevention, spinal cord injury, cardiovascular protection, and prevention of retinopathy of prematurity. The most frequent side effect is hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve hyperplasia of lymphoid tissue, which may require tonsillectomy/adenoidectomy, accumulation of body fat, and coarsening of facies. The anti-apoptotic properties of IGF-I are implicated in cancer

  2. Quantitative analysis using ELISA of vascular endothelial growth factor and basic fibroblast growth factor in human colorectal cancer, liver metastasis of colorectal cancer and hepatocellular carcinoma

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Fran(c)ois Labrousse; Véronique Truffinet; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR Angiogenesis consists of the sprouting of capillaries from pre-existing vessels[1]. It is well-known that tumor growth is angiogenesis-dependent. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)stimulated vascular endothelial cell proliferation and are involved in the neoplastic angiogenesis of several types of tumors including those of the intestinal tract[1-5].

  3. Adverse Reaction to Cetuximab, an Epidermal Growth Factor Receptor Inhibitor.

    Štulhofer Buzina, Daška; Martinac, Ivana; Ledić Drvar, Daniela; Čeović, Romana; Bilić, Ivan; Marinović, Branka

    2016-04-01

    Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities

  4. Inhibition of 125I-epidermal growth factor binding to cultured keratinocytes by antiproliferative molecules gamma interferon, cyclosporin A, and transforming growth factor-beta

    The growth of cultured human keratinocytes (KC) is inhibited by gamma interferon (IFN-gamma), cyclosporin A and transforming growth factor-beta, but not by tumor necrosis factor. When these antiproliferative molecules were added to KC they induced a concentration and time-dependent inhibition of 125I-epidermal growth factor (I-EGF) binding. These anti-proliferative molecules primarily reduced the number of binding sites by approximately 25%-50% without affecting the binding affinity. Tumor necrosis factor did not influence the ligand binding by I-EGF. In parallel with the ability of the antiproliferative molecules to inhibit I-EGF binding, there was an increase in transforming growth factor-alpha production. These results suggest that several different antiproliferative molecules may share a common mechanism to inhibit cell growth by reducing I-EGF binding to KC

  5. Tumour-stromal interactions: Transforming growth factor-beta isoforms and hepatocyte growth factor/scatter factor in mammary gland ductal morphogenesis

    The mammary gland undergoes morphogenesis through the entire reproductive life of mammals. In mice, ductal outgrowth from the nipple across the fat pad results in an intricate, well spaced ductal tree that further ramifies and develops alveolar structures during pregnancy. Ductal morphogenesis is regulated by the concerted action of circulating steroid and polypeptide hormones, and local epithelial-mesenchymal inductive signals. Transforming growth factor (TGF)-β1-3 and hepatocyte growth factor (HGF)/scatter factor (SF) are important components of this latter signaling pathway. TGF-β1 and TGF-β3 have roles in both promotion and inhibition of branching morphogenesis that are dependent on concentration and context. HGF/SF promotes ductal outgrowth and tubule formation in the mammary gland. These data suggest that these two growth factors have complementary roles in promoting mammary ductal morphogenesis and in maintaining ductal spacing. In addition, TGF-β3 triggers apoptosis in the alveolar epithelia, which is a necessary component of mammary gland involution and return of the ductal structure to a virgin-like state after lactation

  6. Neutrino mass, dark energy, and the linear growth factor

    Kiakotou, Angeliki; Elgarøy, Øystein; Lahav, Ofer

    2008-03-01

    We study the degeneracies between neutrino mass and dark energy as they manifest themselves in cosmological observations. In contradiction to a popular formula in the literature, the suppression of the matter power spectrum caused by massive neutrinos is not just a function of the ratio of neutrino to total mass densities fν=Ων/Ωm, but also each of the densities independently. We also present a fitting formula for the logarithmic growth factor of perturbations in a flat universe, f(z,k;fν,w,ΩDE)≈[1-A(k)ΩDEfν+B(k)fν2-C(k)fν3]Ωmα(z), where α depends on the dark energy equation of state parameter w. We then discuss cosmological probes where the f factor directly appears: peculiar velocities, redshift distortion, and the integrated Sachs-Wolfe effect. We also modify the approximation of Eisenstein and Hu [Astrophys. J.ASJOAB0004-637X 511, 5 (1999)10.1086/306640] for the power spectrum of fluctuations in the presence of massive neutrinos and provide a revised code [http://www.star.ucl.ac.uk/~lahav/nu_matter_power.f].

  7. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  8. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases

  9. [Regulation of osteoclastogenesis by osteocytes through growth differentiation factor-15].

    Hinoi, Eiichi

    2014-01-01

    Osteocytes are the most abundant cells in bone. However, little attention has been paid to their role in bone remodeling. In this study, osteoclast differentiation was significantly enhanced by conditioned media derived from cultures of osteocytic MLO-Y4 cells that were cultured under hypoxic conditions. Using microarray analysis, we identified growth differentiation factor-15 (GDF15) as a pivotal factor secreted from osteocytes under hypoxia. Indeed, treatment with recombinant GDF15 markedly increased osteoclast differentiation in vitro. Further to investigate the importance of GDF15 in vivo, we used a hypoxic murine model that involved ligation of the right femoral artery. The volume of cancellous bone in the proximal tibia of the ligated limb was significantly reduced, together with a significant increase in osteoclast-related parameters. Addition of anti-GDF15 antibody prevented bone loss and osteoclastic activation in the tibiae of mice that had undergone femoral artery ligation. These results suggest that GDF15, which is secreted from osteocytes under hypoxia during bone remodeling, may be a positive regulator of osteoclastic differentiation. The in vivo usefulness of the anti-GDF15 antibody might provide insights for the development of novel therapeutics for bone disorders related to hypoxia or ischemic insults. PMID:25452236

  10. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F;

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

  11. The Association between Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-3 Levels and Clinical Prognosis in Patients with Ischemic Stroke

    Hasan Yaşar

    2015-04-01

    Full Text Available OBJECTIVE: Recent studies report that the insulin-like growth factor system may be involved in stroke pathogenesis, and is reported to increase myelination, maturation, cell proliferation and neuronal sprouting of the central nervous system. The aim of the present study is to demonstrate the role of insulin-like growth factor system in ischemic stroke pathogenesis and its association with the prognosis by investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels in patients diagnosed with acute ischemic stroke. METHODS: : Sixty-eight patients and 20 healthy individuals were included to this study. Clinical evaluation of the patients was performed according to National Institute of Health Stroke Scale and functional outcomes were graded according to Modified Rankin Scale. Bamford classification was used for the clinical classification of ischemic strokes, and the TOAST system for etiological classification. Each patient's levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured on the first, fifth and thirtieth day of ischemic stroke. RESULTS: Only the levels of insulin-like growth factor binding protein-3 on the day of 5 were significantly decreased compared to the control group. The decrease in IGF-1 values was associated with an increased risk of death and was accompanied by clinical worsening and decreased functionality. CONCLUSION: It has been concluded that the levels of investigating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 may affect mortality risk, clinical condition and functionality outcomes in patients presenting with ischemic stroke, and further studies are needed for the investigation of different effects of insulin-like growth factor-1 in future.

  12. A transcription factor active on the epidermal growth factor receptor gene

    The authors have developed an in vitro transcription system for the epidermal growth factor receptor (EGFR) oncogene by using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce EGFR. They found that a nuclear factor, termed EGFR-specific transcription factor (ETF), specifically stimulated EGFR transcription by 5- to 10-fold. In this report, ETF, purified by using sequence-specific oligonucleotide affinity chromatography, is shown by renaturing material eluted from a NaDodSO4/polyacrylamide gel to be a protein with a molecular mass of 120 kDa. ETF binds to the promoter region, as measured by DNase I footprinting and gel-mobility-shift assays, and specifically stimulates the transcription of the EGFR gene in a reconstituted in vitro transcription system. These results suggest that ETF could play a role in the overexpression of the cellular oncogene EGFR

  13. Transforming growth factor-β and breast cancer: Transforming growth factor-β/SMAD signaling defects and cancer

    Transforming growth factor-β (TGF-β) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-β are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative responses are mediated by a signaling system that includes two types of cell surface receptors and intracellular signal transducers, the SMAD proteins. Different molecular mechanisms can lead to loss of antiproliferative TGF-β responses in tumor cells, including mutations in components of the signaling system and inhibition of the SMAD signaling pathway by aberrant activities of various regulatory molecules. Some of these mechanisms will be discussed, with emphasis on their potential involvement in breast tumorigenesis

  14. Transforming growth factor-beta as a differentiating factor for cultured smooth muscle cells.

    Gawaziuk, J P; X; Sheikh, F; Cheng, Z-Q; Cattini, P A; Stephens, N L

    2007-10-01

    The aim of the present study was to determine whether the development of supercontractile smooth muscle cells, contributing to the nonspecific hyperreactivity of airways in asthmatic patients, is due to transforming growth factor (TGF)-beta. In cultured smooth muscle cells starved by removal of 10% foetal bovine serum for 7 days, growth arrest was seen; 30% became elongated and demonstrated super contractility. Study of conditioned medium suggested that the differentiating factor was TGF-beta. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was carried out on conditioned medium from the arrested cells. Two protein bands were identified as matrix metalloproteinase (MMP)-2 and TGF-beta1. To determine second messenger signalling by SMAD2, Western blotting and confocal microscopy were employed. Conditioned medium from arrested cultures showed the presence of MMP-2 and TGF-beta1, as revealed by SDS-PAGE; 68- and 25-kDa bands were seen. Differentiation was confirmed by upregulation of marker proteins, smooth muscle type myosin heavy chain and myosin light chain kinase. Confirmation was obtained by downregulating these proteins with decorin treatment, which reduces the levels of active TGF-beta and an adenoviral dominant-negative vector coding for a mutated type II TGF-beta-receptor. Activation of second messenger signalling was demonstrated immunocytochemically by the presence of phosphorylated SMAD2 and SMAD4. Transforming growth factor-beta is likely to be the differentiating factor responsible for the development of these supercontractile smooth muscle cells. The development of such cells in vivo after cessation of an asthmatic attack could contribute to the nonspecific hyperreactivity of airways seen in patients. PMID:17596270

  15. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  16. A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes

    Shannon, M.F.; Pell, L.M.; Kuczek, E.S.; Occhiodoro, F.S.; Dunn, S.M.; Vadas, M.A. (Div. of Human Immunology, Institute of Medical and Veterinary Science, Frame Road, Adelaide 5001 (AU)); Lenardo, M.J. (Lab. of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD (US))

    1990-06-01

    A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. The authors show that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor {alpha} (TNF-{alpha}) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-{alpha}-responsive enhancer in these cells.

  17. Transforming growth factor beta (TGF-β in milk: a review

    Fernanda Lopes da Silva

    2016-06-01

    Full Text Available Bovine milk and colostrum contain growth factors such as insulin-like growth factor IGF-I, IGF-II, transforming growth factor TGF-β1, TGF-β2, epidermal growth factor EGF, basic fibroblast growth factor bFGF and platelet-derived growth factor PDGF. In recent years, intense scientific interest has been focused on the identification of factors within bovine milk that may be relevant to improving human health. Then a number of methodologies for the extraction of milk growth factors from milk, colostrum or whey have been developed. Cation-exchange chromatography has been widely used because of the basic nature of the growth factors. Also, microfiltration has been used for the concentration of some growth factors from colostrum, while ultrafiltration was successful only in separating IGF-I from IGF-II in whey. Growth factor extracts from milk, colostrum or whey have been used as therapeutic preparations for wound healing and in the treatment of inflammatory gut disorders.

  18. Impact of trade factors on economic growth: seemingly unrelated regression model

    Nawaz , Samar; Aziz , Arshad; Khalid ZAMAN

    2014-01-01

    This study explores the impact of trade on the economic growth, using seemingly unrelated regression model for SAARC countries namely Bangladesh, India, Pakistan and Srilanka for the period of 1980-2012. Trade factors include total exports, total imports, terms of trade, trade openness and investment. The results indicate the strong correlation between trade factors and economic growth, however, the magnitude of influencing economic growth varies factors to factors of international trade.

  19. Platelets accelerate gastric ulcer healing through presentation of vascular endothelial growth factor

    Wallace, John L; Dicay, Michael; McKnight, Webb; Dudar, Genevieve K

    2006-01-01

    Platelets contain an array of growth factors that can modulate healing processes, including both pro- (e.g., vascular endothelial growth factor (VEGF)) and antiangiogenic (e.g., endostatin) factors. Previous studies have shown that circulating platelets contribute significantly to gastric ulcer healing, acting as a delivery system for these growth factors to the site of injury. In this study, we examined the effects of orally administered human platelets on the healing of gastric ulcers in ra...

  20. Recombinant basic fibroblast growth factor accelerates wound healing.

    McGee, G S; Davidson, J M; Buckley, A; Sommer, A; Woodward, S C; Aquino, A M; Barbour, R; Demetriou, A A

    1988-07-01

    Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds. PMID:3392988

  1. Assessment of epidermal growth factor receptor status in glioblastomas

    Hui-Jun Zhu

    2013-10-01

    Full Text Available Introduction: Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy-7-ethoxy-4-(3'-iodophenoxyquinazoline ([125I]PYK is promising for the evaluation of the epidermal growth factor receptor (EGFR status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the expressions and mutation of EGFR were tested with [125I] PYK in glioblastoma in vitro and in vivo to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment. Materials and Methods: Glioblastoma cell lines with different expression of EGFR were tested. Growth inhibition of cell lines by gefitinib was assessed by the 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT colorimetric assay. Uptake levels of [125I]PYK were evaluated in cell lines in vitro. Tumor targeting of [125I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT. Results: High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [125I] PYK in cell lines in vitro was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [125I]PYK for xenografts showed no [125I]PYK uptake. Conclusion: The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [125I]PYK, which might be due to the complicated expression of EGFR status in glioblastoma. Thus, new tracers for sites downstream of the mutant EGFR should be investigated in further studies.

  2. Selenoprotein W controls epidermal growth factor receptor surface expression, activation and degradation via receptor ubiquitination

    Epidermal growth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of growth factor receptors that modulate a complex network of intracellular signaling pathways controlling growth, proliferation and differentiation. Selenoprotein W (SEPW1) is a diet-regulated, highly conserved...

  3. Reduced expression of epidermal growth factor receptor related protein in gastric cancer

    Moon, W. S.; Tarnawski, A S; Chai, J.; Yang, J. T.; Majumdar, A.P.N.

    2005-01-01

    Objectives: The recently cloned epidermal growth factor receptor related protein (ERRP) has been proposed to be a negative regulator of the epidermal growth factor receptor (EGFR). Because of the causal involvement of EGFR and its ligands in gastric cancer growth, we investigated expression of ERRP and cell proliferation in human gastric cancer.

  4. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit;

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed as...... production or to increased cleavage by proteases other than MMP-9....

  5. Vascular endothelial growth factor promotes angiogenesis in gastric carcinoma

    LIU Du-hu; ZHANG Xue-yong; HUANG Yu-xin; SU Yong-ping; FAN Dai-ming

    2002-01-01

    Objective: To explore the role of vascular endothelial growth factor (VEGF) in the angiogenesis and development of human gastric carcinoma. Methods: The expressions of VEGF and its receptor KDR (kinase-domain insert containing receptor) in human gastric cancer tissue and SGC-7901 cells were detected with immunohistochemical staining. Microvessel density (MVD) was obtained after immunostaining for FactorVIII. VEGF in SGC-7901 cell line was detected with Western blot. VEGF levels were manipulated in human gastric cancer cell by using eukaryotic expression vector containing the complete VEGF165 complimentary DNA in either the sense or antisense orientation. Finally the biological characteristics of the transfectants were identified. Results: VEGF-positive rate in TNM grade Ⅲ and Ⅳ gastric carcinomas (19. 0%) were significantly higher than that in grade I and Ⅱ (72. 4%) (P<0. 05). Increased MVD was found in VEGF-positive tumors (16. 4± 6. 7), which is significantly larger than in VEGF-negative tumors (6. 5 ±- 2. 1) (P<0. 05). Human gastric cancer cells (SGC-7901) produced 3 kinds of VEGF in molecule. In 2 cases of 50 specimens, a few gastric cancer cells expressed KDR in cytoplasm and cell membranes. SGC-7901 ceils with antisense VEGF165 showed a significant reduction in cell surface VEGF protein with the immunofluorescence intensity from 8. 9% to 31.6% (P<0.05). However, those with stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF with the immunofluorescence intensity from 75.4% to 31.6% (P<0. 05). The decrease of VEGF levels was associated with a marked decrease in the growth of nude mouse xenografted tumor (33 d post-implantation, 345.4±136.3 mm3 in size) (P<0. 05vs control SGC-7901 group), whereas VEGF overexpression resulted in an increase of xenografted tumor size(33 d post-implantation, 2 350. 5±637.7 mm3 in size) (P<0. 05 vs control SGC-7901 group). Conclusion:VEGF plays an

  6. Hyperbaric oxygen and basic fibroblast growth factor promote growth of irradiated bone

    Purpose: The goal of the current experiment is to test for protective effect of hyperbaric oxygen (HBO) and basic fibroblast growth factor (bFGF) on bone growth. Methods and Materials: Control C3H mice received hind leg irradiation at 0, 10, 20, or 30 Gy. HBO-treated groups received radiation 1, 5, or 9 weeks before beginning HBO. The remaining groups began bFGF ± HBO 1 or 5 weeks after 30 Gy. HBO treatments were given 5 days per week for 4 weeks at 2 ATA for 3 h/day. bFGF was given intravenously at 6 μg twice a week for 4 weeks. Results: HBO improved bone growth after radiation in the 10 and 20 Gy groups. At 18 weeks control tibia length discrepancy is 0.0, 4.2, 8.2, and 10.7% after 0, 10, 20, and 30 Gy, respectively. HBO beginning in week 1, 5, or 9 following 10 Gy decreased these discrepancies to 2.0% (p < 0.05), 1.8% (p < 0.05), and 2.4% (p < 0.05), respectively. After 20 Gy, HBO decreased these discrepancies to 7.0% (p = ns), 4.9% (p < 0.05), and 3.6% (p < 0.05), respectively. At 30 Gy, HBO alone had no effect on bone shortening. bFGF improved tibia length discrepancy with or without HBO. At 18 weeks length discrepancies were 6.5% (p < 0.05) and 7.3 (p < 0.05), and after bFGF alone were 6.8% (p < 0.05) and 7.3% (p < 0.05) for treatment beginning in week 1 or 5, respectively. Tibial growth at 18 and 33 weeks following radiation were similar. Conclusion: Radiation effects on bone growth can be significant reduced by HBO after 10 or 20 Gy, but not after 30 Gy. At 30 Gy bFGF still significantly reduced the degree of bone shortening, but HBO provided no added benefit to bFGF therapy

  7. Regulation of vascular endothelial growth factor on the expression of fracture healing-related factors

    CHU Tong-wei; WANG Zheng-guo; ZHU Pei-fang

    2007-01-01

    Objective: To study the effect of vascular endothelial growth factor (VEGF) and anti-VEGF on the expression of fracture healing-related factors and observe pathological changes at fractured sites.Methods: Fracture models were established in 105 New Zealand white rabbits and they were randomly divided into control group, VEGF group and anti-VEGF group.The relevant factors expression at fractured sites was assayed and pathological changes were observed in decalcified samples at 8, 24, 72 hours and 1,3,5,8 weeks after fracture.Results: After application of VGEF, the expression of BMP appeared earlier and expression time lasted longer.On the contrary, anti-VEGF completely inhibited the expression of BMP. The fractured sites were filled with fibrous callus, cartilaginous callus and bony callus at the 3rd week and woven bone was constructed at the 5th week.Fracture healing was accomplished at the 8th week in VEGF group. In anti-VEGF polyclonal antibody group,cellular necrosis increased at early period. Continuous focal necrosis was seen in the fractured sites from the 1st week to 5th week. Vascularization reduced obviously at the 3rd week.Conclusions: Fracture healing is a result of mutual regulation and coordination among many factors. VEGF may be an important factor in fracture healing.

  8. DOES SINGLE INTRAMUSCULAR APPLICATION OF AUTOLOGOUS CONDITIONED PLASMA INFLUENCE SYSTEMIC CIRCULATING GROWTH FACTORS?

    Gert Schippinger

    2012-09-01

    Full Text Available Platelet-rich plasma (PRP has been employed to treat sports injuries to possibly accelerate healing and regeneration. This method offers some potential, especially for athletes. Growth factors are generally prohibited by the World Anti Doping Agency with exception to PRP which may induce adverse effects. The aim of this study was to evaluate any systemic increase of growth factors such as Insulin Like Growth Factor-1, Endothelial Growth Factors, Platelet-Derived Growth Factors, Fibroblast Growth Factors, Vascular-Endothelial Growth Factor and Transforming Growth Factors after local intramuscular administration of PRP in young, healthy male subjects keeping in mind adverse treatment effects. Enriched plasma from centrifuged blood samples was injected into the gluteus muscle. Venous blood was collected and serum prepared before as well as 0.5, 3 and 24 hours after PRP administration. Growth factors were analyzed using ELISA test kits. No significant systemic increase of growth factor levels was found after PRP injection except TGF-ß2. For that reason the PRP method may be applied for muscle injury treatment in elite athletes although further studies are necessary to clarify the response to the unspecific increased TGF-ß2 blood levels, which could increase the risk for local fibrosis

  9. Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression.

    Girer, Nathaniel G; Murray, Iain A; Omiecinski, Curtis J; Perdew, Gary H

    2016-07-15

    The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knock-out mouse model (Cre(Alb)Ahr(Fx/Fx)). Compared with the congenic parental strain (Ahr(Fx/Fx)), non-fasted Cre(Alb)Ahr(Fx/Fx) mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of the FGF21-target gene Igfbp1 Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR-ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor α (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element-binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling. PMID:27226639

  10. Growth and the growth hormone-insulin like growth factor 1 axis in children with chronic inflammation: current evidence, gaps in knowledge and future directions

    Wong, S. C.; Dobie, R.; Altowati, M A; Werther, G A; Farquharson, C; Ahmed, S. F.

    2016-01-01

    Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects...

  11. Mouse Balb/c3T3 cell mutant with low epidermal growth factor receptor activity: induction of stable anchorage-independent growth by transforming growth factor β

    A mutant clone (MO-5) was originally isolated as a clone resistant to Na+/K+ ionophoric antibiotic monensin from mouse Balb/c3T3 cells. MO-5 was found to show low receptor-endocytosis activity for epidermal growth factor (EGF):binding activity for EGF in MO-5 was less than one tenth of that in Balb/c3T3. Anchorage-independent growth of MO-5 was compared to that of Balb/c3T3 when assayed by colony formation capacity in soft agar. Coadministration of EGF and TGF-β efficiently enhanced anchorage-independent growth of normal rat kidney (NRK) cells, but neither factor alone was competent to promote the anchorage-independent growth. The frequency of colonies appearing in soft agar of MO-5 or Balb/c3T3 was significantly enhanced by TGF-β while EGF did not further enhance that of MO-5 or Balb/c3T3. Colonies of Balb/c3T3 formed in soft agar in the presence of TGF-β showed low colony formation capacity in soft agar in the absence of TGF-β. Colonies of MO-5 formed by TGF-β in soft agar, however, showed high colony formation capacity in soft agar in the absence of TGF-β. Pretreatment of MO-5 with TGF-β induced secretion of TGF-β-like activity from the cells, while the treatment of Balb/c3T3 did not induce the secretion of a significant amount of TGF-β-like activity. The loss of EGF-receptor activity in the stable expression and maintenance of the transformed phenotype in MO-5 is discussed

  12. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  13. Saccharin and Cyclamate Inhibit Binding of Epidermal Growth Factor

    Lee, L. S.

    1981-02-01

    The binding of 125I-labeled mouse epidermal growth factor (EGF) to 18 cell lines, including HeLa (human carcinoma), MDCK (dog kidney cells), HTC (rat hepatoma), K22 (rat liver), HF (human foreskin), GM17 (human skin fibroblasts), XP (human xeroderma pigmentosum fibroblasts), and 3T3-L1 (mouse fibroblasts), was inhibited by saccharin and cyclamate. The human cells were more sensitive to inhibition by these sweeteners than mouse or rat cells. EGF at doses far above the physiological levels reversed the inhibition in rodent cells but not in HeLa cells. In HeLa cells, the doses of saccharin and cyclamate needed for 50% inhibition were 3.5 and 9.3 mg/ml, respectively. Glucose, 2-deoxyglucose, sucrose, and xylitol did not inhibit EGF binding. Previous studies have shown that phorbol esters, strongly potent tumor promoters, also inhibit EGF binding to tissue culture cells. To explain the EGF binding inhibition by such greatly dissimilar molecules as phorbol esters, saccharin, and cyclamate, it is suggested that they operate through the activation of a hormone response control unit.

  14. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes.

    Geetanjali Kharmate

    Full Text Available Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa. However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa.

  15. Biochemical and biological properties of the nerve growth factor receptor

    We have utilized a monoclonal antibody (192-IgG) to study the rat nerve growth factor receptor. After intraocular injection, 125I-192-IgG was retrogradely transported in sympathetic neuronal axons to the superior cervical ganglion. When the sciatic nerve was ligated to induce the accumulation of axonally transported materials, 192-IgG immunostaining was observed on both sides of the ligature, indicating that NGF receptors are transported in both orthograde and retrograde directions. By using 125I-NGF crosslinking and 192-IgG immunoprecipitation, we detected receptor molecules throughout the rat brain, thereby supporting the hypothesis that NGF is active in the central nervous system. We also discovered that sciatic nerve transection leads to a dramatic increase in the amount of NGF receptor found in the distal portion of the nerve. Immunostaining revealed that all Schwann cells in the distal axotomized nerve were expressing NGF receptors. We examined phosphorylation of NGF receptor in cultured sympathetic neurons and PC12 cells. We also examined pharmacological effects of 192-IgG. Systemic injection of 192-IgG into neonatal rats caused a permanent partial sympathectomy in a dose-dependent manner; a maximum of 50% of the cells were killed

  16. The ontogeny of epidermal growth factor receptors during mouse development

    In an attempt to understand the role(s) of epidermal growth factor (EGF) in vivo during murine development, we have examined the 125I-EGF binding characteristics of EGF-receptors in membrane preparations of tissues from the 12th day of gestation to parturition. Using autoradiography, the earliest time that we could detect EGF-receptors was on trophoblast cells cultured for 3 days as blastocyst outgrowths. Trophoblast eventually forms a large portion of the placenta, where EGF-receptors have long been recognized. We measured the number and affinity of EGF-receptors on tissues dissected from conceptuses from the 12th day of gestation in order to identify a stage when tissues may be most sensitive to EGF. Whereas the number of EGF receptors increases during gestation for all tissues examined, the affinity of the receptors declines for carcass and placenta and remains relatively unchanged for brain and liver. This suggests that EGF may function differently throughout development. Our hypothesis is that EGF (or its embryonic equivalent) initially stimulates proliferation in embryonic cells and then stimulates differentiation as the tissues mature. In the adult, its main role could be to stimulate tissue repair after damage

  17. Signal transduction by the platelet-derived growth factor receptor

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  18. Epidermal growth factor receptor inhibition in lung cancer: status 2012.

    Hirsch, Fred R; Jänne, Pasi A; Eberhardt, Wilfried E; Cappuzzo, Federico; Thatcher, Nick; Pirker, Robert; Choy, Hak; Kim, Edward S; Paz-Ares, Luis; Gandara, David R; Wu, Yi-Long; Ahn, Myung-Ju; Mitsudomi, Tetsuya; Shepherd, Frances A; Mok, Tony S

    2013-03-01

    Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. PMID:23370315

  19. Fibroblast growth factors as tissue repair and regeneration therapeutics.

    Nunes, Quentin M; Li, Yong; Sun, Changye; Kinnunen, Tarja K; Fernig, David G

    2016-01-01

    Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West. PMID:26793421

  20. Infiltration of Autologous Growth Factors in Chronic Tendinopathies

    Antonio Crescibene

    2015-01-01

    Full Text Available Achilles tendinopathy and patellar tendinopathy are among the most frequent diagnoses in sports medicine. Therapeutic treatment of the disease is difficult, particularly in chronic cases. In literature, several studies suggest the employment of Platelet-Rich Plasma as a therapeutic alternative in tendinopathies. The choice of employing this method is based on the activity of growth factors contained in platelets which activate, amplify, and optimize the healing process. We selected 14 patients affected by Achilles tendinopathy and 7 patients affected by patellar tendinopathy, with a two-year final follow-up. These patients underwent a cycle of three tendinous infiltrations, after clinical and instrumental evaluation carried out by means of specific questionnaires and repeated ultrasound scans. Ultrasound scans of 18 patients showed signs of reduction in insertional irregularities. The result is confirmed by complete functional recovery of the patients, with painful symptomatology disappearing. The patients showed a clear pain reduction, along with an enhanced VISA score after the 24-month follow-up, equal to 84.2 points on a scale of 0 to 100. In conclusion, the present study provides evidence to suggest that PRP infiltration is a valid option to patients with chronic tendinopathy who did not benefit from other treatments.

  1. Role of epidermal growth factor in pathogenesis of uterine leiomyomas

    Chun Su; Mei Fan; Lin Lu; Pei Li

    2015-01-01

    Objective:To investigate the role of epidermal growth factor (EGF) in the pathogenesis of uterine leiomyomas.Methods: Human myometrial smooth muscle cells (HM-SMCs) and smooth muscle cells of human uterine leiomyomas (HL-SMCs) were separated from patients’ specimens and cultured. After processed by EGF or PD98059 (inhibitor of MKK/MEK) +EGF, the proliferation rate of both SMCs was detected by BrdU method and the phosphorylation level of p44/42 mitogen-activated protein kinase (MAPK) was determined by Western-blot. After different processing time by EGF, the phosphorylation levels of p44/42 MAPK and AKT and p27 expression level in both SMCs were detected by Western-blot.Results: EGF could significantly promote HL-SMCs proliferation and PD98059 could inhibit this effect (P<0.05); besides, PD98059 could inhibit the increase of the phosphorylation level of p44/42 MAPK in both SMCs induced by EGF. When the processing time by EGF was over 15min, the phosphorylation levels of p44/42 MAPK and AKT in both SMCs decreased sharply and were close to zero; p27 expression in HM-SMCs raised significantly while the upregulation in HL-SMCs was little.Conclusions: EGF could not cause activation of EGFR because of the dephosphorylation of p44/42 MAPK and AKT in HL-SMCs, which caused p27 expression insufficiently and cell cycle dysregulation.

  2. Fibroblast growth factors, old kids on the new block.

    Li, Xiaokun; Wang, Cong; Xiao, Jian; McKeehan, Wallace L; Wang, Fen

    2016-05-01

    The fibroblast growth factors (FGFs) are a family of cell intrinsic regulatory peptides that control a broad spectrum of cellular activities. The family includes canonic FGFs that elicit their activities by activating the FGF receptor (FGFR) tyrosine kinase and non-canonic members that elicit their activities intracellularly and via FGFR-independent mechanisms. The FGF signaling axis is highly complex due to the existence of multiple isoforms of both ligands and receptors, as well as cofactors that include the chemically heterogeneous heparan sulfate (HS) cofactors, and in the case of endocrine FGFs, the Klotho coreceptors. Resident FGF signaling controls embryonic development, maintains tissue homeostasis, promotes wound healing and tissue regeneration, and regulates functions of multiple organs. However, ectopic or aberrant FGF signaling is a culprit for various diseases, including congenital birth defects, metabolic disorder, and cancer. The molecular mechanisms by which the specificity of FGF signaling is achieved remain incompletely understood. Since its application as a druggable target has been gradually recognized by pharmaceutical companies and translational researchers, understanding the determinants of FGF signaling specificity has become even more important in order to get into the position to selectively suppress a particular pathway without affecting others to minimize side effects. PMID:26768548

  3. Treatment of Skin Avulsion Injuries with Basic Fibroblast Growth Factor

    Hajime Matsumine, MD, PhD

    2015-04-01

    Full Text Available Summary: This report describes favorable outcomes in 9 patients with skin avulsion injuries of the extremities who underwent full-thickness skin grafting and basic fibroblast growth factor (bFGF application. Following removal of contaminated subcutaneous fat tissue on the inside of skin, the avulsed skin was processed into a full-thickness skin graft, with as much of the skin used as possible irrespective of damage. Several drainage holes (5–10 mm in diameter were made on the graft for drainage from the graft bed and to prevent seroma and hematoma formation. Genetically recombinant human bFGF was sprayed at a dose of 1 μg/cm2 onto the graft bed, which was then covered with the graft and sutured. Pressure immobilization with ointment gauzes and elastic bandages was administered for 1 week postoperatively, and the surface of the skin grafts that did not take was scraped away, preserving the revascularized dermal component on the debrided raw surface as much as possible. bFGF was sprayed again onto the debrided surface to promote epithelialization. Wound closure was achieved in all cases with conservative therapy. The surgical procedure was effective in preventing postoperative ulcer formation and scar contracture and resulted in wound healing with the formation of good-quality, flexible scars.

  4. Platelet-derived growth factor stimulated mechanisms of glucosamine incorporation

    Platelet-derived growth factor (PDGF) treatment of density-arrested BALB/c-3T3 cells results in increased [3H]glucosamine (GlcN) incorporation into cellular material. The enhanced GlcN incorporation is not due to a preferential increase in proteoglycan synthesis as measured by [35S]H2SO4 incorporation. Approximately 50% of the GlcN incorporated in PDGF or platelet-poor plasma (PPP)-treated cultures enters N-linked glycoproteins. Addition of dolichol-phosphate (dolichol-P), a required intermediate in N-linked glycosylation, did not alter [3H]GlcN incorporation in PDGF-treated cells but did increase incorporation in PPP-treated cultures to a level comparable to that observed for PDGF-treated cultures. PDGF-treated cultures contained twofold greater quantities of [3H]GlcN dolichol intermediates and lipid-free glycoprotein. Over a 12-h time course 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) activity was similar in cultures treated with PDGF or PPP. Results of these studies reveal that enhanced protein glycosylation in response to PDGF treatment is not the result of a direct effect on HMG CoA reductase

  5. TRANSFORMING GROWTH FACTOR 1 AT LIVER TRANSPLANTATION

    R. M. Kurabekova

    2015-10-01

    Full Text Available This review summarizes the current literature devoted to the analysis of the role of transforming growth factor beta 1 (TGF-β1 at liver transplantation. TGF-β1 plays a key role in the development of liver fi brosis, as well as in development of the immune response; its concentration in the blood and tissue changes in liver diseases. TGF-β1 levels in the blood of the recipients are associated with the development of liver fi brosis, the formation of immune tolerance and immune response to active infection. Measuring the level of TGF-β1 at liver transplantation may have diagnostic and prognostic value for assessing the graft condition. Currently, clinical data on the role of the cytokine at liver transplantation are not accumulated enough and further research on the relation of TGF-β1 levels with different clinical and laboratory parameters in liver transplant patients is needed. The review analyzed 54 sources of literature, more than half of which were published in the last fi ve years.

  6. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  7. Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth

    Sarah K Johnson; Randy S Haun

    2009-01-01

    AIM: To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC).METHODS: The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses.Changes in cell survival and signal transduction were evaluated after mitogen activated protein kinase and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.RESULTS: After serum depr ivat ion, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival.CONCLUSION: These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.

  8. Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

    Bokhari, R.; Zwart, S. R; Fields, E.; Heer, M.; Sibonga, J.; Smith, S. M.

    2014-01-01

    Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1

  9. Enhanced effect of fibroblast growth factor-2-containing dalteparin/protamine nanoparticles on hair growth

    Takabayashi, Yuki; Nambu, Masaki; Ishihara, Masayuki; Kuwabara, Masahiro; Fukuda, Koichi; Nakamura, Shingo; Hattori, Hidemi; Kiyosawa, Tomoharu

    2016-01-01

    Purpose Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs) can effectively carry growth factors (GFs) such as fibroblast GF (FGF)-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs) on hair growth. Patients and methods In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL) and D/P NPs (56 μg/mL) was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter. Results The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience. Conclusion The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia. PMID:27274299

  10. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders;

    2008-01-01

    Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...... investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six...... severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P<0.01), 24-h GH...

  11. Release of transforming growth factor beta 1 and platelet derived growth factor type AB from canine platelet gels obtained by the tube method and activated with calcium salts

    RF Silva; GC Santana; FOP Leme; JU Carmona; CMF Rezende

    2013-01-01

    The objectives of this study were: 1) to measure the concentrations of transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor type AB (PDGF-AB) in plasma and platelet gel (PG) activated with calcium salts (gluconate or chloride) in dogs, and 2) to determine correlations between cell results and growth factors (GF) concentrations. Blood samples were collected from fourteen Brazilian Fila dogs. EDTA was used to obtain whole blood and plasma while ACD-A solution was used t...

  12. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

    Lang, C H; Pollard, V; Fan, J; Traber, L D; Traber, D L; Frost, R A; Gelato, M C; Prough, D S

    1997-07-01

    The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection. PMID:9249574

  13. The sustainability and transition of economic growth in China: from a perspective of factor structure

    Wang Yafei; Wu Xiaohang

    2008-01-01

    After more than 20 years' high speed growth, the sustainable growth of Chinese economy faces serious lim-itation of resources and factors now and in the future. In order to maintain the economic growth, China has to trans, form the way of economic growth. Based on the analysis on the related theories of economic growth and the structur-al transformation in factors of production, this paper proposes that the transformation of the economic growth way has to impel the optimization and the promotion of the utilization structure of factors of production. Finally, based on the analysis of the necessity to change the pattern of economic growth, this paper proposes the strategic measures to promote the continuous economic growth and the transformation of patterns of economic growth.

  14. Increased Serum Levels of Epidermal Growth Factor in Children with Autism

    Iseri, Elvan; Guney, Esra; Ceylan, Mehmet F.; Yucel, Aysegul; Aral, Arzu; Bodur, Sahin; Sener, Sahnur

    2011-01-01

    The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral…

  15. Serum Erythropoietin, Insulin-Like Growth Factor 1 and Vascular Endothelial Growth Factor in Ethiopathogenesis of Retinopathy of Prematurity

    Özlem Yenice

    2012-12-01

    Full Text Available Pur po se: The aim of this study was to determine the serum levels of erythropoietin (EPO, vascular endothelial growth factor (VEGF and insulin-like growth factor-1 (IGF-1 that possibly play an important role in the pathogenesis of retinopathy of prematurity (ROP and to investigate their relationship with each other. Ma te ri al and Met hod: In this study, 93 infants with gestational age of less than 32 weeks or had a birth weight of less than 2000 g were investigated prospectively. To determine levels of EPO, VEGF and IGF-1, samples were collected from cord blood and were reserved at -80°C. Serum levels of cytokines in babies with and without ROP (ROP+ and ROP- were determined and their relationship with each other was investigated. Re sults: ROP was found in 57 (61.3% babies. There was a significant difference between ROP- and ROP+ groups for birth weight (1678.06±326.03 g; 1383.95±343.23 g; p=0,001 and birth week (29.65±2.34 weeks; 32.22±1.49 weeks; p=0,001 correspondingly. Besides, IGF-1 levels correlated significantly with birth weight (r=0.509; p=0.001 and birth week (r=0.586, p=0.001. Median serum levels in ROP(- group were 19.45 ng/ml (0-40 ng/ml for IGF-1, 1159.5 pg/ml (396.59-2389.25 pg/ml for VEGF, and 6.14 mU/ml (2.6-35.4 mU/ml for EPO. The median serum levels in ROP+ group were 0 ng/ml (0-30.6 ng/ml for IGF-1, 864.98 pg/ml (182.57-2133.05 pg/ml for VEGF, and 6.07 mU/ml (2.4-90.2 mU/ml for EPO. Levels of IGF-1 (p=0.008 and VEGF (p=0.011 were significantly lower in the ROP(+ group. Serum VEGF correlated with EPO levels (r=0.275; p=0.019. Dis cus si on: Serum IGF-1 and VEGF levels at birth may be measured to assess the risk for developing ROP. (Turk J Ophthalmol 2012; 42: 423-8

  16. Entrepreneurship and economic growth: An investigation into the relationship between entrpreneurship and total factor productivity growth in the EU

    Andrzej P. Dabkowski

    2011-01-01

    Endogenous growth theory assigns an important role for entrepreneurship in the process of economic development. This paper sets to formally test the impact of entrepreneurship on economic growth. Entrepreneurship is represented by a number of proxy variables, whereas Total Factor Productivity is used as a measure of economic growth. Panel data of 26 European countries repeatedly sampled over a period of 11 years is used to estimate a Random Effects model. This study finds that entrepreneurshi...

  17. Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Postoperative Muscle and Substrate Metabolism

    Folke Hammarqvist

    2010-01-01

    To conclude, growth factors influences urea metabolism, protein degradation and protein synthesis. There was no clearcut additional effect when combining GH and IGF-1 but the study was probably underpowered to outrule this and effects on nitrogen balance.

  18. Some growth factors stimulate cultured adult rabbit ventricular myocyte hypertrophy in the absence of mechanical loading

    Decker, R. S.; Cook, M. G.; Behnke-Barclay, M.; Decker, M. L.

    1995-01-01

    Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

  19. Growth hormone and insulin-like growth factors in fish: Where we are and where to go

    Reinecke, M.; Bjornsson, Bjorn Thrandur; Dickhoff, Walton W.; McCormick, S.D.; Navarro, I.; Power, D.M.; Gutierrez, J.

    2005-01-01

    This communication summarizes viewpoints, discussion, perspectives, and questions, put forward at a workshop on "Growth hormone and insulin-like growth factors in fish" held on September 7th, 2004, at the 5th International Symposium on Fish Endocrinology in Castello??n, Spain. ?? 2005 Elsevier Inc. All rights reserved.

  20. Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions.

    Wong, S C; Dobie, R; Altowati, M A; Werther, G A; Farquharson, C; Ahmed, S F

    2016-02-01

    Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt are often seen during adolescence. The underlying inflammatory state mediated by proinflammatory cytokines, prolonged use of glucocorticoid, and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the GH-IGF axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biological therapy may lead to improvement of growth in some of these children, but approximately one-third continue to grow slowly. There is increasing evidence that the use of relatively high-dose recombinant human GH may lead to partial catch-up growth in chronic inflammatory conditions, although long-term follow-up data are currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease, and cystic fibrosis, systemic abnormalities of the GH-IGF axis, and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human GH in these conditions and discussed the role of recombinant human IGF-1. PMID:26720129

  1. Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain.

    Ward, M C; Cunningham, A M

    2015-09-10

    Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). The early expression pattern of VEGFR3 protein and its cellular associations has not as yet been comprehensively reported. We describe the temporal expression of VEGFR3 protein at a cellular level and its close association with its VEGFC ligand, determined by double-labeling immunohistochemistry in the developing rat brain from embryonic day (E) 13 to postnatal day (P) 23. We found high expression of VEGFR3 in the ventricular zone and along radial glia in early gestation in association with neural stem cells and neuroblasts. Similar expression patterns were seen in the immature olfactory bulb and optic cup. In later development we found less expression by neural progenitors in proliferative regions including the SVZ and dentate gyrus of the hippocampus. In contrast, VEGFR3 expression increased with development in the cortex in neurons and astrocytes, and appeared in the emerging population of oligodendroglial progenitors. High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development

  2. Nerve growth factor: role in growth, differentiation and controlling cancer cell development.

    Aloe, Luigi; Rocco, Maria Luisa; Balzamino, Bijorn Omar; Micera, Alessandra

    2016-01-01

    Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate. PMID:27439311

  3. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

    Igarashi, A; Okochi, H; Bradham, D M; Grotendorst, G R

    1993-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor b...

  4. Trophic action of epidermal growth factor on human duodenal mucosa cultured in vitro.

    Challacombe, D N; Wheeler, E. E.

    1991-01-01

    The action of epidermal growth factor on the human duodenal mucosa has been studied by estimating the crypt cell production rate in cultured explants, using a stathmokinetic technique with crypt microdissection. The addition of epidermal growth factor (400 ng/ml) to paired explants from five patients caused an almost fivefold increase in the crypt cell production rate, showing that epidermal growth factor has a trophic action on the human duodenal mucosa in vitro.

  5. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas.

    Sugawa, N; Ekstrand, A J; James, C D; Collins, V P

    1990-01-01

    The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each of these six tumors contains aberrant transcripts derived from identical...

  6. Altered nerve growth factor in fibroblasts from patients with familial dysautonomia.

    Schwartz, J P; Breakefield, X O

    1980-01-01

    Nerve growth factor was measured in cultured human skin fibroblasts from controls and from patients with familial dysautonomia and dystonia musculoram deformans. Cells from these sources grown over a range of cell densities contained similar levels of beta-nerve growth factor as measured by radioimmunoassay. Results of bioassay demonstrated that the nerve growth factor from dysautonomic cells was only approximately 10% as active per ng of immunoreactive protein as that from control and dyston...

  7. Blocking transforming growth factor- receptor signaling down-regulates transforming growth factor-β1 autoproduction in keloid fibroblasts

    刘伟; 蔡泽浩; 王丹茹; 武小莉; 崔磊; 商庆新; 钱云良; 曹谊林

    2002-01-01

    Objective: To study transforming growth factor-β1(TGF-β1) autoproduction in keloid fibroblasts and theregulation effect of blocking TGF-β intracellular signalingon rhTGF-β1 autoproduction.Methods: Keloid fibroblasts cultured in vitro weretreated with either rhTGF-β1 (5 ng/ml ) or recombinantadenovirus containing a truncated type II TGF-β receptorgene (50 pfu/cell ). Their effects of regulating geneexpression of TGF-β1 and its receptor I and II wereobserved with Northern blot.Results: rhTGF-β1 up-regulated the gene expressionof TGF-β1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated thegene expression of TGF-β1 and its receptor I, but notreceptor II.Conclusions: TGF-β1 autoproduction was observed inkeloid fibroblasts. Over-expression of the truncated TGF-βreceptor H decreased TGF-β1 autoproduction via blockingTGF-β receptor signaling.

  8. THE INVESTMENTS, ECONOMIC GROWTH FACTORS OR CONSUMPTION OF DEVELOPMENT POTENTIAL?

    Huru Dragos; Hrebrenciuc Andrei

    2008-01-01

    In Romania, in the last year the economic growth is a real phenomenon that is not our subject for demonstration or for analyze in this paper. Our concern is related with the way of manifestation for economic growth in the economic system. We study if not the economic growth on the contrary of development for current or further performance (regardless of economic aspect or level of analyze) can unstuck in consumption of the availed resources for consolidate potential for development.

  9. Use of antivascular endothelial growth factor for diabetic macular edema

    Rushmia Karim

    2010-05-01

    Full Text Available Rushmia Karim, Benjamin TangUniversity of Sydney School of Public Health, Concord Repatriation General Hospital, Concord, NSW, AustraliaBackground: Diabetic macular edema (DME is one of the manifestations of diabetic retinopathy leading to loss of central vision and visual acuity. It manifests itself with swelling around the central part of the retina, the area responsible for sharp vision. Current treatment includes laser therapy and intravitreal steroids with preventative measures including diabetes control. No one treatment has guaranteed control of diabetic macular edema which leads to deteriorating visual acuity, function and quality of life in patients. Vascular endothelial growth factor (VEGF has been shown to be a critical stimulus in the pathogenesis of macular edema secondary to diabetes.1 Antiangiogenic therapy encompassed treatment with anti-VEGF which inhibits VEGF-driven neovascularization hence macular edema leading to decreased visual acuity.Objective: For this review, we evaluated the effectiveness of intravitreal anti-VEGF in treating DME.Data sources: We identified five trials (n = 525 using electronic databases (Cochrane Central Register of Controlled Trials [Central], Medline®, and Excerpta Medica Database [EMBASE®] in October 2008, supplemented by hand searching of reference lists, review articles, and conference abstracts.Methods: We included all randomized clinical trials (RCTs evaluating any form of intravitreal anti-VEGF for treating DME. The main outcome factor was change in best-corrected visual acuity and central macular thickness. One author assessed eligibility, methodological quality, and extracted data. Meta analysis was performed when appropriate.Results: We included three trials of adequate methodological quality in our metaanalysis. Patients treated with anti-VEGF showed improvement in visual acuity of -0.17 (95% confidence interval [CI]: -0.23, -0.10 and central macular thickness -84.69 (95% CI: -117

  10. Natural resources as a factor of economic growth in Kosovo

    Haki Shatri

    2015-11-01

    Full Text Available In the history of the economic growth, there are numerous examples of countries that have developed based on their available natural resources. Especially, these assets have been the propulsion of the development in the initial period. But we also find some cases where countries with limited natural resources have experienced dynamic economic development. Kosovo is the last federal unit dismembered from former Yugoslavia after a decade under Milosevic’s Serbian regime and a two years’ war. International intervention and the inclusion of the country under an international protectorate created the conditions for the development of devastated economy by war and the robbery to be recovered together with the creation of institutional and economic infrastructure (Lidhja e Ekonomistëve të Kosovës, 1996. Under these conditions, everything had to start from scratch. The only development factor that Kosovo possessed was the human factor - age structure and the abundant natural resources, especially in key sectors such as the energy and in mining and minerals, agriculture and tourism. Thus it is sustainable the conclusion that “The rapid and sustainable economic and social development of Kosovo depends substantially from the implementation of the appropriate policies and suitable economic reforms that enable more rational use of its natural and human resources”. The list of the available resources of Kosovo is long. Kosovo possesses significant amount of all mineral raw materials in both quality and quantity terms. Among the most important raw materials have been ranked the power-lignite mining that is stretched into three basins and it is estimated to be around 9 billion exploitable tons (Kelmendi, 2012. Kosovo also owns mineral resources which are found in the Trepca’s Metals basin. The geological researches show favorable conditions of exploitation and high quality of the ore. Mainly one can found the lead, zinc, silver and other

  11. VASCULAR ENDOTHELIAL GROWTH FACTORS IN HEART TRANSPLANT REJECTIONS

    O. P. Shevchenko

    2015-01-01

    Full Text Available Aim: to determine the clinical significance of vascular endothelial growth factors VEGF-A, VEGF-D, PlGF-1 to assess the risk of cardiovascular complications in heart recipients. Materials and methods. 103 patients, aged 16 to 73 years, 85 males and 18 females. 65 recipients (47 men and 18 women had dilated cardiomyopathy, 38 – coronary heart disease (CHD. The concentration of VEGF-A, VEGF-D, PlGF-1 was measured using xMAP technology with sets of reagents Simplex ProcartaPlex™. Results. After HTx the level of VEGF-A significantly decreased, p = 0.001. There were no correlations between the levels of VEGF-A, VEGF-D and PlGF-1 with age, gender and diagnosis. After HTx VEGF-A level was higher in recipients with ACR than in those without it (p = 0.001. ACR frequency was significantly higher in patients with high VEGF-A level (≥316.5 pg/ml, RR = 5.8 ± 0.5, AUC = 0.779. After HTx PlGF-1 level was higher in recipients with ACR too (p = 0.039. ACR frequency was significantly higher in patients with high PlGF-1 level (≥5.33 pg/ml, RR = 1.8 ± 0.5, AUC = 0.65. There were no correlations between VEGF-D level with ACR and all three biomarkers with AMR. ACR frequency was significantly higher with both high VEGF-A and PlGF-1 levels (RR = 6.4. Conclusion. Serum levels of VEGF-A and PlGF-1 after HTx may be regarded as indicators of increased risk of ACR.

  12. Vascular endothelial growth factor and acute mountain sickness

    Nilles Eric

    2009-01-01

    Full Text Available Study Objective: Despite causing significant morbidity throughout the mountainous regions of the world, the pathophysiology of acute mountain sickness (AMS remains poorly understood. This study aims to improve the understanding of altitude illness by determining if vascular endothelial growth factor (VEGF plays a role in the development of AMS. The purpose of this study was to determine if elevated plasma VEGF correlates with increased symptoms of AMS at high altitude. Patients and Methods: This is a prospective study of a cohort of healthy climbers on Denali (Mount McKinley in Alaska at 14, 200 feet. Baseline demographics, medications, rates of ascent, and AMS scores were recorded. Pulse oximetry measurements and venous blood samples were obtained. Comparisons were made between mountaineers with and without AMS. Results: Seventy-two climbers were approached for participation in the study; 21 (29% refused. Of the 51 climbers participating in the study, 14 subjects (27.5% had symptoms of AMS and 37 subjects (72.5% were free of symptoms of AMS. Plasma VEGF levels were 79.14 pg/dl (SD: 121.44 and 57.57pg/dl (SD: 102.71 in the AMS and non-AMS groups, respectively. These results were nonsignificant. Similarly, comparison of sex, age, rate of ascent, pulse oximetry values, or history of altitude illness did not reveal significant differences between the AMS and non-AMS groups. Conclusion: This study does not provide evidence in support of the theory that plasma VEGF correlates with symptoms of AMS.

  13. Radiotherapy and receptor of epidermal growth factor; Radiotherapie et recepteur de l'Epidermal Growth Factor

    Deberne, M. [Institut Gustave-Roussy, 94 - Villejuif (France)

    2009-10-15

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  14. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

    Huawei Liu; Weisheng Wen; Min Hu; Wenting Bi; Lijie Chen; Sanxia Liu; Peng Chen; Xinying Tan

    2013-01-01

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as wel as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. Electro-physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation il ustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits com-bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits.

  15. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects.

    Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

    2013-11-25

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

  16. Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain.

    Laura De Laporte

    Full Text Available Tenascin C (TNC is an extracellular matrix protein that is upregulated during development as well as tissue remodeling. TNC is comprised of multiple independent folding domains, including 15 fibronectin type III-like (TNCIII domains. The fifth TNCIII domain (TNCIII5 has previously been shown to bind heparin. Our group has shown that the heparin-binding fibronectin type III domains of fibronectin (FNIII, specifically FNIII12-14, possess affinity towards a large number of growth factors. Here, we show that TNCIII5 binds growth factors promiscuously and with high affinity. We produced recombinant fragments of TNC representing the first five TNCIII repeats (TNCIII1-5, as well as subdomains, including TNCIII5, to study interactions with various growth factors. Multiple growth factors of the platelet-derived growth factor (PDGF family, the fibroblast growth factor (FGF family, the transforming growth factor beta (TGF-β superfamily, the insulin-like growth factor binding proteins (IGF-BPs, and neurotrophins were found to bind with high affinity to this region of TNC, specifically to TNCIII5. Surface plasmon resonance was performed to analyze the kinetics of binding of TNCIII1-5 with TGF-β1, PDGF-BB, NT-3, and FGF-2. The promiscuous yet high affinity of TNC for a wide array of growth factors, mediated mainly by TNCIII5, may play a role in multiple physiological and pathological processes involving TNC.

  17. Growth factor modulation of fibroblast proliferation, differentiation, and invasion: implications for tissue valve engineering.

    Narine, Kishan; De Wever, Olivier; Van Valckenborgh, Dillis; Francois, Katrien; Bracke, Marc; DeSmet, Stefaan; Mareel, Marc; Van Nooten, Guido

    2006-10-01

    We have previously shown that transforming growth factor-beta1 (TGF-beta1) stimulates transdifferentiation of fibroblasts into smooth muscle alpha-actin (alpha-SMA) positive myofibroblasts. However, TGF-beta, as such, is unsuitable for effective population of a heart valve matrix, because it dose-dependently inhibits growth of fibroblasts. The aim of this study was to investigate combinations of other growth factors with TGF-beta to stimulate the proliferation of suitably differentiated cells and to enhance their invasion into aortic valve matrices. Human dermal mesenchymal cells (hDMC1.1) were treated with combinations of growth factors to stimulate these cells to trans-differentiate into myofibroblasts, to proliferate, and to invade. Growth factors were chosen after expression of their respective receptors was confirmed in hDMC1.1 using reverse transcriptase polymerase chain reaction. We combined TGF-beta with several growth factors such as insulin-like growth factor (IGF-1, IGF-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF-AA, PDGF-BB, and PDGFAB). Nuclear Ki67 staining, MTT assay, and cell counting revealed that only EGF and bFGF were capable of overcoming TGF-beta-induced growth inhibition. However, bFGF but not EGF inhibited TGF-beta-induced alpha-SMA expression, as evidenced by immuno-cytochemistry and Western blotting. A growth factor cocktail (TGF-beta, EGF, bFGF) has been established that maintains TGF-beta-induced trans-differentiation but overcomes TGF-beta-induced growth inhibition while stimulating fibroblast proliferation and invasion. PMID:17518640

  18. A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model*

    Huang, Feng-Ying; Li, Yue-nan; WANG Hua; Huang, Yong-hao; Lin, Ying-Ying; Tan, Guang-Hong

    2008-01-01

    Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by r...

  19. Mapping and sequencing of a gene from myxoma virus that is related to those encoding epidermal growth factor and transforming growth factor alpha.

    Upton, C; Macen, J L; McFadden, G

    1987-01-01

    Myxoma virus, a Leporipoxvirus and agent of myxomatosis, was shown to possess a gene with the potential to encode an epidermal growth factorlike factor. Its relationship to other members of this family, including the poxvirus growth factors from Shope fibroma virus and vaccinia virus, was analyzed. Alignment of DNA sequences and related open reading frames of myxoma virus and Shope fibroma virus indicated colinearity of genes between these poxviruses.

  20. Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate

    Tørring, N; Vinter-Jensen, L; Pedersen, S B; Sørensen, Flemming Brandt; Flyvbjerg, A; Nexø, E

    1997-01-01

    PURPOSE: To investigate the effects of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) on the rat prostate. In addition, we investigated the effect of ornithine decarboxylase (ODC) inhibition with alpha-diflouromethylornitine (DFMO) on the expected growth of the prostate....... MATERIALS AND METHODS: Eight week old Wistar rats were allocated into groups of eight, receiving systemic treatment for 3 and 7 days with either IGF-I (400 micrograms/rat/day) or EGF (30 micrograms/rat/day) alone or in combination with DFMO. RESULTS: Systemic treatment with IGF-I for 7 days resulted in a 29...

  1. A role for epidermal growth factor in the growth and development of embryonic chicken lung systems

    Epidermal growth factor (EGF) is known to be mitogenic for a variety of growing tissues, and is thought to play a role in embryonic development. The first aim of this study was to establish whether embryonic chicken lung explants respond to mouse EGF and if so, to determine whether this responsiveness varies with the age of the embryo. Autoradiographic analysis of thymidine incorporation into 3-, 4-, 5- and 6-day old explants revealed them to be highly responsive mitogenically to EGF, with this responsiveness increasing with the age of the explant. Binding studies using 125I-EGF were then carried out to determine whether embryonic chicken lung explants contained specific receptors for EGF. It was found that the lung explants rapidly bound EGF, with a gradual plateau in binding occurring after six hours, suggesting that EGF receptors might be present. Finally an attempt was made to demonstrate the presence of an EGF-like molecule in extracts of embryonic chickens. Furthermore it was found that while both fractions were equally able to compete with 125I-EGF in receptor-binding assays, the LMW fraction was far more potent a stimulator of DNA synthetic acticity than the HMW fraction. The incorporation, by labelling, of 3H-TdR was used in this experimental studies. The results presented in this study show that embryonic chicken lungs contain specific EGF receptors, respond mitogenically to mouse EGF and furthermore it would appear that they produce and endogenous EGF-like molecule. These results strongly suggest that EGF plays and important role in embryonic chicken lung growth

  2. Serum Growth Hormone and Insulin-Like Growth Factor-1 Levels in Women with Postadolescent Acne

    Mualla Polat

    2010-06-01

    Full Text Available Background and Design: Acne vulgaris is an inflammatory disease of pilosebaceous unit. It usually starts after puberty but may continue into adulthood. We studied Growth hormone (GH and insulin-like growth factor (IGF-1 levels in women patients with acne vulgaris in whom all other hormon levels were normal. We aimed to show any relation of the acne vulgaris lesion type and GH and IGF-1 levels. Material and Method: The study conducted on the postadolesance period woman patients applying to out patient dermatology department with complaint of acne symptoms between Semtember 2005 and July 2006. All other hormonal parameters were normal in patients. 25 healthy similar age women were accepted as control. IGF-I and GH were quantified by solid-phase competitive chemiluminescence assays. Results: There was no difference according to age between the groups (p=0.726. The mean IGF-1 level was 336.5±112.88 ng/ml in patients and 194±31.32 ng/ml in control; the difference was significantly important (p=0.000. The mean GH level was 3.16±4.35 µIU/ml in patients and 1.15±1.21 µIU/ml in control; and the diffrence was not found as important (p=0.03. IGF-1 level was significantly important in patients with noduler involvement (p=0.015, and GH level was also significantly important in patients with cystic involvement (p=0.05. Conclusion: We supported the hypothesis that GH and IGF-1 levels were important in postadolasence period women patients with acne vulgaris. We recommend new studies comparing GH and IGF-1 levels in adolesence and postadolesence period women patients in order to support the role of these hormones in pathogenesis of acne vulgaris.

  3. Financial intermediation : a contributing factor to economic growth and employment

    Dominique M. Gross

    2002-01-01

    Reviews evidence from economic research on the relationship between financial intermediation, growth and employment, focusing on macroeconomic aspects. Shows how developments in the financial sector do contribute to economic growth and highlights the importance of the ability of firms to raise capital. Discusses policy implications.

  4. Quantitation of the mRNA expression of the epidermal growth factor system

    Sørensen, B S; Tørring, N; Bor, M V;

    2000-01-01

    curve is used to quantitate the unknown samples, which require only a single RT-PCR reaction. Our method has the advantage that quantitation is based on coamplification of an internal RNA standard, thereby controlling both the PCR and RT reactions. In addition, the RNA standards for all growth factors......The epidermal growth factor (EGF) system is a rapidly expanding system of growth factors involved in many aspects of normal and cancerous growth. We have developed a method for the quantitation of mRNA coding for all six growth factors activating the human EGF receptor (HER-1) and for the...... prostate stromal cells in primary culture express EGF, heparin-binding EGF (HB-EGF), amphiregulin, betacellulin, and epiregulin as well as the HER-1 and HER-2 receptors, whereas no transforming growth factor-alpha mRNA is found. Furthermore, activation of the EGF system in these cells by stimulation with...

  5. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation

  6. Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes

    Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. Methods: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, 125I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and 3H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. Results: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, 125I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although 125I-insulin specific binding was not affected. The decrease in 125I-epidermal growth factor specific binding was explained by the decrease in the number or available epidermal growth factor receptors (21.37±3.08 to 12.16±1.42 fmol/105 cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immuno-detection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of 125I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in 125I-epidermal growth factor binding. (au)

  7. Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

    FU Xiao-yan; DING Ming-xing; ZHANG Ning; LIN Xing-qiu; LI Ji-cheng

    2007-01-01

    Objective: To explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods: In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. Results: VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors (P<0.05 or P<0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively (P<0.05 or P<0.01). VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors (P<0.05). VEGFR-3 positive vessels was significantly correlated with MVD(P<0.01). Conclusion: VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.

  8. Growth hormone and insulin-like growth factor-1 in acute myocardial infarction

    Friberg, L; Werner, S; Eggertsen, G;

    2000-01-01

    Growth hormone therapy after myocardial infarction improves cardiac function and survival in animals. Beneficial effects in humans are reported from studies where patients with idiopathic dilated cardiomyopathy were treated with growth hormone. We have studied the role of the endogenous growth...... hormone system in myocardial infarction....

  9. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  10. Colloid's influences on microalgae growth as a potential environmental factor

    赵新淮; 张正斌; 刘莲生

    2003-01-01

    The role of colloid as "colloid pump" in the ocean is well known. The important influence of colloid in seawater on the growth of microalga was found in our 1999-2000 study. Colloid concentrates were obtained by employing a cross-flow filtration systen to ultrafilter seawater (which had been pre-filtrated by 0.45 μm acetate cellulose membrane) successively with different membranes. Ultrafiltration retentions (we called them colloid concentrates ) together with control sample ( seawater without colloid) were then inoculated with two species of microalgae and cultivated in selected conditions. Monitoring of microalgae growth during cultivation showed that all colloid concentrates had obvious influence on the growth of the microalgae studied. Addition of Fe(OH)3 colloid or organic colloid (protein or carbohydrate) to the control sample enhanced the microalgae's growth.

  11. Circulating insulin-like growth factor I and cognitive function : Neuromodulation throughout the lifespan

    Aleman, Andre; Torres-Aleman, Ignacio

    2009-01-01

    Insulin-like growth factor I (IGF-I) is central to the somatotropic (growth hormone) axis. It promotes tissue growth and continues to have anabolic effects in adulthood. Accumulating evidence from the last decade, however, reveals that circulating levels of IGF-I also significantly affects cognitive

  12. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  13. Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors

    Randazzo, P.A.; Jarett, L. (Univ. of Pennsylvania, Philadelphia (USA))

    1990-09-01

    The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity.

  14. Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors

    The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity

  15. Changes in the level of growth hormone, insulin like growth factor-1 and insulin like growth factor binding proteine-3 in young males 24 hours after submaximaltraining

    Hakkı Çoknaz

    2011-04-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 The study was accomplished as a control study, under the question whether 6-weeks endurance training affects the growth hormone (GH, insulin like growth factor-1 (IGF-1 and the IGF bindings protein-3 (IGFBP-3 levels. Sixty male subjects participated in the study. The subjects were separated into 2 groups as control (n=30; mean age=21,13±1,16 years and study (n=30; mean age=21,53±1,61 years randomly, prior to the runtest. Blood samples were drawn before breakfast and analyzed in the laboratory of the medical faculty of Abant Izzet Baysal University concerning GH, IGF-1and IGFBP-3. VO2max was measured in all individuals. The individuals experimental group trained 3 times a week (Monday, Wednesday, and Friday for 6 weeks, on the other hand the control group had rest/rested for 6 weeks. Trainings included 30-40 minutes submaximal run on the treadmill, per day. After the last session of training, blood samples were drawn from all subjects following day before breakfast, and were analyzed similar to the first measurements. Then, all subjects (experimental and control groups were subjected to VO2max measurement again. There were no differences within groups and between the groups in GH, IGF-1, IGFBP-3levels before (p>0.05 and after the test (p>0.05. VO2max was found to be significantly higher in the study group compare to controls (p<0.05. We conclude that submaximal training does not affect the production of growth hormones, although it may increase oxygen consumption. 

  16. Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery

    Schiødt, I; Jensen, Charlotte Harken; Kjaersgaard, E;

    2000-01-01

    In order to improve prediction of hematopoietic recovery, we conducted a pilot study, analyzing the significance of growth factor receptor expression in autografts as well as endogenous growth factor levels in blood before, during and after stem cell transplantation. Three early acting (stem cell......-CSF receptor positive, CD34+ progenitor cells were measured by flow cytometry in the leukapheresis product used for transplantation in a subgroup of 15 patients (NHL, n = 8, MM, n = 7). Three factors were identified as having a significant impact on platelet recovery. First, the level of Tpo in blood at the...

  17. Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis

    Bonnesen, Barbara; Pappot, Helle; Holmstav, Julie;

    2009-01-01

    elements in neoplastic cells and their microenvironment have recently been and are continuously developed including drugs inhibiting the angiogenic system. Angiogenic factor vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) seem to play key...... stained on whole tumour slides. Kaplan-Meier survival curves were generated to evaluate the significance of immunohistochemical VEGF-A and VEGFR2 expression for the prognosis. RESULTS: VEGF-A and VEGFR2 expression was observed in the majority of NSCLC patients. VEGF-A expression showed a correlation to...

  18. Neural cell adhesion molecule differentially interacts with isoforms of the fibroblast growth factor receptor

    Christensen, Claus; Berezin, Vladimir; Bock, Elisabeth

    2011-01-01

    The fibroblast growth factor receptor (FGFR) can be activated through direct interactions with various fibroblast growth factors or through a number of cell adhesion molecules, including the neural cell adhesion molecule (NCAM). We produced recombinant proteins comprising the ligand...... the expression pattern of various FGFR isoforms determines the cell context-specific effects of NCAM signaling through FGFR....

  19. Problem-Solving Test: The Role of Ubiquitination in Epidermal Growth Factor Receptor Trafficking

    Szeberenyi, Jozsef

    2012-01-01

    Terms to be familiar with before you start to solve the test: growth factor signaling, epidermal growth factor, tyrosine protein kinase, tyrosine phosphorylation, ubiquitin, monoubiquitination, polyubiquitination, site-directed mutagenesis, transfection, expression vector, cDNA, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, Western…

  20. Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

    Go Suzuki

    Full Text Available Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

  1. Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells

    L(U) Yun; ZHANG Ying-chuan; LIU Jing-hua; ZHANG Li-ke; DU Jie; ZENG Xiang-jun; HAO Gang; HUANG Ji; ZHAO Dong-hui; WANG Guo-zhong

    2010-01-01

    Background Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P <0.05).Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

  2. The best-laid plans go oft awry: synaptogenic growth factor signaling in neuropsychiatric disease

    Aislinn Joanmarie Williams

    2014-03-01

    Full Text Available Growth factors play important roles in synapse formation. Mouse models of neuropsychiatric diseases suggest that defects in synaptogenic growth factors, their receptors, and signaling pathways can lead to disordered neural development and various behavioral phenotypes, including anxiety, memory problems, and social deficits. Genetic association studies in humans have found evidence for similar relationships between growth factor signaling pathways and neuropsychiatric phenotypes. Accumulating data suggest that dysfunction in neuronal circuitry, caused by defects in growth factor-mediated synapse formation, contributes to the susceptibility to multiple neuropsychiatric diseases, including epilepsy, autism, and disorders of thought and mood (e.g. schizophrenia and bipolar disorder, respectively. In this review, we will focus on how specific synaptogenic growth factors and their downstream signaling pathways might be involved in the development of neuropsychiatric diseases.

  3. Nerve growth factor promotes in vitro proliferation of neural stem cells from tree shrews

    Liu-lin Xiong; Zhi-wei Chen; Ting-hua Wang

    2016-01-01

    Neural stem cells promote neuronal regeneration and repair of brain tissue after injury, but have limited resources and proliferative ability in vivo. We hypothesized that nerve growth factor would promotein vitro proliferation of neural stem cells derived from the tree shrews, a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research. We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38, and added nerve growth factor (100 μg/L) to the culture medium. Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls. After 3 days, lfuorescence mi-croscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells. These ifndings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews.

  4. Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF - opioid growth factor receptor (OGFr axis

    Donahue Renee N

    2009-10-01

    Full Text Available Abstract Background Carcinoma of the thyroid gland is an uncommon cancer, but the most frequent malignancy of the endocrine system. Most thyroid cancers are derived from the follicular cell. Follicular carcinoma (FTC is considered more malignant than papillary thyroid carcinoma (PTC, and anaplastic thyroid cancer (ATC is one of the most lethal human cancers. Opioid Growth Factor (OGF; chemical term - [Met5]-enkephalin and its receptor, OGFr, form an inhibitory axis regulating cell proliferation. Both the peptide and receptor have been detected in a wide variety of cancers, and OGF is currently used clinically as a biotherapy for some non-thyroid neoplasias. This study addressed the question of whether the OGF-OGFr axis is present and functional in human thyroid follicular cell - derived cancer. Methods Utilizing human ATC (KAT-18, PTC (KTC-1, and FTC (WRO 82-1 cell lines, immunohistochemistry was employed to ascertain the presence and location of OGF and OGFr. The growth characteristics in the presence of OGF or the opioid antagonist naltrexone (NTX, and the specificity of opioid peptides for proliferation of ATC, were established in KAT-18 cells. Dependence on peptide and receptor were investigated using neutralization studies with antibodies and siRNA experiments, respectively. The mechanism of peptide action on DNA synthesis and cell survival was ascertained. The ubiquity of the OGF-OGFr axis in thyroid follicular cell-derived cancer was assessed in KTC-1 (PTC and WRO 82-1 (FTC tumor cells. Results OGF and OGFr were present in KAT-18 cells. Concentrations of 10-6 M OGF inhibited cell replication up to 30%, whereas NTX increased cell growth up to 35% relative to cultures treated with sterile water. OGF treatment reduced cell number by as much as 38% in KAT-18 ATC in a dose-dependent and receptor-mediated manner. OGF antibodies neutralized the inhibitory effects of OGF, and siRNA knockdown of OGFr negated growth inhibition by OGF. Cell survival

  5. Transforming Growth Factor β Regulates P-Body Formation through Induction of the mRNA Decay Factor Tristetraprolin

    Blanco, Fernando F.; Sanduja, Sandhya; Deane, Natasha G; Blackshear, Perry J.; Dixon, Dan A.

    2014-01-01

    Transforming growth factor β (TGF-β) is a potent growth regulator and tumor suppressor in normal intestinal epithelium. Likewise, epithelial cell growth is controlled by rapid decay of growth-related mRNAs mediated through 3′ untranslated region (UTR) AU-rich element (ARE) motifs. We demonstrate that treatment of nontransformed intestinal epithelial cells with TGF-β inhibited ARE-mRNA expression. This effect of TGF-β was promoted through increased assembly of cytoplasmic RNA processing (P) bo...

  6. Innovation and Economic Growth: Factors that Encourages Innovation

    María Teresa Méndez Picazo

    2012-03-01

    Full Text Available The goal of this paper is to analyze the role played by innovations on economic activity. In this sense, the relationship between innovation and economic growth is studied, being economic growth the current main objective of economic policy to reduce unemployment and to increase social welfare. To carry out this analysis we base on Schumpeter's model, playing entrepreneurship and social climate an important role in the process. The empirical analysis an innovations equation for the case of 11 developed countries is included, showing that the social climate, represented by the training and income distribution, and monetary policy, represented by money supply, stimulate innovations.

  7. A growth inhibitory factor from lambsquarters (Chenopodium album).

    Mallik, M A; Puchala, R; Grosz, F A

    1994-04-01

    Aqueous extract of air-dried lambsquarters (Chenopodium album) at 25 mg/ml significantly inhibited germination and growth of radish and wheat seeds. Soybean seed germination was not inhibited; however, hypocotyl growth was significantly reduced. Germination of radish seeds in sand amended with pulverized lambsquarters shoots at 2 and 4 mg/g was reduced 40 and 95%, respectively. Shoot dry weight and plant height were also reduced 30 and 9%, respectively, at 4 mg/g, but not at 2 mg/g concentration. Residues after extraction with water incorporated in sand were not inhibitory, indicating water solubility of the inhibitor(s). Aqueous extract of shoots decomposed for five days lost nearly 40% of its inhibitory effect; 20% of it still persisted in the extract of shoots decomposed for 30 days. The filtrate from ultrafiltration of aqueous extract through a pad of molecular-weight cutoff 1000 inhibited radish seeds germination and growth, indicating that the molecular weight of the inhibitor(s) was less than 1000. Partitioning of the aqueous extract by a series of solvents resulted in isolation of an inhibitor(s) in the butanol fraction. Seven phenolics were identified in this fraction using high-performance liquid chromatography (HPLC). Paper chromatographic analysis of the butanol fraction revealed six bands, of which one band withR f =0.83 inhibited germination and growth of radish seeds. Chlorogenic acid identified by HPLC appeared to be the principal component of the phytotoxin. PMID:24242208

  8. IGF-1 (Insulin-Like Growth Factor -1) Test

    ... 1) may be used to help: Identify growth hormone (GH) deficiency; it is not diagnostic of a GH ... day, making it a useful indicator of average GH levels. IGF-1 may be ordered with other pituitary hormone tests, such as prolactin or FSH and LH , ...

  9. What Factors Sustain Professional Growth among School Counselors?

    Konstam, Varda; Cook, Amy L.; Tomek, Sara; Mahdavi, Esmaeil; Gracia, Robert; Bayne, Alexander H.

    2015-01-01

    This study examined relationships among self-reported professional expertise, organizational support of evidence-based practices (EBP), and professional growth. Data were collected from 85 members of American School Counseling Association (ASCA). School counselors with higher self-reported expertise reported that they were more likely to improve…

  10. Low Insulin-Like Growth Factor-1 Level in Obesity Nephropathy: A New Risk Factor?

    Bancu, Ioana; Navarro Díaz, Maruja; Serra, Assumpta; Granada, Marisa; Lopez, Dolores; Romero, Ramon; Bonet, Josep

    2016-01-01

    Introduction IGF-1 (insulin-like growth factor-1) is a hormone involved in cell growth and other important processes. In the kidney, IGF-1 has a stimulating effect, increasing the blood flow and glomerular filtration rate. Although many experimental animal studies regarding the role of IGF-1 in the kidney have been conducted, few human studies are available in the literature. Obesity is a cause of renal failure, and several glomerular lesions associated with obesity have been described. However, no studies regarding the levels of IGF-1 in morbidly obese patients with renal injury associated with obesity have been conducted. Aim To determine the serum IGF-1 concentrations in morbidly obese patients with normal renal function but with different types of early obesity-related glomerular lesions and to evaluate the possible relationship between IGF-1 and the presence of renal lesions. Methods Eighty morbidly obese patients with renal biopsy, including 11 patients with no evidence of renal lesion, 17 patients with single glomerulomegaly, 21 patients with single podocyte hypertrophy, 10 patients with glomerulomegaly and podocyte hypertrophy, 5 patients with focal segmental hyalinosis, and 16 patients with increased mesangial matrix and/or mesangial proliferation, participated in this study. Biological parameters, including serum IGF-1 concentrations with the standard deviation score for age (SDS-IGF-1), were determined for all patients. Results Eighty patients (50 women and 30 men) with a mean BMI of 52.63 ± 8.71 and a mean age of 42.40 ± 9.45 years were included in this study. IGF-1, IGF-1 SDS and IGF-1BP3 levels according to the renal injury were compared (normal glomeruli: IGF-1 = 190.17 ± 72.46; glomerulomegaly: IGF-1 = 122.3 ± 50.05; podocyte hypertrophy: IGF-1 = 119.81 ± 60.34; focal segmental hyalinosis: IGF-1 170.98 ± 100.83, increased mesangial matrix and/or mesangial proliferation: IGF-1 117.73 ± 63.87). Statistically significant differences were

  11. Burkina Faso - Promoting Growth, Competitiveness and Diversification : Country Economic Memorandum, Volume 3. Enhancing Growth Factors

    World Bank

    2010-01-01

    The main conclusion of Country Economic Memorandum is that the previous model of extensive growth has now exhausted its potential and must be renewed. Given the existing population dynamics, low environmental tolerance due to its Sahelian climate and competition forces imposed due to its open economy, Burkina Faso is heavily investing in growth based on increased productivity to overcome i...

  12. ENDOGLIN Is Dispensable for Vasculogenesis, but Required for Vascular Endothelial Growth Factor-Induced Angiogenesis

    Liu, Zhen; Lebrin, Franck; Maring, Janita A.; van den Driesche, Sander; van der Brink, Stieneke; van Dinther, Maarten; Thorikay, Midory; Martin, Sabrina; Kobayashi, Kazuki; Hawinkels, Lukas J. A. C.; van Meeteren, Laurens A.; Pardali, Evangelia; Korving, Jeroen; Letarte, Michelle; Helen M Arthur

    2014-01-01

    ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) family members that is highly expressed in endothelial cells and has a critical function in the development of the vascular system. Mutations in Eng are associated with the vascular disease known as hereditary hemorrhagic telangiectasia type l. Using mouse embryonic stem cells we observed that angiogenic factors, including vascular endothelial growth factor (VEGF), induce vasculogenesis in embryoid bodies even when Eng d...

  13. ENDOGLIN is dispensable for vasculogenesis, but required for vascular endothelial growth factor-induced angiogenesis

    Liu, Zhen; Lebrin, Franck; Maring, Janita A.; van den Driesche, Sander; van der Brink, Stieneke; van Dinther, Maarten; Thorikay, Midory; Martin, Sabrina; Kobayashi, Kazuki; Hawinkels, Lukas J. A. C.; van Meeteren, Laurens A.; Pardali, Evangelia; Korving, Jeroen; Letarte, Michelle; Helen M Arthur

    2014-01-01

    ENDOGLIN (ENG) is a co-receptor for transforming growth factor-β (TGF-β) family members that is highly expressed in endothelial cells and has a critical function in the development of the vascular system. Mutations in Eng are associated with the vascular disease known as hereditary hemorrhagic telangiectasia type l. Using mouse embryonic stem cells we observed that angiogenic factors, including vascular endothelial growth factor (VEGF), induce vasculogenesis in embryoid bodies even when Eng d...

  14. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1.

    Gohongi, T; Fukumura, D; Boucher, Y; Yun, C O; Soff, G A; Compton, C; Todoroki, T; Jain, R K

    1999-10-01

    Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy. We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and anti-tumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. PMID:10502827

  15. Cartilage-specific over-expression of CCN family member 2/connective tissue growth factor (CCN2/CTGF stimulates insulin-like growth factor expression and bone growth.

    Nao Tomita

    Full Text Available Previously we showed that CCN family member 2/connective tissue growth factor (CCN2 promotes the proliferation, differentiation, and maturation of growth cartilage cells in vitro. To elucidate the specific role and molecular mechanism of CCN2 in cartilage development in vivo, in the present study we generated transgenic mice overexpressing CCN2 and analyzed them with respect to cartilage and bone development. Transgenic mice were generated expressing a ccn2/lacZ fusion gene in cartilage under the control of the 6 kb-Col2a1-enhancer/promoter. Changes in cartilage and bone development were analyzed histologically and immunohistologically and also by micro CT. Primary chondrocytes as well as limb bud mesenchymal cells were cultured and analyzed for changes in expression of cartilage-related genes, and non-transgenic chondrocytes were treated in culture with recombinant CCN2. Newborn transgenic mice showed extended length of their long bones, increased content of proteoglycans and collagen II accumulation. Micro-CT analysis of transgenic bones indicated increases in bone thickness and mineral density. Chondrocyte proliferation was enhanced in the transgenic cartilage. In in vitro short-term cultures of transgenic chondrocytes, the expression of col2a1, aggrecan and ccn2 genes was substantially enhanced; and in long-term cultures the expression levels of these genes were further enhanced. Also, in vitro chondrogenesis was strongly enhanced. IGF-I and IGF-II mRNA levels were elevated in transgenic chondrocytes, and treatment of non-transgenic chondrocytes with recombinant CCN2 stimulated the expression of these mRNA. The addition of CCN2 to non-transgenic chondrocytes induced the phosphorylation of IGFR, and ccn2-overexpressing chondrocytes showed enhanced phosphorylation of IGFR. Our data indicates that the observed effects of CCN2 may be mediated in part by CCN2-induced overexpression of IGF-I and IGF-II. These findings indicate that CCN2

  16. Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

    Nicholson Wanda K

    2008-09-01

    Full Text Available Abstract Background Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area. Methods We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as th percentile and hypertrophy as > 90th percentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a predictors of restricted growth (vs. normal and (b predictors of hypertrophic growth (vs. normal. Results Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth. Conclusion Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms.

  17. Natural resources as a factor of economic growth in Kosovo

    Haki Shatri

    2015-01-01

    In the history of the economic growth, there are numerous examples of countries that have developed based on their available natural resources. Especially, these assets have been the propulsion of the development in the initial period. But we also find some cases where countries with limited natural resources have experienced dynamic economic development. Kosovo is the last federal unit dismembered from former Yugoslavia after a decade under Milosevic’s Serbian regime and a two years’ war. In...

  18. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Petrović Bojana; Ljubić Aleksandar; Nikolić Ljubinka

    2008-01-01

    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. Chromosom...

  19. Growth and aggressiveness factors affecting Monilinia spp. survival peaches.

    Villarino, M; Melgarejo, P; De Cal, A

    2016-06-16

    Brown rot of stone fruit is caused by three species of Monilinia, Monilinia laxa, M. fructigena, and M. fructicola. Eleven components of 20 different isolates of each of the three Monilinia species were analyzed to determine distinct aggressiveness and growth characteristics among the three fungi. M. fructicola showed the greatest lesion diameter, and the lowest incubation and latency period on fruit postharvest, however isolates of M. fructigena exhibited less aggressiveness components. Five growth characteristics of M. fructicola could be used to distinguish M. fructicola from the other two species. The dendrogram generated from only the presence of sclerotia and lesion length on infected fruit separated the 60 isolates into two clusters (r=0.93). One cluster was composed of the M. laxa and M. fructigena isolates and the other cluster comprised the M. fructicola isolates. However, the dendrogram generated based on the presence of stromata and sclerotia in the same colony of the three species when they were grown on potato dextrose agar, and the lesion diameter on fruit infected with each species separated the 60 isolates into three clusters (r=0.81). Each cluster comprised the isolates of each of three Monilinia spp. We discussed the effect of M. fructicola growth and aggressiveness differences on the displacement of M. laxa and M. fructigena by M. fructicola recorded in Spanish peach orchards and their effect on brown rot at postharvest. PMID:27043383

  20. Abnormal growth factor and cytokine expression in Dupuytren's contracture.

    Baird, K S; Crossan, J F; Ralston, S H

    1993-01-01

    AIM--To analyse patterns of gene expression for peptide regulatory factors in patients with Dupuytren's contracture. METHODS--Tissue samples (palmer fascia) from 12 patients with Dupuytren's contracture and 12 controls were studied using the reverse transcription/polymerase chain reaction (RT/PCR) technique. RESULTS--Tissue from patients with Dupuytren's contracture expressed a higher percentage of peptide regulatory factors than that of controls: interleukin-1 alpha (83% v 16%; p < 0.01); in...

  1. Insulin-like Growth Factor Binding Proteins in the Plasma of Growing Horses

    Burk, John Robert

    2002-01-01

    Insulin-like growth factor binding proteins (IGFBP) are modulators of insulin-like growth factor I (IGF-I), which functions as a regulator of cartilage and bone development. Rapid growth and high starch diets have been associated with increased circulating concentrations of IGF-I, which lead to developmental orthopedic disorders in foals. The objective of this study was to assess the effects of age, diet, growth and season on plasma IGFBP and IGF-I concentrations from birth to 16 mo of age in...

  2. Potentiation of Growth Factor Signaling by Insulin-like Growth Factor-binding Protein-3 in Breast Epithelial Cells Requires Sphingosine Kinase Activity*

    Martin, Janet L; Mike Z. Lin; Eileen M. McGowan; Baxter, Robert C.

    2009-01-01

    We have investigated the mechanism underlying potentiation of epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGFR1) signaling by IGF-binding protein-3 (IGFBP-3) in MCF-10A breast epithelial cells, focusing on a possible involvement of the sphingosine kinase (SphK) system. IGFBP-3 potentiated EGF-stimulated EGF receptor activation and DNA synthesis, and this was blocked by inhibitors of SphK activity or small interference RNA-mediated silencing of SphK1...

  3. Solution conformations of the B-loop fragments of human transforming growth factor α and epidermal growth factor by 1H nuclear magnetic resonance and restrained molecular dynamics

    A restrained molecular dynamics simulation approach that explicitly includes the effect of the surrounding solvent molecules is applied to the NMR determination of the conformations of the B-loop fragments of human transforming growth factor α and epidermal growth factor. Backbone interproton distance restraints are obtained by using two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY). The simulations are carried out both in vacuum and in water. The results are discussed in terms of the energetics, agreement with the NMR distances, and the flexibility of the peptides

  4. Posttranslational regulation of insulin-like growth factor binding protein-4 in normal and transformed human fibroblasts. Insulin-like growth factor dependence and biological studies.

    Conover, C A; Kiefer, M C; Zapf, J

    1993-01-01

    Insulin-like growth factor binding protein-4 (IGFBP-4) is a 24-26-kD protein expressed by a variety of cell types in vivo and in vitro. Treatment of normal adult human fibroblasts with 10 nM insulin-like growth factor II (IGF-II) for 24 h resulted in an 85% decrease in endogenous IGFBP-4, as assessed by Western ligand blot analysis of the conditioned medium. Incubation of human fibroblast-conditioned medium (HFCM) with IGF-II under cell-free conditions led to a similar loss of IGFBP-4. This p...

  5. Insulin-like growth factor binding protein-5 modulates muscle differentiation through an insulin-like growth factor-dependent mechanism

    1996-01-01

    The insulin-like growth factor binding proteins (IGFBPs) are a family of six secreted proteins which bind to and modulate the actions of insulin-like growth factors-I and -II (IGF-I and -II). IGFBP-5 is more conserved than other IGFBPs characterized to date, and is expressed in adult rodent muscle and in the developing myotome. We have shown previously that C2 myoblasts secrete IGFBP-5 as their sole IGFBP. Here we use these cells to study the function of IGFBP-5 during myogenesis, a process s...

  6. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs

    Jungbluth, Pascal

    2014-11-01

    Full Text Available In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2 whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF and platelet-derived growth factor (PDGF-bb respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7 and transforming growth factor β1 (TGF-β1 were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001, TGF-β1 (r=0.85, p<0.001, VEGF (r=0.46, p<0.01 and PDGF-bb (r=0.9, p<0.001. Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

  7. Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth

    We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia

  8. A remarkable role of growth factors in resolving oral and specific periodontal pathologies: A strategic review

    Sarita Dabra

    2011-01-01

    Full Text Available The knowledge and the understanding of the role of growth factors, their mechanisms of action, and molecular signaling pathways, which have been reviewed in this article, suggest the potential for many novel therapeutic targets, not only for applying growth factors but also for the potential use of growth factor inhibitors or agents that target specific parts of the intracellular signaling pathways in controlling oral pathologies. There remains an enormous challenge to convert some of the knowledge from basic studies of bone cell physiology and inflammatory cells to therapeutically useful techniques for the future.

  9. Choline Acetyltransferase Activity in Striatum of Neonatal Rats Increased by Nerve Growth Factor

    Mobley, William C.; Rutkowski, J. Lynn; Tennekoon, Gihan I.; Buchanan, Karen; Johnston, Michael V.

    1985-07-01

    Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.

  10. Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

    Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, XinYing

    2013-01-01

    Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups...

  11. News Related to Future GDP Growth as a Risk Factor in Equity Returns

    Vassalou, Maria

    2001-01-01

    A model that includes a factor that captures news related to future Gross Domestic Product (GDP) growth along with the market factor can explain the cross-section of equity returns about as well as the Fama-French model can. Furthermore, the Fama-French factors HML and SMB appear to contain mainly news related to future GDP growth. When news related to future GDP growth is present in the asset-pricing model, HML and SMB lose their ability to explain the cross-section.

  12. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

    Kratchmarova, Irina; Blagoev, Blagoy; Haack-Sorensen, M.; Kassem, Moustapha; Mann, Matthias

    2005-01-01

    Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics...... it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical...

  13. Altered interaction and distribution of glycosaminoglycans and growth factors in mucopolysaccharidosis type I bone disease.

    Kingma, Sandra D K; Wagemans, Tom; IJlst, Lodewijk; Bronckers, Antonius L J J; van Kuppevelt, Toin H; Everts, Vincent; Wijburg, Frits A; van Vlies, Naomi

    2016-07-01

    The mucopolysaccharidoses (MPSs) comprise a group of lysosomal storage disorders characterized by deficient degradation and subsequent accumulation of glycosaminoglycans (GAGs). Progressive bone and joint disease are a major cause of morbidity, and current therapeutic strategies have limited effect on these symptoms. By elucidating pathophysiological mechanisms underlying bone disease, new therapeutic targets may be identified. Longitudinal growth is regulated by interaction between GAGs and growth factors. Because GAGs accumulate in the MPSs, we hypothesized that altered interaction between growth factors and GAGs contribute to the pathogenesis of MPS bone disease. In this study, binding between GAGs from MPS I chondrocytes and fibroblast growth factor 2 (FGF2) was not significantly different from binding of FGF2 to GAGs from control chondrocytes. FGF2 signaling, however, was increased in MPS I chondrocytes after incubation with FGF2, as compared to control chondrocytes. Using bone cultures, we demonstrated decreased growth of WT mouse bones after incubation with FGF2, but no effect on MPS I bone growth. However, MPS I bones showed decreased growth in the presence of GAGs from MPS I chondrocytes. Finally, we demonstrate altered GAG distribution in MPS I chondrocytes, and altered GAG, FGF2 and Indian hedgehog distribution in growth plates from MPS I mice. In summary, our results suggest that altered interaction and distribution of growth factors and accumulated GAGs may contribute to the pathogenesis of MPS bone disease. In the future, targeting growth factor regulation or the interaction between in growth factors and GAGs might be a promising therapeutic strategy for MPS bone disease. PMID:27105565

  14. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth

    Bennewith, Kevin L; Huang, Xin; Ham, Christine M;

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CC...

  15. Rearing Mozambique tilapia in tidally-changing salinities: Effects on growth and the growth hormone/insulin-like growth factor I axis.

    Moorman, Benjamin P; Yamaguchi, Yoko; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2016-08-01

    The growth hormone (GH)/insulin-like growth factor (IGF) axis plays a central role in the regulation of growth in teleosts and has been shown to be affected by acclimation salinity. This study was aimed at characterizing the effects of rearing tilapia, Oreochromis mossambicus, in a tidally-changing salinity on the GH/IGF axis and growth. Tilapia were raised in fresh water (FW), seawater (SW), or in a tidally-changing environment, in which salinity is switched between FW (TF) and SW (TS) every 6h, for 4months. Growth was measured over all time points recorded and fish reared in a tidally-changing environment grew significantly faster than other groups. The levels of circulating growth hormone (GH), insulin-like growth factor I (IGF-I), pituitary GH mRNA, gene expression of IGF-I, IGF-II, and growth hormone receptor 2 (GHR) in the muscle and liver were also determined. Plasma IGF-I was higher in FW and TS than in SW and TF tilapia. Pituitary GH mRNA was higher in TF and TS than in FW and SW tilapia. Gene expression of IGF-I in the liver and of GHR in both the muscle and liver changed between TF and TS fish. Fish growth was positively correlated with GH mRNA expression in the pituitary, and GHR mRNA expression in muscle and liver tissues. Our study indicates that rearing fish under tidally-changing salinities elicits a distinct pattern of endocrine regulation from that observed in fish reared in steady-state conditions, and may provide a new approach to increase tilapia growth rate and study the regulation of growth in euryhaline fish. PMID:27032617

  16. Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

    Saurez-Gonzalez, Darilis

    The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was

  17. Empirical Research on the Factors of Chinese City Growth in the Transitional Period

    2010-01-01

    Based on the definition of the concept of city growth, the paper mainly discussed the factors which impact the growth of Chinese cities in the transitional period by selecting the proportion of city construction land area to the area of the city X1(%), green coverage ratio of the built up area X2(%), the ratio of personnel involved in the secondary industry X3(%), the GDP per capita X4(×104)and other 43 indicators, by relying on the relevant data from China Urban Statistical Yearbook(2008), applying SPSS statistical software and by applying the Factor Analysis and Regression Analysis. The results show that the factors which affect the city growth have four major groups, namely economic and institutional factors, location factors, environmental factors and social cultural services and functions. Among the factors which affect Chinese city growth, the general budgetary expenditures and the general budgetary revenues of local public finance are the most important factors. The general budgetary expenditures of local finance, the general budgetary revenues, the lands of urban construction and other 12 factors obtained by gradually excluding method can be used to present the coefficient of city growth.

  18. Growth factors, aging and age-related diseases.

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  19. Effect of Lanthanum on Mycelium Growth and Some Pathogenic Factors

    2006-01-01

    Three soil-transmitted pathogenic fungi including Rhizoctonia solani, Fusarium solani, and Pythium sp. were selected to investigate the effect of lanthanum on their growth and the pathogenic enzymes using liquid culture. Variance analysis shows significant differences among treatments with different concentrations of lanthanum (Rhizoctonia solani F=6.75>F0.01=5.99; Fusarium solani F=18.1>F0.01=5.99, Pythium sp. F=23.29>F0.01=5.99). The inhibitory effect of lanthanum on pathogenic fungi increased with an increase in La concentration. The activities of the three pathogenic enzymes per gram mycelium were promoted remarkably. However, the quantity or the activities of the total enzymes were inhibited because of the strong inhibition of mycelium growth by lanthanum. Meanwhile, the effect of lanthanum on toxins of pathogenic fungi were studied using the seed germination experiment. Toxins of pathogenic fungi are influenced by lanthanum and the virulence decreases significantly with the increase of lanthanum concentration.

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

    Andreas Androutsellis-Theotokis

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

  1. The Effects of Environmental Factors on the Growth and Competition of Algae

    Jing; WANG; Jiazhang; CHEN; Shunlong; MENG

    2013-01-01

    In order to study the effect of environmental factors on the algae growth and competition,the author summarized overseas and domestic related researches in recent years.Most of the researches are about the influence of single factor on growth of algae.However,there is insufficient investment on the interaction of different factors and the competition between algae growth.This paper briefly introduced the classification of algae and the role they played in ecological system and focused on the influence which included temperature,illumination,nitrogen,phosphorus and pH on the growth and competition of algal.In the end,the author proposed key questions which were still needed to be studied in order to know more about the relationship between environment effects and growth and competition of algae.Therefore,people could better improve the community structure of algae and water ecological environment,and improve water primary productivity.

  2. The diminished expression of proangiogenic growth factors and their receptors in gastric ulcers of cirrhotic patients.

    Jiing-Chyuan Luo

    Full Text Available OBJECTIVES: The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. METHODS: Eligible cirrhotic patients (n = 55 and non-cirrhotic patients (n = 55 who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF] and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2 were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other. RESULTS: The two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (p0.5, p<0.001. CONCLUSIONS: Our findings implied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

  3. Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

    Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10

  4. Release of transforming growth factor beta 1 and platelet derived growth factor type AB from canine platelet gels obtained by the tube method and activated with calcium salts

    RF Silva

    2013-01-01

    Full Text Available The objectives of this study were: 1 to measure the concentrations of transforming growth factor beta 1 (TGF-β1 and platelet-derived growth factor type AB (PDGF-AB in plasma and platelet gel (PG activated with calcium salts (gluconate or chloride in dogs, and 2 to determine correlations between cell results and growth factors (GF concentrations. Blood samples were collected from fourteen Brazilian Fila dogs. EDTA was used to obtain whole blood and plasma while ACD-A solution was used to prepare platelet concentrates (PC. Calcium salts were added to PC to induce their gelification. Platelet and leukocyte count was performed before PC activation. The concentration of growth factors in PG supernatants and plasma was determined by ELISA. Statistically significant differences (P < 0.01 between platelet and leukocyte count were observed when comparing whole blood and PC. No statistically significant differences were found between the concentrations of TGF-β1 and PDGF-AB in PC and plasma according to the calcium salt used for the activation of PC. The TGF-β1 concentration was highly correlated with the number of platelets concentrated in the PC. This methodology was useful for producing PG with therapeutic potential for canine regenerative medicine.

  5. Polypeptide chain fold of human transforming growth factor α analogous to those of mouse and human epidermal growth factors as studied by two-dimensional 1H NMR

    The 1H NMR spectrum of human transforming growth factor α (TGF-α) was analyzed almost completely by the sequential assignment method using two-dimensional NMR techniques. On the basis of the nearly complete sequence-specific resonance assignment, secondary and tertiary structures of human TGF-α in solution (pH 4.9, 28 degree C) were determined to satisfy the upper limits of proton-proton distances derived from nuclear Overhauser effect experiments. Although human TGF-α and mouse epidermal growth factor (EGF) share 27% homology in amino acid sequence, the backbone chain folds in the two growth factors are quite similar. The structure and function of TGF-α is well characterized by the mitten model previously proposed for mouse EGF. The gross shape of the TGF-α molecule resembles a mitten. TGF-α interacts with the receptor as a mitten would grasp an object. However, there is an appreciable structural difference between the two growth factors in the back of the mitten that is formed by the N-terminal polypeptide segment. This is consistent with the evidence that the backs of these molecules are not involved in the receptor binding

  6. Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor (IGF-1) in bovine colostrum samples.

    Ginjala, V; Pakkanen, R

    1998-01-01

    The major growth factors in bovine colostrum are transforming growth factor-beta s (TGF-beta 1 and TGF-beta 2) and insulin-like growth factors (IGF-1 and IGF-2). Recently, TGF-beta 2 content of bovine colostrum was measured using a TGF-beta 2 specific ELISA (1) and now we have validated ELISAs for for bovine TGF-beta 1 and IGF-1. The concentrations of IGF-1 and TGF-beta 1 in the first milking after calving were 248-1850 ng/ml and 12.4-42.6 ng/ml, respectively, and they declined in correlation with total protein concentration to 27.0-101 ng/ml (IGF-1) and 0.80-3.49 ng/ml(TGF-beta 1) by the fifth milkings. The amount of TGF-beta 1 was on average 5.3 +/- 1.4% of that of TGF-beta 2 and there is a high correlation (r = 0.966) between the concentrations of these growth factors in the same samples. No free TGF-beta 1 form of could be detected. PMID:9682131

  7. Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

    Wilczak, N; Ramsaransing, GSM; Mostert, J; Chesik, D; De Keyser, J

    2005-01-01

    Using radioimmunoassay we measured serum levels of insulin- like growth factor ( IGF)- 1 and IGF binding protein ( IGFBP)- 3 in patients with relapsing multiple sclerosis ( MS) and a benign course ( Expanded Disability Status Scale ( EDSS) less than or equal to 3 despite > 10 years disease duration)

  8. Analysis on the Factors that Determine Sustainable Growth of Small Firms in Namibia

    Asa Romeo Asa; Navneel Shalendra Prasad

    2014-01-01

    The demise rate of small firms every year is high worldwide and mostly these businesses struggle for many years without significant growth. Therefore, this study focused on identifying factors that contribute to the sustainability of growth for small firms in a developing country. Small firms are vital in the development and growth of bottom billion economies and are part of solutions to social problems that Namibia experience, inter alia, high unemployment rate. In developing countries, it i...

  9. Factors Influencing Growth of Women owned Micro and Small Enterprises A Survey of Kitale Municipality

    Ruth Niva Ongachi; Henry M. Bwisa

    2013-01-01

    This study was exploring on the growth status of micro and small enterprises owned by women in Kitale municipality, Trans-Nzoia County, Rift valley province in Kenya and the factors that influenced the growth. The dependent variable in the study was growth, while the independent variables were education, social, cultural, environmental condition, skills, technology and financial capacity. A total of 70 respondents were interviewed using an interview guide instrument carefully developed with s...

  10. Transport Sector CO(2) Emissions Growth in Asia : Underlying Factors and Policy Options

    Timilsina, G. R.; Shrestha, A.

    2009-01-01

    This study analyze the potential factors influencing the growth of transport sector carbon dioxide (CO(2)) emissions in selected Asian countries during the 1980-2005 period by decomposing annual emissions growth into components representing changes in fuel mix, modal shift, per capita gross domestic product (GDP) and population, as well as changes in emission coefficients and transportation energy intensity. We find that changes in per capita GDP, population growth and transportation energy i...

  11. Internal and External factors hampering SME growth : a qualitative case study of SMEs in Thailand

    Poblete, Leon; Grimsholm, Elin

    2010-01-01

    Small and medium-sized enterprises (SMEs) in Thailand are very important to economic growth and considerably essential to generate employment as in many other developing countries. SMEs account for 99.5% of the overall enterprises in Thailand while their contribution to the overall employment account for around 76% of all jobs. However, SMEs growth rate is still at a low level. Hence, this is qualitative study of the external and internal factors hampering the growth of SMEs in Thailand. Rega...

  12. Expression of fibroblast growth factor 23 by canine soft tissue sarcomas.

    Hardcastle, M R; Dittmer, K E

    2016-09-01

    Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of humans. Some mesenchymal tumours (often resembling haemangiopericytomas) express molecules that normally regulate phosphorus metabolism; most frequently, fibroblast growth factor 23. Patients develop renal phosphate wasting and inappropriately low serum concentrations of 1, 25 (OH)2 vitamin D3 , leading to osteomalacia. Surgical removal of the tumour is curative. The authors examined expression of canine fibroblast growth factor 23 in 49 soft tissue sarcomas, and control tissues from normal adult dogs. RNA extracted from bone or formalin-fixed, paraffin-embedded tissues was analysed by end point and quantitative reverse transcriptase-polymerase chain reaction. Fibroblast growth factor 23 expression was detected in bone, lung, kidney, lymph node and thymus. Fifteen of 49 sarcomas (31%) expressed fibroblast growth factor 23, three of these had high relative expression and some features resembling phosphatonin-expressing mesenchymal tumours of humans. Further work is required to determine whether TIO may occur in dogs. PMID:24923416

  13. Hyaluronic acid induces the release of growth factors from platelet-rich plasma

    Kohei Iio

    2016-04-01

    Conclusion: The levels of growth factors released by PRP on Day 5 were increased by the addition of HA. A mixture of PRP and HA may be a more effective therapy than PRP or HA alone for osteoarthritis and tendinopathy.

  14. Agonists of fibroblast growth factor receptor induce neurite outgrowth and survival of cerebellar granule neurons

    Li, Shizhong; Christensen, Claus; Køhler, Lene B; Kiselyov, Vladislav V; Berezin, Vladimir; Bock, Elisabeth

    2009-01-01

    Fibroblast growth factor receptor (FGFR) signaling is pivotal in the regulation of neurogenesis, neuronal differentiation and survival, and synaptic plasticity both during development and in adulthood. In order to develop low molecular weight agonists of FGFR, seven peptides, termed hexafins...

  15. Chronic systemic treatment with epidermal growth factor induces hypergastrinaemia in Goettingen minipigs

    Vinter-Jensen, Lars; Juhl, C O; Rehfeld, J F; Poulsen, Steen Seier; Dajani, E Z; Nexø, Ebba

    1995-01-01

    Epidermal growth factor (EGF) is an inhibitor of gastric acid secretion. The impact of chronic systemic treatment with EGF on intragastric pH and serum gastrin concentrations has not been investigated previously....

  16. Degradable PLGA Scaffolds with Basic Fibroblast Growth Factor: Experimental Studies in Myocardial Revascularization

    Wang, Ying(School of Physics, Shandong University, Jinan, 250100, PR China); Liu, Xiao-Cheng; Zhao, Jian; Kong, Xiang-Rong; Shi, Rong-Fang; Zhao, Xiao-Bin; Song, Cun-Xian; Liu, Tian-Jun; Lu, Feng

    2009-01-01

    Our goal was to investigate the efficacy of degradable poly(D,L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.

  17. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3

    The fibroblast growth factors are a family of polypeptide growth factors involved in a variety of activities including mitogenesis, angiogenesis, and wound healing. Fibroblast growth factor receptors (FGFRs) have previously been identified in chicken, mouse, and human and have been shown to contain an extracellular domain with either two or three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tyrosine kinase domain. The authors have isolated a human cDNA for another tyrosine kinase receptor that is highly homologous to the previously described FGFR. Expression of this receptor cDNA in COS cells directs the expression of a 125-kDa glycoprotein. They demonstrate that this cDNA encodes a biologically active receptor by showing that human acidic and basic fibroblast growth factors activate this receptor as measured by 45Ca2+ efflux assays. These data establish the existence of an additional member of the FGFR family that they have named FGFR-3

  18. Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

    Bahrami, A; Behzadi, Sh; Miraei-Ashtiani, S R; Roh, S-G; Katoh, K

    2013-09-15

    The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies. PMID:23747407

  19. Factors affecting the growth of bifidobacteria in human milk

    Ročková, Š.; Nevoral, J.; Rada, V.; Maršík, Petr; Sklenář, Jan; Hlinková, A.; Vlková, E.; Marounek, Milan

    2011-01-01

    Roč. 21, č. 7 (2011), s. 504-508. ISSN 0958-6946 R&D Projects: GA ČR GA523/07/0572; GA ČR GD525/08/H060 Institutional research plan: CEZ:AV0Z50380511; CEZ:AV0Z50200510; CEZ:AV0Z50450515 Keywords : OLIGOSACCHARIDES * INFANTS * PREBIOTICS Subject RIV: EC - Immunology Impact factor: 2.401, year: 2011

  20. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults

    Juul, A; Bang, P; Hertel, Niels;

    1994-01-01

    Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF-...

  1. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    Laursen, Erik; Juul, A; Lanng, S;

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on ...

  2. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells

  3. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Stagg, Brian C., E-mail: briancstagg@gmail.com; Uehara, Hironori; Lambert, Nathan; Rai, Ruju; Gupta, Isha; Radmall, Bryce; Bates, Taylor; Ambati, Balamurali K. [John A Moran Eye Center, University of Utah, Salt Lake City, UT, 65 Mario Capecchi Drive, Salt Lake City, UT 84132 (United States)

    2014-11-26

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

  4. Role of Copper and Vascular Endothelial Growth Factor (VEGF) on Endometrial Angiogenesis

    Yousef Rezaei Chianeh; Pragna Rao

    2013-01-01

    The formation of new blood vessels is the ini-tial step in neovascularisation. The first stagein angiogenesis is the activation of endothelialcells. Copper ions stimulate proliferation andimmigration of endothelial cells. It has beenshown that serum copper concentration in-creases as the cancer disease progresses andcorrelates with tumour incidence and burden.Copper ions also activate several proangiogenicfactors, e.g., vascular endothelial growth fac-tor, basic fibroblast growth factor, andi...

  5. Behavioral Effects of Systemic Transforming Growth Factor-alpha in Syrian Hamsters

    Gilbert, Jenifer; Davis, Fred C.

    2008-01-01

    The growth factor, transforming growth factor-alpha (TGF-α) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-α is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-α suppresses activity. TGF-α suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-α is correlated wi...

  6. Stability and biological activity evaluations of PEGylated human basic fibroblast growth factor

    Hadadian, Shahin; Shamassebi, Dariush Norouzian; Mirzahoseini, Hasan; Shokrgozar, Mohamad Ali; Bouzari, Saeid; Sepahi, Mina

    2015-01-01

    Background: Human basic fibroblast growth factor (hBFGF) is a heparin-binding growth factor and stimulates the proliferation of a wide variety of cells and tissues causing survival properties and its stability and biological activity improvements have received much attention. Materials and Methods: In the present work, hBFGF produced by engineered Escherichia coli and purified by cation exchange and heparin affinity chromatography, was PEGylated under appropriate condition employing 10 kD pol...

  7. Epidermal Growth Factor Receptor Inhibitors: A Review of Cutaneous Adverse Events and Management

    Chanprapaph, K.; Vachiramon, V.; Rattanakaemakorn, P.

    2014-01-01

    Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychos...

  8. Assessment of Growth Factor Treatment on Fibrochondrocyte and Chondrocyte Co-Cultures for TMJ Fibrocartilage Engineering

    Kalpakci, Kerem N.; Kim, Eric J.; Athanasiou, Kyriacos A.

    2010-01-01

    Treatments for patients suffering from severe temporomandibular joint (TMJ) dysfunction are limited, motivating the development of strategies for tissue regeneration. In this study, co-cultures of fibrochondrocytes (FC) and articular chondrocytes (AC) were seeded in agarose wells, and supplemented with growth factors, to engineer tissue with biomechanical properties and ECM composition similar to native TMJ fibrocartilage. In the first phase, growth factors were applied alone and in combinati...

  9. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients

    Bacchi, Carlos E.; Heloísa Ciol; Queiroga, Eduardo M.; Benine, Lucimara C.; Silva, Luciana H.; Ojopi, Elida B.

    2012-01-01

    OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patien...

  10. Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors.

    Vesey, D A; Woodman, A C; Hodgson, H J

    1992-01-01

    The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA...

  11. Increased concentrations of growth factors and activation of the EGFR system in breast cancer

    Aalund Olsen, Dorte; Bechmann, Troels; Østergaard, Birthe;

    2012-01-01

    In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.......In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values....

  12. Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling

    Svystonyuk, Daniyil A; Ngu, Janet MC; Mewhort, Holly EM; Lipon, Brodie D; Teng, Guoqi; Guzzardi, David G; Malik, Getanshu; Belke, Darrell D.; Fedak, Paul WM

    2015-01-01

    Background Tissue fibrosis and chamber remodeling is a hallmark of the failing heart and the final common pathway for heart failure of diverse etiologies. Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1 (TGFβ1) induces cardiac myofibroblast-mediated fibrosis and progressive structural tissue remodeling. Objectives We examined the effects of low molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac myofibroblast-mediated extracellular matrix (ECM)...

  13. Evaluation of the fibroblast growth factor receptor 1 (FGFR1) in experimental autoimmune encephalomyelitis (EAE)

    Rajendran, Ranjithkumar

    2014-01-01

    Fibroblast growth factors (FGFs) exert diverse biological effects by binding and activation of specific fibroblast growth factor receptors (FGFRs). Recent studies on the function of FGF2 in MOG35-55-induced experimental autoimmune encephalitis (EAE) showed that systemic deletion of FGF2 leads to a more severe disease course, increased lymphocyte and macrophage infiltration and decreased remyelination. In the present study the in vivo function of the corresponding receptor Fgfr1 was characteri...

  14. Amphiregulin enhances regulatory T cell suppressive function via the epidermal growth factor receptor

    Zaiss, Dietmar M.W.; van Loosdregt, Jorg; Gorlani, Andrea; Bekker, Cornelis P.J.; Gröne, Andrea; Sibilia, Maria; van Bergen en Henegouwen, Paul M. P.; Roovers, Rob C.; Coffer, Paul J.; Sijts, Alice J.A.M.

    2013-01-01

    Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3+ regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, m...

  15. Purification and characterization of native human insulin-like growth factor binding protein-6

    Taferner, Andrea; Micutkova, Lucia; Hermann, Martin; Jansen-Dürr, Pidder; Pircher, Haymo

    2011-01-01

    Insulin-like growth factor binding proteins (IGFBPs) are key regulators of insulin-like growth factor (IGF) mediated signal transduction and thereby can profoundly influence cellular phenotypes and cell fate. Whereas IGFBPs are extracellular proteins, intracellular activities were described for several IGFBP family members, such as IGFBP-3, which can be reinternalized by endocytosis and reaches the nucleus through routes that remain to be fully established. Within the family of IGFBPs, IGFBP-...

  16. Application of insulin-like growth factor 1 in the treatment of inner ear disorders

    NorioYamamoto

    2014-01-01

    Sensorineural hearing loss is considered an intractable disease, given that hair and supporting cells of the postnatal mammalian cochlea are unable to regenerate. However, with progress in regenerative medicine in the 21st century, several innovative approaches for achieving regeneration of inner ear hair and supporting cells have become available. These methods include stem cell transplantation, overexpression of specific genes, and treatment with growth factors. Insulin-like growth factor 1...

  17. Rapamycin Prevents Transforming Growth Factor-α–Induced Pulmonary Fibrosis

    Korfhagen, Thomas R; Le Cras, Timothy D.; Davidson, Cynthia R.; Stephanie M. Schmidt; Ikegami, Machiko; Whitsett, Jeffrey A.; Hardie, William D.

    2009-01-01

    Transforming growth factor (TGF)-α is a ligand for the epidermal growth factor receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. Overexpression of TGF-α in transgenic mice causes progressive and severe pulmonary fibrosis; however, the intracellular signaling pathways downstream of EGFR mediating this response are unknown. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-α e...

  18. Vascular Endothelial Growth Factor (VEGF) in Seizures: A Double-Edged Sword

    Croll, Susan D.; Goodman, Jeffrey H.; Scharfman, Helen E.

    2004-01-01

    Vascular endothelial growth factor (VEGF) is a vascular growth factor which induces the development of new blood vessels (angiogenesis), vascular permeability, and inflammation. In brain, receptors for VEGF have been localized to vascular endothelium, neurons, and glia. VEGF is upregulated after hypoxic injury to the brain, such as occurs with cerebral ischemia or high-altitude edema, and has been implicated in the blood-brain barrier breakdown which occurs during these conditions. Given its ...

  19. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  20. The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells

    Rooprai, H K; Rucklidge, G J; Panou, C; Pilkington, G. J.

    1999-01-01

    Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix. These enzymes have been implicated in a variety of physiological and pathological conditions including embryogenesis and tumour invasion. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed...

  1. Diabetes and Microvascular Physio-Pathology: Role of Epidermal Growth Factor Receptor Tyrosine Kinase

    Matrougui, Khalid

    2010-01-01

    Type 2 diabetes is responsible for the increased prevalence of ischemic heart disease, generally related to coronary artery disease, which is associated with increased morbidity and death in diabetic patients. Epidermal growth factor receptor (EGFR) tyrosine kinase, one of the many factors involved in cell growth and migration has been shown to be key element in the development of microvessel myogenic tone. In a recent study, we have shown that microvascular dysfunction in type 2 diabetes is ...

  2. Regulation of human cardiac KCNQ1/KCNE1 channel by epidermal growth factor receptor kinase

    Dong, MQ; Sun, HY; Tang, Q.; Tse, HF; Lau, CP; Li, GR

    2010-01-01

    The aim of the present study was to investigate whether/how the recombinant human cardiac I Ks could be regulated by epidermal growth factor receptor kinase in HEK 293 cells stably expressing hKCNQ1/hKCNE1 genes using the approaches of perforated patch clamp technique, immunoprecipitation and Western blot analysis. It was found that the broad spectrum isoflavone tyrosine kinase inhibitor genistein and the selective epidermal growth factor receptor kinase inhibitor tyrphostin AG556 suppressed ...

  3. Assessment of Vascular Endothelial Growth Factor in Fresh versus Frozen Platelet Rich Plasma

    Nada Hosny; Fikry Goubran; Basma BadrEldin Hasan; Noha Kamel

    2015-01-01

    Platelet rich plasma (PRP) is hemoconcentration with platelets concentration above baseline values and high concentration of many growth factors. The aim of this study was to assess freezing effect on vascular endothelial growth factor (VEGF) release from PRP using two different activation methods to simplify its use in different clinical applications. PRP was prepared using two-centrifugation steps method from 12 qualified blood donors. VEGF concentrations were measured in fresh PRP and afte...

  4. Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

    Ma, Li; Elliott, Susan N.; Cirino, Giuseppe; Buret, Andre; Ignarro, Louis J.; Wallace, John L

    2001-01-01

    Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by seros...

  5. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs

    Jungbluth, P; Grassmann, JP; Thelen, S; Wild, M.; Sager, M; Windolf, J.; M Hakimi

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of a...

  6. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, pVEGF (r=0.46, pplatelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors. PMID:26504722

  7. Distribution and number of epidermal growth factor receptors in skin is related to epithelial cell growth

    Green, M R; Basketter, D A; Couchman, J R;

    1983-01-01

    EGF. EGF receptors are detected on the epithelial cells overlying the basement membranes of the epidermis, sebaceous gland, and regions of the hair follicle all of which have proliferative capacity. In marked contrast, tissues which have started to differentiate and lost their growth potential, carry...... in the spatial and temporal control of epithelial proliferation....

  8. Targeting insulin-like growth factor-I and insulin-like growth factor-binding protein-3 signaling pathways. A novel therapeutic approach for asthma.

    Lee, Hyun; Kim, So Ri; Oh, Youngman; Cho, Seong Ho; Schleimer, Robert P; Lee, Yong Chul

    2014-04-01

    Insulin-like growth factor (IGF)-I has been recognized to play critical roles in the pathogenesis of asthma, whereas IGF-binding protein (IGFBP)-3 blocks crucial physiologic manifestations of asthma. IGF-I enhances subepithelial fibrosis, airway inflammation, airway hyperresponsiveness, and airway smooth muscle hyperplasia by interacting with various inflammatory mediators and complex signaling pathways, such as intercellular adhesion molecule-1, and the hypoxia-inducible factor/vascular endothelial growth factor axis. On the other hand, IGFBP-3 decreases airway inflammation and airway hyperresponsiveness through IGFBP-3 receptor-mediated activation of caspases, which subsequently inhibits NF-κB signaling pathway. It also inhibits the IGF-I/hypoxia-inducible factor/vascular endothelial growth factor axis via IGF-I-dependent and/or IGF-I-independent mechanisms. This Translational Review summarizes the role of IGF-I and IGFBP-3 in the context of allergic airway disease, and discusses the therapeutic potential of various strategies targeting the IGF-I and IGFBP-3 signaling pathways for the management of asthma. PMID:24219511

  9. Sciatic nerve regeneration using a nerve growth factor-containing fibrin glue membrane

    Shengzhong Ma; Changliang Peng; Shiqing Wu; Dongjin Wu; Chunzheng Gao

    2013-01-01

    Our previous findings confirmed that the nerve growth factor-containing fibrin glue membrane pro-vides a good microenvironment for peripheral nerve regeneration;however, the precise mechanism remains unclear. p75 neurotrophin receptor (p75NTR) plays an important role in the regulation of pe-ripheral nerve regeneration. We hypothesized that a nerve growth factor-containing fibrin glue membrane can promote neural regeneration by up-regulating p75NTR expression. In this study, we used a silicon nerve conduit to bridge a 15 mm-long sciatic nerve defect and injected a mixture of nerve growth factor and fibrin glue at the anastomotic site of the nerve conduit and the sciatic nerve. Through RT-PCR and western blot analysis, nerve growth factor-containing fibrin glue membrane significantly increased p75NTR mRNA and protein expression in the Schwann cells at the anasto-motic site, in particular at 8 weeks after injection of the nerve growth factor/fibrin glue mixture. These results indicate that nerve growth factor-containing fibrin glue membrane can promote pe-ripheral nerve regeneration by up-regulating p75NTR expression in Schwann cells.

  10. Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation.

    Tanimura, Yuko; Aoi, Wataru; Takanami, Yoshikazu; Kawai, Yukari; Mizushima, Katsura; Naito, Yuji; Yoshikawa, Toshikazu

    2016-06-01

    Fibroblast growth factor 21, a metabolic regulator, plays roles in lipolysis and glucose uptake in adipose tissues and skeletal muscles. Its expression in skeletal muscle is upregulated upon activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, which is induced by exercise and muscle contraction. We examined the increase of fibroblast growth factor 21 after acute exercise in metabolic organs, especially skeletal muscles and circulation. Participants exercised on bicycle ergometers for 60 min at 75% of their V˙O2max. Venous blood samples were taken before exercise and immediately after exercise. In an animal study, male ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed treadmill exercises at 30 m min(-1) for 60 min. Shortly thereafter, blood, liver, and skeletal muscle samples were taken from mice. Acute exercise induced the increase of serum fibroblast growth factor 21 in both humans and mice, and increased fibroblast growth factor 21 expression in the skeletal muscles and the liver of mice. Acute exercise activated Akt in mice skeletal muscle. Acute exercise increases fibroblast growth factor 21 concentrations in both serum and metabolic organs. Moreover, results show that acute exercise increased the expression of fibroblast growth factor 21 in skeletal muscle, accompanied by the phosphorylation of Akt in mice. PMID:27335433

  11. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  12. Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth

    Wan, Xinhai; Li, Zhi-gang; Yingling, Jonathan M.; Yang, Jun; Starbuck, Michael W.; Ravoori, Murali K.; Kundra, Vikas; Vazquez, Elba; Navone, Nora M.

    2011-01-01

    Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice ...

  13. Effects of immune challenge on concentrations of serum insulin-like growth factor-I and growth performance in pigs.

    Hevener, W; Routh, P A; Almond, G W

    1999-01-01

    This study was designed to determine the long-term effects of repeated endotoxin treatment or immunization against human serum albumin on concentrations of serum insulin-like growth factor-I (IGF-I) and other indicators of growth performance in growing pigs. Thirty gilts (38.5 +/- 0.9 kg) were randomly assigned to 5 treatment groups (n = 6 animals/group): 1) lipopolysaccharide injections, 2) lipopolysaccharide pair-fed, 3) human serum albumin immunization, 4) human serum albumin pair-fed, and...

  14. Antisense epidermal growth factor receptor RNA transfection in human glioblastoma cells down-regulates telomerase activity and telomere length

    Tian, X-X; Pang, JC-S; J. Zheng; Chen, J; To, S S T; Ng, H-K

    2002-01-01

    Epidermal growth factor receptor is overexpressed and/or amplified in up to 50% of glioblastomas, suggesting an important role of this gene in glial tumorigenesis and progression. In the present study we demonstrated that epidermal growth factor receptor is involved in regulation of telomerase activity in glioblastoma. Antisense-epidermal growth factor receptor approach was used to inhibit epidermal growth factor receptor expression of glioblastoma U87MG cells. Telomerase activity in antisens...

  15. Human skin in organ culture. Elaboration of proteolytic enzymes in the presence and absence of exogenous growth factors.

    Varani, J.; Perone, P.; Inman, D. R.; Burmeister, W.; Schollenberger, S. B.; Fligiel, S. E.; Sitrin, R G; Johnson, K.J.

    1995-01-01

    Proteinase levels were assessed in organ culture fluids from human neonatal foreskin maintained under growth factor-free conditions and in the presence of a combination of growth factors (ie, epidermal growth factor, insulin, hydrocortisone, pituitary extract, and all-trans-retinoic acid). Analysis of culture fluids by gelatin zymography revealed the presence of 92-kd and 72-kd gelatinases. There was a greater amount of 92-kd gelatinase activity in the presence of growth factors whereas the l...

  16. Lipoteichoic acid and interleukin 1 stimulate synergistically production of hepatocyte growth factor (scatter factor) in human gingival fibroblasts in culture.

    Sugiyama, A; Arakaki, R; Ohnishi, T.; Arakaki, N.; Daikuhara, Y.; Takada, H

    1996-01-01

    Lipoteichoic acids (LTA) from various gram-positive bacteria, including oral streptococci such as Streptococcus sanguis, enhanced the production of hepatocyte growth factor (HGF) (scatter factor) by human gingival fibroblasts in culture, whereas lipopolysaccharides (LPS) from various gram-negative bacteria did not. In contrast, LPS induced interleukin 1 activity in human gingival epithelial cells in culture, while LTA had little effect. LTA and recombinant human interleukin 1 alpha enhanced s...

  17. Temporal Control of Plant Organ Growth by TCP Transcription Factors.

    Huang, Tengbo; Irish, Vivian F

    2015-06-29

    The Arabidopsis petal is a simple laminar organ whose development is largely impervious to environmental effects, making it an excellent model for dissecting the regulation of cell-cycle progression and post-mitotic cell expansion that together sculpt organ form. Arabidopsis petals grow via basipetal waves of cell division, followed by a phase of cell expansion. RABBIT EARS (RBE) encodes a C2H2 zinc finger transcriptional repressor and is required for petal development. During the early phase of petal initiation, RBE regulates a microRNA164-dependent pathway that controls cell proliferation at the petal primordium boundaries. The effects of rbe mutations on petal lamina growth suggest that RBE is also required to regulate later developmental events during petal organogenesis. Here, we demonstrate that, early in petal development, RBE represses the transcription of a suite of CIN-TCP genes that in turn act to inhibit the number and duration of cell divisions; the temporal alleviation of that repression results in the transition from cell division to post-mitotic cell expansion and concomitant petal maturation. PMID:26073137

  18. Economic Growth Factor in Nigeria: The Role of Global Trade

    Samuel Gowon Edoumiekumo

    2013-05-01

    Full Text Available The paper examines the contributions of international trade (proxied with export and import values to economic growth in Nigeria measured by real gross domestic product (RGDP. We used time series data obtained from CBN for a period of 27 years. Augmented Dickey-Fuller (ADF test was used for the unit root test and the variables were stationary at levels I(0. Johansen’s co-integration test was also conducted to establish short and long run relationships between the two variables. The result shows two co-integrating equations which establish the existence of long run relationship among the variables. Ordinary Least Square statistical technique was used to assess the degree of influence the variables have on each other. The results show that positive relationship exists between the variables, RGDP, export and import. The export parameter is insignificant at 5 percent. The overall model is significant at 5 percent. Finally, we used Granger causality test to study the causality between the variables and realized a uni-directional relationship. Real GDP Granger cause export and import Granger cause RGDP and export. Nigeria needs to increase or diversify her export goods to enjoy more of the benefits of international trade. Normal 0 false false false EN-US X-NONE AR-SA

  19. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    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. Factors Affecting Bacterial Growth in Drinking Water Distribution System

    WEI LU; XIAO-JIAN ZHANG

    2005-01-01

    Objective To define the influence of some parameters, including assimilable organic carbon (AOC), chloramine residual, etc. on the bacterial growth in drinking water distribution systems. Methods Three typical water treatment plants in a northern city (City T) of China and their corresponding distribution systems were investigated. Some parameters of the water samples, such as heterotrophic plate content (HPC), AOC, CODMn, TOC, and phosphate were measured. Results The AOC in most water samples were more than 100 μg/L, or even more than 200 μg/L in some cases. The HPC in distribution systems increased significantly with the decrease of residual chlorine. When the residual chlorine was less than 0.1 mg/L, the magnitude order of HPC was 104 CFU/mL; when it was 0.5-0.7 mg/L, the HPC was about 500 CFU/mL. Conclusion For controlling the biostability of drinking water, the controlling of AOC and residual chlorine should be considered simultaneously. The influence of phosphors on the AOC tests of water is not significant. Phosphors may not be the limiting nutrient in the water distribution systems.

  1. Growth differentiation factor 6 as a putative risk factor in neuromuscular degeneration.

    Michèle G DuVal

    Full Text Available Mutation of Glass bottom boat, the Drosophila homologue of the bone morphogenetic protein or growth/differentiation factor (BMP/GDF family of genes in vertebrates, has been shown to disrupt development of neuromuscular junctions (NMJ. Here we tested whether this same conclusion can be broadened to vertebrate BMP/GDF genes. This analysis was also extended to consider whether such genes are required for NMJ maintenance in post-larval stages, as this would argue that BMP genes are viable candidates for analysis in progressive neuromuscular disease. Zebrafish mutants harboring homozygous null mutations in the BMP-family gene gdf6a were raised to adulthood and assessed for neuromuscular deficits. Fish lacking gdf6a exhibited decreased endurance (∼ 50%, p = 0.005 compared to wild type, and this deficit progressively worsened with age. These fish also presented with significantly disrupted NMJ morphology (p = 0.009, and a lower abundance of spinal motor neurons (∼ 50%, p<0.001 compared to wild type. Noting the similarity of these symptoms to those of Amyotrophic Lateral Sclerosis (ALS model mice and fish, we asked if mutations in gdf6a would enhance the phenotypes observed in the latter, i.e. in zebrafish over-expressing mutant Superoxide Dismutase 1 (SOD1. Amongst younger adult fish only bigenic fish harboring both the SOD1 transgene and gdf6a mutations, but not siblings with other combinations of these gene modifications, displayed significantly reduced endurance (75%, p<0.05 and strength/power (75%, p<0.05, as well as disrupted NMJ morphology (p<0.001 compared to wild type siblings. Bigenic fish also had lower survival rates compared to other genotypes. Thus conclusions regarding a role for BMP ligands in effecting NMJ can be extended to vertebrates, supporting conservation of mechanisms relevant to neuromuscular degenerative diseases. These conclusions synergize with past findings to argue for further analysis of GDF6 and other BMP genes as

  2. Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

    Perrone, Carmen E.; Fenwick-Smith, Daniela; Vandenburgh, Herman H.

    1995-01-01

    Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli.

  3. Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts

    Dabelsteen, S; Wandall, H H; Grøn, B;

    1997-01-01

    Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is...... expressed in periodontal ligament fibroblasts, and that the expression is increased upon serum stimulation. Fibroblasts from human periodontal ligament, from buccal mucosa, from gingiva, and from skin were established from explants. Alkaline phosphatase activity was used as an indicator of the periodontal...

  4. Polymorphisms in the Insulin-Like Growth Factor Axis Are Associated with Gastrointestinal Cancer

    Ong, J.; Salomon, J; Morsche, R.H.M. te; Roelofs, H.M.J.; Witteman, B.J.; Dura, P.; Lacko, M; Peters, W H M

    2014-01-01

    INTRODUCTION: Numerous factors influence the development of gastrointestinal (GI) cancer. The insulin-like growth factor (IGF) axis plays a role in embryonic and postnatal growth and tissue repair. Elevated levels of IGFs, low levels of IGF binding proteins (IGFBPs) and over-expression of IGF receptor (IGFR-I) were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormo...

  5. Expression and Purification of Active Recombinant Human Nerve Growth Factor from Escherichia coli

    2007-01-01

    @@ Introduction Nerve growth factor (NGF) was first discovered and purified by Rita Levi-Montalcini and Stanley Cohen in the 1950s[1,2]. It represents the first cellular growth factor ever discovered and involved in the growth, survival, and differentiation of specific nerve cell populations[3]. Although animal tests and phase-Ⅱ clinical trials indicate that rhNGF could be an effective treatment for diabetic[4] and HIV-related neuropathies[5] , a large-scale phase-Ⅲ clinical trial has failed to give similar result[6].

  6. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

    Chen, Zhihong; Yang, Songhe; He, Yaqiang; Song, Chengjun; Liu, Yongping

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in ...

  7. Early diet, insulin-like growth factor-1, growth and later obesity

    Michaelsen, Kim F; Larnkjær, Anni; Mølgaard, Christian

    2013-01-01

    the complementary feeding period does not seem to be a risk factor for later obesity. Thus, the dietary pattern during this period is different from the pattern seen in older children and adults where a high fat intake is associated with a higher risk of obesity and a high protein intake in some studies seems......There is increasing evidence that factors in early life are important for the risk of developing overweight and obesity later in childhood. Among the postnatal factors, breastfeeding and complementary feeding are especially interesting because the pattern of these two factors can be changed....... Breastfeeding has been shown to reduce the risk of later obesity, although the effect is not substantial. Complementary feeding also seems to play a role. There is some evidence that a high protein intake is associated with a higher risk of obesity later in childhood, whereas a high fat intake during...

  8. Exploring the Different Trajectories of Analytical Thinking Ability Factors: An Application of the Second-Order Growth Curve Factor Model

    Saengprom, Narumon; Erawan, Waraporn; Damrongpanit, Suntonrapot; Sakulku, Jaruwan

    2015-01-01

    The purposes of this study were 1) Compare analytical thinking ability by testing the same sets of students 5 times 2) Develop and verify whether analytical thinking ability of students corresponds to second-order growth curve factors model. Samples were 1,093 eighth-grade students. The results revealed that 1) Analytical thinking ability scores…

  9. Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter.

    Zhong, Juan; Guo, Bin; Xie, Jing; Deng, Shuwen; Fu, Na; Lin, Shiyu; Li, Guo; Lin, Yunfeng; Cai, Xiaoxiao

    2016-01-01

    Adipose-derived stem cells (ASCs) and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity. Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes. However, the paracrine action of ASCs on chondrocytes needs to be further elucidated. In this study, we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1% fetal bovine serum to mimic the physiological microenvironment. In ASCs, we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor B (VEGFB), hypoxia inducible factor-1α (HIF-1α), fibroblast growth factor-2 (FGF-2), and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture. In chondrocytes, VEGFA was significantly enhanced after co-culture. Unexpectedly, the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group. Meanwhile, among all the growth factors screened, we found that the BMP family members BMP-2, BMP-4, and BMP-5 were down-regulated and that VEGFB, HIF-1α, FGF-2, and PDGF were significantly decreased after co-culture. These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering. PMID:26848404

  10. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: ► Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. ► Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. ► These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. ► Anti-SEMA4D blocking antibody inhibits Plexin-B1 activation. ► SEMA4D is a valid anti-angiogenic target in the

  11. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    Zhou, Hua; Yang, Ying-Hua [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Binmadi, Nada O. [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Oral Basic and Clinical Sciences, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Proia, Patrizia [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Sports Science (DISMOT), University of Palermo, Via Eleonora Duse 2 90146, Palermo (Italy); Basile, John R., E-mail: jbasile@umaryland.edu [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Greenebaum Cancer Center, 22S. Greene Street, Baltimore, MD 21201 (United States)

    2012-08-15

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: Black-Right-Pointing-Pointer Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. Black-Right-Pointing-Pointer Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. Black-Right-Pointing-Pointer These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. Black-Right-Pointing-Pointer Anti-SEMA4D

  12. Stimulation of DNA synthesis in cultured primary human mesothelial cells by specific growth factors

    Monolayer cultures of human mesothelial cells made quiescent by serum deprivation are induced to undergo one round of DNA synthesis by platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or transforming growth factor type beta 1 (TGF-beta 1). This one-time stimulation is independent of other serum components. The kinetics for induction of DNA synthesis observed for PDGF, EGF, and TGF-beta 1 are all similar to one another, with a peak of DNA synthesis occurring 24-36 h after the addition of the growth factors. Repetitive rounds of DNA synthesis and cell division do not ensue after addition of PDGF, EGF, or TGF-beta 1 alone or in combination; however, in media supplemented with chemically denatured serum, each of these factors is capable of sustaining continuous replication of mesothelial cells. Stimulation of growth by PDGF and TGF-beta 1 is unusual for an epithelial cell type, and indicates that mesothelial cells have growth regulatory properties similar to connective tissue cells

  13. The role of vascular endothelial growth factor in the tissue specific in vivo growth of prostate cancer cells.

    Krupski, T; Harding, M A; Herce, M E; Gulding, K M; Stoler, M H; Theodorescu, D

    2001-01-01

    Despite the fact that cancer cells can be found in many vascular beds, continued growth of the metastatic tumor focus exhibits a significant degree of 'organ tropism', with only certain organs exhibiting the ravages of metastatic disease. Since a limiting factor to the growth of metastases beyond 2 mm in diameter, may be a lack of angiogenesis, we sought to determine whether tumor overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic factor related to prostate cancer metastasis, is causally related to organ specific tumor growth in a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human prostate cancer cell line LnCaP which unlike its parent, has a predilection for growth in bone, a common site for human prostate cancer metastasis. LnCaP-C4-2, is tumorigenic when injected intrafemorally in mice but requires co-injection of stromal components (Matrigel) to be tumorigenic in the subcutaneous site. Because of this site-specific tumorigenicity profile and relatively low VEGF mRNA and protein expression, this line was transfected with a full length cDNA encoding the 165 isoform of VEGF. Cells either overexpressing or not expressing the transfected gene were selected for study in vivo and in vitro. Overexpression of VEGF did not seem to affect in vitro cell growth. Such overexpression did affect tumorigenicity and in vivo tumor growth rates when cells were inoculated in the subcutaneus site. Interestingly, the dependency of subcutaneous tumorigenicity on Matrigel co-inoculation was still observed in cells overexpressing VEGF. In contrast to the impact that VEGF overexpression has on subcutaneous tumorigenicity, no such effect was observed when cells were inoculated in orthotopic/prostate (primary) or intrafemoral (metastatic) sites. In view of the importance of tumor-stromal interactions in growth of xenografts, we sought to determine if the host strain is important to the observed tumorigenicity effects of VEGF overexpression

  14. Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects.

    Li, Dong; Xie, Kun; Zhang, Longzhen; Yao, Xuejing; Li, Hongwen; Xu, Qiaoyu; Wang, Xin; Jiang, Jing; Fang, Jianmin

    2016-07-28

    Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect. Our in vitro data showed that VF-Trap potently blocked proliferation and migration of both VEGF- and FGF-2-induced vascular endothelial cells. In animal models, treatment of xenograft tumors with VF-Trap resulted in significant inhibition of tumor growth compared to blockage of the single molecule, like VEGF or FGF blocker. In addition, VF-Trap was also more potent in inhibition of ocular angiogenesis in a mouse oxygen-induced retinopathy (OIR) model. These data demonstrated the potent anti-angiogenic effects of this novel VF-Trap fusion protein on blockage of VEGF and FGF-2 activity in vitro and in animal models. Further study will assess its effects in clinic as a therapeutic agent for angiogenesis-related disorders, such as cancer and ocular vascular diseases. PMID:27130666

  15. Environmental Factors Associated with the Growth of Chinese Literary Genius: A Test of Rogerian Assumption.

    Kuo, You-Yuk

    1987-01-01

    This study explored relationships between environmental factors (era, standard of living, freedom, and value) and the growth of Chinese literary genius. Using a new measure, the Chinese Creator Rating Scale, the study found that historical top scorers had above average values on the four environmental factors, supporting the humanistic theory of…

  16. Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice

    Salih, Dervis A. M.; Tripathi, Gyanendra; Holding, Cathy; Szestak, Tadge A. M.; Gonzalez, M. Ivelisse; Carter, Emma J.; Cobb, Laura J.; Eisemann, Joan E.; Pell, Jennifer M.

    2004-01-01

    The insulin-like growth factors (IGFs) are essential for development; bioavailable IGF is tightly regulated by six related IGF-binding proteins (IGFBPs). Igfbp5 is the most conserved and is developmentally up-regulated in key lineages and pathologies; in vitro studies suggest that IGFBP-5 functions independently of IGF interaction. Genetic ablation of individual Igfbps has yielded limited phenotypes because of substantial compensation by remaining family members. Therefore, to reveal Igfbp5 a...

  17. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [3H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [3H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

  18. Growth factor regulation of sugar uptake in cultured cells

    Mouse EGF stimulates the uptake of 2-deoxygluclose (dGIc), a non-metabolized glucose analogue, into cultured mouse 3T3 fibroblasts (Clone 1) 2 to 4 fold, and EGF dependent Balb/MK-1 epidermal kerotinocytes, 5 to 8 fold. Initial stimulation is detected at 15 minutes. Maximal effects are seen at 2 hours with 10 ng/ml EGF. Binding of 125I-labeled EGF to cells is rapid and complete by 2 hours at 370C. Antibodies which specifically inhibit 125I-labeled EGF binding to cells inhibit EGF stimulation as much as 85%. Human platelet derived TGF-β stimulates dGlc uptake up to 5 fold. Maximum effects are seen with 1 ng/ml TGF-β within 2 hours and stimulation is detected 30 minutes after exposure to 0.1 ng/ml, the minimum effective concentration. TGF-β, like EGF, stimulates sugar transport into Balb/MK-1 cells without additional factors. However, neither stimulates uptake in a 3T3 variant, NR-6, which is EGF-receptor negative. The co-addition of EGF and/or PDGF enhances TGF-β stimulation. Binding of 125I-labeled TGF-β is nearly complete by 1 hour at 370C, but continues to increase for as long as 4 hours after addition. Antibodies which inhibit EGF binding have no effect on TGF-β binding, but they block TGF-β stimulation of hexose uptake. It is concluded from these results that the TGF-β receptor is distinct from the EGF receptor, and that although TGF-β stimulation of dGLc uptake does not require exogenously added EGF, it does require an active or available EGF receptor kinase system

  19. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 μm) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering

  20. Intrauterine Growth Retardation (IUGR) as a Novel Condition of Insulin-Like Growth Factor-1 (IGF-1) Deficiency.

    Martín-Estal, I; de la Garza, R G; Castilla-Cortázar, I

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) is an anabolic hormone with several biological activities, such as proliferation, mitochondrial protection, cell survival, tissue growth and development, anti-inflammatory, antioxidant, antifibrogenic and antiaging. This hormone plays an important role in embryological and postnatal states, being essential for normal foetal and placental growth and differentiation. During gestation, the placenta is one of the major sources of IGF-1, among other hormones. This intrauterine organ expresses IGF-1 receptors and IGF-1 binding proteins (IGFBPs), which control IGF-1 activities. Intrauterine growth restriction (IUGR) is the second most frequent cause of perinatal morbidity and mortality, defined as the inability to achieve the expected weight for gestational age. Different studies have revealed that IUGR infants have placental dysfunction and low circulating levels of insulin, IGF-1, IGF-2 and IGFBPs. Such data suggest that IGF-1 deficiency in gestational state may be one of the major causes of foetal growth retardation. The aim of this review is to study the epidemiology, physiopathology and possible causes of IUGR. Also, it intends to study the possible role of the placenta as an IGF-1 target organ. The purpose is to establish if IUGR could be considered as a novel condition of IGF-1 deficiency and if its treatment with low doses of IGF-1 could be a suitable therapeutic strategy. PMID:26634242