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Genève, Switzerland
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News Article | December 1, 2016

There are different kinds of growth factors present in the human body. Some of the major growth factors include insulin-like growth factors, platelet-derived growth factors, epidermal growth factors, and nerve growth factor. Moreover, some cytokines, such as small proteins secreted by one cell to regulate the function of another cell, also act as growth factors. Growth factors are mainly used in the treatment of chronic diseases, such as anemia, renal disorders, cancer, etc. For instance, erythropoietin, which stimulates the growth of Red Blood Cells (RBCs), is used to treat anemia. Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and Granulocyte Colony-Stimulating Factor (G-CSF) are involved in the stimulation of White Blood Cells (WBCs) in cancer patients. However, abnormal production of growth factors causes several diseases. For instance, vascular endothelial growth factor provokes endothelial cells to penetrate tumor in blood capillaries. The global growth factors market covers various blood growth factors and tissue growth factors. Blood growth factors include colony stimulating factors, erythropoietins, interferons, and interleukins. In terms of geography, North America dominates the global growth factors market. This is due to improved health care infrastructure and increasing prevalence of chronic diseases in the region. In addition, growing demand for recombinant growth factors has also propelled the growth of the market in North America. The U.S. represents the largest market for growth factors in North America, followed by Canada. In Europe, Germany, France, and the U.K. account for the major share of the growth factors market. The growth factors market in Asia is also expected to expand at a higher rate in the next five years. This is due to the rising awareness about therapeutic applications of growth factors in the treatment of chronic diseases in the region. In addition, increasing prevalence of chronic diseases and growing aging population are driving the expansion of the growth factors market in the region. Growing demographics and economies in developing countries, such as India and China, are expected to lead to the rise in the growth factors market in Asia. Moreover, India, China, and Japan, are expected to be the fastest growing markets for growth factors in the region. Increasing prevalence of chronic diseases and rising awareness about therapeutic applications of growth factors in treatment of various diseases are among the major driving factors for the global growth factors market. Also, increasing research in the field of synthetic blood growth factor has propelled the growth of the global growth factors market. Risk and complications associated with synthetic growth factors in treatment of diseases is a key restraint for the global growth factors market. In addition, the imposition of stringent regulations for the approval of synthetic growth factors inhibits the growth of the market. Rapid product launches and increasing number of mergers and acquisitions between growth factors manufacturing companies are some of the major trends observed in the market. The major companies operating in this market are Wockhardt Ltd., F. Hoffmann-La Roche AG, Alseres Pharmaceuticals, Inc., Bayer HealthCare Pharmaceuticals Inc., Amgen Inc., BioMimetic Therapeutics Inc., Ceregene, Inc., FibroGen, Inc., Novo Nordisk A/S, Johnson & Johnson Limited, Merck Serono International S.A., PeproTech Inc., NsGene A/S, Insmed Inc., Reliance GeneMedix Plc., and Lonza Group. Key geographies evaluated in this report are:

Reutershan J.,University of Virginia | Reutershan J.,University of Tübingen | Saprito M.S.,University of Virginia | Wu D.,Yale University | And 3 more authors.
European Respiratory Journal | Year: 2010

Phosphoinositide 3-kinase γ(PI3Kγ) is a critical mediator of directional cell movement. Here, we sought to characterise the role of PI3Kγ in mediating the different steps of polymorphonuclear leukocyte (PMN) trafficking in the lung. In a murine model of lipopolysaccharide (LPS)-induced lung injury, PMN migration into the different lung compartments was determined in PI3Kγ gene-deficient (PI3Kγ-/-) and wild-type mice. Bone marrow chimeras were created to characterise the role of PI3Kγ on haematopoietic versus nonhaematopoietic cells. A small-molecule PI3Kγ inhibitor was tested in vitro and in vivo. PMN adhesion to the pulmonary endothelium and transendothelial migration into the lung interstitium was enhanced in PI3Kγ-/-mice. However, transepithelial migration into the alveolar space was reduced in these mice. When irradiated PI3Kγ-/- mice were reconstituted with bone marrow from wild-type mice, migratory activity into the alveolar space was restored partially. A small-molecule PI3Kγ inhibitor reduced chemokine-induced PMN migration in vitro when PMNs or epithelial cells, but not when endothelial cells, were treated. The inhibitor also reduced LPS-induced PMN migration in vivo. We conclude that PI3Kγ is required for transepithelial but not for transendothelial migration in LPS-induced lung injury. Inhibition of PI3Kγ activity may be effective at curbing excessive PMN infiltration in lung injury. Copyright©ERS Journals Ltd 201.

Neerup T.S.R.,Zealand Pharma A S | Stahlhut M.,Zealand Pharma A S | Petersen J.S.,Zealand Pharma A S | Petersen J.S.,Merck Serono International S.A. | And 5 more authors.
Bone | Year: 2011

Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac5c1, Aib3, Leu8, Gln10, Har11, Ala12, Trp14, Asp17]PTH(1-17)-NH2), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K13-D17 side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40-160nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats.To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range. © 2011 Elsevier Inc.

Larson R.P.,University of Washington | Larson R.P.,Benaroya Research Institute | Zimmerli S.C.,University of Geneva | Zimmerli S.C.,Merck Serono International SA | And 9 more authors.
Journal of Immunology | Year: 2010

Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. In this study, we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity in mice. TSLP is required for the development of Th2-type contact hypersensitivity induced by the hapten FITC in combination with the sensitizing agent dibutyl phthalate. TSLPR-deficient mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR-deficient mice is likely due to decreased frequency and reduced T cell stimulatory function of skin-derived Ag-bearing FITC +CD11c + dendritic cells in draining lymph nodes following FITC sensitization. These data suggest that skin-derived dendritic cells are direct or indirect targets of TSLP in the development of type 2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naive allergen-specific T cells. Copyright © 2010 by The American Association of Immunologists, Inc.

PubMed | Eli Lilly and Company, Bayer AG, Pfizer, Imperial College London and 6 more.
Type: Journal Article | Journal: Pharmacoepidemiology and drug safety | Year: 2016

The PROTECT Benefit-Risk group is dedicated to research in methods for continuous benefit-risk monitoring of medicines, including the presentation of the results, with a particular emphasis on graphical methods.A comprehensive review was performed to identify visuals used for medical risk and benefit-risk communication. The identified visual displays were grouped into visual types, and each visual type was appraised based on five criteria: intended audience, intended message, knowledge required to understand the visual, unintentional messages that may be derived from the visual and missing information that may be needed to understand the visual.Sixty-six examples of visual formats were identified from the literature and classified into 14 visual types. We found that there is not one single visual format that is consistently superior to others for the communication of benefit-risk information. In addition, we found that most of the drawbacks found in the visual formats could be considered general to visual communication, although some appear more relevant to specific formats and should be considered when creating visuals for different audiences depending on the exact message to be communicated.We have arrived at recommendations for the use of visual displays for benefit-risk communication. The recommendation refers to the creation of visuals. We outline four criteria to determine audience-visual compatibility and consider these to be a key task in creating any visual. Next we propose specific visual formats of interest, to be explored further for their ability to address nine different types of benefit-risk analysis information.

Guo X.,Tokyo Metropolitan Institute for Neuroscience | Harada C.,Tokyo Metropolitan Institute for Neuroscience | Namekata K.,Tokyo Metropolitan Institute for Neuroscience | Matsuzawa A.,Tokyo University of Science | And 12 more authors.
EMBO Molecular Medicine | Year: 2010

Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase which plays important roles in stress and immune responses. Here, we show that ASK1 deficiency attenuates neuroinflammation in experimental autoimmune encephalomyelitis (EAE), without affecting the proliferation capability of T cells. Moreover, we found that EAE upregulates expression of Toll-like receptors (TLRs) in activated astrocytes and microglia, and that TLRs can synergize with ASK1-p38 MAPK signalling in the release of key chemokines from astrocytes. Consequently, oral treatment with a specific small molecular weight inhibitor of ASK1 suppressed EAE-induced autoimmune inflammation in both spinal cords and optic nerves. These results suggest that the TLR-ASK1-p38 pathway in glial cells may serve as a valid therapeutic target for autoimmune demyelinating disorders including multiple sclerosis. © 2010 EMBO Molecular Medicine.

Tanino Y.,Veterans Affairs Puget Sound Medical Center | Tanino Y.,University of Washington | Coombe D.R.,Curtin University Australia | Gill S.E.,University of Washington | And 11 more authors.
Journal of Immunology | Year: 2010

Chemokine-glycosaminoglycan (GAG) interactions are thought to result in the formation of tissue-bound chemokine gradients. We hypothesized that the binding of chemokines to GAGs would increase neutrophil migration toward CXC chemokines instilled into lungs of mice. To test this hypothesis we compared neutrophil migration toward recombinant human CXCL8 (rhCXCL8) and two mutant forms of CXCL8, which do not bind to heparin immobilized on a sensor chip. Unexpectedly, when instilled into the lungs of mice the CXCL8 mutants recruited more neutrophils than rhCXCL8. The CXCL8 mutants appeared in plasma at significantly higher concentrations and diffused more rapidly across an extracellular matrix in vitro. A comparison of the murine CXC chemokines, KC and MIP-2, revealed that KC was more effective in recruiting neutrophils into the lungs than MIP-2. KC appeared in plasma at significantly higher concentrations and diffused more rapidly across an extracellular matrix in vitro than MIP-2. In kinetic binding studies, KC, MIP-2, and rhCXCL8 bound heparin differently, with KC associating and dissociating more rapidly from immobilized heparin than the other chemokines. These data suggest that the kinetics of chemokine-GAG interactions contributes to chemokine function in tissues. In the lungs, it appears that chemokines, such as CXCL8 or MIP-2, which associate and disassociate slowly from GAGs, form gradients relatively slowly compared with chemokines that either bind GAGs poorly or interact with rapid kinetics. Thus, different types of chemokine gradients may form during an inflammatory response. This suggests a new model, whereby GAGs control the spatiotemporal formation of chemokine gradients and neutrophil migration in tissue.

Navis A.C.,Radboud University Nijmegen | Van Den Eijnden M.,Merck Serono International S.A | Schepens J.T.G.,Radboud University Nijmegen | Hooft Van Huijsduijnen R.,Merck Serono International S.A | And 2 more authors.
Acta Neuropathologica | Year: 2010

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas.

Proudfoot A.E.I.,Merck Serono International SA | Power C.A.,Merck Serono International SA | Schwarz M.K.,Merck Serono International SA
Expert Opinion on Investigational Drugs | Year: 2010

Importance of the field: Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migration, but just over a decade ago chemokine receptors were also identified as playing a pivotal role in the entry of the HIV virus into cells. Chemokines activate seven transmembrane G protein-coupled receptors, making them extremely attractive therapeutic targets for the pharmaceutical industry. Areas covered in this review: Although there are now a large number of molecules targeting chemokines and chemokine receptors including neutralizing antibodies in clinical trials for inflammatory diseases, the results to date have not always been positive, which has been disappointing for the field. These failures have often been attributed to redundancy in the chemokine system. However, other difficulties have been encountered in drug discovery processes targeting the chemokine system, and these will be addressed in this review. What the reader will gain: In this review, the reader will get an insight into the hurdles that have to be overcome, learn about some of the pitfalls that may explain the lack of success, and get a glimpse of the outlook for the future. Take home message: In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, a CXCR4 antagonist for hematopoietic stem cell mobilization, was approved by the FDA at the end of 2008. The results of a Phase III trial with a CCR9 inhibitor for Crohn's disease are also promising. This could herald the first success for a chemokine receptor antagonist as an anti-inflammatory therapeutic and confirms the importance of chemokine receptors as a target class for anti-inflammatory and autoimmune diseases. © 2010 Informa UK Ltd.

Yip Y.L.,Merck Serono International S.A.
Yearbook of medical informatics | Year: 2011

To summarize current excellent research in the field of bioinformatics, with an emphasis on those that have direct application in the medical domain. Synopsis of the articles selected for the IMIA Yearbook 2011. The selection process for this yearbook's section on Bioinformatics results in six excellent articles highlighting the continuous progress towards a better understanding of human phenotype. Compared to the selection in Yearbook 2010, several key advancements can be noted. First, year 2010 marked the inaugural use of a complete human genome in a clinical context. This proof-of-principle study represents a large step towards personalized medicine. Second, there is a clear trend to understand diseases beyond the genome level, namely to include environmental and epigenetic information. Third, an innovative framework making use of the web to harness participant-driven genotype-phenotype information sets a new scene for conducting research in an era where social media plays an increasingly important role. The current literature showed that all pieces are now present to enable a much more comprehensive understanding of human diseases and traits, beyond the highly focused genetic or genomic studies seen previously.

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