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INSM - Insmed - Deel 15

2.002 Posts
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  1. [verwijderd] 28 augustus 2007 20:42
    quote:

    The Wishbone schreef:

    Onder de dollar kans op delisting
    Als er te weinig handel is kans op delisting
    Wat is er positief aan ?
    crack
    [quote=crackedtooth]
    volume droogt op, dat vind ik positief
    [/quote]
    voor die tijd al VEEL events
    dec 2007 + extensies dan zit je al mid/eidn 2008

    maw non argument op dit moment
  2. [verwijderd] 29 augustus 2007 19:11
    Composite Indicator
    Trend Spotter TM Sell

    Short Term Indicators
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    Short Term Indicators Average: 60% - Sell
    20-Day Average Volume - 741665

    Medium Term Indicators
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    50 Day Moving Average vs Price Sell
    20 - 100 Day MACD Oscillator Sell
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    Medium Term Indicators Average: 75% - Sell
    50-Day Average Volume - 853650

    Long Term Indicators
    60 Day Commodity Channel Index Sell
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    Long Term Indicators Average: 100% - Sell
    100-Day Average Volume - 1594722

    Overall Average: 80% - Sell

    Price Support Pivot Point Resistance

    0.62 0.61 0.62 0.63

  3. [verwijderd] 30 augustus 2007 16:40
    How IGF1-BP3 attacks and shrinks cancer...
    ORIGINAL ARTICLE
    Insulin-like growth factor-binding protein-3 inhibition of prostate cancer
    growth involves suppression of angiogenesis
    B Liu1, K-W Lee1, M Anzo1, B Zhang2, X Zi3, Y Tao4, L Shiry5, M Pollak4, S Lin6 and P Cohen1
    1Division of Pediatric Endocrinology, Department of Pediatrics, Mattel Children’s Hospital, David Geffen School of Medicine,
    UCLA, Los Angeles, CA, USA; 2Center of Developmental Biology and Genetics, College of Life Sciences, Peking University, Beijing,
    PR China; 3Department of Urology and Chao Family Comprehensive Cancer Center, UCI, Irvine, CA, USA; 4Division of
    Experimental Medicine, Department of Medicine and Department of Oncology, McGill University, Montreal, QC, Canada;
    5INSMED Corp., Glen Allen, Charlottesville, VA, USA and 6Department of Molecular, Cell and Developmental Biology, UCLA,
    Los Angeles, CA, USA
    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.
    Oncogene (2007) 26, 1811–1819. doi:10.1038/sj.onc. 1209977;
    published online 18 September 2006
    Keywords: insulin-like growth factor-binding protein-3;
    prostate cancer; angiogenesis; apoptosis
    Introduction
    Regulation of cellular growth and development by the
    insulin-like growth factors (IGFs) is well accepted
    and interventions that blockthe IGF axis as such
    are currently in development for cancer therapy (Jones
    et al., 2005). In addition, various components of this
    axis are modulated by dietary and pharmacological
    cancer interventions (Voskuil et al., 2005).
    Insulin-like growth factor-binding protein-3 (IGFBP-
    3), one of six members of the IGFBP family that
    noncovalently bind to IGFs with high affinity, is the
    most abundant in human serum (for a review see Firth
    and Baxter, 2002). IGFBP-3 is a multifunctional protein
    that transports and stabilizes IGFs in circulation;
    modulates IGF bioactivity; inhibits the growth of
    cancer cells; and induces apoptosis of cancer cells. The
    effects of IGFBP-3 on cell growth and apoptosis involve
    both sequestering IGFs from their receptors and
    IGF-independent mechanisms that include: binding to
    retinoid X receptor (RXR) and modulation of nuclear
    signalling followed by nucleomitochondrial translocation
    of RXR/Nur77 and induction of rapid apoptosis
    (Lee et al., 2005); binding to membrane receptors
    (Huang et al., 2003); and antagonism of the recently
    described survival factor, humanin (Ikonen et al.,
    2003). We have recently reported the initial description
    of successful therapeutic use of IGFBP-3 as a cancer
    therapy in vivo, and demonstrated that combination
    treatment of IGFBP-3 and RXR ligand had a synergistic
    effect on apoptosis induction leading to substantial
    inhibition of prostate cancer xenograft growth (Liu
    et al., 2005).
    We hypothesized that apart from apoptosis induction,
    IGFBP-3 might have direct effects on angiogenesis
    because: (1) IGFBP-3 contains a highly basic heparinbinding
    area, and specifically binds to vascular endothelial
    cell monolayers (Booth et al., 1996) in a manner
    that may affect vascular angiogenesis; (2) IGFBP-3
    inhibits vascular endothelial growth factor (VEGF)-
    mediated survival of human umbilical vein endothelial
    cells (HUVEC) in an IGF-independent mechanism
    (Zadeh and Binoux, 1997; Franklin et al., 2003) and
    Received 2 March 2006; revised 1 August 2006; accepted 4 August 2006;
    published online 18 September 2006
    Correspondence: Professor P Cohen, Division of Pediatric Endocrinology,
    Department of Pediatrics, Mattel Children’s Hospital, David
    Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
    E-mail: hassy@mednet.ucla.edu
    Oncogene (2007) 26, 1811–1819
    & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00
    www.nature.com/onc
    may also affect angiogenesis in vivo; (3) IGFBP-3 is
    transcriptionally upregulated during hypoxia, a potent
    stimulator of angiogenesis (Diaz-Gonzalez et al.,
    2005) in endothelial cells (Koong et al., 2000); and (4)
    IGFBP-3 mRNA is predominantly expressed in the
    vascular endothelial cells of human (Fraser et al., 2000),
    rat (Erickson et al., 1993), and bovine corpus lutea
    (Brown and Braden, 2001), which suggest a possible
    involvement in angiogenesis regulation, perhaps as part
    of a feedbackmechani sm. Other reports also indicate
    that IGFBP-3 mRNA is more abundantly expressed
    in hypoxia-associated inflammatory angiogenesis (Tucci
    et al., 1998; Lee et al., 1999) and tumor endothelial cells
    (Schmid et al., 2003). Importantly, a recent publication
    identifies IGFBP-3 as a farnesyl transferase inhibitorinduced
    negative regulator of angiogenesis in head and
    necksqu amous cell carcinoma (Oh et al., 2006).
    Here, we report that IGFBP-3 has direct, IGFindependent
    inhibitory effects on angiogenesis. Solid
    tumors require a supply of blood vessels to survive,
    grow and metastasize (Folkman, 2004) and treatments
    that address these issues can be more effective than
    nonspecific chemotherapies. Our results reveal a unique
    mechanism by which IGFBP-3 exerts its tumor suppressive
    effects and supports further investigation into
    the clinical translation of IGFBP-3 as a neoadjuvant in
    prostate cancer therapy.
    Results
    IGFBP-3 inhibits the growth of 22RV-1 prostate cancer
    xenografts in vivo
    To examine the effects of IGFBP-3 as a single therapy on
    inhibiting prostate cancer tumor cell growth in vivo, male
    severe-combined immunodeficiency (SCID) mice with
    22RV-1 prostate cancer xenografts were given daily injections
    of saline, or IGFBP-3 (30mg/kg/day intraperitoneally
    (i.p.)) for 16 days. Treatment with IGFBP-3 resulted
    in significant tumor size inhibition (40% growth inhibition,
    Po0.005; n¼10) relative to control animals (Figure 1a).
    A greater effect (50% inhibition) was seen for IGFBP-3
    therapy on tumor weight (Figure 1b). These studies show
    that treatment of IGFBP-3 as a single therapy inhibits the
    growth of 22RV1 prostate cancer
  4. ludwig mack 30 augustus 2007 23:51
    Last Trade: 0.62
    Trade Time: 3:59PM ET
    Change: 0.02 (3.33%)
    Prev Close: 0.60
    Open: 0.60
    Bid: 0.59 x 4000
    Ask: 0.71 x 100
    1y Target Est: 2.00

    Day's Range: 0.60 - 0.62
    52wk Range: 0.56 - 1.98
    Volume: 466,733
    Avg Vol (3m): 950,048
    Market Cap: 75.46M
    P/E (ttm): N/A
    EPS (ttm): -0.45
    Div & Yield: N/A (N/A)

  5. ludwig mack 31 augustus 2007 23:31
    Last Trade: 0.621
    Trade Time: 4:00PM ET
    Change: 0.001 (0.16%)
    Prev Close: 0.62
    Open: 0.62
    Bid: 0.592 x 4000
    Ask: 0.66 x 5000
    1y Target Est: 2.00

    Day's Range: 0.62 - 0.64
    52wk Range: 0.56 - 1.98
    Volume: 635,666
    Avg Vol (3m): 935,217
    Market Cap: 75.58M
    P/E (ttm): N/A
    EPS (ttm): -0.448
    Div & Yield: N/A (N/A)

  6. [verwijderd] 2 september 2007 14:33
    quote:

    junkbond schreef:

    terefenko.lib.bioinfo.pl/auid:2199524

    Even een vraag.Insmed heeft twee oncology compounds, rhIGFBP-3 and INSM-18. Maar bij welke hoort nordihydroguaiaretic (NDGA)?
    (...)Towards this end, on January 5, 2007, we entered into a license agreement with NAPO Pharmaceuticals, Inc. (“NAPO”), whereby NAPO licensed from us the technology surrounding INSM-18, also known as Masoprocal. The license agreement gives NAPO the right to develop, manufacture and commercialize Masoprocal products for all indications relating specifically to diabetes, cardiac disease, vascular disease, metabolic disease and Syndrome X. The license agreement requires NAPO to make certain payments to us upon the achievement of certain milestones. Pursuant to the terms of the license agreement, on January 12, 2007, we received $500,000 from NAPO, which, as part of the license agreement, we immediately used to purchase 270,611 shares of NAPO common stock at the closing trading price of £0.94 ($1.85 in United States funds). Further, on April 16, 2007, we received $1,000,000 from NAPO for delivering certain clinical information to them in accordance with the terms of the license agreement. We recorded an unrealized loss on the NAPO stock as of June 30, 2007 in the amount of $63,460 due to the change in the closing trading price of £0.81 ($1.61 in United States funds).
    Pagina 16
    www.secinfo.com/d14D5a.u57Vk.htm

    (...)We have discovered that the combination of masoprocol known as nordihydroguaiaretic acid(..)
    www.patentstorm.us/patents/5409690-de...

    Dus, NDGA=INSM 18

    Geluk, F.
  7. [verwijderd] 2 september 2007 14:58
    Ook leuk om te zien dat in het laatste onderzoek van Golfine, zowel Youngren als Schambelan zich hebben gevoegd.

    www.ncbi.nlm.nih.gov/sites/entrez?Db=...

    Technical evaluation of in vivo abdominal fat and IMCL quantification using MRI and MRSI at 3 T.
    Li X, Youngren JF, Hyun B, Sakkas GK, Mulligan K, Majumdar S, Masharani UB, Schambelan M, Goldfine ID.

    Musculoskeletal Quantitative Imaging Research, Department of Radiology, University of California, San Francisco, CA 94107, USA.

    OBJECTIVES: The objectives of this study were to develop protocols that measure abdominal fat and calf muscle lipids with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), respectively, at 3 T and to examine the correlation between these parameters and insulin sensitivity.

    Geluk, F.
  8. junkbond 2 september 2007 15:28
    quote:

    Frederik C schreef:

    [quote=junkbond]
    terefenko.lib.bioinfo.pl/auid:2199524

    Even een vraag.Insmed heeft twee oncology compounds, rhIGFBP-3 and INSM-18. Maar bij welke hoort nordihydroguaiaretic (NDGA)?
    [/quote]
    (...)Towards this end, on January 5, 2007, we entered into a license agreement with NAPO Pharmaceuticals, Inc. (“NAPO”), whereby NAPO licensed from us the technology surrounding INSM-18, also known as Masoprocal. The license agreement gives NAPO the right to develop, manufacture and commercialize Masoprocal products for all indications relating specifically to diabetes, cardiac disease, vascular disease, metabolic disease and Syndrome X. The license agreement requires NAPO to make certain payments to us upon the achievement of certain milestones. Pursuant to the terms of the license agreement, on January 12, 2007, we received $500,000 from NAPO, which, as part of the license agreement, we immediately used to purchase 270,611 shares of NAPO common stock at the closing trading price of £0.94 ($1.85 in United States funds). Further, on April 16, 2007, we received $1,000,000 from NAPO for delivering certain clinical information to them in accordance with the terms of the license agreement. We recorded an unrealized loss on the NAPO stock as of June 30, 2007 in the amount of $63,460 due to the change in the closing trading price of £0.81 ($1.61 in United States funds).
    Pagina 16
    www.secinfo.com/d14D5a.u57Vk.htm

    (...)We have discovered that the combination of masoprocol known as nordihydroguaiaretic acid(..)
    www.patentstorm.us/patents/5409690-de...

    Dus, NDGA=INSM 18

    Geluk, F.
    Oke Frederik bedankt . Gaat een beetje boven mij pet moet ik bekennen ,maar ik kan ze nu iig uit elkaar houden..het is een begin :)
  9. [verwijderd] 2 september 2007 15:38
    quote:

    Frederik C schreef:

    Ook leuk om te zien dat in het laatste onderzoek van Golfine, zowel Youngren als Schambelan zich hebben gevoegd.

    www.ncbi.nlm.nih.gov/sites/entrez?Db=...

    Technical evaluation of in vivo abdominal fat and IMCL quantification using MRI and MRSI at 3 T.
    Li X, Youngren JF, Hyun B, Sakkas GK, Mulligan K, Majumdar S, Masharani UB, Schambelan M, Goldfine ID.

    Musculoskeletal Quantitative Imaging Research, Department of Radiology, University of California, San Francisco, CA 94107, USA.

    OBJECTIVES: The objectives of this study were to develop protocols that measure abdominal fat and calf muscle lipids with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), respectively, at 3 T and to examine the correlation between these parameters and insulin sensitivity.

    Geluk, F.
    frederic wat is jouw huidige timeline/strategie?

    zou graag nog een keer je evaluatie lezen en evt becommentarieren
  10. [verwijderd] 2 september 2007 16:47
    quote:

    crackedtooth schreef:

    frederic wat is jouw huidige timeline/strategie?

    zou graag nog een keer je evaluatie lezen en evt becommentarieren
    Persoonlijk verwacht ik, als de cijfers voor Q3, begin november worden bekend gemaakt, een daling van PPS want enige inkomsten zullen dan zijn, de kostendekkende inkomsten van ALS uit Italie.
    NAPO zal niet zoals in Q2, 1 mio dollar hebben geschonken.
    Voor Insmed wordt het qua PPS, cijfers Q3, update van trials en 17 december, een race tegen de klok.

    Ik verwacht geen significante stijging in de periode nu tot en met cijfers Q3, tenzij de update van de trials positief is en dit nieuws voor de cijfers komt.

    Management heeft al aangegeven dat er een update is te verwachten in Q4, dus het zou zomaar kunnen.

    Ten aanzien van Generieke produktiemogelijkheden, is Insmed volledig afhankelijk van de lobby...verloopt die goed dan kan de FoB/Bill nog dit jaar worden aangenomen en zal er ook hoogstwaarschijnlijk een FoB-partner worden gevonden voor het einde van het jaar.
    Indien de FoB-bill niet dit jaar wordt aangenomen, hetgeen ik verwacht, zal er voor het einde van het jaar ook hoogstwaarschijnlijk geen FoB-partner zijn, waardoor PPS opnieuw onder druk zal komen te staan.

    Kortom: ik verwacht dat PPS bij geen positief trial nieuws voor begin november rond deze prijs zal blijven hangen. Indien Q4-cijfers voor update, zal PPS dalen naar de $0.5x regionen.
    17 december is niet heilig maar wel´n beetje...Insmed kan dan nog eens 180 dagen uitstel krijgen, maar het label van het niet voldoen aan NASDAQ-voorwaarden zal ook in die periode niet echt meewerken met stijgen van de PPS.

    Op LT (2009 en verder), en dat is waar ik op gefocussed ben, zal het goed komen; FoB-Bill, FoB-partner, en mooie resultaten van onderzoeken.
    Gebruik de komende periodes om alles wat in de $0,5x regionen komt te kopen...dit zal niet van vandaag op morgen zijn, maar dat het gebeurt voor midden november is mij wel duidelijk.

    Geluk, F.
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