Loading ...
Sorry, an error occurred while loading the content.

EntreMed/Angiostatin Endostatin/NHL-other

Expand Messages
  • Janice and Ben Haines
    Greetings, A nurse from EntreMed (ENMD) called us today in regards to a question I posed a while ago and I talked to her for twenty minutes, she was really
    Message 1 of 1 , Jun 29, 1998
    • 0 Attachment
      Greetings,
      A nurse from EntreMed (ENMD) called us today in regards to a question I
      posed a while ago and I talked to her for twenty minutes, she was really
      pleasant. They are a small company (50 including EVERYONE) and have had
      over 3,000 inquiries in which they are getting back to people individually.
      So here are the FACTS, according to Denise, a nurse at EntreMed:

      - ENMD is hoping to have enough angiostatin and endostatin for clinical
      trials in 12-18 months.
      - Folkman was MISQUOTED in Chicago (By the Chicago Tribune) saying the FDA
      had approved a trial for 50 people for Angiostatin and Endostatin by the
      end of the year. The truth is: 30 children have been cleared for testing
      TNP-470 with leukemia by the end of the year.
      - So far anti-Angiogenesis drugs have only been tested on SOLID tumors. The
      TNP-470 test at the end of the year will be the FIRST trial of
      anti-angiogenesis drugs in blood born cancers.
      - It is difficult to produce enough endostatin and angiostatin in
      quantities human's would need but they can produce enough for mice
      - People are literally working around the clock to produce Endostatin and
      Angiostatin and they hope to beat the 12-18 month deadline.
      - She had never heard of Vasculostatin (must be another error by the press,
      I can find where it was first mentioned.)
      - She mentioned the 'double whammy' 2-Methoxyestraidol (2-ME2) is in
      pre-clinical and is unique because it kills cancer cells as well (like taxol).
      - She seemed really upbeat for the end of the day and all my questions, but
      used the 'cautiously optimistic' on me. I asked her is she is programmed to
      say that? She laughed and I told her a lot of people are pulling for their
      small company.

      As for NHL-other: it is live, it really needs a list owner though. I have
      had a lot of inquiries asking more about it but no one has posted. You have
      all the information you need to start posting to it and start shaping it
      how you want it for the complementary/alternative stuff or whatever. I have
      already had people asking me to subscribe them...absolutely no way, people
      have to learn at least until there is a new list owner for NHL-other. If
      you lost the directions, go to:

      http://www.findmail.com/listsaver/nhl-other/

      Here are 9 abstracts in the last 180 days from Medline, 4 on Endostatin, 5
      on Angiostatin. For those that are new, many of the posts on here are
      'data' posts or not very meaningful unless someone goes back through
      extracting various pieces. I have been doing this with several e-mails, you
      will see how it works after a while. I have been repeating this process
      over and over since day one and I feel it works very well.

      Regards,
      -Ben(KIA)
      ---8<---8<-----
      Endostatin (4 abstracts in the last 180 days from Medline)

      FEBS Lett 1997 Dec 29;420(2-3):129-133

      Isolation and characterization of the circulating form of human endostatin.

      Standker L, Schrader M, Kanse SM, Jurgens M, Forssmann WG, Preissner KT

      Lower Saxony Institute for Peptide Research (IPF), Hannover, Germany.

      Recently, fragments of extracellular proteins, including endostatin, were
      defined as a novel group of angiogenesis inhibitors. In this study, human
      plasma equivalent hemofiltrate was used as a source for the purification of
      high molecular weight peptides (10-20 kDa), and the isolation and
      identification of circulating human endostatin are described. The
      purification of this C-terminal fragment of collagen alpha1(XVIII) was
      guided by MALDI-MS and the exact molecular mass determined by ESI-MS was
      found to be 18 494 Da. N-terminal sequencing revealed the identity of this
      putative angiogenesis inhibitor and its close relation to mouse endostatin.
      The cysteine residues 1-3 and 2-4 in the molecule are linked by disulfide
      bridges. In vitro biological characterization of the native protein
      demonstrated no anti-proliferative activity on different endothelial cell
      types. These data indicate that human endostatin, which is a putative
      angiogenesis inhibitor, is present in the circulation.

      PMID: 9459295, UI: 98119383

      Matrix Biol 1998 Jan;16(6):319-328

      Complete primary structure of two variant forms of human type XVIII
      collagen and tissue-specific differences in the expression of the
      corresponding transcripts.

      Saarela J, Ylikarppa R, Rehn M, Purmonen S, Pihlajaniemi T

      Collagen Research Unit, University of Oulu, Finland.

      We report on full-length human type XVIII collagen cDNAs that encode 1516-
      or 1336-residue alpha 1 (XVIII) chains. The two chains have different
      signal peptides and variant N-terminal non-collagenous NC1 domains of 493
      (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share
      301 residues of their NC1 domains, a 688-residue highly interrupted
      collagenous portion, and a 312-residue C-terminal non-collagenous portion.
      Alternative splicing affecting a 43-residue stretch at the junction of the
      NC1 domain and the beginning of the collagenous portion was identified. The
      amino acid sequences of the human and previously characterized mouse alpha
      1 (XVIII) chains exhibit an overall identity of 79%. The highest homology
      between these chains was observed in their last 184 residues, corresponding
      to the proteolytic fragment endostatin, which is capable of inhibiting
      endothelial cell proliferation, angiogenesis and tumor growth (O'Reilly, et
      al., Cell 88: 277-285, 1997). Northern analysis of several adult and fetal
      tissues with a probe for the NC1-493 variant revealed marked amounts of the
      corresponding 6.2 and 5.0 kb mRNAs in liver, while other tissues contained
      only faint or undetectable signals. Hybridizations with a probe specific
      for the NC1-303 variant virtually lacked the liver signal but revealed
      clear 5.6 and 4.5 kb bands in heart, kidney, placenta, prostate, ovaries,
      skeletal muscle and small intestine, and faint signals in several other
      tissues. Thus mRNAs for the long variant occur prominently in liver, while
      those for the short variant appear to be the major ones in the other
      tissues analyzed.

      PMID: 9503365, UI: 98164096

      Annu Rev Med 1998;49:407-424

      Angiogenesis and tumor metastasis.

      Zetter BR

      Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115,
      USA. zetter@...

      Angiogenesis, the recruitment of new blood vessels, is an essential
      component of the metastatic pathway. These vessels provide the principal
      route by which tumor cells exit the primary tumor site and enter the
      circulation. For many tumors, the vascular density can provide a prognostic
      indicator of metastatic potential, with the highly vascular primary tumors
      having a higher incidence of metastasis than poorly vascular tumors. Tumor
      angiogenesis is regulated by the production of angiogenic stimulators
      including members of the fibroblast growth factor and vascular endothelial
      growth factor families. In addition, tumors may activate angiogenic
      inhibitors such as angiostatin and endostatin that can modulate
      angiogenesis both at the primary site and at downstream sites of
      metastasis. The potential use of these and other natural and synthetic
      angiogenic inhibitors as anticancer drugs is currently under intense
      investigation. Such agents may have reduced toxicity and be less likely to
      generate drug resistance than conventional cytotoxic drugs. Clinical trials
      are now underway to develop optimum treatment strategies for antiangiogenic
      agents.

      Publication Types:

      Review Review, tutorial

      PMID: 9509272, UI: 98170010

      EMBO J 1998 Mar 16;17(6):1656-1664

      Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A
      resolution.

      Hohenester E, Sasaki T, Olsen BR, Timpl R

      Department of Crystallography, Birkbeck College, London WC1E 7HX, UK.
      e.hohenester.cryst.bbk.ac.uk

      A number of extracellular proteins contain cryptic inhibitors of
      angiogenesis. Endostatin is a 20 kDa C-terminal proteolytic fragment of
      collagen XVIII that potently inhibits endothelial cell proliferation and
      angiogenesis. Therapy of experimental cancer with endostatin leads to
      tumour dormancy and does not induce resistance. We have expressed
      recombinant mouse endostatin and determined its crystal structure at 1.5 A
      resolution. The structure reveals a compact fold distantly related to the
      C-type lectin carbohydrate recognition domain and the hyaluronan-binding
      Link module. The high affinity of endostatin for heparin is explained by
      the presence of an extensive basic patch formed by 11 arginine residues.
      Endostatin may inhibit angiogenesis by binding to the heparan sulphate
      proteoglycans involved in growth factor signalling.

      PMID: 9501087, UI: 98169382

      ==========================================
      Angiostatin (5 abstracts in the last 180 days fromMedline)
      ==========================================

      J Vasc Res 1998 Mar;35(2):109-114

      In vitro tumor angiogenesis assays: plasminogen lysine binding site 1
      inhibits in vitro tumor-induced angiogenesis.

      Barendsz-Janson AF, Griffioen AW, Muller AD, van Dam-Mieras MC, Hillen HF

      Department of Internal Medicine, University Hospital Maastricht, The
      Netherlands.

      It is generally accepted that tumors are angiogenesis-dependent. For
      research and clinical purposes it would be very attractive to have a simple
      in vitro model that allows a rapid screening of the angiogenic potential of
      tumors and to study the effect of angiogenic inhibitors. In vitro
      angiogenesis models were developed, based on endothelial sprouting/tube
      formation on a collagen gel, using both tumor cell lines and tumor
      biopsies. Best results were obtained using conditioned medium of tumor cell
      lines. In this model it was found that the plasminogen fragment lysine
      binding site 1 (LBS-1) inhibited in vitro endothelial cell sprouting. This
      is the first demonstration that LBS-1, which includes angiostatin, is
      inhibitory for new vessel formation in an in vitro angiogenesis model. We
      conclude that the assay system allows for rapid and reliable screening of
      angiogenesis inhibitors.

      PMID: 9588874, UI: 98248288

      Biochem Biophys Res Commun 1998 Apr 28;245(3):906-911

      Angiostatin upregulates E-selectin in proliferating endothelial cells.

      Luo J, Lin J, Paranya G, Bischoff J

      Surgical Research Laboratory, Children's Hospital, Boston, Massachusetts
      02115, USA.

      Angiostatin, a 38 kilodalton fragment of plasminogen, is a potent inhibitor
      of angiogenesis. However, little is known about how angiostatin affects
      endothelial gene expression. To learn more about its effect on
      endothelial-specific genes implicated in angiogenesis, we examined
      E-selectin expression and function in bovine capillary endothelial cells
      treated with recombinant angiostatin. Angiostatin caused a four to
      five-fold increase in E-selection polypeptide levels in proliferating
      endothelial cells but little or no increase in confluent cells. P-selection
      polypeptide levels were unaffected by angiostatin in either proliferating
      or confluent cells. E-selectin mRNA and adhesion activity in proliferating
      endothelial cells were also increased by angiostatin. Angiostatin had
      little effect on the distribution of endothelial cells in G0/G1, S, and
      G2/M, indicating angiostatin does not alter cell cycle progression
      significantly. These data demonstrate that angiostatin selectively
      upregulates E-selectin in proliferating endothelial cells in vitro. This
      selectivity may provide insights into the mechanism by which angiostatin
      inhibits tumor growth in vivo without apparent effects on quiescent
      endothelium.

      PMID: 9588213, UI: 98249812

      Chem Biol 1998 Apr;5(4):R87-R88

      Starving cancer into submission. EntreMed, Inc.

      Wells WA

      Publication Types:

      News

      PMID: 9571213, UI: 98252143

      J Clin Invest 1998 Mar 1;101(5):1055-1063

      Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary
      tumor growth and produces long-term dormancy of metastases.

      Cao Y, O'Reilly MS, Marshall B, Flynn E, Ji RW, Folkman J

      Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center,
      Karolinska Institute, S-171 77, Stockholm, Sweden. yihai.cao@...

      Tumor growth and metastasis are angiogenesis dependent. Previously, we
      reported that angiostatin, a potent angiogenesis inhibitor, produced by a
      primary Lewis lung carcinoma suppressed its growth of lung metastases
      (O'Reilly, M.S., L. Holmgren, Y. Shing, C. Chen, R.A. Rosenthal, M. Moses,
      W.S. Lane, Y. Cao, E.H. Sage, and J. Folkman. 1994. Cell. 79:315-328). Now
      we show that a shift of balance of tumor angiogenesis by gene transfer of a
      cDNA coding for mouse angiostatin into murine T241 fibrosarcoma cells
      suppresses primary and metastatic tumor growth in vivo. Implantation of
      stable clones expressing mouse angiostatin in C57Bl6/J mice inhibits
      primary tumor growth by an average of 77%. After removal of primary tumors,
      the pulmonary micrometastases in approximately 70% of mice remain in a
      microscopic dormant and avascular state for the duration of the
      experiments, e.g., 2-5 mo. The tumor cells in the dormant micrometastases
      exhibit a high rate of apoptosis balanced by a high proliferation rate. Our
      study, to our knowledge, for the first time shows the diminished growth of
      lung metastases after removal of the primary tumor, suggesting that
      metastases are self-inhibitory by halting angiogenesis. Our data may also
      provide a novel approach for cancer therapy by antiangiogenic gene therapy
      with a specific angiogenesis inhibitor.

      PMID: 9486976, UI: 98153232

      Annu Rev Med 1998;49:407-424

      Angiogenesis and tumor metastasis.

      Zetter BR

      Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115,
      USA. zetter@...

      Angiogenesis, the recruitment of new blood vessels, is an essential
      component of the metastatic pathway. These vessels provide the principal
      route by which tumor cells exit the primary tumor site and enter the
      circulation. For many tumors, the vascular density can provide a prognostic
      indicator of metastatic potential, with the highly vascular primary tumors
      having a higher incidence of metastasis than poorly vascular tumors. Tumor
      angiogenesis is regulated by the production of angiogenic stimulators
      including members of the fibroblast growth factor and vascular endothelial
      growth factor families. In addition, tumors may activate angiogenic
      inhibitors such as angiostatin and endostatin that can modulate
      angiogenesis both at the primary site and at downstream sites of
      metastasis. The potential use of these and other natural and synthetic
      angiogenic inhibitors as anticancer drugs is currently under intense
      investigation. Such agents may have reduced toxicity and be less likely to
      generate drug resistance than conventional cytotoxic drugs. Clinical trials
      are now underway to develop optimum treatment strategies for antiangiogenic
      agents.

      Publication Types:

      Review Review, tutorial

      PMID: 9509272, UI: 98170010
    Your message has been successfully submitted and would be delivered to recipients shortly.