To: Nature Boy who wrote (1877 ) 3/30/1999 9:38:00 PM From: EPro Read Replies (1) | Respond to
Perhaps the Monday uptick was in response to news that SUGN is to be featured on "Sixty Minutes" April 4th, in a "rare" two segment piece. (See SUGN board for basis). There are suggestions that the piece will be favorable and follow patients successfully treated in a phase I clinical trial with a SUGN anti-angiogenesis agent. Will ENMD benefit from this favorable angiogensis press? or not?
Also, AACR abstracts were recently published on-line, including this one, indicating further independent verification of Folkman's results and a high level of tumor suppression:
[PROC. AMER. ASSOC. CANCER RES. 40, March 1999]
Copyright © 1999 by the American Association for Cancer Research
#2748 Administration of angiostatin: Bolus or continuously? T.A.
Drixler, E.D. Ritchie, A. Reyerkerk, C.J.M. Aarsman, M. Gebbink, I.H.M.
Borel Rinkes, E.E. Voest. Departments of Medical Oncology and Surgery,
University Hospital Utrecht, The Netherlands.
Since all previous animal studies on angiostatin have involved (bi-)
daily bolus injections and half-life of human angiostatin in mice is
estimated to be approximately 4-6 hours, we hypothesized that optimal
anti-angiogenic and antitumoral action could be improved by continuous
administration of plasminogen derived human angiostatin. [Materials &
Methods] Angiostatin was generated by limited proteolysis of human
plasminogen with pancreatic elastase. In vivo anti-angiogenic effect was
quantified by the corneal neovascularisation assay in mice. Antitumoral
effects were measured using two tumor models: i) a primary tumor
obtained by subcutaneous injection (sc.) of C-26 cells and ii) a
colorectal liver metastases model following intrasplenic injection of
C-26 cells. Mice were treated either by daily bolus injections (sc.) or
by continuous (Alzet® pump, sc) administration of angiostatin to reach a
daily dose of 1, 10, or 100 mg/kg. Tumor growth was evaluated on day 7
and 14. [Results] Dose-dependent inhibition of corneal angiogenesis was
observed in both groups: bolus injection with 1, 10 & 100 mg/kg/day
resulted in 14%, 34% and 71% inhibition, respectively, whereas
continuous administration was significant better than bolus injection at
all dose levels: 24%, 68% and 93% inhibition. So, optimal
anti-angiogenic administration was 100 mg/kg/day with a sc. pump. Using
this schedule development of subcutaneous tumors was inhibited almost
completely (tumor growth: control=686 ± 48 mm3; angiostatin sc. bolus
injection=154 ± 43 mm3; angiostatin continuous sc.=26,8 ± 4 mm3;
p<0,005). Preliminary data revealed similar results in the hepatic
metastases model. [Conclusion] This study shows that optimal
anti-angiogenic and antitumoral effects by angiostatin in mice may be
obtained using continuous administration of 100 mg/kg/day using an
osmotic pump.
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