Linked Life Data

11606410

Source:http://linkedlifedata.com/resource/pubmed/id/11606410

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2001-10-18
pubmed:abstractText
In the first Phase I clinical trials of endostatin as an antiangiogenic therapy for cancer, the protein was administered as an i.v. bolus for approximately 20-30 min each day. This protocol was based on experimental studies in which animals were treated by s.c. bolus once a day. However, it was not clear in the previous studies whether this schedule could be maximized further. Therefore, we developed experimental models involving continuous administration of endostatin to determine the potency and efficacy of this approach. Endostatin was administered to tumor-bearing mice either s.c. or i.p. in single bolus doses. The efficacy of these regimens was compared with endostatin administered continuously via an i.p. implanted mini-osmotic pump. Our results show that endostatin remains stable and active in mini-osmotic pumps for at least 7 days. We show that endostatin injected i.p. is rapidly cleared within 2 h, whereas endostatin administered continuously via mini-osmotic pump maintains systemic concentrations of 200-300 ng/ml for the duration of administration. Furthermore, continuous i.p. administration of endostatin results in more effective tumor suppression at significantly reduced doses (5-fold), compared with bolus administration. Additional experiments using a human pancreatic cancer model in severe combined immunodeficient mice showed that there was a significant decrease in the microvessel density between the treatment groups and the control group. These data show that continuous administration of human endostatin results in sustained systemic concentrations of the protein leading to: (a) increased efficacy manifested as increased tumor regression; and (b) an 8-10-fold decrease in the dose required to achieve the same antitumor effect as the single daily bolus administration of endostatin. On the basis of this approach, an additional clinical trial has been designed and initiated and is under way in two countries.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7669-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11606410-Angiogenesis Inhibitors, pubmed-meshheading:11606410-Animals, pubmed-meshheading:11606410-Antineoplastic Agents, pubmed-meshheading:11606410-Carcinoma, Lewis Lung, pubmed-meshheading:11606410-Collagen, pubmed-meshheading:11606410-Drug Stability, pubmed-meshheading:11606410-Endostatins, pubmed-meshheading:11606410-Fibrosarcoma, pubmed-meshheading:11606410-Humans, pubmed-meshheading:11606410-Infusion Pumps, Implantable, pubmed-meshheading:11606410-Infusions, Parenteral, pubmed-meshheading:11606410-Injections, Intraperitoneal, pubmed-meshheading:11606410-Male, pubmed-meshheading:11606410-Mice, pubmed-meshheading:11606410-Mice, Inbred CBA, pubmed-meshheading:11606410-Mice, SCID, pubmed-meshheading:11606410-Neovascularization, Pathologic, pubmed-meshheading:11606410-Osmotic Pressure, pubmed-meshheading:11606410-Pancreatic Neoplasms, pubmed-meshheading:11606410-Peptide Fragments, pubmed-meshheading:11606410-Xenograft Model Antitumor Assays
pubmed:year
2001
pubmed:articleTitle
Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model.
pubmed:affiliation
Division of Surgical Research, Children's Hospital, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't