Linked Life Data

1567184

Source:http://linkedlifedata.com/resource/pubmed/id/1567184

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-5-19
pubmed:abstractText
A large number of reports have described the potential of transforming growth factor beta 1 (TGF-beta 1) as an antitumor agent on the basis of its antiproliferative action on a wide variety of tumor types in culture. In this report we now extend the assessment of TGF-beta 1's antitumor potential by evaluation in vivo versus the mouse monomyelocytic leukemia, Wehi 3BD+, and the human lung adenocarcinoma, A549. In culture both Wehi 3BD+ and A549 cells, sampled from in vivo, were sensitive to inhibition (greater than or equal to 50%) by TGF-beta 1 (greater than or equal to 1 ng/ml) in a 6 day proliferation assay. Despite their sensitivity to TGF-beta 1 in culture, in vivo the growth of neither tumor was reproducibly altered following treatment with various doses, routes and schedules of TGF-beta 1. For example, the median lifespan of mice inoculated with Wehi 3BD+ cells (10(3) or 10(5) cells, ip) was not increased by TGF-beta 1, given as 9 daily ip injections or 7 days of continuous ip infusion. Dose levels in these studies ranged over greater than 2 logs and were escalated to include those frankly lethal (28 micrograms/mouse by injection or 7 micrograms/mouse/day by infusion). Furthermore, the growth of A549 tumors implanted sc in athymic mice was not inhibited by iv injection (every 3 days for 5 injections or 6 consecutive daily injections), sc treatment distal to the tumor (every 3 days for 5 injections or continuously infused for 14 days), or even sc injection adjacent to the tumor (every 3 days for 5 injections), although dose levels of TGF-beta 1 covered a wide range including those which produced lethalities. On the basis of cumulative dose, continuous infusion of TGF-beta 1 by both ip and sc routes was more toxic than frequent injections given by the same routes. These studies indicate lethality is reached without a meaningful tumor inhibition being produced following ip, sc, or iv injections, and sc or ip infusions of TGF-beta 1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
73-9
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:articleTitle
Transforming growth factor beta 1: lack of in vivo antitumor activity on A549 and Wehi 3BD+ tumors.
pubmed:affiliation
Bristol-Myers Squibb Co., Wallingford, CT 06492.
pubmed:publicationType
Journal Article