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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1997-4-2
|
| pubmed:abstractText |
Gastrin-releasing peptide (GRP) receptor antagonists were synthesized and their ability to interact with small-cell lung cancer (SCLC) cells determined. [125I] BW1023U90, bound with high affinity (Kd = 2 nM) to a single class of sites (Bmax = 55 fmol/mg protein) using SCLC cell line NCI-H345. [125I] BW1023U90 binding was time dependent and reversible even at 37 degrees C as the ligand was minimally internalized. Specific [125I] BW1023U90 binding was inhibited with high affinity by GRP as well as bombesin (BB) but not neuromedin B (NMB). BW1023U90 inhibited the ability of BB to elevate cytosolic Ca2+ and increase the growth of SCLC cells. A BW1023U90 analogue, BW2258U89 (10 micrograms/day, SC) slowed SCLC xenograft format on in nude mice and [125I] BW 1023U90 localized to SCLC tumors 1 h after injection into nude mice. BW2258U89 (4% by weight) was placed in microspheres and slowly released over a 3-week period in nude mice bearing SCLC xenografts. The microspheres containing BW2258U89 strongly inhibited SCLC growth in vivo. A radioimmunoassay was developed for the GRP receptor antagonists and the rabbit antiserum cross-reacted totally with BW2258U89 or BW1023U90. BW2258U89 immunoreactivity (5 nM) was detected in the plasma of nude mice containing the microspheres after 1 week. These data suggest that GRP receptor antagonists bind to receptors on SCLC tumors.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0196-9781
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
17
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1337-43
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:8971929-Amino Acid Sequence,
pubmed-meshheading:8971929-Animals,
pubmed-meshheading:8971929-Carcinoma, Small Cell,
pubmed-meshheading:8971929-Gastrin-Releasing Peptide,
pubmed-meshheading:8971929-Humans,
pubmed-meshheading:8971929-Kinetics,
pubmed-meshheading:8971929-Lung Neoplasms,
pubmed-meshheading:8971929-Mice,
pubmed-meshheading:8971929-Mice, Nude,
pubmed-meshheading:8971929-Neoplasm Transplantation,
pubmed-meshheading:8971929-Oligopeptides,
pubmed-meshheading:8971929-Peptides,
pubmed-meshheading:8971929-Receptors, Bombesin,
pubmed-meshheading:8971929-Structure-Activity Relationship,
pubmed-meshheading:8971929-Transplantation, Heterologous,
pubmed-meshheading:8971929-Tumor Cells, Cultured
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
BW 1023U90: a new GRP receptor antagonist for small-cell lung cancer cells.
|
| pubmed:affiliation |
National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, MD 20850, USA.
|
| pubmed:publicationType |
Journal Article
|