Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P01350 (
gastrin
)
9,683
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effects of bombesin receptor subtype-3 (BRS-3) agonists were investigated on lung cancer cells. The BRS-3 agonist (DTyr(6), (Ala(11), Phe(13), Nle(14)) bombesin(6-14) (BA1), but not
gastrin
releasing peptide (GRP) or neuromedin B (NMB) increased significantly the clonal growth of NCI-H1299 cells stably transfected with BRS-3 (NCI-H1299-BRS-3). Also, BA1 addition to NCI-H727 or NCI-H1299-BRS-3 cells caused Tyr(1068) phosphorylation of the epidermal growth factor receptor (EGFR). Similarly, (DTyr(6), R-Apa(11), Phe(13), Nle(14)) bombesin(6-14) (
BA2
) and (DTyr(6), R-Apa(11), 4-Cl,Phe(13), Nle(14)) bombesin(6-14) (BA3) but not
gastrin
releasing peptide (GRP) or neuromedin B (NMB) caused EGFR transactivation in NCI-H1299-BRS-3 cells. BA1-induced EGFR or ERK tyrosine phosphorylation was not inhibited by addition of BW2258U89 (BB(2)R antagonist) or PD168368 (BB(1)R antagonist) but was blocked by (DNal-Cys-Tyr-DTrp-Lys-Val-Cys-Nal)NH(2) (BRS-3 ant.). The BRS-3 ant. reduced clonal growth of NCI-H1299-BRS-3 cells. BA1,
BA2
, BA3 and BRS-3 ant. inhibit specific (125)I-BA1 binding to NCI-H1299-BRS-3 cells with an IC(50) values of 1.1, 21, 15 and 750nM, respectively. The ability of BRS-3 to regulate EGFR transactivation in NCI-H1299-BRS-3 cells was reduced by AG1478 or gefitinib (EGFR tyrosine kinase inhibitors), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), N-acetylcysteine (anti-oxidant), Tiron (superoxide scavenger) and DPI (NADPH oxidase inhibitor). These results demonstrate that BRS-3 agonists may stimulate lung cancer growth as a result of EGFR transactivation and that the transactivation is regulated by BRS-3 in a Src-, reactive oxygen and matrix metalloprotease-dependent manner.
...
PMID:Bombesin receptor subtype-3 agonists stimulate the growth of lung cancer cells and increase EGF receptor tyrosine phosphorylation. 2171 56
Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine.
Gastrin
-releasing-peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC-Asp-[Phe
13
]BBN(7-13)-NH-CH
2
-CH
2
-CH3:BA1, HYNIC-Pro-[Tyr
13
Met
14
]BBN(7-14)NH
2
:
BA2
as prospective tumor imaging agent with compare to BBN(7-14)NH
2
:BS as standard. The pharmacophores were radiolabeled in high yields with
99m
Tc, characterized for their stability in serum and saline, cysteine/histidine and were found to be substantially stable. Internalization/externalization and receptor binding studies were assessed using MDA-MB-231 cells and showed high receptor binding-affinity and favourable internalization. Fluorescence studies revealed that BA1 changed the morphology of the cells and could localize in the nucleus more effectively than
BA2
/BS. Cell-viability studies displayed substantial antagonistic and nuclear-internalization effect of BA1. BA1 also exhibited antiproliferative effect on MDA-MB-231 cell by inducing apoptosis. In vivo behaviour of the radiopeptides was evaluated in GRP receptor positive tumor bearing mice. The
99m
Tc-BA1/
99m
Tc-
BA2
demonstrated rapid blood/urinary clearance through the renal pathway and comparatively more significant tumor uptake image and favourable tumor-to-non-target ratios provided by
99m
Tc-BA1. The specificity of the in vivo uptake was confirmed by co-injection with BS. Moreover,
99m
Tc-BA1 provided a much clearer tumor image in scintigraphic studies than others. Thus the combination of favourable in vitro and in vivo properties renders BA1 as more potential antagonist bombesin-peptide for targeting GRP-receptor positive tumor. These properties are encouraging to carry out further experiments for non-invasive receptor targeting potential diagnostinc and therapeutic agent for tumors.
...
PMID:Synthesis and exploration of novel radiolabeled bombesin peptides for targeting receptor positive tumor. 2808 45
