Lung cancer is the leading cause of cancar deaths in the U.S. About 25% of cases are small cell lung carcinoma (SCLC), which, despite aggressive and toxic therapy, carries a less than 10% survival at five years. The ultimate goal of this project is to develop new therapeutic strategies for SCLC. SCLC cells secrete and contain a growth factor, bombesin, which stimulates their growth by interaction with a specific cell surface receptor. Disruption of this interaction should lead to cell death. This project proposes 1) to characterize the properties of and purify the receptor for this growth factor, bombesin; 2) to delineate the mechanism of signal transduction biochemically which results in cell proliferation; 3) to utilize the defined properties of the interaction between bombesin and its receptor, and the purified receptor itself, to develop new diagnostic and therapeutic approaches to the management of SCLC using monoclonal antibodies, toxin conjugates and ligand analogs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA044763-02
Application #
3458124
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1987-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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Jones, C L; Beck, L K; Brozna, J P et al. (1995) Properties of classic protein kinase C in human small cell lung carcinoma NCI-H345 cells. Cell Growth Differ 6:1627-34
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Aguayo, S M; King Jr, T E; Kane, M A et al. (1992) Urinary levels of bombesin-like peptides in asymptomatic cigarette smokers: a potential risk marker for smoking-related diseases. Cancer Res 52:2727s-2731s
Kane, M A; Aguayo, S M; Portanova, L B et al. (1991) Isolation of the bombesin/gastrin-releasing peptide receptor from human small cell lung carcinoma NCI-H345 cells. J Biol Chem 266:9486-93
Aguayo, S M; King Jr, T E; Waldron Jr, J A et al. (1990) Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma. J Clin Invest 86:838-44
Antony, A C; Kane, M A; Krishnan, S R et al. (1989) Folate (pteroylglutamate) uptake in human red blood cells, erythroid precursors and KB cells at high extracellular folate concentrations. Evidence against a role for specific folate-binding and transport proteins. Biochem J 260:401-11
Aguayo, S M; Kane, M A; King Jr, T E et al. (1989) Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers. J Clin Invest 84:1105-13