This collaborative investigation is to study steroid hormone receptor biology in ovarian and endometrial tumors. The coordinated program will evaluate the use of radioactive ligands to image and/or treat receptor-rich malignancies and will explore the protein products that result from hormone-receptor interaction as possible aids in the diagnosis of neoplasms.
The specific aims of each of the component projects are: 1. To identify differences in protein synthesis and in estrogen and progestin receptor protein in normal and neoplastic endometrium and related stromal epithelial interactions to understand their nature and regulation. To establish the feasibility of using radiolabeled ligands in humans by studying their receptor affinity and biology in culture and experimental animals. 2. To identify and characterize cellular responses to the estrogen-ER stimulus in normal and neoplastic ovarian ER-rich cells and the effect of Auger electron emissions from ER ligands on target cell functions. Imaging pharmacokinetic in vivo studies will be performed. 3. To develop immunohistologic and immunoelectron microscopic techniques, identifying estrogen and progesterone receptors for characterization of their cellular/subcellular distribution in tissues and cells. To compare immunocytochemical assays with steroid-binding assays of receptors in ovarian and endometrial carcinomas. 4. To synthesize estrogenic and anti-estrogenic radiopharmaceuticals labeled with Auger electron emitting and//or gamma ray emitting isotopes. To collaborate in the evaluation of their utilities and hazards and to determine the potential of these radiopharmaceuticals in therapy and imaging in endometrial and ovarian carcinomas. 5. To conduct human pilot studies to evaluate radiolabeled ligands for imaging and/or therapy of receptor containing tumors. 6. To coordinate the program and provide accurate and timely distribution of tissues for research; to provide for systematic collation and evaluation of experimental results and research planning.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA027476-07
Application #
3093163
Study Section
Cancer Therapeutics Program Project Review Committee (CTR)
Project Start
1980-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Scharl, A; Beckmann, M W; Artwohl, J E et al. (1995) Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection. Int J Radiat Oncol Biol Phys 32:137-46
Hughes, A; Gatley, S J; DeSombre, E R (1993) Comparison of the distribution of radioiodinated-E-17 alpha-iodovinyl-11 beta-methoxyestradiol and 2-iodo-1,1-bis(4-hydroxyphenyl)-phenylethylene estrogens in the immature female rat. J Nucl Med 34:272-80
Shafii, B; Atcher, R W; Desombre, E R (1993) A revised method for the synthesis of 1,1-bis(4-hydroxyphenyl)-2-phenylethylene (BHPE) and its derivatives. Nucl Med Biol 20:371-4
Scharl, A; Holt, J A (1993) Rapid vascular escape of arterially injected 16 alpha-radioiodo,17 beta-estradiol. Int J Radiat Oncol Biol Phys 26:285-90
Beckmann, M W; Scharl, A; Rosinsky, B J et al. (1993) Breaks in DNA accompany estrogen-receptor-mediated cytotoxicity from 16 alpha[125I]iodo-17 beta-estradiol. J Cancer Res Clin Oncol 119:207-14
Holt, J A; Scharl, A; Kullander, S et al. (1992) Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer. Acta Obstet Gynecol Scand Suppl 155:39-54
Beckmann, M W; Toney, L J; Scharl, A et al. (1992) Detection of the HER-2/neu proto-oncogene protein p185erbB2 by a novel monoclonal antibody (MAB-145ww) in breast cancer membranes from oestrogen and progesterone receptor assays. Eur J Cancer 28:322-6
Scharl, A; Kullander, S; Beckmann, M W et al. (1991) Prolonged clearance of intraperitoneal 16 alpha-[125I]iodo-17 beta-estradiol in presence of ascites. Am J Obstet Gynecol 165:1847-53
Scharl, A; Beckmann, M W; Artwohl, J E et al. (1991) Rapid liver metabolism, urinary and biliary excretion, and enterohepatic circulation of 16 alpha-radioiodo-17 beta-estradiol. Int J Radiat Oncol Biol Phys 21:1235-40
Rotmensch, J; Schwartz, J L; Atcher, R W et al. (1991) Increased nuclear damage by high linear energy transfer radioisotopes applicable for radiodirected therapy against radiologic malignancies. Gynecol Obstet Invest 32:180-4

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