We have established the concept that carcinoma is a pathology of embryology. This research is to test the hypothesis that if one embryonic field can regulate its closely related carcinoma (as the blastocyst regulates embryonal carcinoma), then there should be an embryonic field capable of regulating each type of carcinoma. To this end, the neural crest will be tested to see if it regulates tumor formation of neuroblastoma and melanoma. If regulation occurs, attempts will be made to make mice chimeric in neural crest-derived tissues by the injection of small numbers of neuroblastoma cells into mouse embryos of appropriate gestational ages. The injected embryos will be injected into the uteri of appropriate hosts, and the offspring will be analyzed for chimerism using isoenzyme analyses and pigmentation. The cell types responsible for the inductions will be identified using the techniques successful in the studies of blastocyst control of tumor and colony formation of embryonal carcinoma. These studies will involve tissue culture, embryo dissection, microinjection of electron microscopy, etc. Then we will study the mechanism of the control. Is there a diffusible molecule or is it membrane-bound? Is metabolic cooperation required? Melanoma cells do not form tumors when injected into the skin of limb buds of mouse embryos at 14 days of gestational age. Organ cultures made from 14-day limb bud explants produce a factor inhibitory of growth of melanoma cells in vitro. This factor is being characterized. (M)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035367-02
Application #
3172948
Study Section
Pathology B Study Section (PTHB)
Project Start
1983-08-01
Project End
1987-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
2
Fiscal Year
1985
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
Pierce, G B; Parchment, R E (1991) Progression in teratocarcinomas. Basic Life Sci 57:71-8;discussion 78-81
Parchment, R E; Gramzinski, R A; Pierce, G B (1990) Embryonic mechanisms for abrogating the malignancy of cancer cells. Prog Clin Biol Res 354A:331-44
Gramzinski, R A; Parchment, R E; Pierce, G B (1990) Evidence linking programmed cell death in the blastocyst to polyamine oxidation. Differentiation 43:59-65
Parchment, R E; Gramzinski, R A; Pierce, G B (1990) Neoplastic embryoid bodies of embryonal carcinoma C44 as a source of blastocele-like fluid. Differentiation 43:51-8
Pierce, G B; Gramzinski, R A; Parchment, R E (1990) Amine oxidases, programmed cell death, and tissue renewal. Philos Trans R Soc Lond B Biol Sci 327:67-74
Pierce, G B; Gramzinski, R A; Parchment, R E (1989) Programmed cell death in the blastocyst. Ann N Y Acad Sci 567:182-6
Pierce, G B; Lewellyn, A L; Parchment, R E (1989) Mechanism of programmed cell death in the blastocyst. Proc Natl Acad Sci U S A 86:3654-8
Parchment, R E; Pierce, G B (1989) Polyamine oxidation, programmed cell death, and regulation of melanoma in the murine embryonic limb. Cancer Res 49:6680-6
Pierce, G B; Arechaga, J; Muro, C et al. (1988) Differentiation of ICM cells into trophectoderm. Am J Pathol 132:356-64
Pierce, G B; Speers, W C (1988) Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res 48:1996-2004

Showing the most recent 10 out of 14 publications