Abstract

The tentative topic of investigation for Phase II will be the role of growth regulating peptides in the initiation and promotion of carcinomas of the gastrointestinal tract and pancreas. There is no widely effective treatment for adenocarcinoma of the pancreas. The central hypothesis is that the establishment of autocrine stimulation by endogenous growth factors or the inhibition of an inhibitory autocrine loop may contribute to the growth potential of neoplastic pancreatic tissue. I plan to examine cultured pancreatic carcinoma cells for production of transforming growth factors (TGF) alpha and beta for the presence of TGF receptors and for the growth-stimulatory or inhibitory responsiveness to TGF. I further plan to determine whether the gastrointestinal hormones which cause in vivo pancreatic growth in rodents can induce alterations of TGF production, TGF receptors or in vitro responsiveness to TGF. Identification and possibly manipulation of growth factors and growth inhibition provide a potential means of cancer prevention and a potential treatment of established cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Physician Scientist Award (K11)
Project #
5K11CA001309-02
Application #
3085725
Study Section
(SRC)
Project Start
1987-09-01
Project End
1989-06-30
Budget Start
1988-09-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Tsuchiya, T; Ishizuka, J; Sato, K et al. (1995) Effect of ileo-jejunal transposition on the growth of the GI tract and pancreas in young and aged rats. J Gerontol A Biol Sci Med Sci 50:M155-61
Sato, K; Ishizuka, J; Cooper, C W et al. (1994) Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells. Pancreas 9:193-202
Sumi, S; Beauchamp, R D; Townsend Jr, C M et al. (1994) Lovastatin inhibits pancreatic cancer growth regardless of RAS mutation. Pancreas 9:657-61
Seitz, P K; Cooper, K M; Ives, K L et al. (1993) Parathyroid hormone-related peptide production and action in a myoepithelial cell line derived from normal human breast. Endocrinology 133:1116-24
Guo, Y S; Beauchamp, R D; Jin, G F et al. (1993) Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells. Gastroenterology 104:1595-604
Sumi, S; Townsend Jr, C M; Uchida, T et al. (1993) Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue. Int J Pancreatol 13:43-7
Bold, R J; Ishizuka, J; Townsend Jr, C M et al. (1993) Biomolecular advances in gastrointestinal hormones. Arch Surg 128:1268-73
Tsuchiya, T; Ishizuka, J; Sato, K et al. (1993) New experimental model of proximal and distal colon transposition in rats. Lab Anim Sci 43:454-6
Ishizuka, J; Beauchamp, R D; Sato, K et al. (1993) Novel action of transforming growth factor beta 1 in functioning human pancreatic carcinoid cells. J Cell Physiol 156:112-8
Ishizuka, J; Beauchamp, R D; Townsend Jr, C M et al. (1992) Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. J Cell Physiol 150:1-7

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