HYPOTHALAMIC HORMONES IN PANCREATIC CANCER

Project: Research project

Project Details

Description

Analogs of hypothalamic hormones somatostatin and luteinizing
hormone-releasing hormone (LH-RH) given alone or in combination
will be tested in rat and hamster models of transplanted acinar and
ductal pancreatic carcinomas and in nude mice or rats bearing human
pancreatic cancer cell lines e.g. SW-1990, COLO 357, PANC-1, RWP-
1, and 2, CAPAN-2 and Mia PaCa-2. Hamsters with nitrosamine
(B.O.P.)-induced pancreatic tumors will also be used. Our studies
will include: 1) the investigation of pancreatic tumor growth
inhibition induced by: (a) new somatostatin analogs of the D-Phe-
Cys-Tyr-D- Trp-Lys_Val-Cys-Trp-NH2 (RC-160) class and microcapsule
formulations of these analogs in poly(D,L-lactide-co-glycolide)
(pLGA) for continuous delivery for 30 days. More than 300 of these
somatostatin analogs were synthesized and some, such as RC-160 and
RC-121, are superactive and show antitumor activity, (b)
microcapsules of the agonist D-Trp-6-LH-RH in pLGA, (c)
combinations of microcapsules of somatostatin analogs with D-Trp-
6-LH-RH, (d) combination regimens of somatostatin analogs or D-Trp-
6- LH-RH microcapsules with chemotherapeutic agents, e.g.
Ifosfamide, Mitomycin C and Cisplatin; e) microcapsules of N-Ac-D-
p-C1-Phe-1,2, D-Trp-3,D-Arg-6,D-Ala-10-LH-RH (Antagonist I), or
another antagonist in combination with other agents; 2)
investigation of direct antiproliferative effect of somatostatin
analogs on various pancreatic carcinoma cell lines in tissue
cultures which could be mediated by inhibition of growth factors
such as IGF-1 and EGF; 3) an evaluation of the effect of various
G.I. hormones (secretin, gastrin, and CCK) and growth factors e.g.
EGF on the promotion of growth of pancreatic exocrine tumors in
vivo and in vitro. 4) Biochemical studies such as the protein
phosphorylation in pancreatic tumors and the evaluation of tumor
membrane receptors for somatostatin, CCK, gastrin IGF-1 and EGF.
5) Synthesis of somatostatin analogs containing cytostatic radicals
such as Melphalan, Aziridine, Mitomycin C and their evaluation in
models of pancreatic cancer as targeted hormonal carriers for
chemotherapeutic agents; 6) Detailed histological evaluations of
all tumors; 7) Approaches 1-6 will be also tried on a human colon
adenocarcinoma line e.g. COLO 320, since the mechanism of
suppression may be similar. The aim of this project will be to
develop a method for the treatment of hormone-sensitive pancreatic
cancer and colon cancer based on various somatostatin analogs and
LH-RH analogs given alone or in combination and to evaluate the
usefulness of somatostatin analogs with cytostatic radicals for the
inhibition of these tumors.
StatusFinished
Effective start/end date1/1/906/30/92

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

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