USE OF LH-RH AGONISTS AND ANTAGONISTS IN PROSTATE CANCER

Project: Research project

Description

Analogs of luteinizing hormone-releasing hormone (LH-RH) given alone and in
combination will be tested in rats bearing Dunning R-3327H
hormone-dependent prostate tumors, Noble and Pollard rat models of prostate
tumors and nude mice or nude rats with transplanted human prostate tumor
lines. Our studies will include the investigation of prostate tumor growth
inhibition induced by (1) continuous controlled delivery system based on
the microcapsule formulation of the agonistic analog D-Trp-6-LH-RH in
biodegradable poly(D,L-lactide-co-glycolide) (pLGA) for once a month
administration; (2) combination regimens of D-Trp-6-LH-RH microcapsules
with a) other peptides, especially somatostatin analogs, as well as with b)
antiandrogens RU-23908 (Anandron) and Flutamide (SCH 13521), and c)
chemotherapeutic agents such as cyclophosphamide, Mitoxantrone and
Bisantrene; (3) continuous controlled delivery system based on the
microcapsule (pLGA) formulation of
N-Ac-D-p-Cl-Phe-1,2,D-Trp-3,D-Arg-6,D-Ala-10-LH-RH (Antagonist I),
Ac-Beta-D-Nal(2)-1,D-p-Cl-Phe-2,D-Trp-3,D-Arg-6,D-Ala-10-LH-RH (Antagonist
II) or another antagonist; (4) combination regimens of LH-RH antagonists
with somatostatin analogs, antiandrogens, and chemotherapeutic agents; (5)
synthesis of an analog of D-Trp-6-LH-RH containing a cytostatic radical
(alkylating agent Melphalan [nitrogen mustard attached to Phenylalanine])
and its evaluation in animal models of prostate cancer as a hormonal
carrier for chemotherapeutic agent. Some biochemical studies such as DNA,
RNA and protein synthesis and measurement of protein phosphorylation as
well as protein kinases activities in cytoplasma and nuclei of prostate
tumors and histological evaluations will be performed to provide data to
correlate with tumor regression. The aim of this project will be to
improve the response to LH-RH agonists in prostate cancer by combined
therapy with other agents and provide new data on the usefulness of the
LH-RH antagonist given alone or in combination regimens for the inhibition
of this tumor.
StatusFinished
Effective start/end date9/1/854/30/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $144,800.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $149,498.00

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Gonadotropin-Releasing Hormone
Prostatic Neoplasms
Capsules
Hormone Antagonists
Somatostatin
Neoplasms
Prostate
LHRH Receptors
Nude Rats
Flutamide
Androgen Antagonists
Insulin-Like Growth Factor I
Epidermal Growth Factor
Nude Mice
Phosphorylation
Cell Line
IGF Type 1 Receptor
Steroid Receptors
Peptides
Androgen Receptors

ASJC

  • Medicine(all)