Abstract

The specific aims of this proposal are to investigate the mechanism of rejection of the murine ovarian teratocarcinoma that follows intraperitoneal injection of Corynebacterium parvum. We will test the hypothesis that the acute inflammatory response to the injection of microbial biologic response modifiers is capable of influencing tumor growth. The inflammatory neutrophil (PMN) is envisioned as initiating two distinct anti-tumor responses that occur sequentially. The first effect is direct tumor cell lysis induced through activation of the PMN by bacteria complexed to C'3b. Activation results in the release of reduced oxygen metabolites which lyse tumor cells within the peritoneal cavity. The second effect is the activation of tumor-cytostatic macrophages by inflammatory PMNs that have ingested bacteria. The long range goals of the proposal are to improve survival of patients with ovarian cancer. The use of the current animal model as a preclinical system for studying regional immunotherapy in human ovarian cancer is expected to lead to a better understanding of and offer insight into possible improvements in it for these patients. (TA)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037184-02
Application #
3174961
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Okrent, D G; Lichtenstein, A K; Ganz, T (1990) Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells. Am Rev Respir Dis 141:179-85
Lichtenstein, A; Seelig, M; Berek, J et al. (1989) Human neutrophil-mediated lysis of ovarian cancer cells. Blood 74:805-9
Lichtenstein, A (1988) Neutrophil-mediated nonoxidative tumor lysis stimulated by high concentrations of phorbol myristate acetate. Clin Immunol Immunopathol 47:296-309
Lichtenstein, A K; Ganz, T; Nguyen, T M et al. (1988) Mechanism of target cytolysis by peptide defensins. Target cell metabolic activities, possibly involving endocytosis, are crucial for expression of cytotoxicity. J Immunol 140:2686-94
Lichtenstein, A K; Ganz, T; Selsted, M E et al. (1988) Synergistic cytolysis mediated by hydrogen peroxide combined with peptide defensins. Cell Immunol 114:104-16
Lichtenstein, A; Spina, C; Berek, J S et al. (1988) Intraperitoneal administration of human recombinant interferon-alpha in patients with ovarian cancer: effects on lymphocyte phenotype and cytotoxicity. Cancer Res 48:5853-9
Lichtenstein, A (1987) Antitumor effect of the streptococcal preparation OK-432 in a murine model of ovarian cancer. Cancer Immunol Immunother 24:172-7
Lichtenstein, A (1987) Stimulation of the respiratory burst of murine peritoneal inflammatory neutrophils by conjugation with tumor cells. Cancer Res 47:2211-7
Lichtenstein, A; Ganz, T; Selsted, M E et al. (1986) In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood 68:1407-10
Lichtenstein, A K; Pende, D (1986) Enhancement of natural killer cytotoxicity by cis-diamminedichloroplatinum (II) in vivo and in vitro. Cancer Res 46:639-44

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