# INDUCED MACROPHAGE TUMORICIDAL ACTIVATION

> **NIH NIH R01** · CLEVELAND CLINIC FOUNDATION · 1992 · $129,699

## Abstract

Mononuclear phagocytes are well documented as important
participants in host defense against the development and spread
of cancer.  This capability is dependent upon the acquisition of
tumoricidal competence in response to stimuli present in the
tissue microenvironment (e.g., prototypically interferon gamma
(IFN gamma) and bacteria lipopolysaccaride (LPS)).  The response
of macrophages to these agents includes the potentiation of
protein kinase C activity, the hydrolysis of phosphatidylinositol-
4,5-bisphosphate (PIP2), the associated elevation of intracellular
Ca++ and stimulation of endogenous protein kinase C-mediated
protein phosphorylation, and the induction of new gene expression
in both early and late time frames.

On the basis of these considerations we propose the following
hypothesis:

That macrophage tumoricidal activation is dependent in part on
the transcriptional and post-transcriptional modulation of
regulatory and functional gene expression.  Such changes result in
part from IFN gamma and/or LPS induced changes in intracellular
Ca++ and/or protein kinase C-mediated protein phosphorylation.
The expression of early gene products may be causally related to
late gene expression.

We will test this hypothesis by performing the following specific
aims:

1)  To isolate and characterize cloned cDNAs encoding
macrophage gene products induced during tumoricidal activation
by IFN gamma and LPS.

2)  To analyze the regulation of IFN gamma/LPS induced early
gene expression with respect to the PIP2 hydrolysis cascade and
transcriptional versus post-transcriptional mechanisms.

3)  To analyze the regulation of IFN gamma/LPS induced
functional gene expression and acquisition of tumoricidal
competence, focusing upon the relationship with early regulatory
gene expression.

## Key facts

- **NIH application ID:** 3178830
- **Project number:** 5R01CA039621-09
- **Recipient organization:** CLEVELAND CLINIC FOUNDATION
- **SAM.gov UEI:** TDGUJ1WA4UJ9
- **Principal Investigator:** THOMAS A. HAMILTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $129,699
- **Award type:** 5
- **Project period:** 1987-05-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178830

## Citation

> US National Institutes of Health, RePORTER application 3178830, INDUCED MACROPHAGE TUMORICIDAL ACTIVATION (5R01CA039621-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178830. Licensed CC0.

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