# INDUCED MACROPHAGE TUMORICIDAL ACTIVATION

> **NIH NIH R01** · CLEVELAND CLINIC FOUNDATION · 1993 · $164,031

## Abstract

Mononuclear phagocytes may participate in host defense against cancer
through a diverse spectrum of activities which include not only direct
cytotoxicity but also the recruitment and/or activation of other anti-
tumor effector cell populations.  Both direct and indirect anti-tumor
function involves the inducible expression of many new gene products
including inflammatory cytokines and other genes expressed very early
after stimulation.  The diversity of the tumoricidal activation process
reflects the complexity of inducible macrophage inflammatory gene
expression.  The successful therapeutic application of Biologic Response
Modifiers (BRMs), which may act in part through activation of macrophage
tumoricidal function will necessitate understanding the mechanistic
determinants of inflammatory cell behavior.

The guiding hypothesis for the following proposal is that diverse
patterns of macrophage early gene expression derive, at least in part,
from the complex events which control transcriptional activation of
inducible genes.  Previous work supported by this grant has identified
and characterized diverse expression patterns for three genes (IP-10, D3,
and IL-1beta) in macrophages treated with one of several inflammatory
stimuli (IFNgamma, LPS, IFNbeta).  The regulation of inducible expression
of these three genes provides a model in which to study the complexity
evident in transcriptional control in this cell type and to estimate how
much the diversity in macrophage activation may be explained at this
level.  To test this hypothesis and to define the mechanisms controlling
inducible transcription during tumoricidal activation of macrophages we
propose the following specific experimental aims:

1.   To identify and define the nucleotide sequence elements which
     regulate transcriptional activity of a selection of inducible
     inflammatory gene products in response to a selection of prototypic
     stimuli known to promote diverse patterns of gene expression in
     murine macrophages.

2.   To identify and define the nuclear protein(s) which recognize and
     bind to such sequences and to evaluate the relationship between
     stimulation and activity of these factors.

3.   To determine if such sites are occupied in vivo in macrophages
     undergoing response to selected stimuli using in vivo footprinting
     by Ligation Mediated Polymerase Chain Reaction (LMPCR).

## Key facts

- **NIH application ID:** 3178823
- **Project number:** 2R01CA039621-10
- **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:** 1993
- **Award amount:** $164,031
- **Award type:** 2
- **Project period:** 1987-05-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178823

## Citation

> US National Institutes of Health, RePORTER application 3178823, INDUCED MACROPHAGE TUMORICIDAL ACTIVATION (2R01CA039621-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178823. Licensed CC0.

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